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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 .
co. A CIP record for this book is available from the British Library.uk Website: http://www. All rights reserved.uk This edition published in the Taylor & Francis e-Library. No part of this publication may be reproduced. a member of the Taylor & Francis group First published in the United Kingdom in 2002 by Martin Dunitz Ltd. The Livery House. London.co. KY 41042. or transmitted. without the prior permission of the publisher or in accordance with the provisions of the Copyright. USA Toll Free Tel. Kent . Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency. 2004. in any form or by any means. W1P 0LP. or otherwise.: +1 800 634 7064 E-mail: cserve@routledge_ny.: +1 877 226 2237 E-mail: tal_fran@istar.© 2002 Martin Dunitz Ltd.: +44 (0)1264 332424 E-mail: reception@itps. 7–9 Pratt Street. stored in a retrieval system. UK Tel.co. Distributed in the USA by Fulfilment Center Taylor & Francis 7625 Empire Drive Florence.uk Composition by Scribe Design. 90 Tottenham Court Road. mechanical.dunitz. Ontario M1R 4G2. Gillingham. 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.ca Distributed in the rest of the world by ITPS Limited Cheriton House North Way Andover. Canada Toll Free Tel. London NW1 0AE Tel: +44 (0) 20 7482 2202 Fax: +44 (0) 20 7267 0159 E-mail: info@dunitz. photocopying. electronic. we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention. recording.com Distributed in Canada by Taylor & Francis 74 Rolark Drive Scarborough.
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. diagnosis and practical management Androgenetic alopecia: Pathogenesis. clinical features.
Complex issues are presented. The illustrations are extensive. comprehensive text about hair that enriches the reader from bench to bedside. researchers. a collection of unique photographs and photomicrographs from his own collection. 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. His explicit recommendations about management are given. FRCPC Professor of Clinical Dermatology School of Medicine University of California. Jerry Shapiro has accomplished an amazing single-authored. he also includes the treatment preferences of other hair experts. He has written a unique text that will be invaluable for clinicians. The text is exceptionally readable and complements the book’s systematic and inviting organization. all extensively referenced. in clear terms for all readers. Vera H Price MD. which is set apart from others by the blending of rich clinical detail with the latest investigative research and theories of pathogenesis. such as immunological factors in alopecia areata.Foreword Jerry Shapiro is a dedicated clinician/scientist who has devoted himself to all aspects pertaining to the hair follicle. and students of the hair follicle. and where appropriate. This is an organized and rational guide for assessing and managing hair loss. San Francisco .
My Hair Fellows: Dr Chantal Bolduc. Charlotte Mossop and Robert Peden. Each fellow has questioned. Dr David McLean. Dr Liren Tang. who was the first individual to encourage me to take on the field of hair. 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. who took time out of their busy lives to commit a year to studying hair with me. It continues to be an honor for me and I thank them for this. First and foremost. My research associate. who has been my ‘’hair’’ mentor for over 15 years and has been an inspiration and role model. I am most indebted to my hair loss patients who have trusted me and given me the privilege of taking care of their hair. Drs Magda Martinka and David Shum. Next. my Hair Transplant nurse. Dr Harvey Lui. I would like to thank certain individuals who have played an important part in my career. Dr Vera Price. who continue to enlighten me regarding the histopathology of the hair follicle. Dr Shabnam Madani and Dr Olga Bernardo. I thank my editors.Acknowledgements There are certainly many individuals to thank in the making of this book. who was dedicated and helped shape the University of British Columbia Hair Clinic during its early years. who has guided me for the last 10 years with all her great surgical skills and great common sense approach to patients. who has. whose advice. my first Hair Clinic nurse. support and encouragement helped the University of British Columbia Hair Research and Treatment Centre flourish. they truly are very special people. who allowed me to learn from her in Cleveland and from whom I continue to learn. Lucianna Zanet. Dr William Stewart. 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. challenged and inspired me to learn so much more. and continues to guide and nurture me in the field of dermatology. Jerry Shapiro University of British Columbia Hair Research and Treatment Centre . Nina MacDonald. who continues to teach me the molecu- lar biology and basic science of hair. Dr Wilma Bergfeld. whose time and efforts were absolutely essential in making this book possible.
as therapy is dictated by the appropriate diagnosis. and infundibulum. Next. Basic trichologic anatomy and physiology In order to appreciate an organized diagnostic protocol for alopecia. it is important to review the basics of hair anatomy and physiology of the scalp. 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. Bulb: consisting of dermal papilla and matrix intermixed with melanocytes (Figure 1. Suprabulbar area from matrix to insertion of arrector pili muscle 3. A rational. suprabulbar area.2) 1. Infundibulum extending from sebaceous gland to the follicular orifice. 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. An accurate diagnosis can frequently be difficult. Figure 1.1 Assessment of the patient with alopecia Hair loss (alopecia) is a very common patient problem and often a significant source of patient distress.3) 2.1 The first task of the physician is to address the patients’ concerns fully. Ancillary laboratory evaluation may sometimes be necessary to help confirm a diagnosis. Isthmus extending from insertion of arrector pili muscle to sebaceous gland 4. organized approach is crucial. isthmus. The hair follicle is divided into 4 parts: (Figures 1. exploring the impact of alopecia on psychosocial well-being.1 Diagrammatic representation of hair anatomy: The hair follicle is divided into 4 parts: bulb. . Patients are most appreciative of a supportive diagnostic approach.1 and 1.
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. (2) matrix. consisting from inward to outward of medulla. There is a large amount of acid-mucopolysaccharides within the dermal papilla. (3) the hair shaft. inner root sheath (IRS). and (5) the outer root sheath. matrix (M). which contains highly vascularized connective tissue (Figure 1. and cuticle. cortex.) The lower portion of the hair follicle consists of five major portions (1) dermal papilla. (b) Two anagen follicles side by side at the level of fat. staining positively for Alcian blue and metachromatically for . Huxley’s layer on the inside and Henle’s layer on the outside. The base of the follicle is invaginated by the dermal papilla.2 Hair Loss: principles of diagnosis and management of alopecia Figure 1. Note the melanocytes within the matrix providing pigment to the hair. outer root sheath (ORS) and fibrous root sheath (FRS). (4) inner root sheath. (Courtesy of Dr Magdalena Martinka and Dr David Shum. consisting of inner root sheath cuticle.4).
Melanocytes fill the matrix and produce the pigment of the hair. The DP allows capillaries to gain entrance to the cells of the matrix. Melanin. Dopa-positive melanocytes are interspersed between the basal cells of the matrix lying on top of the dermal papilla (Figures 1. varying in quantity in accordance with the color of the hair.3 (a) Close-up of longitudinal section of dermal papilla (DP).2 and 1. which is an invagination of the dermis into the matrix (M).) toluidine blue. The ground substance consists of not only non-sulfated polysaccharides such as hyaluronic acid.3). is produced in these melanocytes and incorporated into the future cells of the hair through phagocytosis of the distal portion of the dendritic melanocyte. (b) Cross-section of the follicle at the level of the dermal papilla.Assessment of the patient with alopecia 3 Figure 1. Alkaline phosphatase activity is also increased in the anagen phase. 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. In persons with dark hair large amounts of melanin can be seen in the dermal hair papilla. The hair matrix has large vesicular nuclei and deeply basophilic cytoplasm.4 The different layers of the hair follicle . Cells of the hair matrix differentiate into six different types of cells. each of which Figure 1. but also sulfated mucopolysaccharides such as chondroitin sulfate. (Courtesy of Dr Magdalena Martinka.
The hair medulla appears amorphous because of its only partial keratinization.) keratinizes at a different level. In the central portion of the follicle the matrix (M) is forming cortex. which is soft keratin. This is subsequently invested by the cuticle of the inner root sheath (IRS). keratinizes first. The cuticle of the IRS consists of one layer of flattened overlapping cells that . It may not always be present.5 (a) Cross-section and (b) longtitudinal sections of the follicle at the suprabulbar level. hyaline membrance and fibrous root sheath (FRS) surround the whole structure. The two apposed cuticles covering the inside portion of the IRS and the outside of the hair keratinize next. and the medulla is last (Figure 1.4 and 1. The hair cortex cells during upward growth from the matrix cells keratinize gradually by losing their nuclei and become filled with keratin fibrils. The hair and the inner root sheath move in unison upward. which is surrounded by the cuticle. No keratohyaline granules (as in keratinizing epidermis) or trichohyaline granules (as in inner root sheath) are formed during keratinization. and all keratinize with trichohyalin granule formation. The outer layer of the inner root sheath (IRS).5).4 Hair Loss: principles of diagnosis and management of alopecia Figure 1. followed by Huxley’s layer. These granules stain eosinophilic. Huxley’s layer with trichohyaline granules. resulting in the firm attachment of the hair to its inner root sheath. The inner root sheath is composed of three layers (Figures 1. None of these layers contain melanin. Henle’s layer. Keratin of the cortex is hard keratin. The cells of the hair cuticle are tightly interlocked with the cells of the inner root sheath cuticle. establishing a firm coat around the soft central portions of the follicle. The hair cuticle located peripheral to the hair cortex consists of overlapping cells arranged like shingles and pointing upward with their peripheral portions. and the already keratinized Henle’s layer. in contrast to the basophilic keratohyalin granules of the epidermis. in contrast to the inner root sheath or epidermis.The outer root sheath (ORS).4). (courtesy of Dr David Shum. The hair cortex then follows.
only one cell layer thick. The glassy or vitreous layer. but serve as a hard molding scaffold up to the arrector pili muscle. below the isthmus. It is lined by surface epidermis Figure 1. The outer root sheath (ORS) extends from the matrix cells to the entrance of the sebaceous duct. The upper portion of the follicle above the entrance of the sebaceous duct is the infundibulum. . Trichohyalin granules are few in the IRS cuticle. They are located usually in the interfibrillary matrix. However.Assessment of the patient with alopecia 5 point downward in the direction of the hair bulb. There is no inner root sheath here. hyaline membrane and fibrous root sheath. already shows numerous trichohyalin granules as it emerges from the matrix.6). All of this is surrounded by outer root sheath.5).) undergoing keratinization with the formation of keratohyaline granules. which forms a homogeneous eosinophilic zone peripheral to the outer root sheath. The point of insertion of the arrector pili muscle is referred to as the bulge area. where it changes into surface epidermis. these two types of cells interlock tightly. Since the cells of the hair cuticle point upward. it is covered by IRS and does not undergo keratinization. at the level of the isthmus the IRS disintegrates. producing large homogeneous keratinized cells without the formation of keratohyaline granules. gradually increases in thickness. The ORS undergoes trichilemmal keratinization. which is composed of thick collagen bundles.2–7 Stem cells from the bulge area likely migrate to other portions of the hair follicle and differentiate into its differing layers. In its lower portion.8 Melanosomes of the hair cortex are larger than those of the epidermis. and is the likely location of the first primordial cells (stem cells) of the hair follicle. Henle’s layer. They lie singly or within groups not within lysosomes. This connective tissue sheath may contain considerable reproductive potential. Peripheral to this vitreous layer lies the fibrous root sheath. the isthmus. The ORS has plentiful vacuolated cytoplasm owing to its plentiful glycogen. is periodic acid Schiff-positive and diastase-resistant. The cells of the IRS do not contribute to the emerging hair. as was recently shown by Reynolds et al. The isthmus is the segment that extends from the arrector pili muscle to the sebaceous gland duct entrance. The ORS is thinnest at the level of the hair bulb.6 Cross-section of the follicle just beneath the isthmus showing the eosinophilic completely keratinized inner root sheath (IRS) enclosing the hair shaft (HS). It is thickest around the lower third of the hair follicle. Huxley’s layer is two cell layers thick and develops numerous trichohyalin granules (Figure 1. Just before the isthmus the IRS becomes fully keratinized (Figure 1. and is thickest in the middle portion of the hair follicle. Only anagen hairs have inner root sheaths. It differs from usual basement membrane zone by being thicker. (Courtesy of Dr David Shum.
Physiologic hair shedding of 100 hairs per day is usual on the average.8) and cannot be pulled out easily.10) and can be pulled out relatively easily. In certain individuals. on the human scalp there is an asynchronous mixture of hairs actively growing and resting. 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. Melanocytes show degenerative changes. where hair cycling is synchronous. Anagen may last up to 2–6 years. The scalp consists of almost 90% of hairs in anagen. melanocytes have higher amounts of eumelanosomes. (Figure 1. and only rarely in the intercellular space (Figure 1.000 hairs. especially of melanosomes. In the eumelanin containing follicle. Both are synthesized from tyrosine. During the hair cycle. and redheads less.000. with a maximal number in late summer. In other hair colors. with fewer hairs per square cm in Blacks and Orientals. Vellus hairs or miniaturized vellus-like hairs of androgenetic alopecia (AGA) have a shaft diameter of less than . either eumelanin or pheomelanin. The sizes of the hair shafts are important in determining a diagnosis. 1% in catagen and 10% in telogen.7 Melanosomes. during anagen are transferred from melanocytes to matrical cortex cells via dendritic ends. the middle and upper portions of the hair follicle are the permanent segment of the hair follicle. January or February. There is ethnic variation. Unlike animals. Hair fiber is produced during anagen at a rate of approximately 1 cm/month or 0.000. at 120. The normal scalp contains 100. The hair shafts only contain the detritus of melanin or no melanin at all. Two types of melanin are present in mammalian hair. telogen 3 months.8 and 1. The growing or anagen hairs are anchored deeply within the subcutaneous fat (Figure 1. Decreased telogen hairs occur in December.6 Hair Loss: principles of diagnosis and management of alopecia within the cells. which is converted to dopaquinone which can then undergo oxidative reactions to form either eumelanin or pheomelanin.35 mm/day.8). at 80. Blonds Figure 1.7). and catagen 3 weeks. tend to have more. with fluctuations over the year. Dark hair contains more eumelanin and blond hair more pheomelanin. while the lower portion is non-permanent. melanocytes at the basal layer of the hair matrix are usually reduced in number or are absent. Increased hair shedding is usually noted in autumn. The telogen hairs are located higher up in the dermis (Figures 1. there is periodicity in the number of telogen hairs. The average number of hairs for a normal scalp is 250 per square cm or 1100 per square inch. In fire-red hair there are high levels of pheomelanosomes. This ratio is usually uniformly distributed over the entire scalp. the black brown pigment eumelanin and the yellow red pheomelanin. In white hair.
06 mm in diameter and can grow up to 3 feet. This ratio is usually uniformly distributed over the entire scalp. and during telogen is closely associated with the stem cells of the bulge area. and catagen 3 weeks. The telogen hairs are located higher up in the dermis and can be pulled out relatively easily.8 During the hair cycle.Assessment of the patient with alopecia 7 Figure 1. while the lower portion is non-permanent. A true vellus hair does not have an attached arrector pili muscle. . Anagen may last up to 2–6 years.9 Vellus-like hairs are less than 0. Only miniaturized vellus-like hairs of androgenetic alopecia have arrector pili muscle. the middle and upper portions of the hair follicle are the permanent segments of the hair follicle. telogen 3 months. The dermal papilla (DP) is pulled upward with each cycle. 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. (a) The growing or anagen hairs are anchored deeply within the subcutaneous fat and cannot be pulled out easily. (b) The newly formed anagen hair pushes out the previous telogen hair. The scalp consists of almost 90% hairs in anagen. 1% in catagen and 10% in telogen. Figure 1.03 mm in diameter and rarely grow more than 1–2 mm. Terminal hairs are coarse over 0.
11). Patient approach Figure 1.10 Cross-section of telogen hair.) There are many etiologic factors that cause clinical hair loss.8 Hair Loss: principles of diagnosis and management of alopecia 0.03 mm). Because of the multiplicity of disorders that can result in hair loss. systemic illness. including endocrine abnormalities. diet. and ancillary laboratory work-up may be necessary. genetic predisposition.9 and 1. 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. drugs. hyaline membrane and fibrous root sheath. The lower portion of terminal telogen hairs is found higher up in the dermis. psychological abnormalities. and structural hair defects.11 Small vellus-like hairs (V) in androgenetic alopecia.06 mm. Figure 1.03 mm (Figures 1. unlike terminal anagen hairs. (Courtesy of Dr David Shum. infections.) . trauma. autoimmunity. A central starshaped area of trichilemmal keratin can be noted. Terminal hairs have a shaft diameter greater than 0. (Courtesy of Dr David Shum and Dr Magdalena Martinka. a thorough history and physical examination are important. (b) The small size of the hairs make the sebaceous glands look more hyperplastic. or alopecia. surrounded by outer root sheath. whose bulbs are found in the area of subcutaneous fat. (a) Hair shafts are small (<.
1).Assessment of the patient with alopecia 9 History The history is of critical importance in developing the initial differential diagnosis (Table 1. crash diets. The patient’s concerns and expectations should be acknowledged and fully explored. permanent waving) may result in hair breakage. 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. since there are completely different causes for each of these situations (Table 1. back brushing. operations/general anesthesia. bleaching. Some hair care practices (e. and body hairs. and a strict vegetarian diet can implicate iron deficiency anemia. eyebrows. A full list of current and past medication should be obtained (see Chapter 5). The duration and pattern (i. It is also important to question about the loss of axillary and pubic hair.2 Differential diagnosis . high fever. eyelashes.g.or hypothyroidism. The two most common forms of hair loss in children are tinea capitis and alopecia areata. the presence or absence of coincidental acne and abnormal menstrual cycles may indicate an androgen excess causing androgenetic alopecia. since any hair-bearing area may be affected by alopecia areata or trichotillomania. It is important to establish whether the hair falls out from the roots or breaks off along the shafts.2). Many patients with hair disorders become frustrated when their worries about hair loss are either ignored or dismissed as insignificant. Key questions implicating a telogen effluvium are: Any pregnancy. Occasionally an underlying depression or dysmorphophobia (pathologically focused Table 1. Certain conditions are more common in childhood compared to the adult.1 Hair loss history questionnaire Table 1. diffuse versus focal) of hair loss is very important to determine. since many medications can induce hair loss. The age of the patient is very important. In addition. Explanation and discussion may resolve the problem without specific intervention. Patients should be asked questions regarding hair shedding (alopecia areata or telogen effluvium) versus simple hair thinning without shedding (androgenetic alopecia). Thyroid screening questions may point to hyper.e.
12 Presence or absence of follicular ostia is crucial in the differential diagnosis. length and shape. Certain characteristic patterns of hair loss are more common for certain diseases. as this introduces an entirely different differential diagnosis. It is important that these psychiatric conditions be recognized and managed before any further treatment is initiated. examine the pattern of density and distribution of hair. Non-cicatricial alopecias demonstrate visible follicular units. If Clinical examination Clinical examination should be performed in three stages. study the quality of the hair shaft in terms of caliber. fragility. Random patterns are more common for alopecia areata. It is useful to take a Table 1. and firmly.3). fixation on body image) may be present. Note: (a) Follicular ostia in a non-scarring alopecia. scale.14). On the scalp. index and middle fingers from the base of the hairs near the scalp. Second. a useful ancillary test. It is important to determine if the hair loss is associated with scalp scarring (Table 1.10 Hair Loss: principles of diagnosis and management of alopecia Figure 1. contrast paper and place the hairs against it to examine the sizes of hairs (Figure 1. Finally. while cicatricial alopecias are devoid of follicular units (Figure 1. tugged away from the scalp (Figure 1.3 Causes of alopecia . should be conducted. first inspect for inflammation.12). Approximately 60 hairs are grasped between the thumb.13). (b) Absence of follicular ostia in a scarring alopecia. the ‘pull test’. Pull test: To determine the ongoing activity of hair loss. but not forcefully. such as alopecia areata. and erythema.
(b) The hairs are then tugged from proximal to distal end. (c) The number of hairs extracted is counted. This alopecia areata patient showed one month of spontaneous regrowth in a bald patch without any treatment.13 A contrast paper positioned at an involved area of the scalp will help determine the length. More than 6/60 hairs is a positive pull test and implies pathology. size and overall caliber of the hair shafts.Assessment of the patient with alopecia 11 Figure 1. It is normal to pull up to 6/60 (< 10%) hairs. This is a 57year-old female with diffuse alopecia areata displaying a very positive pull test. Figure 1. .14 Pull test: (a) Approximately sixty hairs are grasped from the proximal portion of the hairs shafts at the level of the scalp.
owing to hair damage caused by the plucking procedure. 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. Counts of dystrophic hairs are unreliable. (b) Anagen hairs are distinguished from telogen hairs and anagen to telogen ratios are calculated. this constitutes a positive pull test and implies active hair shedding. Hair shafts are then cut off 1 cm above the root sheaths and roots are arranged side by side on a slide. hairs are taken from specified sites9.10 is more accurate than the regular trichogram. The pull test helps to assess the severity and location of hair loss. popularized by Rushton. hairs are taken from specified sites. Because a scalp biopsy can give the physician the same information plus more regarding inflammation and the size of hairs. On the fifth day after the last shampoo. twisting and lifting the hair shafts rapidly in the direction of emergence from the scalp. If less than 6 hairs can be easily pulled away from the scalp. On the fifth day after the last shampoo. this is considered normal physiologic shedding. the trichogram has not become routine. With this technique. .12 Hair Loss: principles of diagnosis and management of alopecia more than 10% or 6 hairs are pulled away from the scalp. twisting and lifting the hair shafts rapidly in the direction of emergence from the scalp (Figure 1. as it takes into account not only anagen/telogen ratios but also hair density and size. Anagen hairs are distinguished from telogen hairs and anagen to telogen ratios are calculated.15). (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. The unit area trichogram. Trichogram/pluck test: The trichogram/ pluck test is another method of assessing hair loss.15 Trichogram/Pluck test: The trichogram/pluck test is another method of assessing hair loss. The patient must not shampoo for at least one day prior to the pull test.
It is normal to lose 100–150 hairs per day. Performing a hair count is tedious and timeconsuming for the patient. Patients are instructed to do this daily for 7 days.16). counter or pillow are collected.) . but only physiologic hair loss. (Courtesy of Dr David Shum.Assessment of the patient with alopecia 13 slide for counting. All hairs shed in the shower. Hair shafts are mounted in parallel Figure 1. (c) hair shaft abnormality: trichorrhexis nodosa secondary to trauma. or sink or on the brush. then there is currently no active shedding. 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. Shampoo days are labeled separately. But it is something that patients can do on their own to follow their progress. This meticulous technique can be quite laborious and requires very special skill.16 Light microscopic examination of hairs: (a) telogen hair with characteristic club.11 Light-microscopic examination Hairs extracted by slow pull can be examined under the light microscope (Figure 1. as it is expected that there will be more shedding on those days. If the patient is losing less than 100 hairs per day. (b) anagen hair with inner root sheath. count them and place them in plastic sandwich bags. Patients are asked to collect all the hairs shed in one day.
which has a hemostatic effect in a highly vascular site such as the scalp.0 mm is sufficient to obtain a full scalp thickness. insert the punch perpendicular to the scalp. In patients who have curly hair as above. Staying away from hair parts or the frontal portion of the scalp is recommended. the scalp biopsy should be taken from an active inflammatory area containing hair follicles or active hair destruction. (c) Direct vertical pressure is applied along with the rotation of the punch.14 Hair Loss: principles of diagnosis and management of alopecia Figure 1.000 is injected with a 30 gauge needle into the scalp.17 How to do a scalp biopsy: (a) In order to obtain sufficient histopathologic information. This allows the vasoconstrictive effect of epinephrine to take effect and hence maximize the hemostasis. Epinephrine causes vasoconstriction. a mandatory waiting period of at least 10 minutes is suggested following the anesthetic injection. The typical punch should be pushed right through to the hub. The area to be biopsied is marked with a red china marker. . Penetration of the punch to a depth of approximately 3.0 mm punch biopsy is placed parallel to follow the direction of the hair.5–4. (b) A 4. In addition. lidocaine 1 % with epinephrine in a concentration of 1:100. For local anesthesia. If possible the biopsy should be taken from a cosmetically less apparent area of the scalp. In noninflammatory conditions a biopsy in a representative area is sufficient.
cut. fractured or weathered. coiling and twisting and extraneous matter. A drop of cyanoacrylic glue placed on the slide will give greater contrast under the microscope compared to a dry mount. The hair shafts need to be examined to detect fractures. If fungal diseases are suspected. particularly with pigmented hairs. The suture needle is passed through the upper dermis. which helps to identify the suture on the hairy scalp.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. hairs should be placed on a glass slide with 20% potassium hydroxide added in order to demonstrate fungal spores and hyphae. preventing damage to the hair bulbs located in the deep dermis. For the most part. (f) The biopsy defect is closed with a bluecolored monofilament suture. (e) Aluminum chloride 20% solution on a Qtip can be used for hemostasis after the biopsy has been removed. between two glass slides taped together. Wound dressings are not necessary for scalp biopsies. The free ends of the hair should be checked to see whether they are tapered. Roots should be examined to determine the stage of the hair cycle and for the presence of dystrophy. Hair shaft abnormalities (which can increase hair fragility and cause hair loss) can be diagnosed with this method. irregularities. and the hair mount is not used routinely at the University of British Columbia (UBC) Hair Clinic unless indicated. . most hair shaft abnormalities are quite rare.
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. and dehydroepiandrosterone sulfate (DHEAS) is advised to rule out hyperandrogenemic states. Table 1. it is obligatory to perform a 4 mm scalp biopsy. if present. will be very prominent at all levels of the biopsy. Not only are the various scarring alopecias difficult to differentiate from each other clinically. 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. a thyroid-stimulating hormone level should be investigated. For cicatrizing alopecias. . This allows a greater number of follicles to be examined. Another 4 mm bi- opsy is bisected longitudinally. The deeper levels contain anagen terminal hairs. and alopecia areata. the number is reduced to 35. as well as terminal and vellus and vellus-like miniaturized hairs. at around 30. At the level of reticular dermis near the base of the infundibulum. an endocrinologic work-up consisting of free testosterone. If thyroid dysfunction is suspected. intra. Usually this involves a depth of 4 mm. Non-cicatricial alopecias In the non-cicatricial alopecias. The upper levels contain telogen and anagen hairs. Peri-. For those difficult cases.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. although they can sometimes be difficult to appreciate when miniaturized. The difference between the mid levels and the lower levels is the number of terminal telogen hairs. or irregular menses. at the deeper levels near the subcutaneous fat. The biopsy must be deep and include the entire follicular unit. The three most common forms of non-cicatricial alopecias are androgenetic alopecia. the numbers are even less. two biopsies are taken. These conditions are discussed at length in other chapters of the book. particularly in women with diffuse alopecia. The mid-levels consist of anagen and telogen hairs with terminal hairs only. In cases of confirmed scarring alopecia due to discoid lupus erythematosus. 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. including some subcutaneous fat (Figure 1.and interfollicular inflammation. Laboratory tests: Lab tests may be helpful in establishing a diagnosis.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. there is preservation of follicles on clinical and histologic examination.17). an antinuclear antibodies (ANA) examination should be performed. The technique of vertical sectioning was popularized by Headington13 and subsequently by Whiting14 and Sperling. The characteristic histologic features of the most common non-cicatrizing and cicatrizing alopecias are discussed in subsequent chapters. In women with androgenetic alopecia and virilizing signs such as hirsutism. At the UBC Hair Clinic all biopsies for non-cicatrizing alopecias are performed with transverse/horizontal sectioning rather than longitudinal/vertical sectioning. The first 4 mm punch biopsy is taken for transverse sectioning. telogen effluvium.4 compares the key clinical features that distinguish these three conditions from each other. acne. The difference between the upper levels and mid levels is usually the number of vellus or vellus-like hairs.
Evidence of cutaneous disease elsewhere on the skin. 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- . Scarring alopecias are considered true trichologic emergencies. acute fungal infections such as tinea capitis. A biopsy is necessary to establish an accurate diagnosis. telangiectasia. and follicular hyperkeratosis. as there is irreversible hair loss once hair follicles have become scarred. Lesions of DLE demonstrate marked erythema. The first task of the physician is to acknowledge the patient’s concerns and have an empathetic approach to the problem of hair loss. viral infections such as herpes zoster. and nails should be looked for carefully.4 Common non-scarring alopecias Cicatricial (scarring) alopecia Localized areas of cicatricial alopecia of the scalp may result from trauma. Discoid lupus erythematosus (DLE) is the most common primary cause of scarring alopecia. burns. oral or genital mucous membranes. atrophy.Assessment of the patient with alopecia 17 Table 1. The importance of prompt appropriate therapy is crucial. The most common causes for scarring alopecia are discussed at length in Chapter 7. and lichen planus is another common etiology. and bacterial infections.
role in hair cycle.T. et al.. and Lavker R. Cotsarelis G. 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]. ed.T. localization and functions.P. J Am Acad Dermatol.Orfanos. and Guthrie V. Nature. J Invest Dermatol Symp Proc. 5. Rushton H. Hair follicle stem cells: their location. Headington J. pp. 8(1):80–8. 2. 1999. Lawrence C. physical examination and any necessary investigations. 4(3):296–301. In: Disorders of Hair Growth Diagnosis and Treatment.G. Kaur P. Wilson C. markers. Berlin: Springer-Verlag.J. ed. Transverse microscopic anatomy of the human scalp. 101(1 Suppl):16S–26S. 1999. and eyelash follicles: the hair cycle and tumor formation.. 1990. J Invest Dermatol. and Mortimer C. J Invest Dermatol. 1994. Dermatol Surg. Transverse scalp sections: a proposed method for laboratory processing. Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype. 2000. discussion. 485–527. Lyle S. hair cycle. Wei Z.. 109(4):429–37. Miller S. 25(7):537–8. 7. Practical management of hair loss. and skin carcinogenesis. CserhalmiFriedman P. In Hair and Hair Diseases... 61(7):1329–37. 96(5): 77S–78S. 1996.C. Trans-gender induction of hair follicles. and Lui H. 402(6757): 33–4. Whiting D. Cotsarelis G. Madani S. and involvement in skin tumor formation. Reynolds A. D..... 1991. and Lavker R. 3. et al.T. 10. Clinical tools for assessing hair loss.M.. Liu Y. The scalp biopsy: making it more efficient. Shapiro J. James K. 642: 214–24. Cell. 15. Ann N Y Acad Sci. Orfanos C. 1983. Hair follicular stem cells: the bulge-activation hypothesis. Frishberg. 13. 9. 4. 8.C. et al.. Lavker R. 120(4): 449–56. New York: McGraw-Hill.. Inc.T. Androgenetic alopecia: clinical aspects and treatment. J Am Acad Dermatol. 28(5 Pt 1): 755–63. Br J Dermatol. and Shapiro J.. vibrissae. 1999.M. An organized diagnostic and management strategy will help both to identify the cause of alopecia and to direct therapy. Dhuailly P. 1993. pp. References 1. Cotsarelis G... 224–5. Sun T. Olsen E.Olsen. Sperling L. 1993. 14. Christofidou-Solomidou M. . 12.M. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells. Cotsarelis G. 46:1469–77. Can Fam Physician.B. Epithelial stem cells in the skin: definition. A basis for a morphometric approach to disorders of the hair follicle. 1990..M. Lavker R.18 Hair Loss: principles of diagnosis and management of alopecia ings obtained from meticulous history. C.H. The unit area trichogram in the assessment of androgen-dependent alopecia. 35(2 Pt 1):220–2. Wiseman M. Exp Dermatol. Sun T. Arch Dermatol. 6. 11. E.. 1991. Stem cells of pelage. 1984. et al. and Sun T.A. 59–69. 1999.M.
5 There is a significantly higher incidence of a positive family history in patients with early onset of AA. and geneticists.6–9 Also. Within the past decade. Genetic and immunologic factors have been important ar- . there have been reports of AA in identical twins.15 The HLA complex has been investigated in AA patients because of the association of other autoimmune diseases with increased frequencies of HLA antigens. Other proposed etiologies include infectious agents.13 Scerri 14 presented a case of 11-year-old identical twin boys. there have been significant advances in our understanding of alopecia areata. At these meetings. ranging from 10% up to 42 % of cases.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. 1994 and 1998.1% with the first patch after 30 years of age. but is likely to be an interaction between genetic and environmental factors.6. emotional stress.15. AA is generally felt to be mediated by T lymphocytes directed at hair follicles. Genetic factors Genetic factors play an important role in the etiology of AA. non-scarring hair loss condition affecting any hair-bearing surface. with ophiasis occurring simultaneously. forming the Major Histocompatibility Complex (MHC). pathologists. clinical features. including immunologists. There is a high frequency of a positive family history of AA in affected individuals. clinical features and state of the art treatment for AA. The exact cause is unknown.4. discussed alopecia areata in an open forum. biochemists. eas of attention.10–14 with up to 55% concordance rate in identical twins. Several closely linked genes. cytokines. intrinsically abnormal melanocytes or keratinocytes and neurological factors. 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. diagnosis and practical management Alopecia areata (AA) is an unpredictable. such as the human leukocyte antigens (HLA) are located on the short arm of chromosome 6. numerous subspecialties.2 Alopecia areata: Pathogenesis. The proceedings of these meetings have been published in the Journal of Investigative Dermatology. molecular biologists.16 Associations with Etiology The etiology of A A is unknown.1–3 This chapter will review the latest information on etiology. usually patchy. dermatologists.
17 B18. The earlier studies identified the association of AA with several class I antigens. and B27.20.21 Recently.28.7–9. b) Alopecia areata and Down’s syndrome. and B8.29 The HLA alleles DRB1*0401 (DR4) and DQB1* . -DP) have been studied in AA. -B. there has been an increased consist- ency in evidence revealing associations between AA and HLA class II antigens.22– 29 The HLA alleles DQB1*03 (DQ3) and HLADRB1*1104 (DR11) appear to be markers of general susceptibility for all forms of AA. The studies reveal a significant association of HLA-DR11 and DQ3 in patients with AA. B7. both HLA class I (HLA-A.20 Hair Loss: principles of diagnosis and management of alopecia Figure 2.1 (a. There is up to an 8.7–9.18 B13.19. such as HLA-A9. -C) and class II (HLA-DR. suggesting involvement of a gene located on chromosome 21 in determining susceptibility to AA. -DQ.8% increased frequency of AA in patients with Down’s Syndrome. There have also been studies showing no correlation with HLA Class I antigens.16 B12.
many studies indicate that AA is a polygenic disease with certain genes correlated with susceptibility and others with severity.31 Thirty per cent of patients with autoimmunepolyglandular syndrome have AA. showed no increase in microsomal antibodies compared to normal controls. we are a step closer to understanding the structure of the epitopes recognized by T cells. IL-1 inhibits growth of the hair fiber33 and induces morphological changes that resemble those seen in AA. 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. which are key to the follicular inflammatory immune response responsible for AA. Several reports reveal an 8.30.5 This evidence has been further confirmed by documentation of an increased prevalence of anti-thyroid antibodies35 and thyroid microsomal antibodies.2 for DRB1*0401.8% increased frequency of AA in patients with Down’s Syndrome. suggesting involvement of a gene located on chromosome 21 in determining susceptibility to AA (Figure 2.59 Tarlow et al. Polymorphism within the IL-1 cluster may modulate IL-1 responses. compared to only 2% in the general population. how and who develops AA. again implicating this chromosome. 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. IL-1 has a direct effect on hair growth. the exact causative genes have not been discovered.Alopecia areata 21 0301(DQ7) are markers for more severe longstanding alopecia totalis/universalis. other autoimmune diseases and a responsiveness to immunosuppressive therapy. there is an interaction between genetic and environmental factors that triggers the disease. By identifying these HLA genetic correlations. HLA associations have been discussed above. In hair follicle organ cultures. their cell membrane receptors and the anti-inflammatory IL1 receptor antagonist. Other investigators 26 also suggest that DRB3*52a may confer resistance to AA. At this point. with a fourfold greater incidence of vitiligo in AA . one must bear in mind that the presence of predisposing HLA is but one component in a cascade of factors leading to autoimmune disease.8% incidence of thyroid disease in patients with AA. Most probably.35 However. Alopecia areata is a complex trait expressed by a number of genes. 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. With the discovery of animal models for AA. The defective gene in this syndrome is mapped to chromosome 21.34 In conclusion. The main associations are with thyroid diseases and vitiligo. it is expected that our understanding of this complex trait will be further clarified. Puavilai et al. Immunological factors Indirect clues for autoimmunity There are indirect clues for autoimmunity that include the association of the disease with a HLA haplotype. and with the final data on the Human Genome Project just completed. There is up to an 8. There are reported associations between AA and classic autoimmune disorders.7–9 with a relative risk for AA of 30.36 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.0–11.4.1). Polygenic influences are clearly involved. However. Genetic research may ultimately explain why.
40 lupus erythematosus. macrophages and Langerhans cells.40 There are also reported associations of AA with pernicious anemia.38 Other studies have revealed an increased prevalence of gastric parietal cell antibodies and anti-smooth muscle antibodies in sera of patients with AA.67 or normal. as compared to controls using indirect immunofluorescence. In addition. The infiltrate is most prominent in active disease.47 ulcerative colitis. Tobin and coworkers reported detection of antibodies to pigmented hair follicles by Western blotting in the sera of 100% of the AA patients examined. The cellular infiltrate first becomes evident around the bulbar blood vessels. Successful treatment of AA with immunosuppressive agents such as oral cyclosporine 60.42–46 polymyalgia rheumatica.68 Friedmann40 suggested that the number of circulating T-cells is reduced in AA. may be correlated with the amount of hair loss.37. to a lesser extent.66 Cell-mediated immunity Studies of cell-mediated immunity in AA have given conflicting results. as can be seen by the expression of DR antigens and IL-2 receptors. inner root sheath.41 myasthenia gravis. and that the level of this reduction is related to disease severity. The T cell helper to suppressor ratio is 2:1– 4:1. resulting in an increase in the ratio of helper to suppressor cells.64 However. A slight increase in helper T-cells (CD4) and decrease in number of suppressor T-cells (CD8).56–59 Thirty per cent of patients with APS-1 have AA.40 diabetes mellitus.48–50 lichen planus. and hair shaft. The most common target structures were the outer root sheath.39. particularly in the dermal papilla/capillary network. 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.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. 51–55 and autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy.22 Hair Loss: principles of diagnosis and management of alopecia patients. 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. also known as autoimmune polyglandular syndrome Type 1(APS-1).4. because different patients develop different patterns of an- . 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. tibodies to different hair follicle structures. as compared to only 44% of normal controls.65 In another study by Tobin et al. The infiltrate subsides in inactive disease and disappears in the regrowth phase.46.61 and systemic steroids 62 also supports the idea of immune-mediated pathogenesis in AA.67 The dense peribulbar lymphocytic infiltrate affecting anagen follicles is one of the most consistent and reproducible immunologic abnormalities in AA. and consists mostly of T lymphocytes and. The antibody response to hair follicles in patients with AA has been found to be heterogeneous. Most of the T cells are activated.66 much higher levels of autoantibodies to multiple structures of anagen hair follicles in AA patients have been reported. followed by the matrix. Circulating total numbers of T-lymphocytes have been reported as reduced40.
Gilhar et al.69 In order for a medical condition to fit as an autoimmune disease.2 illustrates Figure 2. Furthermore. Furthermore. For AA. Figure 2. Increased frequency of hair-specific antibodies. Tsuboi has shown that the CD8+ cells had disappeared completely from almost all portions of the hair follicle. AA induction followed upon injection with CD8+ cells cultured with follicular homogenate.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. The disease being transferred passively by autoantibodies or T cells. more recently. high levels of autoantibodies to multiple structures of anagen hair follicles. They present the responsible epitope to the peribulbar lymphocytes. This study also suggests that AA is mediated by T-cells. with the disappearance of the T cell infiltrate. 1 . This may imply the greater importance of CD8+ in the expression of alopecia areata. particularly CD8+ cells. An autoimmune response to that antigen 3. An autoimmune response specifically associated with the disease 4. In this study. gamma interferon (γIFN) and intercellular adhesion molecules (ICAM). This leads to a cascade of immunologic events with increased interleukin-2 (IL-2). many of the above criteria are indeed met.2 The pathogenesis of alopecia areata. These changes include hair loss. T-cells that had not been cultured with follicular homogenate were not able to induce AA. Gilhar69 and Tsuboi70 have shown that grafting affected scalp AA skin from humans on to SCID mice results in regrowth of hair.Alopecia areata 23 follicles suggests that the process precedes rather than results from injury to hair follicles. The autoimmune response producing. Antigenpresenting cells. This series of events helps to induce hair loss. are increased in the bulb of the affected follicles. HLA-DR and intercellular adhesion molecule-1 (ICAM1) expression of follicular epithelium. while CD4+ cells still remained in the upper portions of the hair follicle. such as Langerhans cells. The necessity of the follicular homogenate to inducing AA suggests that T cells recognize a follicular auto-antigen. but not on injection of the cultured CD4+ cells. not following. 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. This is considered to be a Type 1 T helper cell response (Th ). the following criteria should be met: 1. Unique antigens in the affected organ 2. perifollicular T-cell infiltration. antibodies to pigmented hair follicles. the condition 5. an increase in the ratio of helper to suppressor cells. 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.
72 involves the upregulation of MHC antigens and/or downregulation of locally produced immunosuppressants (melanocyte. This immune privilege may collapse in alopecia areata. and in vitro produce changes in hair follicle morphology similar to those in AA. 2. these cytokine profiles change.79–81 a higher number of stressful events in the 6 months of preceding hair loss.73 As hair regrows with topical immunotherapy. 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 . This initial report showed a convincing positive association with CMV. and ICAM1.71 There is also a unique expression of follicular MHC class Ia/Ib.24 Hair Loss: principles of diagnosis and management of alopecia some of the immunologic cascade events that take place in alopecia areata.76–78 The whole concept of molecular mimicry of the hair follicle with a virus is intriguing.73 T helper cells produce cytokines divided into two subgroups depending on the pattern of cytokine production.80 higher prevalence of psychiatric disorders81 and psychosomatic factors in patients with AA have been reported. The hair follicle has a distinct immune system71 that differs from that of its surrounding skin.34. IL-1β and tumor necrosis factor-α (TNF-α) are potent inhibitors of hair follicle growth. Cytokines are immunomodulators mediating inflammation and regulating cell proliferation. but the evidence for a viral etiology of AA at this point in time is not conclusive. Type 2 helper (Th2) cells produce IL-4 and IL-5. adrenocorticotropin and transforming growth factor). The cellular components of the hair follicle immune system are composed of intrafollicular T lymphocytes and Langerhans cells.stimulating hormone. there are reports revealing that emotional stress does not play any role in the pathogenesis of AA.71 Human hair follicles may even serve as a Langerhans cell reservoir. Infection There has been a report regarding the possibility of cytomegalovirus (CMV) infection found within the patches of scalp AA. interleukins IL-1α.75 but this has not been confirmed. allowing the immune system to recognize the immune-privileged hair follicle antigens. Cytokines derived from epidermal keratinocytes. since the inner root sheath and hair matrix do not express MHC class I molecules. as other investigators have reported negative findings.82 In contrast. Acute psychotrauma before the onset of AA. A recent theory for AA proposed by Paus et al. and perifollicular mast cells and macrophages. leading to onset of AA.2) and IL-1β have been detected in affected areas of the scalp in patients with AA. Emotional stress Several studies suggest that stress may be a precipitating factor in some cases of AA.83 Cytokines It appears that cytokines have a significant pathogenic role in AA.74 Aberrant expression of cytokines of the Th1 type (see Figure 2. located exclusively in the distal outer root sheath. The epithelium of the proximal anagen hair follicle is immune-privileged.
91 Figure 2.3 Alopecia areata animal models: the C3H/HeJ mouse and the DEBR rat. This evidence. . to the entire scalp of two AA patients revealed an enhanced presence of SP in AA perifollicular nerves and induced vellus hair growth.88 The neuropeptide CGRP has a potent anti-inflammatory action.85 Abnormal melanosomes in clinically normal regions. may explain some of the associated pigmentary anomalies seen clinically in acute AA and the preferential effect of AA on pigmented hairs (Figure 2.92 the Dundee experimental bald rat (DEBR)93 (Figure 2. Also.90 In addition. AA can be induced in normal C3H/HeJ mice using full-thickness skin grafts from affected C3H/HeJ mice. melanogenesis and the development of AA. 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. application of capsaicin. Recently. including vacuolation. in outer root sheath of all hair follicles from non-balding lesions of AA.94 The Smyth chicken model also has vitiligo..12). together with degenerative changes.84–86 Abnormal melanogenesis and melanocytes are common findings. who revealed a decrease in calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the scalps of patients with AA.3) and the Smyth chicken.95 AA developed 8–10 weeks after grafting. together with the presence of antibodies to pigmented hairs of AA.Alopecia areata 25 the hair bulbs of anagen hair follicles. 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. Animal models with spontaneous AA include the C3H/HeJ mouse.85 correspond well with the hypothesis of a sub-clinical condition of the disease in clinically normal areas of AA.87 This theory has been supported by Hordinksy et al. which causes neurogenic inflammation and releases SP. investigations of AA have been facilitated by using animal models with either spontaneous or induced AA.89 and neuropeptide SP is capable of inducing hair growth in the mouse. since the peripheral nervous system can deliver neuropeptides that modulate a range of inflammatory and proliferative processes. degeneration of pre-cortical keratinocytes has been shown in follicles of active AA lesions. 88.88. and may suggest a link between vitiligo.
99 have shown efficacy of diphenylcyclopropenone in the C3H/HeJ mouse (Figure 2.32 identified the equivalent chromosome region 2p12–13 as being a location for AA susceptibility.102 These mice develop a normal pelage at about 14 days and then lose their hair over 1 week.100 Animal models with AA-like hair loss are significantly useful in investigations regarding pathogenesis. Figure 2. efficacy and side-effects of available or future treatments.101. Animal models are now used in research for new and improved treatments. disease behavior. AA induction can also be used to produce large numbers of mice for testing pharmaceutical agents. an IL-2 inhibitor.98 Shapiro et al. Lui et al.2/Jß2. Recently investigations have correlated this hairless gene in mice with congenital atrichia in humans.26 Hair Loss: principles of diagnosis and management of alopecia AA-affected mice and transferring them to normal-haired recipients. Non-alopecia areata animal models The hairless mouse has an autosomal recessive allelic mutation that maps to chromosome 14. A preliminary study using C3H/HeJ mice examined potential chromosome locations that may contain genes involved in AA. FreyshmidtPaul has shown the efficacy of squaric acid dibutyl ester in the C3H/HeJ AA mouse. susceptibility genes are not enough to develop the condition.97 The receptor arrangement of these cell clones may help identify targeted antigens in AA. differentiation and apoptosis within the hair follicle. However.5 T cell receptor (TCR) arrangement predominated. This may eventually permit selective immune therapy using antiTCR antibodies or clonal vaccination treatments.4). The human hairless gene has been cloned to chromosome 8p12. whereas individuals may be genetically predisposed toward AA. has some efficacy in the DEBR rat. and T cell clones expressing a Vß8.4 Diphencyprone was applied to half the C3H/ HeJ alopecia areata mouse. These human-animal correlations may have importance to understanding the mapping of the putative genes. Lymphocyte cells from C3H/HeJ AA mice were screened. Hox genes are involved in controlling the position.103 This gene does not cause AA. have shown that leflunomide.96 A separate investigation on human AA by Tarlow et al. this gene may have importance in maintaining hair follicle integrity by balancing cell proliferation. showing significant regrowth on the treated portion of the mouse. Transgenic Hoxc13 defi- . A region on mouse chromosome 6 may contain genes involved in inflammatory events associated with AA. 96 Three gene loci common to AA susceptibility were located.95 The ability to induce AA in a model suggests that. density and development of hair in vertebrate embryos.
The terminal to vellus ratio is decreased and even reversed by the increased numbers of miniaturized hairs.104 More knowledge of Hoxc13 expression in epidermal appendages will in turn provide further insight into the functioning of the normal ordered follicle.108 Also. miniaturization of hairs. AA should be differentiated from androgenetic alopecia.104 Hoxc13 may play a significant role in follicular proliferation and differentiation.Alopecia areata 27 cient mice were unable to synthesize hair keratins and have sparse brittle hair. (c) recovery. Eosinophils are also detectable in all stages of AA. In androgenetic alopecia. 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. the involved hair follicles arrest in the end-stage telogen phase. which in turn will allow us to understand the disordered follicle more clearly.5).115 Histopathologically. 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. The inflammatory cellular infiltrate is composed chiefly of activated Tlymphocytes together with macrophages and Langerhans cells. In these cases. Inflammatory changes in the mid and upper dermis are generally not prominent unless many vellus hairs are affected by the disease. resulting in marked increase in telogen and catagen hairs.105 There are distinct stages in the histopathology of AA: (a) acute alopecia. During the acute phase of hair loss.107.106 A peribulbar lymphocytic infiltrate (‘swarm of bees’) with no scarring is characteristic of the diagnosis of AA (Figure 2. can be observed in horizontal sections of scalp biopsies109. telogen effluvium. with numerous fibrous tracts along with pigment incontinence within these fibrous tracts. In patients with complete recovery. peribulbar infiltration along with an increase in Langerhans cell numbers. with patchy involvement.5e). Although clinical correlation is necessary. trichotillomania and syphilitic alopecia.111 a decrease in follicular density and follicular miniaturization may be present. AA is not a localized process. A decreased anagen to telogen ratio. Following complete matrix failure. the hair cycle is abnormal.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. both within the peribulbar infiltrate and the fibrous tracts. (b) persistent alopecia.110 (Figure 2. with hair follicles entering the telogen or late catagen stage prematurely in the involved areas.114 This shows that. In .112 Mast cells were also noted in a small series of AA slides. this feature is helpful in diagnosis of AA in some biopsy specimens without peribulbar lymphocytic infiltrate. Pathology In early active AA. In patients with long-standing persistent alopecia. the involved follicle enters the end-stage telogen. 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. normal hair follicles with little or no peribulbar lymphocytic infiltration and no decrease in hair density are noted.5). is appreciable (Figure 2. matrix cell and matrical melanocyte failure with a formation of dysplastic hair shafts is noted.
28 Hair Loss: principles of diagnosis and management of alopecia telogen effluvium. while the presence of peribulbar eosinophils and lymphocytes strongly suggests AA. 117 AA affects men and women equally. It accounts for about 2% of new dermatology outpatient attendances in the UK and the USA.4 Patients are frequently quite . Syphilitic alopecia is very difficult to distinguish from AA. was 0. Trichotillomania is characterized by empty anagen follicles. trichomalacia and pigment casts in the follicular infundibulum.1 to 0.7%. as reported by the First National Health and Nutrition Examination Survey conducted from 1971 through 1974.116 Clinical features AA occurs all over the world. Presence of plasma cells along with no peribulbar eosinophils and abundant lymphocytes in the isthmus are features of syphilitic alopecia. multiple catagen hairs.117 The lifetime risk has been estimated at 1. miniaturization of follicles is not present.2 per cent of the population. 117 The prevalence of alopecia areata in the United States.
7).5 Histopathology of alopecia areata. (f) Reduction of follicular numbers in chronic alopecia areata. Colombe et al. (c) Two follicles.) young. The patch may have a mild peachy or pinkish-red color (Figure 2.7).118. resulting in distal fractures. Frequently. Patients usually complain of abrupt hair loss and marked hair shedding. Alopecia areata can manifest with several different clinical features. (a) ‘Swarm of bees’ noted in the deep subcutaneous peribulbar area of the follicle. and family history of the disease and a lateonset form characterized by milder severity. with matrix destruction. (d) Follicular stellae (ST) remnants in alopecia areata.8 suggest a bimodal pattern for AA. . but within the same follicular bundle. not only on the same scalp.7). patients will present to the physician with one or several bags of hair. long duration. while the other does not.120 These hairs are described as ‘exclamation-mark’ hairs. with one showing marked lymphocytic infiltration. and low family incidence.7). The fractured hairs develop owing to damage involving both cortex and medulla. totally bald. with an early-onset form associated with greater severity. (e) The large number of telogen hairs in alopecia areata. David Shum and Martin Trotter.119 (Figure 2. smooth patch involving the scalp or any hair bearing area on the body (Figure 2. shorter duration. Sixty per cent of patients present with their first patch under the age of 20. The intact hairs are dystrophic anagen or telogen hairs. (b) Close-up the lymphocytic infiltrate.6). Almost all follicles within this field are telogen. Hair loss is seen both as intact and as fractured hairs (Figure 2. The characteristic lesion of AA is commonly a round or oval. because the distal segment is broader than the proximal end (Figure 2. (Courtesy of Drs Magda Martinka.Alopecia areata 29 Figure 2. This highlights the fact that AA is a very heterogeneous condition.
This early-onset form of AA is associated with greater severity. longer duration. If categorized by extent of involvement.9). the following forms may be seen: alopecia areata: partial loss of scalp hair. (a) Front view showing loss of hair on scalp. and eyelashes. The clinical presentation of alopecia areata is subcategorized according to pattern or extent of the hair loss. reticular AA—reticulated pattern of patchy hair loss. and alopecia universalis: 100% loss of hair on scalp and body (Figure 2. If categorized according to pattern.8). HLA studies suggest this early-onset group of severe AA patients are a genetically distinct group. (b) Side view. and greater probability of a positive family history of AA.6 Alopecia universalis for 1 year in a 3-yearold girl. (c) Back view. with mild to moderate pruritus. ophiasis inversus (sisapho)119—a rare bandlike pattern of hair loss in fronto-parieto scalp (the exact opposite of ophiasis).30 Hair Loss: principles of diagnosis and management of alopecia Figure 2. alopecia totalis: 100% loss of scalp hair. indicating very active disease. They are prognostically and therapeutically distinguishable. Although hair loss is usually asymptomatic in most cases. eyebrows.121 and diffuse AA—a diffuse decrease in hair density over the entire scalp (Figure 2. tenderness. . before the appearance of the patches. burning sensation or pain. ophiasis-bandlike AA—hair loss in temporo-occipital scalp. some patients describe paresthesias. too. The pull test may be positive at the margins of the patch. the following forms are seen: patchy AA—round or oval patches of hair loss (most common).
(e) Another peach-colored patch of AA.7 Alopecia areata circumscripta. . Patients frequently present with just a patch. This patient complained of burning on the patch before the hair fell out. (a) A single small circular patch. (c) The patch may be skin-colored with broken-off hairs. (b) A single large circular patch totally devoid of hair ‘bare as a baby’s bottom’.Alopecia areata 31 Figure 2. (d) The color of an AA patch may be peach. (f) The AA patch may be red.
) (h) Circumscript patches can be very constant and persistent. (i) Simultaneous circumscript alopecia in mother and son. 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. (Courtesy of Dr Harvey Lui. He has not had any other spots for over a decade.
8 Clinical forms of AA based on pattern: (a) Patchy alopecia areata in multifocal areas. . (e) Sisapho—the diametric opposite of ophiasis. (g) Advanced diffuse AA. mimicking androgenetic alopecia. (f) Early diffuse A A with no distinct patches.Alopecia areata 33 Figure 2. (b) Reticulated patches in AA. (c) Ophiasis (d) Simultaneous ophiasis in mother and daughter.
and only the white hairs remain (Figure 2. onychorrhexis (superficial splitting of the nail extending to the free edge). Pitting with an irregular pattern or in organized transverse or longitudinal rows.12). Changes may be seen in one. The reported incidence of onychodystrophy in AA ranges from 10 to 66%. Where there is hair. The dystrophy may precede. as well as body AA. Both regrowth in one site and extension of the alopecia on another site may be seen at the same time in the same patient. (c) Alopecia universalis in an adult affecting all hairs on the body. The initial regrowth in AA is frequently white.10 and 2. Nail dystrophy may be associated with AA. followed by repigmentation.11). including eyelashes and eyebrows. Most patients present with the limited patchy type that is easily camouflaged.9 Clinical forms of AA based on extent: (a) Alopecia areata with its characteristic circular patches. (b) Alopecia totalis affecting 100% of the scalp. many or all the nails. (Figure 2. affecting the limbs or the thorax area. coincide or follow resolution of the AA. Frequently AA preferentially affects pigmented hair. there can be alopecia areata! Beard AA is very common. thinning or thickening . trachyonychia (longitudinal striations resulting in sandpaper appearance). Any hair-bearing surface can be affected. Beau’s lines (grooves through the nail matching that of the lunula’s margin).122 depending on how diligently it is looked for.34 Hair Loss: principles of diagnosis and management of alopecia Figure 2.
. (d) AA affecting the dorsa of the arms.Alopecia areata 35 Figure 2. (c) AA affecting the chest. (b) AA affecting one eyebrow. (e) A A affecting just the lateral portion of the leg.10 Extracranial AA: (a) AA affecting just the eyelash.
Prognosis The only predictable thing about the progress of the AA is that it is unpredictable. partial or non-existent.36 Hair Loss: principles of diagnosis and management of alopecia Figure 2. The recovery from hair loss may be complete. Patients usually present with several episodes of hair loss and hair regrowth during their lifetime. but not affecting the great head of dreadlocks. onychomadesis (onycholysis with nail loss). (a) Random patches on the beard area. 7–10% . koilonychia (concave dorsal nail plate). punctate or transverse leukonychia and red spotted lunula may be associated with AA. However.11 Alopecia areata of the beard is very common. The majority of patients will regrow their hair entirely within one year without treatment. (b) The characteristic peach color on an A A of the beard. (pseudomycotic).13). (c) Extensive AA of the beard.123-128 (Figure 2.
(b) and (c) White regrowth on the side of the scalp. a young age of onset.Alopecia areata 37 Figure 2. The white hair regrowth proves the diagnosis had always been AA. can eventually end up with the severe chronic form of the condition. (a) Hair regrowth in a young child who had been diagnosed as a case of trichotillomania.82. extensive hair loss and ophiasis. vitiligo and alopecia areata. (d) White regrowth in an area of previous ophiasis.12 White hairs. nail dystrophy.129 . the presence of other immune diseases. a positive family history of AA. Poor prognostic indicators are atopy.
In trichotillomania and traction alopecia twisted and broken hairs are frequently evident. there is an inflammatory component. trichotillomania. Patients with AGA usually demonstrate the typical predictable pattern of balding. Differential diagnosis Clinically. sparing white hairs. (f) AA and vitiligo in the same person. androgenetic alopecia (AGA). In tinea capitis. However. pressure-induced alopecia. The pull test is usually negative in AGA. whereas in AA it is usually patchy. usually. (g) White moustache in a vitiliginous area in the patient illustrated in 12f. and shedding is not prominent. the differential diagnosis is usually between telogen effluvium. traction alopecia. hair loss is generalized over the whole scalp. non-inflammatory tinea .38 Hair Loss: principles of diagnosis and management of alopecia (e) Circumscript AA. In telogen effluvium. triangular temporal alopecia.14). Hairs that are shed are either telogen or dystrophic anagen in AA. tinea capitis and pseudopelade (Figure 2. and purely telogen in telogen effluvium.
13 Nail changes and alopecia areata. (d) and (e) Severe nail dystrophy in AA. and red-spotted lunula on the fingernails. (b) Red-spotted lunula on the toenails. (a) Trachyonychia.Alopecia areata 39 Figure 2. (c) Koilonychia present in AA. .
14 Differential diagnosis of AA. (e) & (f) AA . (d) Morphea mimicking AA. It is crucial to look for the presence of follicular ostia. (a) This is an early case of biopsy-proven diffuse AA which can be difficult to differentiate from telogen effluvium.40 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (b) Temporal triangular alopecia can mimic AA. which may be difficult to see on a shiny smooth scalp. (c) AA may be linear and mimic morphea.
. (j) & (k) Pseudopelade mimicking AA. (h) Simulaneous trichotillomania in a mother and daughter. which can easily mimic AA. Note the loss of follicular ostia. (l) Post surgical pressureinduced alopecia can appear like AA. (g) Trichotillomania.Alopecia areata 41 mimicking AGA in a female patient. but usually has a significant scarred component to it. (i) Broken hairs in trichotillomania.
A biopsy may occasionally be necessary to distinguish TTA from AA. Temporal triangular alopecia (TTA) may mimic AA. There is great difficulty in evaluating the literature on treatment modalities for alopecia areata. Half-head studies are very powerful. Occasionally in AA. He advocated the use of ointments prepared with oil of mace. Usually the history of coma or surgery is present. Woods light examination may help if the patient is in or has been in an area where the fluorescent tineas predominate. this does not mean that there are no effective treatments. Look for the characteristic scaling in tinea capitis. mustard and black pepper. A 4 mm punch biopsy may be necessary to make a definitive diagnosis in some cases. Histologically. large patient populations are necessary. the treatment of AA is very difficult. Clinically. A KOH preparation and fungal culture may be necessary to distinguish noninflammatory tinea capitis from AA. the most common cause of tinea capitis is Microsporum canis. especially for patchy AA.11%. and results can be skewed by this more difficult and severely affected population. This lack of stratification of patient population can have a profound influence on evaluating therapeutic efficacy. Unfortunately. Pressure-induced alopecia131–134 (PIA) may also mimic AA. In British Columbia. and patchy AA may be difficult to differentiate from pseudopelade. While the FDA has never approved any drug for AA. There is controversy as to whether the lesions are present at birth or acquired later in life. Most published studies for AA have been small. Bateman.135 Diffuse AA can be especially difficult to diagnose clinically from other non-cicatrizing alopecias.136 in the 1800s. oval or lancet-shaped patch of non-scarring alopecia overlying the fronto-temporal suture. In order to prove efficacy with sufficient power and statistical significance. Evaluating efficacy is most difficult. and there are no consistently reliable treatments. Most studies have grouped patients with alopecia totalis (AT) and alopecia universalis (AU) with those with just patchy alopecia areata (AA). the scalp may be so shiny and smooth that follicular ostia may be difficult to see. there is usually some scarring with PIA. some current treatment regimens have similar objectives. There is no question that AT/AU is a distinct prognostic and therapeutic group. some of the fundamental principles in the treatment of AA remain unchanged. There is a paucity of studies that distinguish AT/AU from patchy AA.42 Hair Loss: principles of diagnosis and management of alopecia capitis may be most difficult to distinguish from AA. Lesions present as a triangular. The lifetime incidence of TTA is 0. Despite the advance of medicine over the last 200 years. See above for histologic differentiation of noncicatrizing alopecias. which does fluoresce. as there is so much variability as to baseline patient populations and the terms ‘successful regrowth’ or ‘responders’. as it is so unpredictable and frequently improves on its own. Treatment Modern therapy for AA is best appreciated within a historical framework. and an immunologic patient response to modify the perifollicular immunologic milieu. 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. turpentine. much of this published work has involved patient . but again. peribulbar lymphocytic infiltrates are not present. They cause blisters and erythema.130 This is ten times less frequent than AA. Although this may seem crude.
it is important to ascertain clearly what the authors have defined as a ‘responder’. Corticosteroids The main mechanism of action is immunosuppression.141 halcinonide142 and dexamethasone in a penetration-enhancing vehicle have been reported to have some success. and the motivation level of the patient. with 5% minoxidil in 27% and with 5% minoxidil and 0. Treatment guidelines for AA have been published by the American Academy of Dermatology. In addition. .139 Topical corticosteroids Fluocinolone. and must be separated out in order to determine the efficacy of any trichogenic agent. slowgrowth cellular processes. This suggests a synergistic benefit of using both modalities. minoxidil and photo-chemotherapy are available for the treatment of AA. At the present time.Alopecia areata 43 populations with a preponderance of AT/AU. She reports that quality of response in severe recalcitrant AA was fair to good after 16 weeks of treatment with placebo in 13%. intralesional and systemic steroids. Fiedler145 believes that a combination of 0. and measuring the extent of scalp involvement.05% betamethasone dipropionate cream and minoxidil may be more beneficial than either alone. The Guidelines help us to evaluate what is ‘successful regrowth’.05% betamethasone dipropionate in 56%. comparison of data. but do not prevent further spread of the condition. The new Alopecia Areata Investigational Assessment Guidelines are helpful in establishing criteria for selecting and assessing patients for clinical studies of AA. However. This receptor is found to influence long-term.138 All treatment plans for patients depend on three major factors: the extent of scalp involvement. Price and Khoury144 have not had success with topical steroids. only controlling the problem. All local treatments may help the treated areas.139 They showed that patients with AA have abnormalities in glucocorticoid receptors (GCR) for type 2 binding. facilitating collaboration. with 0. and thus hormone binding to GCR. It is of paramount importance that dermatologists should be knowledgeable and conscious of this important segregation when evaluating modalities in the treatment of AA. anthralin. and not curing the condition.140. Most dermatologists consider successful regrowth to be cosmetically acceptable regrowth. The terms ‘responder’ and ‘successful regrowth’ are not used in the same way from one study to another. the age of the patient. Otherwise. When comparing studies. This suggests suppressed cellular transcription.05% betamethasone dipropionate in 22%. topical immunotherapy. At present.143 Only one of these studies was performed in a double-blind controlled manner. This suggests that patients with AA have abnormalities in type 2 GCR activation because of abnormal calcium-calmodulin metabolism. topical. any mode of treatment may require long periods of usage. all results are skewed and will probably show ineffectiveness. Scalp biopsies from 15 untreated AA patients showed a twofold increase in unoccupied GCR. all treatments are palliative. These abnormalities may explain why patients with AA show a varied response in hair area growth when treated with glucocorticoids. meaning being able to abandon one’s wig or cap. some biochemical abnormalities relating to steroid chemistry have been discovered in AA patients by Sawaya and Hordinsky.137 These guidelines highlight the fact that AT and AU are considered a separate entity from AA. It was found that low concentrations of calmodulin stimulate a cytosol kinase. owing to the chronic nature of AA.
15 Intralesional corticosteroid injections for AA. (c) Same patch after 2 months of injections.44 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (b) Patch of alopecia before injection. (a) Injecting triamcinolone acetonide 5 mg/ ml with a 3 ml syringe and a 30 gauge needle. . physician positioned at one end of the table and approaching with needle from the top of the patient. (d) Best position for injecting eyebrows: patient lying flat.
Price.5 ml per eyebrow. At the University of British Columbia Hair Clinic.5 mg/ml for a total of 0.5–10.146 For circumscribed AA. Bergfeld prefers 2. Whiting150 prefers 5–10 mg/ml. Triamcinolone acetonide is administered with a 0. approximately 1 cm apart.3 mg/ ml. Intralesional corticosteroids Intralesional corticosteroid injection is first-line therapy for adult patients with less than 50% of scalp involvement. which is at least 4–8 times what is recommended.0 mg/ml diluted either in xylocaine or sterile saline. (g) Atrophy secondary to injection with triamcinolone acetonide 40 mg/ml. Initial regrowth is often seen in 4–8 weeks.0 mg/ml151 and Thiers152 prefers 3.129 Whiting.Alopecia areata 45 (e) Injection of eyebrows with triamcinolone 2.150 Bergfeld.5–5. (f) Regrowth in eyebrow area after 4 weeks. we inject a concentration of 5 mg/ml with a maximum total of 3 ml of triamcinolone acetonide.147 They are not indicated when more than 50% of the scalp is involved.5 inch long 30-gauge needle as multiple intradermal injections of 0. Concentrations of triamcinolone ac- etonide vary from 2.5 mg/ml is used for the beard area and the eyebrows. Porter and Burton148 demonstrated response rates of 64% using triamcinolone acetonide and 97% using the less soluble and more atrophogenic triamcinolone hexacetonide. Treatments .1 ml per site. Shapiro149 prefers 5 mg/ml. 146 Shapiro. Injections are performed every 4 weeks. for scalp A A.151 and Thiers152 prefer triamcinolone acetonide.149 Mitchell and Krull. Price146 prefers 10mg/ml. A weaker concentration of 2. with the next set in between areas of regrowth. intradermal corticosteroids remain the therapeutic standard.
16). and they do not alter the long-term prognosis (Figure 2. Abdulkareen et al. They are not routinely used. After 6 months of treatment. Ferrando et al. The 27 gauge needles are large. Systemic steroids Systemic corticosteroids are frequently effective in the treatment of AA.46 Hair Loss: principles of diagnosis and management of alopecia Figure 2. in that it permits the simultaneous injec- tion in 5–7 different points at a fixed distance. because of side-effects.5% prilocaine in a cream) in a thick layer with occlusion 1 hour prior to injection can be used. because these patients may lack adequate corticosteroid receptors in the scalp.153 recently published a paper on the use of a multi-injection plate for intralesional corticosteroid injection of patchy AA. are repeated every 4 to 6 weeks. The main sideeffect is minimal transient atrophy. but their use is controversial. Children under 10 years of age are not usually treated with intralesional steroids owing to the local pain at the injection sites. One disadvantage is the needle calibre. and therefore likely to produce pain if the procedure is not performed gently.16 The chronic use of systemic steroids for AA can have significant side-effects.154 recently showed success . This can be prevented by avoiding injections that are too great in volume per injected site. if there is no response. intralesional corticosteroids. and atrophy can occur if the application is not followed by a local massage that spreads the steroid solution uniformly through the treated area. too frequent. this cream can be difficult to use on the hairy scalp. and an extensive alopecic area can be treated in a shorter period of time. Topical anesthesia cream (2. or too superficial (intraepidermal). With this method there is only one painful stimulus instead of five to seven.5% lidocaine and 2. This disposable device has some advantages. leading to uniformity in treatment applications. However. (a) & (b) Striae in a patient with alopecia universalis who had been on systemic steroids for 1 year.139 (Figure 2. discontinue.15).
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 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-
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
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 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 .
clothes and linens (Figure 2. Dinitrochlorobenzene Rosenberg and Drake178 first reported regrowth of hair in two patients following application of DNCB. (d) 4 months of treatment: right (untreated) side showing regrowth. anthralin into the eyes. squaric acid dibutyl ester (SADBE) and diphenylcyclopropenone (DPCP). The immunomodulating effect of the topical sensitizers is supported by . a decrease in the peri-bulbar CD4+/CD8+ lymphocyte ratio.Alopecia areata 51 Figure 2.100 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.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. The overall efficacy of DNCB treatment for AA has been investigated and has varied from 25% to 89%. The mechanism of action of topical immunotherapy is unclear. and thus allow hair to regrow.99. (b) Baseline. Kratka et al. Systemic steroids may be the most effective modality. DNCB is rapidly absorbed after topical application. (f) Marked redness can occur from anthralin.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. Weisburger et al.181 Concerns have been raised about the safety of DNCB. but their safety profile is unacceptable to most dermatologists. (a) 27-year-old female with AA for 8 months. because it may be possible in the future to mimic the effect on the dermatitis by providing specific cytokines or specific inhibitors of cytokines.19). The issue of DNCB safety is controversial. Immunogens may interfere with the initial or continued production of proinflammatory cytokines by the follicular keratinocytes. Therefore. There was clearly unilateral preference for the treated side.. right side. Baseline. and serum half life is 4 hours. (e) Unilateral preferential regrowth of hair with anthralin on the C3H/ HeJ mouse on the treated half. and to be aware of staining of the treated skin. to protect treated skin against sun exposure.19 Anthralin for alopecia areata. untreated side. but less than the treated side. treated with anthralin 1 % cream for 1 hour daily. Excretion is primarily renal.180.182 Stobel and Rohrborn183 and Summer and Goggelman184 found DNCB to be mutagenic in Salmonella typhimurium in the bacterial plate incorporation assay (Ames assay). 178 Happle has proposed the concept of antigenic competition. extreme caution must be used with DNCB.177 and a shift in the position of the T-lymphocytes away from perifollicular areas to the interfollicular area and dermis. (c) 4 months of treatment: left (treated) side showing regrowth. with 53% recoverable in the urine. Careful dissection of the mechanism by which contact dermatitis is able to suppress alopecia areata is important. left side. Three contact sensitizers have been used extensively in alopecia areata—dinitrochlorobenzene (DNCB).
Micali et al. Of 107 who showed a unilateral response.195 also treated children. lifetime subcutaneous injections of squaric acid into ICR/Ha Swiss mice resulted in a low incidence of tumors at the injection site.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. Certain chloronitrobenzenes that are known mutagens are possible contaminants in preparations of DNCB. a paradoxical regrowth of hair on the untreated side of the scalp was seen. Barth et al. is not found in the natural environment and does not react with other chemicals. defined as a required continuous increase in DPCP concentration until a concentration of 2. Giannetti and Orecchia191 reported a good response in 5/26 cases. and thus inhibits induction and elicitation of allergic contact dermatitis. Tosti et al. They concluded that the two associated therapies showed an impaired efficacy because of the inhibition of the SADBE action by PUVA. Two-thirds of the initial responders no longer responded to the SADBE. .0% was reached without producing an adequate dermatitis.201 Efficacy in alopecia has varied from study to study. it loses its stability in the presence of water.192 showed a 49% success rate in 73 cases with over 50% scalp involvement. adenopathy.129 Squaric Acid Dibutyl Ester Happle achieved good results in 70% of patients treated with topical squaric acid dibutyl ester (SADBE). auto-eczematization. In 8/ 107. In 3/107. Orecchia194 has used SADBE in children under 13 and showed a 32% (9/28) chance of cosmetically acceptable regrowth. PUVA impairs Langerhans cells. resulting in loss of all regrown hair. This phenomenon is known as castling. but also as an immunomodulator in the treatment of melanoma200 and warts. Caserio190 showed a success rate of 28% (4/14 cases).202 showed a response rate (on 139 patients) of 50. equaling that of control animals. with excellent or satisfactory results.199 It is an ideal immunogen in that it is a strong topical sensitizer. with an initial success rate of 30% (10/33).196 showed only minimal signs of terminal hair regrowth in 3/17 patients and do not recommend the use of SADBE in AA. with subsequent relapses over the long term. urticaria and tolerance. This would clearly affect any benefits of a contact allergen. Orecchia et al.186 Side-effects of DNCB include a marked blistering reaction. Van der Steen et al.189 showed excellent responses in 11/26 (52%) of cases. Case et al. PUVA also results in a systemic immuno-suppression through direct or indirect (via interleukin-1) stimulation of prostaglandins (PGE2). a tolerance phenomenon was seen. Chua et al. with the effect of an efferent lymphatic blockade. However. Diphenylcyclopropenone Diphenylcyclopropenone (DPCP) has been used not only in the treatment of alopecia areata.198 Furthermore. No mutagenic contaminants were detected on gas chromatography-mass spectrometry. is used only rarely in industry. 30 relapsed and were resistant to further therapy. SADBE has been shown to be Amesassaynegative. 187 Flowers et al.197 used SADBE in combination with PUVA on three patients and did not find increased efficacy with combined treatment.4%. 188 found SADBE to be effective in 4/8 cases. The purity of DNCB samples is also an issue.193 reported a 68% (13/19) success rate in a half-head study. Tolerance can sometimes be reversed with cimetidine 300 mg orally three times a day for 3–4 weeks.
Hatzis et al. Ashworth et al. Factors affecting response were clearly extent of condition and age of onset.9%. Of 78 patients.217 Commercial DPCP may contain a precursor. and teratogenicity and organ toxicity could not be detected in the hen’s egg test or in the mouse teratogenicity test. Those patients with a younger age of onset are less likely to respond. the cumulative patient response at 32 months was 77. DPCP is not mutagenic in the Ames test. MacDonald-Hull et al. Pericin208 showed that in 68 patients.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.Alopecia areata 53 MacDonald-Hull and Norris203 reported 29% (8/28) of patients had a cosmetically acceptable result. Duration of condition. These data suggest that diphencyprone is not absorbed following application to the skin. In 1991. 70. Six months after treatment was discontinued three of the four children with complete regrowth maintained their hair. with complete regrowth in 30.216 Analysis on serum and urine samples following application of at least 0. It appears those with AT/ AU and an early age of onset are prognostically a separate group.1% of subjects with 50–74% hair loss. Berth-Jones and Hutchinson213 showed only an 18% response rate over 6 months.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.4% of subjects with 100% hair loss. 60. Wiseman et al. and 100% of subjects with 25–49% hair loss. The authors felt that eliciting an allergic reaction was an integral part of successful treatment resulting in hair growth. that is positive in the Ames test. the presence of atopy and nail changes were not correlated to response. DPCP is degradable upon exposure to light.6% showed a response.205 reported further results with DPCP on a larger series of patients.211. A lag period of 3 months was present between initiation of therapy and detection of the first clinical response. dibromoketone. with 33% showing complete regrowth. with no significant difference in response with inosine pranobex (inosiplex). although 53% developed patchy alopecia and 10% lost all hair that had re-grown. A cosmetically acceptable endpoint was obtained in 17.219 It is therefore recommended that all DPCP samples be purified as described by van der Steen et al. 25 (32%) showed complete regrowth of hair. the appearance of the scalp 6 months later was cosmetically acceptable.218.207 showed that 38% of 48 patients responded to DPCP with cosmetically acceptable regrowth. MacDonald Hull et al. Using the survival analysis model.9%. The only prognostic indicator correlated with response was extent of the condition. Regarding children. showed efficacy in only 1/26. This fits well with Colombe et al’s8 data that this group is a distinct sub-population of AA. MacDonald-Hull and Cunliffe204 studied post-therapy relapse rates within 6 months after treatment.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.3% of subjects with 75–99% hair loss. Monk209 showed cosmetically acceptable results in 33% (6/18).210 showed satisfactory regrowth in 24% (11/45). Orecchia and Rabiossi212 also had a success rate of 1/26. 88.215 treated 12 children aged 5–15 years. Gordon et al.214 showed that topical 5% minoxidil solution combined with DPCP showed no benefit over DPCP alone. In 68%. They found that 7 of 19 (37%) showed no hair loss after treatment had been stopped for 6 months. and must be stored . Shapiro et al.
(a) Standard diphencyprone (DPCP) tray concentrations varying from 0. (c) DPCP is stored away from the clinic in the fridge in a plastic container.0%. (d) The cotton is wound around the stick to make a reinforced swab approximately three times the thickness of an average cotton-tipped applicator.0001–2. (b) Intermediate concentrations may be necessary.54 Hair Loss: principles of diagnosis and management of alopecia Figure 2.20 Topical immunotherapy for alopecia areata. (e) The physician or nurse must wear gloves when .
(f) After the application. Only unilateral application is performed until hair regrowth is seen on one side. If the swab needs to be remoistened. (i) and (j) One coat is painted is the anteroposterior direction. . k. an eyedropper is used to saturate the swab. gloves must be removed carefully from the inside out.Alopecia areata 55 handling the bottles. (g) Cotton swab is dipped directly into the bottle. Another coat is painted in the lateral direction. (h) An area that has been sensitized one week before with a 2% solution.
A local ethics committee should be asked for consent. 4. an eye-dropper is used to saturate the swab and prevent contamination. the lack of sufficient toxicologic data. and one that is necessary for a good result. A gown covering the arms should be worn and laundered after each treatment session.0% and 2%. such as intralesional corticosteroids. If the swab needs to be remoistened. Post-treatment guidelines for the patient include: 1.25% strengths for sensitive patients. Intermediate concentrations may be necessary. 0.56 Hair Loss: principles of diagnosis and management of alopecia in amber bottles.05% and 0. Spills should be wiped up immediately using a dry towel.01%. or topical anthralin. For adults with more than 50% scalp hair loss.222 The DPCP solution is applied to the scalp using a thick cotton swab that has been dipped into the bottle. The . 0. Patients must be warned that the induction of an allergic contact dermatitis is a desired side-effect. to eradicate all traces of the DPCP.221 suggest. A commitment is made to return for weekly treatments for at least 24 weeks. DPCP is dissolved in acetone and stored away from the staff in the fridge in a special container. The scalp must be protected from all sources of light. topical minoxidil 5% solution in combination with topical corticosteroids. DPCP is compounded in an acetone base and stored in opaque bottles to protect the solution from photodegradation.20). Gloves must be worn and caution used to prevent the DPCP from coming in contact with the skin of the staff member. 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. The standard DPCP tray for AA includes the following concentrations: 0. At the University of British Columbia.0% is best bridged with a 0. The patient is encouraged to meet with and observe other patients undergoing treatment. Safety precautions must be implemented when handling DPCP. it has occasionally been necessary to use 0. These swabs are constructed with long wooden applicator sticks and cotton balls. A low-potency topical corticosteroid is given to the patient for mild inflammatory reactions post-treatment. risks and benefits are carefully reviewed with all patients and an informed consent is signed. DPCP is used at the University of British Columbia Hair Clinic as follows: Prior to commencing treatment. As Peret and Happle220. Although not routinely used. The physician must be notified of severe reactions. 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. All bottles are dated on first use. patients should be thoroughly informed about the experimental character of the treatment. followed by a moist towel. because of the risk of sensitization of staff administering the treatment.1%. 1. and the possible failure to respond. 3. topical immunotherapy with DPCP is our treatment of choice at the University of British Columbia Hair Clinic. because we have found that the shelf life after opening is approximately 6 months. We periodically check the DPCP for purity with high-pressure liquid chromatography.001%.0001%.1% to 1. Scalp/hair should not be washed in the 48 hours following treatment. 2.5% solution of DPCP (Figure 2. the use of a barrier cream and double gloving is helpful. The wearing of a hairpiece or scarf is sufficient. the possible side-effects. If the person administering the DPCP develops eczema.5%. the chance for regrowth. 0. The transition from 0. 0. We use DPCP on patients with less than 50% hair loss only if all other modalities have failed.
(d) 30 weeks of treatment of the left side and 6 weeks on the contralateral side. . (b) 12 weeks of unilateral DPCP treatment.Alopecia areata 57 Figure 2. (c) 24 weeks of unilateral treatment. (f) 5 years of intermittent treatment. (a) baseline. (e) 1 year of treatment.21 40-year-old female with an 18-year history of alopecia involving 99% of the scalp.
20). Two coats are applied. This can be confusing when attempting to titrate the patient to the correct dosage. an initial sensitizing dose of 2% DPCP is administered to a 4×4 cm circular area on the occipital region of the scalp. (a) baseline. a 0. we do not apply any solution until the following week. We avoid application on to the nape of the neck. the first coat in an anteroposterior direction and the second coat in a lateral direction. The nape of the neck is a very sensitive area that will react when other parts of the scalp do not. Cotton-tipped applicators do not retain enough moisture to paint the scalp adequately. Once the patient commits to DPCP treatment. as well as the area where the tape for the hairpiece is applied. (c) 24 weeks of DPCP treatment. If there is a marked reaction. If this area becomes irritated. because severe reactions can discourage the patient and preciptate discontinuation of treatment. showing some white regrowth. Patients return for weekly visits until hair growth is established.58 Hair Loss: principles of diagnosis and management of alopecia Figure 2.0001% solution is applied to half the scalp. it is difficult for the patient to continue wearing a hairpiece. After 1 week. (b) 12 weeks of DPCP treatment. Titration must be conducted carefully. The patient must protect the scalp from light with a cap.22 Ophiasis in a 43-year-old female of 2 years’ duration. DPCP is left on the scalp for 48 hours and then washed off. . cotton is wound around the stick to make a firm swab approximately three times the thickness of an average cotton-tipped applicator (Figure 2. if no reaction or only a mild to moderate reaction is observed.
Figure 2. The concentration is adjusted individually on the basis of the severity of the previous reaction.1%. 0. Concentrations vary (0. Once hair growth is established one one side. The patient had been treated unilaterally for 6 months without a response. 0. the severity of reaction and the presence of any hair growth are assessed. The following week. These refractory areas can be injected once monthly. Each week when the patient returns.5%.01%. 0. the other side is treated (see Figure 2.0%). It is better to be cautious than to be very aggressive and cause a severe reaction. with full regrowth. It is important to listen to your patients. DPCP is applied weekly for 3 weeks out of every month. showing circular areas refractory to treatment. The aim is to maintain erythema and pruritus. .24 Delayed DPCP response. Figure 2. as DPCP is degraded when exposed to light. or a low tolerable eczema.05%.23 Unilateral treatment with DPCP. 0.Alopecia areata 59 wig or scarf during this period of time. on the treated side for 36–48 hours after application. 2. (a) She returned to the clinic after treatment had been discontinued for 6 months with a unilateral response on the treated side. (b) Both sides were then subsequently treated. Intralesional corticosteroid is injected once monthly. DPCP is reapplied to the same half of the scalp. 0. 1.001%. The tolerance to the discomfort from the eczema varies with patients.0001%.0%.20).
(c) Complete regrowth with treatment.26 Eczematous eruptions from DPCP. .25 Treatment of eyebrows with DPCP. (a) Position used to apply DPCP to eyebrows. (b) Marked bulla formation is possible. Eyes are well shielded.60 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (a) Unilateral eczematous response one week after application. Figure 2. (b) Baseline before treatment in a 40-year-old female with no eyebrows for 18 years. This reaction is too strong. No application for 1 full week with a lower concentration applied the following week.
(d).Alopecia areata 61 (c).(e) The neck area is a common area for a bad reaction. (f) Frontal unilateral edema and eczema. . (g) Contact dermatitis to remote areas.
and hyperpigmentation in an African-American patient.28 Pigmentary changes with DPCP: (a) Hypo. .27 Lymphadenopathy occurs in 100% of patients. with most pigmentary changes resolved.62 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (b) The same patient.and hyperpigmentation (‘dychromia in confetti’) after 24 weeks of treatment in an East Indian patient. (d) Vitiligo on the back of the neck. (c) Hypo. Figure 2.
the frequency of treatment is gradually reduced. using the rule of four: treatment is adminstered every other week for 4 weeks. Vitiliginous patches on areas remote to the scalp. This reduction of visits continues until the patient experiences some hair loss and establishes the maintenance requirement. (f). The strength can always be increased later when the patient becomes familiarized with the treatments. . Maintenance requirements vary with individuals and commonly range from biweekly to bimonthly treatments. then every third week for 4 weeks. and so on.22). One patient was able to discontinue treatments for 4 years before she experienced any hair loss. (g). it is difficult to get them to resume therapy.Alopecia areata 63 If patients have discontinued treatment because of intolerable effects. (h). The requirement for (e) Vitilgo on half of the scalp in a patient who had been applying DPCP at home.21 and 2. Once full regrowth has occurred (Figures 2.
232 and erythema multiforme233 have also been reported. . and discontinue treatment.29). most of the scalp regrows hair except for a few small areas refractory to DPCP. the eyes shielded with gauze. and because vitiligo has a tendency to koebnerize on to inflamed skin. Regrowth of hair will take at least 12 weeks.64 Hair Loss: principles of diagnosis and management of alopecia maintenance therapy illustrates the palliative nature of the treatment.28). All female patients are counselled to use reliable birth control while on DPCP. we do not ever give DPCP to the patient for self-application. despite all the warnings on the informed consent form. Photochemotherapy (PUVA) The mechanism of action of PUVA on AA is believed to be a photoimmunologic action. Vitiligo is more common in AA patients. Treatments are administered two to three times a week. and we may abandon topical immunotherapy and proceed to another modality of therapy. DPCP therapy was immediately halted once our clinic was informed. However. and possibly inhibit local immunologic attack against the hair follicle by depleting Langerhans cells. although teratogenicity has not been demonstrated.223 Shah et al. with gradual increase in UVA dosage. 234 (see Figure 2. In certain responders.224 a combination of both referred to as ‘dyschromia in confetti’225 and vitiligo226–229 have been reported. Within 2 years of stopping treatment. DPCP is contraindicated in pregnancy. Vitiligo is a relative contraindication for treatment with topical immunogens.23). These resistant areas are treated with intralesional triamcinolone acetonide 5 mg/ml once monthly.24). Because of the possible side-effects. Side-effects include eczema (Figure 2.234 It may effect T cell function and antigen presentation. and the swab should be minimally moist. Burns are more likely to occur with topical therapy. such as hyperpigmentation. and is followed in 1 hour or 2 hours with UVA irradiation. Upon recommencing treatment. The psoralen is administered either topically or orally.223 severe blistering and lymphadenopathy (Figure 2.26). The process of complete regrowth is lengthy. growth was obtained (Figure 2. after the scalp has been treated (see Figure 2. a small number of individuals have returned with hair growth only on the orginally treated side. DPCP has been used with success to treat eyebrows. Consort dermatitis to spouse/partner has also been reported. Contact urticaria. one must be very cautious about rapid extension of vitiligo in an AA patient who already has the condition. with gradual new growth in multiple areas. six women have become pregnant while on DPCP therapy. Another phenomenon we have seen is the ‘initial non-responder’. hypopigmentation. This is best done at the end of the treatment.231 severe dermographism. but ocular toxicity is avoided. and usually respond well (see Figure 2. Extreme caution must be used. If the patient has not responded by 52 weeks. we consider the patient unlikely to respond.222 report the risk to medical and nursing staff. We have had a few patients that we identify as ‘slow growers’. we have had patients that have taken 41 weeks to see unilateral regrowth. All six pregnancies have produced normal children. The patient should be lying flat. At our clinic. 230. These patients initially do not respond.27) in the neck behind the ears. Pigment changes (Figure 2.25). autoeczematization. Extreme caution should be exercised when treating patients of dark pigmentation. They consistently grow new hair in more areas and do not seem to lose hair.
No significant differences were seen.Alopecia areata 65 Figure 2. the high recurrence rate following .3%) and good regrowth in 2/22 (9%). (a) Baseline before PUVA. owing to the side-effect profile. There was a response rate of almost 50% in each group. The major problem with PUVA therapy is the high relapse rate that frequently sets in after tapering the treatment.60. with median time to relapse being 10 weeks. with a mean total number of treatments of 47. As with systemic corticosteroids. Mitchell and Douglas234 used a combination of topical 0. Claudy and Gagnaire 235 used systemic PUVA with total body irradiation and showed a success of rate of 70%. He was unresponsive to 24 weeks of topical immunotherapy with DPCP. Larko and Swanbeck236 studied 40 patients with systemic PUVA.29 PUVA therapy in alopecia areata: a 22-year-old patient with extensive alopecia affecting 95% of his scalp for 2 years. 240 together with the need for long-term therapy in AA. make PUVA therapy less than satisfactory.239 Today’s concern about PUVA and its promotion of all types of skin cancer. Mean total UVA exposure for responders was 171.61 (Figure 2.1% 8-methoxypsoralen (8-MOP) and UVA and showed excellent regrowth in 8/ 22 (36.30). Almost all the patients available for follow-up experienced relapse when PUVA was tapered. Relapses were frequent. comparing whole body irradiation and scalp irradiation only. Only 10% relapsed after 6–12 months. Lassus et al. He still has refractory patches that are amenable to intralesional corticosteroid therapy. including melanoma.237 studied 41 patients with oral 8-MOP and whole body irradiation. Whole body treatment did not produce significantly better hair growth. and local 8-MOP plus local UVA irradiation. (b) After 1 year of PUVA. Cyclosporin Systemic cyclosporin has been shown to have some benefit in AA.238. Thirty-five percent experienced hair regrowth. but only 20% experienced a full regrowth.1 joules/cm2.
extent of alopecia and motivation for treatment. discontinuation of the treatment. (c) 3 months of systemic cyclosporin (4 mg/kg/day) and prednisone 5 mg/day.30 Cyclosporin in alopecia areata. the long treatment periods and the inability to change the ultimate prognosis of the disease. Treatment plan Therapeutic selection for AA depends on patient age.66 Hair Loss: principles of diagnosis and management of alopecia Figure 2. The dermatologist should first discuss all therapeutic options and outcomes. this treatment is simply not practical in AA. (d) 5 months of therapy.242 could not prove any cosmetic benefit from topical cyclosporin with concentrations of 10%. Gilhar et al. The patient had to discontinue therapy owing to serum transaminase changes and cholesterol elevation.241 and De Prost et al. al- . (b) A 28-year-old male with alopecia universalis for 2 years. (a) Mechanism of action by inhibiting the Th response to the 1 hair follicle.
we will add a minoxidil 5% solution twice daily and a superpotent corticoster- . If there is no response after 3–4 months.31 University of California at San Francisco-University of British Columbia Treatment protocol for alopecia areata (permission granted by Drs Jerry Shapiro. San Francisco—University of British Columbia Alopecia Areata Treatment Protocol (see Figure 2. and Harvey Lui). the following options are offered. Patients are divided into those less than 10 years of age and those over 10 years of age. Topical therapies with minoxidil. First-line therapy for scalp AA is intralesional corticosteroid injections into the alopecic patches. Firstly. lowing the patient to become an active member of the therapeutic team. as many AA patients will regrow their hair without treatment. However.Alopecia areata 67 Figure 2. we always offer the patient the option of no treatment. while in adults other options to be considered include intralesional corticosteroids or immunotherapy.31). most of our patients are well-motivated and want treatment. 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. For those with less than 50% scalp hair loss.Price. Vera H. A practical treatment algorithm for the treatment of AA is the University of California. corticosteroids and anthralin are considered in children of less than 10 years of age.
It should be emphasized to the patient that a prosthesis does not imply permanent hair loss. Other options that can be offered to the patient are systemic PUVA.68 Hair Loss: principles of diagnosis and management of alopecia Figure 2. Scalp prostheses come in an assortment of net linings that are light. minoxidil 5% solution. topical immunotherapy is discontinued. Use of eyeliner or alopecia masking lotion (Figure 2. (a) A lining that will allow one’s own natural hair to be pulled through.32).0% cream applied for up to 1 hour daily combined with topical minoxidil 5% solution applied twice daily. and can give great satisfaction to a majority of patients.32 Scalp prostheses come with different linings that are light and allow air to circulate. our first line is topical immunotherapy with DPCP. another option is short-contact anthralin therapy with anthralin 1. If there is no response by 52 weeks. For those patients with more than 50% scalp involvement. but having one on hand is comforting for episodes of extensive hair loss. (c) Net meshes that are typical. If there is no benefit. oid cream such as clobetasol propionate applied 30 minutes after the minoxidil in addition to the monthly injections. A scalp prosthesis should be available to all patients with more than 50% scalp involvement. short-contact anthralin and superpotent topical steroids.33) can give the AA . and cool and allow air to circulate (see Figure 2. (b).
194. therapeutic options include minoxidil alone or in combination with a mid-potency topical corticosteroid or anthralin. Dermatography of eyebrows is a technique that can be recommended for AA patients with prolonged eyebrow loss243 (Figure 2. The ultimate therapeutic plan is developed through team interaction between the patient. the patient’s family and the physician.34 Dermatography: a semi-permanent tattoo for the eyebrows. For some patients.34).33 Camouflage with eyeliner. He has a small patch of alopecia areata. patient considerable camouflage. and the dermatologist needs to become familiar with sup- Figure 2. port groups and suppliers of hairpieces. (a) The patient is a 23-year-old who likes his hair short. exploring the impact of alopecia on the patient’s emotional . Physicians need to take the time to address the psychological needs of their patients. In those younger than 10 years intralesional corticosteroids are avoided and topical immunotherapy is not implemented.Alopecia areata 69 Figure 2. (b) Camouflage with eyeliner. support groups play an important role in the overall therapeutic strategy. Children: Therapeutic modality choices depend upon patient age.195 For those under 10 years of age. Those older than 10 years are treated with the same protocols as adults. although several European studies have demonstrated efficacy and safety in children as young as 5 years. giving the illusion of hair in the area.
Dermatol Clin. It is imperative that the physician spend sufficient time with the patient. and Koo J. HLA class II alleles in longstanding alopecia totalis/alopecia universalis and long-standing patchy alopecia areata differentiate these two clinical groups. Rodent models currently available have become an important part of therapeutic research. The National Alopecia Areata Foundation (710 C Street. Arch Dermatol. et al. Colombe B. videos for children to take to school and information about support groups. 4(3):197–254. Lou C. 4(3):216–19. 1999. 1996.L. J Invest Dermatol. 1995.V. and Price V. Profile of alopecia areata: a questionnaire analysis of patient and family.W. The National Alopecia Areata Foundation (NAAF) has an annual convention for patients and their families. The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis. 88:290–7. Alopecia areata: an evaluation of 736 patients. Muller R.alopeciaareata. 6. November 7–8. J Invest Dermatol Symp Proc. J Invest Dermatol. The eventual discovery of cytokines specific for hair growth promotion in topical immunotherapy will offer more focused treatments. Int J Dermatol. Bethesda. has the potential to immunomodulate. Heritable factors distinguish two types of alopecia areata. light-emitting diode arrays). Price V. Khoury E. 31(3):186–9. 14(4):679–89. 104(5 Suppl):4S–5S. Alopecia areata. Bethesda. Maryland. 2. safety profiles and outcomes.. and Colombe B. 1994.L. October 25–26.W. sources for scalp prostheses.H. 1991.D. The role of this therapy in the treatment of AA holds great potential for the future. .org) offers patients and physicians information. just as one would with a patient who had recently been diagnosis as diabetic. Colombe B. Newer immunomodulators specific for CD4 or CD8 and IL-2 receptors may further enhance treatments.H.. Outlook for the future for alopecia areata treatments New therapeutic directions for alopecia areata will involve specifically targeted immunomodulatory agents. involving new photosensitizers and novel non-UV light sources (lasers. 1999. 104(5 Suppl):1S–45S. 7. HLA class II antigen associations help to define two types of alopecia areata. 96(5):67S–100S. 2nd International Research Workshop on Alopecia Areata. which are present in many large cities in the USA and Canada. 8.E. including brochures.70 Hair Loss: principles of diagnosis and management of alopecia well-being. Gene replacement therapy based on current genetic studies may eventually allow lasting correction of abnormal gene expression. 1963. 33(5 Pt 1):757–64. It is the role of dermatologist to explain the diagnosis and inform the patient of all the therapeutic options. 1990. 5. 3. Third International Research Workshop on Alopecia Areata. Physicians are welcome to attend. 9. J Am Acad Dermatol. California 94901–3853.W.W. 4. Price V. www.. bimonthly newsletters. San Rafael. 1995. A workshop.H. Colombe B. Khoury E.D.. 1995. Maryland. Suite 11. References 1.H. and this is often the turning-point for them in terms of coping with the condition.. Edwards J. penpals for children. 1992. and Lou C. J Invest Dermatol. Phototherapy beyond PUVA. Shellow W. Other biotechniques to interrupt the peptide-antigen or T-cell receptor are being evaluated..W.Y. Price V.S. J Invest Dermatol. research updates..
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Tan J. Nameda Y. Ned Tijdschr Geneeskd. Perret C. and Hutchinson P.K.R. 1988. 1990.J.. Guerra L. Wilkerson M. and Arase S. and Foulds I. Fernandez-Redondo V.M. Berth-Jones J. Florez A. Br J Dermatol. 228. 1993. Treatment of alopecia areata with diphenylcyclopropenone [see comments].Vitiligo and topical allergens [letter. 12(4):644–9. Acta Derm Venereal.M. 2000. 1990. Henkin J.H. 128(4):518–20.. and Bardazzi F. 230. van Baar H. and Happle R. 42(4):212–15. Perret C. Van der Steen P.. 232. Skrebova N.. 199(2):198. Hatzis J. and Savin R. 29(5 Pt 1):729–35. 24(2 Pt 1):253–7. 179(3):137–8. 177(3):146–8.C.M. Alopecia areata in children: response to treatment with diphencyprone. Zaun H. Topical photochemotherapy for alopecia areata. 21(3):196–7. 231.. C. Gourgiotou K. 1989.. Alam M. 217. 226. Steijlen P. 223.H. Contact Dermatitis.. et al. and Happle R. 227.. Steijlen P. Treatment of alopecia areata. 123(3):415–16. Diphenylcyclopropenone: an important agent known to cause depigmentation [letter. 219. 1991. In Hair and Hair Diseases. and Messenger A. Orecchia G. 216. and Happle R. 233. 1990. Perret C. Hull S. Br J Dermatol. 224. 225. 55(2): 202–3. J Am Acad Dermatol.. Pepall L.M. J Am Acad Dermatol.. Mitchell A.M. Ho V. J Am Acad Dermatol. J Am Acad Dermatol.. 220.J. Diphenylcyclopropenone: examination for potential contaminants. Treatment of chronic severe alopecia areata with topical diphenylcyclopropenone and 5% minoxidil: a clinical and immunopathologic evaluation.Happle.. 1989. 215.. Shapiro J. and Douglass M.A. Perret C. Gross E. 133(3):496–7. Gomez-Centeno P. 1987. pathogenesis and topical immunotherapy].S. Dermatologica. 1994. Wilkerson M. and Stock J. Assessment of diphenylcyclopropenone for photochemically induced mutagenicity in the Ames assay.Erythema multiforme-like eruptions: a rare side effect of topical immunotherapy with diphenylcyclopropenone. and Wilkin J. Persistent vitiligo induced by diphencyprone [letter]. 125(2):164–8. [Alopecia areata. 234.. 180(1):5–7. 17(4):606–11. Tosca A..80 Hair Loss: principles of diagnosis and management of alopecia 214.E. Br J Dermatol. mechanisms of sensitization.M. Severe urticarial reaction to diphenylcyclopropenone therapy for alopecia areata. and Perfetti L. and Happle R.. . 529. 1992. J Am Acad Dermatol.A.Vitiligo complicating diphencyprone sensitization therapy for alopecia universalis [letter].G. Henkin J. Mc Burney A.G. Dermatologica. 74(4):312–3. Arch Dermatol. Takiwaki H. et al.M. Contact urticaria during topical immunotherapy. 40(1):110–12. comment]. 229. 1995. 221.C. 2000.. Dermatologica. Shah M. Vitiligo as a reaction to topical treatment with diphencyprone [see comments]. 133(25):1256–60. 134(6):1153. Henderson C. p. 1991.O. Tosti A. 1984. 1999. 218. J Am Acad Dermatol. Lewis P. Allergy. Hazards in the use of diphencyprone. 1989. Duhra P. comment].M. Hazards in the use of diphencyprone [letter] [see comments].G. 1999.. and Toribio J. Br J Dermatol. and Ilchyshyn A. and photochemical stability. and Cunliffe W... and Tron V.. Orecchia G. 1985. Diphencyprone is not detectable in serum or urine following topical application. New York: Springer Verlag.. 1996. Connor T. 11(5 Pt 1): 802–7. Severe dermographism after topical therapy with diphenylcyclopropenone for alopecia universalis. Van der Steen P. ‘Dyschromia in confetti’ as a side effect of topical immunotherapy with diphenylcyclopropenone. 222. Contact Dermatitis.. Dermatology. ed.
Br J Dermatol. 239. 1993. Lassus A. Lancet. 1986. et al. PUVA treatment of alopecia areata partialis.L. PUVA treatment for alopecia areata. . 243. 242. and Gagnaire D.. Van der Velden E. PUVA treatment for alopecia areata—does it work? A retrospective review of 102 cases. 1980. New Engl J Med. Br J Dermatol.. Gilhar A.. 240.E. Paquez F. et al. and Juvakoski T. Stern R. Photochemotherapy for alopecia areata. Johansson E.H. 37(8): 617–21. 161(5):298–304. The PUVA Follow-Up Study [see comments]. Dermatologica. PUVA treatment of alopecia totalis. Taylor C. 129(1):42–4. 60(2):171–2. and Rogers S.. and Etzioni A. 336(15):1041–5. 238. 1989. and Vakeva L. 1995. Teillac D. Acta Derm Venereal.M.Alopecia areata 81 235. 1998.R. 1980. 2(8510):803–4. Ijsselmuiclen O. Placebo-controlled trial of topical cyclosporin in severe alopecia areata [letter]. Pillar T. and Hawk J. Dermatography as a new treatment for alopecia areata of the eyebrows.H. 236.T. Claudy A.. 1997. 1983. totalis and universalis: audit of 10 years’ experience at St John’s Institute of Dermatology. and Swanbeck G. Kianto U. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). 133(6):914–18. Topical cyclosporin A in alopecia areata.. Acta Derm Venereal. Drost B. de Prost Y. et al. 237. Nichols K.S.. Acta Derm Venereal.L. Larko O. 69(3):252–3.. Int J Dermatol.. 241... Healy E. 63(6):546–9.
1–3 Although it is a medically benign condition. spironolactone and estrogen (personal observation). with progressive shortening of the anagen phase occurring over many cycles. AGA involves both genetic and hormonal factors. A MIM entry that begins with the number one indicates an autosomal dominant inheritance.3 polygenic. clinical features and state of the art medical management of AGA. less so in Africans.21 .1.1). clinical features and practical medical treatment 16 Introduction Androgenetic alopecia (AGA) is by far the most common cause of hair loss. It is still controversial what becomes of these miniaturized follicles. it can have a significant psycho-social impact for patients. This shortening of anagen and subsequent miniaturization of hairs leads to decreased scalp coverage. since cases of severely advanced balding male to female transsexuals have experienced considerable regrowth using finasteride. We are only beginning to understand the different factors underlying AGA.7– The hair cycle is altered.17.19 The gene frequency appears to be most common in Caucasians.3 Androgenetic alopecia: Pathogenesis. Genetic factors The exact inheritance pattern of AGA is still debated. that transform terminal to miniaturized follicles. in AGA the number of follicles per unit of area remains the same. minoxidil.19 and inherited from either parent. 4–6 This chapter will highlight the pathogenesis. However. Complete permanent regression is unlikely.18 These finer small vellus-like hairs of varying lengths and diameters are the hallmark of AGA (Figure 3. Asians and Inuits. After puberty. As its name implies. It is believed to be most likely autosomal dominant.1 Genetics determine both the density and the location of androgen-sensitive hair follicles on site-specific areas of the scalp. It affects approximately 50% of men by the age of 50 and 20% to 53% of women by the age of 50.20 The McKusick Mendelian Inheritance in Man (MIM) number for AGA is 109200. and least frequent in Amerindians. predominantly of the fronto-parietal scalp. The following is a summary of the current knowledge on AGA pathogenesis. Pathogenesis Knowledge of the patho-physiology of AGA is essential in understanding the mechanism of action of current therapeutic agents. androgens trigger a series of events within these genetically-programmed hair follicles.
Osborn22 stated that AGA was a sex-limited autosomal dominant trait similar to the inheritance of horns in sheep. 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. The genotype bb may remain sub-clinical in both sexes. whereas the genotype Bb requires higher amounts of androgen. Fifty-six per cent of bald men had bald fathers. 66% of the brothers were bald if the father of the proband was also bald.26 Kuster and Happle. He studied 119 males with AGA. There was an association of increasing amounts of chest hair.84 Hair Loss: principles of diagnosis and management of alopecia Figure 3. Sixteen had no family history. Salomon25 felt that AGA is inherited through multifactorial or conditioned dominance via an autosomal dominant gene of variable expressivity. Some previous work on the genetics of AGA dates back to 1919. in affected individuals. Harris24 found that of 117 men with AGA. there is miniaturization of coarse terminal hairs into small vellus-like hairs with each subsequent cycle. but not back hair. This observation is quite interesting. although no formal study has been performed. 24 three generations and 3 four generations involved. The authors concluded that this was consistent with an autosomal dominant gene. 65 had two generations. in that Shapiro has noted the same trend in increased body hair distribution in a disproportionately large number of his balding male patients. Eleven had two generations of families with both parents affected. A family has been described in which common baldness with early onset occurred in females only. and 46% of the brothers were bald if the father was not bald.19 favor a polygenic inheritance rather than a simple Mendelian model. and women who presented with AGA were homozygotes only. They present very credible arguments .1 In androgenetic alopecia. She believed that men could be either homozygotes (BB) or heterozygotes (Bb).
may be a part of the polygenic spectrum of genes responsible for AGA. the distribution of the balding patterns in the general population along a Gaussian curve of variation. Hormonal factors A major determinant of AGA is intracellular androgen metabolism.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.33 and this may explain why female AGA is usually less severe than male AGA.28 There was an association with one allele of the steroid metabolism gene CYP17.33. vas deferens. and sweat glands. and the fact that the risk increases with the number of relatives already affected.32. The X-linked mutation for adrenoleukodystrophy.1.34 Both type I and type II isoenzymes play an important role in AGA. Other important factors may still remain to be discovered. lacking androgen receptors.34 The 5a-reductase type II isoenzyme is located mainly in the root sheaths of the scalp hair follicle33. are both part of normal androgen metabolism and reduce testosterone (T) to dihydrotestosterone (DHT).33 DHT levels are increased in balding scalp when compared to non-balding scalp.35. but to a lesser extent in women. which is correlated to premature AGA in men. Shapiro has seen a female teenager with androgen-insensitive syndrome. although this genetic change was not the primary cause of either condition.35–37 Both isoenzymes are increased in frontal balding follicles compared to occipital non-balding follicles.41–43 further supporting the DHT requirement for AGA expression. A recent case report by Orme et al.38–40 Women have 3.27. and fetal genital skin. type I and II.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. prostate. 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. which involves two steroid-metabolizing enzymes (5a-reductase and aromatase) and androgen receptor pro- teins. 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.5 times less 5α-reductase (I and II) than men. The 5a-reductase type I isoenzyme is located mainly in sebaceous glands. dermal papilla cells.28 The search for the gene continues. The high prevalence rate.27.30 Sreekumar 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. with typical female AGA (unpublished personal observa- .0–3. Individuals with a genetic deficiency of 5a-reductase type II isoenzyme do not develop AGA. 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.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.Androgenetic alopecia 85 supporting multi-allelic inheritance. seminal vesicles. Carey et al. showing that this pattern of hair loss is not necessarily androgen-dependent.34 as well as in the epididymis.33 5a-reductase isoenzymes. epidermal and follicular keratinocytes.
androgens upsize.33 Androgen receptor proteins (ARP) are found in the outer root sheath and dermal papilla fibroblasts of scalp hair follicles.32. including starting or stopping the oral contraceptive pills and post-partum and peri.47 The clinical course is gradual. However. hair follicles at puberty. The explanation for this bifurcated action is not known.17 Studying the quail-chick model. although hair density does decrease as they age further. 12% in one study showed a completely negative family history. rather than downsize. the condition may seem stable for years. 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. The shedding may be seasonal in a small number of individuals. Women .and post-menopausal states. consisting of acute episodic phases with increased loss of telogen hair. However. Usually there is a positive family history.25 Hair loss in women may be triggered by hormonal changes. Dermis of the frontoparietal scalp is derived from the neural crest. Clinical features of AGA History Thinning of the hair can occur as early as the age of 12 (Figure 3. which can elicit a telogen effluvium. 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. Norwood and Lehr45 have proposed that female AGA may be a separate entity. alternating with periods when there is little shedding. whereas dermis of the occipital/temporal scalp is derived from the mesoderm. These events. Most cases start between the ages of 15 and 25. However.47 For many individuals.47 Many men reach their maximum pattern by their forties. This likewise helps explain why women with AGA usually retain their frontal hairline and have less hair loss than men with AGA.8. but the total receptor content is 40% less in women than in men.13. Paradoxically. These events within the follicle result in the transformation of terminal to miniaturized hair follicles on the scalp in AGA. may unmask a tendency for AGA. These findings are intriguing.33 Aromatase results in the conversion of T to estradiol and estrone. and may have a protective effect on hair follicles. AGA usually manifests at an early age and progresses slowly. in other androgensensitive areas such as the beard and mustache. Aromatase is significantly higher in the hair follicles of women.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. Ziller46 found differences of embryonic origin of the dermis of the fronto-parietal scalp compared to the occipital scalp. The cytochrome P450 aromatase enzyme is also part of normal androgen metabolism.86 Hair Loss: principles of diagnosis and management of alopecia tion).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. they admit that it is impossible to distinguish male from female hair shaft miniaturization either clinically or histologically.17.2a) and as late as the age of 45 in both sexes. and therefore the resulting shift will lessen conversion of T to DHT.
Lotufo et al. (b) The presence of miniaturized hairs helps to confirm a diagnosis of AGA. Herrera et al. cardiovascular disease. The hair is then closely examined against this backdrop. Baldness was assessed twice. SAHA syndrome.52 showed that vertex pattern balding appears to be a marker for increased risk of coronary heart disease. The relations between the extent and progression of baldness and the aforementioned outcomes were assessed using a Cox proportional hazards model. A contrast paper is placed in a parted area of the scalp.2 (a) Male androgenetic alopecia can appear early. in the vast majority of women with AGA. hirsutism and acne.Androgenetic alopecia 87 Figure 3. 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. This is a 13-year-old boy showing frontotemporal thinning and hair miniaturization. hyperandrogenism is not a problem.50 with an increased risk for atherosclerotic and coronary heart disease in balding men.53 assessed the relation between the extent and progression of baldness and coronary heart disease.017 men from Framingham. Extent of baldness was not associ- .49–51 In one study there appeared to be lipoprotein and triglyceride level differences between males with vertex thinning and non-balding men. The cohort was followed for up to 30 years for new occurrences of coronary heart disease. 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. in 1956 and in 1962. coronary heart disease death. The biologic mecha- nisms for this relationship are unknown. in a cohort of 2. frequently indicates an androgen excess in the female patient.48 An increased risk for coronary artery disease has recently been correlated to vertex balding in men. especially among men with hypertension or high cholesterol levels. and death due to any cause. adjusting for age and other known cardiovascular disease risk factors. Massachusetts. However. alopecia. standing for seborrhea.
although there may be a mild increase in telogen hairs. Psychoneurotic attitudes may ensue. that tend to remain clinically silent until they are advanced. and all-cause mortality (RR =2. A hair pull test is usually negative.55 A total of 3. and is blamed for all social and professional problems. However. Incident cases of prostate cancer were identified by interviews.8). 56 Participants were followed from baseline (1971–4) through to 1992.7).2b). 95% CI 1.56 further hypothesize that AGA in men may predict other age-related pathological processes.3–4. with preservation of follicular ostia. In terms of the pattern of hair loss.5–3. The authors concluded that men with AGA had a 50% excess risk for clinical prostate cancer. 95% confidence interval (CI) 1. These authors suggest that men with early AGA might benefit from screening for cardiovascular risk factors and for insulin resistance.000 person years).9–7.8.4. when compared to age-matched controls. in which the alopecia is merely a symptom that the patient may clutch on to. no association between coronary heart disease and androgenetic alopecia was found. AGA becomes a preoccupation. medical records and death certificates. In some women with AGA.5 vs 12.4. coronary heart disease mortality (RR=3. the amount of progression of baldness was associated with coronary heart disease occurrence (relative risk (RR)=2. The investigators noted that the age-standardized incidence of prostate cancer was greater among men with baldness at baseline (17.54 This finding supports the hypothesis that early AGA could be a clinical marker of insulin resistance. AGA may unmask a psychological lability and/or psychiatric disturbance. The major strengths of this study included its prospective design.47 In some individuals. Prostate cancer was diagnosed in 214 subjects over 17–21 years of follow-up. and dyslipidemia in men with early onset of AGA (< 35 years). 95% CI 1. 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.5 per 10. Men with AGA had a consistently higher incidence of prostate cancer compared with those without AGA. thus limiting the effective power of their study. It was concluded that rapid hair loss may be a marker for coronary heart disease. Hawk et al. 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. extended follow-up. and national representative sampling. including race and age.5. women usually have less severe hair loss than men and . hypertension. though only in involved areas of the scalp.88 Hair Loss: principles of diagnosis and management of alopecia ated with any of the outcomes. such as atherogenesis. The adjusted relative risk for prostate cancer among men with any degree of baldness was 1. and was similar regardless of the severity of baldness at baseline and was independent of other risk factors.47 Physical examination Hair loss is patterned and non-scarring. in a study of 478 men. beginning at approximately 60 years of age. Miniaturized vellus-like hairs can usually be seen with contrast paper placed over a part (Figure 3. 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. On the other hand. and occasionally in men.4).
97:247–54. In a significant percentage of female patients with AGA. Even with this diffuse loss.4 (a) Ludwig classification of female AGA. and women affected may require an endocrine work-up if they show other signs of androgen excess. The presence of global thinning clearly decreases the chances of being a successful female hair transplant candidate. and usually in those with early-onset AGA. Olsen58 feels that 5% show a global decrease in scalp hair density.Androgenetic alopecia 89 Figure 3.8). ‘parting’) found in a woman without AGA. ‘parting’) in the centro-parietal area with that in the occipital area. and is divided in 3 stages according to severity (Figures 3. diffuse hair thinning may be present (Figure 3. most women present with an intact frontal hair line. The hair thinning is mostly on the crown. (b) The characteristically narrow division of bare scalp between areas of combed hair (‘part’. In men. This generally occurs in those women with more advanced hair loss.57 Ludwig Stage I is the most common pattern. Ludwig Stage III is rare. Shapiro feels that approximately 30% of women have a more global thinning. there still remains a variance of hair density on the top of the scalp versus the sides or the back of the scalp. This pattern is recognized as the Ludwig pattern. there is a frontal hairline recession associated with thinning or balding on the Figure 3. Reproduced with permission from the British Journal of Dermatology 1977.9a and b). .3 In female AGA.3). showing the three different stages of severity. Hair loss may only be evident when one compares the relative widths of the division of bare scalp between areas of combed hair (‘part’.4–3. retain their frontal hairline (Figure 3.
8 Ludwig Stage III: Considerable loss of hair.6 Ludwig Stage II: The width of the division of bare scalp (‘part’. 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. There are exceptions. Hamilton originally classified male AGA on the basis of fronto-parietal/fronto-temporal recession and vertex thinning. 60 more than 25 years later. ‘parting’) may be the first complaint of the female patient. ‘parting’) is now considerably more evident than in Ludwig I. as in Figure 3. This pattern is known as the Norwood-Hamilton pattern. improved on this pictorial classification. She will also notice her ponytail diameter may be reduced one-third to one-half of what it used to be.7 Mother (left) with Ludwig Stage II and daughter (right) with Ludwig Stage I. Figure 3.90 Hair Loss: principles of diagnosis and management of alopecia Figure 3. 59 Norwood.5 Ludwig Stage I: A widening of the division of bare scalp between areas of combed hair (‘part’. crown or vertex. and is divided . as before. Figure 3.10a and b. with certain individuals showing no recession and only vertex thinning.
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
Hair Loss: principles of diagnosis and management of alopecia
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.
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.
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
with preservation of the ‘horseshoe’ of hair at the sides and back of the scalp.20 A female with AGA with a NorwoodHamiltion Stage VI pattern. A 40-year-old female with NorwoodHamilton Stage II AGA with fronto-temporal recession.18 Women can show the Norwood-Hamilton pattern.19 A female with AGA with a Norwood-Hamilton Stage V pattern.94 Hair Loss: principles of diagnosis and management of alopecia Figure 3. (a) Frontal view (b) Lateral view. Figure 3. Figure 3.17 Norwood-Hamilton Stage VII. with miniaturized hairs. Figure 3. .
Figure 3. The other two diagnoses that may be difficult to distinguish are telogen effluvium and alopecia areata.Androgenetic alopecia 95 Figure 3. (b) A seventeen-year-old male with the Ludwig Stage I pattern.22a A 40-year-old male with Ludwig Stage II. Telogen effluvium is usually generalized (Figure 3. frequently with an iden- . Figure 3. with an abrupt onset.21 Two male teenagers 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). (a) A fourteen-year-old male with Ludwig Stage I.23a). Both these entities are discussed at length in other chapters.
with remissions and relapses. tifiable trigger.23d A 28-year-old female with telogen effluvium who kept a diary of hair loss for 5 years.96 Hair Loss: principles of diagnosis and management of alopecia Figure 3. (Figure 3. but can be generalized. Onset is at any age. with no bare patches.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. Onset is usually abrupt. This is unusual with AGA. Figure 3. Shedding is prominent. but usually not childhood. Overlapping of AGA and alopecia areata can occur. Shedding is prominent.24). There is thinning. Alopecia areata (AA) is usually randomly patchy. This amount of hair loss would not be seen in AGA. It is ex- . with over 60% presenting under the age of 20.23c Patients with telogen effluvium frequently present with bag of hair to show the physician. The pull test is positive with telogen hairs. Figure 3. with a positive pull test for both dystrophic anagen and telogen hairs. Onset is at any age.
0 mm scalp biopsy with transverse sectioning is the best laboratory test to distinguish AGA from AA or telogen effluvium. If an AGA patient has a previous. he or she must be warned that that it could recur after surgery. are very popular in Europe and are useful. have. However. If an AGA patient has a previous recent or remote history of AA.Androgenetic alopecia 97 Figure 3. The 4. but also more information on hair density and inflammatory perifollicular changes. This may have great significance if one is contemplating hair transplantation surgery for AGA. (b) A 35-year-old male with AGA with a 3-month history of a patch of AA. no laboratory work-up is necessary unless there is concomitant diffuse hair loss. or will have AA. (a) A 25-year-old female with female AGA with a 6-month history of a patch of AA. have.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. Laboratory tests In men. recent or remote history of AA. However. It is expected that almost 2% of patients with AGA have had. it requires special skill and is fairly labor-intensive. he or she must be warned that that it could recur after surgery. Standard trichograms.7% of patients with AGA have had. The meticulous ‘unit area trichogram’ introduced by Rushton61 will also give information on hair density. or will have AA. the scalp biopsy will give the physician not only the same information with respect to anagen/telogen and terminal/vellus ratios. involving the hair pluck. pected that 1. In .
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 . and therefore an androgen work-up is not indicated.28).03 mm in diameter.25a and b Stelae or fibrous streamers (FSt) commonly seen in AGA (courtesy of Dr Magdalena Martinka). a free testosterone and dehydroepiandrosterone sulfate (DHEAS) test should be ordered. Primary vellus hairs are small hairs.25). both terminal. Terminal hair bulbs predominate in anagen phase. and vellus-like hairs are identified. The vast majority of women with AGA do not display hyper-androgenism. In papillary dermis.26). this author recommends a routine thyroid stimulating hormone test (TSH). only the Pathology The histologic features of AGA are similar in males and females. because of the frequency of thyroid abnormalities and the difficulty of distinguishing AGA from telogen effluvium. In reticular dermis there are no vellus or vellus-like hairs. telogen or miniaturizing hair shaft and bulb (Figure 3.29).) Horizontal sections show distinctive changes in papillary and reticular dermis and in the deeper subcutaneous sections. women. hairs on horizontal section are arranged in follicular bundles of 2–4 hairs with sebaceous glands and arrector pili muscle63 (Figure 3. In fat. Catagen and telogen terminal hairs are noted as well (Figure 3. papillary dermis.98 Hair Loss: principles of diagnosis and management of alopecia Figure 3. This patterning is typical of scalp hair.62–64 (Stelae are the residual fibrous tracts that mark the upward migration of the catagen. Androgen levels should only be ordered in those women who appear clinically to have an androgen excess. Vellus and vellus-like hairs are less than 0. vellus. If one suspects an androgen excess. and originate in the upper half of the dermis (Figure 3. Usually. have a thin outer root sheath. Ferritin levels are also ordered routinely on menstruating females.27). as low iron levels can trigger a telogen effluvium that may mimic AGA. 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.
Note the prominence of the sebaceous glands (SG) when hairs are miniaturized (courtesy of Dr Magdalena Martinka). and in the fat is usually around 30.27 Secondary vellus hair (V) with small hair shaft and large outer root sheath (ORS). showing a vellus hair (V) and a telogen hair (T).30).28 Follicular bundles with miniaturized hairs (courtesy of Dr Magdalena Martinka). in the upper papillary dermis counts are usually around 40–50. deeper anagen terminal hairs are present (Figure 3. Follicular counts vary from level to level. Figure 3.26 Primary vellus hair (V) with a small hair shaft and small outer root sheath (ORS) (courtesy of Dr Magdalena Martinka).Androgenetic alopecia 99 Figure 3. Normally. Figure 3. indicating true miniaturization (courtesy of Dr Magdalena Martinka). Figure 3. In the reticular dermis the number is usually reduced to 35. The difference of counts between papillary dermis and reticular dermis represents the number of .29 A close-up of a follicular bundle in AGA.
Hair Loss: principles of diagnosis and management of alopecia
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-
light could cause some inflammation. These causes may be more pronounced in the less protected scalp.62
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.
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
Hair Loss: principles of diagnosis and management of alopecia
hair loss, surgery or hairpiece may be the only options. Each option will be discussed in detail on the basis of classification.
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
there was no significant difference in the change in hair count between the finasteride and placebo groups.75 Van Neste et al. 78. 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. visit number and treatment. This study enrolled 212 men age 18–40 years with AGA. blinded ratings of standardized photographs by an expert panel. While improvement for finasteride-treated men compared to baseline was greater at 24 months. In this study. randomized. the difference between the group treated with finasteride and the placebo group continued to increase throughout the 5 years of the study. Macrophotographs were taken to measure total as well as anagen hair counts in a 1 cm2 target area of the scalp. Based on hair counts. patient and investigator assessments. Patients were randomized to receive either finasteride 1 mg daily or placebo for 48 weeks. Finasteride was generally well tolerated. leading to a net improvement in hair count of 277 hairs (31%) for men treated with finasteride compared with placebo after 5 years. investigator. 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. patient. Sixty-six men aged 18–40 years with Norwood-Hamilton Stage III and IV were enrolled in a randomized. double-blind. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. multicenter trial. At 6week intervals.79 In this 1-year. double-blind. placebocontrolled study.Androgenetic alopecia 103 in up to 90% of men. Similarly. compared with 25% on placebo. 136 postmenopausal women (41–60 years of age) with AGA received finasteride 1 mg/day or placebo. provided direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. 26 men continued to receive finasteride 1 mg and 23 men remained on placebo. Efficacy was evaluated by scalp hair counts. A study of finasteride in 136 postmenopausal women with AGA showed no benefit compared with placebo. increasing hair growth. The hair weight study demonstrated that treatment with finasteride 1 mg provides continued maintenance and improvement of hair growth over 96 weeks.. The study was extended for 48 weeks for a total of 96 weeks. After 96 weeks. placebo-controlled. Treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47%. Finasteride may show improvement in older men. hair in a marked site was handclipped using a magnifying light. 76 using the phototrichogram method. and histologic analysis of scalp biopsy specimens. 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. or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. After 1 year of therapy.74 In a study of hair weights done by Price.77 A 2-year study in balding men between the ages of 41 and 60 years is ongoing. Thirty-three men received finasteride 1 mg daily and 33 received placebo for 48 weeks. 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. In the extension study. In . All hair samples were weighed in a single session by a technician who was blinded to patient. the total hair weight showed a statistically significant increase from baseline weight in the finasteridetreated subjects.
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.4% placebo).1 A recent study by Overstreet et al.83. The risk of teratogenicity in humans has not been directly evaluated.104 Hair Loss: principles of diagnosis and management of alopecia post-menopausal women with AGA.79 Propecia™ 1 mg is to be taken every day.8% vs 2. with or without food. but may be too low for female AGA. This is adequate for the treatment of acne.81 confirmed that finasteride 1 mg daily for 48 weeks did not effect spermatogenesis or semen production in men aged 19– 41 years.80 Finasteride is well tolerated.1%). and side-effects occur in less than 2% of patients. but there is a statistical difference when all side-effects are considered together (3.80 Finasteride tablets are coated to prevent contact with the active ingredients during manipulation. gynecomastia and feminization. CPA is available in Europe. and no drug interactions have been reported.7% placebo) and 0. .80 but there is a risk that finasteride exposure during pregnancy may cause hypospadias in the developing male fetus. They are suitable only in women and are contraindicated in men because of side-effects such as impotence.17 Exposure to semen of men who are taking finasteride does not pose a risk to a pregnant woman’s male fetus.73. Cyproterone acetate: Cyproterone acetate (CPA) is a potent progestin and an androgen receptor antagonist. The bioavailability after oral intake is 65%. it is recommended a baseline PSA be taken for older men prior to initiation of therapy with finasteride. This was confirmed by histologic analysis on 94 women with AGA.8% decreased ejaculate volume (0. and are reversible upon cessation of treatment.72 Side-effects include 1.40.80 Dosage does not need to be adjusted in case of renal insufficiency. decreased libido.17 Diane-35 contains 2 mg of CPA. Asia and Canada.3% erectile dysfunction (0.81 Finasteride can decrease PSA levels by 50% in older men. on a regular schedule.40 Side-effects will subside spontaneously in 58% of those who decide to continue the treatment. CPA is an effective treatment for hirsutism and acne.3% placebo).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.72 There was no significant difference from the placebo group for each of these side-effects taken alone.83–85 There are no large controlled clinical studies in AGA with CPA. 80 Ninety per cent of circulating finasteride is bound to plasma proteins and can cross the blood-brain barrier. We also advise the patient’s family doctor to double the PSA value while patients are taking finasteride. Androgen-receptor blockers (ARP inhibitors) Systemic ARP inhibitors decrease both T and DHT by binding to the androgen receptor. Women who are or potentially may be pregnant should not take finasteride or handle crushed or broken tablets. 1.82 At the University of British Columbia Hair Research and Treatment Centre.40. but not in the United States. finasteride 1 mg/day taken for 12 months did not increase hair growth or slow the progression of hair thinning.8% decreased libido (1. although regrowth is quite rare in this author’s experience. It may have some effect on stabilization of hair loss.80 Finasteride does not affect the cytochrome P450 metabolizing enzyme system. and therefore caution should be taken in patients with liver function abnormalities.80 Finasteride is metabolized in the liver.
a topical solution was developed to treat hair loss. . Calcium normally enhances epidermal growth factors (EGF) and inhibits hair growth. It is a competitive inhibitor of androgen receptor protein binding. Estrogens are weak 5a-reductase inhibitors. weight gain. The 5% solution has not yet been approved for women. thereby reducing circulating free T.90 Spironolactone is effective mostly for hirsutism. Minimal increases in serum potassium may occur.91. the 2% solution was approved in 1991. menstrual irregularity. In men with AGA. estrogens may help to maintain the status quo and to slow the progression of AGA. 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. but it has been used worldwide by many dermatologists for many years.66 Since one of its sideeffects is hypertrichosis.Androgenetic alopecia 105 Side-effects include depression. breast tenderness and loss of libido.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. For women. Biologic response modifiers Minoxidil Minoxidil (Rogaine™) was the first agent shown to promote hair regrowth. Its exact mechanism of action is still unclear. nausea. It is a piperidinopyrimidine derivative that is used orally as an antihypertensive drug.89. Local vasodilatation does not seem to play a major role in hair growth. Small open trials have shown some clinical effect in AGA.93 but appear to have little effect on stimulating regrowth.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).99 Minoxidil was approved for men by the FDA as a 2% solution in 1988 and as a 5% solution in 1997. and 200 mg per day is usually required. thus opposing the entry of calcium into cells.95 Another possible mechanism of action is the opposition to intracellular calcium entry.17 Spironolactone: Spironolactone is an aldosterone antagonist.84. although no controlled studies have been done. They also inhibit secretion of luteinizing hormonereleasing hormone (LH-RH) by the hypothalamus.98. and interferes with the translocation of this complex into the cell nucleus.90 It also depletes the cytochrome P450 enzyme (CYP 450) complex. The main side-effect is menstrual irregularities.89. which is a potassium channel agonist and enhances potassium ion permeability. reducing androgen synthesis by the gonads. It does not appear to have either a hormonal or an immunosuppressant effect.98 This would decrease EGF and subsequently enhance hair growth. 97 Minoxidil is converted to minoxidil-sulfate.97. Clinically. which weakly inhibits androgen biosynthesis in the adrenal glands. a double-blind.85 The drug is less effective in female AGA.92 but Spironolactone rarely offers the benefit of hair regrowth.96 It has also been shown to prolong the survival time of keratinocytes in vitro. and its anti-androgenic effect is only mild. Both solutions are available without a prescription in the United States.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.94 Minoxidil increases duration of anagen and enlarges miniaturized and suboptimal hair follicles. but are uncommon.85. placebo-controlled trial.
9% with placebo. this may not be an issue. For some patients. approximately 30–35% of patients. In patients with very early AGA.1 The major increase is usually seen within the first 4 months of therapy.104 The hair loss becomes stabilized after the initial period of regrowth.100 Clinically.1 Minoxidil should be used for one full year before its efficacy is assessed.108 Twicedaily application is needed for efficacy. he will not know whether it is either minoxidil. found that topically minoxidil solutions of both 2% and 5% were significantly more effective than a placebo lotion or no treatment. not a hair lotion. double-blind placebo-controlled study of 256 women between the ages of 18 and 45 with AGA. 63% who applied 2% topical minoxidil solution twice daily showed minimal to moderate regrowth using hair counts in macrophotographs for assessment. is a reasonable option. compared to 25% with the 2% solution. while both the placebotreated men and the untreated men had an approximately 6% decrease in hair weight per year. since most of the sprayed solution will be applied on the hairs. physicians must rely mostly on the patient’s impression.103 In a multicenter. it is hard to appreciate any regrowth or hair loss because of the great hair density. In those cases.65 The 5% solution produced a 35% increase in hair weights. Therapeutic efficacy is evaluated by patient satisfaction and physician comparison with a baseline photograph.17 Patients must be told that minoxidil solution is a scalp lotion. Minoxidil can be used for either frontal or vertex scalp thinning. topical minoxidil solution must be continued indefinitely. one study of 32 weeks used hair weights to assess efficacy.17 No more than 2 ml should be applied every day.101–107 The rapid loss of hair weight after treatment confirms its trichogenic effects. finasteride or the combination that is having the effect.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.5% increase was found with the 2% solution compared to 1. 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. if affordable. double-blind study involving 2294 men between the ages of 18 and 50. The spray applicator is not recommended. For someone with moderate amounts of hair. where it is ineffective and thus wasted.106 Hair Loss: principles of diagnosis and management of alopecia using hair weight measurements.109 One study in the stump-tailed macaque showed additive benefit in using both minoxidil and finasteride.65 In women. showed moderate to dense regrowth as assessed by hair counts using macro-photographs. applying 2% topical minoxidil solution twice daily.108 The increase in density is mostly due to miniaturized hairs that are converted into terminal hairs rather than a de novo regrowth. every day in order to be effective. and combination therapy.110 but there are no data on this combination therapy in humans. In a multi-center. For those male patients already using minoxidil and wanting to switch to finasteride. Twenty-five drops (1 ml) must be applied directly on to a dry scalp and then slightly spread with the fingers.65 The major increase in hair weight was observed within the first 20 weeks following initiation of therapy. and a 42. Practically. . One millilitre of minoxidil solution must be used twice daily. if one starts both medications simultaneously in a male patient. the best mode of application is to divide it into 5 parts and apply 5 drops to each part. Thus. loss of hair is evident once treatment with topical minoxidil is discontinued. regardless of the extent of the affected area. Minoxidil application halted hair loss over the 96 weeks.
probably due to the propylene glycol in the vehicle. the concentration should be lowered to 2%. Minoxidil is poorly absorbed after topical application on normal intact skin.80 Minoxidil is secreted in human milk.80 If patients experience an irritant contact dermatitis due to the 5% solution. and side-effects are mainly dermatologic.17 Occasionally.1.103 Contact with any mucosal surface (usually the eyes) should be avoided. because it will cause burning and irritation. thoroughly rinse the eyes with cool tap water. minoxidil itself causes an allergic contact dermatitis. (b) Lateral view. but it is possibly either through a systemic effect or via a transfer of .80 Only 0. The maximum oral daily dose for the treatment of hypertension is 100 mg. but in humans data are lacking.32 Hypertrichosis of the face can occur in women using topical minoxidil solution.5% reaches the systemic circulation. Each ml of the 5% solution contains 50 mg of minoxidil. (a) Frontal view.1.103 Minoxidil should not be used by pregnant or nursing women. and may be slightly higher with the 5% solution.80 It is metabolized in the liver and excreted in the urine.80 Accidental ingestion of topical minoxidil could lead to serious adverse effects.80 Topical minoxidil solution is very safe.80 The effects of concomitant occlusion or abnormal skin are unknown 80 . The percentage of minoxidil that is absorbed is eliminated within 4 days. and is usually not a problem in men. Facial hypertrichosis (Figure 3.80. If they again develop dermatitis on the second trial.80 There is no evidence of teratogenicity in rats and rabbits.17. Patients will be unlikely to develop a tolerance to this side-effect. Studies have not shown any change in blood pressure or any other hemodynamic effect. and the treatment may have to be discontinued altogether.111–113 Incidence of scalp irritation is approximately 7% with the 2% solution. they should stop the treatment until all symptoms have resolved. The most frequent side-effect is an irritant contact der- matitis. but minoxidil solution should be used with caution in patients with cardiovascular disease. If such an event occurs.17 It is not clear yet why the hypertrichosis occurs.3 to 4.32) may occur in 3–5% of women.Androgenetic alopecia 107 Figure 3.
For those with more advanced hair loss and a poor donor area. An algorithmic approach to AGA in women.35). In women with stage I or II hair loss.e. or hair transplantation if the patient has a good occipital scalp donor area. then it is continued for as long as hair loss is perceived to be important to the patient. seborrheic dermatitis.116 However. menstrual irregularities. 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. For women with Ludwig stage III. Treatment of AGA in women Many factors must be considered in the treatment of AGA.5% minoxidil. as they can give excellent results. during the day. the irritation of tretinoin is not always well tolerated. Rogaine® and Retin-A®.116 A small study on men with AGA showed some hair regrowth when treated for 1 to 2 years with a combination solution of 0.114 It promotes angiogenesis115 and increases percutaneous absorption by affecting the fluidity and the lipid composition of cell membranes. It is a potent cell mitogen that promotes and regulates epithelial cell growth and differentiation. topical therapies are usually ineffective. hirsutism. are incompatible and become ineffective if compounded in the same solution. In addition. A partial hairpiece may also give a natural and satisfying appearance. If patients respond to treatment. If there is any sign of virilization (i. Even though there seems to be some benefit in using the combination. is presented in Figure 3. Hair transplantation in female AGA will be discussed in Chapter 4. Hyper-androgen excess should be checked by history and physical examination. formulated using generic powder forms. If ongoing hair loss is detected after 1 year. a hairpiece is suggested.17 It affects mostly the forehead. already have mild hirsutism are more likely develop this side-effect. severe acne.108 Hair Loss: principles of diagnosis and management of alopecia the drug. prior to treatment. topical 5% minoxidil solution is offered and continued for 1 year (Figures 3.025% tretinoin and 0.114 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. structured about the Ludwig classification. malar areas.17 Those women who. Hypertrichosis is totally reversible upon discontinuation of the drug. making this combination an impractical option for most patients. serum testosterone and dehydroepiandrosterone-sulfate (DHEAS) tests should be ordered and referral to an endocrinologist may be indicated. Patients often need guidance as to where to get hairpieces. Rogaine® must be applied every morning and night and Retin-A ® during the day. and sides of the face.34. Patients should be reassured on the cosmetic appearance of hairpieces.17 They must either be mixed using generic powder forms or be applied as separate treatments. patients may be offered androgen blockade with CPA or spironolactone. the proprietary products.33. Tretinoin Tretinoin (all-trans-retinoic acid) is a biologic response modifier. and it is most appreciated when they are given a few options.17 Thorough hand-washing after each use may minimize irritation and possibly hypertrichosis in other body areas. or infertility). most patients are not compliant with the need for an extra application . 3.
An algorithmic approach to male AGA. If evaluation reveals stabilization or regrowth. Treatment of AGA in men For men.37). In those with less severe hair loss and numerous miniaturized hairs.36.33 An algorithmic approach on the treatment of female AGA: UCSF-UBC Treatment Protocol for androgenetic alopecia in women (courtesy of Jerry Shapiro. structured around the Norwood- Hamilton classification.Androgenetic alopecia 109 Figure 3. patient age. MD. MD and Harvey Lui.Price. is outlined in Figure 3. such as the extent of hair loss. medical therapeutic options include finasteride or minoxidil (Figure 3. the presence or absence of miniaturized hairs. then patients are counseled to continue with treatment for as long as they feel hair loss is im- . preference for topical or systemic therapy. MD). Therapeutic efficacy is evaluated at 1 year (Figure 3.38). the final decision is based on many factors. financial considerations and patient expectations. Vera H.
35 A 53-year-old female with AGA (a) before topical minoxidil solution. then a surgical approach or a hairpiece should be discussed.110 and can be prescribed to very motivated patients. Figure 3.34 A 40-year-old female with AGA (a) before topical minoxidil solution. In those with more advanced hair loss and few miniaturized hairs. If ongoing hair loss occurs despite treatment. It is . Studies are currently under way evaluating the effect of finasteride on the number of hair transplantation sessions. showing marked improvement. portant to them.110 Hair Loss: principles of diagnosis and management of alopecia Figure 3. and (b) after 8 months of topical minoxidil solution. showing marked improvement. medical therapy is unlikely to work. Combination therapy with both finasteride and minoxidil has been shown to have additive hair regrowth effects in a balding stump-tail macaque model. and (b) after 6 months of use of topical minoxidil. with narrowing of her part/ parting. and a surgical approach or a hairpiece is recommended.
37 A good candidate for medical treatment of male AGA (note the presence of miniaturized hair). Vera H.Price. MD. MD and Harvey Lui. MD).Androgenetic alopecia 111 Figure 3. . 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.
A 33-year-old male with AGA (c) before the use of finasteride 1 mg/day and (d) after 11 months of therapy.38 A 24-year-old male with AGA (a) before the use of finasteride 1 mg/day and (b) one year later. patient impressions . showing improvement. Patient monitoring How is response to therapy assessed. likely that the combination of the two will reduce the number of sessions. showing improvement.39). This author recommends finasteride on all patients undergoing hair transplants if they are Stage IIIV–V pre-transplantation (Figure 3. and what methods can be used to determine treatment success or failure? First.112 Hair Loss: principles of diagnosis and management of alopecia Figure 3.
Both patient and physician should realize that these uncontrolled snapshots are not accurate. New Jersey. (b) The same individual 12 months after the use of finasteride 1 mg/day. In men. each patient has digital photography taken at a standardized distance and position (Figure 3. Unfortunately. Photographs do not need to be taken annually. Ideally. The photograph is reviewed with the patient at each follow-up and compared to current hairgrowth status. then an ordinary photograph should be taken.39 (a) A 35-year-old male with two previous sessions of hair transplants. thereby imparting some kind of objective measurement of response. the last transplant four years before the photo. showing significant improvement. The key features to distinguish between are prevention and regrowth.40 Digital photography with a stereotactic device (Canfield Scientific. serial part diameters can be taken from the same areas of the scalp with each visit. Figure 3. many patients are often unreliable and unsatisfied with subjective estimates. If one does Patient expectations are an important factor when discussing therapeutic options and goals.Androgenetic alopecia 113 Figure 3. but do give a general impression of the kind of coverage present at baseline. USA) is ideal as a means for monitoring patients.40). Finally. He was considering another session. This patient felt he did not need another transplant session. those . Matching therapy to patient expectations are determined. not have a digital set-up with a stereotactic device. Expectations are largely dictated by the extent of hair loss.
Hair Loss: principles of diagnosis and management of alopecia
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.
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.
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-
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
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
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
327(17):1185–91.. Unger W. Miller B.Androgenetic alopecia 117 55. Hamilton J. South Med J. Lancet. Br J Dermatol. 1994. Drake L. Hawk E.. pp. 356(9236): 1165–6.. J Steroid Biochem Mol Biol. Disorders of Hair Growth. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia [published erratum appears in J Am Acad Dermatol. 1994. 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. and Strauss P.L.H.. James K. 1992. finasteride. Roberts J.T.. Bruskewitz R.T. androgenetic alopecia as a marker of insulin resistance [letter] [in process citation]. Stoner E. J Am Acad Dermatol. 68. et al. 58. Propecia: New Clinical Data—Five Year Experience. 1977. Abstract. 1983..C. Semin Cutan Med Surg. Cancer Epidemiol Biomarkers Prev. 8:24–33. Fiedler V. Sadick N. Olsen. and Mortimer C. 1999. E. or no treatment.I. Sanchez M.A. 257–279. Inc. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. 101(4):455–8. 1951. 72. Ludwig E. 60. 59. after 66. 1998.. 74. Leyden J. Price V. et al. 37(3): 375–8.A. Novel agents for the treatment of alopecia. J Am Acad Dermatol. 53:708–28. 64. 41(4):550–4. 62. 1990. application of 5% and 2% topical minoxidil. Dermatol Ther. 1999.. 1984. 71. New Engl J Med.E. Finasteride in the treatment of men with frontal male pattern hair loss [see comments]. Dallob A. 79(3):703–6. Hordinsky M. 1993. 1998. 29(4):554]. The effect of finasteride. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. 41(5 Pt 1):717–21. 1975. Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the first National Health and Nutrition Examination Survey.J. Breslow R.C. et al. Cooke N. 17(4):276–83. J Am Acad Dermatol.. 1999. 56.C. J Am Acad Dermatol. a type 2 5 alpha reductase inhibitor in men with male pattern hair loss. 68(11):1359–65. Clinical dose ranging studies with finasteride. The Finasteride Study Group [see comments]. 41(4):555–63.. 1999. Sawaya M.. 1979. In European Academy of Dermatovenereology Annual Meeting. and Graubard B. 1993 Oct. 65. 67. J Am Acad Dermatol. Stoner E. Male pattern alopecia and coronary artery disease in men. 1999. Male pattern baldness: classification and incidence. The unit area trichogram in the assessment of androgen-dependent alopecia. Whiting D.. Br J Dermatol.. 4(3):282–4. 70.S. The effect of finasteride in men with benign prostatic hyperplasia. 2000. Transverse microscopic anatomy of the human scalp. 63.D.. 97(3):247–54. 73. et al. Gormley G. Waldstreicher J. 109(4):429–37. . 69. Norwood O.. J Clin Endocrinol Metab. Scalp biopsy as a diagnostic tool in androgenetic alopecia. J Invest Dermatol Symp Proc. The clinical development of a 5 alpha-reductase inhibitor. 28(5 Pt 1):755–63. New York: McGraw-Hill.. Whiting D. Br J Dermatol. 9(5):523–7. 40(6 Pt 1):930–7. a 5 alpha-reductase inhibitor. Menefee E. Ann NY Acad Sci. 57. ed. 61. et al. Arch Dermatol.A. Dunlap F.H. Changes in hair weight and hair count in men with androgenetic alopecia. and Kaufman K. Rushton H.. placebo.T. Patterned loss of hair in men: Types and incidence. Oct 2000.. on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. Geneva. Whiting D. Olsen E. A basis for a morphometric approach to disorders of the hair follicle. Headington J. 120(4): 449–56. 2000.
78. Rushton H.. Serafini P.H.. Quantitative assessment of spironolactone treatment in women with diffuse androgen-dependent alopecia. Treatment of hirsutism.H.. Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. Abdel-Salam M. Dermatologica. Fuh V. Dermatologica. and Ruedi B. Oral spironolactone therapy for female patients with acne. 76. et al. In Compendium of Pharmaceuticals and Specialties (CPS) 34th Edition. and Kubilus J. 143(4):804–10. Roberts J.118 Hair Loss: principles of diagnosis and management of alopecia 75. J Invest Dermatol. Pharmacology and potential use of cyproterone acetate. et al. Ottawa.. Improvement in androgenetic alopecia in 53–76-year-old men using oral finasteride. Int J Dermatol... Shaw J. Kan H. comment]. Gould J. 1996. et al. Neumann F. Br J Urol. 81. hirsutism and virilism. 1983.P. 1985. et al.M.. Minoxidil stimulates mouse vibrissae follicles in organ culture [letter. Matzkin H. Local therapy of androgenetic alopecia with 17 alphaestradiol.. 1977. Clin Exp Dermatol. Guenthner T.. hirsutism or androgenic alopecia [letter]. 86. 91. Fertil Steril. with cyproterone acetate. 1999. 96(2):295–6. et al. Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.E. Hordinsky M... Clinical applications of antiandrogens.. 43(5): 768–76.H. and Vogels L. 38(12):928–30. Price V. Rushton D.. and Schell H. 1979. randomized doubleblind study. J Steroid Biochem. 1999. Price V. Khoury E.. Namer M. 1999. 89. Studies on the destruction of adrenal and testicular cytochrome P-450 by spironolactone. . et al. Brussels. Ekoe J. Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia.. Use of cyproterone acetate (CPA) in the treatment of acne.H.H. 161(2): 124–32. Requirement for the 7alphathio group and evidence for the loss of the heme and apoproteins of cytochrome P-450. The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women. 6(6):827–36. Langer P. Antiandrogen therapy in dermatology. Effective medical treatment of common baldness in women.A. 94. 1996.H.C. J Steroid Biochem. 92. Meckies J.. and Cunliffe W. Lobo R. 1991. Overstreet J.. 88. Effect of finasteride on free and total serum prostatespecific antigen in men with benign prostatic hyperplasia. J Biol Chem. Orfanos C. 95.R. Br J Dermatol. Leo-Rossberg I. 99(1):40–7. Amsterdam. 1988. Van Neste D. Price V. 162(4):1295–300.J. 83. 9(1):1–13. Presentation at European Academy of Dermatology. Br J Dermatol 2000. 1999. 1984.. Mortimer C. Baden H.W. and James K. 1992. 35(11): 770–8. J Invest Dermatol. 1985. 78(3):405–8. A controlled. 80.L. 254(5): 1726–33. 2000. Effect of minoxidil on cultured keratinocytes. Finesteride increases anagen hair in men with androgenetic alopecia.L. J Urol. 85. Menard R. Olsen E. 93. 160(6):398–404. 90. Int J Dermatol. and Braf Z. Shoupe D. 42:317.. Canada..M.. 1998. 1980..L.C. 84. 43(2): 200–5. Canadian Pharmacists Association Monography. 31(4B):719–29. Kiesewetter F. 81(6):558–60.. Barak M. and Gillette J. 82. Changes in hair weight in men with androgenetic alopecia after taking finasteride. Roberts J. acne and alopecia 87. and Matz H. Price V. J Invest Dermatol. Burke B. 112(1):124–5. Belgium. Burckhardt P.M. 9(4):342–50. Horm Metab Res. Hammerstein J. 1975. 1991. The effects of finasteride on post-menopausal women with androgenetic alopecia. J Am Acad Dermatol.. 96. 1980. 77.. J Soc Cosmet Chem.M. Minoxidil and Finasteride. In Hair Workshop. Brenner S. et al. 79.
DeVillez R. Walkden V. J Am Acad Dermatol.A.. Powell S. Weiner S. Bardazzi F.R. J Am Acad Dermatol. 22(4):643–6.S. 1987. Contact dermatitis in reaction to 2% topical minoxidil solution. J Am Acad Dermatol. and Kealey T. Contact Dermatitis.A.. Clin Exp Dermatol. 1992. Olsen E. Roberts A. Hair loss with minoxidil withdrawal [letter]. Olsen E.B. 102. Amsterdam: Elsevier Science. et al. and Menefee E. and Pinnell S. 1991. Topical minoxidil in male pattern baldness: effects of discontinuation of treatment. et al. Natural history of androgenetic alopecia. Ohtsuyama M..P. a steroid 5 alpha-reductase inhibitor. Epidermal effects of retinoids: supramolecular observations and clinical implications. 1987. et al. 104. and Weiner M. J Invest Dermatol.. Olsen E.R.H.S. Olsen E.. 13(4):275–6. 111. 1985. p. 101.A. Contact Dermatitis. et al. J Am Acad Dermatol. 481. 1985. 1994. Amara I. Olsen E.A. 14(4):595–607.R. 17(1):97–101. Mechanism of action of retinoids.S. androgenetic alopecia in women: effect of minoxidil.S. 1996.L. 109. Minoxidil sulfate effect of internal calcium of cell in the epidermis and epidermal appendages. Res Staff Phys. Contact dermatitis to minoxidil. 114. Treatment with 2% topical minoxidil solution. 1991. 1986. 1995.R. ed. V. Elias P. 100. Bazzano G.. De Padora M. Wilson C. J Am Acad Dermatol.. 98. Hair growth effects of oral administration of finasteride. 105. alone and in combination with topical minoxidil in the balding stumptail macaque. Buller T. 890–3. J Am Acad Dermatol.Androgenetic alopecia 119 97. 106.B.J. 32(5):316–17. 1989.R. Sanders D. Shull K.D. Topical tretinoin for hair growth promotion.A. J Invest Dermatol. Diani A. Weiner M. 340(8819):609–10. J Clin Endocrinol Metab. 103. J Am Acad Dermatol.. and Galen W.E.. 96(5): 73S–74S. 115.. et al. Five-year follow-up of men with androgenetic alopecia treated with topical minoxidil. Olsen E.S. Dermatol Clin. Topical minoxidil in early male 107. Treatment of androgenetic alopecia with topical minoxidil solution. 1986. Ebner H. Philpott M. and Muller E. Kidwai B. 15(4 Pt 2):756–64. 112. and George M. Terezakis N. 16(3 Pt 2):688–95.A. 1986.A. DeLong E. Olsen E. Cutis..P.M.A. 99. pattern baldness.R. 15(4 Pt 2):880–3. Sporn M. and DeLong E.. I. 108..R.L. 110. 95(6): 683–7.J. Quantitative estimation of hair growth. 113.. Mulholland M. 35:53. .. 1990. Weiner M. DeLong E. Androgenetic alopecia in the female. In Hair Reseach for the Next Millennium. 1996. Lancet. 1991. 1990.. 15(4 Pt 2):797–809. Arch Dermatol.. 130(3):303–7. 116. DeLong E. Price V. Whole hair follicle culture.....Van Neste. 74(2):345–50. 1990. 13(2 Pt 1):185–92. 15(1): 34–6.S. Topical minoxidil in the treatment of androgenetic alopecia in women. 24(4):661–2. and Weiner M. Buhl A.A. Allergic contact dermatitis from minoxidil. Tosti A. Roche N. J Am Acad Dermatol. Long-term follow-up of men with male pattern baldness treated with topical minoxidil. 48(3):243–8. Minoxidil’s action in hair follicles.. 1992.
Note the unnatural corn-row tufting of hair surgery performed in the 1960s and 1970s. These hairs are unlikely ever to become vellus-like. Figure 4. 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). (d). (b). .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.
4.3) and anesthetized using the tumescent technique (Figure 4.2.3 It has been shown that tumescent anesthesia significantly reduces the total . The field of hair transplantation has changed markedly within the past 10 years (Figure 4. Figure 4. and (3) the use of slits for the recipient area have revolutionized the field of hair transplantation. as this is the most commonly performed surgical procedure for androgenetic alopecia (AGA). and is the basis for the success of hair transplantation.2 This chapter will discuss hair transplantation as it is performed at the University of British Columbia Hair Clinic. The tumescent technique involves the injection of large volumes of very dilute lidocaine and epinephrine.4). more natural-appearing grafts. This is termed donor dominance of the grafts.2 Donor area is chosen in the occipital portion of the scalp. The advent of (1) strip harvesting for the donor area. This anesthetic approach was first developed for patients undergoing liposuction.3 Donor area at the back of the scalp is trimmed. (2) the introduction of finer.1). The chapter will deal solely with hair transplantation.122 Hair Loss: principles of diagnosis and management of alopecia Figure 4.1. The donor site The selected donor area is initially trimmed (Figures 4.4 Donor area is injected with tumescent anesthesia. Figure 4. There are many differing approaches to hair transplantation. and these are discussed thoroughly elsewhere.
it can cause unnecessary harm to underlying arteries and veins. Approximately 6–7 injections are performed with an action pump syringe and a 25 gauge needle into the trimmed occipital area. number of milligrams of lidocaine required and maximizes the vasoconstrictive benefits of epinephrine. This angle is crucial and varies from 100 to 120 degrees. A multi-bladed knife with #10 Personna blades is angled parallel to the hair shafts (Figures 4. If the angle is not pre- . 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.Surgical management of androgenetic alopecia 123 Figure 4. Any ‘hot spots’ that are not completely anesthetized can be further anesthetized with small amounts of 2% lidocaine. repeat injections of anesthesia are given to the patient’s donor area. The hair follicle with its dermal papilla usually extends to a depth of 4–6 mm. and varies from 100 to 120 degrees. This increases skin turgor in the area and allows easier visualization and excision of the donor area. It is important to keep this in mind when harvesting strips.5b). If the angle is not precise there will be considerable follicular transection and subsequent follicular wastage. Constant monitoring of the angle is necessary. Any curly hairs will also become more ‘straightened’ with this increased turgor. Harvesting with strips as opposed to punches allows for more efficient harvesting and better cosmesis. If an excision is too deep. thus decreasing bleeding.4 A solution prepared by adding 25 ml of 2% lidocaine without epinephrine. and as a result are less likely to be later transected.5 (a) Multiple-bladed knife is prepared. Tissue more than 1 mm below the dermal papilla is not necessary for transplanting.4% sodium bicarbonate solution and 0. (b) The blades are angled in the direction of the hairs. A mandatory period of 20 minutes is required for the anesthetic to have its full effect in terms of anesthesia and vasoconstriction. This angle is crucial.5a and 4.5 ml of 8. 2.
For an average megasession involving considerably more harvesting.75 mm width are excised. three strips of 2. Figure 4. The strips are released at the ends with a V shape and from underlying tissue with a #15 Figure 4. Personna scalpel blade (Figures 4. at the University of British Columbia (UBC) Hair Clinic.7. This will usually yield 1100–1350 grafts on average.5 mm strips taken for a total width of 1 cm. This is done meticulously. For an average regular session.5 mm for a megasession. with four 2. 4. Small bleeders can be cauterized or tied off with 3–0 Vicryl absorbable sutures.0 cm in width.75 mm-1. Strips vary in size depending on whether it is a regular or a megasession.6.124 Hair Loss: principles of diagnosis and management of alopecia Figure 4. with avoidance of any kind of ‘sawing’ motions. After the stab incision.25 mm each for a total of 6.8). cise there will be considerable follicular transection and subsequent follicular wastage. blades are maintained at a constant depth.25 mm are removed with a regular session or four strips of 2. 4. Usually three strips of 2. .7 Strips are released from the rest of the scalp with a #15 blade. This will yield an average total of 600–800 grafts. Most strips are 12–16 cm in length.8 Strips are removed with a V shape at the ends.6 Strips are excised from the donor area. Length is usually 10–14 cm. the strips will usually be longer and wider. The surgical defect will range from 6. The width of each strip varies for each individual. so as not to harm the lower portions of the follicle as well as not injure any underlying blood vessels.
and it was not discovered until he returned two years later for his subsequent second session. usually with a diameter of 1–2 mm (Figure 4. However. This particular Asian patient did not mind the keloid.5 The resulting scar is linear. Alternatively. as it was well camouflaged by his donor hair. . ethnicity and scalp elasticity. and as a result prefer closure by a continuous suture (Figure 4. certain centers have found the exactly the opposite. another scar can be created above or below the previous Figure 4. We have found that sutures are more confortable than staples for the patient. wider strips are necessary. (b) A rare complication of the donor area is the formation of a keloid. if an individual’s scalp is too tight. AfricanAmericans in particular usually have a lower scalp follicular density and frequently require a greater total width of strips. He did not inform our center of this complication. The donor site is sutured with blue nylon 3–0 Novafil. hair density.10). These scars can be excised at subsequent sessions.9 The surgical defect is closed with a continuous stitch.9). Larger areas of alopecia will require greater coverage and thus larger strips.Surgical management of androgenetic alopecia 125 Figure 4. leaving only one final scar. which is more commonly seen in African-Americans or Asians. The size of the strips taken varies according to how much area needs to be covered. However. Keloids can subsequently be treated with intralesional corticosteroid. the total width of strips removed will be lessened.10 (a) The scar 6 months after the procedure. If donor follicular density is low. and just use staples.
and any scar tissue (especially from a previous transplant) is removed (Figure 4. one. It is essential that during this whole process strips and grafts are not permitted to dry out and are well moistened with saline.10b) wound dehiscence.14). Because of the natural appearance of the small grafts. Appropriate magnification is necessary to perform this. Stough has presented guidelines.12 Much of the fat is trimmed away.11 Strips are placed on a tongue depressor and are sectioned with a #10 blade into smaller grafts. This is performed by meticulous dissection of the strips with a #10 Personna blade and fine jewelers’ forceps (Figure 4. facial framing is frequently what the patient wants. which must have a prerequisite length of 2 cm.11).13 and 4. 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). the patient is not committed to have to continue through many sessions to get that final natural look. grafts are grouped according to size and density on Petri dishes on ice (Figures 4. Figure 4. and paresthesias. hair without matrices. All of this is camouflaged nicely by the patient’s hair. and include keloid formation (Figure 4. During preparation. This is drawn in before the surgery.12). The most obvious advantage of using these small grafts is the elimination of tufting reminiscent of the old grafts. The recipient area In the frontal area. Complications in the donor are very rare. leaving only 1 mm of fat underneath the follicle.126 Hair Loss: principles of diagnosis and management of alopecia Figure 4.6 At . Excessive amounts of fat. and must be discussed at length with the patient. Positioning the hairline is critical.
Surgical management of androgenetic alopecia 127 Figure 4. . On lateral view. The hairline is drawn onto the recipient area.13 Grafts are subdivided into micrografts containing single hairs (bottom) or minigrafts with single follicular bundles of 2–3 hairs (top). Figure 4. the area marked is always parallel to the ground and on the flat portion of the scalp (Figure 4.15b). the UBC hair clinic we mark an area 8–11 cm midline above the glabella and create a curved.15a).15 (a) and (b). Figure 4.14 The grafts are grouped on to Petri dishes according to the number of hairs per graft. bell-shaped hairline (Figure 4.
5 or 2 mm spear tip.128 Hair Loss: principles of diagnosis and management of alopecia Figure 4.5 mm between the slits laterally and 1 mm anteriorly or posteriorly (Figure 4. They are directed parallel to the direction of the hair. 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 1.5 mm or 2. The majority of patients get satisfactory cosmetic results with 3 sessions of slit grafting in a totally bald area.16 On the vertex of the scalp.17). On the vertex. Usually we allow 1.17 Slits into the recipient area are made with an Ellis 1. Slits are made into the recipient area.5–2.18). the area is marked as to hair direction prior to the surgery (Figure 4. the hair direction is planned.18 (a) and (b). Figure 4. Those with pre-existing hair may only need 2 . Figure 4.0 mm spear tip on a handle (Figure 4.16).
Figure 4. Scalp after placement of grafts.19 and 4. A megasession increases coverage. sessions. with a total of 1100–1400 grafts. In the frontal area.21 (a) and (b). 600–900 total grafts are transplanted.19 Grafts are placed on to the fingers of the nurses. usually covering 30–50% of the anterior portion of the scalp. and allows the placement of grafts into the anterior portion as well as the vertex of the scalp. The remaining minigrafts are placed behind this frontal zone. Planting into the slits is done meticulously with jewelers’ forceps (Figures 4.20 Grafts are placed into slits with jewelers’ forceps. Figure 4.20).Surgical management of androgenetic alopecia 129 Figure 4. a zone of approximately 300 pure micrografts is created. Special care is taken not to harm any of the grafts. For a regular session. The hairs in the grafts are aligned with .
The grafts can be flush or slightly elevated above the surrounding tissue (Figures 4.36.22).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.25). The average patient with marked hair loss will receive on the average 3 sessions (Figures 4. The dressing is removed the next day. A regular session will usually take 5–6 hours. especially with megasessions.39a and 3. Patients are warned of a telogen effluvium that can occur with the transplanted grafts as well as with pre-existing recipient hair.130 Hair Loss: principles of diagnosis and management of alopecia Figure 4. This allows the transplanted hair to grow in visibly and allows us to visualize where to put the new set of grafts. A megasession may take 6–8 hours to complete. Patients leave the office with a moist dressing covering the donor and recipient areas (Figure 4. 3. Patients are warned appropriately and are told to expect it.23–4. Patients must wait for up to six months to see the full benefits of a hair transplant. 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. This would logically reduce the number of sessions necessary. If the facial edema does not then happen. It is best for patients to take one week off work. We frequently recommend our male patients with pre-transplant Norwood-Hamilton Stages III–V to take finasteride 1 mg daily. There also is a possibility of regrowth as well as in the patient illustrated in Fig. Graftcyte® dressings are placed over the recipient area. then this becomes a bonus for the patient. Finasteride and hair transplants the appropriate angle and direction fitting directly into the slits. . after one week virtually all crusting will have disappeared.21b).22 Post-operative dressing covering donor and recipient area.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 may stabilize any further thinning of pre-existing hair in the recipient area. With appropriate postoperative care and daily shampooing.21a and 4. (See Figures 3. Facial edema beginning 48 hours after the procedure and lasting for 5 days is certainly common. We perform repeat sessions after a minimum of six months between sessions. A full working schedule and exercise can be resumed 1 week after the procedure.
1 year later. A 40-year-old male prior to hair transplant. after two regular sessions. (b).Surgical management of androgenetic alopecia 131 Figure 4. the occipital donor area may be affected. Two years later.24 (a). A 27-year-old male prior to hair transplant. Atleast 30% (in the author’s experience) have significant thinning in the donor area and are not good candidates.23 (a). It is area. (b). 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 . Hair transplantation in Women Because AGA in women may be more diffuse. Figure 4. important to choose the appropriate fe- male surgical candidate. after four regular sessions.
25 (a). In such cases the patient will experience effluvium of both the transplanted hair and her preexisting hair. Side view of the same patient before hair transplant. mini-grafting and strip harvest- . she is not a candidate for hair transplant surgery. (d). If she is not able to accept this fact. but frequently will still occur even then. Micro-grafting. (c). A 43-year-old male prior to hair transplant. 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. (b).132 Hair Loss: principles of diagnosis and management of alopecia Figure 4. daily. Conclusion Hair transplant surgery has become very popular. then she will be prepared emotionally. Two megasessions and a regular session and 3 years later. and will feel that her situation has worsened significantly compared to her pre-transplant state. Side view after hair transplant. as its results are cosmetically very natural.
pp. Stough D. J Am Acad Dermatol 1987. Determination of hairline placement.Klein. dermabrasion. ed. 139–49. 7.D. The donor site. Missouri: Mosby. Combination medical therapy with systemic finasteride or topical minoxidil solution may certainly add to the cosmetic result. Stough D. D.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. 425–9. 6. A pilot study. 1996.A. D. Klein J. 1996: St Louis. pp. 3. Unger W.J. St Louis. Missouri: Mosby. 2.Stough. References 1.Stough.P. 1st edn. 3rd edn. Use of the tumescent technique for scalp surgery. 4:263–7. 5. Coleman W. Use of topical minoxidil as a possible adjunct to hair transplant surgery. J Dermatol Surg Oncol 1992. St Louis. 16(3 Pt 2):685–7. . Stough D. 1996. In Hair replacement surgical and medical. Kassimir J. ed. In Hair replacement surgical and medical. and soft tissue reconstruction. Hair replacement surgical and medical. and J. New York: Marcel Dekker. Missouri: Mosby. 1995. 4. Am J Cosmet Surg 1987. Hair Transplantation. The tumescent technique for liposuction surgery. 18(2):130–5.
Drugs are capable of producing a wide spectrum of alopecia. from complete baldness to slight. Each human scalp follicle produces hair cyclically and behaves independently of neighboring follicles. The scalp itself is usually unremarkable. and so may go unreported or may be reported without adequate documentation. barely noticeable shedding. Repeated questioning may be necessary because of forgetfulness or ignorance. Following anagen. The telogen phase lasts for three . Drugs that cause alopecia The true incidence of drug-related alopecia is hard to determine accurately.5 Drug-induced alopecia Drugs can affect hair by causing alopecia. the loss of hair is considered to be trivial. but it is also true that they rarely see the vast majority of such patients—those receiving chemotherapy. and will detect any inflammatory process. Some drugs can cause a severe drug-induced lichenoid eruption of the scalp. a brief transitional catagen phase of two weeks leads to a metabolically inactive resting telogen phase. the axillary and pubic regions and the body may also be involved. Subtle cases can be difficult to detect. although the eyebrows. Female androgenetic alopecia (AGA) poses a real problem. The pattern of hair loss is almost always diffuse. because it is very prevalent and can co-exist with diffuse alopecia. Practicing dermatologists make the diagnosis infrequently. which lasts 4–8 years. This is all reviewed in detail in Chapter 1. The work-up for any patient with hair loss must include a thorough drug history. A scalp biopsy with obligatory transverse sectioning will give you the anagen-telogen ratio and the terminalvellus ratio. Certain laboratory tests such as scalp biopsy and blood work can be helpful in ruling out other causes of alopecia. and it is possible that many patients may lose small amounts of hair and never realize it. This will help rule out AGA and alopecia areata. The scalp follicle passes through a growing. 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. metabolically active phase known as anagen. A drug-induced alopecia can certainly unmask a tendency for androgenetic alopecia and accelerate the miniaturization process of AGA. except in rare instances. Even if they do notice it. One must understand the basic mechanisms of hair growth and cycling in order to understand drug-induced hair loss. as well as helping to confirm an anagen or telogen effluvium. Drug-induced alopecia is usually confined to the scalp.
136 Hair Loss: principles of diagnosis and management of alopecia months. During the anagen phase.4 The resultant hair contains fewer cells per unit length. Almost 90% of scalp follicles are in anagen. 10% in telogen. impede hair cortex formation and cause an anagen effluvium in almost 100% of patients. There are two mechanisms of drug-induced alopecia—direct and indirect effects. The intensity of damage to the cortex of the hair shaft depends on the drug dosage and the duration of its administration. in the clinical setting. the most common mechanism by far for drug-induced alopecia is the precipitation of catagen. because many diseases for which drugs are administered also produce a precipitation of catagen. after which the club hair is shed as the hair follicle initiates a new cycle. with hair fall beginning in 7–14 days (see Figure 5. and 1% in catagen. Scalp follicles are in differing phases of the hair cycle and are randomly scattered over the scalp. Continued treatment with a smaller constant dose produces a slow decrease in hair shaft diameter to a tapered point. Hair loss occurring a few days after drug intake indicates an effect on hair matrix cells. A small single dose will produce constriction of the hair shaft. precipitation of catagen. A large single dose that strongly suppresses mitosis produces a sharp point-constriction. In some cases. such as the eyebrows and eyelashes. 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. while catagen and telogen follicles are relatively safe.1) Cytostatic drugs Any drug that affects cell division can alter hair growth. namely bone marrow and mucous membranes. resulting in hair shaft damage. and the predominant effect may depend on the dose and timing of the administration. The hair breaks at the point of constriction. If one excludes anti-mitotics. is thin and breaks easily. Combined therapy with two or more anti-mitotic agents has a greater effect than a larger dose of only one agent. 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. the mitotic activity of the hair matrix is so high that it can be compared with the most actively kinetic tissues of the body. there is confusion. An example of such a dilemma is highlighted by Reeves and Maibach. are more likely to be affected by drugs than the regions of the body with the lowest percentage of anagen follicles. The regions of the body with highest percentage of anagen hairs.1). Drug-induced alopecia usually involves pharmaceutical alteration of the cycling process. Only the actively dividing matrix cells of anagen hairs are affected by cytostatic drugs. usually when they are actively growing. the percentage of hairs in anagen and telogen phases. Anagen effluvium (Table 5. The duration of anagen and telogen phases. Hair loss developing weeks to months after drug intake may be due to hair matrix effects. Direct effects include anagen growth interruption. Cytostatic drugs suppress hair matrix cell mitosis. especially . A spectrum of changes seems to occur. Follicles are susceptible to noxious agents. Of course. such as the scalp and beard. For this reason anagen hair matrix is highly susceptible to noxious events. and the density of the follicles will account for the varying severity of alopecia in different areas of hair growth. but may result from changes in keratin production or changes in the hair cycle. and disturbed keratinization.3.
chlormethamine (mechlormetha- mine). A 33-year-old female with lymphoma on dacarbazine.1 Drug-induced anagen effluvium46 in-patients subjected to multiple cycles of chemotherapy. Drugs that may aggravate alopecia when used in combination chemotherapy include chlorambucil. Figure 5. vinblastine and dactinomycin. bleomycin and hydroxy-carbamide.1 Anagen effluvium. cyclophosphamide. doxorubicin and vinblastine. vincristine. daunorubicin. bleomycin.Drug-induced alopecia 137 Table 5. thiotepa. (a) posterior view (b) lateral view . methotrexate. Alopecia most commonly occurs with the use of doxorubicin (adriamycin). Note the marked hair loss over the entire scalp. hair loss may be almost complete. fluorouracil. cytarabine.
Hairs were dystrophic and broken off 1–2 cm above the scalp. characterized by a relatively short onset—usually 3– 5 weeks. Cells with the highest rates of division are affected earliest. is shortened to just a few days. melphalan. Immediate anagen release (IAR). 5. has anti-mitotic activity operating through failure of spindle formation. hydroxyurea.8 Vasopressin Vasopressin. used in the treatment of gout. dacarbazine). Immediate anagen release probably characterizes most drug-related events. Cimetidine has also been implicated as causing DAR. thiotepa. 3. procarbazine. 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. a vasoconstrictor and anti-diuretic pituitary hormone. The mode of action is due to metaphase arrest. and may be reversible even if the drug is continued.5 Colchicine can produce diffuse hair loss in 1–10% of cases.6 Harms7 reported a case of diffuse alopecia that occurred after 2 months of colchicine therapy. 4.10 Three . All follicles in telogen may be susceptible. has been reported to cause alopecia by causing an anagen effluvium from cutaneous infarcts.9 of these types are related to events in anagen and two related to telogen. There is some good evidence that topical minoxidil solution may effect IMR. If anagen is decreased by 50%. The M phase of mitosis is affected greatly by vincristine and vinblastine. there is a corresponding doubling of telogen hairs. ifosfamide. 6-mercaptopurine and methotrexate. Those drugs that are S phase-specific include cytosine arabinoside. Etretinate may cause SA. Most of the cytotoxic agents are not phase-specific: these include alkylating agents (cyclophosphamide. and cisplatin. the clinical sign of increased shedding will be found. carmustine. if sufficient are involved. which may last 4–12 weeks. 2. All areas affected by anagen effluvium had normal hair growth after the medication was discontinued. as the affected follicles are promptly stimulated to cycle into anagen. Hair loss is dose-dependent. nitrosoureas. It may persist for 1–3 months. DAR is probably associated with postpartum hair loss and oral contraceptives. Delayed anagen release (DAR). Colchicine Colchicine.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. When follicles are finally released from anagen. 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. The five types are as follows: 1. Immediate telogen release (IMR): normal telogen. busulfan. characterized by a prolonged anagen rather than cycling normally into telogen. Follicles that would normally complete a longer cycle by remaining in anagen prematurely enter telogen. Shortened anagen (SA) occurs when the anagen phase is significantly decreased in time. antitumor antibiotics.
5) occurs in more than 10% of patients. The following list of drugs have been implicated as causing telogen effluvium (Tables 5. TE . and carbimazole. appears to be related to drug dosage. methylthiouracil. but reports of delayed-onset shedding with drug treatment might be a result of DTR. Anti-thyroid drugs that may produce telogen effluvium include iodine. No drugs have been implicated with this mechanism conclusively. Telogen effluvium is frequently associated with hair dryness and brittleness. Anti-coagulants All forms of anti-coagulants may induce hair loss. Anti-thyroid drugs Reversible alopecia is a constant finding in iatrogenic hypothyroidism. and tends to be more frequent in women (Figure 5. which occurs during treatment of thyrotoxicosis.2 Drug-induced telogen effluvium (incidence less than 1 %)46 fallout on the scalp.2).Drug-induced alopecia 139 Table 5.2–5. propylthiouracil. These include heparin and coumarins.
12–17 A review described 101 cases of lithiumrelated hair loss in over 25 years of use. A correlation between hair loss and lithium blood level and/or dosage is suspected. 11 Headington feels it is due to immediate anagen release. In most reports.19 Patients on lithium who develop alopecia must undergo a thyroid function assessment. 23% described their hair as also becoming straighter. However. since this drug is known for its ability to affect the thyroid gland. and may be noticed within weeks or years after commencing therapy.4 Meq/L.5 and 1. but not established.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 1.5 g/ day. doses ranged from 0. with serum lithium assays between 0. in those patients in whom the onset of the hair loss may take years. Hypothyroidism (commonly) and thyrotoxicosis (rarely) have been described in patients on lithium therapy. this mechanism is less likely.18 A 3year survey of lithium-treated subjects reported a 12% incidence of alopecia. who had high lithium levels.140 Hair Loss: principles of diagnosis and management of alopecia Table 5.3 Drug-induced telogen effluvium (incidence of 1–5%)46 Table 5. reported hair thinning.13 About 20% of patients on long-term lithium therapy. and both conditions may manifest with hair .
5 Drug-induced telogen effluvium (exact incidence unreported)46 .Drug-induced alopecia 141 Table 5.
2 Telogen effluvium. dissociates in the gastrointestinal tract into a salt or ionic form.0% reported frequency.23.25 It is not completely estabThere are 177 documented cases of carbamazepine-induced alopecia. (b) Lateral view. A 63-year-old female on warfarin showing general shedding.26 Valproate Carbamazepine Valproic acid (VPA).29 Carbamazepine and VPA possibly have different mechanisms of hair loss.18 with a 0.24 Patients on VPA who develop hair loss tend to have a high valproate blood concentration. illustrating marked thinning on the temporal area. Hair loss is not as marked as in anagen effluvium. showing a disproportionate number of telogen hairs. but usually dosage reduction leads to regrowth of hair in individuals with valproate-associated alopecia.27.22 This is probably coincidental. (c) Pathology of telogen effluvium. VPA and divalproex (a stable combination of valproate sodium and valproic acid) may cause hair changes. despite a documented decrease in serum amounts of zinc and copper caused by both medications.18 With a reported incidence of 1. lished whether alopecia is dose-related. A review of the literature mentions 643 cases of valproateinduced alopecia.21 There is a case report of alopecia areata occurring during lithium therapy. valproate.5%–12. with a slightly increased width of hair-part.6% and 6%. once ingested. (a) Top view.20.142 Hair Loss: principles of diagnosis and management of alopecia Figure 5.30 Some individuals may have an .28 A threefold dose reduction of 200 mg/day helped one female patient. changes.
generally do not result in alopecia.42 . There is no relationship between dosage and time of onset or severity of hair loss. Females are more commonly affected.33 and paroxetine in 30 subjects 18 The majority of these have a typical pattern of reversible diffuse alopecia.41 Tricyclic/tetracyclic antidepressants A few instances of diffuse hair loss associated with tricyclic antidepressants (TCA) have been documented. but also extends to eyelashes and eyebrows. with a 2–6 month latency period. Significant recovery is seen after 4–8 months from the time use of the solution is discontinued. Topical ophthalmic beta-blockers Topical ophthalmic beta-blockers can cause hair loss.36 Other anti-psychotics/anxiolytics Haloperidol. Sometimes alopecia may develop 1. Anxiolytic medicines of the barbiturate and benzodiazepine classes.5 years following fluoxetine introduction. In some cases. The utilization of lowdose estrogen contraceptives is only occasionally associated with this effect. Clonazepam is one exception. owing to the estrogens.31 The tetracyclic antidepressant drug maprotiline and trazodone may also result in hair loss. amoxapine. It may form a complex with zinc. a fluoxetine-induced alopecia was still evident 1. Fluoxetine is the most frequently prescribed anti-depressant. olanzapine and respiridone have been documented as causing hair loss.18 Sertraline has been reported in 46 instances.31 Buspirone is also associated with hair loss on rare occasions. Antihypertensive agents Several anti-hypertensive agents are known to cause hair loss. and protriptyline.37 This is believed by Headington to be a delayed anagen release. and with this there are 725 documented cases.32. Hair loss is not confined to the scalp alone.5 years after drug discontinuation. none of the monoamine oxide inhibitors are known to cause alopecia. particularly in those patients with renal disease. All TCA versions have been implicated with alopecia: amitriptyline.35 In another case. and thus decrease zinc levels. Pathogenesis is probably similar to that in post-partum hair loss. Serotonin reuptake inhibitors Several serotonin reuptake inhibitors can also cause hair loss on rare occasions. nortriptyline.34. telogen loss subsides despite continuing treatment. This sideeffect is reversible once medication is terminated. as well as zolpidem. imipramine. Oral contraceptives Telogen hair is lost 2–3 months after discontinuation of treatment with oral contraceptives.10 There is prolongation of the anagen phase. Beta-blockers may have a direct toxic effect on the hair follicles. doxepin.31 Interferons Telogen effluvium occurs in 20–30% of patients treated with interferons.31 However. Captopril can also cause hair loss.38–40 Low zinc levels can cause hair loss. It occurs 1–24 months after treatment.Drug-induced alopecia 143 increased genetic predisposition to medicinal alopecias. despiramine.
keratinization. Retinoid-induced alopecia has a later onset and is almost always reversible. unmanageable. Patients may temporarily Retinoids Soriatane and accutane can produce brittle. retinoids can certainly unmask a tendency for androgenetic alopecia.31 Cholesterol-lowering agents Agents that block cholesterol synthesis through a variety of mechanisms can disrupt . the negative implications of stopping or changing the regimen also need to be considered. rather than an immediate anagen release. but may be ingested accidentally in rodent poisons or contaminated foods. an informed patient and physician should discuss the risks and benefits of continuing.144 Hair Loss: principles of diagnosis and management of alopecia Keratin production interference Thallium Thallium is no longer used as a drug. Such choices are especially difficult when the offending agent is otherwise effective. Cholesterol is a component of cellular lipids. Hair losses of several months’ to years’ duration. dry. However. with subsequent disturbed keratinization. Diffuse hair loss is commonly observed during soriatane treatment. which is what is more commonly seen with other drugs. Triparanol. breakage of the hair shaft and the induction of telogen is seen in thallium alopecia. joint pains and weakness. During the early conversion of telogen to anagen hairs. loss of hair color and ichthyosis. fatigue. accumulation of air bubbles in the hair shaft. have been reported in chronic thallium intoxication. Similarly.31 How to manage druginduced alopecia In cases where an effective therapeutic agent causes alopecia and no appropriate alternative can be found. Intrafollicular thinning. loosely anchored hairs. can cause significant alopecia. just like any telogen effluvium. 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. Clofibrate may occasionally produce hair loss. there is surge of ‘telogen release’. The advantages and disadvantages of maintaining the drug must be reviewed. The package insert for accutane mentions hair loss. More research may further clarify drug-induced hair-loss issues. with muscle aches. Available evidence indicates that thallium inhibits the utilization of cystine in the production of the keratin molecule. along with ataxia. It is due to a shortened anagen release. Acute poisoning produces hair loss in 10 days. and its synthesis and metabolism are essential for the production of normal epidermal structures. Thallium ingestion produces changes in the matrix cells. stopping or changing the dose or medication. Decisions are based on alternative medications and hair loss severity and its emotional impact. which has been withdrawn from the market because of cataract induction. and offer new therapeutic recommendations. It certainly can be offered to the patient. with evident alopecia occurring in about 20% of patients. Minoxidil tends to maintain hairs in anagen and convert telogen hairs into anagen hairs more quickly.
D. Orwin A. 9. McCreadie R. 1988. pp. 1985. Yassa R. and Morrison D.I. Kirov G. 2. Semin Oncol. Inc. 31(1):111–13. 107(1):124–5. 1982. Cimetidine and alopecia [letter]. Lithium and hair loss... 22. topical minoxidil 5% solution has been reported to work.S. 1989. Telogen effluvium. and DeVane C. et al. and Schweizer C. Drugs. 91(6):930. Arch Dermatol.H. 13. Hair growth and alopecia in hypothyroidism. Clinical toxicity of chemotherapeutic agents: dermatologic toxicity. McKinney P. 23(9):603–4. 16.A. Washington DC: Horizon Books.44.K. 3. 1994. Br J Dermatol. The use of cooling scalp devices is still controversial. 47(2): 332–72. Hair loss in the course of lithium treatment: a report of two cases. 1979. 1983. Hair loss and lithium.. alopecia. Br J Dermatol. New York: McGraw-Hill. Ahmad S. Gen Hosp Psychiatr. Dunagin W. 14. Vidimos A. 1965. Drugs and alopecia. 15. Mortimer P. 21. Alopecia areata during lithium therapy. 1995. Pillans P. Limbird L.F. Reeves J. and Ananth J.L.T. A cutaneous side effect of lithium: report of two cases. Thyroid disorders in lithiumtreated patients. and Maibach H. Dis Nerv Syst. 9th edn. Some chemical influences on hair growth and pigmentation. Hautarzt. 1986. 1994. 647–9.P. 11. Klotz U. New concepts and review [see comments]. Alopecia and hair changes following colchicine therapy. 14:23. Br J Dermatol. as the alopecia is usually reversible. 1980.. . Finkenbine R. 24(3):100–4. and Woods D. 25. Harms M. Drug. 8. Jefferson J. 12. Vasopressin-associated cutaneous infarcts. and Dawber R. 1983.J. Davis R. 5. A case report. 4. 6. J Am Acad Dermatol. Hair loss during lithium treatment [letter]. and Paggiarin D. Australas J Dermatol. Arch Dermatol. Rook A. 34(3): 149–58. 1980.P. Lithium-induced reaction [letter]. 1996. 146:70–4. Dawber R. Hair loss following lithium therapy [letter]. 1983. 1979. 129(3):356–63. 17. 20. 1996.D.and chemical induced hair loss.43 We rarely need to use it.L. 106(3):349–52. The impact of lithium in South-west Scotland.. and Freinkel N. 1972. Silvestri A. Int J Clin Pharmacol Ther Toxicol. Peters D. Kusumi Y. Patients should be warned of this temporary setback. Blankenship M. 1983. 1982. 18(10): 461–5. [Cutaneous side effects of antitumor chemotherapy]. J Hardman. Int Drug Ther News. and McTavish D. 108(4):503–4. Int J Dermatol. 1993. 31(3):161–3. 116(4):347–61. Headington J. 9(1): 14–22. Demographic and clinical findings.T. Eustace D. 19. shedding telogen hairs and subsequently replacing them with the more desired anagen hairs. Ann Intern Med. Drug-associated alopecia. Molinoff P. and Steck W. I. J Affect Disord. Ann Clin Psychiatr. Can J Psychiatr.G.. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 28(2):132–3. and Mortimer P. 1971. Ann Dermatol Venereal. Valproic acid. Br J Psychiatr. 18. 32(12):853–4. Santonastaso P.Drug-induced alopecia 145 (for the first month of minoxidil application) experience more hair loss. Delaunay M. 1984. 148:752. 10.P. 10(1):46–8. Maceyko R. Alopecia and mood stabilizer therapy. Br J Psychiatr. For drug-induced anagen effluvium. Int J Dermatol. 24. 23. Valproic acid in childhood epilepsy: anticonvulsive efficacy in relation to its plasma levels. 1998.G. and neuropathy. 506–17. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy.45 References 1. 7. 50(1):33–40. 77:115–29. Freinkel R. 8(3):183–5.
1997. 44. Montvale. Lancet. and Collins J.J. 1992.T.. Katsimbri P.C... Leaker B. JAMA. 342(8884): 1423. (ed. Hoorntje S. Naylor S.S. 43. Schweiz Med Wochenschr. J Am Acad Dermatol. Alopecia possibly secondary to topical ophthalmic beta-blockers [letter]. Meyer S. Drug-related alopecia. 16(1):91–2. 2000. Zinc deficiency during captopril treatment. 39. Jenike M. New York: The Parthenon Publishing Group. J Am Acad Dermatol. Dermatology. Henriksen O.J. 35. 18(1):62–6.A. 1993.J.D. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. et al. 148(3):392. Brodkin E. The Department of Veterans Affairs Epilepsy Cooperative Study No. 1999. 36. Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation. and Menacker S. 1991..M. Maruyama K. 159:737–8. Bamias A. Acta Neurol Scand. and Donker A. 1992. 1984. Verity C. 1990. 37(2):97–108. Misciali C. 1982.. Valero V. A multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy. 45. 112(16):568–71. 263(11):1493–4. Cytoprotective effects of 4.A. Litt J. 184(2):124–5. and Major L. 41. The Paediatric EPITEG Collaborative Group. Ikeda M. New Engl J Med. and magnesium in hair and serum of epileptics. Telogen effluvium due to recombinant interferon alpha-2b. 27. 10(6):929–40. Aust NZ J Med.. Lemak N. Two cases of hair loss after sertraline use... 1992. 34(3):196–7. 65(5):504–23. Duvic M. Suzuki T. 5(3):571–9. Severe hair loss associated with fluoxetine use [letter]. 33. Kiser J. Smit A. Goldhirsch A. .... 35(1):74–8. Dermatol Clin. Eur J Cancer. et al.N..T. et al. 1984. Biol Psychiatr. 1996. 46. and Easter D. Wong R.A. 37. 1991.. Cramer J.ethanol-induced gastric lesions in rats. Effects of long-term anticonvulsant therapy on copper. Am J Psychiatr. and Johannessen S. A randomized trial of minoxidil in chemotherapy-induced alopecia. 1983. 1996. 31.A.I. and Pavlidis N. 42.F.).. 14(6):866.J. et al. Fraunfelder F. Drug eruption reference manual.. [Prevention of cytostatic-related hair loss by hypothermia of a hairy scalp using a cooling cap]... et al. Ogilvie A.B. Koizumi J. 264 Group [see comments]. Gupta S.6-bis(1H-pyrazol-1yl)pyrimidine and related compounds on HCI. Clinical and pharmacokinetic observations on sodium valproate—a 5-year follow-up study in 100 children with epilepsy. 32. Bardazzi F. J Clin Psychopharmacol. Ross R.. 2000. Moroji T. J Clin Psychopharmacol. Dev Med Child Neurol. Millennium edn. 327(11):765–71. Hair loss associated with fluoxetine [letter]. 31(6):571–81.J.. and Ellis C. zinc. Tosti A. 1987. Bourgeois J. Alopecia associated with captopril treatment [letter]. Chem Pharm Bull (Tokyo).146 Hair Loss: principles of diagnosis and management of alopecia 26.J. 28. Brodin M. NJ: Medical Economics. 30. 34... 36(6):766–71. et al. Br J Psychiatr.. 40. 38. Mattson R. Physician Desk Reference. and Whitworth J.M. Nobuhara Y.F. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. McDougle C. 1995. 45(3):549–51.H. 1998. Nephron. 1982. Hosking G. Hair loss during fluoxetine treatment [letter]. 29.. Physiologic skin changes in pregnancy.
It can be quite severe.2 Endogenous pyrogens. is not total and is usually reversible. Rooth and Carlstrom10 noted hair loss. may slow down matrix proliferation.6 After parturition. and must be questioned on taking history.6 Telogen effluvium: acute and chronic Telogen effluvium (TE) is discussed at length in Chapter 5 as it relates to medications. This also can lead to hair loss. Metabolic imbalances.1). Telogen effluvium tends to be less severe in subsequent pregnancies.5. Obese adolescents sometimes inflict on themselves a diet of salads and fruits lacking in protein. percentages of anagen hairs increase during pregnancy from 84% in the first trimester to 94% in the final trimester. such as those described below. and. such as interferons a and ?.3. However. Full recovery is usual in 4–12 months. Postpartum During pregnancy anagen is prolonged. would probably impair the ability of the rapidly multiplying follicular matrix cells to proliferate normally. there is a delayed anagen release.4 Crash dieting/hypo-proteinemia Acute voluntary starvation in young women is not uncommon. Fever.8.7. It is never total. such as psycho-physical trauma. .5 Acute telogen effluvium secondary to a known cause Fever Fever can cause alopecia 8–10 weeks after the bout. Increased hair loss may occur 1–4 months after childbirth. may cause an immediate anagen release (IAR) as described by Headington. but may be generalized (see Figure 6. and may continue for several months. which augments metabolic demands.9 Loss is more marked in the frontal and temporal regions. as described by Headington.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.8 There may be aggravating factors. 2 Interferons a and ? have been shown to decrease epithelial proliferation and to affect follicular matrix cells directly. and low plasma protein. TE can occur as a result of a systemic disturbance. as a result. but these changes were prevented by the addition of a small amount of protein. edemas and weakness in 20 obese patients on a 200 calorie diet or on a total fast. blood loss. 1 Follicles enter catagen and then telogen.
(a) Side view. Major interventions and prolonged anesthesias Blood loss and surgery with prolonged anesthesia may cause telogen effluvium15. It is possible that telogen effluvium from iron deficiency may unmask an underlying androgenetic alopecia.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. cold tolerance. A thorough history regarding weight gain. This is clearly different from the patchy alopecia occurring after localized pressure from surgery. Patients usually respond to thyroxine replacement11 unless the problem has been of very long duration and some follicles have atrophied. and energy level is important. Thyroid influences There is no consistent correlation between the degree and duration of hypothyroidism and the severity of hair loss.2). The hair loss is diffuse. (b) Top view.14 Because androgenetic alopecia and iron deficiency are both common conditions in women. with regrowth after 4 months. showing a widening of the central part. the two not infrequently occur together. showing fronto-temporal thinning. Severe thyrotoxicosis can also cause diffuse alopecia of the scalp.16 (see Figure 6. Desai and Roaf17 report telogen effluvium in a patient after prolonged surgery. Iron deficiency even in the absence of anemia (low hemoglobin) has also been reported by Hard.12 of women with diffuse alopecia13.148 Hair Loss: principles of diagnosis and management of alopecia Figure 6.9 Diffuse alopecia may sometimes be the first or only cutaneous sign of hypothyroidism.18 Iron deficiency Iron deficiency with or without anemia has been reported to be present in as many as 72% .
15 Scalp hair can become dry. including pubic or axillary hair. (a) Side view. displaying a significant widening of the parting. Hepatic disease has been reported to be associated with diffuse alopecia. showing thinning of the central part. Zaun 22 studied 53 patients who had either hepati- tis.21 There may thinning of body hair.2 35-year-old female with a 6-week history of abrupt diffuse hair shedding commencing 8 weeks after bowel surgery. The liver is the major site of amino acid inter-conversion. Malignant disease. 9 Inflammatory bowel disease has been reported to be associated with hair loss. (b) Top view. cirrhosis or fatty liver. renal failure. malabsorption should be investigated. It has been suggested that disturbed liver metabolism of cystine and methionine may be related to alopecia.20.19 This kind of hair loss is also referred to as ‘toxic telogen effluvium’. particularly with Crohn’s disease. (c) Occipital view. brittle and sparse with chronic renal disease.22 When sparse hair and growth retardation are associated with chronic frequent loose pale and bulky stools. hepatic disease and malabsorption Hodgkin’s disease may present with telogen effluvium as its first sign. showing marked thinning.Telogen effluvium: acute and chronic 149 Figure 6. He found increased telogen counts in 34 patients and evident hair loss in 11.23 .
CTE contrasts with classic acute telogen effluvium by its persistence and its tendency to fluctuate for a period of years.27 They describe a ‘not uncommon condition’ presenting with transitory episodes of shedding lasting several weeks with no apparent cause.’— CBerg. frequently with a positive pull test. showing a disproportionate number of telogen hairs on transverse section (courtesy of Dr Magdalena Martinka). would be Chronic Telogen Effluvium (CTE). Females present with a diffuse thinning.2 Medications These are discussed extensively in Chapter 5. increased parting widths over the entire scalp and increased telogen shedding. reduction in pony tail diameter.28. It is a form of diffuse hair loss affecting the entire scalp for which no obvious cause can be found. Chronic telogen effluvium of unknown cause in the female patient ‘Woman is herself constantly doing something to her hair. 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.15.24. acute anxiety. it is a source of anxiety to her.29 CTE is not uncommon. and depression Acute anxiety or depression may cause a telogen effluvium.25 but the paucity of reports suggests that it is uncommon. The onset is usually abrupt. There is literature that does support the notion of psychogenic telogen effluvium. The degree of shedding is usually severe in the early stages. A modern term for this condition. 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. Diffuse cyclic hair loss in women was first described by Guy et al. in 1959. The typical patient is a ‘vigorous otherwise healthy woman’ who presents with diffuse hair loss that is cyclic and reversible. They considered Figure 6.3 A histological transverse section of chronic telogen effluvium.150 Hair Loss: principles of diagnosis and management of alopecia Psychological stress. 195126 this to be a physiological phenomenon. Obviously. Women who present with this type of hair loss frequently are upset and want a satisfactory explanation for their problem. . Patients are particularly troubled by Frequently encountered in dermatological practice is the woman who presents with chronic diffuse hair loss of unknown cause. coined by Whiting. with or without a recognizable initiating factor. and the hair may come out in handfuls.
CTE may unmask their AGA. The patient should be monitored every 4–6 months with repeat ferritin levels until they have reached this threshold level. as one must temporarily shed more telogen hairs to increase the eventual percentage of anagen hairs. Scalp dysesthesia or a sensation of pain in the hair (trichodynia) is an accompanying symptom in a significant proportion of cases. the amount of shed hair here is greater than that in androgenetic alopecia. and fear total baldness.3). (3) Top up ferritin levels to greater than 30 µg/1. (4) Topical minoxidil 5% solution twice daily. Nutritional supplements (except for iron when indicated) are not recommended. However. and hair will not necessarily grow back to the same density as before. and involving the entire scalp area in increased shedding of telogen hair. in those women who have a genetic predisposition to androgenetic alopecia (AGA). Typically this occurs in women. laboratory testing may often show ferritin levels below the normal male reference range of 25–30 µg/l. Trueb et al. large amounts of zinc in supplements (> 25 mg/day) may affect iron absorption adversely.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. Patients must be warned that initially there may increased shedding with topical minoxidil solution. Scalp biopsies show an increase percentage of telogen hairs (see Figure 6. and correlates better with emotional upset than with actual hair loss.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. CTE is usually reversible. Repeated reassurance that the condition does not cause complete baldness is necessary. further studies with double-blinded placebo controls analyzing the single and combinational benefits of supplemental iron and topical minoxidil solution for CTE are needed. as a large number of the ‘normal control’ group are menstruating women. 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. hair thinning is usually discrete which contrasts to the intense emotional overtones brought about by this situation. . However.31 For example. Overlap with androgenetic alopecia and/or psychogenic pseudo-effluvium is not uncommon.Telogen effluvium: acute and chronic 151 the continuing hair loss. starting abruptly without a recognizable initiating factor. 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. With the exception of bitemporal recession.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. No apparent cause can be found. Owing to the synchronization of the hair cycle. This may initially lead to the differential diagnosis of psychogenic pseudoeffluvium. Sufficient nutrition is obtained in a normal diet. (2) Make sure you have ruled out any underlying cause of telogen effuvium. We have found that topical minoxidil solution is beneficial in maintaining hairs in anagen and increasing conversion of hairs from telogen to anagen.3). CTE does appear to be self-limiting in the long run. In certain cases of CTE. Usually normal reference levels for women are considerably lower. while miniaturized hairs are not a feature of the disorder.31 The normal ferritin levels for men and women differ in most laboratories. There is evidence that the taking of excessive and unnecessary supplements could actually induce telogen effluvium.
1989. 11. 81:83–5. 6. Tabibzadeh. 136–66. 123(2):187–97. Camacho F. 9. Diffuse cyclic hair loss in women. 35: 323–7. 1963. Schiff B. p. New concepts and review. Karassik R. Effect of pregnancy on the human hair cycle. Klein A. 18. Telogen effluvium after anesthesia and surgery. James K. 1959. Pecoraro V. Anesth Analg. 7.Roaf. S.K. 1993. Thyroid and adrenal interrelations with special reference to hypotrichosis and axillairis in thyrotoxicosis.Freinkel. W.P. Thompson J. R. 1961. Rushton D.Montagna. Abel R. 32(6):457–65. Telogen effluvium: hair loss after spinal cord injury. J. Rook A.George and J. 129(3):356–63.I. 1960. Arch Dermatol. Wachstumsstorungen der kopfhaare als folge von hepatopathien. Br J Dermatol. 15. J Clin Endocrinol Metab. [Dermatological changes in patients receiving long-term hemodialysis]. J Obstet Gynecol.R. 16. and N. Dis Colon Rectum.A. 1980. Kligman A. 23. and Y.. ed. Effects of alpha and beta interferons on cultured human keratinocytes. Arch Phys Med Rehabil. Telogen effluvium as a sign of Hodgkin disease. 1966. 1963. 3. and Gilchrest B.C. Fiedler V.L.A. 1990. 10. Pathologic dynamics of human hair loss. 8. Acta Derm Venereol. Crohn’s ileocolitis presenting as chronic diffuse hair loss. In Disorders of hair growth. Dahlin P. 82(5):303–4. 1969. Cutaneous manifestations of hyperlipidemia and uraemia. 1969. Hard S. Non-anemic iron deficiency as an etiologic factor in diffuse loss of hair of the scalp in women. 1989. Yaar M. Aula Medica Group SA: Madrid. Schnipper L.152 Hair Loss: principles of diagnosis and management of alopecia References 1. 25. 5. 27. Arch Dermatol. 1960. 1984. .E. Schattner A. J R Soc Med. Scoggins R. 20. J Invest Dermatol. 1988. 17. Diffuse alopecia: Endocrine. 1984.H. The normal trichogram of pregnant women. 1991. 67(1):131–8. 87:609.Rudolph and J. Desai S.T.Nerette. Arch Dermatol. J Invest Dermatol. 1993. E. Arch Dermatol. 403–9. Freinkel R. 26. 106(3):349–52. Headington J. 65(8): 485–6. and E. 108(5):702–3. and S. 13. Guy W. Blackwell Scientific Publications: Oxford. Arch Dermatol. 7:52. pp. 41:357.Camacho. 43:562–9. F.Olsen. 187(6): 455–63. Alopecia after ileal pouchanal anastomosis. 83:175–98. Alopecias due to telogen effluvium. 94:125. Biochemical and trichological characterization of diffuse alopecia in women.. Arch Dermatol. In Diseases of the hair and scalp.Shanon. metabolic and chemical influences on the follicular cycle. Antiproliferative effect of interferon-gamma in human endometrial epithelial cells in vitro: potential local growth modulatory role in endometrium. Telogen effluvium. 1985. Therapeutic fasting. Hautarzt. 2.D. Post partum alopecia. A. Arch Klin Exp Derm. 1951.. Diffuse alopecia: telogen hair loss. Lubach D.. 203. 22.S.Rao.G. Pergamon Press: Oxford.Leyden. Skelton J. 31(2):82–5. Post operative (pressure) alopecia. Rooth G. Lynfield Y. 19.W. pp.. Ramsay I. 1997.N.. 235:386–93. In Advances of biology of the skin.Rook. 1973. P.J. The unconscious significance of hair. 1972. London: George Allen & Unwin Ltd. 12. Hair growth and alopecia in hypothyroidism. 81:34. Zaun H.S. ed. 21. Acta Med Scand 1970.. 63(1):83–4.Carlstrom. 24.C. 14.. Satyaswaroop and P. ed. Williams R. 85(1):70–4. In Trichology: diseases of the pilosebaeous follicle. Study of postpartum alopecia. ed. Berg C.: New York. 1947. 4. et al. 241–252. Postgrad Med 1967. McGraw-Hill. Arch Dermatol. J Clin Endocrinol Metab. Inc. pp.
14(4):723–31. J Am Acad Dermatol.J.A. Clin Dermatol. Dermatol Clin. 1996. Whiting D.A. 31. Trueb R. [Idiopathic chronic telogen effluvium in the woman]. 30.M. Van Neste D. 2000. Chronic telogen effluvium. and D. Chronic telogen effluvium: increased scalp hair shedding in middleaged women. 1997. 51(12):899–905. . 29. Hautarzt.Telogen effluvium: acute and chronic 153 28.Rushton. 35(6): 899–906. 15(1):113–25. Whiting D.H. 1996. Hair problems in women.
1. When the inflammation is located deep. there is a permanent upper portion of the hair follicle and a non-permanent lower portion. The terms cicatricial and scarring are used interchangeably. then a cicatrizing alopecia is more likely to occur.1 Lack of follicular ostia is the hallmark sign of scarring hair loss. because the location of the inflammatory infiltrate is crucial in determining irreversibility of alopecia.8). These cells migrate down into the hair follicle. catagen. while FD presents with pus- Figure 7. (see Chapter 1. Scarring alopecias are true trichologic emergencies. histological or proposed pathogenic criteria. in the vicinity of the non-permanent portion.2 Clinically. Figure 1.1) and irreversible alopecia. lichen planopilaris (LPP) and folliculitis decalvans (FD). A basic knowledge of follicular anatomy is important in the understanding of scarring alopecias. CCLE and LPP are characterized by keratotic follicular papules. If the inflammation is located within the permanent portion. and subsequently differentiate into the various layers of the hair follicle. and telogen. As the hair cycles through anagen. a scarring alopecia is unlikely to develop.7 Cicatricial (scarring) alopecias Introduction Cicatricial (scarring) alopecia represents a diverse group of diseases characterized by lack of follicular ostia (Figure 7. . Classification Classification schemes for cicatrizing alopecias have been based upon clinical. Follicular stem cells are located in the bulge area where the arrector pili muscle inserts into the follicles. particularly around the stem cells of the bulge area and the infundibulum. scarring alopecias are categorized as either inflammatory or non-inflammatory. The non-infectious inflammatory scarring alopecias include chronic cutaneous lupus erythematosus (CCLE). Follicles can be saved from irreversible damage if this peribulge infiltrate can be controlled.
A less cosmetically important site. and lidocane with epinephrine is infiltrated into the area. PP. First. Ten minutes is then allowed to take advantage of the vasoconstrictive effect of the epinephrine. LPP and PP. The blue suture allows for easier recognition and differentiation from hair during suture removal 7 to 10 days later. may also be requested. preferably with a positive pull test and a paucity of follicular orifices. The biopsy should include the subcutaneous fat. The area is marked with a red marker.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. with disease activity limited to the peripheral zone surrounding the alopecic zone. such as PAS and elastin.156 Hair Loss: principles of diagnosis and management of alopecia tules. and folliculitis decalvans. the hair follicle is simply an ‘innocent bystander’. the hair follicle is the primary target of destruction. A second scheme. LPP. a biopsy site is selected. The non-inflammatory scarring alopecias are pseudopelade of Brocq (PP) and follicular degeneration syndrome. and FD are primary alopecias. classifies the cicatrizing alopecias according to inflammatory infiltrate cell type: lymphocyte or neutrophil. In these cases. and neoplastic infiltrates. The biopsy for cicatrizing alopecias A scalp biopsy is crucial in the diagnosis of a cicatrizing alopecia. The lymphocytic-mediated disorders include CCLE. The hair in the biopsy site is clipped. In primary scarring alopecias. LPP. such as the posterior scalp. Lymphocytic-mediated cicatricial alopecias Clinical features The three most common lymphocytic-mediated cicatricizing alopecias are CCLE. . Two 4 mm punch biopsies are performed. The punch is placed parallel to the direction of the hairs and inserted to the depth of the bevel. because this is the location of terminal anagen hair bulbs. Sperling has coined the term central. One is submitted for transverse sectioning and the other is divided in half and submitted for both direct immunofluorescence and longitudinal sectioning. Sarcoidosis and morphea are examples of secondary scarring alopecias. Follicular destruction is not the primary event.0 nylon suture. This pathologically based classification system assists the clinician both in therapeutic decision-making and in gaining a better patho-physiological understanding of these disorders. centrifugal scarring alopecia (CCSA). Pressure is then applied to the biopsy site with a cotton applicator that may be saturated with aluminium chloride. is preferable. Special stains.4 This grouping includes pseudopelade. This site should be representative of active disease (primary lesion). CCLE. Scarring alopecias can also be classified as primary or secondary. while the neutrophilic mediated conditions include FD. and PP. Secondary scarring alopecias result from events outside the follicular unit that impinge upon and eventually eradicate the follicle. developmental abnormalities. dissecting cellulitis. follicular degeneration syndrome. and acne keloidalis. based upon pathology. genetic disorders. The biopsy site is then closed with a blue 4. These conditions are centered on the crown or vertex and progress in a roughly symmetrical pattern.
More than half these patients had scalp involvement at the onset of the condition.1 years. (c). Follicular hyperkeratosis occurring centrally within a plaque of lupus erythematosus. the scalp was the most prominent finding.Cicatricial (scarring) alopecias 157 Figure 7. A 60-year-old female with frontal scalp involvement.5 A published report6 of 89 patients with CCLE showed that 34% had scalp involvement. because the scalp is a relatively light-protected area.2 Chronic cutaneous lupus erythematosus of the scalp.7 In three out of the seven. (a) and (b). an ANA is recommended for all patients with CCLE. Very few patients (< 10%) who present with CCLE ever progress to systemic LE. 7/17 patients (41%) with CCLE had cicatricial scalp involvement. A 23-year-old female with painful erythematous atrophic plaques.8 Age of .7 This common involvement of the scalp is intriguing. In a smaller study by Callen. CCLE accounts for 30 to 40% of patients with scarring alopecias and has a definite female predilection. In a series of 86 patients with CCLE of a mean duration of 15. In 10% of patients with CCLE. However. (d). 35 per cent (30/86) had scarring alopecia. scalp involvement may be the sole manifestation of LE.
In 1915. A prominent thickened and adherent scale may develop. At this point patients may experience loss of hair. Tufted folliculitis consisting of several hair shafts emerging from a single ostium can also . 7% nail involvement. 7.3d).2). rather than centrally (Figures 7. owing to torsional within the hair follicle. with its extent not clearly apparent unless the scalp is shaved (Figures 7. and ulcerations may even develop (Figure 7.12 showed that 50% of their series of 45 patients with scalp LPP had strictly scalp involvement only. and represent follicular hyperkeratosis. The term lichen planopilaris was first introduced in 1895 by Pringle.3h. patients with scalp lichen planus should be followed up to assess whether lichen planus develops elsewhere (Figures 7. atrophy. and a female predominance (2:1) has been noted. and fails to account for the majority of intermediate cases. These keratinous plugs are from the follicular openings. Lesions typical of lichen planus do not occur on the scalp. a series of 807 patients showed that only 10 (< 1%) had scalp involvement. LPP may be very widespread.3j).3b and 7.3a). This initial alopecia induced by follicular inflammation is potentially reversible. Hypopigmentation and depigmentation begin to appear. It usually occurs between 30 and 70 years of age. the oral mucosa and the nails must be examined. 7. with a predilection for areas of greater hair density. Clearly. These two presentations are now considered variants of lichen planus. With continued spread of the disease. large. edematous plaques. Of all patients who have lichen planus. This view is limited.3e. Seven per cent had either axillary or groin involvement. Follicular hyperkeratosis is present at the periphery of the plaques. a characteristic feature of the scarring alopecias. A clinical triad of classic plaquetype lichen planus.3i and 7. Graham-Little10 described folliculitis decalvans et atrophicans or follicular scalp lesions resulting in cicatricial alopecia associated with follicular keratotic lesions at other sites.11 It was felt 40 years ago that one had to have this triad to make a diagnosis of LPP. These lesions slowly progress to large erythematous. spinous or acuminate lesions.158 Hair Loss: principles of diagnosis and management of alopecia onset of scalp CCLE is usually at between 20 and 60 years of age. and alopecia of the scalp or other hairy areas has been described. The whole skin surface. which when removed reveals keratinous plugs on its under-surface. Mehregan et al. white atrophic scarred alopecic plaques will predominate over their inflammatory precursors.9 who described the association of lichen planus with follicular keratotic lesions. There is also increased curliness of hairs in scarred areas. LPP is usually an insidious process evolving over several years. Patients present with erythematous plaques of alopecia. 27% mucous membrane involvement and 40% glabrous skin involvement.3c). As the lesion expands. such as the occipital scalp in men with AGA (Figures 7. 7. telangiectasia and follicular hyperkeratosis (Figure 7. a clue to help distinguish CCLE from LPP (Figure 7. and anagen hairs can be extracted with gentle hair-pulling. In addition.3g). Scalp lesions begin as erythematous papules or irregular small scaly plaques. and scarring develops.3f. Pruritus and tenderness are often a prominent feature. Central atrophy and telangiectasia eventually become prominent. normal anagen hairs can easily be pulled out of the scalp. the central erythema fades and the surface flattens.2d). There is a spectrum of LPP.13 LPP accounts for 30–40% of scarring alopecias. Follicular hyperkeratosis is more active in the center of a plaque. Occasionally drugs such as gold14 or mepacrine (atabrine)15 can trigger scalp lichen planus and cause irreversible hair loss.
(b) and (c) LPP affecting the spared areas of male androgenetic alopecia. (e) Extensive case of LPP at the back of the scalp. (a) Follicular hyperkeratosis at the periphery of erythematous alopecic areas. (b) Showing active inflammation. (d) Ulcerative lesion of LPP of the scalp.Cicatricial (scarring) alopecias 159 Figure 7. .3 Lichen planopilaris (LPP). (c) Burnt out LPP.
(i). Tufting of hairs in LPP.160 Hair Loss: principles of diagnosis and management of alopecia (f) and (g). (k). (h). Close-up after the head has been shaved. This fits well with GrahamLittle disease. . (j). 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. showing marked involvement of much of the scalp.
(b) A 5year-old with pseudopelade (Brocq).4 Pseudopelade of Brocq (a). (c). Scarring hair loss affecting central portion of the scalp. .Cicatricial (scarring) alopecias 161 Figure 7. (d). (e) An 8-year-old boy with scattered pseudopelade (Brocq).
(h) PP affecting the area spared by 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. . (i) PP affecting the area most affected by androgenetic alopecia and mimicking androgenetic alopecia. (j) pp affecting tne beard area.
.3k). Brocq of Paris described what later became known as Pseudopelade19a. The parietal and vertex areas of the scalp are primarily involved (Figures 7.4b-e).4i). 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 7.4b). Eyebrow loss was described in 13/16 women. the follicular ostia are not present while in AA they are most certainly present. However. extension of the process takes place only very slowly (Figures 7. End-stage LPP or CCLE may mimic an early pseudopelade (Brocq) as discussed below. There is controversy as to whether PP is a distinct entity or is effectively the same as end-stage CCLE or LLP.25. asymmetrical. post-menopausal frontal fibrosing alopecia.23 The course is extremely variable.16 There is a variant of LPP. overlaps significantly with PP with marked non-inflammatory cicatricial alopecia on the top of the scalp in black patients. extension occurs more rapidly.19c.6%) in the age range of 11–20. Indeed. Braun-Falco et al.20 PP presents with small.Cicatricial (scarring) alopecias 163 occur in LPP (Figure 7.2%) patients with PP without any previous underlying condition.4a and 7.19 Histological findings were indistinguishable from LPP. PP is an idiopathic disorder.4f and 7. Tufting is common as an endstage phenomenon in many scarring alopecias.21 Detailed studies by Braun-Falco et al. PP in children has been described..4g). Occasionally PP may affect the beard area and not just the scalp (Figure 7. PP is usually asymptomatic and without inflammation. His group described 94/142 (66.5). irregular. This is known as polytrichia. The course is often protracted and prolonged. producing a frontal fibrosing hair loss extending to the temporal and parietal hair margins. A form of central centrifugal scarring alopecia in African-Americans. In 1885.24 and the diagnosis of PP may be missed (Figure 7. This has been classically described as ‘footprints in the snow’.35%) cases of PP under the age of 11 and nine patients (9. Pseudopelade refers to ‘like alopecia areata but not alopecia areata’.4j).22 strongly support the idea that pseudopelade can exist as a distinct entity.20. In pseudopelade (Brocq). Occasionally the pattern of hair loss of PP can mimic androgenetic alopecia as described by Zinkernagel et al. ivory porcelain white patches devoid of follicular units.26 Although initially thought to be a consequence of hair-care practices. Occasionally there may be erythema and mild pruritus. in some cases. and occurs because the infundibular epithelium of damaged follicles often heals so as to cause the formation of a common large infundibulum. In the majority of cases.17–19 Kossard has described an entity occurring in postmenopausal women presenting with perifollicular erythema along the marginal hairline. As with other cicatrizing alopecias. Brocq subsequently admitted that this term does confuse the Iiterature 19b. However. and exceptionally there may be almost total baldness after 2 to 3 years. reported an incidence of 4/ 142 (4. This author has seen at least 3 cases in children under the age of 10 (Figures 7. it is now believed to represent an idiopathic disorder unrelated to trauma or hair cosmetics. Pelade is the French word for alopecia areata (AA). usually of adulthood. 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. also known as follicular degeneration syndrome (FDS). after 15– 20 years the patient may still be able to arrange his/her hair to conceal the patches effectively. anagen hairs are easily extracted.
(d) Close-up of patient illustrating lack of follicular ostia.164 Hair Loss: principles of diagnosis and management of alopecia Figure 7. . (a) Black female with significant alopecia. (c) Black male with significant alopecia.5 Central centrifugal scarring alopecia (follicular degeneration syndrome) in African-Americans. (b) Close-up showing obliteration of follicular ostia.
Cicatricial (scarring) alopecias 165 Figure 7. then FD is the most likely diagnosis. Pigment incontinence is present. while a peripheral distribution is seen in LPP.6 Algorithm for diagnosis of major non-infectious scarring alopecias. Second. Pigment incontinence is present. Pathology The histopathology of CCLE reveals follicular vacuolar interface changes.7 Pathology of lupus erythematosus showing peri-adnexal and perivascular lymphocytic infiltration with follicular hyperkeratosis. First. loss of sebaceous epithelium.6). The presence of a focally thinned epidermis. Some clinical pearls can be helpful in establishing a diagnosis (Figure 7. and fibrosis (Figure 7. . Direct immunofluorescence demonstrates granular deposits of C3 of IgG distributed along the dermal-epidermal junction. Perifollicular inflammation is most severe at the level of the infundibulum. The lymphocytic infiltrate of LPP is lichenoid.1 Figure 7.7). a central localization tends to occur in CCLE. but may extend down the length of the follicle. with a characteristic perifollicular interface dermatitis (Figure 7.8). Inflammation affects the upper portion of the follicle. if pustules are present. the most likely diagnosis is PP if the scarring alopecia is non-inflammatory. Other features include loss of sebaceous epithelium and marked perifollicular lamellar fibrosis. and inflammatory cells may invade the follicular epithelium. a superficial and deep perivascular and periadnexal lymphocytic infiltrate. a thickened basement membrane zone and an increased dermal mucin helps support the diagnosis of CCLE. Finally. if follicular hyperkeratosis is present.
The pathology of PP depends on disease duration.8 (a). a peri-infundibular lymphocytic infiltrate is present beneath a normal epidermis. Pigment incontinence is less evident than in LE or LPP. The end stage of PP is characterized by marked scarring and the absence of an inflammatory infiltrate.) Perivascular and peri-eccrine infiltrates are usually not present. rete ridges vanish. In the early stages. As PP progresses. the epidermis becomes atrophic. (Courtesy of Dr Magdalena Martinka. (Courtesy of Dr Magdalena Martinka. Special staining techniques may help in establishing a diagnosis of a scarring alopecia. Elastin staining demonstrated normal or abundant elastic tissue in PP. as in LE. and sebaceous glands and hair follicles are obliterated. Direct immunofluoresence is negative. Pathology of lichen planopilaris displaying the characteristic follicular lymphocytic interface dermatitis. There may also be tufted folliculitis in the upper portion of the epidermis (Figure 7. (b) and (c). Direct immunofluorescence may demonstrate grouped globular IgM cytoid bodies in follicular epithelium. while in LE and LPP the quantity of elastin is significantly dimin- Figure 7.) .166 Hair Loss: principles of diagnosis and management of alopecia Figure 7.9).9 Numerous hairs exiting from one infundibulum which clinically appears as polytrichia or tufted folliculitis.
11 Neutrophilic infiltrate in folliculitis decalvans. (Courtesy of Dr Magdalena Martinka.10 dividing entities into lymphocytic.Cicatricial (scarring) alopecias 167 Figure 7. Folliculitis decalvans is neutrophilic-mediated (Figure 7. but again there is no follicular plugging or atrophy.) ished. The lymphocytic scarring alopecias can certainly be difficult to tell apart from each other. 7.28 Inflammatory changes in the infundibular area of the follicle in psoriasis may disrupt follicular stem cells and result in scarring alopecia. Keratoacanthomas and squamous cell carcinomas can mimic hypertrophic lupus erythematosus. the co-existence of LPP and CCLE Figure 7.11). A potassium hydroxide preparation and/or culture will help confirm the diagnosis. However. An algorithmic approach to the pathology of scarring alopecias is presented in Figure . and will be described below. Early CCLE and LLP can look quite similar. there are reported cases of scarring alopecia in severe scalp psoriasis.10 Algorithm for pathological assessment of major noninfectious scarring alopecias. Tinea capitis can be scarring. Differential diagnosis Scalp psoriasis has the presence of follicular ostia and the lack of follicular plugging and atrophy. In addition.versus neutrophilic-mediated.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.
can halt further spread of the condition and reduce symptoms of itch and burning. has been reported.12 Algorithmic approach to treatment of lymphocytic-mediated scarring alopecias. The goals of treatment are to arrest the cicatrizing process. the severity of symptoms. decrease follicular inflammation and prevent further fibrosis. and the extent of scalp involvement. This is summarized in algorithmic form in Figure 7. and disease severity. . Figure 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.1 ml/injection for 20 injections. Triamcinolone 10 mg/ml.13 Injecting intralesional cortisone into the surrounding hairy areas of scarring alopecia.6 and 7. the degree of inflammation. patient age. injected with a volume of 0.29 Differentiating clinical and histopathological features of lymphocytic scarring alopecias are discussed above and are summarized in Figures 7.168 Hair Loss: principles of diagnosis and management of alopecia Figure 7. Treatment The treatment of scarring alopecia depends on three variables: diagnosis.10. The severity is determined by the rapidity of the progression of the condition.12. Injections are performed once monthly.
Dapsone (100 mg/day)34–37 and thalidomide (100 mg/day)38–40 are other alternatives. is administered to scarring areas once every four weeks (Figure 7. and symptomatic. showing marked improvement after 1 year of hydroxychloroquine 200 mg twice daily.15 Lichen planopilaris: the patient from Figure 7. Premature transplantation may actually aggravate the condition. The prednisone provides bridge therapy. than other treatments can be attempted. inflamed. Again. If there is more than 10% scalp involvement. triple therapy is immediately initiated with intralesional steroid. rapidly progressive.31–33 at doses of 1 mg per kg per day. and an ultra-potent topical corticosteroid is applied twice daily. Increasing the number of hairs. If the alopecia is very severe. intralesional corticosteroid and topical corticosteroid.30 is added for a minimum of six months (Figures 7. If improvement is not noted after six months. 2 ml of 10 mg per ml. When a pull test is negative for over two years and alopecia is clinically stable. and therapy is continued for six to twenty-four months until the pull test is negative. Intralesional corticosteroid. monthly intralesional corticosteroid injections and topical superpotent corticosteroid ointment twice daily.14 Lupus erythematosus: the patient from Figure 7. then hydroxychloroquine. then scalp reduction and/or hair transplantation are further options. If the patient is not responding within eight weeks to this double therapy.13).14 and 7. then prednisone is added at 1 mg per kilogram per day and tapered over two months. If there is less than 10% scalp involvement.Cicatricial (scarring) alopecias 169 Figure 7.3d with previous ulcerative LPP improved markedly with hydroxychloroquine. Figure 7. can be initiated and then tapered once improvement is detected. very inflamed and symptomatic. 200 mg twice a day. because of a delay in the therapeutic effects of hydroxychloroquine. double therapy with topical and intralesional corticosteriods is initiated. ultra-potent topical corticosteroid and hydroxychloroquine. Isotretinoin.2c. A pull test is conducted with each visit. therapy is tapered once improvement is acheived.15). then a systemic steroid is also administered for eight to twelve weeks. which can serve as a primary target in scarring . If the alopecia is rapidly progressive.
showing much improvement. may cause the patient to become more symptomatic with increased inflammation. The use of topical minoxidil is controversial. alopecias. topical minoxidil solution for scarring alopecias. many clinicians feel that topical minoxidil. by retaining unaffected hairs in anagen for a longer period of time. enables the overall density to be better than that of untreated individuals.170 Hair Loss: principles of diagnosis and management of alopecia Figure 7. Figure 7. showing hair shafts embedded within the skin. (a) Marked erythema and folliculitis. pruritus or burning if the condition is remotely still active. Although there are no controlled trials for Figure 7.16 Folliculitis decalvans in a 30-year-old male.17 Folliculitis decalvans in a 17-year-old female. (b) After 6 months of isotretinoin 1 mg/kg/day. most evident after the scalp has been shaved.18 Tufted folliculitis in dissecting cellulitis.41 .
44 Dissecting cellulitis can present as a boggy cystic inflammatory process (Figure 7. cephalosporins. scale or crust. rifampin and fusidic acid. Patients present with round patches of alopecia with overlying erosion.43 Systemic fusidic acid may also have some benefit.18).16).11).43. Hair shafts are occasionally embedded within the scalp (Figure 7. cloxacillin. Follicular-based pustules develop in successive crops (Figure 7.19). are considered an abnormal immune response to the normal scalp flora. Laser-assisted hair removal50 may help for this subset of patients.Cicatricial (scarring) alopecias 171 Figure 7. such as FD. high-dose isotretinoin for a prolonged course is recommended.45–49 Patients may be so symptomatic with discomfort. that controlling the inflammation for these individuals is more important than salvaging the hair.17) Tufted folliculitis is a feature frequently seen in FD (Figure 7. Close-up of boggy cysts. fibrosis is prominent. however. as the disease progresses. such as topical fusidic acid. Neutrophil-mediated cicatricial alopecias The neutrophil-mediated cicatricial alopecias. (b). Dissecting cellulitis of the scalp with characteristic boggy cysts. the pathology demonstrates a neutrophilic folliculitis (Figure 7.44 For severe dissecting folliculitis. 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.44 Topical therapy can also be added.19 (a). itch and burning. . The therapeutic strategy for the neutrophilmediated cicatrizing alopecias is targeted at anti-staphylococcal therapy with systemic erythromycin.42 In the early stages.
and S. Brocq L. 19b. Arch Dermatol. Lupus. 4. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. LoPresti P. Dermatol Clin.Ahn. Scarring alopecia. 98(3):234–8.K.Van Hale. H. Clinical. Br J Dermatol. 14(4):773–82. A new look at scarring alopecia [editorial.. Ann Int Med.C. 1992. 1949.. 8.. Templeton S. 12(2 Pt 1):278–88. Silver H. et al. 1.Bergner and G..Lee and B.R.P.S. Frontal fibrosing alopecia in a postmenopausal woman. Dermatol Clin. Hot comb alopecia. Journal of Cutaneous and Venereal Diseases 1885. . 60(6):299–300.C.. 5(3):603–18. C.M.M. 17:77–102. 2. Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus. 126(4):307–14.Alopecia.M. M. Sperling L. 1994. 12. Altman J. 1992. Cicatricial alopecia.. Hautarzt.Solomon. J Am Acad Dermatol. 1985. 19. 3:49. 27: 183–5. 1994. Whiting. 17. 1905. An aggressive multiplemodality therapeutic approach is often necessary to gain disease control. Kossard S.F. Pseudopelade in Traite elementaire de dermatolgie Practique. 5.Hwang and S. 1997. 6. 6.. In Transactions of the St John’s Hospital Dermatological Society. 84:179.L. Chronic cutaneous lupus erythematosus.. Clinical and laboratory findings in seventeen patients. laboratory. Arch Dermatol. 1968.. Scarring alopecia: a classification based on microscopic criteria.S. 97. Annales de Dermatologie et de Syphiligraphie. Braun-Falco O.R.A. Brocq L.P.Dissaneyeka and S. Pringle J. References 1. Br J Dermatol. Callen J.Solomon and D. 18. and A.Burge.Kligman. Mehregan D. 11. Arch Dermatol Syph. 1996. Lichen planopilaris: clinical and pathologic study of forty-five patients. 209.Wilkinson. J Am Acad Dermatol. 16. 67: 346–54. 118(6):412–6. 3. The variations and course of lichen planus.P. Lichen post-aurique. Brocq L. J Cutan Pathol. 1982. Folliculitis decalvans et atrophicans: Report of a case. varieté psuedopelade. Muller. M. Postmenopausal frontal fibrosing alopecia. Freese T. Newton R. 130(6):770–4. Woods B. J Am Acad Dermatol. Hebert A. Arch Dermatol. Follicular lichen planus (lichen planopilaris). and prognostic examination of 62 patients. S. de Berker D. 130(11):1407].. 1961. 1(3):181–6.T. Paris Vol. Scarring alopecia in discoid lupus erythematosus. 9. London: The Society.A. Kossard S. Doin.R. Heilgemeir. 1992. A. 14. Br J Dermatol. An accurate diagnosis is arrived at through a careful clinical and histo-pathological assessment.W. R. P648. Arch Dermatol. comment]. 2000. 15. Arch Dermatol. 1915. 1997.P. Wilson C. 19c. Feder A. Lichen pilaris spinulosus. 19a. Lee W.A. T. [The Brocq pseudopelade—a disease picture or disease entity].Papa and A. 21(2):97–109. 36(1):59–66. Callen J. 1989. Dean D. Burge S. therapeutic. 1953. 7. and Dawber. 2. 20. 1968. Réchèrches sur 1’alopecie atrophiante. 1987.. 40(2):77–83.172 Hair Loss: principles of diagnosis and management of alopecia Conclusion The scarring alopecias are trichological emergencies.A.M. Scarring alopecia in a pattern distribution [published erratum appears in Arch Dermatol 1994 Nov. 13. Cutis.. 27(6 Pt 1):935–42. The sequelae of chronic cutaneous lupus erythematosus. Headington J. 31: 1078. 136(2):235–42.M. Little E. 10. and Solomon A. Clinical observations of atypical lichen planus and related dermatoses due to atabrine toxicity.
M. histological and therapeutic findings. Lindskov R. 138(5):799–805. ed.Shapiro. and Gaspari A. 1995. Green S. 30. 1994. 23(5 Pt 1):944–5. Treatment of cutaneous lupus erythematosus. and Bergfeld W. 43. and J.E. Pseudopelade of Brocq in beard area. Arch Dermatol. London: Martin Dunitz Ltd.Trotter and J.J. Br J Dermatol.Coviello and G. 32.Formica and A. Dawber R.S. Arch Dermatol. McCollough M. 28.. Duna G..A. 17(2 Pt 2):364–8. 31.G.. and F. biology. 1999. 21(1): 99– 115. 39.Cash. 1992. 128(1):68–74. F. 37.F. Lupus. J Am Acad Dermatol. Sperling L. Folliculitis decalvans.C. Rothe M.Reymann. 40(11): 735–6. 22.K.Gatter. 29. Verma K. Bowers K. 1987. Update of minoxidil treatment of hair loss. The follicular degeneration syndrome in black patients. Scarring alopecia in psoriasis. Folliculitis decalvans including tufted folliculitis: clinical. Madani S.. 17(5):305–6.E. 40. Arch Dermatol. 130(6):763–9.. Vena G. 1992. 1982. 1983. 167–76. N. Knop J. J Assoc Physicians India.G. M. In Hair and its disorders. Acta Derm Venereol. Imai S. 41. 3rd and Smith K.H. Treatment of refractory cutaneous lupus erythematosus. Bonsmann G. 38. Elastic tissue in scars and alopecia. Rheum Dis Clin North Am. Shornick J. 1989. 2000. Pseudopelade of Brocq in a child [see comments].A.Cicatricial (scarring) alopecias 173 21. 24(1):49–52. 26. Long-lasting response to combined therapy with fusidic .J. Elston D. Adya C. 172(4):214–7. Arch Dermatol.Camacho.. Dapsone in cutaneous lesions of SLE: an open study. 24. 27(3):147–52. 33. 1983.. 1991.Angelini. et al.L. and F.. 136(2): 205–11. 129(12):1548–50. What is pseudopelade? Clin Exp Dermatol. J Am Acad Dermatol. J Am Acad Dermatol. Thalidomide in the treatment of chronic discoid lupus erythematosus. 34.M.G. Dapsone in the treatment of cutaneous lupus erythematosus. 1986. Sperling L. Follicular degeneration syndrome in men. Warschaw K. and Schmoeckel C. and A.. 172(1):18–23. Dawber R. Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus. Zinkernagel M. 1990. Happle R.. Br J Dermatol. et al. and P.N. C. 36. and R.K.Kerdel.. 124(6):311–15.. 140(2):328–33... Braun-Falco O.Piette.Klokke. and J. 44.M. Messenger. 1992. 2000.. 1992.F.M. Singh Y. and management.A. 62(4):321–4. 23. 27.J. 1993. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? [see comments].. Skelton H. Bulengo-Ransby S. R.O.C. 25. 2000. Powell J. Abeck D. Annessi G.Braun-Falco. and W. Wright A.W. et al.P. Mixed lichen planus-lupus erythematosus disease: A distinict entity: Clinical. 1990. pathology. Dermatologica. 1998. 1(6):351–6. pp. and A. [Use of oral isotretinoin in the treatment of cutaneous lupus erythematosus].C. Holm A. Pseudopelade of Brocq. 108(4):461–6.. Vanderhorst J.Headington. 8:631–40. Isotretinoin for refractory lupus erythematosus. 42(5 Pt 2):895–6. 42.T. 2000. McMeekin T. Br J Dermatol. Chronic cutaneous lupus erythematosus treated with thalidomide. J Am Acad Dermatol. et al.L.L.Parke. Acta Derm Venereol. histopathological and immunopathological studies in six patients. Dermatologica 1986. Tufted folliculitis of the scalp: a distinctive clinicohistological variant of folliculitis decalvans [see comments]. ‘Hot comb alopecia’ revisited and revised. G Ital Dermatol Venereol.M... Clin Exp Dermatol. Hasper M. 70(2):156–9.F.Dawber and K.J.Korting and O. 35. H.Sau.L. Successful treatment of hypertrophic lupus erythematosus with isotretinoin. J Cutan Pathol.Trueb.
Dissecting cellulitis of the scalp: response to isotretinoin.H.C. Recalcitrant scarring follicular disorders treated by laser-assisted hair removal: a preliminary report.C. Efficacy of isotretinoin]. Scerri L. 1994. 49. 6(4 Pt 2 Suppl): 766–85. Shaffer N. and B. 72(2): 143–5.. R.G. Dubost-Brama A... Alfandari S. Action of isotretinoin in acne rosacea and gram-negative folliculitis. and isotretinoin. A case report of combined treatment using tissue expansion. Bachynsky T. 1992. et al. Resolution with combination therapy. 48. 134(6): 1105–8. 45. Ross. 18(10):877–80. J Am Acad Dermatol.Srolovitz.Antonyshyn and J. 25(1):34–7. 1992. Delaporte E. H.R. Dissecting folliculitis of the scalp.. [Perifolliculitis capitis abscedens and suffidiens. Berger T.M. 1999.T.Allen. 46. Arch Dermatol. 47. Perifolliculitis capitis abscedens et suffodiens.H. 1992. Plewig G. 121(4):328–30.. Acta Derm Venereal. Ann Dermatol Venereal. J..B..Nikolowski and H. O. Price V. 128(10):1329–31.. . 1996. radical excision. 50. Br J Dermatol.Williams.Wolff. J Dermatol Surg Oncol.B. Dermatol Surg.Billick and H. 1982. Chui C.. and Zachary C.174 Hair Loss: principles of diagnosis and management of alopecia acid and zinc.
16. 89f. 69 anti-coagulants. 83–119. 19–81. tricyclic/tetracyclic 143 antihypertensive agents 143 antinuclear antibodies (ANA) examination 16. 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. 34f. 91f. 36f clinical features of 28–36 cyclosporin in 66f cytokines and 24 differential diagnosis of 38–42. telogen effluvium and 139 antidepressants. 136–8. 157 antitumor antibiotics 138 anxiety. 137f drug-induced 137t anagen (growing) hairs 6. 88. 42 amitriptyline 143 amoxapine 143 ANA see antinuclear antibodies examination anagen effluvium 134. AA and non-AA 25–7 anthralin 43. 34f. 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. hair loss and 139 anti-psychotics/anxiolytics 143 anti-thyroid drugs. 21 emotional stress and 24 etiology of 19 extent of hair loss 30. 134 anemia. iron deficiency 16 anesthesias. 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. 47. 143 see also hair loss alopecia areata (AA) 9. tretinoin and 108 animal models. 10. 16. vitiligo and 37f alopecia areata circumscripta 31–2f Alopecia Areata Investigational Assessment Guidelines 43 alopecia masking lotion 68 alopecia totalis (AT) 30. 27. alkaline phosphatase activity and 3 anagen-telogen hair ratio 12. 40–1f Down’s syndrome and 20f. 156 adrenoleukodystrophy. 155 anagen phase.Index Note: References to figures are indicated by ‘f’ and references to tables by ‘t’. 68. telogen effluvium and acute 150 . 151. AA see alopecia areata acne 16. 134 androgen blockade 102–4. 48. premature male AGA and 85 adriamycin (doxorubicin). 163 AGA and 96–7 autoimmune disorders and 21 of beard 34. 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. 49–51. 42 alopecia universalis (AU) 30. 114 androgen receptor blockers (ARP inhibitors) 104–5 androgen receptor proteins (ARP) 85 androgenetic alopecia (AGA) 10t. telogen effluvium and prolonged 148 angiogenesis.
16. 105–8. 155 buspirone 143 busulfan 138 C3H/HeJ mice 25. alopecia and 142–3 carbimazole 139 cardiovascular disease 87 carmustine 138 castling. 114 bitemporal recession 91. 136. 167 chronic telogen effluvium (CTE) 150. 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. 48 biologic response modifiers 101. DPCP and 52 catagen 134. 108 delayed anagen release (DAR) 138 delayed telogen release (DTR) 138 depression 9. thinning of 149 bulge area. injection of intralesional 168f coumarins 139 Cox proportional hazards model 87 Crohn’s disease 149 cyclophosphamide 137. 27. 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. 36f Beau’s lines 34 beta-blockers 143 betamethasone dipropionate 43. stem cells of 5. 138 cyclosporin 65–6 cyproterone acetate (CPA) 101. 150 dermal acid mucopolysaccharides 167 dermographism. 69 cortisone. severe 64 despiramine 143 dexamethasone 43 .176 Index arrector pili muscle 5. clues for 21–4 baldness coronary heart disease and 87 drugs and 134 patterns in population 85 prostate cancer and 88 beard. 17. 98. 22 autoimmunity. 151 bleomycin 137 body. 151 cicatricial (scarring) alopecias 10t. alopecia areata of 34 body hair. 26 calcitonin gene-related peptide 25 captopril 143 carbamazepine. 98. alopecia areata of 34. 23 autoimmune polyglandular syndrome 21. 155–72 algorithm for diagnosis for 165f inflammatory 155 lymphocytic 167 pathology algorithm 167f cimetidine. 98 catagen-telogen hair ratio 101 cell-mediated immunity 22–4 cellulitis 156 central centrifugal scarring alopecia (CCSA) 156. 108 cysts. boggy 171f cytarabine 137 cytochrome P450 aromatase enzyme 86 cytokines. 155 catagen hairs 6. 104–5. 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. 156. 155 atherogenesis 88 autoeczematization 64 autoimmune diseases 21. 157 histopathology of 165 vs LPP 158.
164f follicular hyperkeratosis 58. 170f. 143. levels of 98. 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. tufted 166. 21 doxepin 143 doxorubicin (adriamycin). 51. 163. 171 fronto-parietal/fronto-temporal recession 90 fusidic acid 171 gastric parietal cell antibodies 22 gene replacement therapy 70 gold. 145 lichenoid eruption of scalp 134 telogen effluvium 139t. loss of 144 hair cortex 4. 133 hair transplants and 130 and minoxidil combination therapy 110 fluocinolone 43 fluorouracil 137 fluoxetine 143 follicular bundles. 141t Dundee experimental bald rat (DEBR) 25 dyslipidemia 88 dysmorphobia 9 dystrophic anagen hairs. 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. 109. 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. 158 pattern in a family 95f prevention of 101. positive pull test 96 dystrophic hairs. 167. 140t. with miniaturized hairs 99f follicular degeneration syndrome (FDS) 156. 156. in women 150 dihydrotestosterone 85 dinitrochlorobenzene (DNCB) 51–2 diphenylcyclopropenone (DPCP) 26. 148 diffuse alopecia areata 30. 165 follicular ostia 10. 11f . 136 hair counts 13. 5.Index 177 diabetes mellitus 22 dibromoketone 53 diffuse alopecia 16. 6 abnormalities of 15 quality of 10. alopecia and 137 drug-induced alopecia 134–46 anagen effluvium 137f. alopecia and 147 finasteride 101. 171 folliculitis decalvans (FD) 155. 16. 88. alopecia areata and 20f. 166 eosinophils 27 epidermal growth factors (EGF) 105 erythema 163. laser-assisted 171 hair shafts 2. counts of 12 dystrophy. 102–4. 170f erythema multiforme 64 estrogen. 113 severity of 148 see also alopecia hair matrix cell mitosis 136 hair removal. checking for presence of 15 eczema. planting of 129 hair loss 9. 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. 155 follicular scalp lesions 158 follicular stem-cell gene therapy 114 follicular stem-cells 155 folliculitis. 52–64. 17 divalproex 142 dopaquinone 6 Down’s syndrome. DPCP and 64 elastin staining 156. 158. 151 fever. 33f diffuse cyclic hair loss. 170f. 103 hair cycling.
158–63. in teenagers 95f Ludwig Stage III. 140. 108. 12 abrupt diffuse 148f. 151 hair transplants 101. 5. 5 Kaplan-Meier survival analysis 53 keloids 125 keratin 4 keratinization. 4. 148 isotretinoin 169. 5 hen’s egg test 53 heparin 139 hepatic disease 149 hirsutism 16. 158 lichenoid eruption 136 lithium 140–2 Ludwig pattern. 155. 169f cicatricial alopecia 10t pathology of 166f peripheral distribution 165 lichen planus 17. 159– 60f. 169 complication of donor area 126 finasteride and 130 male 113f. 89. 22. 98. AGA and 85 intralesional corticosteroids 67. 147 immediate telogen release 138 immunosuppressive therapy. 83 halcinonide 43 haloperidol 143 Henle’s layer 2. 4. 121–2f. 169 intramuscular corticosteroid therapy 47 iodine. 64 lymphocytic-mediated cicatricial (scarring) alopecias 156–70 treatment algorithm 168f M phase drugs 138 . 156. 148 iatrogenic hypothyroidism 139 ICAM-1 27 ichthyosis 144 ifosfamide 138 imipramine 143 immediate anagen release 138. 171 isthmus 1. abnormal 24 keratoacanthomas 167 keratotic follicular papules 155 leflunomide 26 lichen planopilaris (LPP) 155. study of 103 hair-growth promoters 101 hair-specific antibodies 23 hairpieces 69. women with 108 Ludwig Stages I–III 90f lupus erythematosus 22. 144 keratinocytes. 149f physiological 6 hair thinning 9. 87. 108 hyper-insulinemia 88 hyperpigmentation 64 hypertension 47. 108 Hodgkin’s disease 149 hormone modifiers 101. 102–5 Hox genes 26–7 human leukocyte antigens (HLA) 19–21 Huxley’s layer 2. 5 hyaluronic acid 3 hydroxycarbamide 137 hydroxychloroquine 169 hydroxyurea 138 hyper-androgenism 16. 158 hypopituitarism 85 hypothyroidism 9.178 Index hair shedding 9. 4. 101 hairs light-microscopic examination of 13–16 miniaturization of 27. 87. 158. responsiveness to 21 inflammatory bowel disease 149 infundibulum 1. 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. 69. 110. 5 insulin-resistance-associated disorders 88 interferons 143 intracellular androgen metabolism. telogen effluvium and 139 iron deficiency 16. disturbed 136. stages of 89 Ludwig Stage I pattern. 136. 169f chronic cutaneous scalp 157f luteinizing hormone-releasing hormone (LH-RH) 105 lymphadenopathy 62f. 88 hyperthryoidism 9 hypertrichosis 108 hypertrophic lupus erythematosus 167 hypo-proteinemia 147 hypopigmentation 64. 163 inner root sheath (IRS) 2.
hair loss and 158 6-mercaptopurine 138 mesenchymal-derived dermal papilla 86 methotrexate 137. 42 procarbazine 138 Propecia 102. 33f oral contraceptives 143 oral cyclosporine 22 outer root sheath (ORS) 2. 17f non-inflammatory cicatrizing alopecias 155 nortriptyline 143 Norwood-Hamilton classification 92. 109 Norwood-Hamilton pattern 90. 93 minoxidil (Rogaine) 43. 37 National Alopecia Areata Foundation (NAAF) 19.Index 179 McKusick Mendelian Inheritance in Man (MIM) 83 Major Histocompatibility Complex (MHC) 19 malignant diseases 149 maprotiline 143 mechlormethamine 137 medulla 2. 138 men AGA treatment options 101 frontal hairline recession 89 vertex balding in 87 mepacrine (atabrine). 163 pseudopelade (PP) 38. 16. intravenous methylprednisolone 47 pustules 156 PUVA therapy see photochemotherapy pyrogens. 101. 156. 47–8. therapy and 113–14 peri-infundibular lymphocytic infiltrate 166 perifollicular interface dermatitis 165 pernicious anemia 22 pheomelanin 6 photochemotherapy (PUVA) 64–5. 6 melanocytes 6. alopecia areata and 34. 166 psycho-physical trauma 147 psychogenic pseudoeffluvium 151 psychopharmacologic medications 140–3 pull-tests 10. 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. 42 patient. 147 prednisolone. endogenous 147 quail-chick model 86 5α-reductase 85 . 169 pulse therapy. 24–5 melphalan 18. 11f. 161f. 5 papular atrichia 85 paroxetine 143 PAS stain 156 patchy alopecia areata 30. 58f ophiasis inversus (sisapho) 30. 156. 88 olanzapine 143 onychorrhexis 34 ophiasis 33f. 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. pulsed oral 47 pressure-induced alopecia (PIA) 38. 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. 104 propylthiouracil 139 prostate cancer. hairless 26 micro-grafting 132 Microsporum canis 42 mini-grafting 132 miniaturized hairs 88. 105–8. 138 methylprednisolone 47 methylthiouracil 139 mice. 37. AGA and incidents of 88 protriptyline 143 pruritus 158. 109 and hair transplants 130 hypertrichosis of the face and 107f topical 133. 93. history of 9 patient expectations. 163. 170 use of betamethasone dipropionate and 48f monoamine oxide inhibitors 143 morphea 156 mouse teratogenicity test 53 myasthenia gravis 22 nail dystrophy. 4 melanin 3. 33f.
hirsutism. 155 cross-section of 8f positive pull test 96 temporal triangular alopecia (TTA) 42 terminal-vellus hair ratio 27. loss of 165 seborrheic dermatitis 100 serotonin reuptake inhibitors 143 sertraline 143 serum ferritin. 10t. 28 systemic diseases 136 systemic erythromycin 171 targeted follicular gene therapy 114 telangiectasia 158 telogen effluvium 9. 27. 142f acute and chronic 147–53 alopecia areata and 27. 16. 28. alopecia. 27. 108 squamous cell carcinomas 167 squaric acid dibutyl ester (SADBE) 26. 105.180 Index renal failure 149 respiridone 143 reticular alopecia areata 30. 33f skin diseases. 156 scalp irritation. 16. 148 thyroid screening 9 thyroid stimulating hormone test (TSH) 98 thyrotoxicosis 139. 4f syphilitic alopecia 27. 134 drug-induced 139–44 pathology of 28 types of 138–9 in women 86 telogen hairs 6. 33f Retin-A 108 rifampin 171 Rogaine see Minoxidil S phase-specific drugs 138 SAHA (seborrhea. 167 topical immunotherapy 43. 134. 38. 52 steroid-metabolizing enzymes 85 steroids systemic 22. 134 testosterone 85 thalidomide 169 thallium. 96f. 51. 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. 138 thyroid dysfunction 16 thyroid function assessment 140 thyroid influences 21. evaluation of 16 sex hormone binding globulin (SHBG) 105 short-contact therapy 49 shortened anagen (SA) 138 sisapho 30. 98. hair loss and 144 thiotepa 137. 10t. 28. 46–7 topical. 38 triparanol 144 tufting. acne) syndrome 87 Salmonella typhimurium 51 sarcoidosis 156 scalp cellulitis of 171f physiology of 1–8 scalp biopsies 14–15f. alopecia and severe 136 Smyth chicken model 25 soriatane 144 spironolactone 101. intralesional and systemic 43 stress alopecia areata and emotional 24 telogen effluvium and psychological 150 striae. 25 support groups 69 suprabulbar area 1. systemic steroids and 47 substance P (SP) expression 24. 140 tinea capitis 9. 51–64. 151. 69 topical ophthalmic beta-blockers 143 trachyonychia 34 traction alopecia 10t. cicatricial alopecias and 163 tyrosine 6 ulcerative colitis 22 valproic acid (VPA) 142 vasopressin 138 . minoxidil and 10 scalp lesions 158 scalp prostheses 68f scalp psoriasis 167 scalp reduction 169 scarring alopecia see cicatricial alopecia sebaceous epithelium. 95 differential diagnosis 38.
98. 99f vellus-like hairs 7f vertex pattern balding 87 vertex thinning 90 vinblastine 137. 64 women AGA in 88.Index 181 vellus hairs 6. 108–9 Woods light examination 42 zolpidem 143 . 91f finasteride and 104 hair loss in 86 hair transplantation in 131–2 treatment of AGA in 101. 89f. 138 vincristine 137. 138 vitiligo 63f.
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