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Hair Loss

Hair Loss

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Hair Loss: Principles of Diagnosis and Management of Alopecia

Hair Loss: Principles of Diagnosis and Management of Alopecia Jerry Shapiro. FRCPC Clinical Professor and Director of the UBC Hair Research and Treatment Centre Division of Dermatology University of British Columbia Vancouver Canada Martin Dunitz .

photocopying.uk This edition published in the Taylor & Francis e-Library. Kent . The Livery House. we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention. London.uk Website: http://www.ca Distributed in the rest of the world by ITPS Limited Cheriton House North Way Andover. A CIP record for this book is available from the British Library.© 2002 Martin Dunitz Ltd. electronic. Ontario M1R 4G2.: +1 877 226 2237 E-mail: tal_fran@istar.com Distributed in Canada by Taylor & Francis 74 Rolark Drive Scarborough. All rights reserved. KY 41042. recording. UK Tel. Canada Toll Free Tel. mechanical. 7–9 Pratt Street. 2004. without the prior permission of the publisher or in accordance with the provisions of the Copyright. or transmitted. stored in a retrieval system. Distributed in the USA by Fulfilment Center Taylor & Francis 7625 Empire Drive Florence. Gillingham. Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency.uk Composition by Scribe Design.: +1 800 634 7064 E-mail: cserve@routledge_ny. No part of this publication may be reproduced.co. W1P 0LP. or otherwise.dunitz.co. a member of the Taylor & Francis group First published in the United Kingdom in 2002 by Martin Dunitz Ltd.co. in any form or by any means. London NW1 0AE Tel: +44 (0) 20 7482 2202 Fax: +44 (0) 20 7267 0159 E-mail: info@dunitz.: +44 (0)1264 332424 E-mail: reception@itps. USA Toll Free Tel. ISBN 0-203-42852-8 Master e-book ISBN ISBN 0-203-44903-7 (Adobe eReader Format) ISBN 1-85317-876-4 (Print Edition) Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication. Hampshire SP10 5BE. 90 Tottenham Court Road.

diagnosis and practical management Androgenetic alopecia: Pathogenesis. clinical features. clinical features and practical medical treatment vii ix 4 Surgical management of androgenetic alopecia Drug-induced alopecia Telogen effluvium: acute and chronic Cicatricial (scarring) alopecia 121 135 5 1 6 147 2 7 19 155 175 3 Index 83 .Contents Foreword Acknowledgements 1 Assessment of the patient with alopecia Alopecia areata: Pathogenesis.

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Jerry Shapiro has accomplished an amazing single-authored. in clear terms for all readers. researchers.Foreword Jerry Shapiro is a dedicated clinician/scientist who has devoted himself to all aspects pertaining to the hair follicle. FRCPC Professor of Clinical Dermatology School of Medicine University of California. he also includes the treatment preferences of other hair experts. San Francisco . The illustrations are extensive. It is a practical and personal approach that reflects Dr Shapiro’s long experience with hair problems both in the clinic and in the laboratory. a collection of unique photographs and photomicrographs from his own collection. such as immunological factors in alopecia areata. comprehensive text about hair that enriches the reader from bench to bedside. and students of the hair follicle. The text is exceptionally readable and complements the book’s systematic and inviting organization. Complex issues are presented. which is set apart from others by the blending of rich clinical detail with the latest investigative research and theories of pathogenesis. Vera H Price MD. This is an organized and rational guide for assessing and managing hair loss. all extensively referenced. He has written a unique text that will be invaluable for clinicians. His explicit recommendations about management are given. and where appropriate.

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Dr Wilma Bergfeld. My Hair Fellows: Dr Chantal Bolduc. who took time out of their busy lives to commit a year to studying hair with me. my Hair Transplant nurse. who allowed me to learn from her in Cleveland and from whom I continue to learn. who has. Next. I would like to thank the University of British Columbia’s Division of Dermatology and the Vancouver General Hospital Skin Care Centre for providing the environment for me to work in the field of hair. who has guided me for the last 10 years with all her great surgical skills and great common sense approach to patients. First and foremost. Lucianna Zanet. my first Hair Clinic nurse. Drs Magda Martinka and David Shum. I am most indebted to my hair loss patients who have trusted me and given me the privilege of taking care of their hair. Dr Harvey Lui. who was dedicated and helped shape the University of British Columbia Hair Clinic during its early years. who has been my ‘’hair’’ mentor for over 15 years and has been an inspiration and role model. Each fellow has questioned. whose advice. whose time and efforts were absolutely essential in making this book possible. Dr David McLean. I would like to thank certain individuals who have played an important part in my career. and continues to guide and nurture me in the field of dermatology. I also would like to especially thank my family and friends who stood back and allowed me to take the weekends and evenings to finally accomplish this endeavor. Jerry Shapiro University of British Columbia Hair Research and Treatment Centre . Dr Shabnam Madani and Dr Olga Bernardo. Dr Liren Tang. Charlotte Mossop and Robert Peden. I thank my editors. It continues to be an honor for me and I thank them for this.Acknowledgements There are certainly many individuals to thank in the making of this book. Nina MacDonald. Dr William Stewart. who continue to enlighten me regarding the histopathology of the hair follicle. challenged and inspired me to learn so much more. who was the first individual to encourage me to take on the field of hair. Dr Vera Price. My research associate. they truly are very special people. support and encouragement helped the University of British Columbia Hair Research and Treatment Centre flourish. who continues to teach me the molecu- lar biology and basic science of hair.

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A rational. Figure 1. as therapy is dictated by the appropriate diagnosis. Bulb: consisting of dermal papilla and matrix intermixed with melanocytes (Figure 1. Isthmus extending from insertion of arrector pili muscle to sebaceous gland 4. An accurate diagnosis can frequently be difficult. it is important to review the basics of hair anatomy and physiology of the scalp. exploring the impact of alopecia on psychosocial well-being.2) 1. isthmus. Ancillary laboratory evaluation may sometimes be necessary to help confirm a diagnosis.3) 2. Basic trichologic anatomy and physiology In order to appreciate an organized diagnostic protocol for alopecia. . organized approach is crucial. Patients are most appreciative of a supportive diagnostic approach.1 Assessment of the patient with alopecia Hair loss (alopecia) is a very common patient problem and often a significant source of patient distress. Knowledge of the hair cycle is essential in understanding the patho-physiology of hair diseases and the mechanism of action of the present therapeutic agents used to modulate hair growth.1 Diagrammatic representation of hair anatomy: The hair follicle is divided into 4 parts: bulb. Next.1 The first task of the physician is to address the patients’ concerns fully. Infundibulum extending from sebaceous gland to the follicular orifice. an organized diagnostic approach can assist the physician in the recognition of the characteristic differential features of each disorder and help to identify the cause of alopecia and guide therapeutic direction. The hair follicle is divided into 4 parts: (Figures 1.1 and 1. Suprabulbar area from matrix to insertion of arrector pili muscle 3. and infundibulum. suprabulbar area.

staining positively for Alcian blue and metachromatically for . (3) the hair shaft.2 Hair Loss: principles of diagnosis and management of alopecia Figure 1. (4) inner root sheath. cortex. (Courtesy of Dr Magdalena Martinka and Dr David Shum. consisting from inward to outward of medulla. Huxley’s layer on the inside and Henle’s layer on the outside. (2) matrix. matrix (M). and (5) the outer root sheath.2 (a) Histology of the hair follicle on longitudinal section showing dermal papilla (DP). Dermal papilla fibroblasts are inherently different from non-follicular dermal fibroblasts.) The lower portion of the hair follicle consists of five major portions (1) dermal papilla. and cuticle.4). consisting of inner root sheath cuticle. which contains highly vascularized connective tissue (Figure 1. inner root sheath (IRS). There is a large amount of acid-mucopolysaccharides within the dermal papilla. The base of the follicle is invaginated by the dermal papilla. Note the melanocytes within the matrix providing pigment to the hair. (b) Two anagen follicles side by side at the level of fat. outer root sheath (ORS) and fibrous root sheath (FRS).

3).2 and 1. The hair matrix has large vesicular nuclei and deeply basophilic cytoplasm. which is an invagination of the dermis into the matrix (M). (b) Cross-section of the follicle at the level of the dermal papilla. The ground substance consists of not only non-sulfated polysaccharides such as hyaluronic acid. Dopa-positive melanocytes are interspersed between the basal cells of the matrix lying on top of the dermal papilla (Figures 1. Melanocytes fill the matrix and produce the pigment of the hair. Alkaline phosphatase activity is also increased in the anagen phase. Melanin. Cells of the hair matrix differentiate into six different types of cells.) toluidine blue. In persons with dark hair large amounts of melanin can be seen in the dermal hair papilla. The DP allows capillaries to gain entrance to the cells of the matrix. (Courtesy of Dr Magdalena Martinka.Assessment of the patient with alopecia 3 Figure 1.3 (a) Close-up of longitudinal section of dermal papilla (DP). but also sulfated mucopolysaccharides such as chondroitin sulfate. It is the signal transduction and communication between the DP and the matrix that determines how long a hair will grow and how thick a shaft will be produced. is produced in these melanocytes and incorporated into the future cells of the hair through phagocytosis of the distal portion of the dendritic melanocyte. each of which Figure 1. varying in quantity in accordance with the color of the hair.4 The different layers of the hair follicle .

resulting in the firm attachment of the hair to its inner root sheath. (courtesy of Dr David Shum. which is soft keratin. and the medulla is last (Figure 1. The hair medulla appears amorphous because of its only partial keratinization. The two apposed cuticles covering the inside portion of the IRS and the outside of the hair keratinize next. and all keratinize with trichohyalin granule formation. These granules stain eosinophilic.5 (a) Cross-section and (b) longtitudinal sections of the follicle at the suprabulbar level. The hair cortex then follows. None of these layers contain melanin. The cells of the hair cuticle are tightly interlocked with the cells of the inner root sheath cuticle. in contrast to the basophilic keratohyalin granules of the epidermis. The inner root sheath is composed of three layers (Figures 1. This is subsequently invested by the cuticle of the inner root sheath (IRS).4). The hair and the inner root sheath move in unison upward.4 Hair Loss: principles of diagnosis and management of alopecia Figure 1. No keratohyaline granules (as in keratinizing epidermis) or trichohyaline granules (as in inner root sheath) are formed during keratinization. The hair cortex cells during upward growth from the matrix cells keratinize gradually by losing their nuclei and become filled with keratin fibrils. keratinizes first. Huxley’s layer with trichohyaline granules. The outer layer of the inner root sheath (IRS). The hair cuticle located peripheral to the hair cortex consists of overlapping cells arranged like shingles and pointing upward with their peripheral portions. Henle’s layer.4 and 1.5). hyaline membrance and fibrous root sheath (FRS) surround the whole structure. and the already keratinized Henle’s layer. It may not always be present. Keratin of the cortex is hard keratin. establishing a firm coat around the soft central portions of the follicle. In the central portion of the follicle the matrix (M) is forming cortex.The outer root sheath (ORS). in contrast to the inner root sheath or epidermis. The cuticle of the IRS consists of one layer of flattened overlapping cells that . followed by Huxley’s layer. which is surrounded by the cuticle.) keratinizes at a different level.

already shows numerous trichohyalin granules as it emerges from the matrix. it is covered by IRS and does not undergo keratinization. Only anagen hairs have inner root sheaths. gradually increases in thickness. The cells of the IRS do not contribute to the emerging hair. It is lined by surface epidermis Figure 1. Huxley’s layer is two cell layers thick and develops numerous trichohyalin granules (Figure 1.2–7 Stem cells from the bulge area likely migrate to other portions of the hair follicle and differentiate into its differing layers. Since the cells of the hair cuticle point upward. these two types of cells interlock tightly. It is thickest around the lower third of the hair follicle. at the level of the isthmus the IRS disintegrates.Assessment of the patient with alopecia 5 point downward in the direction of the hair bulb. The point of insertion of the arrector pili muscle is referred to as the bulge area. Henle’s layer. Peripheral to this vitreous layer lies the fibrous root sheath. the isthmus. Trichohyalin granules are few in the IRS cuticle. The glassy or vitreous layer. where it changes into surface epidermis. The outer root sheath (ORS) extends from the matrix cells to the entrance of the sebaceous duct. The isthmus is the segment that extends from the arrector pili muscle to the sebaceous gland duct entrance.6). but serve as a hard molding scaffold up to the arrector pili muscle. The ORS has plentiful vacuolated cytoplasm owing to its plentiful glycogen. . is periodic acid Schiff-positive and diastase-resistant.6 Cross-section of the follicle just beneath the isthmus showing the eosinophilic completely keratinized inner root sheath (IRS) enclosing the hair shaft (HS). They are located usually in the interfibrillary matrix. There is no inner root sheath here. The ORS undergoes trichilemmal keratinization. (Courtesy of Dr David Shum.8 Melanosomes of the hair cortex are larger than those of the epidermis. They lie singly or within groups not within lysosomes. However. Just before the isthmus the IRS becomes fully keratinized (Figure 1. and is the likely location of the first primordial cells (stem cells) of the hair follicle.5). In its lower portion. The ORS is thinnest at the level of the hair bulb. The upper portion of the follicle above the entrance of the sebaceous duct is the infundibulum. and is thickest in the middle portion of the hair follicle. This connective tissue sheath may contain considerable reproductive potential. which forms a homogeneous eosinophilic zone peripheral to the outer root sheath. All of this is surrounded by outer root sheath. producing large homogeneous keratinized cells without the formation of keratohyaline granules. which is composed of thick collagen bundles. only one cell layer thick.) undergoing keratinization with the formation of keratohyaline granules. It differs from usual basement membrane zone by being thicker. below the isthmus. hyaline membrane and fibrous root sheath. as was recently shown by Reynolds et al.

In certain individuals.000. This ratio is usually uniformly distributed over the entire scalp. at 80. which is converted to dopaquinone which can then undergo oxidative reactions to form either eumelanin or pheomelanin. where hair cycling is synchronous. Blonds Figure 1. Unlike animals.7). Anagen may last up to 2–6 years. and catagen 3 weeks. with fewer hairs per square cm in Blacks and Orientals. and only rarely in the intercellular space (Figure 1. the middle and upper portions of the hair follicle are the permanent segment of the hair follicle. Dark hair contains more eumelanin and blond hair more pheomelanin. There is ethnic variation. In white hair. Physiologic hair shedding of 100 hairs per day is usual on the average.35 mm/day.8). (Figure 1. Vellus hairs or miniaturized vellus-like hairs of androgenetic alopecia (AGA) have a shaft diameter of less than . The hair shafts only contain the detritus of melanin or no melanin at all. 1% in catagen and 10% in telogen. The normal scalp contains 100. In other hair colors. on the human scalp there is an asynchronous mixture of hairs actively growing and resting.000. tend to have more. Both are synthesized from tyrosine. especially of melanosomes. The telogen hairs are located higher up in the dermis (Figures 1. there is periodicity in the number of telogen hairs. Hair fiber is produced during anagen at a rate of approximately 1 cm/month or 0.000 hairs. January or February. and redheads less. the black brown pigment eumelanin and the yellow red pheomelanin. The average number of hairs for a normal scalp is 250 per square cm or 1100 per square inch.10) and can be pulled out relatively easily. melanocytes have higher amounts of eumelanosomes.8 and 1. either eumelanin or pheomelanin. Melanocytes show degenerative changes. at 120. while the lower portion is non-permanent. melanocytes contain ellipsoidal melanosomes with a lamellar internal structure (eumelanosomes) Pheomelanogenesis is associated with melanocyte-containing spherical melanosomes which have a less well defined internal structure containing granules or vesicles. The sizes of the hair shafts are important in determining a diagnosis. In the eumelanin containing follicle.7 Melanosomes. The growing or anagen hairs are anchored deeply within the subcutaneous fat (Figure 1. Decreased telogen hairs occur in December.8) and cannot be pulled out easily. During the hair cycle. with fluctuations over the year. with a maximal number in late summer. Two types of melanin are present in mammalian hair. In fire-red hair there are high levels of pheomelanosomes. Increased hair shedding is usually noted in autumn. during anagen are transferred from melanocytes to matrical cortex cells via dendritic ends. The scalp consists of almost 90% of hairs in anagen. melanocytes at the basal layer of the hair matrix are usually reduced in number or are absent. telogen 3 months.6 Hair Loss: principles of diagnosis and management of alopecia within the cells.

(b) The newly formed anagen hair pushes out the previous telogen hair. This ratio is usually uniformly distributed over the entire scalp. telogen 3 months.8 During the hair cycle. while the lower portion is non-permanent. (a) The growing or anagen hairs are anchored deeply within the subcutaneous fat and cannot be pulled out easily. and during telogen is closely associated with the stem cells of the bulge area.9 Vellus-like hairs are less than 0. Only miniaturized vellus-like hairs of androgenetic alopecia have arrector pili muscle. A true vellus hair does not have an attached arrector pili muscle. the middle and upper portions of the hair follicle are the permanent segments of the hair follicle. The dermal papilla (DP) is pulled upward with each cycle. Figure 1.Assessment of the patient with alopecia 7 Figure 1. . 1% in catagen and 10% in telogen. Terminal hairs are coarse over 0.06 mm in diameter and can grow up to 3 feet. Anagen may last up to 2–6 years. Communication signals between dp and stem cells of the bulge probably determine the length of anagen and the matrix girth of the next hair cycle. The scalp consists of almost 90% hairs in anagen. The telogen hairs are located higher up in the dermis and can be pulled out relatively easily. and catagen 3 weeks.03 mm in diameter and rarely grow more than 1–2 mm.

(Courtesy of Dr David Shum. a thorough history and physical examination are important. Terminal hairs have a shaft diameter greater than 0. One can induce hair growth promotion by increasing the number of anagen hairs per unit area and by increasing the duration of the anagen phase.11). whose bulbs are found in the area of subcutaneous fat. surrounded by outer root sheath.8 Hair Loss: principles of diagnosis and management of alopecia 0.) . diet. trauma. autoimmunity. or alopecia.11 Small vellus-like hairs (V) in androgenetic alopecia. (a) Hair shafts are small (<. psychological abnormalities. Because of the multiplicity of disorders that can result in hair loss. infections. (b) The small size of the hairs make the sebaceous glands look more hyperplastic. A central starshaped area of trichilemmal keratin can be noted. and ancillary laboratory work-up may be necessary.06 mm. (Courtesy of Dr David Shum and Dr Magdalena Martinka. including endocrine abnormalities. systemic illness. unlike terminal anagen hairs.03 mm (Figures 1. drugs.03 mm). genetic predisposition. Figure 1.9 and 1. hyaline membrane and fibrous root sheath. and structural hair defects.) There are many etiologic factors that cause clinical hair loss.10 Cross-section of telogen hair. The lower portion of terminal telogen hairs is found higher up in the dermis. Patient approach Figure 1.

Certain conditions are more common in childhood compared to the adult. back brushing. The duration and pattern (i. Explanation and discussion may resolve the problem without specific intervention. eyelashes. A full list of current and past medication should be obtained (see Chapter 5). crash diets.2). the presence or absence of coincidental acne and abnormal menstrual cycles may indicate an androgen excess causing androgenetic alopecia. since many medications can induce hair loss.or hypothyroidism. Key questions implicating a telogen effluvium are: Any pregnancy. operations/general anesthesia. The two most common forms of hair loss in children are tinea capitis and alopecia areata. It is important to establish whether the hair falls out from the roots or breaks off along the shafts. bleaching. Thyroid screening questions may point to hyper. eyebrows. since any hair-bearing area may be affected by alopecia areata or trichotillomania.g.2 Differential diagnosis . Patients should be asked questions regarding hair shedding (alopecia areata or telogen effluvium) versus simple hair thinning without shedding (androgenetic alopecia). It is also important to question about the loss of axillary and pubic hair. since there are completely different causes for each of these situations (Table 1. Occasionally an underlying depression or dysmorphophobia (pathologically focused Table 1. or weight loss in the preceding 6 months? A positive family history of alopecia areata or androgenetic alopecia may point to a genetic predisposition for hair loss. diffuse versus focal) of hair loss is very important to determine.Assessment of the patient with alopecia 9 History The history is of critical importance in developing the initial differential diagnosis (Table 1. In addition. Many patients with hair disorders become frustrated when their worries about hair loss are either ignored or dismissed as insignificant. Some hair care practices (e.1 Hair loss history questionnaire Table 1. high fever. permanent waving) may result in hair breakage.1). The patient’s concerns and expectations should be acknowledged and fully explored. The age of the patient is very important. and body hairs.e. and a strict vegetarian diet can implicate iron deficiency anemia.

Random patterns are more common for alopecia areata. Note: (a) Follicular ostia in a non-scarring alopecia.3).12). and firmly. first inspect for inflammation. Second. study the quality of the hair shaft in terms of caliber. while cicatricial alopecias are devoid of follicular units (Figure 1. It is useful to take a Table 1. the ‘pull test’. On the scalp. fragility. Non-cicatricial alopecias demonstrate visible follicular units. scale. If Clinical examination Clinical examination should be performed in three stages. Finally. contrast paper and place the hairs against it to examine the sizes of hairs (Figure 1. (b) Absence of follicular ostia in a scarring alopecia. length and shape. Approximately 60 hairs are grasped between the thumb. index and middle fingers from the base of the hairs near the scalp. It is important that these psychiatric conditions be recognized and managed before any further treatment is initiated. such as alopecia areata. Pull test: To determine the ongoing activity of hair loss.3 Causes of alopecia . It is important to determine if the hair loss is associated with scalp scarring (Table 1. but not forcefully. a useful ancillary test.13). examine the pattern of density and distribution of hair. should be conducted. tugged away from the scalp (Figure 1. fixation on body image) may be present.10 Hair Loss: principles of diagnosis and management of alopecia Figure 1.14).12 Presence or absence of follicular ostia is crucial in the differential diagnosis. Certain characteristic patterns of hair loss are more common for certain diseases. as this introduces an entirely different differential diagnosis. and erythema.

.Assessment of the patient with alopecia 11 Figure 1. It is normal to pull up to 6/60 (< 10%) hairs. This alopecia areata patient showed one month of spontaneous regrowth in a bald patch without any treatment. This is a 57year-old female with diffuse alopecia areata displaying a very positive pull test. (b) The hairs are then tugged from proximal to distal end. size and overall caliber of the hair shafts. More than 6/60 hairs is a positive pull test and implies pathology. (c) The number of hairs extracted is counted.14 Pull test: (a) Approximately sixty hairs are grasped from the proximal portion of the hairs shafts at the level of the scalp.13 A contrast paper positioned at an involved area of the scalp will help determine the length. Figure 1.

twisting and lifting the hair shafts rapidly in the direction of emergence from the scalp (Figure 1.15). On the fifth day after the last shampoo. hairs are taken from specified sites. owing to hair damage caused by the plucking procedure. this is considered normal physiologic shedding. On the fifth day after the last shampoo. .12 Hair Loss: principles of diagnosis and management of alopecia more than 10% or 6 hairs are pulled away from the scalp. Hair shafts are then cut off 1 cm above the root sheaths and roots are arranged side by side on a slide.15 Trichogram/Pluck test: The trichogram/pluck test is another method of assessing hair loss. With this technique. Anagen hairs are distinguished from telogen hairs and anagen to telogen ratios are calculated. If less than 6 hairs can be easily pulled away from the scalp. The pull test helps to assess the severity and location of hair loss.10 is more accurate than the regular trichogram. a fixed area is marked on the scalp through a template and all the hairs in that area are individually epilated with tweezers and mounted on a Figure 1. the trichogram has not become routine. hairs are taken from specified sites9. as it takes into account not only anagen/telogen ratios but also hair density and size. (b) Anagen hairs are distinguished from telogen hairs and anagen to telogen ratios are calculated. Trichogram/pluck test: The trichogram/ pluck test is another method of assessing hair loss. The unit area trichogram. twisting and lifting the hair shafts rapidly in the direction of emergence from the scalp. (a) The surrounding hair is fixed with clips and 60–80 hairs are grasped with a hemostat covered with rubber and are plucked. For noncicatrizing alopecias this anagen/telogen ratio has diagnostic significance. since much of the observed hair dystrophy is artefactual. The surrounding hair is fixed with clips and 60–80 hairs are grasped with a hemostat covered with rubber and are plucked. popularized by Rushton. The patient must not shampoo for at least one day prior to the pull test. Because a scalp biopsy can give the physician the same information plus more regarding inflammation and the size of hairs. Counts of dystrophic hairs are unreliable. this constitutes a positive pull test and implies active hair shedding.

but only physiologic hair loss. If the patient is losing less than 100 hairs per day. Performing a hair count is tedious and timeconsuming for the patient. It is normal to lose 100–150 hairs per day. Hair counts: Daily scalp counts can be useful to the physician to help quantify how much the patient is losing and make sure this is not more than physiologic hair loss. All hairs shed in the shower. (Courtesy of Dr David Shum. Patients are instructed to do this daily for 7 days. then there is currently no active shedding. count them and place them in plastic sandwich bags. This meticulous technique can be quite laborious and requires very special skill. or sink or on the brush. But it is something that patients can do on their own to follow their progress.16 Light microscopic examination of hairs: (a) telogen hair with characteristic club.16). (c) hair shaft abnormality: trichorrhexis nodosa secondary to trauma. counter or pillow are collected. Hair shafts are mounted in parallel Figure 1.) .Assessment of the patient with alopecia 13 slide for counting. (b) anagen hair with inner root sheath.11 Light-microscopic examination Hairs extracted by slow pull can be examined under the light microscope (Figure 1. Patients are asked to collect all the hairs shed in one day. Shampoo days are labeled separately. as it is expected that there will be more shedding on those days.

(c) Direct vertical pressure is applied along with the rotation of the punch. For local anesthesia. Epinephrine causes vasoconstriction.14 Hair Loss: principles of diagnosis and management of alopecia Figure 1. (b) A 4. The area to be biopsied is marked with a red china marker. In patients who have curly hair as above. The typical punch should be pushed right through to the hub. This allows the vasoconstrictive effect of epinephrine to take effect and hence maximize the hemostasis. In noninflammatory conditions a biopsy in a representative area is sufficient. insert the punch perpendicular to the scalp. lidocaine 1 % with epinephrine in a concentration of 1:100.0 mm punch biopsy is placed parallel to follow the direction of the hair.000 is injected with a 30 gauge needle into the scalp. . If possible the biopsy should be taken from a cosmetically less apparent area of the scalp. Staying away from hair parts or the frontal portion of the scalp is recommended.0 mm is sufficient to obtain a full scalp thickness. a mandatory waiting period of at least 10 minutes is suggested following the anesthetic injection. Penetration of the punch to a depth of approximately 3. which has a hemostatic effect in a highly vascular site such as the scalp.5–4. In addition.17 How to do a scalp biopsy: (a) In order to obtain sufficient histopathologic information. the scalp biopsy should be taken from an active inflammatory area containing hair follicles or active hair destruction.

Wound dressings are not necessary for scalp biopsies. cut. (e) Aluminum chloride 20% solution on a Qtip can be used for hemostasis after the biopsy has been removed. which helps to identify the suture on the hairy scalp. (f) The biopsy defect is closed with a bluecolored monofilament suture. The suture needle is passed through the upper dermis. For the most part. Roots should be examined to determine the stage of the hair cycle and for the presence of dystrophy.Assessment of the patient with alopecia 15 (d) The same needle for the anesthesia can be used to hook the tissue beneath the hair bulbs. most hair shaft abnormalities are quite rare. between two glass slides taped together. If fungal diseases are suspected. particularly with pigmented hairs. coiling and twisting and extraneous matter. irregularities. hairs should be placed on a glass slide with 20% potassium hydroxide added in order to demonstrate fungal spores and hyphae. The hair shafts need to be examined to detect fractures. fractured or weathered. Hair shaft abnormalities (which can increase hair fragility and cause hair loss) can be diagnosed with this method. preventing damage to the hair bulbs located in the deep dermis. A drop of cyanoacrylic glue placed on the slide will give greater contrast under the microscope compared to a dry mount. The free ends of the hair should be checked to see whether they are tapered. . and the hair mount is not used routinely at the University of British Columbia (UBC) Hair Clinic unless indicated.

and dehydroepiandrosterone sulfate (DHEAS) is advised to rule out hyperandrogenemic states. if present. For those difficult cases. it is obligatory to perform a 4 mm scalp biopsy. Non-cicatricial alopecias In the non-cicatricial alopecias. or irregular menses. . two biopsies are taken. at the deeper levels near the subcutaneous fat. The mid-levels consist of anagen and telogen hairs with terminal hairs only. and alopecia areata. The three most common forms of non-cicatricial alopecias are androgenetic alopecia. One half is sent for direct immuno-fluorescence and the other half for longitudinal sectioning. Evaluation of serum ferritin may be necessary to exclude iron deficiency anemia.and interfollicular inflammation. The difference between the mid levels and the lower levels is the number of terminal telogen hairs. a thyroid-stimulating hormone level should be investigated. Usually this involves a depth of 4 mm.16 Hair Loss: principles of diagnosis and management of alopecia The scalp biopsy: Scalp biopsies are indicated in all cases of cicatrizing alopecias and in all cases of unexplained non-cicatrizing alopecias12. although they can sometimes be difficult to appreciate when miniaturized. The biopsy must be deep and include the entire follicular unit. Another 4 mm bi- opsy is bisected longitudinally. acne.4 compares the key clinical features that distinguish these three conditions from each other. Peri-. The characteristic histologic features of the most common non-cicatrizing and cicatrizing alopecias are discussed in subsequent chapters. These conditions are discussed at length in other chapters of the book. telogen effluvium. At the UBC Hair Clinic all biopsies for non-cicatrizing alopecias are performed with transverse/horizontal sectioning rather than longitudinal/vertical sectioning. the number is reduced to 35. In women with androgenetic alopecia and virilizing signs such as hirsutism. Laboratory tests: Lab tests may be helpful in establishing a diagnosis. the numbers are even less. The difference between the upper levels and mid levels is usually the number of vellus or vellus-like hairs. Table 1. The deeper levels contain anagen terminal hairs. an endocrinologic work-up consisting of free testosterone.15 At the UBC Hair Clinic a 4 mm punch biopsy is trisected at two levels and subsequently horizontal sections are read from the base of the follicle to the papillary dermis. including some subcutaneous fat (Figure 1.17). For cicatrizing alopecias. an antinuclear antibodies (ANA) examination should be performed. there is preservation of follicles on clinical and histologic examination. particularly in women with diffuse alopecia. The upper levels contain telogen and anagen hairs. at around 30. At the level of reticular dermis near the base of the infundibulum. The technique of vertical sectioning was popularized by Headington13 and subsequently by Whiting14 and Sperling. In cases of confirmed scarring alopecia due to discoid lupus erythematosus. If thyroid dysfunction is suspected. Not only are the various scarring alopecias difficult to differentiate from each other clinically. will be very prominent at all levels of the biopsy. but occasionally they may also be difficult to distinguish clinically from non-scarring alopecias. Normally a scalp biopsy has 35–40 hairs at the upper levels in papillary dermis. This allows a greater number of follicles to be examined. The first 4 mm punch biopsy is taken for transverse sectioning. Anagen/telogen ratios as well as terminal/vellus ratios can easily be calculated on the basis of the above and the morphology of the follicles. as well as terminal and vellus and vellus-like miniaturized hairs. intra.

Lesions of DLE demonstrate marked erythema. burns.Assessment of the patient with alopecia 17 Table 1. as there is irreversible hair loss once hair follicles have become scarred. Conclusion The majority of common hair disorders can be readily diagnosed in the physician’s office through the recognition of the characteristic differential features of each disorder. The diagnosis depends upon a combination of find- .4 Common non-scarring alopecias Cicatricial (scarring) alopecia Localized areas of cicatricial alopecia of the scalp may result from trauma. The importance of prompt appropriate therapy is crucial. The first task of the physician is to acknowledge the patient’s concerns and have an empathetic approach to the problem of hair loss. A biopsy is necessary to establish an accurate diagnosis. viral infections such as herpes zoster. The most common causes for scarring alopecia are discussed at length in Chapter 7. atrophy. Evidence of cutaneous disease elsewhere on the skin. and bacterial infections. and lichen planus is another common etiology. oral or genital mucous membranes. Scarring alopecias are considered true trichologic emergencies. and follicular hyperkeratosis. Discoid lupus erythematosus (DLE) is the most common primary cause of scarring alopecia. telangiectasia. and nails should be looked for carefully. acute fungal infections such as tinea capitis.

Cotsarelis G.P. 1991.. Wei Z. The unit area trichogram in the assessment of androgen-dependent alopecia. Whiting D.T. Hair follicle stem cells: their location. 46:1469–77. ed.M. New York: McGraw-Hill. Kaur P. 101(1 Suppl):16S–26S.M. physical examination and any necessary investigations. 485–527. Br J Dermatol. 1996. Liu Y.Olsen. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells. localization and functions. 10. D.T. 28(5 Pt 1): 755–63. Epithelial stem cells in the skin: definition.J. Frishberg. Christofidou-Solomidou M. and Shapiro J. References 1. Inc. and Sun T.T. Sun T. 642: 214–24.H. Rushton H. Shapiro J. 1983. CserhalmiFriedman P. Dermatol Surg. An organized diagnostic and management strategy will help both to identify the cause of alopecia and to direct therapy.M. Transverse scalp sections: a proposed method for laboratory processing. 1984. 1999. and eyelash follicles: the hair cycle and tumor formation. 1993. 2. vibrissae. 59–69.. Trans-gender induction of hair follicles. 8.. Nature. E. 1999. 109(4):429–37. J Am Acad Dermatol. Exp Dermatol. In Hair and Hair Diseases. 4. 5.. Sun T. ed. Orfanos C. Practical management of hair loss...M. Lyle S. James K.. Berlin: Springer-Verlag. Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype. 13. Wiseman M. 15. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia [published erratum appears in J Am Acad Dermatol 1993 29(4):554]. et al. A basis for a morphometric approach to disorders of the hair follicle. J Invest Dermatol Symp Proc. Cotsarelis G. Cotsarelis G. C. 14. Cotsarelis G.. and Lui H. role in hair cycle.. and involvement in skin tumor formation. markers. and Lavker R. 1999. Clinical tools for assessing hair loss. and Guthrie V. 1993. Transverse microscopic anatomy of the human scalp.B. Miller S. Can Fam Physician. 9.. Stem cells of pelage.. J Invest Dermatol. 402(6757): 33–4. The scalp biopsy: making it more efficient. Wilson C. 3. and Mortimer C. 1990.C. 2000. In: Disorders of Hair Growth Diagnosis and Treatment.C.. and Lavker R.M. 224–5. et al. Sperling L. 61(7):1329–37. discussion. Reynolds A. J Invest Dermatol. et al.. 120(4): 449–56. Androgenetic alopecia: clinical aspects and treatment. 1990. 25(7):537–8.18 Hair Loss: principles of diagnosis and management of alopecia ings obtained from meticulous history. J Am Acad Dermatol.T. 11. Ann N Y Acad Sci. Headington J. 1991. Dhuailly P. . Madani S... 6. 7.G.Orfanos. Lavker R. Arch Dermatol. et al.. Hair follicular stem cells: the bulge-activation hypothesis. and skin carcinogenesis. 35(2 Pt 1):220–2. Lawrence C. 4(3):296–301. 1999. pp. pp. 1994. 12. hair cycle..A. Lavker R. 96(5): 77S–78S. 8(1):80–8. Cell. Olsen E.

15. emotional stress. molecular biologists. but is likely to be an interaction between genetic and environmental factors. The exact cause is unknown. Within the past decade.10–14 with up to 55% concordance rate in identical twins. cytokines. there have been reports of AA in identical twins.1–3 This chapter will review the latest information on etiology. At these meetings. and geneticists.13 Scerri 14 presented a case of 11-year-old identical twin boys. intrinsically abnormal melanocytes or keratinocytes and neurological factors. forming the Major Histocompatibility Complex (MHC). with ophiasis occurring simultaneously. eas of attention. clinical features. dermatologists. usually patchy.4. 1994 and 1998. Other proposed etiologies include infectious agents.2 Alopecia areata: Pathogenesis.15 The HLA complex has been investigated in AA patients because of the association of other autoimmune diseases with increased frequencies of HLA antigens. numerous subspecialties.16 Associations with Etiology The etiology of A A is unknown. such as the human leukocyte antigens (HLA) are located on the short arm of chromosome 6. ranging from 10% up to 42 % of cases. biochemists.5 There is a significantly higher incidence of a positive family history in patients with early onset of AA. diagnosis and practical management Alopecia areata (AA) is an unpredictable. there have been significant advances in our understanding of alopecia areata.6–9 Also. clinical features and state of the art treatment for AA.1% with the first patch after 30 years of age. including immunologists. There is a high frequency of a positive family history of AA in affected individuals. Genetic factors Genetic factors play an important role in the etiology of AA. AA is generally felt to be mediated by T lymphocytes directed at hair follicles. Most recent research and future directions in alopecia areata originate from three major research workshops co-sponsored by the National Alopecia Areata Foundation (NAAF) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in 1990.6 Familial incidence of AA has been reported to be 37% in patients who had their first patch by 30 years of age and 7. Genetic and immunologic factors have been important ar- . discussed alopecia areata in an open forum.6. The proceedings of these meetings have been published in the Journal of Investigative Dermatology. pathologists. Several closely linked genes. non-scarring hair loss condition affecting any hair-bearing surface.

The earlier studies identified the association of AA with several class I antigens.18 B13. both HLA class I (HLA-A. there has been an increased consist- ency in evidence revealing associations between AA and HLA class II antigens. such as HLA-A9.21 Recently.7–9. -C) and class II (HLA-DR.20.16 B12.1 (a. -DP) have been studied in AA. The studies reveal a significant association of HLA-DR11 and DQ3 in patients with AA.7–9.28. There is up to an 8. -DQ.19.20 Hair Loss: principles of diagnosis and management of alopecia Figure 2. -B. b) Alopecia areata and Down’s syndrome.22– 29 The HLA alleles DQB1*03 (DQ3) and HLADRB1*1104 (DR11) appear to be markers of general susceptibility for all forms of AA. There have also been studies showing no correlation with HLA Class I antigens. and B8. suggesting involvement of a gene located on chromosome 21 in determining susceptibility to AA.8% increased frequency of AA in patients with Down’s Syndrome. B7.17 B18. and B27.29 The HLA alleles DRB1*0401 (DR4) and DQB1* .

The defective gene in this syndrome is mapped to chromosome 21.Alopecia areata 21 0301(DQ7) are markers for more severe longstanding alopecia totalis/universalis. IL-1 has a direct effect on hair growth.30. The main associations are with thyroid diseases and vitiligo. the exact causative genes have not been discovered.35 However. other autoimmune diseases and a responsiveness to immunosuppressive therapy. Identification of the AA antigens will be a major step in understanding the mechanisms of AA and in the design of therapies for prevention and treatment. Puavilai et al.2 for DRB1*0401. Immunological factors Indirect clues for autoimmunity There are indirect clues for autoimmunity that include the association of the disease with a HLA haplotype. compared to only 2% in the general population. suggesting involvement of a gene located on chromosome 21 in determining susceptibility to AA (Figure 2.36 AA has been shown to have a significant association with vitiligo.32 The IL-1 gene cluster on chromosome 2 includes genes for the proinflammatory IL-1 proteins. reported an association between the severity of AA and inheritance of allele 2 of a five-allele polymorphism in intron 2 of the interleukin-1 receptor antagonist gene. and with the final data on the Human Genome Project just completed. Genetic research may ultimately explain why. there is an interaction between genetic and environmental factors that triggers the disease. There are reported associations between AA and classic autoimmune disorders. how and who develops AA. HLA associations have been discussed above. Alopecia areata is a complex trait expressed by a number of genes.8% increased frequency of AA in patients with Down’s Syndrome. their cell membrane receptors and the anti-inflammatory IL1 receptor antagonist.59 Tarlow et al. There is up to an 8.5 This evidence has been further confirmed by documentation of an increased prevalence of anti-thyroid antibodies35 and thyroid microsomal antibodies. The investigators 9 suggest that amino acid sequencing of the antigen binding grooves of these HLA antigens may indicate the structure and identity of the elusive AA target antigens.31 Thirty per cent of patients with autoimmunepolyglandular syndrome have AA.8% incidence of thyroid disease in patients with AA. Several reports reveal an 8. Other investigators 26 also suggest that DRB3*52a may confer resistance to AA. In hair follicle organ cultures. Polygenic influences are clearly involved.1). By identifying these HLA genetic correlations.7–9 with a relative risk for AA of 30. it is expected that our understanding of this complex trait will be further clarified. showed no increase in microsomal antibodies compared to normal controls.4. again implicating this chromosome. which are key to the follicular inflammatory immune response responsible for AA. Most probably.0–11. with a fourfold greater incidence of vitiligo in AA . we are a step closer to understanding the structure of the epitopes recognized by T cells. However. one must bear in mind that the presence of predisposing HLA is but one component in a cascade of factors leading to autoimmune disease. IL-1 inhibits growth of the hair fiber33 and induces morphological changes that resemble those seen in AA.34 In conclusion. Polymorphism within the IL-1 cluster may modulate IL-1 responses. many studies indicate that AA is a polygenic disease with certain genes correlated with susceptibility and others with severity. At this point. With the discovery of animal models for AA.

inner root sheath. and consists mostly of T lymphocytes and.40 lupus erythematosus. as compared to controls using indirect immunofluorescence. and hair shaft.61 and systemic steroids 62 also supports the idea of immune-mediated pathogenesis in AA. Successful treatment of AA with immunosuppressive agents such as oral cyclosporine 60.46.42–46 polymyalgia rheumatica.67 or normal. The presence of cellular infiltrates around unaffected hair Direct clues for autoimmunity Humoral immunity Studies in the past with direct immunofluorescence have failed to show particular antibodies to epidermal cells or hair follicles in AA.38 Other studies have revealed an increased prevalence of gastric parietal cell antibodies and anti-smooth muscle antibodies in sera of patients with AA.39.63 Studies of passive transfer of serum from AA patients to nude mice failed to inhibit hair growth in grafted transplants of human scalp skin. In addition. tibodies to different hair follicle structures.22 Hair Loss: principles of diagnosis and management of alopecia patients.67 The dense peribulbar lymphocytic infiltrate affecting anagen follicles is one of the most consistent and reproducible immunologic abnormalities in AA. macrophages and Langerhans cells. as can be seen by the expression of DR antigens and IL-2 receptors. The antibody response to hair follicles in patients with AA has been found to be heterogeneous. as compared to only 44% of normal controls. The infiltrate is most prominent in active disease.40 diabetes mellitus. The implication of these observations is that there may be an immune response to antigens in the lower half of hair follicles or in the peribulbar blood vessels in AA.41 myasthenia gravis. may be correlated with the amount of hair loss.68 Friedmann40 suggested that the number of circulating T-cells is reduced in AA.65 In another study by Tobin et al. resulting in an increase in the ratio of helper to suppressor cells. and that the level of this reduction is related to disease severity.40 There are also reported associations of AA with pernicious anemia. Tobin and coworkers reported detection of antibodies to pigmented hair follicles by Western blotting in the sera of 100% of the AA patients examined. Circulating total numbers of T-lymphocytes have been reported as reduced40. Most of the T cells are activated. The infiltrate subsides in inactive disease and disappears in the regrowth phase. also known as autoimmune polyglandular syndrome Type 1(APS-1).66 much higher levels of autoantibodies to multiple structures of anagen hair follicles in AA patients have been reported. 51–55 and autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy. followed by the matrix.4. A slight increase in helper T-cells (CD4) and decrease in number of suppressor T-cells (CD8).64 However. The cellular infiltrate first becomes evident around the bulbar blood vessels.66 Cell-mediated immunity Studies of cell-mediated immunity in AA have given conflicting results.56–59 Thirty per cent of patients with APS-1 have AA.37. to a lesser extent. The most common target structures were the outer root sheath. because different patients develop different patterns of an- .48–50 lichen planus. particularly in the dermal papilla/capillary network. The T cell helper to suppressor ratio is 2:1– 4:1. he suggested that the impairment of helper T-cell function and the change in suppressor T-cell numbers may also reflect changes in disease activity.47 ulcerative colitis.

Tsuboi has shown that the CD8+ cells had disappeared completely from almost all portions of the hair follicle. antibodies to pigmented hair follicles. AA induction followed upon injection with CD8+ cells cultured with follicular homogenate.69 In order for a medical condition to fit as an autoimmune disease. The autoimmune response producing. an increase in the ratio of helper to suppressor cells. This leads to a cascade of immunologic events with increased interleukin-2 (IL-2). For AA. This may imply the greater importance of CD8+ in the expression of alopecia areata. many of the above criteria are indeed met.Alopecia areata 23 follicles suggests that the process precedes rather than results from injury to hair follicles. particularly CD8+ cells. This series of events helps to induce hair loss. These changes include hair loss. The necessity of the follicular homogenate to inducing AA suggests that T cells recognize a follicular auto-antigen. perifollicular T-cell infiltration. This is considered to be a Type 1 T helper cell response (Th ). In this study. such as Langerhans cells. They present the responsible epitope to the peribulbar lymphocytes. 1 . not following. Figure 2. high levels of autoantibodies to multiple structures of anagen hair follicles. An autoimmune response specifically associated with the disease 4. Furthermore. Unique antigens in the affected organ 2.69 reported that AA can be induced in human scalp explants from AA patients transplanted on to SCID mice by transfer of autologous Tlymphocytes isolated from involved scalp. HLA-DR and intercellular adhesion molecule-1 (ICAM1) expression of follicular epithelium. gamma interferon (γIFN) and intercellular adhesion molecules (ICAM). but not on injection of the cultured CD4+ cells. Gilhar69 and Tsuboi70 have shown that grafting affected scalp AA skin from humans on to SCID mice results in regrowth of hair. with the disappearance of the T cell infiltrate. Antigenpresenting cells. Increased frequency of hair-specific antibodies. The disease being transferred passively by autoantibodies or T cells. and induction of AA on SCID mice by transfer of T-lymphocytes cultured with follicular homogenates are evidence supporting the view that AA is an autoimmune disease targeting the hair follicle. Gilhar et al. the following criteria should be met: 1. This study also suggests that AA is mediated by T-cells. the condition 5.2 The pathogenesis of alopecia areata. Furthermore. An autoimmune response to that antigen 3. T-lymphocytes that had been cultured with hair follicle homogenate along with antigen-presenting cells and melanocytederived protein were capable of inducing the changes of AA.2 illustrates Figure 2. are increased in the bulb of the affected follicles. T-cells that had not been cultured with follicular homogenate were not able to induce AA. more recently. while CD4+ cells still remained in the upper portions of the hair follicle.

A recent theory for AA proposed by Paus et al. and perifollicular mast cells and macrophages. Acute psychotrauma before the onset of AA.75 but this has not been confirmed. Infection There has been a report regarding the possibility of cytomegalovirus (CMV) infection found within the patches of scalp AA. these cytokine profiles change. as other investigators have reported negative findings.34.73 T helper cells produce cytokines divided into two subgroups depending on the pattern of cytokine production. 2. Cytokines derived from epidermal keratinocytes.71 There is also a unique expression of follicular MHC class Ia/Ib. located exclusively in the distal outer root sheath. The cellular components of the hair follicle immune system are composed of intrafollicular T lymphocytes and Langerhans cells.76–78 The whole concept of molecular mimicry of the hair follicle with a virus is intriguing.74 Aberrant expression of cytokines of the Th1 type (see Figure 2.82 In contrast. since the inner root sheath and hair matrix do not express MHC class I molecules.80 higher prevalence of psychiatric disorders81 and psychosomatic factors in patients with AA have been reported.stimulating hormone. The hair follicle has a distinct immune system71 that differs from that of its surrounding skin.79–81 a higher number of stressful events in the 6 months of preceding hair loss. interleukins IL-1α. Emotional stress Several studies suggest that stress may be a precipitating factor in some cases of AA. but the evidence for a viral etiology of AA at this point in time is not conclusive.24 Hair Loss: principles of diagnosis and management of alopecia some of the immunologic cascade events that take place in alopecia areata. Type 1 T helper (Th1) cells produce interferon γ (IFN-γ) and IL- Intrinsically abnormal melanocytes or keratinocytes Morphological analysis of follicles in active AA lesions has revealed regressive changes in .83 Cytokines It appears that cytokines have a significant pathogenic role in AA.2) and IL-1β have been detected in affected areas of the scalp in patients with AA. Type 2 helper (Th2) cells produce IL-4 and IL-5. This initial report showed a convincing positive association with CMV. there are reports revealing that emotional stress does not play any role in the pathogenesis of AA. Cytokines are immunomodulators mediating inflammation and regulating cell proliferation.71 Human hair follicles may even serve as a Langerhans cell reservoir.72 involves the upregulation of MHC antigens and/or downregulation of locally produced immunosuppressants (melanocyte. and in vitro produce changes in hair follicle morphology similar to those in AA.73 As hair regrows with topical immunotherapy. leading to onset of AA. This immune privilege may collapse in alopecia areata. and ICAM1. allowing the immune system to recognize the immune-privileged hair follicle antigens. The epithelium of the proximal anagen hair follicle is immune-privileged. IL-1β and tumor necrosis factor-α (TNF-α) are potent inhibitors of hair follicle growth. adrenocorticotropin and transforming growth factor).

85 correspond well with the hypothesis of a sub-clinical condition of the disease in clinically normal areas of AA.90 In addition. AA can be induced in normal C3H/HeJ mice using full-thickness skin grafts from affected C3H/HeJ mice.94 The Smyth chicken model also has vitiligo. These same investigators95 noted that AA could be induced in 8–10 weeks by taking skin-draining lymph node cells from Neurological factors It has been suggested that local changes in the peripheral nervous system at the level of the dermal papilla or bulge region may play a role in the evolution of AA. 88. melanogenesis and the development of AA. who revealed a decrease in calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the scalps of patients with AA.87 This theory has been supported by Hordinksy et al.. to the entire scalp of two AA patients revealed an enhanced presence of SP in AA perifollicular nerves and induced vellus hair growth.3) and the Smyth chicken. .Alopecia areata 25 the hair bulbs of anagen hair follicles.95 AA developed 8–10 weeks after grafting.88 The neuropeptide CGRP has a potent anti-inflammatory action.88.92 the Dundee experimental bald rat (DEBR)93 (Figure 2.3 Alopecia areata animal models: the C3H/HeJ mouse and the DEBR rat. and may suggest a link between vitiligo. since the peripheral nervous system can deliver neuropeptides that modulate a range of inflammatory and proliferative processes. in outer root sheath of all hair follicles from non-balding lesions of AA. Also.89 and neuropeptide SP is capable of inducing hair growth in the mouse.85 Abnormal melanosomes in clinically normal regions. This evidence. including vacuolation.12). application of capsaicin. Recently. together with degenerative changes. Animal models with spontaneous AA include the C3H/HeJ mouse. investigations of AA have been facilitated by using animal models with either spontaneous or induced AA. together with the presence of antibodies to pigmented hairs of AA. Animal models Alopecia areata animal models In the past our understanding of the pathogenesis of AA was slow to progress owing to the lack of animal models for this disease. may explain some of the associated pigmentary anomalies seen clinically in acute AA and the preferential effect of AA on pigmented hairs (Figure 2.91 Figure 2.84–86 Abnormal melanogenesis and melanocytes are common findings. which causes neurogenic inflammation and releases SP. degeneration of pre-cortical keratinocytes has been shown in follicles of active AA lesions.

efficacy and side-effects of available or future treatments. an IL-2 inhibitor. differentiation and apoptosis within the hair follicle.101. Hox genes are involved in controlling the position. Non-alopecia areata animal models The hairless mouse has an autosomal recessive allelic mutation that maps to chromosome 14.103 This gene does not cause AA.97 The receptor arrangement of these cell clones may help identify targeted antigens in AA. whereas individuals may be genetically predisposed toward AA.102 These mice develop a normal pelage at about 14 days and then lose their hair over 1 week. However. FreyshmidtPaul has shown the efficacy of squaric acid dibutyl ester in the C3H/HeJ AA mouse. disease behavior. Lui et al.4 Diphencyprone was applied to half the C3H/ HeJ alopecia areata mouse. Recently investigations have correlated this hairless gene in mice with congenital atrichia in humans.4).5 T cell receptor (TCR) arrangement predominated. has some efficacy in the DEBR rat. The human hairless gene has been cloned to chromosome 8p12. Lymphocyte cells from C3H/HeJ AA mice were screened.96 A separate investigation on human AA by Tarlow et al.26 Hair Loss: principles of diagnosis and management of alopecia AA-affected mice and transferring them to normal-haired recipients. A region on mouse chromosome 6 may contain genes involved in inflammatory events associated with AA.99 have shown efficacy of diphenylcyclopropenone in the C3H/HeJ mouse (Figure 2. A preliminary study using C3H/HeJ mice examined potential chromosome locations that may contain genes involved in AA. showing significant regrowth on the treated portion of the mouse. this gene may have importance in maintaining hair follicle integrity by balancing cell proliferation. susceptibility genes are not enough to develop the condition. density and development of hair in vertebrate embryos. Animal models are now used in research for new and improved treatments.2/Jß2. Transgenic Hoxc13 defi- . have shown that leflunomide. 96 Three gene loci common to AA susceptibility were located.98 Shapiro et al.95 The ability to induce AA in a model suggests that. These human-animal correlations may have importance to understanding the mapping of the putative genes. AA induction can also be used to produce large numbers of mice for testing pharmaceutical agents. Figure 2. and T cell clones expressing a Vß8. This may eventually permit selective immune therapy using antiTCR antibodies or clonal vaccination treatments.32 identified the equivalent chromosome region 2p12–13 as being a location for AA susceptibility.100 Animal models with AA-like hair loss are significantly useful in investigations regarding pathogenesis.

the hair cycle is abnormal. The terminal to vellus ratio is decreased and even reversed by the increased numbers of miniaturized hairs.105 There are distinct stages in the histopathology of AA: (a) acute alopecia. Although clinical correlation is necessary.111 a decrease in follicular density and follicular miniaturization may be present.112 Mast cells were also noted in a small series of AA slides. resulting in marked increase in telogen and catagen hairs. (b) persistent alopecia. can be observed in horizontal sections of scalp biopsies109.104 Hoxc13 may play a significant role in follicular proliferation and differentiation.5). miniaturization of hairs. the involved follicle enters the end-stage telogen. trichotillomania and syphilitic alopecia. In patients with long-standing persistent alopecia. AA should be differentiated from androgenetic alopecia. Non-AA animal hair mutations may eventually help us to unravel the delicate mechanisms of the hair cycle and subsequently bring us closer to understanding the disordered hair follicle as it is found in AA. is appreciable (Figure 2. In androgenetic alopecia.108 Also. Following complete matrix failure. the involved hair follicles arrest in the end-stage telogen phase. (c) recovery.106 A peribulbar lymphocytic infiltrate (‘swarm of bees’) with no scarring is characteristic of the diagnosis of AA (Figure 2. In patients with complete recovery. In these cases. with patchy involvement. telogen effluvium. normal hair follicles with little or no peribulbar lymphocytic infiltration and no decrease in hair density are noted. both within the peribulbar infiltrate and the fibrous tracts. which in turn will allow us to understand the disordered follicle more clearly. Immunohistochemical evaluation of clinically normal AA specimens reveals a prominent expression of ICAM-1 in the dermal papilla and keratinocytes of the matrix and outer root sheath. with numerous fibrous tracts along with pigment incontinence within these fibrous tracts.115 Histopathologically. In . with hair follicles entering the telogen or late catagen stage prematurely in the involved areas. AA is not a localized process. During the acute phase of hair loss.107. Pathology In early active AA.Alopecia areata 27 cient mice were unable to synthesize hair keratins and have sparse brittle hair. this feature is helpful in diagnosis of AA in some biopsy specimens without peribulbar lymphocytic infiltrate. Inflammatory changes in the mid and upper dermis are generally not prominent unless many vellus hairs are affected by the disease.5e). miniaturization of hairs is present with lack of lymphoid infiltration at the level of the bulb and a lack of pigment incontinence within fibrous tracts.104 More knowledge of Hoxc13 expression in epidermal appendages will in turn provide further insight into the functioning of the normal ordered follicle.114 This shows that. peribulbar infiltration along with an increase in Langerhans cell numbers. matrix cell and matrical melanocyte failure with a formation of dysplastic hair shafts is noted.5). Eosinophils are also detectable in all stages of AA.110 (Figure 2.113 Electron-microscopic examination of microdissected hair follicles from AA scalps demonstrated ultrastructural abnormalities in the dermal papillae of both lesional and clinically normal hair follicles. A decreased anagen to telogen ratio. The inflammatory cellular infiltrate is composed chiefly of activated Tlymphocytes together with macrophages and Langerhans cells.

117 The prevalence of alopecia areata in the United States. miniaturization of follicles is not present. Syphilitic alopecia is very difficult to distinguish from AA. 117 AA affects men and women equally. was 0. while the presence of peribulbar eosinophils and lymphocytes strongly suggests AA.7%.28 Hair Loss: principles of diagnosis and management of alopecia telogen effluvium. trichomalacia and pigment casts in the follicular infundibulum. multiple catagen hairs.1 to 0. Presence of plasma cells along with no peribulbar eosinophils and abundant lymphocytes in the isthmus are features of syphilitic alopecia.116 Clinical features AA occurs all over the world.2 per cent of the population. as reported by the First National Health and Nutrition Examination Survey conducted from 1971 through 1974. Trichotillomania is characterized by empty anagen follicles.4 Patients are frequently quite .117 The lifetime risk has been estimated at 1. It accounts for about 2% of new dermatology outpatient attendances in the UK and the USA.

(e) The large number of telogen hairs in alopecia areata. totally bald. Alopecia areata can manifest with several different clinical features. because the distal segment is broader than the proximal end (Figure 2. smooth patch involving the scalp or any hair bearing area on the body (Figure 2. with one showing marked lymphocytic infiltration. The patch may have a mild peachy or pinkish-red color (Figure 2. long duration. Patients usually complain of abrupt hair loss and marked hair shedding.7). patients will present to the physician with one or several bags of hair. with an early-onset form associated with greater severity. and family history of the disease and a lateonset form characterized by milder severity. (b) Close-up the lymphocytic infiltrate. shorter duration. Hair loss is seen both as intact and as fractured hairs (Figure 2. The characteristic lesion of AA is commonly a round or oval. while the other does not. Colombe et al. and low family incidence.119 (Figure 2.Alopecia areata 29 Figure 2.8 suggest a bimodal pattern for AA. (c) Two follicles. David Shum and Martin Trotter. (d) Follicular stellae (ST) remnants in alopecia areata.7). (a) ‘Swarm of bees’ noted in the deep subcutaneous peribulbar area of the follicle. Sixty per cent of patients present with their first patch under the age of 20. but within the same follicular bundle.120 These hairs are described as ‘exclamation-mark’ hairs. (f) Reduction of follicular numbers in chronic alopecia areata. Frequently. . The intact hairs are dystrophic anagen or telogen hairs. (Courtesy of Drs Magda Martinka.7). not only on the same scalp. with matrix destruction.118. Almost all follicles within this field are telogen.5 Histopathology of alopecia areata. The fractured hairs develop owing to damage involving both cortex and medulla. This highlights the fact that AA is a very heterogeneous condition. resulting in distal fractures.7).) young.6).

6 Alopecia universalis for 1 year in a 3-yearold girl. . some patients describe paresthesias. burning sensation or pain. Although hair loss is usually asymptomatic in most cases. the following forms may be seen: alopecia areata: partial loss of scalp hair. ophiasis-bandlike AA—hair loss in temporo-occipital scalp. alopecia totalis: 100% loss of scalp hair. with mild to moderate pruritus. (c) Back view. They are prognostically and therapeutically distinguishable. The pull test may be positive at the margins of the patch. The clinical presentation of alopecia areata is subcategorized according to pattern or extent of the hair loss. If categorized by extent of involvement. longer duration. tenderness. ophiasis inversus (sisapho)119—a rare bandlike pattern of hair loss in fronto-parieto scalp (the exact opposite of ophiasis). too.121 and diffuse AA—a diffuse decrease in hair density over the entire scalp (Figure 2. (b) Side view. and eyelashes. and alopecia universalis: 100% loss of hair on scalp and body (Figure 2. before the appearance of the patches.8). If categorized according to pattern.30 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (a) Front view showing loss of hair on scalp. HLA studies suggest this early-onset group of severe AA patients are a genetically distinct group. reticular AA—reticulated pattern of patchy hair loss. the following forms are seen: patchy AA—round or oval patches of hair loss (most common). eyebrows. indicating very active disease. This early-onset form of AA is associated with greater severity. and greater probability of a positive family history of AA.9).

7 Alopecia areata circumscripta. This patient complained of burning on the patch before the hair fell out. Patients frequently present with just a patch. . (d) The color of an AA patch may be peach. (a) A single small circular patch. (c) The patch may be skin-colored with broken-off hairs. (f) The AA patch may be red. (e) Another peach-colored patch of AA.Alopecia areata 31 Figure 2. (b) A single large circular patch totally devoid of hair ‘bare as a baby’s bottom’.

. He has not had any other spots for over a decade. This is a patch on a 40-year-old male that has been present in the same place and has been the same size for 10 years.32 Hair Loss: principles of diagnosis and management of alopecia (g) Exclamation point hairs may be seen during an active phase of the condition.) (h) Circumscript patches can be very constant and persistent. (Courtesy of Dr Harvey Lui. (i) Simultaneous circumscript alopecia in mother and son.

(c) Ophiasis (d) Simultaneous ophiasis in mother and daughter. mimicking androgenetic alopecia. (b) Reticulated patches in AA.8 Clinical forms of AA based on pattern: (a) Patchy alopecia areata in multifocal areas. (e) Sisapho—the diametric opposite of ophiasis. . (f) Early diffuse A A with no distinct patches.Alopecia areata 33 Figure 2. (g) Advanced diffuse AA.

Changes may be seen in one. The reported incidence of onychodystrophy in AA ranges from 10 to 66%. (c) Alopecia universalis in an adult affecting all hairs on the body. (Figure 2.11). coincide or follow resolution of the AA.122 depending on how diligently it is looked for. affecting the limbs or the thorax area. Pitting with an irregular pattern or in organized transverse or longitudinal rows.34 Hair Loss: principles of diagnosis and management of alopecia Figure 2. Nail dystrophy may be associated with AA. The initial regrowth in AA is frequently white. there can be alopecia areata! Beard AA is very common. Beau’s lines (grooves through the nail matching that of the lunula’s margin). many or all the nails. onychorrhexis (superficial splitting of the nail extending to the free edge). and only the white hairs remain (Figure 2. Both regrowth in one site and extension of the alopecia on another site may be seen at the same time in the same patient.9 Clinical forms of AA based on extent: (a) Alopecia areata with its characteristic circular patches. Where there is hair.12). Any hair-bearing surface can be affected. trachyonychia (longitudinal striations resulting in sandpaper appearance). The dystrophy may precede.10 and 2. Frequently AA preferentially affects pigmented hair. Most patients present with the limited patchy type that is easily camouflaged. (b) Alopecia totalis affecting 100% of the scalp. including eyelashes and eyebrows. followed by repigmentation. as well as body AA. thinning or thickening .

(d) AA affecting the dorsa of the arms. (e) A A affecting just the lateral portion of the leg. (c) AA affecting the chest. (b) AA affecting one eyebrow.Alopecia areata 35 Figure 2. .10 Extracranial AA: (a) AA affecting just the eyelash.

(a) Random patches on the beard area.11 Alopecia areata of the beard is very common. The majority of patients will regrow their hair entirely within one year without treatment. but not affecting the great head of dreadlocks.36 Hair Loss: principles of diagnosis and management of alopecia Figure 2.13). Prognosis The only predictable thing about the progress of the AA is that it is unpredictable. koilonychia (concave dorsal nail plate). However. (pseudomycotic). punctate or transverse leukonychia and red spotted lunula may be associated with AA. (b) The characteristic peach color on an A A of the beard. The recovery from hair loss may be complete.123-128 (Figure 2. (c) Extensive AA of the beard. Patients usually present with several episodes of hair loss and hair regrowth during their lifetime. partial or non-existent. 7–10% . onychomadesis (onycholysis with nail loss).

82. vitiligo and alopecia areata.12 White hairs. nail dystrophy. Poor prognostic indicators are atopy. (d) White regrowth in an area of previous ophiasis.Alopecia areata 37 Figure 2. can eventually end up with the severe chronic form of the condition. the presence of other immune diseases. a young age of onset. The white hair regrowth proves the diagnosis had always been AA.129 . (a) Hair regrowth in a young child who had been diagnosed as a case of trichotillomania. (b) and (c) White regrowth on the side of the scalp. a positive family history of AA. extensive hair loss and ophiasis.

(f) AA and vitiligo in the same person. and purely telogen in telogen effluvium. In telogen effluvium. tinea capitis and pseudopelade (Figure 2. pressure-induced alopecia. (g) White moustache in a vitiliginous area in the patient illustrated in 12f. In tinea capitis. triangular temporal alopecia. However. hair loss is generalized over the whole scalp. usually. trichotillomania. Differential diagnosis Clinically. Patients with AGA usually demonstrate the typical predictable pattern of balding. Hairs that are shed are either telogen or dystrophic anagen in AA. whereas in AA it is usually patchy. The pull test is usually negative in AGA. sparing white hairs.14). there is an inflammatory component. traction alopecia. In trichotillomania and traction alopecia twisted and broken hairs are frequently evident. and shedding is not prominent. androgenetic alopecia (AGA). the differential diagnosis is usually between telogen effluvium.38 Hair Loss: principles of diagnosis and management of alopecia (e) Circumscript AA. non-inflammatory tinea .

and red-spotted lunula on the fingernails.13 Nail changes and alopecia areata. (a) Trachyonychia. (b) Red-spotted lunula on the toenails. (c) Koilonychia present in AA.Alopecia areata 39 Figure 2. (d) and (e) Severe nail dystrophy in AA. .

40 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (e) & (f) AA . (a) This is an early case of biopsy-proven diffuse AA which can be difficult to differentiate from telogen effluvium. (c) AA may be linear and mimic morphea. (d) Morphea mimicking AA.14 Differential diagnosis of AA. (b) Temporal triangular alopecia can mimic AA. It is crucial to look for the presence of follicular ostia. which may be difficult to see on a shiny smooth scalp.

Alopecia areata 41 mimicking AGA in a female patient. Note the loss of follicular ostia. which can easily mimic AA. (j) & (k) Pseudopelade mimicking AA. (i) Broken hairs in trichotillomania. (l) Post surgical pressureinduced alopecia can appear like AA. (g) Trichotillomania. . but usually has a significant scarred component to it. (h) Simulaneous trichotillomania in a mother and daughter.

There is a paucity of studies that distinguish AT/AU from patchy AA. mustard and black pepper. A biopsy may occasionally be necessary to distinguish TTA from AA.136 in the 1800s. the scalp may be so shiny and smooth that follicular ostia may be difficult to see. They cause blisters and erythema. there is usually some scarring with PIA. Pressure-induced alopecia131–134 (PIA) may also mimic AA. Half-head studies are very powerful. this does not mean that there are no effective treatments. There is great difficulty in evaluating the literature on treatment modalities for alopecia areata. the most common cause of tinea capitis is Microsporum canis.42 Hair Loss: principles of diagnosis and management of alopecia capitis may be most difficult to distinguish from AA. Although this may seem crude. as there is so much variability as to baseline patient populations and the terms ‘successful regrowth’ or ‘responders’. some of the fundamental principles in the treatment of AA remain unchanged. Usually the history of coma or surgery is present. Clinically. and there are no consistently reliable treatments. This lack of stratification of patient population can have a profound influence on evaluating therapeutic efficacy. While the FDA has never approved any drug for AA.11%. Histologically. wrote about AA and concluded that the application of a caustic substance with the subsequent production of bullae was often successful in the treatment of AA. See above for histologic differentiation of noncicatrizing alopecias. He advocated the use of ointments prepared with oil of mace. which does fluoresce.135 Diffuse AA can be especially difficult to diagnose clinically from other non-cicatrizing alopecias. Occasionally in AA. A KOH preparation and fungal culture may be necessary to distinguish noninflammatory tinea capitis from AA. A 4 mm punch biopsy may be necessary to make a definitive diagnosis in some cases. Most studies have grouped patients with alopecia totalis (AT) and alopecia universalis (AU) with those with just patchy alopecia areata (AA). Evaluating efficacy is most difficult. In order to prove efficacy with sufficient power and statistical significance. turpentine. the treatment of AA is very difficult. and an immunologic patient response to modify the perifollicular immunologic milieu. Bateman. large patient populations are necessary. In British Columbia. peribulbar lymphocytic infiltrates are not present. especially for patchy AA. some current treatment regimens have similar objectives. Look for the characteristic scaling in tinea capitis. but again. Treatment Modern therapy for AA is best appreciated within a historical framework. much of this published work has involved patient . Most published studies for AA have been small. Despite the advance of medicine over the last 200 years. and results can be skewed by this more difficult and severely affected population. as it is so unpredictable and frequently improves on its own. Temporal triangular alopecia (TTA) may mimic AA. and patchy AA may be difficult to differentiate from pseudopelade.130 This is ten times less frequent than AA. There is controversy as to whether the lesions are present at birth or acquired later in life. The lifetime incidence of TTA is 0. Woods light examination may help if the patient is in or has been in an area where the fluorescent tineas predominate. oval or lancet-shaped patch of non-scarring alopecia overlying the fronto-temporal suture. Lesions present as a triangular. There is no question that AT/AU is a distinct prognostic and therapeutic group. Unfortunately.

all results are skewed and will probably show ineffectiveness. with 5% minoxidil in 27% and with 5% minoxidil and 0.05% betamethasone dipropionate in 22%. This receptor is found to influence long-term. The terms ‘responder’ and ‘successful regrowth’ are not used in the same way from one study to another.141 halcinonide142 and dexamethasone in a penetration-enhancing vehicle have been reported to have some success. It is of paramount importance that dermatologists should be knowledgeable and conscious of this important segregation when evaluating modalities in the treatment of AA. and thus hormone binding to GCR. When comparing studies. some biochemical abnormalities relating to steroid chemistry have been discovered in AA patients by Sawaya and Hordinsky. and not curing the condition. topical immunotherapy. Corticosteroids The main mechanism of action is immunosuppression. slowgrowth cellular processes. facilitating collaboration. At present. anthralin. all treatments are palliative. topical. it is important to ascertain clearly what the authors have defined as a ‘responder’. only controlling the problem.143 Only one of these studies was performed in a double-blind controlled manner.137 These guidelines highlight the fact that AT and AU are considered a separate entity from AA. The Guidelines help us to evaluate what is ‘successful regrowth’. This suggests suppressed cellular transcription. It was found that low concentrations of calmodulin stimulate a cytosol kinase. and must be separated out in order to determine the efficacy of any trichogenic agent. Scalp biopsies from 15 untreated AA patients showed a twofold increase in unoccupied GCR. meaning being able to abandon one’s wig or cap. intralesional and systemic steroids. However. Otherwise. with 0. and the motivation level of the patient. owing to the chronic nature of AA. All local treatments may help the treated areas. Fiedler145 believes that a combination of 0. The new Alopecia Areata Investigational Assessment Guidelines are helpful in establishing criteria for selecting and assessing patients for clinical studies of AA.05% betamethasone dipropionate in 56%. minoxidil and photo-chemotherapy are available for the treatment of AA. Treatment guidelines for AA have been published by the American Academy of Dermatology. In addition. These abnormalities may explain why patients with AA show a varied response in hair area growth when treated with glucocorticoids.140. At the present time.Alopecia areata 43 populations with a preponderance of AT/AU. the age of the patient. She reports that quality of response in severe recalcitrant AA was fair to good after 16 weeks of treatment with placebo in 13%. and measuring the extent of scalp involvement.139 Topical corticosteroids Fluocinolone. any mode of treatment may require long periods of usage. Price and Khoury144 have not had success with topical steroids. .05% betamethasone dipropionate cream and minoxidil may be more beneficial than either alone. This suggests that patients with AA have abnormalities in type 2 GCR activation because of abnormal calcium-calmodulin metabolism. This suggests a synergistic benefit of using both modalities. but do not prevent further spread of the condition. Most dermatologists consider successful regrowth to be cosmetically acceptable regrowth.139 They showed that patients with AA have abnormalities in glucocorticoid receptors (GCR) for type 2 binding.138 All treatment plans for patients depend on three major factors: the extent of scalp involvement. comparison of data.

physician positioned at one end of the table and approaching with needle from the top of the patient. (c) Same patch after 2 months of injections. (d) Best position for injecting eyebrows: patient lying flat.15 Intralesional corticosteroid injections for AA. (a) Injecting triamcinolone acetonide 5 mg/ ml with a 3 ml syringe and a 30 gauge needle. (b) Patch of alopecia before injection.44 Hair Loss: principles of diagnosis and management of alopecia Figure 2. .

Shapiro149 prefers 5 mg/ml. Price. Treatments .0 mg/ml151 and Thiers152 prefers 3.151 and Thiers152 prefer triamcinolone acetonide.5 ml per eyebrow. Concentrations of triamcinolone ac- etonide vary from 2. intradermal corticosteroids remain the therapeutic standard. (g) Atrophy secondary to injection with triamcinolone acetonide 40 mg/ml. Injections are performed every 4 weeks. Intralesional corticosteroids Intralesional corticosteroid injection is first-line therapy for adult patients with less than 50% of scalp involvement. Whiting150 prefers 5–10 mg/ml. approximately 1 cm apart.3 mg/ ml.5–5.5–10. we inject a concentration of 5 mg/ml with a maximum total of 3 ml of triamcinolone acetonide.146 For circumscribed AA. Initial regrowth is often seen in 4–8 weeks.129 Whiting. for scalp A A.5 inch long 30-gauge needle as multiple intradermal injections of 0. Triamcinolone acetonide is administered with a 0. (f) Regrowth in eyebrow area after 4 weeks. with the next set in between areas of regrowth. Bergfeld prefers 2. A weaker concentration of 2.5 mg/ml for a total of 0.Alopecia areata 45 (e) Injection of eyebrows with triamcinolone 2.0 mg/ml diluted either in xylocaine or sterile saline.5 mg/ml is used for the beard area and the eyebrows. Price146 prefers 10mg/ml.1 ml per site.147 They are not indicated when more than 50% of the scalp is involved. At the University of British Columbia Hair Clinic. 146 Shapiro. which is at least 4–8 times what is recommended. Porter and Burton148 demonstrated response rates of 64% using triamcinolone acetonide and 97% using the less soluble and more atrophogenic triamcinolone hexacetonide.149 Mitchell and Krull.150 Bergfeld.

if there is no response. Abdulkareen et al.139 (Figure 2.154 recently showed success . and an extensive alopecic area can be treated in a shorter period of time. and atrophy can occur if the application is not followed by a local massage that spreads the steroid solution uniformly through the treated area. because of side-effects. The main sideeffect is minimal transient atrophy. The 27 gauge needles are large. They are not routinely used. (a) & (b) Striae in a patient with alopecia universalis who had been on systemic steroids for 1 year. Ferrando et al.16 The chronic use of systemic steroids for AA can have significant side-effects. but their use is controversial. One disadvantage is the needle calibre. After 6 months of treatment. too frequent. discontinue. and therefore likely to produce pain if the procedure is not performed gently.153 recently published a paper on the use of a multi-injection plate for intralesional corticosteroid injection of patchy AA. in that it permits the simultaneous injec- tion in 5–7 different points at a fixed distance. because these patients may lack adequate corticosteroid receptors in the scalp. With this method there is only one painful stimulus instead of five to seven. or too superficial (intraepidermal). leading to uniformity in treatment applications. This can be prevented by avoiding injections that are too great in volume per injected site. Topical anesthesia cream (2.16).46 Hair Loss: principles of diagnosis and management of alopecia Figure 2. this cream can be difficult to use on the hairy scalp. intralesional corticosteroids. are repeated every 4 to 6 weeks. and they do not alter the long-term prognosis (Figure 2. However. Systemic steroids Systemic corticosteroids are frequently effective in the treatment of AA. Children under 10 years of age are not usually treated with intralesional steroids owing to the local pain at the injection sites.5% lidocaine and 2.5% prilocaine in a cream) in a thick layer with occlusion 1 hour prior to injection can be used. This disposable device has some advantages.15).

Alopecia areata

47

with systemic steroids in 38% of patients with extensive patchy AA and AT/AU. However, in all patients, once the steroid was discontinued, the hair fell out. At the UBC Hair Clinic, we use systemic steroids only in exceptional cases. Winter et al.155 reported the occurrence of numerous side-effects such as striae, acne, obesity, cataracts and hypertension while using alternate-day prednisone. The authors concluded that alternateday prednisone does not appreciably alter the course of AA. Unger and Schemmer,156 however, believe that the initial administration of somewhat lower doses of prednisone, 30–40 mg/d, together with the use of topical and intralesional steroids, frequently yields good results while minimizing the risk of side-effects. Price146 feels that systemic corticosteroids may be indicated in select patients with progressive AA, either to slow progression or to initiate growth. For patients weighing more than 60 kg with active, extensive or rapidly spreading AA, she recommends prednisone 40 mg/day for 1 week, 35 mg/day for 1 week, 30 mg/day for 1 week, 25 mg/day for 1 week, 20 mg/day for 3 days, 15 mg/day for 3 days, 10 mg for 3 days and 5 mg for 3 days. She will use this regimen in combination with minoxidil 5% solution twice daily with or without intralesional corticosteroid injections every 4– 6 weeks. For active, less extensive AA, she uses prednisone 20 mg daily or every second day, which can be tapered slowly by decrements of 1 mg after the condition is stable. Whiting150 has found systemic steroids useful in reversing some cases of rapidly progressing alopecia that appear to be evolving into alopecia totalis. In adults, prednisone, 20–40 mg/d for 1–2 months may be necessary to control the hair loss. Reduction of the dosage after that depends on the patient’s progress. Whiting tries to maintain hair regrowth with the lowest possible dose

of prednisone, even if it is necessary to continue it for 6 months or until concomitant treatments such as minoxidil can take effect. Sharma et al. have used pulsed oral prednisolone at 300 mg once per month for a minimum of 4 months for patients with extensive patchy AA and AT/AU.157 They showed an initial response at 2.4 months and a 58% success rate for cosmetically acceptable regrowth after 4 months. They feel this treatment is safe on an outpatient basis. This study was uncontrolled. The long-term safety of this regimen has yet to be determined. Intramuscular corticosteroid therapy has a very high rate of recurrence, and as a result has very little to offer patients.158 Pulse therapy with intravenous methylprednisolone 250 mg twice daily for three successive days for rapidly progressive extensive multi-focal AA was found to be effective in controlling the active phase of hair loss. Twelve out of 20 with extensive patchy disease showed 50–100% regrowth after 12 months. This regimen was not effective for ophiasic AA or AT/AU.159 This study was not controlled, and a controlled-randomized study needs to be performed to confirm efficacy. The treatment of AA with systemic steroids is not recommended for children.

Minoxidil
Minoxidil is a biologic response-modifier that enhances hair growth. Minoxidil stimulates follicular DNA synthesis, has a direct effect on the proliferation and differentiation of follicular keratinocytes in vitro, and regulates hair physiology independently of blood flow influences.144,160 Minoxidil does not have an immunomodulatory effect. 161 Topical minoxidil 5% solution is the most effective concentration compared to other lower con-

48

Hair Loss: principles of diagnosis and management of alopecia

Figure 2.17 The use of minoxidil and topical betamethasone dipropionate. (a) 4-year-old patient with a 2year history of AA. (b) After 8 months of treatment there was cosmetically acceptable regrowth. It is difficult to know if this was truly the effect of therapy or spontaneous regrowth.

centrations.162–166 There clearly is a dose-response effect.162–166 Cosmetically acceptable hair regrowth using topical 5% minoxidil solution has been shown in approximately 40% in patients, with 20–99% scalp involvement after one year.163 More successful results are seen in less severe cases of the disease. This treatment should not be expected to be effective in patients with alopecia totalis/ universalis.163 At the University of British Columbia Hair Clinic only the extrastrength topical minoxidil 5% solution is used for patchy AA. It must be applied twice daily. Initial hair regrowth is usually seen after 12 weeks. The response is usually maximized at 1 year. It must be continued until remission occurs. It can be used on the scalp and eyebrows. It can also be used on the beard area in men. There are negative studies with topical minoxidil.167–169 However, all these studies did not maximize on the 5% solution. More im-

portant, the vast majority of patients within these studies had AT/AU. One would not expect efficacy with topical 5% minoxidil solution in this difficult sub-population. The efficacy of minoxidil solution can be enhanced with anthralin170 or betamethasone dipropionate.145 In combination with topical minoxidil, anthralin is applied 2 hours after the second minoxidil application. Betamethasone dipropionate cream is applied twice daily, 30 minutes after each use of minoxidil (Figure 2.17). Although combination therapy has been found to be more effective than monotherapy, this therapy is not effective in patients with alopecia totalis/ universalis. Side-effects of minoxidil are rare. These include local irritation, allergic contact dermatitis and facial hair growth (Figure 2.18), which tends to diminish with continued treatment. Systemic absorption is minimal.146

Alopecia areata

49

Figure 2.18 Hypertrichosis with topical minoxidil solution. (a), (b) 5-year-old boy who had used topical 5% minoxidil solution for over 6 months. There is marked symmetrical hypertrichosis on the forehead and cheeks.

Anthralin
Anthralin may have a non-specific immunomodulating effect (anti-Langerhans cell), as it does in psoriasis.171 Clinical irritation is not necessary for efficacy, just as clinical irritation is not necessary in psoriasis. There are citations in the literature that suggest that skin irritants are not effective in AA.172,173 Cosmetically acceptable regrowth has been reported to vary from 20% to 25% for patchy AA.174 Schmoekel et al.175 have shown with photographs that anthralin has benefit in a half-head study and is effective for patchy AA. Anthralin 0.5%–1.0% cream is applied once daily.146,147,149,174 Short-contact therapy is preferred. It is left on 20–30 minutes daily for 2 weeks, and then 45 minutes daily for 2 weeks, up to a maximum of 1 hour daily. It is

not to be used on the eyebrows or the beard area. Some patients may tolerate overnight therapy.146 When therapy is effective, new hair growth is usually seen within 3 months. It may take 24 or more weeks for a cosmetically acceptable response. Because of its good safety profile, anthralin is a good choice for children. Combination therapy with minoxidil may have a synergistic effect, as was mentioned above.170 Nelson and Speilvogel report a negative study with anthralin.176 However, AT/AU patients were grouped in with patchy AA in this small study of 10 people—it is not specified how many AT/AU. It is unlikely that anthralin has as much efficacy, if any, in AT/AU as it does in patchy AA. Side-effects of anthralin are irritation, scaling, folliculitis, and regional lymphadenopathy. Patients are cautioned to avoid getting

50 Hair Loss: principles of diagnosis and management of alopecia .

(e) Unilateral preferential regrowth of hair with anthralin on the C3H/ HeJ mouse on the treated half.19 Anthralin for alopecia areata. left side.100 It has been suggested that the immunogen may attract a new population of T cells into the treated area of the scalp that could eliminate the antigenic stimulus present in AA.181 Concerns have been raised about the safety of DNCB. The mechanism of action of topical immunotherapy is unclear. Dinitrochlorobenzene Rosenberg and Drake178 first reported regrowth of hair in two patients following application of DNCB. There was clearly unilateral preference for the treated side. (f) Marked redness can occur from anthralin. but their safety profile is unacceptable to most dermatologists. untreated side. (c) 4 months of treatment: left (treated) side showing regrowth. Careful dissection of the mechanism by which contact dermatitis is able to suppress alopecia areata is important. Kratka et al.99. The issue of DNCB safety is controversial. anthralin into the eyes. and serum half life is 4 hours.19). (a) 27-year-old female with AA for 8 months.177 and a shift in the position of the T-lymphocytes away from perifollicular areas to the interfollicular area and dermis.182 Stobel and Rohrborn183 and Summer and Goggelman184 found DNCB to be mutagenic in Salmonella typhimurium in the bacterial plate incorporation assay (Ames assay).180. squaric acid dibutyl ester (SADBE) and diphenylcyclopropenone (DPCP). and thus allow hair to regrow. Three contact sensitizers have been used extensively in alopecia areata—dinitrochlorobenzene (DNCB). Excretion is primarily renal. 178 Happle has proposed the concept of antigenic competition. because it may be possible in the future to mimic the effect on the dermatitis by providing specific cytokines or specific inhibitors of cytokines. Baseline.. right side. and to be aware of staining of the treated skin.185 found DNCB to Topical immunotherapy Topical immunotherapy is the most effective therapeutic modality with the best safety profile in the treatment of chronic severe AA. a decrease in the peri-bulbar CD4+/CD8+ lymphocyte ratio. but less than the treated side. Therefore. Immunogens may interfere with the initial or continued production of proinflammatory cytokines by the follicular keratinocytes. with 53% recoverable in the urine. Weisburger et al. to protect treated skin against sun exposure. treated with anthralin 1 % cream for 1 hour daily. The overall efficacy of DNCB treatment for AA has been investigated and has varied from 25% to 89%.Alopecia areata 51 Figure 2. (b) Baseline.179 This theory presumes that the generation of T-suppressor cells into the area may exert a non-specific inhibitory effect on the autoimmune reaction to the hair-associated antigen. The immunomodulating effect of the topical sensitizers is supported by . Systemic steroids may be the most effective modality. DNCB is rapidly absorbed after topical application. clothes and linens (Figure 2. (d) 4 months of treatment: right (untreated) side showing regrowth. extreme caution must be used with DNCB.

202 showed a response rate (on 139 patients) of 50. Caserio190 showed a success rate of 28% (4/14 cases). In 3/107.201 Efficacy in alopecia has varied from study to study. Diphenylcyclopropenone Diphenylcyclopropenone (DPCP) has been used not only in the treatment of alopecia areata. 188 found SADBE to be effective in 4/8 cases. and thus inhibits induction and elicitation of allergic contact dermatitis.193 reported a 68% (13/19) success rate in a half-head study. 30 relapsed and were resistant to further therapy. SADBE has been shown to be Amesassaynegative.199 It is an ideal immunogen in that it is a strong topical sensitizer. resulting in loss of all regrown hair. This would clearly affect any benefits of a contact allergen. Tosti et al.197 used SADBE in combination with PUVA on three patients and did not find increased efficacy with combined treatment.192 showed a 49% success rate in 73 cases with over 50% scalp involvement. . Orecchia194 has used SADBE in children under 13 and showed a 32% (9/28) chance of cosmetically acceptable regrowth. equaling that of control animals. Giannetti and Orecchia191 reported a good response in 5/26 cases. In 8/ 107. but also as an immunomodulator in the treatment of melanoma200 and warts. with the effect of an efferent lymphatic blockade. Tolerance can sometimes be reversed with cimetidine 300 mg orally three times a day for 3–4 weeks. with an initial success rate of 30% (10/33). Micali et al. Van der Steen et al. The purity of DNCB samples is also an issue. This phenomenon is known as castling.0% was reached without producing an adequate dermatitis. No mutagenic contaminants were detected on gas chromatography-mass spectrometry. a tolerance phenomenon was seen.196 showed only minimal signs of terminal hair regrowth in 3/17 patients and do not recommend the use of SADBE in AA. lifetime subcutaneous injections of squaric acid into ICR/Ha Swiss mice resulted in a low incidence of tumors at the injection site.198 Furthermore. Case et al. is not found in the natural environment and does not react with other chemicals. a paradoxical regrowth of hair on the untreated side of the scalp was seen.129 Squaric Acid Dibutyl Ester Happle achieved good results in 70% of patients treated with topical squaric acid dibutyl ester (SADBE). 187 Flowers et al. PUVA also results in a systemic immuno-suppression through direct or indirect (via interleukin-1) stimulation of prostaglandins (PGE2). Barth et al. Chua et al. defined as a required continuous increase in DPCP concentration until a concentration of 2. with excellent or satisfactory results. Orecchia et al. Certain chloronitrobenzenes that are known mutagens are possible contaminants in preparations of DNCB. adenopathy. Two-thirds of the initial responders no longer responded to the SADBE. Of 107 who showed a unilateral response. is used only rarely in industry. auto-eczematization.189 showed excellent responses in 11/26 (52%) of cases.195 also treated children. with subsequent relapses over the long term. PUVA impairs Langerhans cells.52 Hair Loss: principles of diagnosis and management of alopecia be non-carcinogenic when fed in large doses to mice and rats up to 4 months. urticaria and tolerance. However.186 Side-effects of DNCB include a marked blistering reaction. it loses its stability in the presence of water.4%. They concluded that the two associated therapies showed an impaired efficacy because of the inhibition of the SADBE action by PUVA.

216 or that a pharmaceutical chemist do high-pressure liquid chromatography on the DPCP sample to ensure that there are no detectable amounts of this dibromoketone compound. A cosmetically acceptable endpoint was obtained in 17. with 33% showing complete regrowth. Ashworth et al.6% showed a response. Berth-Jones and Hutchinson213 showed only an 18% response rate over 6 months. Gordon et al. The authors felt that eliciting an allergic reaction was an integral part of successful treatment resulting in hair growth. Pericin208 showed that in 68 patients.219 It is therefore recommended that all DPCP samples be purified as described by van der Steen et al. that is positive in the Ames test. with no significant difference in response with inosine pranobex (inosiplex). Factors affecting response were clearly extent of condition and age of onset. This fits well with Colombe et al’s8 data that this group is a distinct sub-population of AA. 60. It appears those with AT/ AU and an early age of onset are prognostically a separate group. although 53% developed patchy alopecia and 10% lost all hair that had re-grown. MacDonald-Hull et al. showed efficacy in only 1/26. Duration of condition.5 ml of a 1% solution of diphencyprone to the scalp of 18 patients under treatment for alopecia areata revealed no detectable amounts of diphencyprone in any sample of serum or urine from these subjects. Regarding children. the presence of atopy and nail changes were not correlated to response. the appearance of the scalp 6 months later was cosmetically acceptable. They found that 7 of 19 (37%) showed no hair loss after treatment had been stopped for 6 months.211. and 100% of subjects with 25–49% hair loss.9%.205 reported further results with DPCP on a larger series of patients. Using the survival analysis model. A lag period of 3 months was present between initiation of therapy and detection of the first clinical response. DPCP is degradable upon exposure to light.206 utilized Kaplan-Meier survival analysis to determine cosmetically acceptable regrowth over time and a cox regression model to determine factors predictive of regrowth in the largest series to date of 148 AA patients.216 Analysis on serum and urine samples following application of at least 0.215 treated 12 children aged 5–15 years. MacDonald Hull et al. DPCP is not mutagenic in the Ames test. 70. 25 (32%) showed complete regrowth of hair.3% of subjects with 75–99% hair loss. dibromoketone. and teratogenicity and organ toxicity could not be detected in the hen’s egg test or in the mouse teratogenicity test. 88. Shapiro et al. the cumulative patient response at 32 months was 77.217 Commercial DPCP may contain a precursor. The only prognostic indicator correlated with response was extent of the condition. Orecchia and Rabiossi212 also had a success rate of 1/26.4% of subjects with 100% hair loss. These data suggest that diphencyprone is not absorbed following application to the skin.1% of subjects with 50–74% hair loss.Alopecia areata 53 MacDonald-Hull and Norris203 reported 29% (8/28) of patients had a cosmetically acceptable result. Monk209 showed cosmetically acceptable results in 33% (6/18). In 1991.9%. Of 78 patients. with complete regrowth in 30.207 showed that 38% of 48 patients responded to DPCP with cosmetically acceptable regrowth. Wiseman et al. MacDonald-Hull and Cunliffe204 studied post-therapy relapse rates within 6 months after treatment.218. Those patients with a younger age of onset are less likely to respond.210 showed satisfactory regrowth in 24% (11/45). In 68%. and must be stored . Six months after treatment was discontinued three of the four children with complete regrowth maintained their hair.214 showed that topical 5% minoxidil solution combined with DPCP showed no benefit over DPCP alone. Hatzis et al.

0%.20 Topical immunotherapy for alopecia areata.54 Hair Loss: principles of diagnosis and management of alopecia Figure 2.0001–2. (e) The physician or nurse must wear gloves when . (d) The cotton is wound around the stick to make a reinforced swab approximately three times the thickness of an average cotton-tipped applicator. (b) Intermediate concentrations may be necessary. (a) Standard diphencyprone (DPCP) tray concentrations varying from 0. (c) DPCP is stored away from the clinic in the fridge in a plastic container.

(i) and (j) One coat is painted is the anteroposterior direction.Alopecia areata 55 handling the bottles. k. an eyedropper is used to saturate the swab. (g) Cotton swab is dipped directly into the bottle. Another coat is painted in the lateral direction. . gloves must be removed carefully from the inside out. Only unilateral application is performed until hair regrowth is seen on one side. If the swab needs to be remoistened. (f) After the application. (h) An area that has been sensitized one week before with a 2% solution.

Scalp/hair should not be washed in the 48 hours following treatment. Patients must be warned that the induction of an allergic contact dermatitis is a desired side-effect. DPCP is compounded in an acetone base and stored in opaque bottles to protect the solution from photodegradation.01%. the use of a barrier cream and double gloving is helpful. As Peret and Happle220.20). 1. to eradicate all traces of the DPCP. 0. because of the risk of sensitization of staff administering the treatment. All the screw-top lid bottles of DPCP are stored in a large plastic bin with a lid to prevent both accidental spillage and inadvertent staff sensitization.05% and 0. The .222 The DPCP solution is applied to the scalp using a thick cotton swab that has been dipped into the bottle. patients should be thoroughly informed about the experimental character of the treatment. The scalp must be protected from all sources of light. 0. 4. We use DPCP on patients with less than 50% hair loss only if all other modalities have failed. At the University of British Columbia. The patient is encouraged to meet with and observe other patients undergoing treatment. because we have found that the shelf life after opening is approximately 6 months. If the swab needs to be remoistened. A low-potency topical corticosteroid is given to the patient for mild inflammatory reactions post-treatment. We periodically check the DPCP for purity with high-pressure liquid chromatography. The standard DPCP tray for AA includes the following concentrations: 0. or topical anthralin. A local ethics committee should be asked for consent. Intermediate concentrations may be necessary. 0. There is a report in the literature where DPCP treatment had to be abandoned in a clinic owing to the large number of staff becoming sensitized to DPCP. topical minoxidil 5% solution in combination with topical corticosteroids. Gloves must be worn and caution used to prevent the DPCP from coming in contact with the skin of the staff member. Safety precautions must be implemented when handling DPCP. it has occasionally been necessary to use 0. and the possible failure to respond.25% strengths for sensitive patients.1% to 1. DPCP is dissolved in acetone and stored away from the staff in the fridge in a special container.221 suggest.5% solution of DPCP (Figure 2. These swabs are constructed with long wooden applicator sticks and cotton balls. 3. The transition from 0. and one that is necessary for a good result. A commitment is made to return for weekly treatments for at least 24 weeks. risks and benefits are carefully reviewed with all patients and an informed consent is signed. the possible side-effects. 0. All bottles are dated on first use. For adults with more than 50% scalp hair loss.1%. If the person administering the DPCP develops eczema.0% is best bridged with a 0. DPCP is used at the University of British Columbia Hair Clinic as follows: Prior to commencing treatment. 2. The physician must be notified of severe reactions. an eye-dropper is used to saturate the swab and prevent contamination. such as intralesional corticosteroids. Spills should be wiped up immediately using a dry towel.0% and 2%. the lack of sufficient toxicologic data. followed by a moist towel.56 Hair Loss: principles of diagnosis and management of alopecia in amber bottles.0001%. topical immunotherapy with DPCP is our treatment of choice at the University of British Columbia Hair Clinic. Post-treatment guidelines for the patient include: 1. The wearing of a hairpiece or scarf is sufficient.001%.5%. the chance for regrowth. Although not routinely used. A gown covering the arms should be worn and laundered after each treatment session.

. (d) 30 weeks of treatment of the left side and 6 weeks on the contralateral side. (e) 1 year of treatment.Alopecia areata 57 Figure 2. (c) 24 weeks of unilateral treatment. (a) baseline.21 40-year-old female with an 18-year history of alopecia involving 99% of the scalp. (f) 5 years of intermittent treatment. (b) 12 weeks of unilateral DPCP treatment.

(c) 24 weeks of DPCP treatment.58 Hair Loss: principles of diagnosis and management of alopecia Figure 2.22 Ophiasis in a 43-year-old female of 2 years’ duration. If there is a marked reaction. (b) 12 weeks of DPCP treatment. cotton is wound around the stick to make a firm swab approximately three times the thickness of an average cotton-tipped applicator (Figure 2. because severe reactions can discourage the patient and preciptate discontinuation of treatment.0001% solution is applied to half the scalp. Once the patient commits to DPCP treatment. (a) baseline. The nape of the neck is a very sensitive area that will react when other parts of the scalp do not. Patients return for weekly visits until hair growth is established. After 1 week. If this area becomes irritated.20). We avoid application on to the nape of the neck. Cotton-tipped applicators do not retain enough moisture to paint the scalp adequately. an initial sensitizing dose of 2% DPCP is administered to a 4×4 cm circular area on the occipital region of the scalp. showing some white regrowth. The patient must protect the scalp from light with a cap. Titration must be conducted carefully. DPCP is left on the scalp for 48 hours and then washed off. Two coats are applied. . a 0. if no reaction or only a mild to moderate reaction is observed. it is difficult for the patient to continue wearing a hairpiece. the first coat in an anteroposterior direction and the second coat in a lateral direction. as well as the area where the tape for the hairpiece is applied. we do not apply any solution until the following week. This can be confusing when attempting to titrate the patient to the correct dosage.

These refractory areas can be injected once monthly. .05%.0%. It is better to be cautious than to be very aggressive and cause a severe reaction. 1. Each week when the patient returns. Once hair growth is established one one side.0%). as DPCP is degraded when exposed to light. DPCP is applied weekly for 3 weeks out of every month. Concentrations vary (0.0001%. The patient had been treated unilaterally for 6 months without a response. The aim is to maintain erythema and pruritus. or a low tolerable eczema. on the treated side for 36–48 hours after application. 0. DPCP is reapplied to the same half of the scalp.5%. 2.1%.Alopecia areata 59 wig or scarf during this period of time. It is important to listen to your patients.01%. with full regrowth. 0. 0. (b) Both sides were then subsequently treated. showing circular areas refractory to treatment. The following week. The tolerance to the discomfort from the eczema varies with patients. The concentration is adjusted individually on the basis of the severity of the previous reaction.001%.24 Delayed DPCP response. 0. (a) She returned to the clinic after treatment had been discontinued for 6 months with a unilateral response on the treated side. Intralesional corticosteroid is injected once monthly. Figure 2. the severity of reaction and the presence of any hair growth are assessed.20).23 Unilateral treatment with DPCP. Figure 2. 0. the other side is treated (see Figure 2.

(c) Complete regrowth with treatment. Eyes are well shielded. This reaction is too strong. (b) Marked bulla formation is possible. (a) Unilateral eczematous response one week after application. Figure 2. No application for 1 full week with a lower concentration applied the following week.25 Treatment of eyebrows with DPCP. (b) Baseline before treatment in a 40-year-old female with no eyebrows for 18 years.26 Eczematous eruptions from DPCP.60 Hair Loss: principles of diagnosis and management of alopecia Figure 2. . (a) Position used to apply DPCP to eyebrows.

(d). (f) Frontal unilateral edema and eczema.Alopecia areata 61 (c). (g) Contact dermatitis to remote areas.(e) The neck area is a common area for a bad reaction. .

27 Lymphadenopathy occurs in 100% of patients.62 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (c) Hypo. with most pigmentary changes resolved. Figure 2.and hyperpigmentation in an African-American patient. .28 Pigmentary changes with DPCP: (a) Hypo. (d) Vitiligo on the back of the neck. (b) The same patient.and hyperpigmentation (‘dychromia in confetti’) after 24 weeks of treatment in an East Indian patient.

Maintenance requirements vary with individuals and commonly range from biweekly to bimonthly treatments. then every third week for 4 weeks. and so on. it is difficult to get them to resume therapy. Once full regrowth has occurred (Figures 2. Vitiliginous patches on areas remote to the scalp. One patient was able to discontinue treatments for 4 years before she experienced any hair loss. The requirement for (e) Vitilgo on half of the scalp in a patient who had been applying DPCP at home. (f). (h).Alopecia areata 63 If patients have discontinued treatment because of intolerable effects.21 and 2.22). The strength can always be increased later when the patient becomes familiarized with the treatments. . the frequency of treatment is gradually reduced. (g). This reduction of visits continues until the patient experiences some hair loss and establishes the maintenance requirement. using the rule of four: treatment is adminstered every other week for 4 weeks.

Photochemotherapy (PUVA) The mechanism of action of PUVA on AA is believed to be a photoimmunologic action. Vitiligo is more common in AA patients. Pigment changes (Figure 2. and the swab should be minimally moist. All female patients are counselled to use reliable birth control while on DPCP.223 severe blistering and lymphadenopathy (Figure 2. . six women have become pregnant while on DPCP therapy. Treatments are administered two to three times a week. The psoralen is administered either topically or orally. and discontinue treatment.223 Shah et al. DPCP has been used with success to treat eyebrows. DPCP is contraindicated in pregnancy.27) in the neck behind the ears. after the scalp has been treated (see Figure 2. and possibly inhibit local immunologic attack against the hair follicle by depleting Langerhans cells. such as hyperpigmentation. we do not ever give DPCP to the patient for self-application. and because vitiligo has a tendency to koebnerize on to inflamed skin.24). we consider the patient unlikely to respond. one must be very cautious about rapid extension of vitiligo in an AA patient who already has the condition. The process of complete regrowth is lengthy. If the patient has not responded by 52 weeks. The patient should be lying flat.26). and is followed in 1 hour or 2 hours with UVA irradiation. Side-effects include eczema (Figure 2. However.234 It may effect T cell function and antigen presentation.23). and we may abandon topical immunotherapy and proceed to another modality of therapy. and usually respond well (see Figure 2. although teratogenicity has not been demonstrated. Contact urticaria. Consort dermatitis to spouse/partner has also been reported. We have had a few patients that we identify as ‘slow growers’. most of the scalp regrows hair except for a few small areas refractory to DPCP. DPCP therapy was immediately halted once our clinic was informed. with gradual new growth in multiple areas.64 Hair Loss: principles of diagnosis and management of alopecia maintenance therapy illustrates the palliative nature of the treatment. At our clinic.231 severe dermographism. autoeczematization.25). Vitiligo is a relative contraindication for treatment with topical immunogens. Upon recommencing treatment. They consistently grow new hair in more areas and do not seem to lose hair. despite all the warnings on the informed consent form. Burns are more likely to occur with topical therapy.224 a combination of both referred to as ‘dyschromia in confetti’225 and vitiligo226–229 have been reported. 230. Regrowth of hair will take at least 12 weeks. we have had patients that have taken 41 weeks to see unilateral regrowth. Extreme caution should be exercised when treating patients of dark pigmentation. These patients initially do not respond. but ocular toxicity is avoided.28). All six pregnancies have produced normal children. These resistant areas are treated with intralesional triamcinolone acetonide 5 mg/ml once monthly. This is best done at the end of the treatment. Another phenomenon we have seen is the ‘initial non-responder’. hypopigmentation. Extreme caution must be used. Because of the possible side-effects. In certain responders.222 report the risk to medical and nursing staff. the eyes shielded with gauze. growth was obtained (Figure 2. 232 and erythema multiforme233 have also been reported. with gradual increase in UVA dosage. a small number of individuals have returned with hair growth only on the orginally treated side. 234 (see Figure 2. Within 2 years of stopping treatment.29).

Mean total UVA exposure for responders was 171.29 PUVA therapy in alopecia areata: a 22-year-old patient with extensive alopecia affecting 95% of his scalp for 2 years. the high recurrence rate following .3%) and good regrowth in 2/22 (9%).1% 8-methoxypsoralen (8-MOP) and UVA and showed excellent regrowth in 8/ 22 (36. 240 together with the need for long-term therapy in AA.60. including melanoma.30).239 Today’s concern about PUVA and its promotion of all types of skin cancer.1 joules/cm2. He was unresponsive to 24 weeks of topical immunotherapy with DPCP.238. There was a response rate of almost 50% in each group. Almost all the patients available for follow-up experienced relapse when PUVA was tapered. with median time to relapse being 10 weeks. (a) Baseline before PUVA. Mitchell and Douglas234 used a combination of topical 0. owing to the side-effect profile. Claudy and Gagnaire 235 used systemic PUVA with total body irradiation and showed a success of rate of 70%. Larko and Swanbeck236 studied 40 patients with systemic PUVA.61 (Figure 2.Alopecia areata 65 Figure 2. Cyclosporin Systemic cyclosporin has been shown to have some benefit in AA.237 studied 41 patients with oral 8-MOP and whole body irradiation. As with systemic corticosteroids. Relapses were frequent. comparing whole body irradiation and scalp irradiation only. and local 8-MOP plus local UVA irradiation. Thirty-five percent experienced hair regrowth. (b) After 1 year of PUVA. Lassus et al. but only 20% experienced a full regrowth. make PUVA therapy less than satisfactory. No significant differences were seen. with a mean total number of treatments of 47. Only 10% relapsed after 6–12 months. Whole body treatment did not produce significantly better hair growth. He still has refractory patches that are amenable to intralesional corticosteroid therapy. The major problem with PUVA therapy is the high relapse rate that frequently sets in after tapering the treatment.

The dermatologist should first discuss all therapeutic options and outcomes.66 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (c) 3 months of systemic cyclosporin (4 mg/kg/day) and prednisone 5 mg/day.242 could not prove any cosmetic benefit from topical cyclosporin with concentrations of 10%. (b) A 28-year-old male with alopecia universalis for 2 years. extent of alopecia and motivation for treatment. this treatment is simply not practical in AA. (a) Mechanism of action by inhibiting the Th response to the 1 hair follicle. the long treatment periods and the inability to change the ultimate prognosis of the disease. Gilhar et al. Treatment plan Therapeutic selection for AA depends on patient age. The patient had to discontinue therapy owing to serum transaminase changes and cholesterol elevation. discontinuation of the treatment. al- .30 Cyclosporin in alopecia areata. (d) 5 months of therapy.241 and De Prost et al.

most of our patients are well-motivated and want treatment. Topical therapies with minoxidil. lowing the patient to become an active member of the therapeutic team.31 University of California at San Francisco-University of British Columbia Treatment protocol for alopecia areata (permission granted by Drs Jerry Shapiro. For those with less than 50% scalp hair loss. If there is no response after 3–4 months.31). we will add a minoxidil 5% solution twice daily and a superpotent corticoster- . Patients are divided into those less than 10 years of age and those over 10 years of age. A practical treatment algorithm for the treatment of AA is the University of California. Vera H. Firstly. San Francisco—University of British Columbia Alopecia Areata Treatment Protocol (see Figure 2. while in adults other options to be considered include intralesional corticosteroids or immunotherapy. Pa- tients over 10 are then subdivided into those with less than 50% scalp hair loss and those with more than 50% scalp hair loss. the following options are offered. and Harvey Lui).Price. we always offer the patient the option of no treatment. corticosteroids and anthralin are considered in children of less than 10 years of age. as many AA patients will regrow their hair without treatment. However. First-line therapy for scalp AA is intralesional corticosteroid injections into the alopecic patches.Alopecia areata 67 Figure 2.

If there is no response by 52 weeks.33) can give the AA .0% cream applied for up to 1 hour daily combined with topical minoxidil 5% solution applied twice daily. (c) Net meshes that are typical.32).68 Hair Loss: principles of diagnosis and management of alopecia Figure 2. oid cream such as clobetasol propionate applied 30 minutes after the minoxidil in addition to the monthly injections. If there is no benefit. and cool and allow air to circulate (see Figure 2. our first line is topical immunotherapy with DPCP. topical immunotherapy is discontinued. minoxidil 5% solution. Use of eyeliner or alopecia masking lotion (Figure 2. (a) A lining that will allow one’s own natural hair to be pulled through. another option is short-contact anthralin therapy with anthralin 1. For those patients with more than 50% scalp involvement. (b). It should be emphasized to the patient that a prosthesis does not imply permanent hair loss.32 Scalp prostheses come with different linings that are light and allow air to circulate. short-contact anthralin and superpotent topical steroids. A scalp prosthesis should be available to all patients with more than 50% scalp involvement. Scalp prostheses come in an assortment of net linings that are light. Other options that can be offered to the patient are systemic PUVA. and can give great satisfaction to a majority of patients. but having one on hand is comforting for episodes of extensive hair loss.

In those younger than 10 years intralesional corticosteroids are avoided and topical immunotherapy is not implemented. (a) The patient is a 23-year-old who likes his hair short. Those older than 10 years are treated with the same protocols as adults. He has a small patch of alopecia areata. Physicians need to take the time to address the psychological needs of their patients. For some patients. exploring the impact of alopecia on the patient’s emotional . Children: Therapeutic modality choices depend upon patient age.195 For those under 10 years of age. The ultimate therapeutic plan is developed through team interaction between the patient. therapeutic options include minoxidil alone or in combination with a mid-potency topical corticosteroid or anthralin.34 Dermatography: a semi-permanent tattoo for the eyebrows.34). Dermatography of eyebrows is a technique that can be recommended for AA patients with prolonged eyebrow loss243 (Figure 2.194. support groups play an important role in the overall therapeutic strategy. giving the illusion of hair in the area. (b) Camouflage with eyeliner. port groups and suppliers of hairpieces.Alopecia areata 69 Figure 2. patient considerable camouflage.33 Camouflage with eyeliner. and the dermatologist needs to become familiar with sup- Figure 2. the patient’s family and the physician. although several European studies have demonstrated efficacy and safety in children as young as 5 years.

1995. and Colombe B. Colombe B.H..W. 1990. 7. Outlook for the future for alopecia areata treatments New therapeutic directions for alopecia areata will involve specifically targeted immunomodulatory agents. 1991. November 7–8. References 1. Profile of alopecia areata: a questionnaire analysis of patient and family.W. Phototherapy beyond PUVA.H. research updates. 1995. Colombe B. Price V. 104(5 Suppl):1S–45S. J Invest Dermatol. Khoury E. Maryland. 1995.Y. penpals for children.L. Dermatol Clin. and Lou C.W. Other biotechniques to interrupt the peptide-antigen or T-cell receptor are being evaluated.. 1963. light-emitting diode arrays).. 104(5 Suppl):4S–5S..S. Shellow W. which are present in many large cities in the USA and Canada. 1996. Newer immunomodulators specific for CD4 or CD8 and IL-2 receptors may further enhance treatments. Edwards J. Muller R. 14(4):679–89. Physicians are welcome to attend. 8.70 Hair Loss: principles of diagnosis and management of alopecia well-being. safety profiles and outcomes. The National Alopecia Areata Foundation (NAAF) has an annual convention for patients and their families. has the potential to immunomodulate.V. 1992. 4. 1999. October 25–26. 9. et al. HLA class II alleles in longstanding alopecia totalis/alopecia universalis and long-standing patchy alopecia areata differentiate these two clinical groups. Heritable factors distinguish two types of alopecia areata. California 94901–3853. bimonthly newsletters. 31(3):186–9. A workshop. Khoury E. Lou C. 6. HLA class II antigen associations help to define two types of alopecia areata. It is the role of dermatologist to explain the diagnosis and inform the patient of all the therapeutic options. 5. and this is often the turning-point for them in terms of coping with the condition. 2. San Rafael. 4(3):197–254.L. Arch Dermatol. J Am Acad Dermatol. Maryland. The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis. The eventual discovery of cytokines specific for hair growth promotion in topical immunotherapy will offer more focused treatments.D. The role of this therapy in the treatment of AA holds great potential for the future. It is imperative that the physician spend sufficient time with the patient. Price V. J Invest Dermatol.. 88:290–7. 3.E. The National Alopecia Areata Foundation (710 C Street. videos for children to take to school and information about support groups. sources for scalp prostheses. Rodent models currently available have become an important part of therapeutic research.H.alopeciaareata. Bethesda.D. Third International Research Workshop on Alopecia Areata. Alopecia areata. 2nd International Research Workshop on Alopecia Areata..W. J Invest Dermatol. 1994. Colombe B. 96(5):67S–100S. just as one would with a patient who had recently been diagnosis as diabetic. and Koo J. J Invest Dermatol. .W. 4(3):216–19. Gene replacement therapy based on current genetic studies may eventually allow lasting correction of abnormal gene expression.H. Bethesda. www. J Invest Dermatol Symp Proc. 1999.org) offers patients and physicians information. including brochures. Int J Dermatol. 33(5 Pt 1):757–64. and Price V. involving new photosensitizers and novel non-UV light sources (lasers. Alopecia areata: an evaluation of 736 patients. Suite 11. Price V..

[HLA antigens of patients with alopecia areata]. Epstein S. Vestn Dermatol Venerol.. 33. Cohen C. 12. Braun-Falco O. Alopecia areata and Down syndrome. Dmitrienko L. Vestn Dermatol Venerol.. and Down’s syndrome.. Jackow C. Carter D..A. Tissue Antigens.. [Class I alloantigens in alopecia areata].. ed.E. Alopecia areata and cytomegalovirus infection in twins: genes versus environment? J Am Acad Dermatol. Weinrauch L. 36(1):40–1. 19. Orecchia G. 53(2):189–91. polymorphism and regulation of expression of HLA region genes.M. 1977(9):59–61. Duvic M. 1977.C. 23(4):283.. J Invest Dermatol.. Clark H.. R. Human leukocyte antigen-DQB1*03 alleles are associated with alopecia areata. 1994. Jackow C. 38(2):89–91. 1990. and Pospelov L. San Diego: Academic Press. 27(5 Pt 1):766–7. 1991. Hacham-Zadeh S. Analysis of HLA-D locus alleles in alopecia areata patients and families.P. Thomsen K.E. 1998. 23. 1992. Bowen J. Tissue Antigens. Genetics. Du Vivier A. 14. Clay F. Kianto U. and Brautbar C.. and Nevins T. 1986.W.. HLA associations with alopecia areata. 38(3):418–25. et al. et al.V. 1978(10):36–8. and Bauer R. HLA-B12 in alopecia areata.. Bergfeld. Frentz G.. 17.A. 127(1):64–8. and Shakhnes I.J.. 15. 9(1): 35–42..D. Z Hautkr.P. Friedmann P.M. HLA-DR antigens in alopecia areata.F. et al. 1987. et al. 30. Brautbar C. 34. Dermatologica. and Cohen T.Z. So A. J Invest Dermatol... In HLA and disease. and Herzlinger D. HLA antigens in alopecia areata. Selzle D.K. IL-1 alpha inhibits human hair follicle growth and hair fiber production in whole-organ cultures. 112(10):1397–9. and Pace J.C. Kessler M. Int J Dermatol. Arch Dermatol. 104(5 Suppl):5S–6S. 113(12):1716. colonystimulating factor and tumour necrosis factor on human hair follicle . 175(1):10–14 Zhang L. Philpott M. and Braun W. 1. Effects of interleukins. 1991. et al. Lutz G. 1975. Human leukocyte antigen region involvement in the genetic predisposition to alopecia areata... Reunala T. 1986. HLA-DR4 in alopecia areata [letter]. Preliminary report. DRw52a may confer disease resistance. Kuntz B. Cleve Clin Q. J Am Acad Dermatol. 28. 1994.F. p.V. 29. 1:24–6. and Svejgaard A. J Invest Dermatol. Gol’dshtein L. Martinetti M. 18. 1984. Welsh E.K.A. Alopecia areata.. W. Puffer N.S. Fugger L. 1991. 1995. 1981. Duvic M.. 113(12):1717.. Weetman A. Scerri L.. 1986.. 20. Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene.L. Arch Dermatol.. Averbakh E. 13. Arch Dermatol. DNA polymorphism of HLA class II genes in alopecia areata.. and Kealey T. Lymphokine Cytokine Res... Dis Markers.A. autoimmunity.. 1993.Alopecia areata 71 10. Belvedere M.E. Hordinsky M.A. 14(1): 129–30. Br Med J. 103(6):758–63. 31. 11. HLA and alopecia areata in Jerusalem. 1976.K..P. 1994. 16. 61(14):1014. HLA-D locus associations in alopecia areata. Tissue Antigens. [Familial alopecia in twins].Lechler. Morling N. et al.H.B. Identical twins with identical alopecia areata. 25. et al. 1019–22. Frentz G. 26. 27. Zlotogorski A. Welsh E. Arch Dermatol. Jacobsen B..M.. Familial alopecia areata: no linkage with HLA. 1(5951):191–2. 103(3):387–90. 12(4): 197–203. Tarlow J. 18(1): 71–4. 1977. Cork M. 32. Mikesell J. Karvonen J. Harmon C. and Jegasothy B. J Am Acad Dermatol.. Cole G. et al.S. Hordinsky M. Sanders D.. and Chipizhenko V. and Munro D. 24. and Oliveira D. [Familial alopecia areata]. Fiedler V.. Vestn Dermatol Venerol.. et al..D.E. 21.. 1986. Alopecia universalis in identical twins. 22.

Br J Dermatol.. and Gschnait F.. alopecia 67(3):195–6.P.Vitiligo in autoimmune thyroid disease. 1993. Bunnag P. 49..A. 1996. Alopecia areata associated with myasthenia gravis and thymoma: a case of alopecia with marked improvement following thymectomy and high level prednisolone administration. Acta Paediatr Jap. 1990. 67(10):1010–12. Arch Dermatol. 1995. and polymyalgia rheumatica found in the same patient. J Dermatol. Colonna S. Italian Group of Epidemiological Studies in Dermatology (IGESD)]..B.N. 1997.R. and Shinkai H. 50. vitiligo. et al. [Association of lichen ruber planus.K.S. Charuwichitratana S. Conte A. 57.. and Hasegawa O.72 Hair Loss: principles of diagnosis and management of alopecia 35. Virozov Y.. 1998. 128(3):368–71. 1987.M. Aloi P.. 3(2):89–91.M. 1996. Coincidence of vitiligo. 23(6):757–8. Myasthenia gravis and alopecia areata [letter. Werth V. and Manzoni R. Neurology. alopecia areata. 43. and Wuthrich B. Robinson T. Thompson D.A.K. Trueb R. Kamada N. Treem W. Int J Dermatol. J. prospects. 6(3):425–34.. G Ital Dermatol Venereol. 1992. 48(3):774–5. Dermatol Clin. Alopecia areata in a patient with candidiasis-endocrinopathy syndrome: unsuccessful treatment trial with diphenylcyclopropenone. Kumar B. G Ital Dermatol Venereol.. 50(2): 578. Ulcerative colitis and total alopecia in a mother and her son. 38.. 33(9):632–3. 36..P. 48. Thyroidology.Ulcerative colitis. Proc R Soc Med. myasthenia gravis. 42. Friedmann P. alopecia areata and vitiligo]. 56. Boni R. 46. 47. Inverardi D. Decreased lymphocyte reactivity and auto-immunity in alopecia areata. 1994. Noguchi Y. Morimoto S. Int J Dermatol. Br J Dermatol. Pediatr Dermatol. Dhar S. 41. Faergemann J. Prevalence of thyroid diseases in patients with alopecia areata. Cutis. Myasthenia gravis with alopecia totalis. vitiligo.Alopecia areata. Puarilai G. 1990. 106(3): 357–60. Colocalization of alopecia areata and lichen planus [letter]. 159(4): 356–60. and Klar A. Lichen planus with late onset hypogammaglobulinaemia: a causal relationship? Br J Dermatol.. 53. Gastroenterology. 1981. Tan R. Kenney Jr. Shong Y. comment]. 105(2):145–51. 1982. Komiyama A.. Fuchigami T. 1991. 125(12):563–7. Proc R Soc Med. Alopecia areata and thyroid disease. Korn-Lubetzki I. 51. [Study of lichen planus conducted by the IGESD: results. 13(3):258–9. 24(12):769–72. areata. 1998. localized scleroderma and lichen planus. Veligati L. Myasthenia gravis and alopecia areata [see comments].Vitiligo. 54. Polyglandular autoimmune (PGA) syndromes: report of .S... 1974. and Lennard-Jones J. and Warin R. 4(3):252. G Ital Dermatol Venereol. 1979. Kubota A. 1988... 40(1): 99– 101. Bergfeld W. Rotter J. Diem E. onychodystrophy. Dermatologica. et al. [A retrospective study of 200 cases of lichen]. et al. scleroderma and ulcerative colitis.J.. 1999. 1997. Incidence of alopecia areata in lupus erythematosus.M. 44. 39. 34(8):542–5. and Sehgal S. 1995. 1974. Antismooth muscle and antiparietal cell antibodies in Indians with alopecia areata.G.Lichen sclerosus et atrophicus generalisatus. Puavilai S.L. and Rajatanavin R. 104(4):1187–91. J Invest Dermatol. et al. Mann R. atypical lichen planus. and Kim J. Hatamochi A. implications for clinical practice.. 37. Brenner W. 52.W. 55. 125(3):85–9. 1979. Sharma V. 45. 40. 191(1):68–71. growth in vitro: a possible role for interleukin-1 and tumour necrosis factoralpha in alopecia areata. Dermatology. Wallington T. Neurology. 135(6):942–8. 122(4):197–200. Loconsole F. alopecia areata.. and Harada K..

. Assay B. Audring H. 120(2):188–94. Failure of passive transfer of serum from patients with alopecia areata and alopecia universalis to inhibit hair growth in transplants of human scalp skin grafted on to nude mice. Hair follicle structures targeted by antibodies in patients with alopecia areata.S.. J Clin Invest. three cases and review of the literature. Tobin D. 74.F.. [Autoimmune polyendocrinopathy and chronic mucocutaneous candidiasis].. Arch Dermatol. Christoph T.R.J.C.. Bale G. Eicheler W. 71. 69. Lui H.L. 1998.S. 83(4):1049–55. La Placa M.. Berkutzki T. Paus R..K..A. Immunology of the hair follicle: a short journey into terra incognita. Possible implications for the pathogenesis and treatment of alopecia areata. The human hair follicle immune system: cellular composition and immune privilege.. 116(2): 117–21. 7: 145–73. 1992. Arch Dermatol Res. J Dermatol.C. 63. et al. Br J Dermatol. 66. Christoph T.. Ellis C. Arch Dermatol. Alopecia areata and presence of cytomegalovirus DNA [letter]. Br J Dermatol.K. Taylor D. and Coffman R. and Kubba R. 1994. Greggio N. et al. et al. 72. A clinical and immunohistochemical analysis. Pillar T. 1989.. 62. Cytokines and growth factors influence hair growth in vitro.. Huth A. 4(3):226–34. 1984. Tanei R. Gupta A... Hann S. 26(12):797–802.H. 126(2):166–71.. 101(1):62–7. Fujimura T. et al. No correlation between cytomegalovirus and .A.. J Invest Dermatol Symp Proc. Light W. 77(6):327–33. Skinner Jr. Increased ratio of helper to suppressor T cells in alopecia areata. Tobin D. 102(5):609–10.. Carson S. 128(11):1467–73. Antibodies to hair follicles in alopecia areata. Hoffmann R. and de Prost Y. 22(2 Pt 1):242–50. Oral cyclosporine for the treatment of alopecia areata. Ann Dermatol Venereal. Koh M. 1996. 1984.. 1998.. 1992. et al. Olsen E. 64.. Nelson D..H. and Turney E...A. et al.. 2000. 68. Gilhar A. J Invest Dermatol.N. Muller-Rover S.. Cooper K. 1980. Ullmann Y. 110(2):171–5.J. 142(5): 862–73. 1997. 67. Br J Dermatol.J. Fenton D. 1989. 60.. J Clin Endocrinol Metab. Bystryn J. J Am Acad Dermatol.K.. Tosti A. 75.. Delambre C. Suppressor cell number and function in alopecia areata... Hallgren H. 1990. et al. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. 133(1):57–61.. Rook A.Alopecia areata 73 58. 273(18):1419–20. Teillac D. 59. et al.. Immunohistology and autoantibody studies in alopecia areata. 1995. Song M.. Characterization of infiltrating T cells in human scalp explants from alopecia areata to SCID nude mice: possible role of the disappearance of CD8+ T lymphocytes in the process of hair regrowth. and Ho V. 73.B. and Filipovich A. Clinical review 93: Autoimmune polyglandular syndrome type 1.. and Volpato M.. Mosmann T. Muller H. Annu Rev Immunol. Arch Dermatol. J Med Assoc Thai. Betterle C.R. 61. 1997.. 102(5):721–4. Br J Dermatol. 288(3): 153–6. Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice. 36(1):114–17. and David M... Tsuboi H. Orentreich N. JAMA. 65. Shapiro J.K. 1994.C. Gilhar A. Hordinsky M. Majewski B. Placucci F. Tron V. J Am Acad Dermatol. 1999..A. and Muller-Rover S. Bystryn J. Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata.. Brauner R. R.. Systemic cyclosporine and low-dose prednisone in the treatment of chronic severe alopecia areata: a clinical and immunopathologic evaluation.D.B. 76. 70. 1999.

Sundberg J.. Nature.A. Lifetime prevalence of psychiatric disorders in patients with alopecia areata. Tobin.. et al. Alopecia areata in aging C3H/HeJ mice. 94.I. 84.B. Clin Exp Dermatol. Juvenile versus maturity-onset alopecia areata—a comparative retrospective clinical study. 87. 125(2):94–100. J Invest Dermatol. Brodda-Jansen G. Ultrastructural observations on the hair bulb melanocytes and melanosomes in acute alopecia areata. Lundeberg T. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. J Invest Dermatol.P.R. 1999. Microsc Res Tech .D. 91. 1994.J..... Paus R. J Invest Dermatol. Kennedy W. Compr Psychiatry..H. Murphy G.J. Nutbrown M.. Acta Derm Venereol.J.. Structure and function of cutaneous nerves in alopecia areata. 1994.. J Invest Dermatol.P. 180(3): 1429–35.P.A.D. De Waard-van der Spek F. Hair growth induction by substance P.. Boggess D. Baker G.L. and King Jr. van der Steen P. J Invest Dermatol.075% (Zostrix) in controls and patients with alopecia areata. Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Oliver R.A. Colon E. 102(6):847–56. Garcia-Hernandez M. et al. and Kendall M. J Invest Dermatol. Smyth Jr. De Raeymaecker D. et al.J. 83.A. 1989.J. 93. 1991. Cipriani R. The DEBR rat: an animal model of human alopecia areata.. 112(5):822–4.. 1992. et al. 86... No evidence of cytomegalovirus DNA in alopecia areata [letter]. Abnormalities in the ultrastructure of melanocytes and the outer root sheath of clinically normal hair follicles from alopecia areata scalps.R. et al. Cunliffe W. J Invest Dermatol. Duller P. 111(5):797–803. J Invest Dermatol. and Price V. J Invest Dermatol Symp Proc. Ericson M. 71(1):134–40..H. 1995..D. Can alopecia areata be triggered by emotional stress? An uncontrolled evaluation of 178 patients with extensive hair loss. Raud J. Callies A. S. 1999.. 1995. 110(6):986–7. Psychological factors and immunity. Life events and alopecia areata. 1993.E.. 82. Tobin D. Wendelschafer-Crable G.J.. McElwee K. 1984. 1990.J. Burgett B. 94(6):803–7. 110(2):185. 4(3): 211–15. and Randall V. J Invest Dermatol. J Invest Dermatol Symp Proc. 1999.. Alopecia areata and universalis in the Smyth chicken model for spontaneous autoimmune vitiligo. Oranje A. Egan C. McElwee K. 95.E.P. 90.C. 97. Sundberg J. et al. McElwee K... Morphological analysis of hair follicles in alopecia areata. 112:653. 1997. Boggess D. 1987. and Johnson B. 104(5 Suppl):28S–29S. 92.74 Hair Loss: principles of diagnosis and management of alopecia 77.. Heinzelmann T. 1991.. 79. 4(3):224–5. Veller Fornasa C. 32(3):245–51. 81. Third International Research Workshop on Alopecia Areata. T cell repertoire in mice with alopecia areata.E.. alopecia areata [letter].. 78.F. Baezman J. 363(6425):159–63. Torres M. 72(4): 279–80. J Invest Dermatol. Hosoi J. Potent anti-inflammatory action of calcitonin gene-related peptide. and Happle R. Lab Invest. 104(5 Suppl):12S–13S. 1998.J. 31(1): 1–10.. 1998. 1996. 107(3):443. Michie H. Benichou G.A. et al. Hull S. Perini G. Br J Dermatol. 88. 1991. 38(4):443–51. 1998.J. Schultz K. 96.F. Murine cytomegalovirus is not associated with alopecia areata in C3H/HeJ mice [letter]. and McNeil M. J.. L.. and PeereboomWynia J. King L. and Lewis S. . 89.. 1999. 85..M... Psychother Psychosom.L... J Psychosom Res. 80. Cordy W. Palomares J. Popkin M.. Fenton D. Differential expression of substance P in perifollicular scalp blood vessels and nerves after topical therapy with capsaicin 0. Hordinsky M.K. 14(6):429–33. Biochem Biophys Res Commun. Jahoda C. 41(1):48–52.

Y.A. 4(3):239. Marzouk S. McLean D. 104(5 Suppl):26S–27S. Alopecia areata-like hair loss in C3H/HeJ mice and DEBR rats can be reversed using topical diphencyprone. and Happle R. 1986. J Invest Dermatol. Increased number of OKT6-positive dendritic cells in the hair follicles of patients with alopecia areata. Safavi K.. Wiesner-Menzel L.. Snowden J. Sundberg J..J. Whiting.Sundberg.. pp. Cedar Grove: Canfield Publishing.A.A. 1991. 107. Liu H...G.Alopecia areata 75 98. Price V..P. 1992. Boca Raton. Shapiro J. 114(3):337–47.A. 104. Alopecia areata: alterations in the hair growth cycle and correlation with the follicular pathology. J. Hair defects in Hoxc13 mutant mice. 1991. J Invest Dermatol Symp Proc. et al. Arch Dermatol Res.. Whiting D. Tang L. 114. Alopecia areata.. 1993. J Invest Dermatol Symp Proc. J Am Acad Dermatol. J Invest Dermatol. Br J Dermatol.. D. Hatamochi A. Whiting D. 135(2): 204–10. Stierle C.. 109. Eosinophils in fibrous tracts and near hair bulbs: A helpful diagnostic feature of alopecia areata [letter.. et al. 2000.H. et al. 1994. ed. 106. Bissonette R. 118. ed.G. Kohchiyama A. 1984. 117. chromosome 14. 105. 96(5):68S. 129(3):250–6. 1999.. Happle R. J Am Acad Dermatol. Histopathology of alopecia areata in horizontal sections of scalp biopsies. J Invest Dermatol. J Invest Dermatol. Ultrastructural abnormalities in the dermal papillae of both lesional and clinically normal follicles from alopecia areata scalps. and Ueki H.L.. 1991. Br J Dermatol. Elston D.. 32–7. MacDonald Hull S. Slater D. 111. 1997. 96:69S.P. McCollough M. In Handbook of mouse mutations with skin and hair abnormalities. Alopecia syphilitica. Baker T. 101. Sundberg J.M.M.N. J Invest Dermatol Symp Proc. Alopecia areata: clinical aspects. The molecular basis of congenital atrichia in humans and mice: mutations in the hairless gene. Dermatologica.. 103. 1995. Lee J. The hairless and rhino mutations. comment]. Green M.R. Leflunomide in the alopecia areata DEBR rat. et al. Headington J. et al. The histology of alopecia areata. 102. and Christiano A. Perret C.L. pp.S. and Sharawi E. a simulator of alopecia areata: histopathology and differential diagnosis. 1989. et al. In Genetic variants and strains of the laboratory mouse. Freyschmidt-Paul P. Panteleyev A.. Arch Dermatol.. Nutbrown M. 1996. 1999. Godwin A. J Invest Dermatol. In Color atlas of differential diagnosis of hair loss. 64(1):26–30. 113. M. 4(3):249.. 1999. . 1984. Wiesner-Menzel L.P. Eosinophils in fibrous tracts and near hair bulbs: a helpful diagnostic feature of alopecia areata [see comments]. Intrabulbar and peribulbar accumulation of dendritic OKT 6-positive cells in alopecia areata. 128(5):702. J Cutan Pathol. 99. 4(3):244–7. 42(2 Pt 1):305–7.F. Successful treatment of alopecia areata-like hair loss with the contact sensitizer squaric acid dibutylester (SADBE) in C3H/HeJ mice. 112. El Darouti M. 1985. 1996.. 110.. Sundberg J. and Capecchi M. Ahmad W. 108.. Bergfeld W.R. Catalog of mutant genes and polymorphic loci. Br J Dermatol.. and Happle R. Acta Derm Venereol. Lyon. 1999. 115. FL: CRC Press. 1999. 113(1):61–8. Immunohistochemical analysis of T-cell subsets in the peribulbar and intrabulbar infiltrates of alopecia areata. 18(2):87–92. Oxford: Oxford University Press. Messenger A. 37(1):101–6. 276(5): 333–4. 100. 171(5):327–31. HLA and ICAM-1 expression in alopecia areata in vivo and in vitro: the role of cytokines. Prevalence of alopecia areata in the First National Health and Nutrition Examination Survey [letter]. McDonagh A. 116. 291–312. ed. and Hsu M. 4(3):240–3. and Bleehen S.

1817. 1994.. 11(2):112–15. and Kligman A.R. Scanning electron microscopy comparing exclamation mark hairs in alopecia areata with normal hair fibres. 14(1):47–50. Oxford.. et al. 1995.C. Treatment of alopecia areata with steroid solution. Trachyonychia associated with alopecia areata: a clinical and pathologic study. Olsen E. Dermatol Surg. and Camacho F. 104(5 Suppl):27S–28S. Tosti A. Stolz E. 1999. 124. 137. [Nail changes and alopecia areata].. Practical Synopsis of Cutaneous Disease. Van Joost T. Spain: Aula Medica Group. 104(5 Suppl):30S. Postoperative (pressure) alopecia: report of a case after elective cosmetic surgery. 22(4):219–21. Topical halcinonide in alopecia areata and in alopecia totalis. 1991. 25(2 Pt 1):266–70.A.. Alopecia totalis—treatment with fluocinolone acetonide. DeBerker and R. 120(3):169–71. Madrid.. 89(4):1062–3. 106(6):924. Arch Dermatol. 1997. 133. Madani S. G Ital Dermatol Venereol.K. Hordinsky M.. Farmer E. Wiles J. J Am Acad Dermatol. 123. Handbook of the diseases of the nails and their management. et al. ed. lichen planus]. 129. 1985. Alopecia areata: clinical features. 12(1 Pt 2):195–8. Koerten H. ed. 1999. 128.. Steijlen P. 1977. Pressure-induced alopecia. alopecia areata. 73(2):308–9. Pathogenesis and topical immunotherapy. Montes L. 1985. 15(4):326–7. 4th edn. Ophiasis inversus: a rare pattern of alopecia areata [letter] [see comments]. DeBerker D. Sharma V. Prevalence of nail abnormalities in children with alopecia areata.. 1984. 140. Congenital triangular 131. 135. Br J Dermatol. Tosti A.J. limited to the nails? J Invest Dermatol.A. Eslinger M. Tosti A..M. 1995. Dominguez E. 1979. Arch Dermatol.M. 125. Pediatr Dermatol. 120. Camacho F. Postoperative (pressure) alopecia. National Alopecia Areata Foundation. Guidelines of care for alopecia areata. 40(2 Pt 1):242–6. In Trichology: Diseases of the pilosebaceous follicle. Poma P. J Cutan Pathol. 1990. 122. pp. F. Tosti A. G Ital Dermatol Venereol.K. Alopecia areata: pathogenesis and treatment. Anesth Analg. Sawaya M.. Peereboom-Wynia J. Gill K. 121. and Barwick W. Mitchell A. 126. Is trachyonychia. J Am Acad Dermatol . and Happle R. 131(6): 866–72. Pediatr Dermatol. Piraccini B. and Veronesi S.Dawber. 1994. and Shapiro J. 1999. 139.F. Int J Dermatol. Report of a case after gynecologic surgery. 417–50. Muralidhar S.. Kosanin R. 134. Postoperative alopecia in a woman after a lengthy plastic surgical procedure. J Reprod Med.. 26(2 Pt 1):247–50. 1998. Palmerio B. 1963. Drake L.76 Hair Loss: principles of diagnosis and management of alopecia 119. 87:384. and Krull E.. 142. and Hansen R. McDonald-Hull S.. 25(7):537–8. 1989. and McCord S. 143.M. J Am Acad Dermatol. 1995. pp..L. Tosti A. et al.E. Plast Reconstr Surg.C.. Blackwell Science.. Garcia-Hernandez M.. and Hordinsky M.K. et al. 130. [20 nail dystrophy. 1995.V.M. Alopecia areata investigational assessment guidelines. Glucocorticoid regulation of hair growth in alopecia areata.R. J Am Acad Dermatol. et al. 120(2):131–2. mechanically broken by traction. Pediatr Dermatol..M. a variety of alopecia areata.M. and Kaur S.A. 1985. 4(2):47–50. 138. Barclazzi F. 141.J. 12(4):301–3. Clin Exp Dermatol. Alopecia areata. J Invest Dermatol.D. 136. 1992..Camacho. 1984. Rodriguez-Pichardo A. 76–7. Tosti A. Dinehart S. The scalp biopsy: making it more efficient [In Process Citation]. Idiopathic trachyonychia (twenty-nail dystrophy): a pathological study of 23 patients. alopecia (Brauer nevus). Leyden J. 1972.D. 11(5 Pt 1):763–75.J.. 132. Riefkohl R.B. 29(2):83–8. J Am Acad Dermatol. Bateman T. 127. et al. Perret C. R. .

2000.H. Fiedler V. Cleve Clin J Med. 167. prospective study of 45 patients. Hair regrowth. J Am Acad Dermatol.J. 341(13):964–73. Price V. 150. Pulse methylprednisolone therapy for severe alopecia areata: an open 160. Br J Dermatol. Topical minoxidil in extensive alopecia areata. 39(4 Pt 1):597–602. 156. Bull Dermatol Foundation. 128(11):1519–29. 149.H. Arch Dermatol. 1976.L. Topical minoxidil (3%) in extensive alopecia areata.H. 11(1):35–46.F. A follow-up report.M. 151. Sharma V. comment]. Thiers B. 126(6):756–9. 146. 1998. 4:136.C. et al. A trial of 1% minoxidil used topically for severe alopecia areata.A. Fransway A.E. 155. Alopecia areata. Systemic effects. 99(1):40–7. 1987. A review of therapy. Price V. Pediat Dermatol. New Engl J Med. and mechanism [editorial] [see comments]. Therapeutic agents. et al. efficacy. Response to combination therapy with minoxidil plus anthralin. and Savin J.P. Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration. 1992. 1978. 66(2): 179–80. Fiedler V. Alabdulkareem A. Topical minoxidil solution (1% and 5%) in the treatment of alopecia areata. 1971. 152. Severe alopecia areata treated with systemic corticosteroids... Treatment-resistant alopecia areata. 170. 114(10):1486–90. 16(3 Pt 2):737–44.H. 1991. Shapiro J.C. 1987. and Rumsfield J. 164.P. Alopecia areata: current therapy. 112(11):1549–52. 147. Treatment of hair loss.. West D. Alopecia areata totalis/ universalis and systemic corticosteroids [letter. Progress in Dermatology. Int J Dermatol.Alopecia areata 77 144. Minoxidil’s action in hair follicles. and Okoro A. and Blizzard R. Dermatol Clin. Arch Dermatol. 37(8):622–4.P. 1993.J. 96(5):69S–70S. and Schemmer R. Buhl A.F. 148. Shapiro J.J.A. Bagfeld W. Price V. 1998.A. and Moreno-Arias G. Arch Dermatol. 122(2):180–2. Extensive alopecia areata.A. Buys C. 157. 161. and Muller S. Ferrando J. Michalowski R. Ranchoff R. 163. 165. Alopecia areata. 3 percent topical minoxidil compared with placebo for the treatment of chronic severe alopecia areata. Kern F. 168.. 158..M. 4:144. Wendraw A. Unger W. J Invest Dermatol. Abahussein A. 16(2):341–56. 35(2):133–6. 153. 1987. . 175(Suppl 2):36–41. 166. 1998.. J Invest Dermatol. 1991.D. Alopecia areata symposium.. 1987. 40(3):247–50.L.A. Int J Dermatol. Fiedler-Weiss V. 1990. 16(3 Pt 2):745–8. and Price V. 1986. J Am Acad Dermatol. Pediat Dermatol. 154. 41(6):431–5. Friedli A. 1999. et al. 1999. 1989. A comparison of intra-lesional triamcinolone hexacetonide and triamcinolone acetonide in alopecia areata. Winter R. safety. Arch Dermatol. 56(2): 149–54. 162.. Cutis. Alopecia areata symposium. Khoury E. Abdel-Salam M. Update on therapy. Fiedler V. 26(7):690–1. Topical minoxidil doseresponse effect in alopecia areata.. J Invest Dermatol. Szpunar G. 1987.H.A. Vestey J. Corticosteroids in the treatment of alopecia totalis. Cutis..E. 1991. 1986. 145. Arch Dermatol. 38(12):947. and Subichin S. Stack W. 85(3):272–3... J Am Acad Dermatol. Dermatol Clin. Pulsed administration of corticosteroids in the treatment of alopecia areata. Int J Dermatol.S.C. 169.J. 1988.K. including 3-year follow-up. 96(5):73S–74S. 25:1.M. Prednisone therapy for alopecia areata. Acta Derm Venereol. Fiedler-Weiss V. Price V. and Burton J. Multiinjection plate for intralesional corticosteroid treatment of patchy alopecia areata. Dermatol Surg.C. The treatment of alopecia areata.C. Price V. Dermatologica. Porter D. including longterm efficacy. 1987. 159. Results of treatment with 3% topical minoxidil. Bergfeld W. 1992. 1996.. Whiting D.

..J. 264:123.. Hehir M. 1979.4dinitrobenzene (DNCB) and squaricaciddibutylester (SADBE). 35(1):52–6. and Sapuppo A. and Smith R. 1980. 189. Chua S.. Topical treatment of alopecia areata.. and Drake L. Homburger F. Goh C. 117(7):384–7. J Am Acad Dermatol. Mutagenic and cell transforming activities of 1-chlor-2.. and Pullara T. 1980. 187.A. Wilkerson M. Int J Dermatol. Cutis. 191. Treatment of alopecia areata with dinitrochlorobenzene. 181.4-dinitrobenzene depletes glutathione in rat skin and is mutagenic in Salmonella typhimurium. 1978..A. Swanson N.R.. 1980. 1987. 1986. 172. Happle R. 175. 77(1):91–3. 161(5): 289–97.. Contact allergy as a therapeutic tool for alopecia areata: application of squaric acid dibutylester. Summer K. Testing of twenty-one environmental aromatic amines or derivatives for longterm toxicity or carcinogenicity. Arch Dermatol Res.P. 115(10):1254–5..A. Arch Dermatol.L. Weissman I. 186. Nasca M. Mutat Res.. Daman L. 123(11):1491–3.. and Orecchia G. Kratka J.. Evaluation of anthralin in the treatment of alopecia areata. Flowers F. Weisburger E. 178. 1996. and du Vivier A. 24(9):606–7. Cebulla K.K. 1981. Orenberg E. J Invest Dermatol. Happle R. and Macher E.A. 123(8):1036–41.H. 1979. Kaplan J. Caserio R. and Goggelmann W. and Strobel R. Goerz G. et al.L. 1983. 1979. Arch Dermatol. Arch Dermatol Res.J. 174. Dinitrochlorobenzene therapy for alopecia areata. et al. Treatment of alopecia areata by anthralin-induced dermatitis.. 81(1):23–7. Dermatologica.C. Arch Dermatol. et al.. 4(3):385–7. and Rohrborn G. and Spielvogel R.. Arch Dermatol Res. Anthralin therapy for alopecia areata. Giannetti A. Klein H. 30(6):733–6. Irritant versus allergic contact dermatitis for the treatment of alopecia areata. and Braun-Falco O. Treatment of alopecia areata with squaric acid dibutylester. Happle R. Buchner U. 1978. 1979.. 193. Happle R.B. et al.. 45(4):307–14. 114(11):1629–31. Arch Dermatol.. 267(1):109–14. Mitchell A. 1982.78 Hair Loss: principles of diagnosis and management of alopecia 171. 1983. 180. Alopecia areata treated with DNCB.B. Swanson N. Inhibition of a Langerhans cell-mediated immune response by treatment modalities useful in psoriasis. Clinical experience on the treatment of alopecia areata with squaric acid dibutyl ester. Clin Exp Dermatol. 1987.. J Environ Pathol Toxicol. 177. Schmoeckel C.J. Vizethum W.M. 190. 9(4):554–7. Fiedler-Weiss V. Arch Dermatol. J Am Acad Dermatol.J.C. et al. Dinitrochlorobenzene: influence on the cytochrome P-450 system and mutagenic effects. Plewig G. 167(5):280–2.H. Micali G. Contaminants of dinitrochlorobenzene. 1984. Antigenic competition as a therapeutic concept for alopecia areata. Mitchell A.L.J. 183.S.. Arch Dermatol Res. Treatment of alopecia areata with squaric acid dibutylester.K. 1985. and Buys C. Rosenberg E. and Ang C. and EchternachtHapple K. 188. Int J Dermatol. 185. 176. Nelson D. 1980.G..K..A. Topical immunotherapy changes the composition of the peribulbar infiltrate in alopecia areata.B. 266(3):315–18. Kalveram K. Buchner U.G.. Topical therapy of alopecia areata with squaric acid dibutylester. Morhenn V. Case P.M. 10(3):447–50. 1983. 1978. Leahy M.E. 114(7):1036–8. Arch Dermatol. Cicero R. 173. 179. l-chloro2.. Slazinski L. Dermatologica. 278(3):214–8. 184. Strobel R.W. Topical squaric acid dibutylester therapy for alopecia areata. 2(2):325–56. Topical squaric acid dibutylester therapy for alopecia areata: a double-sided . Fenske N.. Russfield A. Arch Toxicol... 192. 182. Wilkin J.

137: in press. Clin Exp Dermatol.M. Gordon P. Ashworth J. J Am Acad Dermatol. 120(3):397–401. Pediatr Dermatol. Topical immunotherapy of severe alopecia areata with diphenylcyclopropenone: evaluation of 68 cases. 211.D. and Happle R. 203. Boezeman J.. and Norris J. 119(3): 367–74.. Dermatologica. Induction of hair growth in alopecia totalis with diphencyprone sensitization. 181(2):167–9. 196(4):418–21. Dermatology. Van Duuren B. Treatment of alopecia areata with diphencyprone. and Trueb R. and related compounds. 170(1):40–2. and Hogan D. Perfetti L. 213. Lui H. Topical diphencyprone for alopecia areata: evaluation of 48 cases after 30 months’ follow-up. and Gibson J.. 1985.G. Squaric acid and esters: analysis for contaminants and stability in solvents. 11(1):65–8. Tuyp E.B. and Hunter J. Treatment of alopecia areata with diphencyprone..E. Blair R. A comparison of the value of topical diphencyprone and tretinoin gel.. Orecchia G. Dermatology. 2(8660):445. 13(2 Pt 1): 229–34. Ann Acad Med Singapore..R. Orecchia G. et al.J. 35(2 Pt 1):199–201. Borroni G. and Santagostino L. and Rabbiosi G. 1990.. Hatzis J.F. 1:71. Aldridge R. J Am Acad Dermatol. 134(5):869–71. 2001. 124(2):212–13. Treatment of severe alopecia areata with squaric acid dibutylester in pediatric patients. Carcinogenicity of isosters of epoxides and lactones: aziridine ethanol. Malagoli P. 1988.. MacDonald-Hull S.S. Diphencyprone in the treatment of long-standing alopecia areata. Dermatologica. Squaric acid dibutyl ester in the treatment of alopecia areata. 1989. J Dermatol Treat. 198.L. McVitie E.. Pericin M. and Miscali C. and Saihan E.Alopecia areata 79 194. Hull S. 1988. Post therapy relapse rate in alopecia areata after successful treatment with diphencyprone. 202. 184(3): 198– 201. 207. Kostakis P. and Smith R. 212. 1996. 206. Darley C. patientcontrolled study. Orecchia G.G. Predictive model for immunotherapy of alopecia areata with diphencyprone. 197. Henkin J. Br J Dermatol.. 200. 1998.K. Shapiro J.. Georgiotono K. and Cunliffe W. 1989. 199.R. J Am Acad Dermatol.H. J Natl Cancer Inst.M. Successful treatment of alopecia areata using the contact allergen diphencyprone [letter].. propane sultone. Regression of cutaneous metastatic malignant melanoma with topical diphencyprone and oral cimetidine [letter]. Wilkin J.M. 1991. 171(3):193–6. 1985.. 25(6):842–7.. 208. 209. et al. Wilkerson M.M.. Hull S. 1985. 205.A. 201. Diphencyprone [letter]...M. 1988. Br J Dermatol. Allergic and irritant contact dermatitis compared in the treatment of alopecia totalis and universalis. Berth-Jones J.. Barth J. Harland C. Guidetti M. 1996. Bardazzi F.. Clin Exp Dermatol. Lane P. 16(3): 172–5. 29(1):33–6. 1989.C. Topical immunotherapy for alopecia areata: re-evaluation of 139 cases after an additional follow-up period of 19 months. 19(2 Pt 1):364–5. Treatment of alopecia totalis with a combination of inosine pranobex and diphencyprone compared to each treatment alone. Wiseman M. Van der Steen P. Arch Derm.. Lancet. Br J Dermatol.H. Tosti A.R. 1992. 195. Photochemotherapy plus squaric acid dibutylester in alopecia areata treatment [letter].M.. 14(2):154–7. Dermatologica. 1996.J. and Mackie R. . and Hutchinson P. 1994. 46(1):143–9. Australas J Dermatol. 196. Melchionne S. Br J Dermatol. Long-term results of topical immunotherapy in children with alopecia totalis or alopecia universalis. 1971. 204. MacDonald N. 1991. 1989. 210. and Rabbiosi G. Monk B.

1999. Arch Dermatol. 229. 133(3):496–7. and Perfetti L. 1999. 1996. . 134(6):1153.A. 221. Guerra L. 218.M. 180(1):5–7.. 222. and Cunliffe W. Br J Dermatol. 225.Happle. and Stock J. Br J Dermatol. Vitiligo as a reaction to topical treatment with diphencyprone [see comments]. pathogenesis and topical immunotherapy].O. van Baar H. Diphencyprone is not detectable in serum or urine following topical application. Perret C. Topical photochemotherapy for alopecia areata.. J Am Acad Dermatol. 230. Diphenylcyclopropenone: an important agent known to cause depigmentation [letter. Alam M.J. and Happle R. Diphenylcyclopropenone: examination for potential contaminants. 1990. 219. 1990. et al. Berth-Jones J. 234.M. and Tron V.. Steijlen P. 2000... 40(1):110–12. and Happle R. Henkin J. 17(4):606–11.M. 216. 224.S. 1990. Perret C.H.. and Messenger A. Gourgiotou K.. 215. 125(2):164–8. Orecchia G. Henderson C. 1991. 1994. 177(3):146–8. Severe urticarial reaction to diphenylcyclopropenone therapy for alopecia areata. 123(3):415–16.G. Shapiro J. 231. and Bardazzi F.. Ho V..M.. Van der Steen P. mechanisms of sensitization. Hatzis J.H.M. 220..80 Hair Loss: principles of diagnosis and management of alopecia 214. New York: Springer Verlag.Vitiligo complicating diphencyprone sensitization therapy for alopecia universalis [letter]. Duhra P. [Alopecia areata. 74(4):312–3. 232. 1989. Pepall L. and Arase S. 227. and Foulds I. 2000.C. Fernandez-Redondo V.G. comment]. J Am Acad Dermatol. Orecchia G. 128(4):518–20. 217. Lewis P. 29(5 Pt 1):729–35. p. 179(3):137–8. 24(2 Pt 1):253–7. 223. 1984. Zaun H. Treatment of chronic severe alopecia areata with topical diphenylcyclopropenone and 5% minoxidil: a clinical and immunopathologic evaluation. Wilkerson M. Skrebova N.A. Dermatologica. Connor T. Gomez-Centeno P. Dermatology. and Savin R. 133(25):1256–60.. 1995. Assessment of diphenylcyclopropenone for photochemically induced mutagenicity in the Ames assay...E. Acta Derm Venereal. Florez A. Perret C. and Douglass M. Perret C.J. 12(4):644–9. 1988. Dermatologica. Contact Dermatitis. Hazards in the use of diphencyprone [letter] [see comments]. Br J Dermatol.M. and Toribio J. Br J Dermatol. 1991. 228. 1989. J Am Acad Dermatol. 226.. and Wilkin J.G. Gross E. Shah M. ed.M.. Treatment of alopecia areata with diphenylcyclopropenone [see comments]. 1992. Tosti A.. Hull S. Allergy. J Am Acad Dermatol. 1989. Alopecia areata in children: response to treatment with diphencyprone.C. 11(5 Pt 1): 802–7. J Am Acad Dermatol. Henkin J. Ned Tijdschr Geneeskd.. 21(3):196–7. Mc Burney A. comment]. Dermatologica. Van der Steen P. In Hair and Hair Diseases. Tosca A...R. 529. 1993. Takiwaki H.. Nameda Y. Contact Dermatitis. Severe dermographism after topical therapy with diphenylcyclopropenone for alopecia universalis.M. 233. J Am Acad Dermatol. Persistent vitiligo induced by diphencyprone [letter]. C.K. and photochemical stability.. et al. ‘Dyschromia in confetti’ as a side effect of topical immunotherapy with diphenylcyclopropenone. Contact urticaria during topical immunotherapy. and Happle R. 55(2): 202–3. Mitchell A. and Hutchinson P. and Ilchyshyn A. Treatment of alopecia areata. and Happle R. Tan J. 199(2):198. Wilkerson M. Hazards in the use of diphencyprone. Steijlen P.Vitiligo and topical allergens [letter. 1987. 1985.Erythema multiforme-like eruptions: a rare side effect of topical immunotherapy with diphenylcyclopropenone.. 42(4):212–15.

Kianto U.T. Teillac D. Placebo-controlled trial of topical cyclosporin in severe alopecia areata [letter].Alopecia areata 81 235.H. 2(8510):803–4. 240. and Juvakoski T. et al. de Prost Y.. Pillar T. 238. Gilhar A. 1997.. PUVA treatment for alopecia areata—does it work? A retrospective review of 102 cases.. Br J Dermatol.L. 133(6):914–18. 1980. Acta Derm Venereal. and Gagnaire D. and Vakeva L.. Larko O. 1995.. 1980.M. 129(1):42–4. 237.. 239. 1998. Acta Derm Venereal. and Rogers S. Taylor C. Ijsselmuiclen O..H. 1989. PUVA treatment of alopecia areata partialis. . The PUVA Follow-Up Study [see comments]. 60(2):171–2. 37(8): 617–21. Johansson E. Paquez F. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). 243. 69(3):252–3. and Swanbeck G. et al. 161(5):298–304. Healy E. Topical cyclosporin A in alopecia areata. Dermatography as a new treatment for alopecia areata of the eyebrows. 1993. 236.E. Stern R. et al. Lassus A. PUVA treatment of alopecia totalis. Dermatologica. 1986. Photochemotherapy for alopecia areata. Acta Derm Venereal. Nichols K. Van der Velden E. Br J Dermatol. totalis and universalis: audit of 10 years’ experience at St John’s Institute of Dermatology.R. New Engl J Med.L. Int J Dermatol. 1983. Lancet.. Drost B..S. 63(6):546–9. 241.. Claudy A. and Hawk J. 242. PUVA treatment for alopecia areata. 336(15):1041–5.. and Etzioni A.

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androgens trigger a series of events within these genetically-programmed hair follicles. It is still controversial what becomes of these miniaturized follicles. Pathogenesis Knowledge of the patho-physiology of AGA is essential in understanding the mechanism of action of current therapeutic agents.18 These finer small vellus-like hairs of varying lengths and diameters are the hallmark of AGA (Figure 3. less so in Africans. It affects approximately 50% of men by the age of 50 and 20% to 53% of women by the age of 50. Asians and Inuits. clinical features and practical medical treatment 16 Introduction Androgenetic alopecia (AGA) is by far the most common cause of hair loss. it can have a significant psycho-social impact for patients. and least frequent in Amerindians.1 Genetics determine both the density and the location of androgen-sensitive hair follicles on site-specific areas of the scalp. As its name implies.3 polygenic. Complete permanent regression is unlikely.20 The McKusick Mendelian Inheritance in Man (MIM) number for AGA is 109200. AGA involves both genetic and hormonal factors.21 . spironolactone and estrogen (personal observation). with progressive shortening of the anagen phase occurring over many cycles. clinical features and state of the art medical management of AGA. However. After puberty.19 and inherited from either parent.3 Androgenetic alopecia: Pathogenesis. minoxidil. A MIM entry that begins with the number one indicates an autosomal dominant inheritance.7– The hair cycle is altered. This shortening of anagen and subsequent miniaturization of hairs leads to decreased scalp coverage. It is believed to be most likely autosomal dominant. Genetic factors The exact inheritance pattern of AGA is still debated.1. 4–6 This chapter will highlight the pathogenesis.1). that transform terminal to miniaturized follicles.1–3 Although it is a medically benign condition. since cases of severely advanced balding male to female transsexuals have experienced considerable regrowth using finasteride. The following is a summary of the current knowledge on AGA pathogenesis. predominantly of the fronto-parietal scalp.17. We are only beginning to understand the different factors underlying AGA.19 The gene frequency appears to be most common in Caucasians. in AGA the number of follicles per unit of area remains the same.

He studied 119 males with AGA. and 46% of the brothers were bald if the father was not bald. Fifty-six per cent of bald men had bald fathers. 24 three generations and 3 four generations involved. although no formal study has been performed. Harris24 found that of 117 men with AGA. there is miniaturization of coarse terminal hairs into small vellus-like hairs with each subsequent cycle. in that Shapiro has noted the same trend in increased body hair distribution in a disproportionately large number of his balding male patients. This observation is quite interesting. They present very credible arguments . Osborn22 stated that AGA was a sex-limited autosomal dominant trait similar to the inheritance of horns in sheep.1 In androgenetic alopecia. but not back hair. The genotype bb may remain sub-clinical in both sexes. Smith and Wells23 have hypothesized that the expressivity of the gene might be partly determined by the androgen level: the genotype BB may lead to the clinical picture of AGA even at low androgen levels in women.26 Kuster and Happle. Eleven had two generations of families with both parents affected.84 Hair Loss: principles of diagnosis and management of alopecia Figure 3. 65 had two generations. 66% of the brothers were bald if the father of the proband was also bald. The authors concluded that this was consistent with an autosomal dominant gene. There was an association of increasing amounts of chest hair.19 favor a polygenic inheritance rather than a simple Mendelian model. in affected individuals. and women who presented with AGA were homozygotes only. whereas the genotype Bb requires higher amounts of androgen. Some previous work on the genetics of AGA dates back to 1919. Sixteen had no family history. She believed that men could be either homozygotes (BB) or heterozygotes (Bb). A family has been described in which common baldness with early onset occurred in females only. Salomon25 felt that AGA is inherited through multifactorial or conditioned dominance via an autosomal dominant gene of variable expressivity.

Variances in levels of these androgen-metabolizing enzymes and androgen receptor proteins help explain the differences between balding and non-balding scalp at various ages and the different clinical patterns and severities between men and women. Shapiro has seen a female teenager with androgen-insensitive syndrome.28 There was an association with one allele of the steroid metabolism gene CYP17.33 and this may explain why female AGA is usually less severe than male AGA. The 5a-reductase type I isoenzyme is located mainly in sebaceous glands.33 DHT levels are increased in balding scalp when compared to non-balding scalp. although this genetic change was not the primary cause of either condition. which involves two steroid-metabolizing enzymes (5a-reductase and aromatase) and androgen receptor pro- teins. and fetal genital skin. are both part of normal androgen metabolism and reduce testosterone (T) to dihydrotestosterone (DHT). showing that this pattern of hair loss is not necessarily androgen-dependent.35–37 Both isoenzymes are increased in frontal balding follicles compared to occipital non-balding follicles. described several families in which premature balding in male members appeared to denote carrier status for an autosomal dominant gene responsible for polycystic ovarian disease. Hormonal factors A major determinant of AGA is intracellular androgen metabolism.34 as well as in the epididymis.31 did not find any evidence of linkage of early-onset AGA to any markers of chromosomes 2 and 5 that are known to code for 5 a-reductase Type I and II.27. and the fact that the risk increases with the number of relatives already affected. the distribution of the balding patterns in the general population along a Gaussian curve of variation. lacking androgen receptors. The X-linked mutation for adrenoleukodystrophy.33 5a-reductase isoenzymes. and sweat glands. The high prevalence rate. with typical female AGA (unpublished personal observa- .0–3. A recent case report by Orme et al. It is expected over the next decade that the information from the Human Genome Project will have great relevance in mapping out the genes that express the complex trait of AGA.1.41–43 further supporting the DHT requirement for AGA expression.30 Sreekumar et al. vas deferens. may be a part of the polygenic spectrum of genes responsible for AGA.34 The 5a-reductase type II isoenzyme is located mainly in the root sheaths of the scalp hair follicle33. Other important factors may still remain to be discovered. Carey et al. but to a lesser extent in women.34 Both type I and type II isoenzymes play an important role in AGA.27.Androgenetic alopecia 85 supporting multi-allelic inheritance.29 The human hairless gene responsible for papular atrichia was shown not to be correlated to AGA when studying 31 heterozygous male carriers of this mutation with respect to onset or extent of AGA. Individuals with a genetic deficiency of 5a-reductase type II isoenzyme do not develop AGA.35. epidermal and follicular keratinocytes. prostate. seminal vesicles.5 times less 5α-reductase (I and II) than men.33.38–40 Women have 3. dermal papilla cells. type I and II. and that there is an increased risk to relatives of severely affected women as compared to the relatives of mildly affected women all support a more complex polygenic inheritance.44 described a young women with hypopituitarism who presented with clinical and histologic features of female AGA in the absence of detectable androgens or other signs of post-pubertal androgenization.32. which is correlated to premature AGA in men.28 The search for the gene continues.

33 The binding of androgens to ARP results in modification of signal transduction between the mesenchymal-derived dermal papilla and the epithelial-derived follicular cells. One can speculate that this difference in embryonic origin may influence the well-known differential response of follicles in the occipital region as against the rest of the scalp in AGA. and may have a protective effect on hair follicles. However. These events within the follicle result in the transformation of terminal to miniaturized hair follicles on the scalp in AGA. hair follicles at puberty. Clinical features of AGA History Thinning of the hair can occur as early as the age of 12 (Figure 3. 12% in one study showed a completely negative family history. The shedding may be seasonal in a small number of individuals. However. Norwood and Lehr45 have proposed that female AGA may be a separate entity. There is 6 times more aromatase in the frontal follicles and 4 times more in the occipital follicles of women than in those of men. in other androgensensitive areas such as the beard and mustache.2a) and as late as the age of 45 in both sexes.33 The receptor levels were found to be 30% greater in balding frontal hair follicles than in nonbalding occipital follicles in both men and women with AGA. although hair density does decrease as they age further. Dermis of the frontoparietal scalp is derived from the neural crest.33 Aromatase results in the conversion of T to estradiol and estrone. Most cases start between the ages of 15 and 25.17 Studying the quail-chick model. Ziller46 found differences of embryonic origin of the dermis of the fronto-parietal scalp compared to the occipital scalp. which can elicit a telogen effluvium. This likewise helps explain why women with AGA usually retain their frontal hairline and have less hair loss than men with AGA. Usually there is a positive family history.47 The clinical course is gradual. The cytochrome P450 aromatase enzyme is also part of normal androgen metabolism.32. including starting or stopping the oral contraceptive pills and post-partum and peri. they admit that it is impossible to distinguish male from female hair shaft miniaturization either clinically or histologically. Women . rather than downsize.13. alternating with periods when there is little shedding. Paradoxically.86 Hair Loss: principles of diagnosis and management of alopecia tion).and post-menopausal states. However. but the total receptor content is 40% less in women than in men. androgens upsize. The explanation for this bifurcated action is not known. Aromatase is significantly higher in the hair follicles of women. These events. AGA usually manifests at an early age and progresses slowly.47 Many men reach their maximum pattern by their forties. and therefore the resulting shift will lessen conversion of T to DHT. the condition may seem stable for years.17. These findings are intriguing.25 Hair loss in women may be triggered by hormonal changes. may unmask a tendency for AGA.8. consisting of acute episodic phases with increased loss of telogen hair.33 Androgen receptor proteins (ARP) are found in the outer root sheath and dermal papilla fibroblasts of scalp hair follicles. whereas dermis of the occipital/temporal scalp is derived from the mesoderm.47 For many individuals.

hirsutism and acne. Baldness was assessed twice. and death due to any cause. coronary heart disease death. especially among men with hypertension or high cholesterol levels. in 1956 and in 1962. However.52 showed that vertex pattern balding appears to be a marker for increased risk of coronary heart disease. cardiovascular disease.48 An increased risk for coronary artery disease has recently been correlated to vertex balding in men. It was felt by these authors that early vertex balding may be a useful marker to identify men at increased risk who may benefit from aggressive screening and primary prevention efforts directed toward other known modifiable risk factors for coronary heart disease. Extent of baldness was not associ- .017 men from Framingham. hyperandrogenism is not a problem.2 (a) Male androgenetic alopecia can appear early. Massachusetts. (b) The presence of miniaturized hairs helps to confirm a diagnosis of AGA. standing for seborrhea. A contrast paper is placed in a parted area of the scalp. The relations between the extent and progression of baldness and the aforementioned outcomes were assessed using a Cox proportional hazards model.50 with an increased risk for atherosclerotic and coronary heart disease in balding men. Herrera et al.Androgenetic alopecia 87 Figure 3. The hair is then closely examined against this backdrop. must be questioned about the regularity of their periods and the presence or absence of hirsutism in an attempt to determine if hyperandrogenism is a problem. adjusting for age and other known cardiovascular disease risk factors. SAHA syndrome. This is a 13-year-old boy showing frontotemporal thinning and hair miniaturization.49–51 In one study there appeared to be lipoprotein and triglyceride level differences between males with vertex thinning and non-balding men. in a cohort of 2. Lotufo et al. frequently indicates an androgen excess in the female patient.53 assessed the relation between the extent and progression of baldness and coronary heart disease. The cohort was followed for up to 30 years for new occurrences of coronary heart disease. The biologic mecha- nisms for this relationship are unknown. alopecia. in the vast majority of women with AGA.

and national representative sampling. women usually have less severe hair loss than men and . in a study of 478 men. and dyslipidemia in men with early onset of AGA (< 35 years). the amount of progression of baldness was associated with coronary heart disease occurrence (relative risk (RR)=2. These authors suggest that men with early AGA might benefit from screening for cardiovascular risk factors and for insulin resistance. including race and age. A practice-based case-control study in men aged 19–50 years showed a strikingly increased risk of hyper-insulinemia and insulinresistance-associated disorders such as obesity.88 Hair Loss: principles of diagnosis and management of alopecia ated with any of the outcomes. when compared to age-matched controls. and was similar regardless of the severity of baldness at baseline and was independent of other risk factors. 95% confidence interval (CI) 1.5 per 10. that tend to remain clinically silent until they are advanced. extended follow-up.4. The major strengths of this study included its prospective design. beginning at approximately 60 years of age. thus limiting the effective power of their study. Hawk et al. Men with AGA had a consistently higher incidence of prostate cancer compared with those without AGA. no association between coronary heart disease and androgenetic alopecia was found.47 In some individuals. Miniaturized vellus-like hairs can usually be seen with contrast paper placed over a part (Figure 3.3–4. coronary heart disease mortality (RR=3. in which the alopecia is merely a symptom that the patient may clutch on to. On the other hand. Incident cases of prostate cancer were identified by interviews. and all-cause mortality (RR =2. A hair pull test is usually negative. 95% CI 1.5. AGA becomes a preoccupation. A drawback was that approximately 1/3 of their cohort had not yet reached the advanced age-range in which clinical prostate cancer is typically present.7).5–3.8.47 Physical examination Hair loss is patterned and non-scarring. large sample size.421 men age 25–75 years (median age at baseline 55) without a history of prostate cancer were examined for AGA in the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey. Prostate cancer was diagnosed in 214 subjects over 17–21 years of follow-up.5 vs 12. Psychoneurotic attitudes may ensue. 56 Participants were followed from baseline (1971–4) through to 1992.55 A total of 3.8). AGA may unmask a psychological lability and/or psychiatric disturbance.2b). 95% CI 1. The adjusted relative risk for prostate cancer among men with any degree of baldness was 1. and occasionally in men. and is blamed for all social and professional problems. though only in involved areas of the scalp.54 This finding supports the hypothesis that early AGA could be a clinical marker of insulin resistance. with preservation of follicular ostia.4. hypertension.9–7. In terms of the pattern of hair loss. In some women with AGA. although there may be a mild increase in telogen hairs. However.000 person years). The authors concluded that men with AGA had a 50% excess risk for clinical prostate cancer. medical records and death certificates.56 further hypothesize that AGA in men may predict other age-related pathological processes. The investigators noted that the age-standardized incidence of prostate cancer was greater among men with baldness at baseline (17. It was concluded that rapid hair loss may be a marker for coronary heart disease.4). such as atherogenesis.

4 (a) Ludwig classification of female AGA. In a significant percentage of female patients with AGA.4–3. ‘parting’) in the centro-parietal area with that in the occipital area. Shapiro feels that approximately 30% of women have a more global thinning. Olsen58 feels that 5% show a global decrease in scalp hair density. diffuse hair thinning may be present (Figure 3. there is a frontal hairline recession associated with thinning or balding on the Figure 3.57 Ludwig Stage I is the most common pattern. Reproduced with permission from the British Journal of Dermatology 1977. and is divided in 3 stages according to severity (Figures 3. retain their frontal hairline (Figure 3.Androgenetic alopecia 89 Figure 3. most women present with an intact frontal hair line. ‘parting’) found in a woman without AGA. there still remains a variance of hair density on the top of the scalp versus the sides or the back of the scalp. showing the three different stages of severity. In men. Hair loss may only be evident when one compares the relative widths of the division of bare scalp between areas of combed hair (‘part’. This generally occurs in those women with more advanced hair loss. (b) The characteristically narrow division of bare scalp between areas of combed hair (‘part’. 97:247–54. The hair thinning is mostly on the crown. and usually in those with early-onset AGA.9a and b).3 In female AGA. The presence of global thinning clearly decreases the chances of being a successful female hair transplant candidate. . This pattern is recognized as the Ludwig pattern. and women affected may require an endocrine work-up if they show other signs of androgen excess.3). Even with this diffuse loss. Ludwig Stage III is rare.8).

She will also notice her ponytail diameter may be reduced one-third to one-half of what it used to be. crown or vertex. as in Figure 3.6 Ludwig Stage II: The width of the division of bare scalp (‘part’.8 Ludwig Stage III: Considerable loss of hair. Hamilton originally classified male AGA on the basis of fronto-parietal/fronto-temporal recession and vertex thinning. and is divided . improved on this pictorial classification. with certain individuals showing no recession and only vertex thinning. ‘parting’) is now considerably more evident than in Ludwig I. as before. This pattern is known as the Norwood-Hamilton pattern. 60 more than 25 years later. ‘parting’) may be the first complaint of the female patient.10a and b.90 Hair Loss: principles of diagnosis and management of alopecia Figure 3. Figure 3. There are exceptions.7 Mother (left) with Ludwig Stage II and daughter (right) with Ludwig Stage I.5 Ludwig Stage I: A widening of the division of bare scalp between areas of combed hair (‘part’. Figure 3. 59 Norwood. The elastic band that she usually uses to tie up her ponytail can now be wound several times around her hair in contrast to only once or twice. Figure 3.

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Figure 3.9 Female AGA may be totally diffuse, involving not only (a) the centro-parietal area but also (b) the sides and the back of the scalp.

Figure 3.10a and b A rare case of a 55-year-old male with absolutely no recession and simply vertex thinning.

into 7 stages according to severity (Figures 3.11–3.16).60 The first change is bitemporal recession, which is seen in 96% of sexually mature Caucasian males, including those men not destined to progress to further hair loss. Resculpturing of the frontal hairline with some bi-temporal recession, seen post-puberty in

most men, does not necessarily herald the expression of AGA, and is unlikely to reverse with current therapies. However, a deeper bitemporal recession of greater than 1 inch from the frontal hair line is part of the AGA phenotype, and, if treated early, may respond to therapy.40

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Figure 3.11 Norwood-Hamilton Classification of Hair Loss based on severity.

These patterns are not restrictive, and some women can present with the Norwood-Hamilton pattern (Figures 3.17–3.19) and some men with the Ludwig pattern (Figures 3.20 and 3.21). Norwood and Lehr45 feel that 10% of their male AGA patients present with a female AGA pattern. Venning and Dawber48 when they examined 564 women aged over 20 years found that 80% of pre-menopausal women had thinning in the Ludwig pattern and 13% had Hamilton Type II–IV patterns. After menopause the proportion exhibiting the male pattern increased to 37%, and, although they did not progress to beyond Hamilton Stage IV, some had marked M-shaped recession at both temples.

Figure 3.12 (a) A 33-year-old male showing the classic M hairline with fronto-temporal recession. (b) He also has vertex thinning, making him a Norwood-Hamilton Stage III. Reproduced with permission from Southern Medical Journal 1975; 68:1359–65.

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Figure 3.13 Early Norwood-Hamilton Stage IV, with the emergence of a bridge connecting lateral portions of the scalp.

Figure 3.15 Norwood-Hamilton Stage V, with the bridge gone but still a significant number of miniaturized hairs on the top of the scalp.

Figure 3.14 Late Norwood-Hamilton Stage IV, with the bridge less intact.

Figure 3.16 Norwood-Hamilton Stage VI, with very little hair on the top of the scalp.

Differential diagnosis
Usually the diagnosis of AGA is not a difficult one in men. However, in women, the diagnosis may be more difficult. The diagnosis of AGA is usually supported with the following cardinal features:

• • • • •

usual focal balding pattern with miniaturized hairs gradual onset with progression thinning with or without gradually developing bare patches onset after puberty negative pull test

A 40-year-old female with NorwoodHamilton Stage II AGA with fronto-temporal recession. (a) Frontal view (b) Lateral view.18 Women can show the Norwood-Hamilton pattern.20 A female with AGA with a NorwoodHamiltion Stage VI pattern. . Figure 3. Figure 3. Figure 3. with miniaturized hairs.19 A female with AGA with a Norwood-Hamilton Stage V pattern. with preservation of the ‘horseshoe’ of hair at the sides and back of the scalp.94 Hair Loss: principles of diagnosis and management of alopecia Figure 3.17 Norwood-Hamilton Stage VII.

Figure 3. frequently with an iden- . The other two diagnoses that may be difficult to distinguish are telogen effluvium and alopecia areata. Telogen effluvium is usually generalized (Figure 3. Both these entities are discussed at length in other chapters. (a) A fourteen-year-old male with Ludwig Stage I.22a A 40-year-old male with Ludwig Stage II. Figure 3. (b) A seventeen-year-old male with the Ludwig Stage I pattern.22b Patterns of hair loss can intermix within the same family and within the same sex. Norwood-Hamilton Stage VII in a 48-year-old father (right) and Ludwig Stage I occurring in his 20-year-old son (left).Androgenetic alopecia 95 Figure 3. with an abrupt onset.23a).21 Two male teenagers with the Ludwig Stage I pattern.

Shedding is prominent. (Figure 3. Figure 3. Onset is usually abrupt.24).96 Hair Loss: principles of diagnosis and management of alopecia Figure 3. but usually not childhood. tifiable trigger. It is ex- . with over 60% presenting under the age of 20. This is unusual with AGA. with no bare patches. Overlapping of AGA and alopecia areata can occur. but can be generalized. Shedding is prominent.23c Patients with telogen effluvium frequently present with bag of hair to show the physician. with remissions and relapses.23a and b Telogen effluvium consists of hair thinning in a generalized manner not only (a) on top of the scalp but also (b) on the sides. This amount of hair loss would not be seen in AGA. The pull test is positive with telogen hairs.23d A 28-year-old female with telogen effluvium who kept a diary of hair loss for 5 years. Figure 3. with a positive pull test for both dystrophic anagen and telogen hairs. Onset is at any age. There is thinning. Onset is at any age. Alopecia areata (AA) is usually randomly patchy.

The meticulous ‘unit area trichogram’ introduced by Rushton61 will also give information on hair density. the scalp biopsy will give the physician not only the same information with respect to anagen/telogen and terminal/vellus ratios. If an AGA patient has a previous. involving the hair pluck. he or she must be warned that that it could recur after surgery. or will have AA. However. are very popular in Europe and are useful. it requires special skill and is fairly labor-intensive.Androgenetic alopecia 97 Figure 3. have. or will have AA. It is expected that almost 2% of patients with AGA have had. no laboratory work-up is necessary unless there is concomitant diffuse hair loss. he or she must be warned that that it could recur after surgery. If an AGA patient has a previous recent or remote history of AA. In . (b) A 35-year-old male with AGA with a 3-month history of a patch of AA. recent or remote history of AA.7% of patients with AGA have had. have.0 mm scalp biopsy with transverse sectioning is the best laboratory test to distinguish AGA from AA or telogen effluvium. The 4. Standard trichograms. but also more information on hair density and inflammatory perifollicular changes. pected that 1.24a and b Overlapping of AGA and alopecia areata (AA) can occur. This may have great significance if one is contemplating hair transplantation surgery for AGA. This may have great significance if one is contemplating hair transplantation surgery for AGA. (a) A 25-year-old female with female AGA with a 6-month history of a patch of AA. However. Laboratory tests In men.

only the Pathology The histologic features of AGA are similar in males and females.29). In fat.25). Usually. In papillary dermis. papillary dermis.) Horizontal sections show distinctive changes in papillary and reticular dermis and in the deeper subcutaneous sections. and vellus-like hairs are identified.25a and b Stelae or fibrous streamers (FSt) commonly seen in AGA (courtesy of Dr Magdalena Martinka). have a thin outer root sheath. a free testosterone and dehydroepiandrosterone sulfate (DHEAS) test should be ordered.26). Catagen and telogen terminal hairs are noted as well (Figure 3.28). Vellus and vellus-like hairs are less than 0. In reticular dermis there are no vellus or vellus-like hairs. women. This patterning is typical of scalp hair. both terminal. and therefore an androgen work-up is not indicated. Terminal hair bulbs predominate in anagen phase. hairs on horizontal section are arranged in follicular bundles of 2–4 hairs with sebaceous glands and arrector pili muscle63 (Figure 3.62 Vertical sections show terminal hairs and follicular stelae in the subcutaneous tissue and reticular dermis and terminal and vellus hairs and stelae in the .62–64 (Stelae are the residual fibrous tracts that mark the upward migration of the catagen. and originate in the upper half of the dermis (Figure 3. Androgen levels should only be ordered in those women who appear clinically to have an androgen excess. because of the frequency of thyroid abnormalities and the difficulty of distinguishing AGA from telogen effluvium. Ferritin levels are also ordered routinely on menstruating females. The vast majority of women with AGA do not display hyper-androgenism.03 mm in diameter. this author recommends a routine thyroid stimulating hormone test (TSH).98 Hair Loss: principles of diagnosis and management of alopecia Figure 3. If one suspects an androgen excess. as low iron levels can trigger a telogen effluvium that may mimic AGA.27). Primary vellus hairs are small hairs. Vellus-like hairs are miniaturized hairs that have a thick outer root sheath and originate from a terminal hair rooted in reticular dermis or subcutaneous fat with underlying stelae (Figure 3. vellus. telogen or miniaturizing hair shaft and bulb (Figure 3.

29 A close-up of a follicular bundle in AGA. Figure 3. The difference of counts between papillary dermis and reticular dermis represents the number of . Figure 3. In the reticular dermis the number is usually reduced to 35. indicating true miniaturization (courtesy of Dr Magdalena Martinka).27 Secondary vellus hair (V) with small hair shaft and large outer root sheath (ORS). in the upper papillary dermis counts are usually around 40–50. showing a vellus hair (V) and a telogen hair (T).28 Follicular bundles with miniaturized hairs (courtesy of Dr Magdalena Martinka). and in the fat is usually around 30.26 Primary vellus hair (V) with a small hair shaft and small outer root sheath (ORS) (courtesy of Dr Magdalena Martinka). Follicular counts vary from level to level. Note the prominence of the sebaceous glands (SG) when hairs are miniaturized (courtesy of Dr Magdalena Martinka).Androgenetic alopecia 99 Figure 3. deeper anagen terminal hairs are present (Figure 3.30). Normally. Figure 3.

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Figure 3.30 In AGA, subcutaneous fat (F) contains anagen hairs (AH) (courtesy of Dr Magdalena Martinka).

Figure 3.31 Inflammatory infiltrate in AGA is not uncommon. Note the perifollicular lymphocytic infiltrate around this follicular bundle, which contains a miniaturized hair (MH) (courtesy of Dr Magdalena Martinka). creased in diameter, but eventually a mixture of follicular sizes is apparent. Sebaceous glands seem enlarged in relation to these miniaturized follicles (Figure 3.26). Arao-Perkins bodies may be seen. These are small clusters of elastic fibers in the neck of dermal papillae. They are clumped in catagen and located at the lowest point of origin of the follicular stela. Stacks of these Arao-Perkins bodies may be seen, like rungs of ladders, in these stelae of miniaturized anagen hairs. One-third of patients with AGA show mild inflammation, just as one-third of normal controls do. Forty per cent of patients with AGA show moderate lymphohistiocytic inflammation, compared to only 10% of normal controls.62 (Figure 3.31). The role of inflammation is controversial. Possible causes for inflammation include seborrheic dermatitis, actinic damage, and the application of comedogenic, irritant, sensitizing or otherwise toxic cosmetics and grooming agents to the scalp. Even porphyrins elaborated by follicular bacteria and activated by UV

vellus hairs present in the papillary dermis. The difference in follicular counts between reticular dermis and fat represents the number of terminal telogen hairs. In AGA, the total number of follicular counts is usually normal in the papillary dermis. However, Whiting has seen a reduction in 10% of cases of AGA, indicating a decreased capacity for follicular regrowth in this small number of AGA patients.63 Ratios of anagen to telogen and terminal to vellus change in AGA. Normally 90–94% of hairs are in anagen and 6–10% in telogen. In AGA, as few as 80% of hairs are in anagen and up to 20% in telogen. In AGA, since miniaturization is due to the shortening of the anagen phase, with no decrease in telogen, there is clearly an increase in telogen hairs. The terminal to vellus ratio is normally 7:1. In AGA, the ratio is 2:1, indicating a marked shift to miniaturization in AGA. A characteristic microscopic finding in AGA is volumetric reduction of terminal follicles. Initially the follicles are only minimally de-

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light could cause some inflammation. These causes may be more pronounced in the less protected scalp.62

Treatment
The whole raison d’être for treating AGA is the psycho-social aspect. Hair loss can truly detract from an individual’s holistic sense of well-being. It is important to address AGA in the context of overall patient health by taking the time to discuss the impact that AGA has on the patient’s life. Balding men are perceived as older and less physically and socially attractive.4–6 Some balding men feel less attractive, and struggle to cope with hair loss.4– 6 They worry and search for ways to compensate or restore body image. Behavioral coping mechanisms include changing hairstyle, improving physique or growing a beard or mustache.4–6 Women also experience great stress from AGA, which can affect their lives significantly. 5 These psycho-social issues should be addressed before the implementation of medical or surgical therapy.

Treatment options
Two decades ago hair-growth promoters were non-existent. From a medical perspective, little could be offered to patients with AGA. Today there are new classes of evidence-based hair-growth promoters with unquestionable proven efficacy. A hair-growth promoting agent must either prolong the anagen phase or increase matrix girth by influencing follicular growth controls. For example, in AGA, drug targets may include steroid receptors, steroid metabolizing en-

zymes and growth factors or cytokines that are implicated in controlling cell cycling and conversion of terminal to miniaturized hairs. We are currently just beginning to unravel the molecular control mechanisms and their location within the hair follicle. Further understanding of this cascade of orchestrated events is crucial for the development of more effective agents. Hair-growth promoters can be classified according to their mode of action: hormone modifiers versus biologic response modifiers. Hormone modifiers for AGA alter the perifollicular endocrine milieu by blocking either 5areductase or androgen receptor proteins. Biologic response modifiers have a non-endocrine effect on follicular cycling. The aim of all these agents is to prevent the apoptotic events precipitating catagen/telogen and to maintain a longer anagen state, so that genetically programmed miniaturization will be delayed or prevented. Another aim is to reverse miniaturization by providing the appropriate hormonal and cytokine factors that nurture hair growth and inhibit factors that have a negative effect on hair growth. There is still no cure for AGA and, without any treatment, those affected by AGA can experience a mean steady decrease in hair weight of about 6% per year.65 If treatment is desired, options can be summarized as follows: For men, options include finasteride, minoxidil, hair transplantation (HT) or a hairpiece. For women, options include minoxidil, spironolactone, cyproterone acetate, hair transplantation or a hairpiece. It is important that patients have realistic expectations regarding their medical treatment outcome, and the emphasis should be placed on the prevention of further hair loss. Medical treatments will only be effective if there is sufficient hair to salvage, with at least miniaturized hairs to convert into terminal hair. For those with more advanced

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hair loss, surgery or hairpiece may be the only options. Each option will be discussed in detail on the basis of classification.

Hormone modifiers
Androgen blockade 5a-reductase inhibitor Finasteride: Finasteride (Propecia™) is a synthetic 4-azasteroid compound that is a specific inhibitor of type II 5a-reductase, an intracellular enzyme that converts T into DHT.38,40,66 Finasteride does not have any hormonal properties in itself,38,40 and has no estrogenic, antiestrogenic or progestational effects. By inhibiting type II 5a-reductase, it blocks the peripheral conversion of T to DHT, resulting in significant decreases in serum and tissue DHT concentrations.38,40,67–71 A recent study by Drake et al.69 showed that median scalp DHT levels decreased by 13% with placebo and by 64.1% and 69.4% with 1 mg and 5 mg of finasteride, respectively, after 42 days of treatment. Median serum DHT levels decreased by 71.4% and 72.2% with 1 mg and 5 mg on the same schedule. This study also showed that doses as low as 0.2 mg daily decreased .scalp and serum DHT. The study by Roberts et al.70 confirmed that finasteride 1 mg daily was the optimal dose, with 1 mg and 5 mg superior to lower doses such as 0.2 mg/daily. The daily 5 mg dose was not more efficacious than the 1 mg dose. In 1997 the FDA approved finasteride for use in the United States at a dose of 1 mg/day in men with AGA. Three double-blind, randomized, placebo-controlled studies were conducted in 1879 men ages 18 to 41 years with mild to moderate hair loss.40,72 Two of the studies enrolled men with predominantly vertex hair loss40 and one

study enrolled men with predominantly frontal hair loss.72 Finasteride 1 mg oral tablets or placebo tablets were taken once daily for 24 months in the vertex studies and 12 months in the frontal study. All three studies showed a significant hair count increase at 6 and 12 months in men treated with finasteride, while a significant decrease in hair counts was demonstrated in men treated with placebo. In the second year, hair counts remained stable at the increased level in the men who continued to receive finasteride. In the vertex studies, those individuals who were crossed over after 12 months from finasteride to placebo showed loss of the benefit achieved in the first 12 months by hair count, and those who were switched from placebo to finasteride showed significant gains. A histologic study by Whiting et al.73 showed a significant increase in terminal anagen hairs from baseline in scalp biopsies taken from men at baseline and after 12 months of finasteride. This was also significantly different from the placebo group. Histologically, vellus-like hairs decreased, and the terminal to vellus ratio increased, in the finasteride group compared with the placebo group, suggesting reversal of the miniaturization process. Therapeutic efficacy was assessed with a blinded rating of standardized photographs, patient self-assessment and investigator assessment. From these studies, it can be concluded that finasteride can stabilize hair loss in 83% of the cases with vertex hair loss after 2 years, and in 70% of cases with frontal hair loss after 1 year. The chances of mild to moderate regrowth are 61% on the vertex after 2 years and 37% on the frontal area after 1 year. Continued daily use of 1 mg oral finasteride is needed for sustained benefit. In two studies in men with vertex hair loss, treatment with finasteride 1 mg/day or placebo was continued for 5 years. Based on photographic assessment, treatment with finasteride for 5 years resulted in stabilization of hair loss

Thirty-three men received finasteride 1 mg daily and 33 received placebo for 48 weeks. multicenter trial. regrowth was observed in 65% of men treated with finasteride for 5 years compared to gradual hair loss observed in 100% of men treated with placebo. The study was extended for 48 weeks for a total of 96 weeks. visit number and treatment. This study enrolled 212 men age 18–40 years with AGA. investigator. compared with 25% on placebo. The hair weight study demonstrated that treatment with finasteride 1 mg provides continued maintenance and improvement of hair growth over 96 weeks. and photographic assessments did not demonstrate any improvement in slowing hair thinning. significant differences between finasteride and placebo were seen with small numbers of subjects. and histologic analysis of scalp biopsy specimens. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. double-blind. Macrophotographs were taken to measure total as well as anagen hair counts in a 1 cm2 target area of the scalp. A study of finasteride in 136 postmenopausal women with AGA showed no benefit compared with placebo. blinded ratings of standardized photographs by an expert panel. Finasteride was generally well tolerated. patient. After 1 year of therapy. 136 postmenopausal women (41–60 years of age) with AGA received finasteride 1 mg/day or placebo. In the extension study. hair in a marked site was handclipped using a magnifying light. In this study.Androgenetic alopecia 103 in up to 90% of men.74 In a study of hair weights done by Price. placebocontrolled study. Based on hair counts. Efficacy was evaluated by scalp hair counts. In . Treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47%. increasing hair growth.75 Van Neste et al. or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. there was no significant difference in the change in hair count between the finasteride and placebo groups. After 96 weeks. double-blind. While improvement for finasteride-treated men compared to baseline was greater at 24 months. Patients were randomized to receive either finasteride 1 mg daily or placebo for 48 weeks. randomized.77 A 2-year study in balding men between the ages of 41 and 60 years is ongoing. 76 using the phototrichogram method. patient and investigator assessments. leading to a net improvement in hair count of 277 hairs (31%) for men treated with finasteride compared with placebo after 5 years.. All hair samples were weighed in a single session by a technician who was blinded to patient. At 6week intervals. A small 24-month double-blind placebocontrolled study on 28 men aged 53– 76 years taking finasteride 5 mg per day for benign prostatic hypertrophy showed statistically significant improvement in hair counts in a circular balding 1-inch target area in the finasteride group compared to the placebo group. placebo-controlled. treatment with finasteride 1 mg per day for 48 weeks significantly increased both total and anagen hair counts and improved anagen to telogen ratios compared to placebo. the total hair weight showed a statistically significant increase from baseline weight in the finasteridetreated subjects. provided direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. Sixty-six men aged 18–40 years with Norwood-Hamilton Stage III and IV were enrolled in a randomized. Finasteride may show improvement in older men. the difference between the group treated with finasteride and the placebo group continued to increase throughout the 5 years of the study.79 In this 1-year. 78. Similarly. 26 men continued to receive finasteride 1 mg and 23 men remained on placebo.

and are reversible upon cessation of treatment.1 A recent study by Overstreet et al. gynecomastia and feminization.79 Propecia™ 1 mg is to be taken every day. .40.83–85 There are no large controlled clinical studies in AGA with CPA. and therefore caution should be taken in patients with liver function abnormalities. but not in the United States.73. but there is a statistical difference when all side-effects are considered together (3.40. 80 Ninety per cent of circulating finasteride is bound to plasma proteins and can cross the blood-brain barrier.81 confirmed that finasteride 1 mg daily for 48 weeks did not effect spermatogenesis or semen production in men aged 19– 41 years.17 Exposure to semen of men who are taking finasteride does not pose a risk to a pregnant woman’s male fetus. but may be too low for female AGA. finasteride 1 mg/day taken for 12 months did not increase hair growth or slow the progression of hair thinning. We also advise the patient’s family doctor to double the PSA value while patients are taking finasteride.17 Diane-35 contains 2 mg of CPA. CPA is an effective treatment for hirsutism and acne. Cyproterone acetate: Cyproterone acetate (CPA) is a potent progestin and an androgen receptor antagonist. They are suitable only in women and are contraindicated in men because of side-effects such as impotence. with or without food.80 Finasteride tablets are coated to prevent contact with the active ingredients during manipulation.40 Side-effects will subside spontaneously in 58% of those who decide to continue the treatment.83.4% placebo). Androgen-receptor blockers (ARP inhibitors) Systemic ARP inhibitors decrease both T and DHT by binding to the androgen receptor. 1.3% erectile dysfunction (0.3% placebo).80 Finasteride is metabolized in the liver. CPA is available in Europe.80 Finasteride is well tolerated. This is adequate for the treatment of acne.80 Finasteride does not affect the cytochrome P450 metabolizing enzyme system.72 There was no significant difference from the placebo group for each of these side-effects taken alone.86–88 Fifty to 100 mg per day of CPA taken on days 5 to 14 of the menstrual cycle can be used in combination with an oral contraceptive to regulate menstrual cycles and to avoid pregnancy. on a regular schedule. This was confirmed by histologic analysis on 94 women with AGA.1%).7% placebo) and 0.8% decreased ejaculate volume (0.80 Dosage does not need to be adjusted in case of renal insufficiency. decreased libido. it is recommended a baseline PSA be taken for older men prior to initiation of therapy with finasteride. The bioavailability after oral intake is 65%.82 At the University of British Columbia Hair Research and Treatment Centre.80 but there is a risk that finasteride exposure during pregnancy may cause hypospadias in the developing male fetus.8% vs 2.72 Side-effects include 1. The effect on prostate volume and serum PSA in this young population without benign prostate hypertrophy was small and reversible upon discontinuation of the drug. Women who are or potentially may be pregnant should not take finasteride or handle crushed or broken tablets. The risk of teratogenicity in humans has not been directly evaluated.81 Finasteride can decrease PSA levels by 50% in older men. It may have some effect on stabilization of hair loss.8% decreased libido (1. and no drug interactions have been reported. and side-effects occur in less than 2% of patients. Asia and Canada. although regrowth is quite rare in this author’s experience.104 Hair Loss: principles of diagnosis and management of alopecia post-menopausal women with AGA.

93 but appear to have little effect on stimulating regrowth. Estrogens are weak 5a-reductase inhibitors.Androgenetic alopecia 105 Side-effects include depression. 95 plucked anagen hair bulbs from men applying minoxidil show a significant increase in proliferation index as measured by DNA flow cytometry. Topical and oral estrogens have been used in women with AGA.98. and interferes with the translocation of this complex into the cell nucleus. reducing androgen synthesis by the gonads. Its exact mechanism of action is still unclear.95 Another possible mechanism of action is the opposition to intracellular calcium entry. and its anti-androgenic effect is only mild.96 It has also been shown to prolong the survival time of keratinocytes in vitro. Both solutions are available without a prescription in the United States.66 Since one of its sideeffects is hypertrichosis. . It is a piperidinopyrimidine derivative that is used orally as an antihypertensive drug. and 200 mg per day is usually required.90 It also depletes the cytochrome P450 enzyme (CYP 450) complex. Minimal increases in serum potassium may occur.94 Minoxidil increases duration of anagen and enlarges miniaturized and suboptimal hair follicles.17 Spironolactone: Spironolactone is an aldosterone antagonist. although no controlled studies have been done. They also inhibit secretion of luteinizing hormonereleasing hormone (LH-RH) by the hypothalamus.84. Calcium normally enhances epidermal growth factors (EGF) and inhibits hair growth. but it has been used worldwide by many dermatologists for many years. Small open trials have shown some clinical effect in AGA.99 Minoxidil was approved for men by the FDA as a 2% solution in 1988 and as a 5% solution in 1997.85 The drug is less effective in female AGA. but are uncommon. nausea. Clinically.90 Spironolactone is effective mostly for hirsutism. Local vasodilatation does not seem to play a major role in hair growth. which weakly inhibits androgen biosynthesis in the adrenal glands.1 It has been shown to have a direct mitogenic effect on epidermal cells both in vitro and in vivo. Estrogen mediated: Estrogens increase levels of sex hormone binding globulin (SHBG). placebo-controlled trial.97. Biologic response modifiers Minoxidil Minoxidil (Rogaine™) was the first agent shown to promote hair regrowth. In men with AGA.89. a double-blind. which is a potassium channel agonist and enhances potassium ion permeability. thereby reducing circulating free T. The 5% solution has not yet been approved for women. thus opposing the entry of calcium into cells. It is a competitive inhibitor of androgen receptor protein binding. breast tenderness and loss of libido. weight gain.89 Women of childbearing age must use acceptable birth control methods and be aware there is a risk for feminization of a male fetus if they become pregnant. The main side-effect is menstrual irregularities. menstrual irregularity.89. the 2% solution was approved in 1991.92 but Spironolactone rarely offers the benefit of hair regrowth. It does not appear to have either a hormonal or an immunosuppressant effect.17 Women of childbearing potential must use an effective birth control method and be warned of the potential for feminization and the unknown teratogenicity risk if they become pregnant. For women.98 This would decrease EGF and subsequently enhance hair growth. 97 Minoxidil is converted to minoxidil-sulfate.91. estrogens may help to maintain the status quo and to slow the progression of AGA.85. a topical solution was developed to treat hair loss.

topical minoxidil solution must be continued indefinitely. Practically. approximately 30–35% of patients.100 Clinically. For some patients.17 Patients must be told that minoxidil solution is a scalp lotion.101–107 The rapid loss of hair weight after treatment confirms its trichogenic effects.1 The major increase is usually seen within the first 4 months of therapy.110 but there are no data on this combination therapy in humans. One millilitre of minoxidil solution must be used twice daily. In patients with very early AGA. every day in order to be effective. 63% who applied 2% topical minoxidil solution twice daily showed minimal to moderate regrowth using hair counts in macrophotographs for assessment. if one starts both medications simultaneously in a male patient. finasteride or the combination that is having the effect. he will not know whether it is either minoxidil. The spray applicator is not recommended. loss of hair is evident once treatment with topical minoxidil is discontinued. double-blind study involving 2294 men between the ages of 18 and 50. applying 2% topical minoxidil solution twice daily. showed moderate to dense regrowth as assessed by hair counts using macro-photographs.65 The 5% solution produced a 35% increase in hair weights. this may not be an issue. .1 Minoxidil should be used for one full year before its efficacy is assessed. not a hair lotion. For someone with moderate amounts of hair.65 Discontinuation of therapy results in loss of hair weight over 6 months to match the level in the placebo-treated group and untreated men. Minoxidil can be used for either frontal or vertex scalp thinning. it is important to continue using minoxidil for at least 4 months after starting finasteride to prevent the loss of hair that occurs with the discontinuation of minoxidil.17 No more than 2 ml should be applied every day. is a reasonable option.106 Hair Loss: principles of diagnosis and management of alopecia using hair weight measurements.103 In a multicenter. In a multi-center.108 The increase in density is mostly due to miniaturized hairs that are converted into terminal hairs rather than a de novo regrowth.108 Twicedaily application is needed for efficacy. if affordable. compared to 25% with the 2% solution. Minoxidil application halted hair loss over the 96 weeks. where it is ineffective and thus wasted. while both the placebotreated men and the untreated men had an approximately 6% decrease in hair weight per year. double-blind placebo-controlled study of 256 women between the ages of 18 and 45 with AGA. and combination therapy. found that topically minoxidil solutions of both 2% and 5% were significantly more effective than a placebo lotion or no treatment.65 The major increase in hair weight was observed within the first 20 weeks following initiation of therapy. In those cases.104 The hair loss becomes stabilized after the initial period of regrowth. regardless of the extent of the affected area. the best mode of application is to divide it into 5 parts and apply 5 drops to each part.65 In women. Twenty-five drops (1 ml) must be applied directly on to a dry scalp and then slightly spread with the fingers. Thus.9% with placebo. For those male patients already using minoxidil and wanting to switch to finasteride. it is hard to appreciate any regrowth or hair loss because of the great hair density.5% increase was found with the 2% solution compared to 1. Therapeutic efficacy is evaluated by patient satisfaction and physician comparison with a baseline photograph. one study of 32 weeks used hair weights to assess efficacy.109 One study in the stump-tailed macaque showed additive benefit in using both minoxidil and finasteride. since most of the sprayed solution will be applied on the hairs. physicians must rely mostly on the patient’s impression. and a 42.

1. Facial hypertrichosis (Figure 3. the concentration should be lowered to 2%.17.103 Contact with any mucosal surface (usually the eyes) should be avoided. The maximum oral daily dose for the treatment of hypertension is 100 mg. and may be slightly higher with the 5% solution.3 to 4.17 Occasionally.80 Only 0.111–113 Incidence of scalp irritation is approximately 7% with the 2% solution.32) may occur in 3–5% of women. The most frequent side-effect is an irritant contact der- matitis. and is usually not a problem in men. Minoxidil is poorly absorbed after topical application on normal intact skin.32 Hypertrichosis of the face can occur in women using topical minoxidil solution. The percentage of minoxidil that is absorbed is eliminated within 4 days. (a) Frontal view.80 If patients experience an irritant contact dermatitis due to the 5% solution.103 Minoxidil should not be used by pregnant or nursing women.80 Topical minoxidil solution is very safe. and side-effects are mainly dermatologic. If such an event occurs. (b) Lateral view. minoxidil itself causes an allergic contact dermatitis. and the treatment may have to be discontinued altogether. Studies have not shown any change in blood pressure or any other hemodynamic effect. thoroughly rinse the eyes with cool tap water. but minoxidil solution should be used with caution in patients with cardiovascular disease. they should stop the treatment until all symptoms have resolved. If they again develop dermatitis on the second trial.17 It is not clear yet why the hypertrichosis occurs. probably due to the propylene glycol in the vehicle. Patients will be unlikely to develop a tolerance to this side-effect.Androgenetic alopecia 107 Figure 3. but in humans data are lacking.80 It is metabolized in the liver and excreted in the urine. Each ml of the 5% solution contains 50 mg of minoxidil.5% reaches the systemic circulation.80 The effects of concomitant occlusion or abnormal skin are unknown 80 . because it will cause burning and irritation.80 Minoxidil is secreted in human milk.80 Accidental ingestion of topical minoxidil could lead to serious adverse effects.80.1.80 There is no evidence of teratogenicity in rats and rabbits. but it is possibly either through a systemic effect or via a transfer of .

17 Thorough hand-washing after each use may minimize irritation and possibly hypertrichosis in other body areas.17 They must either be mixed using generic powder forms or be applied as separate treatments. If patients respond to treatment. prior to treatment.108 Hair Loss: principles of diagnosis and management of alopecia the drug. the proprietary products. as they can give excellent results. Tretinoin Tretinoin (all-trans-retinoic acid) is a biologic response modifier. or hair transplantation if the patient has a good occipital scalp donor area.116 However. Patients should be reassured on the cosmetic appearance of hairpieces. Patients often need guidance as to where to get hairpieces.17 Those women who. For women with Ludwig stage III. are incompatible and become ineffective if compounded in the same solution. a hairpiece is suggested. or infertility). structured about the Ludwig classification. Rogaine® must be applied every morning and night and Retin-A ® during the day. Rogaine® and Retin-A®. Hyper-androgen excess should be checked by history and physical examination. Treatment of AGA in women Many factors must be considered in the treatment of AGA. and it is most appreciated when they are given a few options. hirsutism. patients may be offered androgen blockade with CPA or spironolactone. is presented in Figure 3. A partial hairpiece may also give a natural and satisfying appearance. topical therapies are usually ineffective. seborrheic dermatitis. Even though there seems to be some benefit in using the combination.17 It affects mostly the forehead. In women with stage I or II hair loss. Hypertrichosis is totally reversible upon discontinuation of the drug. malar areas. An algorithmic approach to AGA in women. Hair transplantation in female AGA will be discussed in Chapter 4. In addition. and sides of the face. For those with more advanced hair loss and a poor donor area. topical 5% minoxidil solution is offered and continued for 1 year (Figures 3.025% tretinoin and 0. already have mild hirsutism are more likely develop this side-effect. severe acne.34.e.35). formulated using generic powder forms.5% minoxidil. If there is any sign of virilization (i. during the day. It is a potent cell mitogen that promotes and regulates epithelial cell growth and differentiation.114 It has been proposed that tretinoin may have an effect on AGA by stimulating the growth of suboptimal hairs and could also act synergistically with minoxidil to produce more dense hair regrowth than either compound alone.33. the irritation of tretinoin is not always well tolerated. most patients are not compliant with the need for an extra application .114 It promotes angiogenesis115 and increases percutaneous absorption by affecting the fluidity and the lipid composition of cell membranes. making this combination an impractical option for most patients. then it is continued for as long as hair loss is perceived to be important to the patient. Those patients who are affected and continue with the treatment usually notice a decrease in and even a disappearance of the facial hair within a year. menstrual irregularities. If ongoing hair loss is detected after 1 year. serum testosterone and dehydroepiandrosterone-sulfate (DHEAS) tests should be ordered and referral to an endocrinologist may be indicated.116 A small study on men with AGA showed some hair regrowth when treated for 1 to 2 years with a combination solution of 0. 3.

Treatment of AGA in men For men. Vera H. such as the extent of hair loss. then patients are counseled to continue with treatment for as long as they feel hair loss is im- . MD. financial considerations and patient expectations.Price. structured around the Norwood- Hamilton classification. If evaluation reveals stabilization or regrowth. MD). In those with less severe hair loss and numerous miniaturized hairs. MD and Harvey Lui. the final decision is based on many factors.36. the presence or absence of miniaturized hairs.33 An algorithmic approach on the treatment of female AGA: UCSF-UBC Treatment Protocol for androgenetic alopecia in women (courtesy of Jerry Shapiro.37).38). An algorithmic approach to male AGA.Androgenetic alopecia 109 Figure 3. preference for topical or systemic therapy. patient age. Therapeutic efficacy is evaluated at 1 year (Figure 3. medical therapeutic options include finasteride or minoxidil (Figure 3. is outlined in Figure 3.

then a surgical approach or a hairpiece should be discussed. If ongoing hair loss occurs despite treatment. and (b) after 6 months of use of topical minoxidil. Studies are currently under way evaluating the effect of finasteride on the number of hair transplantation sessions. portant to them. showing marked improvement.110 Hair Loss: principles of diagnosis and management of alopecia Figure 3. medical therapy is unlikely to work.35 A 53-year-old female with AGA (a) before topical minoxidil solution.110 and can be prescribed to very motivated patients.34 A 40-year-old female with AGA (a) before topical minoxidil solution. showing marked improvement. with narrowing of her part/ parting. In those with more advanced hair loss and few miniaturized hairs. Figure 3. and (b) after 8 months of topical minoxidil solution. It is . and a surgical approach or a hairpiece is recommended. Combination therapy with both finasteride and minoxidil has been shown to have additive hair regrowth effects in a balding stump-tail macaque model.

MD.37 A good candidate for medical treatment of male AGA (note the presence of miniaturized hair). MD and Harvey Lui. Figure 3.36 An algorithmic approach on the treatment of male AGA: the UCSF-UBC Treatment Protocol for androgenetic alopecia in men (courtesy of Jerry Shapiro. . Vera H.Price. MD).Androgenetic alopecia 111 Figure 3.

showing improvement. This author recommends finasteride on all patients undergoing hair transplants if they are Stage IIIV–V pre-transplantation (Figure 3. Patient monitoring How is response to therapy assessed.38 A 24-year-old male with AGA (a) before the use of finasteride 1 mg/day and (b) one year later.112 Hair Loss: principles of diagnosis and management of alopecia Figure 3. A 33-year-old male with AGA (c) before the use of finasteride 1 mg/day and (d) after 11 months of therapy. and what methods can be used to determine treatment success or failure? First. patient impressions . likely that the combination of the two will reduce the number of sessions. showing improvement.39).

many patients are often unreliable and unsatisfied with subjective estimates. (b) The same individual 12 months after the use of finasteride 1 mg/day.40 Digital photography with a stereotactic device (Canfield Scientific. Figure 3. He was considering another session. The photograph is reviewed with the patient at each follow-up and compared to current hairgrowth status. Ideally. USA) is ideal as a means for monitoring patients. Matching therapy to patient expectations are determined. Photographs do not need to be taken annually. then an ordinary photograph should be taken. Unfortunately. thereby imparting some kind of objective measurement of response.39 (a) A 35-year-old male with two previous sessions of hair transplants.Androgenetic alopecia 113 Figure 3. This patient felt he did not need another transplant session.40). If one does Patient expectations are an important factor when discussing therapeutic options and goals. The key features to distinguish between are prevention and regrowth. Finally. each patient has digital photography taken at a standardized distance and position (Figure 3. serial part diameters can be taken from the same areas of the scalp with each visit. Both patient and physician should realize that these uncontrolled snapshots are not accurate. the last transplant four years before the photo. those . Expectations are largely dictated by the extent of hair loss. not have a digital set-up with a stereotactic device. but do give a general impression of the kind of coverage present at baseline. showing significant improvement. In men. New Jersey.

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with stage II or III hair loss have lower expectations and are primarily seeking prevention. It is also important to reset these expectations, emphasizing that regrowth can be difficult to perceive and only stabilization may be detected. Those with more advanced balding have higher expectations and are hoping for regrowth. If expectation levels are high, they may less likely to be satisfied with medical therapy. It is important to keep the expectations of this group low, emphasizing prevention and minimizing expectations of regrowth. Those seeking hair transplants all have high expectations and are usually satisfied.

reductase or the androgen receptor protein. Follicular stem-cell gene therapy will also be explored in the future, and would allow alteration of specific DNA transcription, RNA translation and modified synthesis of putative enzymes and receptors involved in the process of hair follicle miniaturization.

References
1. Price V.H. Treatment of hair loss. New Engl J Med, 1999; 341(13):964–73. 2. Rhodes T., Girman C.J., Savin R.C., et al. Prevalence of male pattern hair loss in 18–49 year old men. Dermatol Surg, 1998; 24(12): 1330–2. 3. Bergfeld W.F. Androgenetic alopecia: an autosomal dominant disorder. Am J Med, 1995; 98(1A):95S–98S. 4. Cash T.F. The psychosocial consequences of androgenetic alopecia: a review of the research literature. Br J Dermatol, 1999; 141(3):398–405. 5. Cash T.F., Price V.H. and Savin R.C. Psychological effects of androgenetic alopecia on women: comparisons with balding men and with female control subjects. J Am Acad Dermatol, 1993; 29(4):568–75. 6. Cash T.F. The psychological effects of androgenetic alopecia in men. J Am Acad Dermatol, 1992; 26(6):926–31. 7. Randall V.A. The use of dermal papilla cells in studies of normal and abnormal hair follicle biology. Dermatol Clin, 1996; 14(4):585–94. 8. Hibberts N.A., Howell A.E. and Randall V.A. Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp. J Endocrinol, 1998; 156(1):59–65. 9. Randall V.A., Hibberts N.A. and Hamada K. A comparison of the culture and growth of dermal papilla cells from hair follicles from non-balding and balding (androgenetic alopecia) scalp. Br J Dermatol, 1996; 134(3): 437–44.

Conclusions
The treatment of AGA has advanced tremendously in the last 10 years. The consultation process is no longer a disappointing meeting with the physician, but consists of an interactive session with choices and discussion. The algorithmic approach to AGA allows the clinician to select an appropriate therapeutic modality based on stage of hair loss. It is important to present patients with all therapeutic options, while addressing realistic expectations.

Outlook for the future
There are currently two treatment modalities for AGA: androgen blockade and biologic response modifiers. It is expected that more agents will be developed in both categories. Dual inhibitors, such as combined type I and type II 5a-reductase inhibitors, will probably be evaluated. Topical androgen receptor protein inhibitors and new biologic response modifiers will also undoubtedly be available. Targeted follicular gene therapy has the potential to block or intercept the synthesis of 5a-

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10. Randall V.A. Androgens and human hair growth. Clin Endocrinol (Oxf), 1994; 40(4): 439–57. 11. Randall V.A., Thornton M.J., Hamada K. and Messenger A.G. Androgen action in cultured dermal papilla cells from human hair follicles. Skin Pharmacol, 1994; 7(1–2):20–6. 12. Randall V.A. Role of 5 alpha-reductase in health and disease. Baillière’s Clin Endocrinol Metab, 1994; 8(2):405–31. 13. Randall V.A., Thornton M.J. and Messenger A.G. Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp. J Endocrinol , 1992; 133(1):141–7. 14. Randall V.A., Thornton M.J., Hamada K. and Messenger A.G. Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo. J Invest Dermatol, 1992; 98(6 Suppl):86S–91S. 15. Randall V.A., Thornton M.J., Hamada K., et al. Androgens and the hair follicle. Cultured human dermal papilla cells as a model system. Ann N Y Acad Sci, 1991; 642: 355–75. 16. Thornton M.J., Messenger A.G., Elliott K. and Randall V.A. Effect of androgens on the growth of cultured human dermal papilla cells derived from beard and scalp hair follicles. J Invest Dermatol, 1991; 97(2):345–8. 17. Shapiro J. and Price V.H. Hair regrowth. Therapeutic agents. Dermatol Clin, 1998; 16(2):341–56. 18. Rushton D.H., Ramsay I.D., Norris M.J. and Gilkes J.J. Natural progression of male pattern baldness in young men. Clin Exp Dermatol , 1991; 16(3):188–92. 19. Kuster W. and Happle R. The inheritance of common baldness: two B or not two B? J Am Acad Dermatol, 1984; 11(5 Pt 1):921–6. 20. Sybert V. Genetic Skin Disorders, pp. 165–7. 1997; New York: Oxford University Press. 21. McKusick V. Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic

22. 23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

Disorders. 1998; Baltimore, MD: Johns Hopkins University Press. Osborn D. Inheritance of baldness. J Hered, 1919; 7:347–55. Smith M. Male type alopecia, alopecia areata and normal hair in women: family histories. Arch Dermatol, 1964; 89:95–8. Harris D. The inheritance of premature baldness in men. Ann Eugen, 1946; 13: 172–81. Salamon T. Genetic factors in male pattern alopecia. In Biopathology of Pattern Alopecia, ed. G.M.A.Baccaredda-Boy and J.R.Frey, pp. 39–49. 1968; New York: Karger. Verbov J.L. Common baldness occurring in females only, in one generation. Br J Clin Pract, 1978; 32(9):261–2. Carey A.H.,Chan K.L., Short F., et al. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol (Oxf), 1993; 38(6):653–8. Carey A.H., Waterworth D., Patel K., et al. Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum Mol Genet, 1994; 3(10):1873–6. Konig A., Happle R., Tchitcherina E., et al. An X-linked gene involved in androgenetic alopecia: A lesson to be learned from adrenoleukodystrophy. [In Process Citation]. Dermatology, 2000; 200(3):213–18. Sprecher E., Shalata A., Dabhah K., et al. Androgenetic alopecia in heterozygous carriers of a mutation in the human hairless gene. J Am Acad Dermatol, 2000; 42(6): 978–82. Sreekumar G.P., Pardinas J., Wong C.O., et al. Serum androgens and genetic linkage analysis in early onset androgenetic alopecia [letter]. J Invest Dermatol, 1999; 113(2): 277–9. Sawaya M.E. Purification of androgen receptors in human sebocytes and hair. J Invest Dermatol, 1992; 98(6 Suppl): 92S– 96S.

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d33.Sawaya M.E. and Price V.H. Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Invest Dermatol, 1997; 109(3):296–300. 34. Chen W., Zouboulis C.C. and Orfanos C.E. The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders. Dermatology, 1996; 193(3): 177–84. 35. Bingham K.D. and Shaw D.A. The metabolism of testosterone by human male scalp skin. J Endocrinol, 1973; 57(1): 111–21. 36. Itami S., Kurata S., Sonoda T. and Takayasu S. Mechanism of action of androgen in dermal papilla cells. Ann N Y Acad Sci, 1991; 642:385–95. 37. Itami S., Kurata S., Sonoda T. and Takayasu S. Characterization of 5 alpha-reductase in cultured human dermal papilla cells from beard and occipital scalp hair. J Invest Dermatol, 1991; 96(1):57–60. 38. Kaufman K.D. Androgen metabolism as it affects hair growth in androgenetic alopecia. Dermatol Clin, 1996; 14(4):697–711. 39. Schweikert H.U. and Wilson J.D. Regulation of human hair growth by steroid hormones. I. Testerone metabolism in isolated hairs. J Clin Endocrinol Metab, 1974; 38(5):811–19. 40. Kaufman K.D., Olsen E.A., Whiting D., et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol, 1998; 39(4 Pt 1):578–89. 41. Imperato-McGinley J. 5-alpha-reductase deficiency. Curr Ther Endocrinol Metab, 1994; 5:351–4. 42. Imperato-McGinley J., Guerrero L., Gautier T. and Peterson R.E. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science, 1974; 186(4170):1213–15. 43. Price V.H. Testosterone metabolism in the skin. A review of its function in androgenetic alopecia, acne vulgaris, and

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

idiopathic hirsutism including recent studies with antiandrogens. Arch Dermatol, 1975; 111(11):1496–1502. Orme S., Cullen D.R. and Messenger A.G. Diffuse female hair loss: are androgens necessary? Br J Dermatol, 1999; 141(3):521–3. Norwood O.T. and Lehr B. Female androgenetic alopecia: a separate entity. Dermatol Surg, 2000; 26(7):679–82. Ziller C. Pattern formation in neural crest derivatives. In Hair research for the next millenium, ed. V.R.D.Van Neste, p. 1. 1996; Amsterdam: Elsevier Science. Orfanos C. Androgenetic alopecia: clinical aspects and treatment. In Hair and Hair Diseases, ed. C.Orfanos, pp. 485–527. 1990; Berlin: Springer-Verlag. Venning V.A. and Dawber R.P. Patterned androgenic alopecia in women. J Am Acad Dermatol, 1988; 18(5 Pt 1):1073–7. Lesko S.M., Rosenberg L. and Shapiro S. A case-control study of baldness in relation to myocardial infarction in men [published erratum appears in JAMA 1993 May 19; 269(19):2508] [see comments]. JAMA, 1993; 269(8):998–1003. Sasmaz S., Senol M., Ozcan A., et al. The risk of coronary heart disease in men with androgenetic alopecia. J Eur Acad Dermatol Venereol, 1999; 12(2):123–5. Ford E.S., Freedman D.S. and Byers T. Baldness and ischemic heart disease in a national sample of men [see comments]. Am J Epidemiol, 1996; 143(7):651–7. Lotufo P.A., Chae C.U., Ajani U.A., et al. Male pattern baldness and coronary heart disease: the Physicians’ Health Study. Arch Intern Med, 2000; 160(2):165–71. Herrera C.R., D’Agostino R.B., Gerstman B.B., et al. Baldness and coronary heart disease rates in men from the Framingham Study. Am J Epidemiol, 1995; 142(8): 828–33. Matilainen V., Koskela P. and KeinanenKiukaanniemi S. Early

1977. 68(11):1359–65. or no treatment. Cooke N. J Clin Endocrinol Metab. The clinical development of a 5 alpha-reductase inhibitor. Whiting D. et al.S.. Oct 2000. 57. Roberts J. 1992. 2000.J. 1979. 356(9236): 1165–6. Hordinsky M. Stoner E. et al. 8:24–33. 1998.D.Androgenetic alopecia 117 55.. 101(4):455–8.A.. 257–279. 1994. Patterned loss of hair in men: Types and incidence. finasteride. 29(4):554]. 1998.A.. Dunlap F. Measuring reversal of hair miniaturization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and postmenopausal women. J Am Acad Dermatol. 1975.. 97(3):247–54.A. New York: McGraw-Hill. Fiedler V. 2000. Br J Dermatol. Changes in hair weight and hair count in men with androgenetic alopecia. Menefee E. 9(5):523–7. 1994. 68. placebo.H. 1999. 41(4):550–4. Bruskewitz R. J Steroid Biochem Mol Biol. Cancer Epidemiol Biomarkers Prev. South Med J. 4(3):282–4. 1999. androgenetic alopecia as a marker of insulin resistance [letter] [in process citation]. 1984. Semin Cutan Med Surg. and Strauss P.H. 1999..T. 1993. 53:708–28. 63. 74. 67. New Engl J Med. Lancet. Hawk E. Rushton H.. Male pattern alopecia and coronary artery disease in men. and Mortimer C. The Finasteride Study Group [see comments]. Scalp biopsy as a diagnostic tool in androgenetic alopecia. a type 2 5 alpha reductase inhibitor in men with male pattern hair loss. 72. Ann NY Acad Sci. 1951. 327(17):1185–91. Propecia: New Clinical Data—Five Year Experience. 59.. Headington J. J Am Acad Dermatol. The effect of finasteride. 1999. 79(3):703–6. 17(4):276–83.E.I. 40(6 Pt 1):930–7. Sadick N.T. 60. Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the first National Health and Nutrition Examination Survey. Sawaya M. Clinical dose ranging studies with finasteride. Br J Dermatol. 64. and Graubard B. A basis for a morphometric approach to disorders of the hair follicle. 65. J Am Acad Dermatol. 71. Disorders of Hair Growth. Abstract.. Sanchez M. et al. 70. Hamilton J. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Whiting D.. Leyden J. Dallob A. 1990. pp.C. Drake L. et al. . J Am Acad Dermatol. Unger W. Transverse microscopic anatomy of the human scalp. 41(4):555–63. 109(4):429–37.. Dermatol Ther.. 120(4): 449–56. Olsen. Male pattern baldness: classification and incidence. Br J Dermatol.. Miller B. 1983. Gormley G. 69. Inc. after 66. Norwood O. 56. 37(3): 375–8. Stoner E. 1999. Breslow R. 61..C. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. 62. 28(5 Pt 1):755–63. 1993 Oct. et al. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia [published erratum appears in J Am Acad Dermatol. Whiting D.. 58. J Am Acad Dermatol. Arch Dermatol. ed. Geneva. E. a 5 alpha-reductase inhibitor.L.. Price V. Olsen E. The effect of finasteride in men with benign prostatic hyperplasia. In European Academy of Dermatovenereology Annual Meeting. on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness.. The unit area trichogram in the assessment of androgen-dependent alopecia. Ludwig E. and Kaufman K. 41(5 Pt 1):717–21. application of 5% and 2% topical minoxidil.T. Finasteride in the treatment of men with frontal male pattern hair loss [see comments]. 73. Waldstreicher J.C. Novel agents for the treatment of alopecia.. J Invest Dermatol Symp Proc. James K.

H. 90. 1985. Serafini P. 43(2): 200–5. 82. and Cunliffe W. hirsutism and virilism. 43(5): 768–76. 1996..118 Hair Loss: principles of diagnosis and management of alopecia 75. hirsutism or androgenic alopecia [letter]. The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women. et al. and Kubilus J. Shoupe D. 76. Barak M. J Soc Cosmet Chem.H. randomized doubleblind study. 83.R. Gould J. Requirement for the 7alphathio group and evidence for the loss of the heme and apoproteins of cytochrome P-450..C. et al. . 1999. Roberts J.H. Price V. Kan H. 81(6):558–60. Mortimer C. 1999. J Am Acad Dermatol... J Steroid Biochem.. Minoxidil stimulates mouse vibrissae follicles in organ culture [letter. Canadian Pharmacists Association Monography. Khoury E. Van Neste D. Price V. Roberts J. 85. Burke B. 254(5): 1726–33. In Compendium of Pharmaceuticals and Specialties (CPS) 34th Edition. 1999. 99(1):40–7. Langer P. 92.M. Ottawa. 86. Changes in hair weight in men with androgenetic alopecia after taking finasteride. Dermatologica. Orfanos C. Belgium. Br J Dermatol.H.. Kiesewetter F. and Vogels L. A controlled.L. and Gillette J. Antiandrogen therapy in dermatology. Effect of finasteride on free and total serum prostatespecific antigen in men with benign prostatic hyperplasia. Menard R. Fertil Steril. Amsterdam.. and Schell H. et al. Presentation at European Academy of Dermatology. 79. 1980. Brussels. Quantitative assessment of spironolactone treatment in women with diffuse androgen-dependent alopecia. J Invest Dermatol. Studies on the destruction of adrenal and testicular cytochrome P-450 by spironolactone. Olsen E.. 6(6):827–36.. 1991. The effects of finasteride on post-menopausal women with androgenetic alopecia. Dermatologica.H.. Int J Dermatol.. Horm Metab Res. 1996. Lobo R. J Invest Dermatol.W. 38(12):928–30.L. Ekoe J.. Hordinsky M. 1975.. Baden H. Guenthner T. Clin Exp Dermatol. 81. 1988. 93.M. 161(2): 124–32. Fuh V. 78. Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. Effective medical treatment of common baldness in women.J. Namer M. Clinical applications of antiandrogens. 1992... 1999. Use of cyproterone acetate (CPA) in the treatment of acne. Br J Dermatol 2000.H. 84. Local therapy of androgenetic alopecia with 17 alphaestradiol. 77. 2000. 78(3):405–8. Treatment of hirsutism. Rushton D. et al. Matzkin H. Oral spironolactone therapy for female patients with acne. Minoxidil and Finasteride. 1980. comment]. 88. 42:317. Neumann F.L. Leo-Rossberg I. Effect of minoxidil on cultured keratinocytes. J Biol Chem. Finesteride increases anagen hair in men with androgenetic alopecia. 1979.P. Br J Urol. Overstreet J.E. and Braf Z. Abdel-Salam M. Price V. 95.. Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.. 1991. Meckies J.. 31(4B):719–29. J Urol.M. 1998. et al. Int J Dermatol. 1984. Hammerstein J.A. Price V. Shaw J. J Invest Dermatol. Pharmacology and potential use of cyproterone acetate. 80. 35(11): 770–8. 1983.. and Matz H. and Ruedi B.M.. 9(1):1–13. 112(1):124–5. et al.. acne and alopecia 87. 162(4):1295–300. 160(6):398–404. with cyproterone acetate. 1977.. 91. 143(4):804–10. 96(2):295–6. 1985. Brenner S. 89. 94. Rushton H. 9(4):342–50. J Steroid Biochem. In Hair Workshop. Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia. et al. and James K... Improvement in androgenetic alopecia in 53–76-year-old men using oral finasteride.. 96.C. Burckhardt P. Canada.

J Am Acad Dermatol.A. 108. Arch Dermatol. 1996. and Weiner M. 1987. 102. 104. Weiner S.. Hair loss with minoxidil withdrawal [letter]. Mechanism of action of retinoids.R. 32(5):316–17.L. and Menefee E.S. Weiner M. Olsen E. . Buhl A. 1991. 114. 101. and Pinnell S. Weiner M. 74(2):345–50. 106. Bardazzi F. 1989. DeVillez R. Natural history of androgenetic alopecia. Dermatol Clin.J. Roche N.. I. 1990.H.A. DeLong E.J. Contact Dermatitis.. 115. Wilson C. Cutis. Amsterdam: Elsevier Science. Bazzano G. 15(4 Pt 2):756–64.A. 112.. 1991. ed. pattern baldness.A. DeLong E. 95(6): 683–7. 890–3. and Galen W. Olsen E. J Invest Dermatol.A.S. J Am Acad Dermatol.. 103. Powell S..S. Sanders D. Topical tretinoin for hair growth promotion. Treatment of androgenetic alopecia with topical minoxidil solution. 1994. Clin Exp Dermatol. et al. Olsen E.. 98.R. Minoxidil’s action in hair follicles.. Price V. Ohtsuyama M. Olsen E.. Five-year follow-up of men with androgenetic alopecia treated with topical minoxidil.. J Invest Dermatol. DeLong E. Topical minoxidil in early male 107.. Terezakis N. 1992. Mulholland M. Whole hair follicle culture. Epidermal effects of retinoids: supramolecular observations and clinical implications.B. 116.. 1992... 14(4):595–607. 1985.B.R. J Am Acad Dermatol. Topical minoxidil in the treatment of androgenetic alopecia in women. androgenetic alopecia in women: effect of minoxidil. De Padora M. 105.. J Am Acad Dermatol. Hair growth effects of oral administration of finasteride.Androgenetic alopecia 119 97. and Kealey T. 13(2 Pt 1):185–92. and Muller E. Sporn M. Contact Dermatitis. p. 1986. Olsen E. a steroid 5 alpha-reductase inhibitor. Diani A. et al. 13(4):275–6. 15(1): 34–6. 130(3):303–7. In Hair Reseach for the Next Millennium. V. and DeLong E. 1991. and George M. 109. Shull K... 340(8819):609–10. Olsen E. 17(1):97–101. alone and in combination with topical minoxidil in the balding stumptail macaque. Elias P. 1986. Topical minoxidil in male pattern baldness: effects of discontinuation of treatment. 24(4):661–2.L. 100. Androgenetic alopecia in the female. 99. 1990.D..S. Allergic contact dermatitis from minoxidil.. Philpott M.R. 1985. J Am Acad Dermatol. 1987. 15(4 Pt 2):880–3. et al.A. 111. 48(3):243–8. 110. et al. 35:53. 1986.M. J Am Acad Dermatol.Van Neste. Contact dermatitis in reaction to 2% topical minoxidil solution.A.. 481. Walkden V. Roberts A. 16(3 Pt 2):688–95. Minoxidil sulfate effect of internal calcium of cell in the epidermis and epidermal appendages. Kidwai B. Olsen E. Quantitative estimation of hair growth. J Am Acad Dermatol. 96(5): 73S–74S. J Am Acad Dermatol. 15(4 Pt 2):797–809. Tosti A. et al.R. Ebner H. 1990.E. Amara I.R. Lancet. J Clin Endocrinol Metab.A.S. Res Staff Phys. 1996..P. Contact dermatitis to minoxidil..S. Long-term follow-up of men with male pattern baldness treated with topical minoxidil.A. 22(4):643–6. 113. Buller T. Treatment with 2% topical minoxidil solution.R.P. and Weiner M. 1995.

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4 Surgical management of androgenetic alopecia Most follicles at the occiput of the scalp have been ‘genetically programmed’ to persist as non-miniaturized terminal hairs throughout the life of a patient with AGA. This patient requested laser hair removal to remove his grafts from twenty years ago. (b). (d). These hairs are unlikely ever to become vellus-like. These follicles can be transplanted anywhere on the same individual and will produse coarce terminal hairs for the lifetime of the individual. (c).1 Hair transplantation two decades ago: (a). Figure 4. Note the unnatural corn-row tufting of hair surgery performed in the 1960s and 1970s. .

and is the basis for the success of hair transplantation.4 Donor area is injected with tumescent anesthesia.1.3 It has been shown that tumescent anesthesia significantly reduces the total .3 Donor area at the back of the scalp is trimmed.1). The advent of (1) strip harvesting for the donor area. This is termed donor dominance of the grafts. more natural-appearing grafts. The chapter will deal solely with hair transplantation. 4. There are many differing approaches to hair transplantation. Figure 4. (2) the introduction of finer. The tumescent technique involves the injection of large volumes of very dilute lidocaine and epinephrine. Figure 4. as this is the most commonly performed surgical procedure for androgenetic alopecia (AGA).2 This chapter will discuss hair transplantation as it is performed at the University of British Columbia Hair Clinic. and (3) the use of slits for the recipient area have revolutionized the field of hair transplantation.3) and anesthetized using the tumescent technique (Figure 4.2.122 Hair Loss: principles of diagnosis and management of alopecia Figure 4. This anesthetic approach was first developed for patients undergoing liposuction.4).2 Donor area is chosen in the occipital portion of the scalp. and these are discussed thoroughly elsewhere. The field of hair transplantation has changed markedly within the past 10 years (Figure 4. The donor site The selected donor area is initially trimmed (Figures 4.

A multi-bladed knife with #10 Personna blades is angled parallel to the hair shafts (Figures 4. It is important to keep this in mind when harvesting strips.5b). The hair follicle with its dermal papilla usually extends to a depth of 4–6 mm.4 A solution prepared by adding 25 ml of 2% lidocaine without epinephrine. If the angle is not pre- . This angle is crucial.4% sodium bicarbonate solution and 0. repeat injections of anesthesia are given to the patient’s donor area. Tissue more than 1 mm below the dermal papilla is not necessary for transplanting. If an excision is too deep. This increases skin turgor in the area and allows easier visualization and excision of the donor area. Constant monitoring of the angle is necessary. 2. thus decreasing bleeding. Just before excision.4 ml of 1:1000 epinephrine is added to a 250 ml IV bag of saline. Strip harvesting has truly replaced the older punch-harvesting methods. Harvesting with strips as opposed to punches allows for more efficient harvesting and better cosmesis. If the angle is not precise there will be considerable follicular transection and subsequent follicular wastage.Surgical management of androgenetic alopecia 123 Figure 4.5a and 4. and as a result are less likely to be later transected. Any ‘hot spots’ that are not completely anesthetized can be further anesthetized with small amounts of 2% lidocaine. (b) The blades are angled in the direction of the hairs. it can cause unnecessary harm to underlying arteries and veins. This angle is crucial and varies from 100 to 120 degrees.5 ml of 8. A mandatory period of 20 minutes is required for the anesthetic to have its full effect in terms of anesthesia and vasoconstriction.5 (a) Multiple-bladed knife is prepared. number of milligrams of lidocaine required and maximizes the vasoconstrictive benefits of epinephrine. Approximately 6–7 injections are performed with an action pump syringe and a 25 gauge needle into the trimmed occipital area. Any curly hairs will also become more ‘straightened’ with this increased turgor. and varies from 100 to 120 degrees.

7.124 Hair Loss: principles of diagnosis and management of alopecia Figure 4. This will usually yield 1100–1350 grafts on average. Small bleeders can be cauterized or tied off with 3–0 Vicryl absorbable sutures. . Length is usually 10–14 cm.25 mm each for a total of 6. After the stab incision. the strips will usually be longer and wider. so as not to harm the lower portions of the follicle as well as not injure any underlying blood vessels.5 mm strips taken for a total width of 1 cm.75 mm-1. The width of each strip varies for each individual. at the University of British Columbia (UBC) Hair Clinic. This will yield an average total of 600–800 grafts.7 Strips are released from the rest of the scalp with a #15 blade. Figure 4. with avoidance of any kind of ‘sawing’ motions. 4.6 Strips are excised from the donor area. Strips vary in size depending on whether it is a regular or a megasession. Personna scalpel blade (Figures 4. three strips of 2.8).8 Strips are removed with a V shape at the ends. The strips are released at the ends with a V shape and from underlying tissue with a #15 Figure 4. 4. This is done meticulously. Most strips are 12–16 cm in length. with four 2. blades are maintained at a constant depth. For an average megasession involving considerably more harvesting.6.0 cm in width. The surgical defect will range from 6.25 mm are removed with a regular session or four strips of 2. For an average regular session. Usually three strips of 2.75 mm width are excised.5 mm for a megasession. cise there will be considerable follicular transection and subsequent follicular wastage.

Keloids can subsequently be treated with intralesional corticosteroid. as it was well camouflaged by his donor hair. ethnicity and scalp elasticity. This particular Asian patient did not mind the keloid. He did not inform our center of this complication. The size of the strips taken varies according to how much area needs to be covered. certain centers have found the exactly the opposite. If donor follicular density is low.5 The resulting scar is linear.Surgical management of androgenetic alopecia 125 Figure 4. and just use staples. These scars can be excised at subsequent sessions.9 The surgical defect is closed with a continuous stitch. usually with a diameter of 1–2 mm (Figure 4. the total width of strips removed will be lessened. We have found that sutures are more confortable than staples for the patient.9). .10). Larger areas of alopecia will require greater coverage and thus larger strips. if an individual’s scalp is too tight. Alternatively. leaving only one final scar.10 (a) The scar 6 months after the procedure. another scar can be created above or below the previous Figure 4. wider strips are necessary. The donor site is sutured with blue nylon 3–0 Novafil. AfricanAmericans in particular usually have a lower scalp follicular density and frequently require a greater total width of strips. which is more commonly seen in African-Americans or Asians. However. (b) A rare complication of the donor area is the formation of a keloid. and as a result prefer closure by a continuous suture (Figure 4. and it was not discovered until he returned two years later for his subsequent second session. hair density. However.

Figure 4. Excessive amounts of fat. Positioning the hairline is critical. grafts are grouped according to size and density on Petri dishes on ice (Figures 4. one. Graft hair preparation The strips are placed in saline on ice packs and subsequently subdivided into grafts with only one single hair follicle (micrografts) or one to two follicular bundles/follicular units containing two to four hairs (minigrafts).11 Strips are placed on a tongue depressor and are sectioned with a #10 blade into smaller grafts. and include keloid formation (Figure 4.6 At . hair without matrices. Because of the natural appearance of the small grafts. the patient is not committed to have to continue through many sessions to get that final natural look. which must have a prerequisite length of 2 cm.126 Hair Loss: principles of diagnosis and management of alopecia Figure 4.13 and 4. and any scar tissue (especially from a previous transplant) is removed (Figure 4. Stough has presented guidelines.10b) wound dehiscence. It is essential that during this whole process strips and grafts are not permitted to dry out and are well moistened with saline. All of this is camouflaged nicely by the patient’s hair. leaving only 1 mm of fat underneath the follicle. Appropriate magnification is necessary to perform this.14).11). This is drawn in before the surgery. The most obvious advantage of using these small grafts is the elimination of tufting reminiscent of the old grafts. During preparation. and paresthesias. and must be discussed at length with the patient. The recipient area In the frontal area. Complications in the donor are very rare. facial framing is frequently what the patient wants.12). This is performed by meticulous dissection of the strips with a #10 Personna blade and fine jewelers’ forceps (Figure 4.12 Much of the fat is trimmed away.

15a).13 Grafts are subdivided into micrografts containing single hairs (bottom) or minigrafts with single follicular bundles of 2–3 hairs (top).Surgical management of androgenetic alopecia 127 Figure 4. . On lateral view. the area marked is always parallel to the ground and on the flat portion of the scalp (Figure 4. The hairline is drawn onto the recipient area.15b). Figure 4.15 (a) and (b).14 The grafts are grouped on to Petri dishes according to the number of hairs per graft. Figure 4. bell-shaped hairline (Figure 4. the UBC hair clinic we mark an area 8–11 cm midline above the glabella and create a curved.

5–2. Those with pre-existing hair may only need 2 .0 mm spear tip on a handle (Figure 4. The recipient area is anesthetized with a field block of 2% lidocaine with a mandatory 20-minute waiting period to maximize vasoconstriction. Slits are made with an Ellis 1.16 On the vertex of the scalp. Figure 4. Figure 4.5 mm or 2. the hair direction is planned. The majority of patients get satisfactory cosmetic results with 3 sessions of slit grafting in a totally bald area. Slits are made into the recipient area.16).5 or 2 mm spear tip. the area is marked as to hair direction prior to the surgery (Figure 4.17 Slits into the recipient area are made with an Ellis 1. They are directed parallel to the direction of the hair.17). Usually we allow 1.18).18 (a) and (b).128 Hair Loss: principles of diagnosis and management of alopecia Figure 4. On the vertex.5 mm between the slits laterally and 1 mm anteriorly or posteriorly (Figure 4.

20). Planting into the slits is done meticulously with jewelers’ forceps (Figures 4. Figure 4. In the frontal area.19 and 4. A megasession increases coverage. usually covering 30–50% of the anterior portion of the scalp. 600–900 total grafts are transplanted. Scalp after placement of grafts.19 Grafts are placed on to the fingers of the nurses. Figure 4. Special care is taken not to harm any of the grafts.21 (a) and (b). The remaining minigrafts are placed behind this frontal zone.Surgical management of androgenetic alopecia 129 Figure 4. with a total of 1100–1400 grafts. and allows the placement of grafts into the anterior portion as well as the vertex of the scalp. a zone of approximately 300 pure micrografts is created. For a regular session. sessions. The hairs in the grafts are aligned with .20 Grafts are placed into slits with jewelers’ forceps.

Patients must wait for up to six months to see the full benefits of a hair transplant. then this becomes a bonus for the patient.22). A full working schedule and exercise can be resumed 1 week after the procedure. 3.130 Hair Loss: principles of diagnosis and management of alopecia Figure 4.23–4.21b). The average patient with marked hair loss will receive on the average 3 sessions (Figures 4. Patients are warned appropriately and are told to expect it. Patients leave the office with a moist dressing covering the donor and recipient areas (Figure 4. The dressing is removed the next day.21a and 4. especially with megasessions. It is best for patients to take one week off work. Graftcyte® dressings are placed over the recipient area. Forehead swelling is treated with the frequent application of ice-packs and upright positioning (at at least a 45 degree angle) for one week while sleeping.25). .39b in Chapter 3 on androgenetic alopecia) Minoxidil and hair transplants There are reports in the literature that topical minoxidil solution twice daily may lessen the effluvium usually seen postoperatively. Finasteride and hair transplants the appropriate angle and direction fitting directly into the slits. Facial edema beginning 48 hours after the procedure and lasting for 5 days is certainly common. (See Figures 3. With appropriate postoperative care and daily shampooing. We perform repeat sessions after a minimum of six months between sessions. There also is a possibility of regrowth as well as in the patient illustrated in Fig. Patients are warned of a telogen effluvium that can occur with the transplanted grafts as well as with pre-existing recipient hair.36. The grafts can be flush or slightly elevated above the surrounding tissue (Figures 4. after one week virtually all crusting will have disappeared. This allows the transplanted hair to grow in visibly and allows us to visualize where to put the new set of grafts. A regular session will usually take 5–6 hours. This would logically reduce the number of sessions necessary.7 Many of our female patients continue to use topical minoxidil 5% solution after transplantation to help stabilize any further loss and further reduce the number of sessions. A megasession may take 6–8 hours to complete. Finasteride may stabilize any further thinning of pre-existing hair in the recipient area.22 Post-operative dressing covering donor and recipient area. We frequently recommend our male patients with pre-transplant Norwood-Hamilton Stages III–V to take finasteride 1 mg daily.39a and 3. If the facial edema does not then happen.

It is area. Two years later. A 27-year-old male prior to hair transplant. Another problem with women is the resulting effluvium of pre-existing hair in the recipient This can be somewhat lessened with the use of topical minoxidil solution applied twice . 1 year later. Hair transplantation in Women Because AGA in women may be more diffuse.24 (a). Figure 4. (b).23 (a). after two regular sessions. Atleast 30% (in the author’s experience) have significant thinning in the donor area and are not good candidates. (b). A 40-year-old male prior to hair transplant. the occipital donor area may be affected.Surgical management of androgenetic alopecia 131 Figure 4. after four regular sessions. important to choose the appropriate fe- male surgical candidate.

(d). Conclusion Hair transplant surgery has become very popular. If she is not able to accept this fact.25 (a). Our experience is that as long as the female patient is warned that there may be significant worsening before improvement and that the lag time is 6 months. (c). and will feel that her situation has worsened significantly compared to her pre-transplant state.132 Hair Loss: principles of diagnosis and management of alopecia Figure 4. mini-grafting and strip harvest- . daily. she is not a candidate for hair transplant surgery. then she will be prepared emotionally. Side view after hair transplant. Two megasessions and a regular session and 3 years later. In such cases the patient will experience effluvium of both the transplanted hair and her preexisting hair. Micro-grafting. Side view of the same patient before hair transplant. but frequently will still occur even then. A 43-year-old male prior to hair transplant. as its results are cosmetically very natural. (b).

J Am Acad Dermatol 1987.Klein. In Hair replacement surgical and medical. A pilot study. In Hair replacement surgical and medical. J Dermatol Surg Oncol 1992. dermabrasion. Combination medical therapy with systemic finasteride or topical minoxidil solution may certainly add to the cosmetic result. Klein J. and soft tissue reconstruction. Use of topical minoxidil as a possible adjunct to hair transplant surgery. 139–49. . pp.J. 1st edn. pp.A. 18(2):130–5. 4:263–7. Stough D. 2. The tumescent technique for liposuction surgery. Hair Transplantation. Use of the tumescent technique for scalp surgery. 1996. 3. Kassimir J. Missouri: Mosby. Determination of hairline placement.Stough. and J. ed. 7. St Louis.D. The donor site. 1995. D. Coleman W. 6. 1996: St Louis. 3rd edn. 4. ed. Stough D. New York: Marcel Dekker. 425–9. Am J Cosmet Surg 1987. St Louis. Missouri: Mosby.P.Surgical management of androgenetic alopecia 133 ing have made the transplant an efficient technique for increasing the number of follicles in specific areas affected by AGA. 1996. Unger W. Missouri: Mosby. Hair replacement surgical and medical. Stough D. 16(3 Pt 2):685–7. D. 5. References 1.Stough.

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except in rare instances. Even if they do notice it. and will detect any inflammatory process. Practicing dermatologists make the diagnosis infrequently. Drug-induced alopecia is usually confined to the scalp. from complete baldness to slight. One must understand the basic mechanisms of hair growth and cycling in order to understand drug-induced hair loss. This will help rule out AGA and alopecia areata. Certain laboratory tests such as scalp biopsy and blood work can be helpful in ruling out other causes of alopecia. The telogen phase lasts for three . barely noticeable shedding. Subtle cases can be difficult to detect. Drugs are capable of producing a wide spectrum of alopecia. Female androgenetic alopecia (AGA) poses a real problem. Repeated questioning may be necessary because of forgetfulness or ignorance. The pattern of hair loss is almost always diffuse. and it is possible that many patients may lose small amounts of hair and never realize it. Following anagen. The scalp itself is usually unremarkable. although the eyebrows.5 Drug-induced alopecia Drugs can affect hair by causing alopecia. metabolically active phase known as anagen. A scalp biopsy with obligatory transverse sectioning will give you the anagen-telogen ratio and the terminalvellus ratio. and so may go unreported or may be reported without adequate documentation. a brief transitional catagen phase of two weeks leads to a metabolically inactive resting telogen phase. A drug-induced alopecia can certainly unmask a tendency for androgenetic alopecia and accelerate the miniaturization process of AGA. but it is also true that they rarely see the vast majority of such patients—those receiving chemotherapy. This is all reviewed in detail in Chapter 1. Each human scalp follicle produces hair cyclically and behaves independently of neighboring follicles. which lasts 4–8 years. the axillary and pubic regions and the body may also be involved. Some drugs can cause a severe drug-induced lichenoid eruption of the scalp. because it is very prevalent and can co-exist with diffuse alopecia. The work-up for any patient with hair loss must include a thorough drug history. Drugs that cause alopecia The true incidence of drug-related alopecia is hard to determine accurately. the loss of hair is considered to be trivial. This chapter will review which drugs have been implicated in hair loss and explore the mechanisms of how pharmaceutical agents can alter hair cycling and structure. The scalp follicle passes through a growing. as well as helping to confirm an anagen or telogen effluvium.

Indirect effects include causing a systemic disease (hypothyroidism or zinc deficiency) or a severe skin disease (lichenoid eruption or toxic epidermal necrolysis) of which alopecia is a feature. because many diseases for which drugs are administered also produce a precipitation of catagen. The hair breaks at the point of constriction. Scalp follicles are in differing phases of the hair cycle and are randomly scattered over the scalp. such as the eyebrows and eyelashes. If one excludes anti-mitotics. There are two mechanisms of drug-induced alopecia—direct and indirect effects.4 The resultant hair contains fewer cells per unit length. and disturbed keratinization. Cytostatic drugs suppress hair matrix cell mitosis. A small single dose will produce constriction of the hair shaft. 10% in telogen. are more likely to be affected by drugs than the regions of the body with the lowest percentage of anagen follicles. in the clinical setting. 1 Ahmad 2 in reporting a case of cimetidine-induced alopecia failed to take into account the fact that the stress from a duodenal ulcer might have caused the alopecia. and 1% in catagen. and the density of the follicles will account for the varying severity of alopecia in different areas of hair growth. the mitotic activity of the hair matrix is so high that it can be compared with the most actively kinetic tissues of the body. The duration of anagen and telogen phases. A large single dose that strongly suppresses mitosis produces a sharp point-constriction. Only the actively dividing matrix cells of anagen hairs are affected by cytostatic drugs. Anagen effluvium (Table 5. the most common mechanism by far for drug-induced alopecia is the precipitation of catagen. Follicles are susceptible to noxious agents. there is confusion. impede hair cortex formation and cause an anagen effluvium in almost 100% of patients. In some cases. An example of such a dilemma is highlighted by Reeves and Maibach.136 Hair Loss: principles of diagnosis and management of alopecia months. and the predominant effect may depend on the dose and timing of the administration. resulting in hair shaft damage. The regions of the body with highest percentage of anagen hairs. namely bone marrow and mucous membranes. For this reason anagen hair matrix is highly susceptible to noxious events. Of course. usually when they are actively growing. but may result from changes in keratin production or changes in the hair cycle. such as the scalp and beard.1) Cytostatic drugs Any drug that affects cell division can alter hair growth. Continued treatment with a smaller constant dose produces a slow decrease in hair shaft diameter to a tapered point. while catagen and telogen follicles are relatively safe. after which the club hair is shed as the hair follicle initiates a new cycle. Hair loss developing weeks to months after drug intake may be due to hair matrix effects. The intensity of damage to the cortex of the hair shaft depends on the drug dosage and the duration of its administration. A spectrum of changes seems to occur. especially .3. Direct effects include anagen growth interruption. with hair fall beginning in 7–14 days (see Figure 5. Combined therapy with two or more anti-mitotic agents has a greater effect than a larger dose of only one agent. Hair loss occurring a few days after drug intake indicates an effect on hair matrix cells. is thin and breaks easily. the percentage of hairs in anagen and telogen phases. precipitation of catagen. During the anagen phase. Almost 90% of scalp follicles are in anagen. Drug-induced alopecia usually involves pharmaceutical alteration of the cycling process.1).

fluorouracil. Note the marked hair loss over the entire scalp. Figure 5. A 33-year-old female with lymphoma on dacarbazine. Drugs that may aggravate alopecia when used in combination chemotherapy include chlorambucil. vinblastine and dactinomycin. (a) posterior view (b) lateral view .1 Anagen effluvium. daunorubicin. cyclophosphamide. chlormethamine (mechlormetha- mine). Alopecia most commonly occurs with the use of doxorubicin (adriamycin). bleomycin. bleomycin and hydroxy-carbamide. cytarabine. thiotepa. hair loss may be almost complete.Drug-induced alopecia 137 Table 5.1 Drug-induced anagen effluvium46 in-patients subjected to multiple cycles of chemotherapy. doxorubicin and vinblastine. vincristine. methotrexate.

The mode of action is due to metaphase arrest. has been reported to cause alopecia by causing an anagen effluvium from cutaneous infarcts. busulfan.6 Harms7 reported a case of diffuse alopecia that occurred after 2 months of colchicine therapy. 2. a vasoconstrictor and anti-diuretic pituitary hormone. Hairs were dystrophic and broken off 1–2 cm above the scalp. used in the treatment of gout. thiotepa. melphalan. It may persist for 1–3 months. if sufficient are involved. which may last 4–12 weeks. Immediate anagen release probably characterizes most drug-related events. Immediate anagen release (IAR). 3. DAR is probably associated with postpartum hair loss and oral contraceptives. as the affected follicles are promptly stimulated to cycle into anagen. Immediate telogen release (IMR): normal telogen.9 of these types are related to events in anagen and two related to telogen. Most of the cytotoxic agents are not phase-specific: these include alkylating agents (cyclophosphamide. Delayed telogen release (DTR) occurs when telogen is prolonged and there is slightly more synchronous growth and Telogen effluvium There are 5 functional types of telogen effluvium (TE) as proposed by Headington. has anti-mitotic activity operating through failure of spindle formation. ifosfamide. There is some good evidence that topical minoxidil solution may effect IMR. the clinical sign of increased shedding will be found. Etretinate may cause SA. nitrosoureas.10 Three . The five types are as follows: 1. Colchicine Colchicine. Cells with the highest rates of division are affected earliest. characterized by a prolonged anagen rather than cycling normally into telogen. 4. 5.138 Hair Loss: principles of diagnosis and management of alopecia Certain drugs affect specific phases of the mitotic process within the actively dividing hair matrix. 6-mercaptopurine and methotrexate.8 Vasopressin Vasopressin. Hair loss is dose-dependent. IAR is probably underreported because of reporting inertia by physicians whose clinical judgement is that a probable drug-related hair loss is a trivial event with expected reversal when the drug has been discontinued. When follicles are finally released from anagen. Those drugs that are S phase-specific include cytosine arabinoside. and cisplatin.5 Colchicine can produce diffuse hair loss in 1–10% of cases. If anagen is decreased by 50%. procarbazine. Follicles that would normally complete a longer cycle by remaining in anagen prematurely enter telogen. All follicles in telogen may be susceptible. characterized by a relatively short onset—usually 3– 5 weeks. hydroxyurea. Cimetidine has also been implicated as causing DAR. carmustine. is shortened to just a few days. dacarbazine). Delayed anagen release (DAR). antitumor antibiotics. The M phase of mitosis is affected greatly by vincristine and vinblastine. there is a corresponding doubling of telogen hairs. All areas affected by anagen effluvium had normal hair growth after the medication was discontinued. Shortened anagen (SA) occurs when the anagen phase is significantly decreased in time. and may be reversible even if the drug is continued.

The following list of drugs have been implicated as causing telogen effluvium (Tables 5. and carbimazole. These include heparin and coumarins. Anti-coagulants All forms of anti-coagulants may induce hair loss. Anti-thyroid drugs that may produce telogen effluvium include iodine. appears to be related to drug dosage. methylthiouracil.2 Drug-induced telogen effluvium (incidence less than 1 %)46 fallout on the scalp. which occurs during treatment of thyrotoxicosis.5) occurs in more than 10% of patients.2).2–5. Anti-thyroid drugs Reversible alopecia is a constant finding in iatrogenic hypothyroidism. Telogen effluvium is frequently associated with hair dryness and brittleness. and tends to be more frequent in women (Figure 5. but reports of delayed-onset shedding with drug treatment might be a result of DTR. TE . propylthiouracil. No drugs have been implicated with this mechanism conclusively.Drug-induced alopecia 139 Table 5.

12–17 A review described 101 cases of lithiumrelated hair loss in over 25 years of use. reported hair thinning.5 g/ day. who had high lithium levels.5 and 1. and both conditions may manifest with hair . Hypothyroidism (commonly) and thyrotoxicosis (rarely) have been described in patients on lithium therapy.18 A 3year survey of lithium-treated subjects reported a 12% incidence of alopecia. and may be noticed within weeks or years after commencing therapy. doses ranged from 0. in those patients in whom the onset of the hair loss may take years. this mechanism is less likely. but not established.140 Hair Loss: principles of diagnosis and management of alopecia Table 5.3 Drug-induced telogen effluvium (incidence of 1–5%)46 Table 5. with serum lithium assays between 0. A correlation between hair loss and lithium blood level and/or dosage is suspected. 11 Headington feels it is due to immediate anagen release.13 About 20% of patients on long-term lithium therapy.4 Drug-induced telogen effluvium (incidence of more than 5%)46 Psychopharmacologic medications Lithium Hair loss is a possible adverse effect of lithium carbonate.4 to 1. since this drug is known for its ability to affect the thyroid gland. In most reports. 23% described their hair as also becoming straighter. However.4 Meq/L.19 Patients on lithium who develop alopecia must undergo a thyroid function assessment.

Drug-induced alopecia 141 Table 5.5 Drug-induced telogen effluvium (exact incidence unreported)46 .

29 Carbamazepine and VPA possibly have different mechanisms of hair loss.6% and 6%.2 Telogen effluvium.23. despite a documented decrease in serum amounts of zinc and copper caused by both medications. (c) Pathology of telogen effluvium. once ingested. but usually dosage reduction leads to regrowth of hair in individuals with valproate-associated alopecia.18 With a reported incidence of 1.0% reported frequency. VPA and divalproex (a stable combination of valproate sodium and valproic acid) may cause hair changes. A review of the literature mentions 643 cases of valproateinduced alopecia. A 63-year-old female on warfarin showing general shedding. (b) Lateral view.142 Hair Loss: principles of diagnosis and management of alopecia Figure 5. dissociates in the gastrointestinal tract into a salt or ionic form. Hair loss is not as marked as in anagen effluvium.20.26 Valproate Carbamazepine Valproic acid (VPA). lished whether alopecia is dose-related. valproate. (a) Top view.30 Some individuals may have an . showing a disproportionate number of telogen hairs.22 This is probably coincidental.24 Patients on VPA who develop hair loss tend to have a high valproate blood concentration.18 with a 0. with a slightly increased width of hair-part.25 It is not completely estabThere are 177 documented cases of carbamazepine-induced alopecia. illustrating marked thinning on the temporal area.5%–12.21 There is a case report of alopecia areata occurring during lithium therapy. changes.28 A threefold dose reduction of 200 mg/day helped one female patient.27.

and protriptyline. This sideeffect is reversible once medication is terminated. imipramine. Serotonin reuptake inhibitors Several serotonin reuptake inhibitors can also cause hair loss on rare occasions.33 and paroxetine in 30 subjects 18 The majority of these have a typical pattern of reversible diffuse alopecia.38–40 Low zinc levels can cause hair loss. Oral contraceptives Telogen hair is lost 2–3 months after discontinuation of treatment with oral contraceptives.18 Sertraline has been reported in 46 instances. none of the monoamine oxide inhibitors are known to cause alopecia. Significant recovery is seen after 4–8 months from the time use of the solution is discontinued. Females are more commonly affected. There is no relationship between dosage and time of onset or severity of hair loss. despiramine.31 However.31 Interferons Telogen effluvium occurs in 20–30% of patients treated with interferons. generally do not result in alopecia. Topical ophthalmic beta-blockers Topical ophthalmic beta-blockers can cause hair loss. and thus decrease zinc levels.31 Buspirone is also associated with hair loss on rare occasions. telogen loss subsides despite continuing treatment. Hair loss is not confined to the scalp alone. particularly in those patients with renal disease. All TCA versions have been implicated with alopecia: amitriptyline. Captopril can also cause hair loss. The utilization of lowdose estrogen contraceptives is only occasionally associated with this effect. owing to the estrogens.41 Tricyclic/tetracyclic antidepressants A few instances of diffuse hair loss associated with tricyclic antidepressants (TCA) have been documented. olanzapine and respiridone have been documented as causing hair loss. Sometimes alopecia may develop 1.34.5 years following fluoxetine introduction. Clonazepam is one exception. It occurs 1–24 months after treatment. Anxiolytic medicines of the barbiturate and benzodiazepine classes. nortriptyline.5 years after drug discontinuation.35 In another case. amoxapine. Fluoxetine is the most frequently prescribed anti-depressant. doxepin. as well as zolpidem. but also extends to eyelashes and eyebrows. a fluoxetine-induced alopecia was still evident 1. Pathogenesis is probably similar to that in post-partum hair loss. Antihypertensive agents Several anti-hypertensive agents are known to cause hair loss. In some cases.32.Drug-induced alopecia 143 increased genetic predisposition to medicinal alopecias.31 The tetracyclic antidepressant drug maprotiline and trazodone may also result in hair loss.42 . and with this there are 725 documented cases. Beta-blockers may have a direct toxic effect on the hair follicles.36 Other anti-psychotics/anxiolytics Haloperidol.37 This is believed by Headington to be a delayed anagen release.10 There is prolongation of the anagen phase. with a 2–6 month latency period. It may form a complex with zinc.

which has been withdrawn from the market because of cataract induction. have been reported in chronic thallium intoxication. and its synthesis and metabolism are essential for the production of normal epidermal structures. Retinoid-induced alopecia has a later onset and is almost always reversible. which is what is more commonly seen with other drugs. Similarly. loss of hair color and ichthyosis. accumulation of air bubbles in the hair shaft. with muscle aches. just like any telogen effluvium. stopping or changing the dose or medication.144 Hair Loss: principles of diagnosis and management of alopecia Keratin production interference Thallium Thallium is no longer used as a drug. Hair losses of several months’ to years’ duration. Diffuse hair loss is commonly observed during soriatane treatment. Triparanol. retinoids can certainly unmask a tendency for androgenetic alopecia. Acute poisoning produces hair loss in 10 days. with subsequent disturbed keratinization. the negative implications of stopping or changing the regimen also need to be considered. Clofibrate may occasionally produce hair loss. an informed patient and physician should discuss the risks and benefits of continuing. The package insert for accutane mentions hair loss. However. and offer new therapeutic recommendations. Minoxidil tends to maintain hairs in anagen and convert telogen hairs into anagen hairs more quickly. Decisions are based on alternative medications and hair loss severity and its emotional impact. joint pains and weakness. During the early conversion of telogen to anagen hairs. Such choices are especially difficult when the offending agent is otherwise effective. fatigue.31 How to manage druginduced alopecia In cases where an effective therapeutic agent causes alopecia and no appropriate alternative can be found. loosely anchored hairs. Thallium ingestion produces changes in the matrix cells. It certainly can be offered to the patient. Available evidence indicates that thallium inhibits the utilization of cystine in the production of the keratin molecule. More research may further clarify drug-induced hair-loss issues.31 Cholesterol-lowering agents Agents that block cholesterol synthesis through a variety of mechanisms can disrupt . can cause significant alopecia. keratinization. The advantages and disadvantages of maintaining the drug must be reviewed. along with ataxia. It is due to a shortened anagen release. but may be ingested accidentally in rodent poisons or contaminated foods. Patients may temporarily Retinoids Soriatane and accutane can produce brittle. Cholesterol is a component of cellular lipids. there is surge of ‘telogen release’. The use of topical 5% minoxidil solution for drug-induced telogen effluvium in those cases when the offending drug cannot be terminated or switched is certainly a therapeutic option we use at the University of British Columbia Hair Clinic. Intrafollicular thinning. breakage of the hair shaft and the induction of telogen is seen in thallium alopecia. unmanageable. with evident alopecia occurring in about 20% of patients. rather than an immediate anagen release. dry.

9. Gen Hosp Psychiatr. Maceyko R. Br J Dermatol. Some chemical influences on hair growth and pigmentation. New concepts and review [see comments]. 1984.T. 148:752. and Ananth J. Washington DC: Horizon Books. and Steck W. 31(1):111–13. J Hardman. 116(4):347–61. Headington J. 21. Int J Clin Pharmacol Ther Toxicol. For drug-induced anagen effluvium.D.I. Goodman & Gilman’s The Pharmacological Basis of Therapeutics.T. 8. Int J Dermatol. Hair loss following lithium therapy [letter]. Hair loss during lithium treatment [letter]. Demographic and clinical findings. Cimetidine and alopecia [letter]. 1986. Australas J Dermatol. Can J Psychiatr. Hair loss in the course of lithium treatment: a report of two cases. Ann Dermatol Venereal. A case report. 11.G. Valproic acid in childhood epilepsy: anticonvulsive efficacy in relation to its plasma levels. 34(3): 149–58. et al. and Morrison D. 91(6):930. 16.F. Thyroid disorders in lithiumtreated patients.P. and Dawber R. 24(3):100–4. Klotz U.Drug-induced alopecia 145 (for the first month of minoxidil application) experience more hair loss. Molinoff P. Dawber R. 4. Clinical toxicity of chemotherapeutic agents: dermatologic toxicity. Lithium-induced reaction [letter]. Inc. 1979. 12. Kirov G.. 1983. Rook A. and McTavish D. 18(10): 461–5. 15. Peters D. Eustace D. Reeves J. 1994. Br J Dermatol. alopecia. 1995. 1971. 32(12):853–4. 1983. 1988. Pillans P. A cutaneous side effect of lithium: report of two cases. Davis R. 9th edn. Silvestri A. and Maibach H. 647–9. 1985. J Am Acad Dermatol. 1996. 9(1): 14–22. Delaunay M. 1980. Alopecia and mood stabilizer therapy. Vidimos A. 23(9):603–4. and Mortimer P. 506–17. Alopecia and hair changes following colchicine therapy. I. The use of cooling scalp devices is still controversial. 10.P. Mortimer P. Freinkel R.L. McKinney P. 10(1):46–8. 1972. [Cutaneous side effects of antitumor chemotherapy].P. Dunagin W. Santonastaso P. and neuropathy. Ann Intern Med. 77:115–29. Harms M. 2. Telogen effluvium. 1989. Drugs.. 1980. 25. 108(4):503–4. Hair loss and lithium. Vasopressin-associated cutaneous infarcts. . 28(2):132–3. Br J Psychiatr. 14. shedding telogen hairs and subsequently replacing them with the more desired anagen hairs.. Hair growth and alopecia in hypothyroidism. 13. Yassa R. 107(1):124–5. 23. 8(3):183–5. Drug-associated alopecia.J.44. 50(1):33–40. Blankenship M. Alopecia areata during lithium therapy. Br J Psychiatr.. 1982. 1979. 31(3):161–3. 1994. 146:70–4. 18. Valproic acid. 22. 5. Int J Dermatol. Patients should be warned of this temporary setback. and Woods D. 129(3):356–63.43 We rarely need to use it. Orwin A. 20. McCreadie R. 1996. 1983. 17. and Paggiarin D.. 1983.45 References 1. 7. pp.D. Dis Nerv Syst.K. Br J Dermatol. 1998. 106(3):349–52. and DeVane C. Drugs and alopecia. and Freinkel N. The impact of lithium in South-west Scotland.S. Limbird L. 3. Jefferson J. 6. 1993. Kusumi Y. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy.. Ann Clin Psychiatr. Hautarzt. Arch Dermatol.and chemical induced hair loss.A.H. 1965. Semin Oncol. and Schweizer C. 19. Arch Dermatol. Finkenbine R. 14:23. J Affect Disord. New York: McGraw-Hill. Lithium and hair loss.G. 47(2): 332–72. as the alopecia is usually reversible. Int Drug Ther News. Drug.L. topical minoxidil 5% solution has been reported to work. Ahmad S. 24. 1982.

. Two cases of hair loss after sertraline use. Hair loss associated with fluoxetine [letter]. 1990. 34. Gupta S..T.. 27.S. and Whitworth J. Cytoprotective effects of 4. 1998... NJ: Medical Economics. 1984. et al. 1996. 35. 28. 45. 32.. Suzuki T. 34(3):196–7. Verity C. and magnesium in hair and serum of epileptics. Nephron. 16(1):91–2.. 1993. 36. Telogen effluvium due to recombinant interferon alpha-2b. Dermatology. J Clin Psychopharmacol. Bourgeois J. Duvic M. Am J Psychiatr.A. Severe hair loss associated with fluoxetine use [letter]. Jenike M. 2000. Dermatol Clin.F.. and Menacker S. Millennium edn. J Am Acad Dermatol.M.). 40.. Aust NZ J Med. 46. Lemak N. Effects of long-term anticonvulsant therapy on copper. et al. (ed. 263(11):1493–4.. 41. 1992. et al. 1999.. 45(3):549–51. Physician Desk Reference. J Clin Psychopharmacol. 37.A. Schweiz Med Wochenschr. 112(16):568–71.6-bis(1H-pyrazol-1yl)pyrimidine and related compounds on HCI. and Johannessen S. Biol Psychiatr.C.J.J. and Easter D. Eur J Cancer.D. 1995. 5(3):571–9. Henriksen O. Chem Pharm Bull (Tokyo). 43. 148(3):392. Physiologic skin changes in pregnancy. 1984.J. 1982. The Paediatric EPITEG Collaborative Group. 44. 1987. 1982.. Naylor S. Katsimbri P. JAMA. Tosti A. 42. Alopecia possibly secondary to topical ophthalmic beta-blockers [letter]. Ikeda M. and Major L. zinc. Wong R. The Department of Veterans Affairs Epilepsy Cooperative Study No. 10(6):929–40. and Pavlidis N.. 31. New Engl J Med. 327(11):765–71. 38.. Goldhirsch A. Moroji T.. Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation. Leaker B... Acta Neurol Scand. Ogilvie A... 36(6):766–71.T. 31(6):571–81. 30. 2000. Br J Psychiatr. Lancet. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. Drug-related alopecia.J. 1991. Hoorntje S. Zinc deficiency during captopril treatment. Cramer J. Bamias A. Montvale. Drug eruption reference manual. et al. and Collins J. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. 35(1):74–8. Ross R. Meyer S. 1992. Clinical and pharmacokinetic observations on sodium valproate—a 5-year follow-up study in 100 children with epilepsy. et al. 14(6):866.J. and Ellis C.H..146 Hair Loss: principles of diagnosis and management of alopecia 26. 33. Maruyama K. McDougle C. Dev Med Child Neurol. 1991.J. 18(1):62–6. 1997.. Kiser J.N. et al.. A randomized trial of minoxidil in chemotherapy-induced alopecia. 1983. 37(2):97–108.. Misciali C. 65(5):504–23. Alopecia associated with captopril treatment [letter].A. Hosking G.I. 184(2):124–5. Hair loss during fluoxetine treatment [letter]. 159:737–8. A multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy. 264 Group [see comments]. 39.ethanol-induced gastric lesions in rats. Bardazzi F. Brodin M.F. Smit A. Valero V. Mattson R. Litt J.B. Fraunfelder F. New York: The Parthenon Publishing Group. [Prevention of cytostatic-related hair loss by hypothermia of a hairy scalp using a cooling cap].. J Am Acad Dermatol. 29.M. Nobuhara Y. 1992. Brodkin E. 342(8884): 1423. and Donker A.A. Koizumi J. 1996.

Postpartum During pregnancy anagen is prolonged. and must be questioned on taking history.1 Follicles that would normally complete a longer cycle by remaining in anagen prematurely enter telogen and are subsequently shed 2–3 months after the offending insult has been instituted.7. Increased hair loss may occur 1–4 months after childbirth.5. such as those described below.1). . as described by Headington. but may be generalized (see Figure 6. and low plasma protein. such as interferons a and ?. there is a delayed anagen release.6 Telogen effluvium: acute and chronic Telogen effluvium (TE) is discussed at length in Chapter 5 as it relates to medications. and.3. which augments metabolic demands. Obese adolescents sometimes inflict on themselves a diet of salads and fruits lacking in protein. Metabolic imbalances. Full recovery is usual in 4–12 months. It can be quite severe.8 There may be aggravating factors.9 Loss is more marked in the frontal and temporal regions. 2 Interferons a and ? have been shown to decrease epithelial proliferation and to affect follicular matrix cells directly. However.5 Acute telogen effluvium secondary to a known cause Fever Fever can cause alopecia 8–10 weeks after the bout. It is never total. Telogen effluvium tends to be less severe in subsequent pregnancies. may slow down matrix proliferation. blood loss. and may continue for several months. This also can lead to hair loss. TE can occur as a result of a systemic disturbance.8. Fever. such as psycho-physical trauma. may cause an immediate anagen release (IAR) as described by Headington. percentages of anagen hairs increase during pregnancy from 84% in the first trimester to 94% in the final trimester.4 Crash dieting/hypo-proteinemia Acute voluntary starvation in young women is not uncommon. would probably impair the ability of the rapidly multiplying follicular matrix cells to proliferate normally. Rooth and Carlstrom10 noted hair loss. as a result. edemas and weakness in 20 obese patients on a 200 calorie diet or on a total fast. 1 Follicles enter catagen and then telogen. is not total and is usually reversible. but these changes were prevented by the addition of a small amount of protein.6 After parturition.2 Endogenous pyrogens.

16 (see Figure 6.12 of women with diffuse alopecia13. (b) Top view. Iron deficiency even in the absence of anemia (low hemoglobin) has also been reported by Hard.9 Diffuse alopecia may sometimes be the first or only cutaneous sign of hypothyroidism. The hair loss is diffuse. showing fronto-temporal thinning.2). Desai and Roaf17 report telogen effluvium in a patient after prolonged surgery. A thorough history regarding weight gain. (a) Side view. Major interventions and prolonged anesthesias Blood loss and surgery with prolonged anesthesia may cause telogen effluvium15. the two not infrequently occur together.1 A 30-year-old female presenting with a one-month history of abrupt diffuse hair shedding commencing 6 weeks after the birth of her last child. Thyroid influences There is no consistent correlation between the degree and duration of hypothyroidism and the severity of hair loss. Severe thyrotoxicosis can also cause diffuse alopecia of the scalp. with regrowth after 4 months.148 Hair Loss: principles of diagnosis and management of alopecia Figure 6. showing a widening of the central part. Patients usually respond to thyroxine replacement11 unless the problem has been of very long duration and some follicles have atrophied. cold tolerance.18 Iron deficiency Iron deficiency with or without anemia has been reported to be present in as many as 72% . It is possible that telogen effluvium from iron deficiency may unmask an underlying androgenetic alopecia. This is clearly different from the patchy alopecia occurring after localized pressure from surgery. and energy level is important.14 Because androgenetic alopecia and iron deficiency are both common conditions in women.

particularly with Crohn’s disease. including pubic or axillary hair.19 This kind of hair loss is also referred to as ‘toxic telogen effluvium’. (b) Top view.20.23 . cirrhosis or fatty liver. hepatic disease and malabsorption Hodgkin’s disease may present with telogen effluvium as its first sign. showing thinning of the central part. brittle and sparse with chronic renal disease. displaying a significant widening of the parting. 9 Inflammatory bowel disease has been reported to be associated with hair loss.21 There may thinning of body hair. The liver is the major site of amino acid inter-conversion. Malignant disease.15 Scalp hair can become dry.2 35-year-old female with a 6-week history of abrupt diffuse hair shedding commencing 8 weeks after bowel surgery. He found increased telogen counts in 34 patients and evident hair loss in 11. malabsorption should be investigated. Zaun 22 studied 53 patients who had either hepati- tis. showing marked thinning. (a) Side view. It has been suggested that disturbed liver metabolism of cystine and methionine may be related to alopecia. Hepatic disease has been reported to be associated with diffuse alopecia.Telogen effluvium: acute and chronic 149 Figure 6. renal failure. (c) Occipital view.22 When sparse hair and growth retardation are associated with chronic frequent loose pale and bulky stools.

.150 Hair Loss: principles of diagnosis and management of alopecia Psychological stress. frequently with a positive pull test. 195126 this to be a physiological phenomenon.28. would be Chronic Telogen Effluvium (CTE).15.3 A histological transverse section of chronic telogen effluvium. it is a source of anxiety to her.25 but the paucity of reports suggests that it is uncommon.27 They describe a ‘not uncommon condition’ presenting with transitory episodes of shedding lasting several weeks with no apparent cause. CTE contrasts with classic acute telogen effluvium by its persistence and its tendency to fluctuate for a period of years. acute anxiety. It usually affects women of 30 to 60 years of age who generally have a full head of hair prior to the onset of shedding. The degree of shedding is usually severe in the early stages. increased parting widths over the entire scalp and increased telogen shedding. Women who present with this type of hair loss frequently are upset and want a satisfactory explanation for their problem. A modern term for this condition.29 CTE is not uncommon.2 Medications These are discussed extensively in Chapter 5. in 1959. The typical patient is a ‘vigorous otherwise healthy woman’ who presents with diffuse hair loss that is cyclic and reversible. with or without a recognizable initiating factor. and depression Acute anxiety or depression may cause a telogen effluvium. and the hair may come out in handfuls. coined by Whiting. Diffuse cyclic hair loss in women was first described by Guy et al. showing a disproportionate number of telogen hairs on transverse section (courtesy of Dr Magdalena Martinka). There is literature that does support the notion of psychogenic telogen effluvium. Females present with a diffuse thinning.24. Obviously. Patients are particularly troubled by Frequently encountered in dermatological practice is the woman who presents with chronic diffuse hair loss of unknown cause. Chronic telogen effluvium of unknown cause in the female patient ‘Woman is herself constantly doing something to her hair. She even carries a little mirror everywhere with her with the principal object of looking at her hair to see that it is all right. They considered Figure 6.’— CBerg. reduction in pony tail diameter. It is a form of diffuse hair loss affecting the entire scalp for which no obvious cause can be found. The onset is usually abrupt.

(4) Topical minoxidil 5% solution twice daily. Overlap with androgenetic alopecia and/or psychogenic pseudo-effluvium is not uncommon. and involving the entire scalp area in increased shedding of telogen hair.3).3). laboratory testing may often show ferritin levels below the normal male reference range of 25–30 µg/l. However. (3) Top up ferritin levels to greater than 30 µg/1. while miniaturized hairs are not a feature of the disorder. (2) Make sure you have ruled out any underlying cause of telogen effuvium. This may initially lead to the differential diagnosis of psychogenic pseudoeffluvium. Sufficient nutrition is obtained in a normal diet. further studies with double-blinded placebo controls analyzing the single and combinational benefits of supplemental iron and topical minoxidil solution for CTE are needed. CTE is usually reversible. Repeated reassurance that the condition does not cause complete baldness is necessary. With the exception of bitemporal recession. and correlates better with emotional upset than with actual hair loss. There is evidence that the taking of excessive and unnecessary supplements could actually induce telogen effluvium. starting abruptly without a recognizable initiating factor.30 feel that in approximately 30% of cases of chronic diffuse loss of scalp hair with a duration of at least 6 months no underlying abnormality can be found. as one must temporarily shed more telogen hairs to increase the eventual percentage of anagen hairs. Patients must be warned that initially there may increased shedding with topical minoxidil solution. Nutritional supplements (except for iron when indicated) are not recommended.31 The normal ferritin levels for men and women differ in most laboratories.31 At the University of British Columbia Hair Clinic our approach to CTE is: (1) Confirm the diagnosis with a 4 mm scalp biopsy with transverse sectioning (see Figure 6. Trueb et al. large amounts of zinc in supplements (> 25 mg/day) may affect iron absorption adversely.Telogen effluvium: acute and chronic 151 the continuing hair loss. In certain cases of CTE. Usually normal reference levels for women are considerably lower. CTE does appear to be self-limiting in the long run. We feel that it is likely that topping up ferritin levels will maximize the hair growth potential of topical minoxidil in those menstruating women with low ferritins. CTE may unmask their AGA. in those women who have a genetic predisposition to androgenetic alopecia (AGA). the amount of shed hair here is greater than that in androgenetic alopecia. Scalp biopsies show an increase percentage of telogen hairs (see Figure 6.31 These authors also feel that hemoglobin levels should be above the lower male range (greater than 13 g/ dl) to maintain the normal anagen to telogen ratio of 9:1. Owing to the synchronization of the hair cycle. and fear total baldness. Typically this occurs in women. as a large number of the ‘normal control’ group are menstruating women. and hair will not necessarily grow back to the same density as before. No apparent cause can be found. Van Neste and Rushton feel that topping ferritin levels to at least the lower limit for men may correct this problem to a certain degree. We have found that topical minoxidil solution is beneficial in maintaining hairs in anagen and increasing conversion of hairs from telogen to anagen. The patient should be monitored every 4–6 months with repeat ferritin levels until they have reached this threshold level. . However. hair thinning is usually discrete which contrasts to the intense emotional overtones brought about by this situation.31 For example. Scalp dysesthesia or a sensation of pain in the hair (trichodynia) is an accompanying symptom in a significant proportion of cases.

10. Arch Klin Exp Derm. Telogen effluvium: hair loss after spinal cord injury. Blackwell Scientific Publications: Oxford. Study of postpartum alopecia. 1961. Schiff B. Satyaswaroop and P. 1984. E. and E. Scoggins R. 1980. J Clin Endocrinol Metab. 65(8): 485–6. 5. In Advances of biology of the skin. In Disorders of hair growth. ed.Olsen. 1985. 7:52. and N. Yaar M. James K. 12. 1997. 1989.C. 7. 235:386–93. 20.. Arch Dermatol. Ramsay I. Arch Dermatol. 403–9. 94:125. 87:609. Pecoraro V. Effect of pregnancy on the human hair cycle. Freinkel R. 1969. 1963. W.. Rook A. Postgrad Med 1967. 6. Williams R. Klein A. Cutaneous manifestations of hyperlipidemia and uraemia.C. Rushton D. ed. Hautarzt. 1988.A. Post partum alopecia. 106(3):349–52. Kligman A. 35: 323–7. A.A. London: George Allen & Unwin Ltd. J Obstet Gynecol. 23. and S. Anesth Analg. In Trichology: diseases of the pilosebaeous follicle. Wachstumsstorungen der kopfhaare als folge von hepatopathien. R. Diffuse alopecia: Endocrine. 14. McGraw-Hill. Arch Dermatol.H. Dahlin P. Abel R. 82(5):303–4. Acta Med Scand 1970. J Clin Endocrinol Metab. J Invest Dermatol. S. 1947. 27. Thompson J.W. Desai S. Fiedler V. Zaun H. 129(3):356–63. J Invest Dermatol.P. Antiproliferative effect of interferon-gamma in human endometrial epithelial cells in vitro: potential local growth modulatory role in endometrium. Tabibzadeh. ed.Roaf. Crohn’s ileocolitis presenting as chronic diffuse hair loss. [Dermatological changes in patients receiving long-term hemodialysis].L.S.George and J. 1969. Dis Colon Rectum. The unconscious significance of hair. et al. Post operative (pressure) alopecia.Nerette. Arch Dermatol. P. 8. 41:357. Effects of alpha and beta interferons on cultured human keratinocytes. 1993. Biochemical and trichological characterization of diffuse alopecia in women. Pergamon Press: Oxford.E.T. 1960. Schattner A.Shanon. 1966. Non-anemic iron deficiency as an etiologic factor in diffuse loss of hair of the scalp in women. 63(1):83–4. F. 1963. 1972. Berg C. 108(5):702–3. 26. Alopecia after ileal pouchanal anastomosis. Telogen effluvium as a sign of Hodgkin disease. 1989. Diffuse cyclic hair loss in women.152 Hair Loss: principles of diagnosis and management of alopecia References 1. 81:83–5. 4. In Diseases of the hair and scalp.J. 25. 24.Montagna.Rook.K. 18. J R Soc Med.S. Karassik R. J. 83:175–98. ed.. Hair growth and alopecia in hypothyroidism. Camacho F. 67(1):131–8. Guy W. Hard S.I. 9. 1993. Telogen effluvium after anesthesia and surgery. 2.. 203. 13. 43:562–9. New concepts and review.. . Lubach D.. Pathologic dynamics of human hair loss. pp. The normal trichogram of pregnant women.Rao. metabolic and chemical influences on the follicular cycle.. Headington J. 1960. 15. pp.Leyden. 17. pp. 1973. 1991. 31(2):82–5. Thyroid and adrenal interrelations with special reference to hypotrichosis and axillairis in thyrotoxicosis. Skelton J. 1990.Rudolph and J. Aula Medica Group SA: Madrid. Telogen effluvium. Inc. 3. 85(1):70–4. Alopecias due to telogen effluvium. Schnipper L. 241–252.Carlstrom.. 136–66. 11. 1951. 32(6):457–65.: New York. Rooth G. 16. 22. p. Arch Dermatol. and Y.R.N. and Gilchrest B. Diffuse alopecia: telogen hair loss. 19. 21. Lynfield Y.Camacho. Therapeutic fasting.D. Arch Phys Med Rehabil. Br J Dermatol. 81:34. 1984. 187(6): 455–63.Freinkel. 123(2):187–97. Arch Dermatol. Acta Derm Venereol. 1959. Arch Dermatol.G.

14(4):723–31. 51(12):899–905. Chronic telogen effluvium.A. 1996. 15(1):113–25. and D. 30. Dermatol Clin. 31. 35(6): 899–906. Clin Dermatol. 1997.M. J Am Acad Dermatol. [Idiopathic chronic telogen effluvium in the woman].A. Whiting D. Hautarzt.H. Trueb R. Chronic telogen effluvium: increased scalp hair shedding in middleaged women. 2000.Telogen effluvium: acute and chronic 153 28. Whiting D. 1996.J. 29. Van Neste D. .Rushton. Hair problems in women.

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while FD presents with pus- Figure 7. (see Chapter 1.1 Lack of follicular ostia is the hallmark sign of scarring hair loss. . Scarring alopecias are true trichologic emergencies.1) and irreversible alopecia. lichen planopilaris (LPP) and folliculitis decalvans (FD). When the inflammation is located deep. catagen. CCLE and LPP are characterized by keratotic follicular papules. and telogen. in the vicinity of the non-permanent portion. Figure 1. scarring alopecias are categorized as either inflammatory or non-inflammatory. a scarring alopecia is unlikely to develop. and subsequently differentiate into the various layers of the hair follicle. Follicular stem cells are located in the bulge area where the arrector pili muscle inserts into the follicles. histological or proposed pathogenic criteria. there is a permanent upper portion of the hair follicle and a non-permanent lower portion.1. These cells migrate down into the hair follicle. Classification Classification schemes for cicatrizing alopecias have been based upon clinical. If the inflammation is located within the permanent portion.8). A basic knowledge of follicular anatomy is important in the understanding of scarring alopecias. The non-infectious inflammatory scarring alopecias include chronic cutaneous lupus erythematosus (CCLE). then a cicatrizing alopecia is more likely to occur. because the location of the inflammatory infiltrate is crucial in determining irreversibility of alopecia. Follicles can be saved from irreversible damage if this peribulge infiltrate can be controlled.7 Cicatricial (scarring) alopecias Introduction Cicatricial (scarring) alopecia represents a diverse group of diseases characterized by lack of follicular ostia (Figure 7. As the hair cycles through anagen. particularly around the stem cells of the bulge area and the infundibulum.2 Clinically. The terms cicatricial and scarring are used interchangeably.

Two 4 mm punch biopsies are performed. One is submitted for transverse sectioning and the other is divided in half and submitted for both direct immunofluorescence and longitudinal sectioning. and lidocane with epinephrine is infiltrated into the area. because this is the location of terminal anagen hair bulbs. These conditions are centered on the crown or vertex and progress in a roughly symmetrical pattern. a biopsy site is selected. CCLE. preferably with a positive pull test and a paucity of follicular orifices. Ten minutes is then allowed to take advantage of the vasoconstrictive effect of the epinephrine. and folliculitis decalvans. The non-inflammatory scarring alopecias are pseudopelade of Brocq (PP) and follicular degeneration syndrome. The blue suture allows for easier recognition and differentiation from hair during suture removal 7 to 10 days later. First. Follicular destruction is not the primary event. while the neutrophilic mediated conditions include FD. LPP and PP. A less cosmetically important site. In primary scarring alopecias. such as the posterior scalp. the hair follicle is the primary target of destruction. and FD are primary alopecias. Sperling has coined the term central. and acne keloidalis. and neoplastic infiltrates. The area is marked with a red marker. The lymphocytic-mediated disorders include CCLE. The hair in the biopsy site is clipped. the hair follicle is simply an ‘innocent bystander’. Secondary scarring alopecias result from events outside the follicular unit that impinge upon and eventually eradicate the follicle. . Sarcoidosis and morphea are examples of secondary scarring alopecias. Special stains.0 nylon suture. follicular degeneration syndrome. classifies the cicatrizing alopecias according to inflammatory infiltrate cell type: lymphocyte or neutrophil. The biopsy site is then closed with a blue 4.3 Primary scarring alopecia is defined microscopically as preferential destruction of follicular epithelium and / or its associated adventitial dermis with relative sparing of the interfollicular reticular dermis. centrifugal scarring alopecia (CCSA). Pressure is then applied to the biopsy site with a cotton applicator that may be saturated with aluminium chloride. A second scheme. dissecting cellulitis. such as PAS and elastin. The punch is placed parallel to the direction of the hairs and inserted to the depth of the bevel. developmental abnormalities. may also be requested. This pathologically based classification system assists the clinician both in therapeutic decision-making and in gaining a better patho-physiological understanding of these disorders.156 Hair Loss: principles of diagnosis and management of alopecia tules. and PP. is preferable.4 This grouping includes pseudopelade. LPP. This site should be representative of active disease (primary lesion). The biopsy for cicatrizing alopecias A scalp biopsy is crucial in the diagnosis of a cicatrizing alopecia. PP. The biopsy should include the subcutaneous fat. genetic disorders. Scarring alopecias can also be classified as primary or secondary. LPP. based upon pathology. Lymphocytic-mediated cicatricial alopecias Clinical features The three most common lymphocytic-mediated cicatricizing alopecias are CCLE. with disease activity limited to the peripheral zone surrounding the alopecic zone. In these cases.

an ANA is recommended for all patients with CCLE. However.7 In three out of the seven. (a) and (b). (c). Follicular hyperkeratosis occurring centrally within a plaque of lupus erythematosus. the scalp was the most prominent finding.7 This common involvement of the scalp is intriguing. (d). Very few patients (< 10%) who present with CCLE ever progress to systemic LE. 7/17 patients (41%) with CCLE had cicatricial scalp involvement. More than half these patients had scalp involvement at the onset of the condition. 35 per cent (30/86) had scarring alopecia.1 years. In a series of 86 patients with CCLE of a mean duration of 15. CCLE accounts for 30 to 40% of patients with scarring alopecias and has a definite female predilection.8 Age of . In 10% of patients with CCLE. because the scalp is a relatively light-protected area.Cicatricial (scarring) alopecias 157 Figure 7. A 23-year-old female with painful erythematous atrophic plaques. A 60-year-old female with frontal scalp involvement.2 Chronic cutaneous lupus erythematosus of the scalp. scalp involvement may be the sole manifestation of LE.5 A published report6 of 89 patients with CCLE showed that 34% had scalp involvement. In a smaller study by Callen.

2d). There is also increased curliness of hairs in scarred areas. As the lesion expands. Pruritus and tenderness are often a prominent feature.3h. the central erythema fades and the surface flattens. Follicular hyperkeratosis is present at the periphery of the plaques. These two presentations are now considered variants of lichen planus. and represent follicular hyperkeratosis. The term lichen planopilaris was first introduced in 1895 by Pringle. In addition. There is a spectrum of LPP. These keratinous plugs are from the follicular openings. Occasionally drugs such as gold14 or mepacrine (atabrine)15 can trigger scalp lichen planus and cause irreversible hair loss. with a predilection for areas of greater hair density. rather than centrally (Figures 7. normal anagen hairs can easily be pulled out of the scalp. It usually occurs between 30 and 70 years of age. Central atrophy and telangiectasia eventually become prominent. atrophy. These lesions slowly progress to large erythematous. At this point patients may experience loss of hair. with its extent not clearly apparent unless the scalp is shaved (Figures 7. a characteristic feature of the scarring alopecias. a clue to help distinguish CCLE from LPP (Figure 7.12 showed that 50% of their series of 45 patients with scalp LPP had strictly scalp involvement only.2).13 LPP accounts for 30–40% of scarring alopecias. Seven per cent had either axillary or groin involvement. and fails to account for the majority of intermediate cases. Scalp lesions begin as erythematous papules or irregular small scaly plaques. With continued spread of the disease.3a). Patients present with erythematous plaques of alopecia. edematous plaques. The whole skin surface.3e.3f. and anagen hairs can be extracted with gentle hair-pulling.158 Hair Loss: principles of diagnosis and management of alopecia onset of scalp CCLE is usually at between 20 and 60 years of age. Graham-Little10 described folliculitis decalvans et atrophicans or follicular scalp lesions resulting in cicatricial alopecia associated with follicular keratotic lesions at other sites. A prominent thickened and adherent scale may develop. Hypopigmentation and depigmentation begin to appear. Mehregan et al.9 who described the association of lichen planus with follicular keratotic lesions. and ulcerations may even develop (Figure 7. such as the occipital scalp in men with AGA (Figures 7. and a female predominance (2:1) has been noted. This initial alopecia induced by follicular inflammation is potentially reversible. Tufted folliculitis consisting of several hair shafts emerging from a single ostium can also . white atrophic scarred alopecic plaques will predominate over their inflammatory precursors. 7. telangiectasia and follicular hyperkeratosis (Figure 7. 7. and alopecia of the scalp or other hairy areas has been described. Lesions typical of lichen planus do not occur on the scalp. patients with scalp lichen planus should be followed up to assess whether lichen planus develops elsewhere (Figures 7. large. the oral mucosa and the nails must be examined. LPP is usually an insidious process evolving over several years. Clearly. and scarring develops.3g). This view is limited.3j).11 It was felt 40 years ago that one had to have this triad to make a diagnosis of LPP. In 1915.3d).3b and 7. which when removed reveals keratinous plugs on its under-surface.3c). Of all patients who have lichen planus. spinous or acuminate lesions. 7. A clinical triad of classic plaquetype lichen planus. LPP may be very widespread. 7% nail involvement.3i and 7. owing to torsional within the hair follicle. 27% mucous membrane involvement and 40% glabrous skin involvement. Follicular hyperkeratosis is more active in the center of a plaque. a series of 807 patients showed that only 10 (< 1%) had scalp involvement.

Cicatricial (scarring) alopecias 159 Figure 7.3 Lichen planopilaris (LPP). (a) Follicular hyperkeratosis at the periphery of erythematous alopecic areas. (b) Showing active inflammation. (b) and (c) LPP affecting the spared areas of male androgenetic alopecia. (c) Burnt out LPP. . (e) Extensive case of LPP at the back of the scalp. (d) Ulcerative lesion of LPP of the scalp.

LPP in a 45-year-old male with scarring alopecia as well as acuminate lesions on the arms and lichen planus-like lesions in the groin. (j). (i).160 Hair Loss: principles of diagnosis and management of alopecia (f) and (g). (k). Tufting of hairs in LPP. This fits well with GrahamLittle disease. . Close-up after the head has been shaved. showing marked involvement of much of the scalp. (h).

(d). . (c). (b) A 5year-old with pseudopelade (Brocq). (e) An 8-year-old boy with scattered pseudopelade (Brocq). Scarring hair loss affecting central portion of the scalp.4 Pseudopelade of Brocq (a).Cicatricial (scarring) alopecias 161 Figure 7.

(i) PP affecting the area most affected by androgenetic alopecia and mimicking androgenetic alopecia.162 Hair Loss: principles of diagnosis and management of alopecia (f) and (g) PP progressing over 10 years in a 40-year-old male. . (h) PP affecting the area spared by androgenetic alopecia. (j) pp affecting tne beard area.

extension occurs more rapidly. it is now believed to represent an idiopathic disorder unrelated to trauma or hair cosmetics. usually of adulthood.17–19 Kossard has described an entity occurring in postmenopausal women presenting with perifollicular erythema along the marginal hairline. There is controversy as to whether PP is a distinct entity or is effectively the same as end-stage CCLE or LLP.3k).4f and 7. PP is an idiopathic disorder. Braun-Falco et al.16 There is a variant of LPP.19 Histological findings were indistinguishable from LPP.4b-e).4b).19c. Brocq of Paris described what later became known as Pseudopelade19a. Pseudopelade refers to ‘like alopecia areata but not alopecia areata’. However. . after 15– 20 years the patient may still be able to arrange his/her hair to conceal the patches effectively. Occasionally the pattern of hair loss of PP can mimic androgenetic alopecia as described by Zinkernagel et al. irregular. End-stage LPP or CCLE may mimic an early pseudopelade (Brocq) as discussed below. reported an incidence of 4/ 142 (4. Occasionally PP may affect the beard area and not just the scalp (Figure 7. Brocq subsequently admitted that this term does confuse the Iiterature 19b. As with other cicatrizing alopecias. His group described 94/142 (66.35%) cases of PP under the age of 11 and nine patients (9. The parietal and vertex areas of the scalp are primarily involved (Figures 7. extension of the process takes place only very slowly (Figures 7. the follicular ostia are not present while in AA they are most certainly present. Occasionally there may be erythema and mild pruritus.4a and 7.23 The course is extremely variable. A form of central centrifugal scarring alopecia in African-Americans. and occurs because the infundibular epithelium of damaged follicles often heals so as to cause the formation of a common large infundibulum. Sperling believes the main etiology for FDS is that the inner root sheath desquamates prematurely far below the level of the isthmus not only in alopecic areas but even in non-inflamed follicles or the clinically normal scalp of affected individuals (Figure 7. In the majority of cases.. Pseudopelade (Brocq) (which is referred to as PP in this text) is regarded by most as a condition in which destruction of follicles leading to permanent patchy baldness is not accompanied by any clinically evident inflammatory pathology.22 strongly support the idea that pseudopelade can exist as a distinct entity. post-menopausal frontal fibrosing alopecia. and exceptionally there may be almost total baldness after 2 to 3 years.6%) in the age range of 11–20. However. Eyebrow loss was described in 13/16 women. anagen hairs are easily extracted. asymmetrical. overlaps significantly with PP with marked non-inflammatory cicatricial alopecia on the top of the scalp in black patients. This has been classically described as ‘footprints in the snow’. Indeed. also known as follicular degeneration syndrome (FDS). The course is often protracted and prolonged.21 Detailed studies by Braun-Falco et al. in some cases. Tufting is common as an endstage phenomenon in many scarring alopecias.20.20 PP presents with small. In 1885.4j).4g). ivory porcelain white patches devoid of follicular units. producing a frontal fibrosing hair loss extending to the temporal and parietal hair margins.5). In pseudopelade (Brocq).26 Although initially thought to be a consequence of hair-care practices. This is known as polytrichia. PP is usually asymptomatic and without inflammation. This author has seen at least 3 cases in children under the age of 10 (Figures 7. Pelade is the French word for alopecia areata (AA).25.Cicatricial (scarring) alopecias 163 occur in LPP (Figure 7.24 and the diagnosis of PP may be missed (Figure 7.4i). PP in children has been described.2%) patients with PP without any previous underlying condition.

(d) Close-up of patient illustrating lack of follicular ostia. . (a) Black female with significant alopecia. (c) Black male with significant alopecia.164 Hair Loss: principles of diagnosis and management of alopecia Figure 7.5 Central centrifugal scarring alopecia (follicular degeneration syndrome) in African-Americans. (b) Close-up showing obliteration of follicular ostia.

and fibrosis (Figure 7. with a characteristic perifollicular interface dermatitis (Figure 7. Second. but may extend down the length of the follicle. Other features include loss of sebaceous epithelium and marked perifollicular lamellar fibrosis. a central localization tends to occur in CCLE. if pustules are present.1 Figure 7. while a peripheral distribution is seen in LPP. loss of sebaceous epithelium.7 Pathology of lupus erythematosus showing peri-adnexal and perivascular lymphocytic infiltration with follicular hyperkeratosis. Inflammation affects the upper portion of the follicle. Perifollicular inflammation is most severe at the level of the infundibulum. Pigment incontinence is present.Cicatricial (scarring) alopecias 165 Figure 7.8). the most likely diagnosis is PP if the scarring alopecia is non-inflammatory. Pigment incontinence is present. a thickened basement membrane zone and an increased dermal mucin helps support the diagnosis of CCLE. Pathology The histopathology of CCLE reveals follicular vacuolar interface changes. and inflammatory cells may invade the follicular epithelium. .7). if follicular hyperkeratosis is present. The presence of a focally thinned epidermis. Finally. First. Some clinical pearls can be helpful in establishing a diagnosis (Figure 7. a superficial and deep perivascular and periadnexal lymphocytic infiltrate. The lymphocytic infiltrate of LPP is lichenoid. then FD is the most likely diagnosis. Direct immunofluorescence demonstrates granular deposits of C3 of IgG distributed along the dermal-epidermal junction.6).6 Algorithm for diagnosis of major non-infectious scarring alopecias.

Pathology of lichen planopilaris displaying the characteristic follicular lymphocytic interface dermatitis.166 Hair Loss: principles of diagnosis and management of alopecia Figure 7. Elastin staining demonstrated normal or abundant elastic tissue in PP. The end stage of PP is characterized by marked scarring and the absence of an inflammatory infiltrate. the epidermis becomes atrophic. while in LE and LPP the quantity of elastin is significantly dimin- Figure 7.) . as in LE. In the early stages. (Courtesy of Dr Magdalena Martinka. As PP progresses.8 (a). The pathology of PP depends on disease duration. Direct immunofluorescence may demonstrate grouped globular IgM cytoid bodies in follicular epithelium. and sebaceous glands and hair follicles are obliterated. Pigment incontinence is less evident than in LE or LPP. There may also be tufted folliculitis in the upper portion of the epidermis (Figure 7. Direct immunofluoresence is negative. (Courtesy of Dr Magdalena Martinka.9 Numerous hairs exiting from one infundibulum which clinically appears as polytrichia or tufted folliculitis. (b) and (c). a peri-infundibular lymphocytic infiltrate is present beneath a normal epidermis.) Perivascular and peri-eccrine infiltrates are usually not present. rete ridges vanish.9). Special staining techniques may help in establishing a diagnosis of a scarring alopecia.

11). (Courtesy of Dr Magdalena Martinka.10 Algorithm for pathological assessment of major noninfectious scarring alopecias. An algorithmic approach to the pathology of scarring alopecias is presented in Figure . and will be described below. Keratoacanthomas and squamous cell carcinomas can mimic hypertrophic lupus erythematosus. Early CCLE and LLP can look quite similar.versus neutrophilic-mediated. there are reported cases of scarring alopecia in severe scalp psoriasis. Tinea capitis can be scarring. However. The lymphocytic scarring alopecias can certainly be difficult to tell apart from each other. Differential diagnosis Scalp psoriasis has the presence of follicular ostia and the lack of follicular plugging and atrophy. In addition. 7. A potassium hydroxide preparation and/or culture will help confirm the diagnosis.Cicatricial (scarring) alopecias 167 Figure 7.28 Inflammatory changes in the infundibular area of the follicle in psoriasis may disrupt follicular stem cells and result in scarring alopecia.27 Periodic acid Schiff staining in LE will demonstrate a thickened basement membrane zone and alcian blue stain or colloidal iron stains will show increased dermal acid mucopolysaccharides.10 dividing entities into lymphocytic.) ished. but again there is no follicular plugging or atrophy. the co-existence of LPP and CCLE Figure 7.11 Neutrophilic infiltrate in folliculitis decalvans. Folliculitis decalvans is neutrophilic-mediated (Figure 7.

decrease follicular inflammation and prevent further fibrosis. This is summarized in algorithmic form in Figure 7.13 Injecting intralesional cortisone into the surrounding hairy areas of scarring alopecia.6 and 7. At the University of British Columbia Hair Clinic the therapeutic strategy for patients with lymphocytic-mediated scarring alopecias is based upon the extent of the alopecia: groups with less than 10% scalp involvement and those with more than 10% scalp involvement are treated differently. . patient age.1 ml/injection for 20 injections. has been reported. and the extent of scalp involvement. the severity of symptoms.29 Differentiating clinical and histopathological features of lymphocytic scarring alopecias are discussed above and are summarized in Figures 7.10. can halt further spread of the condition and reduce symptoms of itch and burning.168 Hair Loss: principles of diagnosis and management of alopecia Figure 7. injected with a volume of 0. and disease severity. The severity is determined by the rapidity of the progression of the condition. Triamcinolone 10 mg/ml.12. the degree of inflammation.12 Algorithmic approach to treatment of lymphocytic-mediated scarring alopecias. Figure 7. The goals of treatment are to arrest the cicatrizing process. Treatment The treatment of scarring alopecia depends on three variables: diagnosis. Injections are performed once monthly.

Intralesional corticosteroid. If the alopecia is very severe. showing marked improvement after 1 year of hydroxychloroquine 200 mg twice daily. is administered to scarring areas once every four weeks (Figure 7. Dapsone (100 mg/day)34–37 and thalidomide (100 mg/day)38–40 are other alternatives.Cicatricial (scarring) alopecias 169 Figure 7. ultra-potent topical corticosteroid and hydroxychloroquine. rapidly progressive. then scalp reduction and/or hair transplantation are further options.15 Lichen planopilaris: the patient from Figure 7. double therapy with topical and intralesional corticosteriods is initiated. because of a delay in the therapeutic effects of hydroxychloroquine.14 Lupus erythematosus: the patient from Figure 7. 200 mg twice a day. Premature transplantation may actually aggravate the condition. very inflamed and symptomatic. If there is more than 10% scalp involvement. can be initiated and then tapered once improvement is detected.3d with previous ulcerative LPP improved markedly with hydroxychloroquine. than other treatments can be attempted. If the alopecia is rapidly progressive. then hydroxychloroquine. Figure 7. then prednisone is added at 1 mg per kilogram per day and tapered over two months. therapy is tapered once improvement is acheived. When a pull test is negative for over two years and alopecia is clinically stable.2c.13). inflamed. Isotretinoin. If the patient is not responding within eight weeks to this double therapy. and symptomatic. A pull test is conducted with each visit. Again. which can serve as a primary target in scarring . and an ultra-potent topical corticosteroid is applied twice daily.15). monthly intralesional corticosteroid injections and topical superpotent corticosteroid ointment twice daily. Increasing the number of hairs. 2 ml of 10 mg per ml.14 and 7.31–33 at doses of 1 mg per kg per day. If improvement is not noted after six months. then a systemic steroid is also administered for eight to twelve weeks.30 is added for a minimum of six months (Figures 7. triple therapy is immediately initiated with intralesional steroid. intralesional corticosteroid and topical corticosteroid. If there is less than 10% scalp involvement. and therapy is continued for six to twenty-four months until the pull test is negative. The prednisone provides bridge therapy.

(b) After 6 months of isotretinoin 1 mg/kg/day. alopecias.18 Tufted folliculitis in dissecting cellulitis. enables the overall density to be better than that of untreated individuals. many clinicians feel that topical minoxidil. most evident after the scalp has been shaved. may cause the patient to become more symptomatic with increased inflammation.41 . topical minoxidil solution for scarring alopecias. showing hair shafts embedded within the skin. showing much improvement. Figure 7.170 Hair Loss: principles of diagnosis and management of alopecia Figure 7.16 Folliculitis decalvans in a 30-year-old male. pruritus or burning if the condition is remotely still active. (a) Marked erythema and folliculitis.17 Folliculitis decalvans in a 17-year-old female. by retaining unaffected hairs in anagen for a longer period of time. Although there are no controlled trials for Figure 7. The use of topical minoxidil is controversial.

however.43. such as topical fusidic acid.43 Systemic fusidic acid may also have some benefit. Dissecting cellulitis of the scalp with characteristic boggy cysts. Laser-assisted hair removal50 may help for this subset of patients. Close-up of boggy cysts.44 For severe dissecting folliculitis. Hair shafts are occasionally embedded within the scalp (Figure 7. as the disease progresses. are considered an abnormal immune response to the normal scalp flora. Follicular-based pustules develop in successive crops (Figure 7.19).11). cloxacillin. The therapeutic strategy for the neutrophilmediated cicatrizing alopecias is targeted at anti-staphylococcal therapy with systemic erythromycin. cephalosporins.45–49 Patients may be so symptomatic with discomfort. high-dose isotretinoin for a prolonged course is recommended. itch and burning. such as FD. that controlling the inflammation for these individuals is more important than salvaging the hair.19 (a). rifampin and fusidic acid. Neutrophil-mediated cicatricial alopecias The neutrophil-mediated cicatricial alopecias.44 Topical therapy can also be added.42 In the early stages. (b).44 Dissecting cellulitis can present as a boggy cystic inflammatory process (Figure 7. the pathology demonstrates a neutrophilic folliculitis (Figure 7. . Patients present with round patches of alopecia with overlying erosion. There is some evidence that a combination of rifampin 300 mg twice daily and clindamycin 300 mg twice daily for twelve weeks affords more benefit than single-agent therapy.18).17) Tufted folliculitis is a feature frequently seen in FD (Figure 7. scale or crust.16).Cicatricial (scarring) alopecias 171 Figure 7. fibrosis is prominent.

et al. Clinical and laboratory findings in seventeen patients. Clinical. 5(3):603–18. 14(4):773–82. 1953. Feder A. 1989. T. 2. A.M. Brocq L. Newton R.Wilkinson. Réchèrches sur 1’alopecie atrophiante. and Dawber. J Am Acad Dermatol. 20. Doin. 17. 97. Silver H. Braun-Falco O. M.Solomon and D. 2000. 1982.. 13.Dissaneyeka and S. Brocq L. R. Cutis.L. Scarring alopecia.R. Hebert A. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. 15.. 14. 1915. therapeutic. Arch Dermatol.Van Hale.P. J Am Acad Dermatol. 1994. 7. Lupus. 1949.. Callen J.. 98(3):234–8. 3.Lee and B. Muller. Journal of Cutaneous and Venereal Diseases 1885. . Arch Dermatol. Folliculitis decalvans et atrophicans: Report of a case. Woods B. Lichen post-aurique. Follicular lichen planus (lichen planopilaris).S. and S. 1905. Sperling L. 4. 40(2):77–83.Bergner and G. C. Br J Dermatol.A. 2. Headington J.K. 27(6 Pt 1):935–42..W.Hwang and S. Scarring alopecia in a pattern distribution [published erratum appears in Arch Dermatol 1994 Nov. 60(6):299–300. 36(1):59–66. S. Pringle J. Freese T.P.C.M. 1961.P.Alopecia. Arch Dermatol Syph. Heilgemeir. 17:77–102. 1992. P648. and A. Arch Dermatol. 31: 1078.M. 67: 346–54. comment]. Mehregan D.T.Burge. 21(2):97–109. 19. The sequelae of chronic cutaneous lupus erythematosus. 19b. 1987. laboratory. Br J Dermatol. An aggressive multiplemodality therapeutic approach is often necessary to gain disease control. The variations and course of lichen planus. Scarring alopecia in discoid lupus erythematosus.. Frontal fibrosing alopecia in a postmenopausal woman. Postmenopausal frontal fibrosing alopecia. and Solomon A. 3:49. 1997. Dermatol Clin. Ann Int Med. Cicatricial alopecia.. Hautarzt. 12.A. Whiting.M. In Transactions of the St John’s Hospital Dermatological Society.A. Lichen planopilaris: clinical and pathologic study of forty-five patients. 19c. 84:179. Lichen pilaris spinulosus. 16. References 1. 1. [The Brocq pseudopelade—a disease picture or disease entity]. A new look at scarring alopecia [editorial. 1996. 12(2 Pt 1):278–88. Clinical observations of atypical lichen planus and related dermatoses due to atabrine toxicity. 5.C. Br J Dermatol. 136(2):235–42. Pseudopelade in Traite elementaire de dermatolgie Practique. 1985. An accurate diagnosis is arrived at through a careful clinical and histo-pathological assessment. 130(6):770–4. Kossard S. 9. Paris Vol. 6. 6. Callen J.Solomon..Ahn. Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus. Altman J. Dean D. Kossard S. de Berker D. and prognostic examination of 62 patients. Scarring alopecia: a classification based on microscopic criteria. 209.S. 118(6):412–6. 8. Hot comb alopecia. 11.. 1(3):181–6.Kligman.. varieté psuedopelade. 1968. 1994.Papa and A.P. Dermatol Clin. 1992.R. London: The Society. Lee W. M. Arch Dermatol. Brocq L. 18. Wilson C. 130(11):1407].A. Chronic cutaneous lupus erythematosus. J Am Acad Dermatol.. 27: 183–5. Annales de Dermatologie et de Syphiligraphie. 1992. 1997. 19a.R. Arch Dermatol. H.. Burge S. 10.F. LoPresti P. Little E.172 Hair Loss: principles of diagnosis and management of alopecia Conclusion The scarring alopecias are trichological emergencies. 126(4):307–14. 1968.M. Templeton S. J Cutan Pathol.

J.Cash. 1983. and Gaspari A. 1990. 1989. Pseudopelade of Brocq in a child [see comments].M. biology.. Braun-Falco O. 172(1):18–23. Acta Derm Venereol. Green S. 2000.F. Hasper M. 44. Pseudopelade of Brocq in beard area... and A. 1998. 172(4):214–7.Sau...C. 2000. 124(6):311–15. R. 1994... Elastic tissue in scars and alopecia. 1999. Treatment of refractory cutaneous lupus erythematosus. 42..Klokke.. Adya C. and W. 2000. Acta Derm Venereol. 1987. Scarring alopecia in psoriasis. Lupus. 22. 43. and P. H.J. 1991. 1992.M.M.. F. [Use of oral isotretinoin in the treatment of cutaneous lupus erythematosus]. J Assoc Physicians India. 33. Tufted folliculitis of the scalp: a distinctive clinicohistological variant of folliculitis decalvans [see comments]. Rothe M. Elston D.J. Follicular degeneration syndrome in men.Trotter and J.. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? [see comments]. 1993.. Dawber R.. pathology.T. 17(5):305–6. G Ital Dermatol Venereol. Sperling L. Knop J. 167–76.Reymann.Piette. Powell J. 27.M.Korting and O.G. and R. Messenger. and Schmoeckel C. 23(5 Pt 1):944–5..Dawber and K. Long-lasting response to combined therapy with fusidic . In Hair and its disorders. 29.Angelini. 138(5):799–805. Thalidomide in the treatment of chronic discoid lupus erythematosus.F. McCollough M. 1990. Folliculitis decalvans. and F. 1(6):351–6. 42(5 Pt 2):895–6. Vanderhorst J.L. Pseudopelade of Brocq.L. 27(3):147–52. 40(11): 735–6. 128(1):68–74. 1986. N. 3rd and Smith K.Parke.O. J Am Acad Dermatol. Dapsone in cutaneous lesions of SLE: an open study. M. Br J Dermatol.Coviello and G. ed. Rheum Dis Clin North Am. 2000. What is pseudopelade? Clin Exp Dermatol.Braun-Falco. et al. Bulengo-Ransby S. Arch Dermatol. Successful treatment of hypertrophic lupus erythematosus with isotretinoin. Imai S. Bonsmann G.Camacho. The follicular degeneration syndrome in black patients.Formica and A.C. and F. Sperling L. J Am Acad Dermatol. Mixed lichen planus-lupus erythematosus disease: A distinict entity: Clinical. 41. Arch Dermatol.K.Kerdel. 31.S. Happle R. Wright A.L. et al.. 1992.. Abeck D. et al. McMeekin T. 34. Dermatologica. Singh Y. Bowers K.G. Arch Dermatol. C. 25. et al. 28. J Am Acad Dermatol.Gatter. and J.M. Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus.Trueb.J. Dermatologica 1986.A.C. 32. 8:631–40. Treatment of cutaneous lupus erythematosus. 62(4):321–4. 140(2):328–33. Zinkernagel M.A. 35. London: Martin Dunitz Ltd. Update of minoxidil treatment of hair loss. J Cutan Pathol. Arch Dermatol. Isotretinoin for refractory lupus erythematosus. Chronic cutaneous lupus erythematosus treated with thalidomide. 17(2 Pt 2):364–8. 1982. 39. Shornick J. and Bergfeld W. 23. 1995. 108(4):461–6. Verma K. 37. 1983. 1992. 21(1): 99– 115.P. pp. Folliculitis decalvans including tufted folliculitis: clinical. histopathological and immunopathological studies in six patients. Warschaw K. 40. Clin Exp Dermatol. and J. Annessi G.W. Holm A.A.Shapiro. Skelton H..N. Dawber R. 24. Br J Dermatol.K.H. Vena G.L. 130(6):763–9. 24(1):49–52.Headington. 136(2): 205–11. Duna G. 36. and A.E.Cicatricial (scarring) alopecias 173 21.E. 38. ‘Hot comb alopecia’ revisited and revised. 1992..F. 26. Dapsone in the treatment of cutaneous lupus erythematosus. and management. histological and therapeutic findings. J Am Acad Dermatol.G. 70(2):156–9.. 129(12):1548–50. Madani S. Br J Dermatol. Lindskov R. 30.

Shaffer N. Dubost-Brama A.G.. 45. Recalcitrant scarring follicular disorders treated by laser-assisted hair removal: a preliminary report. 49.. Br J Dermatol. Bachynsky T. 72(2): 143–5.. Delaporte E.. Chui C. 1994..B. Berger T. 1992. and B.Srolovitz.174 Hair Loss: principles of diagnosis and management of alopecia acid and zinc.Allen.B.Antonyshyn and J.C. 134(6): 1105–8. Dissecting folliculitis of the scalp. 18(10):877–80. J Dermatol Surg Oncol. Alfandari S.Billick and H. Arch Dermatol. Perifolliculitis capitis abscedens et suffodiens. 1992. 50. Scerri L. 1996.. et al.H. Action of isotretinoin in acne rosacea and gram-negative folliculitis.. 1982. Ross. J. 1992. 128(10):1329–31. radical excision. and isotretinoin. Price V. 121(4):328–30. 1999..M. Dissecting cellulitis of the scalp: response to isotretinoin. and Zachary C.T. 46. Resolution with combination therapy. Plewig G. Dermatol Surg.Williams..Nikolowski and H. R. Ann Dermatol Venereal. Efficacy of isotretinoin]. 6(4 Pt 2 Suppl): 766–85. . 48. 47.Wolff.H. O. A case report of combined treatment using tissue expansion. 25(1):34–7.R.C. H. J Am Acad Dermatol. Acta Derm Venereal. [Perifolliculitis capitis abscedens and suffidiens.

telogen effluvium and 139 antidepressants. 69 anti-coagulants. 16. 156 adrenoleukodystrophy. 34f. 136–8. 10. 34f extracranial 35f genetic factors and 19–21 histopathology of 29f immunological factors and 21–4 intralesional corticosteroid injections for 44f nail changes and 39f nail dystrophy and 34. 34f. 134 anemia. 114 androgen receptor blockers (ARP inhibitors) 104–5 androgen receptor proteins (ARP) 85 androgenetic alopecia (AGA) 10t. 155 anagen phase. 91f. 134 androgen blockade 102–4. vitiligo and 37f alopecia areata circumscripta 31–2f Alopecia Areata Investigational Assessment Guidelines 43 alopecia masking lotion 68 alopecia totalis (AT) 30. AA see alopecia areata acne 16. hair loss and 139 anti-psychotics/anxiolytics 143 anti-thyroid drugs. 40–1f Down’s syndrome and 20f. iron deficiency 16 anesthesias. 157 antitumor antibiotics 138 anxiety. 36f clinical features of 28–36 cyclosporin in 66f cytokines and 24 differential diagnosis of 38–42. 47.Index Note: References to figures are indicated by ‘f’ and references to tables by ‘t’. alkaline phosphatase activity and 3 anagen-telogen hair ratio 12. 89f. 143 see also hair loss alopecia areata (AA) 9. AA and non-AA 25–7 anthralin 43. 137f drug-induced 137t anagen (growing) hairs 6. 88. 68. 49–51. telogen effluvium and prolonged 148 angiogenesis. 42 amitriptyline 143 amoxapine 143 ANA see antinuclear antibodies examination anagen effluvium 134. 151. 48. 21 emotional stress and 24 etiology of 19 extent of hair loss 30. premature male AGA and 85 adriamycin (doxorubicin). 19–81. 163 AGA and 96–7 autoimmune disorders and 21 of beard 34. tretinoin and 108 animal models. alopecia and 137 AGA see androgenetic alopecia alkylating agents 138 alopecia assessment of patient with 1–18 causes of 10t DPCP treatment of 57f drug-induced 134–46 irreversible 155 reversible 139. 39f neurological factors and 25 pathogenesis 23f pathology of 27–8 pattern of hair loss 30 prognosis of 36–7 systemic steroids and 46–7 telogen effluvium and 95–6 topical immunotherapy for 54–5f treatment of children with systemic steroids 47 treatment of 42–66 treatment plan 66–70 white hairs. 158 differential diagnosis 38 history 9 iron deficiency and 148 miniaturization of hairs 27 surgical management of 121–33 treatment in men 109–12 treatment in women 108–9 vellus hairs in 6–8 in women 16. 27. 42 alopecia universalis (AU) 30. 83–119. tricyclic/tetracyclic 143 antihypertensive agents 143 antinuclear antibodies (ANA) examination 16. telogen effluvium and acute 150 . 16.

105–8. stem cells of 5. injection of intralesional 168f coumarins 139 Cox proportional hazards model 87 Crohn’s disease 149 cyclophosphamide 137. alopecia induced by 136 circumscript alopecia 32f circumscript alopecia areata 38 clindamycin 171 clobetasol propionate 68 clofibrate 144 clonazepam 143 cloxacillin 171 colchicine 138 corticosteroids 43–7. 26 calcitonin gene-related peptide 25 captopril 143 carbamazepine. 155–72 algorithm for diagnosis for 165f inflammatory 155 lymphocytic 167 pathology algorithm 167f cimetidine. 155 atherogenesis 88 autoeczematization 64 autoimmune diseases 21. 104–5. 27. 155 buspirone 143 busulfan 138 C3H/HeJ mice 25. 23 autoimmune polyglandular syndrome 21. 98. 164f cephalosporins 171 chemotherapy 134 children anthralin and 49 hair loss in 9 systemic steroid treatment in 47 therapeutic modality choices for 69 topical therapies for 67 chlorambucil 137 chlormethamine 137 cholesterol-lowering agents 144 chondroitin sulfate 3 chromosome 8p 12 26 chronic cutaneous lupus erythematosus (CCLE) 155. boggy 171f cytarabine 137 cytochrome P450 aromatase enzyme 86 cytokines. 155 catagen hairs 6. 157 histopathology of 165 vs LPP 158. alopecia areata of 34 body hair. 150 dermal acid mucopolysaccharides 167 dermographism. clues for 21–4 baldness coronary heart disease and 87 drugs and 134 patterns in population 85 prostate cancer and 88 beard. 36f Beau’s lines 34 beta-blockers 143 betamethasone dipropionate 43. 108 cysts. 48 biologic response modifiers 101. 108 delayed anagen release (DAR) 138 delayed telogen release (DTR) 138 depression 9. 69 cortisone. 22 autoimmunity. 138 cyclosporin 65–6 cyproterone acetate (CPA) 101. alopecia areata of 34. alopecia areata and 24 cytomegalovirus (CMV) infection 24 cytosine arabinoside 138 cytostatic drugs 136–8 dacarbazine 138 dactinomycin 137 dapsone 169 daunorubicin 137 dehydroepiandrosterone sulfate (DHEAS) test 16. thinning of 149 bulge area. 156. 114 bitemporal recession 91. 136. alopecia and 142–3 carbimazole 139 cardiovascular disease 87 carmustine 138 castling. 17.176 Index arrector pili muscle 5. 98. 16. DPCP and 52 catagen 134. 151 bleomycin 137 body. severe 64 despiramine 143 dexamethasone 43 . 167 chronic telogen effluvium (CTE) 150. 151 cicatricial (scarring) alopecias 10t. 98 catagen-telogen hair ratio 101 cell-mediated immunity 22–4 cellulitis 156 central centrifugal scarring alopecia (CCSA) 156.

155 follicular scalp lesions 158 follicular stem-cell gene therapy 114 follicular stem-cells 155 folliculitis. 163. 17 divalproex 142 dopaquinone 6 Down’s syndrome. with miniaturized hairs 99f follicular degeneration syndrome (FDS) 156. 171 fronto-parietal/fronto-temporal recession 90 fusidic acid 171 gastric parietal cell antibodies 22 gene replacement therapy 70 gold. 170f erythema multiforme 64 estrogen. 156. 103 hair cycling. 151 fever. 164f follicular hyperkeratosis 58. 133 hair transplants and 130 and minoxidil combination therapy 110 fluocinolone 43 fluorouracil 137 fluoxetine 143 follicular bundles. 5. tufted 166. 167. 88. 148 diffuse alopecia areata 30. 170f. 143. alopecia areata and 20f. 113 severity of 148 see also alopecia hair matrix cell mitosis 136 hair removal. alopecia and 147 finasteride 101. in women 150 dihydrotestosterone 85 dinitrochlorobenzene (DNCB) 51–2 diphenylcyclopropenone (DPCP) 26. counts of 12 dystrophy. loss of 144 hair cortex 4. 170f. 6 abnormalities of 15 quality of 10. laser-assisted 171 hair shafts 2. delayed response 59f eczematous eruptions from 60–1 f pigmentary changes with 62f treatment of eyebrows with 60f unilateral treatment with 59f discoid lupus erythematosus (DLE) 10t. 21 doxepin 143 doxorubicin (adriamycin). 51. 52–64. 166 eosinophils 27 epidermal growth factors (EGF) 105 erythema 163. 16. alopecia and 137 drug-induced alopecia 134–46 anagen effluvium 137f. 158 pattern in a family 95f prevention of 101. 33f diffuse cyclic hair loss. AGA and 105 eumelanin 6 exclamation point hairs 32f eyebrows dermatography of 69 injection with triamcinolone 45f loss of 163 treatment with DPCP 64 facial edema 130 facial hypertrichosis 107 ferritin. 165 follicular ostia 10. 102–4. 136 hair counts 13. hair loss and 158 graft hair preparation 126 Graham-Little disease 160f hair density and distribution of 10 dryness of 139 thinning of 86 hair anatomy 1–8 hair color.Index 177 diabetes mellitus 22 dibromoketone 53 diffuse alopecia 16. positive pull test 96 dystrophic hairs. 171 folliculitis decalvans (FD) 155. DPCP and 64 elastin staining 156. 11f . planting of 129 hair loss 9. 140t. 109. checking for presence of 15 eczema. 145 lichenoid eruption of scalp 134 telogen effluvium 139t. on human scalp 6 hair follicles 1–2 cellular components of 24 growth inhibitors 24 layers of 3f non-permanent and permanent segments 7 hair grafts. levels of 98. 158. 141t Dundee experimental bald rat (DEBR) 25 dyslipidemia 88 dysmorphobia 9 dystrophic anagen hairs.

178 Index hair shedding 9. 132f minoxidil and 130 multiple-bladed knife for 123f positioning of hairline 126–8 recipient area 126–30 removal of donor strips 124f hair weights. 158 hypopituitarism 85 hypothyroidism 9. 108 Hodgkin’s disease 149 hormone modifiers 101. 4. 22. 102–5 Hox genes 26–7 human leukocyte antigens (HLA) 19–21 Huxley’s layer 2. 88 hyperthryoidism 9 hypertrichosis 108 hypertrophic lupus erythematosus 167 hypo-proteinemia 147 hypopigmentation 64. 108. 147 immediate telogen release 138 immunosuppressive therapy. women with 108 Ludwig Stages I–III 90f lupus erythematosus 22. 89. 136. 5 Kaplan-Meier survival analysis 53 keloids 125 keratin 4 keratinization. 87. stages of 89 Ludwig Stage I pattern. 171 isthmus 1. 110. 98. 169 intramuscular corticosteroid therapy 47 iodine. 69. AGA and 85 intralesional corticosteroids 67. 158. 148 iatrogenic hypothyroidism 139 ICAM-1 27 ichthyosis 144 ifosfamide 138 imipramine 143 immediate anagen release 138. 149f physiological 6 hair thinning 9. 121–2f. 169 complication of donor area 126 finasteride and 130 male 113f. 159– 60f. 108 hyper-insulinemia 88 hyperpigmentation 64 hypertension 47. 64 lymphocytic-mediated cicatricial (scarring) alopecias 156–70 treatment algorithm 168f M phase drugs 138 . 163 inner root sheath (IRS) 2. 140. 169f cicatricial alopecia 10t pathology of 166f peripheral distribution 165 lichen planus 17. 155. 151 hair transplants 101. 158 lichenoid eruption 136 lithium 140–2 Ludwig pattern. 144 keratinocytes. 4. 5 insulin-resistance-associated disorders 88 interferons 143 intracellular androgen metabolism. 12 abrupt diffuse 148f. study of 103 hair-growth promoters 101 hair-specific antibodies 23 hairpieces 69. responsiveness to 21 inflammatory bowel disease 149 infundibulum 1. in teenagers 95f Ludwig Stage III. 5 hyaluronic acid 3 hydroxycarbamide 137 hydroxychloroquine 169 hydroxyurea 138 hyper-androgenism 16. 158–63. disturbed 136. 4. telogen effluvium and 139 iron deficiency 16. 5 hen’s egg test 53 heparin 139 hepatic disease 149 hirsutism 16. 87. abnormal 24 keratoacanthomas 167 keratotic follicular papules 155 leflunomide 26 lichen planopilaris (LPP) 155. 83 halcinonide 43 haloperidol 143 Henle’s layer 2. 148 isotretinoin 169. 156. 5. 169f chronic cutaneous scalp 157f luteinizing hormone-releasing hormone (LH-RH) 105 lymphadenopathy 62f. 101 hairs light-microscopic examination of 13–16 miniaturization of 27.

pulsed oral 47 pressure-induced alopecia (PIA) 38. 138 men AGA treatment options 101 frontal hairline recession 89 vertex balding in 87 mepacrine (atabrine). 88 olanzapine 143 onychorrhexis 34 ophiasis 33f. 138 methylprednisolone 47 methylthiouracil 139 mice. alopecia areata and 34. 37 National Alopecia Areata Foundation (NAAF) 19. AGA and incidents of 88 protriptyline 143 pruritus 158. 70 National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 19 neutrophil-mediated cicatricial alopecias 171 nitrosoureas 138 non-cicatricial (non-scarring) alopecias 10f. 161f. hair loss and 158 6-mercaptopurine 138 mesenchymal-derived dermal papilla 86 methotrexate 137. 94f Norwood-Hamilton Stage III 92f Norwood-Hamilton Stage III and IV 103 Norwood-Hamilton Stage VII 94f Norwood-Hamilton Stages IV–VI 93f obesity 47. 58f ophiasis inversus (sisapho) 30. therapy and 113–14 peri-infundibular lymphocytic infiltrate 166 perifollicular interface dermatitis 165 pernicious anemia 22 pheomelanin 6 photochemotherapy (PUVA) 64–5. endogenous 147 quail-chick model 86 5α-reductase 85 . 109 and hair transplants 130 hypertrichosis of the face and 107f topical 133. 42 procarbazine 138 Propecia 102. 70 squaric acid dibutyl ester and 52 phototrichogram method 103 pigment incontinence 165 cis-platin 138 polymyalgia rheumatica 22 polytrichia 163 polytrichia folliculitis 166f post-menopausal frontal fibrosing alopecia 163 postpartum hair loss 138. 11f. 105–8. 5 papular atrichia 85 paroxetine 143 PAS stain 156 patchy alopecia areata 30. 24–5 melphalan 18. 47–8. 17f non-inflammatory cicatrizing alopecias 155 nortriptyline 143 Norwood-Hamilton classification 92. 169 pulse therapy. 33f oral contraceptives 143 oral cyclosporine 22 outer root sheath (ORS) 2. history of 9 patient expectations. 101. 16. 166 psycho-physical trauma 147 psychogenic pseudoeffluvium 151 psychopharmacologic medications 140–3 pull-tests 10. 33f. 163 pseudopelade (PP) 38. 170 use of betamethasone dipropionate and 48f monoamine oxide inhibitors 143 morphea 156 mouse teratogenicity test 53 myasthenia gravis 22 nail dystrophy. 37. 93.Index 179 McKusick Mendelian Inheritance in Man (MIM) 83 Major Histocompatibility Complex (MHC) 19 malignant diseases 149 maprotiline 143 mechlormethamine 137 medulla 2. 6 melanocytes 6. 163. 42 patient. 147 prednisolone. hairless 26 micro-grafting 132 Microsporum canis 42 mini-grafting 132 miniaturized hairs 88. 156. 4 melanin 3. 93 minoxidil (Rogaine) 43. intravenous methylprednisolone 47 pustules 156 PUVA therapy see photochemotherapy pyrogens. 156. 109 Norwood-Hamilton pattern 90. 104 propylthiouracil 139 prostate cancer.

hair loss and 144 thiotepa 137. alopecia and severe 136 Smyth chicken model 25 soriatane 144 spironolactone 101. 134 testosterone 85 thalidomide 169 thallium. 151. hirsutism. 33f Retin-A 108 rifampin 171 Rogaine see Minoxidil S phase-specific drugs 138 SAHA (seborrhea. 108 squamous cell carcinomas 167 squaric acid dibutyl ester (SADBE) 26. 155 cross-section of 8f positive pull test 96 temporal triangular alopecia (TTA) 42 terminal-vellus hair ratio 27. 142f acute and chronic 147–53 alopecia areata and 27. evaluation of 16 sex hormone binding globulin (SHBG) 105 short-contact therapy 49 shortened anagen (SA) 138 sisapho 30. cicatricial alopecias and 163 tyrosine 6 ulcerative colitis 22 valproic acid (VPA) 142 vasopressin 138 . alopecia. 69 topical ophthalmic beta-blockers 143 trachyonychia 34 traction alopecia 10t. minoxidil and 10 scalp lesions 158 scalp prostheses 68f scalp psoriasis 167 scalp reduction 169 scarring alopecia see cicatricial alopecia sebaceous epithelium. 28. 16. 38 triparanol 144 tufting. 140 tinea capitis 9. 4f syphilitic alopecia 27. 105. 167 topical immunotherapy 43. loss of 165 seborrheic dermatitis 100 serotonin reuptake inhibitors 143 sertraline 143 serum ferritin. intralesional and systemic 43 stress alopecia areata and emotional 24 telogen effluvium and psychological 150 striae. 10t. 16. 46–7 topical. systemic steroids and 47 substance P (SP) expression 24. 156 scalp irritation. 134. 98. 27. 51. 96f. 27.180 Index renal failure 149 respiridone 143 reticular alopecia areata 30. 95 differential diagnosis 38. 51–64. 10t. 52 steroid-metabolizing enzymes 85 steroids systemic 22. 25 support groups 69 suprabulbar area 1. 148 thyroid screening 9 thyroid stimulating hormone test (TSH) 98 thyrotoxicosis 139. 38 trazodone 143 tretinoin (all-trans-retinoic acid) 108 triamcinolone acetonide 45 triamcinolone hexacetonide 45 triangular temporal alopecia 38 trichodynia 151 trichogram/pluck test 12 trichologic anatomy 1–8 trichomalacia 28 trichotillomania 9. acne) syndrome 87 Salmonella typhimurium 51 sarcoidosis 156 scalp cellulitis of 171f physiology of 1–8 scalp biopsies 14–15f. 134 drug-induced 139–44 pathology of 28 types of 138–9 in women 86 telogen hairs 6. 28 systemic diseases 136 systemic erythromycin 171 targeted follicular gene therapy 114 telangiectasia 158 telogen effluvium 9. 28. 138 thyroid dysfunction 16 thyroid function assessment 140 thyroid influences 21. 38. 33f skin diseases.

89f. 99f vellus-like hairs 7f vertex pattern balding 87 vertex thinning 90 vinblastine 137. 108–9 Woods light examination 42 zolpidem 143 .Index 181 vellus hairs 6. 64 women AGA in 88. 98. 138 vitiligo 63f. 138 vincristine 137. 91f finasteride and 104 hair loss in 86 hair transplantation in 131–2 treatment of AGA in 101.

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