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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 .
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Contents Foreword Acknowledgements 1 Assessment of the patient with alopecia Alopecia areata: Pathogenesis. 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 . diagnosis and practical management Androgenetic alopecia: Pathogenesis. clinical features.
comprehensive text about hair that enriches the reader from bench to bedside. and where appropriate. He has written a unique text that will be invaluable for clinicians. Jerry Shapiro has accomplished an amazing single-authored. This is an organized and rational guide for assessing and managing hair loss. The illustrations are extensive. Vera H Price MD. The text is exceptionally readable and complements the book’s systematic and inviting organization. His explicit recommendations about management are given. 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. FRCPC Professor of Clinical Dermatology School of Medicine University of California. all extensively referenced. and students of the hair follicle. researchers. Complex issues are presented. he also includes the treatment preferences of other hair experts. a collection of unique photographs and photomicrographs from his own collection. 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. San Francisco . in clear terms for all readers.Foreword Jerry Shapiro is a dedicated clinician/scientist who has devoted himself to all aspects pertaining to the hair follicle.
who has. It continues to be an honor for me and I thank them for this. whose time and efforts were absolutely essential in making this book possible. and continues to guide and nurture me in the field of dermatology. whose advice. who has been my ‘’hair’’ mentor for over 15 years and has been an inspiration and role model. who allowed me to learn from her in Cleveland and from whom I continue to learn. who was dedicated and helped shape the University of British Columbia Hair Clinic during its early years. My research associate. support and encouragement helped the University of British Columbia Hair Research and Treatment Centre flourish. My Hair Fellows: Dr Chantal Bolduc. Dr Vera Price. Jerry Shapiro University of British Columbia Hair Research and Treatment Centre . First and foremost. my Hair Transplant nurse. Dr Shabnam Madani and Dr Olga Bernardo. I would like to thank certain individuals who have played an important part in my career. they truly are very special people. Lucianna Zanet. who continue to enlighten me regarding the histopathology of the hair follicle. Dr Wilma Bergfeld. who was the first individual to encourage me to take on the field of hair. Dr Liren Tang. Each fellow has questioned. Next. 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.Acknowledgements There are certainly many individuals to thank in the making of this book. Dr David McLean. who took time out of their busy lives to commit a year to studying hair with me. Charlotte Mossop and Robert Peden. Drs Magda Martinka and David Shum. my first Hair Clinic nurse. 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. Dr Harvey Lui. I thank my editors. challenged and inspired me to learn so much more. who continues to teach me the molecu- lar biology and basic science of hair. Dr William Stewart. who has guided me for the last 10 years with all her great surgical skills and great common sense approach to patients. I am most indebted to my hair loss patients who have trusted me and given me the privilege of taking care of their hair. Nina MacDonald.
Bulb: consisting of dermal papilla and matrix intermixed with melanocytes (Figure 1. as therapy is dictated by the appropriate diagnosis. it is important to review the basics of hair anatomy and physiology of the scalp. Ancillary laboratory evaluation may sometimes be necessary to help confirm a diagnosis.1 The first task of the physician is to address the patients’ concerns fully. isthmus.1 Assessment of the patient with alopecia Hair loss (alopecia) is a very common patient problem and often a significant source of patient distress.2) 1. Figure 1. . The hair follicle is divided into 4 parts: (Figures 1. 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 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. Infundibulum extending from sebaceous gland to the follicular orifice. organized approach is crucial. Suprabulbar area from matrix to insertion of arrector pili muscle 3. An accurate diagnosis can frequently be difficult. suprabulbar area.3) 2. Isthmus extending from insertion of arrector pili muscle to sebaceous gland 4. exploring the impact of alopecia on psychosocial well-being.1 and 1. Patients are most appreciative of a supportive diagnostic approach. Next. and infundibulum.1 Diagrammatic representation of hair anatomy: The hair follicle is divided into 4 parts: bulb. Basic trichologic anatomy and physiology In order to appreciate an organized diagnostic protocol for alopecia. A rational.
There is a large amount of acid-mucopolysaccharides within the dermal papilla. which contains highly vascularized connective tissue (Figure 1. Note the melanocytes within the matrix providing pigment to the hair. Dermal papilla fibroblasts are inherently different from non-follicular dermal fibroblasts. (2) matrix.4). consisting from inward to outward of medulla.) The lower portion of the hair follicle consists of five major portions (1) dermal papilla. (4) inner root sheath. inner root sheath (IRS). (b) Two anagen follicles side by side at the level of fat. and (5) the outer root sheath. (Courtesy of Dr Magdalena Martinka and Dr David Shum.2 Hair Loss: principles of diagnosis and management of alopecia Figure 1. matrix (M). consisting of inner root sheath cuticle. cortex. staining positively for Alcian blue and metachromatically for .2 (a) Histology of the hair follicle on longitudinal section showing dermal papilla (DP). Huxley’s layer on the inside and Henle’s layer on the outside. (3) the hair shaft. outer root sheath (ORS) and fibrous root sheath (FRS). and cuticle. The base of the follicle is invaginated by the dermal papilla.
4 The different layers of the hair follicle .Assessment of the patient with alopecia 3 Figure 1. The hair matrix has large vesicular nuclei and deeply basophilic cytoplasm. each of which Figure 1. The ground substance consists of not only non-sulfated polysaccharides such as hyaluronic acid. In persons with dark hair large amounts of melanin can be seen in the dermal hair papilla. (b) Cross-section of the follicle at the level of the dermal papilla. but also sulfated mucopolysaccharides such as chondroitin sulfate.2 and 1. is produced in these melanocytes and incorporated into the future cells of the hair through phagocytosis of the distal portion of the dendritic melanocyte. (Courtesy of Dr Magdalena Martinka. The DP allows capillaries to gain entrance to the cells of the matrix. which is an invagination of the dermis into the matrix (M). Cells of the hair matrix differentiate into six different types of cells.3 (a) Close-up of longitudinal section of dermal papilla (DP). Dopa-positive melanocytes are interspersed between the basal cells of the matrix lying on top of the dermal papilla (Figures 1. Alkaline phosphatase activity is also increased in the anagen phase.) toluidine blue.3). varying in quantity in accordance with the color of the hair. Melanin. 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. Melanocytes fill the matrix and produce the pigment of the hair.
resulting in the firm attachment of the hair to its inner root sheath. and the already keratinized Henle’s layer. It may not always be present. (courtesy of Dr David Shum.5). Keratin of the cortex is hard keratin. None of these layers contain melanin. and the medulla is last (Figure 1. and all keratinize with trichohyalin granule formation. The hair cortex then follows. The hair cuticle located peripheral to the hair cortex consists of overlapping cells arranged like shingles and pointing upward with their peripheral portions. The inner root sheath is composed of three layers (Figures 1. The outer layer of the inner root sheath (IRS). The cuticle of the IRS consists of one layer of flattened overlapping cells that . In the central portion of the follicle the matrix (M) is forming cortex. The hair medulla appears amorphous because of its only partial keratinization. The hair and the inner root sheath move in unison upward. These granules stain eosinophilic. No keratohyaline granules (as in keratinizing epidermis) or trichohyaline granules (as in inner root sheath) are formed during keratinization. keratinizes first. in contrast to the basophilic keratohyalin granules of the epidermis.) keratinizes at a different level.4 Hair Loss: principles of diagnosis and management of alopecia Figure 1. in contrast to the inner root sheath or epidermis.The outer root sheath (ORS). The cells of the hair cuticle are tightly interlocked with the cells of the inner root sheath cuticle. This is subsequently invested by the cuticle of the inner root sheath (IRS).4 and 1. which is soft keratin. followed by Huxley’s layer. hyaline membrance and fibrous root sheath (FRS) surround the whole structure.4).5 (a) Cross-section and (b) longtitudinal sections of the follicle at the suprabulbar level. Henle’s layer. Huxley’s layer with trichohyaline granules. which is surrounded by the cuticle. The two apposed cuticles covering the inside portion of the IRS and the outside of the hair keratinize next. establishing a firm coat around the soft central portions of the follicle. The hair cortex cells during upward growth from the matrix cells keratinize gradually by losing their nuclei and become filled with keratin fibrils.
and is thickest in the middle portion of the hair follicle. The ORS is thinnest at the level of the hair bulb. Trichohyalin granules are few in the IRS cuticle. where it changes into surface epidermis. below the isthmus. at the level of the isthmus the IRS disintegrates. It is lined by surface epidermis Figure 1. However. All of this is surrounded by outer root sheath.8 Melanosomes of the hair cortex are larger than those of the epidermis.2–7 Stem cells from the bulge area likely migrate to other portions of the hair follicle and differentiate into its differing layers.6).5). Huxley’s layer is two cell layers thick and develops numerous trichohyalin granules (Figure 1. In its lower portion. .) undergoing keratinization with the formation of keratohyaline granules. The glassy or vitreous layer. which forms a homogeneous eosinophilic zone peripheral to the outer root sheath. which is composed of thick collagen bundles. Henle’s layer. only one cell layer thick. The isthmus is the segment that extends from the arrector pili muscle to the sebaceous gland duct entrance.Assessment of the patient with alopecia 5 point downward in the direction of the hair bulb. producing large homogeneous keratinized cells without the formation of keratohyaline granules. is periodic acid Schiff-positive and diastase-resistant. It differs from usual basement membrane zone by being thicker. Only anagen hairs have inner root sheaths. Peripheral to this vitreous layer lies the fibrous root sheath. The upper portion of the follicle above the entrance of the sebaceous duct is the infundibulum.6 Cross-section of the follicle just beneath the isthmus showing the eosinophilic completely keratinized inner root sheath (IRS) enclosing the hair shaft (HS). and is the likely location of the first primordial cells (stem cells) of the hair follicle. It is thickest around the lower third of the hair follicle. There is no inner root sheath here. gradually increases in thickness. The ORS has plentiful vacuolated cytoplasm owing to its plentiful glycogen. (Courtesy of Dr David Shum. They are located usually in the interfibrillary matrix. This connective tissue sheath may contain considerable reproductive potential. the isthmus. but serve as a hard molding scaffold up to the arrector pili muscle. The ORS undergoes trichilemmal keratinization. hyaline membrane and fibrous root sheath. The cells of the IRS do not contribute to the emerging hair. as was recently shown by Reynolds et al. Just before the isthmus the IRS becomes fully keratinized (Figure 1. The outer root sheath (ORS) extends from the matrix cells to the entrance of the sebaceous duct. Since the cells of the hair cuticle point upward. already shows numerous trichohyalin granules as it emerges from the matrix. these two types of cells interlock tightly. it is covered by IRS and does not undergo keratinization. They lie singly or within groups not within lysosomes. The point of insertion of the arrector pili muscle is referred to as the bulge area.
Blonds Figure 1. Anagen may last up to 2–6 years. the black brown pigment eumelanin and the yellow red pheomelanin. In certain individuals. especially of melanosomes. During the hair cycle. and redheads less. Two types of melanin are present in mammalian hair. with fewer hairs per square cm in Blacks and Orientals. and only rarely in the intercellular space (Figure 1. In the eumelanin containing follicle. The scalp consists of almost 90% of hairs in anagen. There is ethnic variation. where hair cycling is synchronous. melanocytes at the basal layer of the hair matrix are usually reduced in number or are absent. Dark hair contains more eumelanin and blond hair more pheomelanin. The sizes of the hair shafts are important in determining a diagnosis. at 80. there is periodicity in the number of telogen hairs. The growing or anagen hairs are anchored deeply within the subcutaneous fat (Figure 1. Physiologic hair shedding of 100 hairs per day is usual on the average. In white hair. Both are synthesized from tyrosine.000 hairs.10) and can be pulled out relatively easily. and catagen 3 weeks. at 120. during anagen are transferred from melanocytes to matrical cortex cells via dendritic ends.6 Hair Loss: principles of diagnosis and management of alopecia within the cells. with a maximal number in late summer.8 and 1. The average number of hairs for a normal scalp is 250 per square cm or 1100 per square inch.7 Melanosomes. Vellus hairs or miniaturized vellus-like hairs of androgenetic alopecia (AGA) have a shaft diameter of less than .7).8) and cannot be pulled out easily. Melanocytes show degenerative changes. melanocytes have higher amounts of eumelanosomes. tend to have more. Unlike animals. The hair shafts only contain the detritus of melanin or no melanin at all.000. while the lower portion is non-permanent.8). 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. either eumelanin or pheomelanin. Hair fiber is produced during anagen at a rate of approximately 1 cm/month or 0. Increased hair shedding is usually noted in autumn.000. telogen 3 months. with fluctuations over the year.35 mm/day. In other hair colors. In fire-red hair there are high levels of pheomelanosomes. This ratio is usually uniformly distributed over the entire scalp. January or February. (Figure 1. which is converted to dopaquinone which can then undergo oxidative reactions to form either eumelanin or pheomelanin. 1% in catagen and 10% in telogen. Decreased telogen hairs occur in December. The telogen hairs are located higher up in the dermis (Figures 1. on the human scalp there is an asynchronous mixture of hairs actively growing and resting. The normal scalp contains 100. the middle and upper portions of the hair follicle are the permanent segment of the hair follicle.
06 mm in diameter and can grow up to 3 feet. 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. and during telogen is closely associated with the stem cells of the bulge area. The dermal papilla (DP) is pulled upward with each cycle.Assessment of the patient with alopecia 7 Figure 1. telogen 3 months. the middle and upper portions of the hair follicle are the permanent segments of the hair follicle. The scalp consists of almost 90% hairs in anagen. Only miniaturized vellus-like hairs of androgenetic alopecia have arrector pili muscle. A true vellus hair does not have an attached arrector pili muscle. 1% in catagen and 10% in telogen.9 Vellus-like hairs are less than 0. while the lower portion is non-permanent. (a) The growing or anagen hairs are anchored deeply within the subcutaneous fat and cannot be pulled out easily. This ratio is usually uniformly distributed over the entire scalp. (b) The newly formed anagen hair pushes out the previous telogen hair. Figure 1.8 During the hair cycle. Anagen may last up to 2–6 years. Terminal hairs are coarse over 0. . and catagen 3 weeks.03 mm in diameter and rarely grow more than 1–2 mm. The telogen hairs are located higher up in the dermis and can be pulled out relatively easily.
Because of the multiplicity of disorders that can result in hair loss. (Courtesy of Dr David Shum.) .8 Hair Loss: principles of diagnosis and management of alopecia 0. a thorough history and physical examination are important.11). The lower portion of terminal telogen hairs is found higher up in the dermis. (Courtesy of Dr David Shum and Dr Magdalena Martinka.) There are many etiologic factors that cause clinical hair loss. A central starshaped area of trichilemmal keratin can be noted. Terminal hairs have a shaft diameter greater than 0. Patient approach Figure 1.06 mm. and structural hair defects.10 Cross-section of telogen hair. and ancillary laboratory work-up may be necessary. whose bulbs are found in the area of subcutaneous fat. psychological abnormalities. (b) The small size of the hairs make the sebaceous glands look more hyperplastic. diet. or alopecia.03 mm (Figures 1. systemic illness. autoimmunity. unlike terminal anagen hairs. (a) Hair shafts are small (<.11 Small vellus-like hairs (V) in androgenetic alopecia. hyaline membrane and fibrous root sheath.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. infections. including endocrine abnormalities.03 mm). surrounded by outer root sheath. drugs. trauma. genetic predisposition. Figure 1.
2). It is also important to question about the loss of axillary and pubic hair. high fever. back brushing. bleaching. Patients should be asked questions regarding hair shedding (alopecia areata or telogen effluvium) versus simple hair thinning without shedding (androgenetic alopecia).2 Differential diagnosis .1 Hair loss history questionnaire Table 1. the presence or absence of coincidental acne and abnormal menstrual cycles may indicate an androgen excess causing androgenetic alopecia. Certain conditions are more common in childhood compared to the adult. operations/general anesthesia. The patient’s concerns and expectations should be acknowledged and fully explored. Many patients with hair disorders become frustrated when their worries about hair loss are either ignored or dismissed as insignificant. diffuse versus focal) of hair loss is very important to determine. eyelashes. since many medications can induce hair loss. permanent waving) may result in hair breakage. The duration and pattern (i.1). or weight loss in the preceding 6 months? A positive family history of alopecia areata or androgenetic alopecia may point to a genetic predisposition for hair loss. A full list of current and past medication should be obtained (see Chapter 5). In addition. crash diets.e. Key questions implicating a telogen effluvium are: Any pregnancy. since there are completely different causes for each of these situations (Table 1. The age of the patient is very important.g.Assessment of the patient with alopecia 9 History The history is of critical importance in developing the initial differential diagnosis (Table 1. eyebrows. The two most common forms of hair loss in children are tinea capitis and alopecia areata. and a strict vegetarian diet can implicate iron deficiency anemia. Some hair care practices (e. Thyroid screening questions may point to hyper. Explanation and discussion may resolve the problem without specific intervention. It is important to establish whether the hair falls out from the roots or breaks off along the shafts.or hypothyroidism. since any hair-bearing area may be affected by alopecia areata or trichotillomania. Occasionally an underlying depression or dysmorphophobia (pathologically focused Table 1. and body hairs.
should be conducted. such as alopecia areata.13). index and middle fingers from the base of the hairs near the scalp. and firmly. length and shape. Second.3 Causes of alopecia . Note: (a) Follicular ostia in a non-scarring alopecia.3). Random patterns are more common for alopecia areata. a useful ancillary test. Non-cicatricial alopecias demonstrate visible follicular units. study the quality of the hair shaft in terms of caliber. tugged away from the scalp (Figure 1. fragility. examine the pattern of density and distribution of hair.12 Presence or absence of follicular ostia is crucial in the differential diagnosis. Certain characteristic patterns of hair loss are more common for certain diseases. It is important to determine if the hair loss is associated with scalp scarring (Table 1. On the scalp. as this introduces an entirely different differential diagnosis. first inspect for inflammation. If Clinical examination Clinical examination should be performed in three stages.14).10 Hair Loss: principles of diagnosis and management of alopecia Figure 1. Approximately 60 hairs are grasped between the thumb. the ‘pull test’.12). contrast paper and place the hairs against it to examine the sizes of hairs (Figure 1. scale. Finally. fixation on body image) may be present. (b) Absence of follicular ostia in a scarring alopecia. It is useful to take a Table 1. It is important that these psychiatric conditions be recognized and managed before any further treatment is initiated. and erythema. but not forcefully. while cicatricial alopecias are devoid of follicular units (Figure 1. Pull test: To determine the ongoing activity of hair loss.
More than 6/60 hairs is a positive pull test and implies pathology. . (b) The hairs are then tugged from proximal to distal end.14 Pull test: (a) Approximately sixty hairs are grasped from the proximal portion of the hairs shafts at the level of the scalp. It is normal to pull up to 6/60 (< 10%) hairs.13 A contrast paper positioned at an involved area of the scalp will help determine the length. (c) The number of hairs extracted is counted.Assessment of the patient with alopecia 11 Figure 1. This alopecia areata patient showed one month of spontaneous regrowth in a bald patch without any treatment. size and overall caliber of the hair shafts. This is a 57year-old female with diffuse alopecia areata displaying a very positive pull test. Figure 1.
popularized by Rushton. The unit area trichogram.10 is more accurate than the regular trichogram. For noncicatrizing alopecias this anagen/telogen ratio has diagnostic significance. hairs are taken from specified sites. hairs are taken from specified sites9. With this technique. Counts of dystrophic hairs are unreliable.15 Trichogram/Pluck test: The trichogram/pluck test is another method of assessing hair loss. 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. as it takes into account not only anagen/telogen ratios but also hair density and size. The surrounding hair is fixed with clips and 60–80 hairs are grasped with a hemostat covered with rubber and are plucked. Anagen hairs are distinguished from telogen hairs and anagen to telogen ratios are calculated. the trichogram has not become routine. The pull test helps to assess the severity and location of hair loss. On the fifth day after the last shampoo. twisting and lifting the hair shafts rapidly in the direction of emergence from the scalp. Hair shafts are then cut off 1 cm above the root sheaths and roots are arranged side by side on a slide. this is considered normal physiologic shedding. (a) The surrounding hair is fixed with clips and 60–80 hairs are grasped with a hemostat covered with rubber and are plucked.15). since much of the observed hair dystrophy is artefactual. Because a scalp biopsy can give the physician the same information plus more regarding inflammation and the size of hairs. owing to hair damage caused by the plucking procedure. (b) Anagen hairs are distinguished from telogen hairs and anagen to telogen ratios are calculated. . twisting and lifting the hair shafts rapidly in the direction of emergence from the scalp (Figure 1. this constitutes a positive pull test and implies active hair shedding. On the fifth day after the last shampoo. The patient must not shampoo for at least one day prior to the pull test.12 Hair Loss: principles of diagnosis and management of alopecia more than 10% or 6 hairs are pulled away from the scalp. Trichogram/pluck test: The trichogram/ pluck test is another method of assessing hair loss. If less than 6 hairs can be easily pulled away from the scalp.
16). as it is expected that there will be more shedding on those days. All hairs shed in the shower. But it is something that patients can do on their own to follow their progress. Patients are instructed to do this daily for 7 days. 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.16 Light microscopic examination of hairs: (a) telogen hair with characteristic club. It is normal to lose 100–150 hairs per day. Patients are asked to collect all the hairs shed in one day.11 Light-microscopic examination Hairs extracted by slow pull can be examined under the light microscope (Figure 1. counter or pillow are collected. but only physiologic hair loss. then there is currently no active shedding.Assessment of the patient with alopecia 13 slide for counting. or sink or on the brush. If the patient is losing less than 100 hairs per day. (b) anagen hair with inner root sheath. Hair shafts are mounted in parallel Figure 1.) . (c) hair shaft abnormality: trichorrhexis nodosa secondary to trauma. This meticulous technique can be quite laborious and requires very special skill. (Courtesy of Dr David Shum. Performing a hair count is tedious and timeconsuming for the patient. count them and place them in plastic sandwich bags.
In patients who have curly hair as above. Staying away from hair parts or the frontal portion of the scalp is recommended. Epinephrine causes vasoconstriction. insert the punch perpendicular to the scalp. This allows the vasoconstrictive effect of epinephrine to take effect and hence maximize the hemostasis. Penetration of the punch to a depth of approximately 3. lidocaine 1 % with epinephrine in a concentration of 1:100. For local anesthesia.0 mm punch biopsy is placed parallel to follow the direction of the hair. 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. The typical punch should be pushed right through to the hub. In addition.000 is injected with a 30 gauge needle into the scalp. If possible the biopsy should be taken from a cosmetically less apparent area of the scalp. (b) A 4. In noninflammatory conditions a biopsy in a representative area is sufficient.0 mm is sufficient to obtain a full scalp thickness. which has a hemostatic effect in a highly vascular site such as the scalp.14 Hair Loss: principles of diagnosis and management of alopecia Figure 1. . a mandatory waiting period of at least 10 minutes is suggested following the anesthetic injection.5–4. The area to be biopsied is marked with a red china marker.17 How to do a scalp biopsy: (a) In order to obtain sufficient histopathologic information.
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. The free ends of the hair should be checked to see whether they are tapered. between two glass slides taped together. (f) The biopsy defect is closed with a bluecolored monofilament suture. . hairs should be placed on a glass slide with 20% potassium hydroxide added in order to demonstrate fungal spores and hyphae. Roots should be examined to determine the stage of the hair cycle and for the presence of dystrophy. which helps to identify the suture on the hairy scalp. A drop of cyanoacrylic glue placed on the slide will give greater contrast under the microscope compared to a dry mount. Hair shaft abnormalities (which can increase hair fragility and cause hair loss) can be diagnosed with this method. Wound dressings are not necessary for scalp biopsies. and the hair mount is not used routinely at the University of British Columbia (UBC) Hair Clinic unless indicated. The hair shafts need to be examined to detect fractures. preventing damage to the hair bulbs located in the deep dermis. If fungal diseases are suspected. coiling and twisting and extraneous matter. particularly with pigmented hairs. The suture needle is passed through the upper dermis. For the most part. irregularities. (e) Aluminum chloride 20% solution on a Qtip can be used for hemostasis after the biopsy has been removed. most hair shaft abnormalities are quite rare. fractured or weathered. cut.
Evaluation of serum ferritin may be necessary to exclude iron deficiency anemia. or irregular menses.17). The characteristic histologic features of the most common non-cicatrizing and cicatrizing alopecias are discussed in subsequent chapters. a thyroid-stimulating hormone level should be investigated. telogen effluvium. although they can sometimes be difficult to appreciate when miniaturized. One half is sent for direct immuno-fluorescence and the other half for longitudinal sectioning. The technique of vertical sectioning was popularized by Headington13 and subsequently by Whiting14 and Sperling. In cases of confirmed scarring alopecia due to discoid lupus erythematosus. there is preservation of follicles on clinical and histologic examination. The upper levels contain telogen and anagen hairs. Peri-. The difference between the mid levels and the lower levels is the number of terminal telogen hairs. Usually this involves a depth of 4 mm. Another 4 mm bi- opsy is bisected longitudinally. The biopsy must be deep and include the entire follicular unit. at around 30. but occasionally they may also be difficult to distinguish clinically from non-scarring alopecias. Table 1. and alopecia areata. For those difficult cases. If thyroid dysfunction is suspected. The three most common forms of non-cicatricial alopecias are androgenetic alopecia. This allows a greater number of follicles to be examined. the number is reduced to 35. it is obligatory to perform a 4 mm scalp biopsy. an antinuclear antibodies (ANA) examination should be performed.and interfollicular inflammation. At the level of reticular dermis near the base of the infundibulum. The first 4 mm punch biopsy is taken for transverse sectioning. Non-cicatricial alopecias In the non-cicatricial alopecias. particularly in women with diffuse alopecia. The difference between the upper levels and mid levels is usually the number of vellus or vellus-like hairs. and dehydroepiandrosterone sulfate (DHEAS) is advised to rule out hyperandrogenemic states.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. at the deeper levels near the subcutaneous fat. acne. the numbers are even less. two biopsies are taken. At the UBC Hair Clinic all biopsies for non-cicatrizing alopecias are performed with transverse/horizontal sectioning rather than longitudinal/vertical sectioning. intra. The deeper levels contain anagen terminal hairs. will be very prominent at all levels of the biopsy. 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. Not only are the various scarring alopecias difficult to differentiate from each other clinically. The mid-levels consist of anagen and telogen hairs with terminal hairs only. as well as terminal and vellus and vellus-like miniaturized hairs. For cicatrizing alopecias. In women with androgenetic alopecia and virilizing signs such as hirsutism. if present. These conditions are discussed at length in other chapters of the book. an endocrinologic work-up consisting of free testosterone. Laboratory tests: Lab tests may be helpful in establishing a diagnosis. .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.4 compares the key clinical features that distinguish these three conditions from each other. Normally a scalp biopsy has 35–40 hairs at the upper levels in papillary dermis. including some subcutaneous fat (Figure 1.
Scarring alopecias are considered true trichologic emergencies. oral or genital mucous membranes. The importance of prompt appropriate therapy is crucial. The first task of the physician is to acknowledge the patient’s concerns and have an empathetic approach to the problem of hair loss. A biopsy is necessary to establish an accurate diagnosis. Lesions of DLE demonstrate marked erythema. The diagnosis depends upon a combination of find- . and bacterial infections. atrophy.Assessment of the patient with alopecia 17 Table 1. acute fungal infections such as tinea capitis. telangiectasia.4 Common non-scarring alopecias Cicatricial (scarring) alopecia Localized areas of cicatricial alopecia of the scalp may result from trauma. as there is irreversible hair loss once hair follicles have become scarred. viral infections such as herpes zoster. burns. 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. Evidence of cutaneous disease elsewhere on the skin. and nails should be looked for carefully. The most common causes for scarring alopecia are discussed at length in Chapter 7. and follicular hyperkeratosis. Discoid lupus erythematosus (DLE) is the most common primary cause of scarring alopecia. and lichen planus is another common etiology.
J Invest Dermatol. CserhalmiFriedman P. 642: 214–24. D. pp. 15. 1999. Clinical tools for assessing hair loss. 224–5. 59–69.C. 12. 14. Trans-gender induction of hair follicles. Ann N Y Acad Sci. 1994. 402(6757): 33–4.. localization and functions. 1983. 7. Wei Z. and Lui H. C. J Invest Dermatol. Sperling L. 4(3):296–301.. vibrissae. 1991. and Sun T. Transverse scalp sections: a proposed method for laboratory processing. Dhuailly P. and Lavker R. 1999. A basis for a morphometric approach to disorders of the hair follicle. role in hair cycle. James K. 8(1):80–8. Lavker R. 3. Epithelial stem cells in the skin: definition. Sun T. Wilson C.. Cotsarelis G.T. 1999. 1999.. J Invest Dermatol Symp Proc.J. In: Disorders of Hair Growth Diagnosis and Treatment. Wiseman M. physical examination and any necessary investigations. 101(1 Suppl):16S–26S. J Am Acad Dermatol. and Mortimer C. Br J Dermatol.. and skin carcinogenesis. Rushton H. et al. pp. 2000..M. 1990. References 1. Cell. 11. Cotsarelis G. Can Fam Physician. 10. 8. Whiting D.T.. 28(5 Pt 1): 755–63. Frishberg. 35(2 Pt 1):220–2. Christofidou-Solomidou M..Olsen.. Reynolds A. Arch Dermatol. discussion. and Shapiro J. The scalp biopsy: making it more efficient. Olsen E. Lavker R. 4. Kaur P..M.Orfanos. Stem cells of pelage.P. et al.. 120(4): 449–56. Liu Y. Shapiro J. Miller S.. 1990. ed. Lawrence C..G. Practical management of hair loss.T. Lyle S.B.. Sun T. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells.T. 9. 13. and eyelash follicles: the hair cycle and tumor formation. Inc. Hair follicular stem cells: the bulge-activation hypothesis. Cotsarelis G.. and involvement in skin tumor formation.M. Androgenetic alopecia: clinical aspects and treatment. New York: McGraw-Hill. Dermatol Surg. 6. 1984. .. J Am Acad Dermatol.. 1996. Madani S. 5. An organized diagnostic and management strategy will help both to identify the cause of alopecia and to direct therapy. Hair follicle stem cells: their location.C.A. The unit area trichogram in the assessment of androgen-dependent alopecia.M. 109(4):429–37. hair cycle. Berlin: Springer-Verlag.18 Hair Loss: principles of diagnosis and management of alopecia ings obtained from meticulous history. 96(5): 77S–78S.H. et al. 46:1469–77. E. 61(7):1329–37. and Lavker R. 1993. Exp Dermatol. et al. 1991. Orfanos C. markers. Cotsarelis G. Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype. Nature. Transverse microscopic anatomy of the human scalp. ed.M. and Guthrie V. In Hair and Hair Diseases. 2. 485–527. 1993. Headington J. 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]. 25(7):537–8.
10–14 with up to 55% concordance rate 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. clinical features and state of the art treatment for AA. Genetic and immunologic factors have been important ar- . intrinsically abnormal melanocytes or keratinocytes and neurological factors.2 Alopecia areata: Pathogenesis. 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 1990.1–3 This chapter will review the latest information on etiology.6–9 Also. clinical features. usually patchy. AA is generally felt to be mediated by T lymphocytes directed at hair follicles. eas of attention. such as the human leukocyte antigens (HLA) are located on the short arm of chromosome 6. At these meetings. with ophiasis occurring simultaneously. and geneticists.6. Several closely linked genes. there have been reports of AA in identical twins. pathologists. diagnosis and practical management Alopecia areata (AA) is an unpredictable.15. forming the Major Histocompatibility Complex (MHC). The proceedings of these meetings have been published in the Journal of Investigative Dermatology. There is a high frequency of a positive family history of AA in affected individuals. but is likely to be an interaction between genetic and environmental factors.4.13 Scerri 14 presented a case of 11-year-old identical twin boys. Within the past decade. numerous subspecialties.16 Associations with Etiology The etiology of A A is unknown. biochemists. including immunologists. molecular biologists. dermatologists. The exact cause is unknown. emotional stress. there have been significant advances in our understanding of alopecia areata.5 There is a significantly higher incidence of a positive family history in patients with early onset of AA.1% with the first patch after 30 years of age. discussed alopecia areata in an open forum. Other proposed etiologies include infectious agents. Genetic factors Genetic factors play an important role in the etiology of AA. non-scarring hair loss condition affecting any hair-bearing surface. cytokines.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. ranging from 10% up to 42 % of cases. 1994 and 1998.
21 Recently.18 B13.29 The HLA alleles DRB1*0401 (DR4) and DQB1* . such as HLA-A9.20. and B8. b) Alopecia areata and Down’s syndrome.17 B18. The studies reveal a significant association of HLA-DR11 and DQ3 in patients with AA.28. and B27.7–9. The earlier studies identified the association of AA with several class I antigens.19. both HLA class I (HLA-A. -B. -C) and class II (HLA-DR.1 (a. -DQ. there has been an increased consist- ency in evidence revealing associations between AA and HLA class II antigens. There is up to an 8. -DP) have been studied in AA.16 B12.22– 29 The HLA alleles DQB1*03 (DQ3) and HLADRB1*1104 (DR11) appear to be markers of general susceptibility for all forms of AA. suggesting involvement of a gene located on chromosome 21 in determining susceptibility to AA. B7. There have also been studies showing no correlation with HLA Class I antigens.20 Hair Loss: principles of diagnosis and management of alopecia Figure 2.8% increased frequency of AA in patients with Down’s Syndrome.7–9.
31 Thirty per cent of patients with autoimmunepolyglandular syndrome have AA. which are key to the follicular inflammatory immune response responsible for AA. there is an interaction between genetic and environmental factors that triggers the disease. Alopecia areata is a complex trait expressed by a number of genes. 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. suggesting involvement of a gene located on chromosome 21 in determining susceptibility to AA (Figure 2.8% incidence of thyroid disease in patients with AA. Most probably. With the discovery of animal models for AA. and with the final data on the Human Genome Project just completed.32 The IL-1 gene cluster on chromosome 2 includes genes for the proinflammatory IL-1 proteins. There are reported associations between AA and classic autoimmune disorders. IL-1 inhibits growth of the hair fiber33 and induces morphological changes that resemble those seen in AA. There is up to an 8. 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. However. HLA associations have been discussed above.35 However. with a fourfold greater incidence of vitiligo in AA .8% increased frequency of AA in patients with Down’s Syndrome. the exact causative genes have not been discovered.59 Tarlow et al.30.1). Polymorphism within the IL-1 cluster may modulate IL-1 responses.5 This evidence has been further confirmed by documentation of an increased prevalence of anti-thyroid antibodies35 and thyroid microsomal antibodies. one must bear in mind that the presence of predisposing HLA is but one component in a cascade of factors leading to autoimmune disease.4. how and who develops AA.2 for DRB1*0401. At this point. we are a step closer to understanding the structure of the epitopes recognized by T cells. Other investigators 26 also suggest that DRB3*52a may confer resistance to AA. other autoimmune diseases and a responsiveness to immunosuppressive therapy. 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. The main associations are with thyroid diseases and vitiligo. it is expected that our understanding of this complex trait will be further clarified. IL-1 has a direct effect on hair growth. Polygenic influences are clearly involved. Puavilai et al. Genetic research may ultimately explain why. Several reports reveal an 8. compared to only 2% in the general population.36 AA has been shown to have a significant association with vitiligo. showed no increase in microsomal antibodies compared to normal controls. By identifying these HLA genetic correlations. Immunological factors Indirect clues for autoimmunity There are indirect clues for autoimmunity that include the association of the disease with a HLA haplotype. their cell membrane receptors and the anti-inflammatory IL1 receptor antagonist.7–9 with a relative risk for AA of 30.0–11. again implicating this chromosome. many studies indicate that AA is a polygenic disease with certain genes correlated with susceptibility and others with severity.Alopecia areata 21 0301(DQ7) are markers for more severe longstanding alopecia totalis/universalis.34 In conclusion. In hair follicle organ cultures. The defective gene in this syndrome is mapped to chromosome 21.
may be correlated with the amount of hair loss.67 The dense peribulbar lymphocytic infiltrate affecting anagen follicles is one of the most consistent and reproducible immunologic abnormalities in AA.48–50 lichen planus. Most of the T cells are activated. particularly in the dermal papilla/capillary network. and hair shaft.67 or normal.47 ulcerative colitis. as compared to only 44% of normal controls. 51–55 and autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy. The most common target structures were the outer root sheath. as can be seen by the expression of DR antigens and IL-2 receptors. also known as autoimmune polyglandular syndrome Type 1(APS-1). as compared to controls using indirect immunofluorescence. The infiltrate is most prominent in active disease. Circulating total numbers of T-lymphocytes have been reported as reduced40. to a lesser extent.56–59 Thirty per cent of patients with APS-1 have AA.64 However. A slight increase in helper T-cells (CD4) and decrease in number of suppressor T-cells (CD8).41 myasthenia gravis. 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.22 Hair Loss: principles of diagnosis and management of alopecia patients.39. 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.4. In addition.68 Friedmann40 suggested that the number of circulating T-cells is reduced in AA.38 Other studies have revealed an increased prevalence of gastric parietal cell antibodies and anti-smooth muscle antibodies in sera of patients with AA. Tobin and coworkers reported detection of antibodies to pigmented hair follicles by Western blotting in the sera of 100% of the AA patients examined.65 In another study by Tobin et al.46. 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.66 Cell-mediated immunity Studies of cell-mediated immunity in AA have given conflicting results.37.42–46 polymyalgia rheumatica. The infiltrate subsides in inactive disease and disappears in the regrowth phase. because different patients develop different patterns of an- . The T cell helper to suppressor ratio is 2:1– 4:1.40 diabetes mellitus. The antibody response to hair follicles in patients with AA has been found to be heterogeneous. resulting in an increase in the ratio of helper to suppressor cells.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. and consists mostly of T lymphocytes and.40 There are also reported associations of AA with pernicious anemia. and that the level of this reduction is related to disease severity.40 lupus erythematosus. macrophages and Langerhans cells.61 and systemic steroids 62 also supports the idea of immune-mediated pathogenesis in AA. The cellular infiltrate first becomes evident around the bulbar blood vessels. Successful treatment of AA with immunosuppressive agents such as oral cyclosporine 60. followed by the matrix. inner root sheath.66 much higher levels of autoantibodies to multiple structures of anagen hair follicles in AA patients have been reported. tibodies to different hair follicle structures.
are increased in the bulb of the affected follicles. The autoimmune response producing. HLA-DR and intercellular adhesion molecule-1 (ICAM1) expression of follicular epithelium. These changes include hair loss. the following criteria should be met: 1. antibodies to pigmented hair follicles. Tsuboi has shown that the CD8+ cells had disappeared completely from almost all portions of the hair follicle. The necessity of the follicular homogenate to inducing AA suggests that T cells recognize a follicular auto-antigen. AA induction followed upon injection with CD8+ cells cultured with follicular homogenate. Increased frequency of hair-specific antibodies. This series of events helps to induce hair loss. They present the responsible epitope to the peribulbar lymphocytes. In this study. This is considered to be a Type 1 T helper cell response (Th ). an increase in the ratio of helper to suppressor cells. while CD4+ cells still remained in the upper portions of the hair follicle. This leads to a cascade of immunologic events with increased interleukin-2 (IL-2). 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.2 illustrates Figure 2. not following. Unique antigens in the affected organ 2. with the disappearance of the T cell infiltrate. more recently.Alopecia areata 23 follicles suggests that the process precedes rather than results from injury to hair follicles.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. perifollicular T-cell infiltration.69 In order for a medical condition to fit as an autoimmune disease. the condition 5. This study also suggests that AA is mediated by T-cells. 1 . Furthermore. This may imply the greater importance of CD8+ in the expression of alopecia areata. An autoimmune response to that antigen 3. particularly CD8+ cells. Gilhar et al. but not on injection of the cultured CD4+ cells. Gilhar69 and Tsuboi70 have shown that grafting affected scalp AA skin from humans on to SCID mice results in regrowth of hair. An autoimmune response specifically associated with the disease 4. The disease being transferred passively by autoantibodies or T cells. T-cells that had not been cultured with follicular homogenate were not able to induce AA. high levels of autoantibodies to multiple structures of anagen hair follicles.2 The pathogenesis of alopecia areata. Furthermore. such as Langerhans cells. many of the above criteria are indeed met. Antigenpresenting cells. For AA. 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. Figure 2. gamma interferon (γIFN) and intercellular adhesion molecules (ICAM).
72 involves the upregulation of MHC antigens and/or downregulation of locally produced immunosuppressants (melanocyte. but the evidence for a viral etiology of AA at this point in time is not conclusive.stimulating hormone.73 As hair regrows with topical immunotherapy.74 Aberrant expression of cytokines of the Th1 type (see Figure 2. Cytokines derived from epidermal keratinocytes. located exclusively in the distal outer root sheath. 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 . Cytokines are immunomodulators mediating inflammation and regulating cell proliferation.24 Hair Loss: principles of diagnosis and management of alopecia some of the immunologic cascade events that take place in alopecia areata. Emotional stress Several studies suggest that stress may be a precipitating factor in some cases of AA. IL-1β and tumor necrosis factor-α (TNF-α) are potent inhibitors of hair follicle growth. This initial report showed a convincing positive association with CMV. The hair follicle has a distinct immune system71 that differs from that of its surrounding skin. these cytokine profiles change. allowing the immune system to recognize the immune-privileged hair follicle antigens. and in vitro produce changes in hair follicle morphology similar to those in AA.73 T helper cells produce cytokines divided into two subgroups depending on the pattern of cytokine production.34.76–78 The whole concept of molecular mimicry of the hair follicle with a virus is intriguing. Type 2 helper (Th2) cells produce IL-4 and IL-5.71 Human hair follicles may even serve as a Langerhans cell reservoir.75 but this has not been confirmed. Infection There has been a report regarding the possibility of cytomegalovirus (CMV) infection found within the patches of scalp AA. since the inner root sheath and hair matrix do not express MHC class I molecules. A recent theory for AA proposed by Paus et al. 2. interleukins IL-1α. as other investigators have reported negative findings. there are reports revealing that emotional stress does not play any role in the pathogenesis of AA. leading to onset of AA.79–81 a higher number of stressful events in the 6 months of preceding hair loss. This immune privilege may collapse in alopecia areata. Acute psychotrauma before the onset of AA. adrenocorticotropin and transforming growth factor).2) and IL-1β have been detected in affected areas of the scalp in patients with AA.83 Cytokines It appears that cytokines have a significant pathogenic role in AA. The cellular components of the hair follicle immune system are composed of intrafollicular T lymphocytes and Langerhans cells.71 There is also a unique expression of follicular MHC class Ia/Ib.82 In contrast. The epithelium of the proximal anagen hair follicle is immune-privileged. and perifollicular mast cells and macrophages. and ICAM1.80 higher prevalence of psychiatric disorders81 and psychosomatic factors in patients with AA have been reported.
94 The Smyth chicken model also has vitiligo. who revealed a decrease in calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the scalps of patients with AA. AA can be induced in normal C3H/HeJ mice using full-thickness skin grafts from affected C3H/HeJ mice. may explain some of the associated pigmentary anomalies seen clinically in acute AA and the preferential effect of AA on pigmented hairs (Figure 2.. Recently.95 AA developed 8–10 weeks after grafting. 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.3) and the Smyth chicken. in outer root sheath of all hair follicles from non-balding lesions of AA. melanogenesis and the development of AA.85 correspond well with the hypothesis of a sub-clinical condition of the disease in clinically normal areas of AA.85 Abnormal melanosomes in clinically normal regions. since the peripheral nervous system can deliver neuropeptides that modulate a range of inflammatory and proliferative processes.92 the Dundee experimental bald rat (DEBR)93 (Figure 2.90 In addition. together with the presence of antibodies to pigmented hairs of AA. Also.12).88 The neuropeptide CGRP has a potent anti-inflammatory action. application of capsaicin. together with degenerative changes. .84–86 Abnormal melanogenesis and melanocytes are common findings. These same investigators95 noted that AA could be induced in 8–10 weeks by taking skin-draining lymph node cells from Neurological factors It has been suggested that local changes in the peripheral nervous system at the level of the dermal papilla or bulge region may play a role in the evolution of AA.88.Alopecia areata 25 the hair bulbs of anagen hair follicles. degeneration of pre-cortical keratinocytes has been shown in follicles of active AA lesions.87 This theory has been supported by Hordinksy et al. investigations of AA have been facilitated by using animal models with either spontaneous or induced AA. to the entire scalp of two AA patients revealed an enhanced presence of SP in AA perifollicular nerves and induced vellus hair growth. This evidence.91 Figure 2.3 Alopecia areata animal models: the C3H/HeJ mouse and the DEBR rat.89 and neuropeptide SP is capable of inducing hair growth in the mouse. including vacuolation. Animal models with spontaneous AA include the C3H/HeJ mouse. 88. which causes neurogenic inflammation and releases SP. and may suggest a link between vitiligo.
Animal models are now used in research for new and improved treatments. Figure 2.32 identified the equivalent chromosome region 2p12–13 as being a location for AA susceptibility. disease behavior. differentiation and apoptosis within the hair follicle. Lymphocyte cells from C3H/HeJ AA mice were screened.26 Hair Loss: principles of diagnosis and management of alopecia AA-affected mice and transferring them to normal-haired recipients. has some efficacy in the DEBR rat.95 The ability to induce AA in a model suggests that. an IL-2 inhibitor. whereas individuals may be genetically predisposed toward AA. showing significant regrowth on the treated portion of the mouse.4 Diphencyprone was applied to half the C3H/ HeJ alopecia areata mouse. have shown that leflunomide. 96 Three gene loci common to AA susceptibility were located. Transgenic Hoxc13 defi- .101.103 This gene does not cause AA.100 Animal models with AA-like hair loss are significantly useful in investigations regarding pathogenesis. AA induction can also be used to produce large numbers of mice for testing pharmaceutical agents.4). A preliminary study using C3H/HeJ mice examined potential chromosome locations that may contain genes involved in AA.102 These mice develop a normal pelage at about 14 days and then lose their hair over 1 week. The human hairless gene has been cloned to chromosome 8p12.99 have shown efficacy of diphenylcyclopropenone in the C3H/HeJ mouse (Figure 2. susceptibility genes are not enough to develop the condition.97 The receptor arrangement of these cell clones may help identify targeted antigens in AA. and T cell clones expressing a Vß8.96 A separate investigation on human AA by Tarlow et al. efficacy and side-effects of available or future treatments. However. this gene may have importance in maintaining hair follicle integrity by balancing cell proliferation. density and development of hair in vertebrate embryos. FreyshmidtPaul has shown the efficacy of squaric acid dibutyl ester in the C3H/HeJ AA mouse.5 T cell receptor (TCR) arrangement predominated.98 Shapiro et al. Lui et al. These human-animal correlations may have importance to understanding the mapping of the putative genes. Hox genes are involved in controlling the position. A region on mouse chromosome 6 may contain genes involved in inflammatory events associated with AA. Non-alopecia areata animal models The hairless mouse has an autosomal recessive allelic mutation that maps to chromosome 14. This may eventually permit selective immune therapy using antiTCR antibodies or clonal vaccination treatments. Recently investigations have correlated this hairless gene in mice with congenital atrichia in humans.2/Jß2.
A decreased anagen to telogen ratio. the hair cycle is abnormal.5). 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. the involved follicle enters the end-stage telogen.5). In these cases.5e). In patients with complete recovery. AA should be differentiated from androgenetic alopecia. Eosinophils are also detectable in all stages of AA. can be observed in horizontal sections of scalp biopsies109. with patchy involvement.108 Also.111 a decrease in follicular density and follicular miniaturization may be present. Following complete matrix failure. resulting in marked increase in telogen and catagen hairs. Inflammatory changes in the mid and upper dermis are generally not prominent unless many vellus hairs are affected by the disease.112 Mast cells were also noted in a small series of AA slides.106 A peribulbar lymphocytic infiltrate (‘swarm of bees’) with no scarring is characteristic of the diagnosis of AA (Figure 2. During the acute phase of hair loss. which in turn will allow us to understand the disordered follicle more clearly.105 There are distinct stages in the histopathology of AA: (a) acute alopecia.110 (Figure 2. with hair follicles entering the telogen or late catagen stage prematurely in the involved areas. both within the peribulbar infiltrate and the fibrous tracts.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. 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. trichotillomania and syphilitic alopecia. The inflammatory cellular infiltrate is composed chiefly of activated Tlymphocytes together with macrophages and Langerhans cells. AA is not a localized process. with numerous fibrous tracts along with pigment incontinence within these fibrous tracts. normal hair follicles with little or no peribulbar lymphocytic infiltration and no decrease in hair density are noted.107. Although clinical correlation is necessary. In patients with long-standing persistent alopecia. (b) persistent alopecia.114 This shows that. this feature is helpful in diagnosis of AA in some biopsy specimens without peribulbar lymphocytic infiltrate. The terminal to vellus ratio is decreased and even reversed by the increased numbers of miniaturized hairs.104 Hoxc13 may play a significant role in follicular proliferation and differentiation. Pathology In early active AA. the involved hair follicles arrest in the end-stage telogen phase. miniaturization of hairs.115 Histopathologically. (c) recovery.104 More knowledge of Hoxc13 expression in epidermal appendages will in turn provide further insight into the functioning of the normal ordered follicle. peribulbar infiltration along with an increase in Langerhans cell numbers. 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. In . is appreciable (Figure 2.Alopecia areata 27 cient mice were unable to synthesize hair keratins and have sparse brittle hair. matrix cell and matrical melanocyte failure with a formation of dysplastic hair shafts is noted. telogen effluvium.
117 AA affects men and women equally.28 Hair Loss: principles of diagnosis and management of alopecia telogen effluvium.116 Clinical features AA occurs all over the world.7%. as reported by the First National Health and Nutrition Examination Survey conducted from 1971 through 1974. Presence of plasma cells along with no peribulbar eosinophils and abundant lymphocytes in the isthmus are features of syphilitic alopecia. miniaturization of follicles is not present. Trichotillomania is characterized by empty anagen follicles. multiple catagen hairs. It accounts for about 2% of new dermatology outpatient attendances in the UK and the USA.117 The lifetime risk has been estimated at 1. while the presence of peribulbar eosinophils and lymphocytes strongly suggests AA.4 Patients are frequently quite . was 0.1 to 0. Syphilitic alopecia is very difficult to distinguish from AA. 117 The prevalence of alopecia areata in the United States.2 per cent of the population. trichomalacia and pigment casts in the follicular infundibulum.
not only on the same scalp.7).5 Histopathology of alopecia areata. . totally bald. resulting in distal fractures.7). This highlights the fact that AA is a very heterogeneous condition.7). The fractured hairs develop owing to damage involving both cortex and medulla. shorter duration.Alopecia areata 29 Figure 2. smooth patch involving the scalp or any hair bearing area on the body (Figure 2. Almost all follicles within this field are telogen. Hair loss is seen both as intact and as fractured hairs (Figure 2. and family history of the disease and a lateonset form characterized by milder severity.118.7). patients will present to the physician with one or several bags of hair.) young.120 These hairs are described as ‘exclamation-mark’ hairs. but within the same follicular bundle. (c) Two follicles. (d) Follicular stellae (ST) remnants in alopecia areata. long duration. Alopecia areata can manifest with several different clinical features. (b) Close-up the lymphocytic infiltrate.119 (Figure 2. (f) Reduction of follicular numbers in chronic alopecia areata. (a) ‘Swarm of bees’ noted in the deep subcutaneous peribulbar area of the follicle. Sixty per cent of patients present with their first patch under the age of 20. and low family incidence. The characteristic lesion of AA is commonly a round or oval. The intact hairs are dystrophic anagen or telogen hairs. David Shum and Martin Trotter. because the distal segment is broader than the proximal end (Figure 2. Patients usually complain of abrupt hair loss and marked hair shedding. Colombe et al.6). The patch may have a mild peachy or pinkish-red color (Figure 2. with matrix destruction. Frequently. (e) The large number of telogen hairs in alopecia areata. with an early-onset form associated with greater severity.8 suggest a bimodal pattern for AA. (Courtesy of Drs Magda Martinka. with one showing marked lymphocytic infiltration. while the other does not.
with mild to moderate pruritus. This early-onset form of AA is associated with greater severity. burning sensation or pain. the following forms may be seen: alopecia areata: partial loss of scalp hair. Although hair loss is usually asymptomatic in most cases. ophiasis inversus (sisapho)119—a rare bandlike pattern of hair loss in fronto-parieto scalp (the exact opposite of ophiasis). (c) Back view. too. If categorized according to pattern. They are prognostically and therapeutically distinguishable. (b) Side view.30 Hair Loss: principles of diagnosis and management of alopecia Figure 2. The pull test may be positive at the margins of the patch. tenderness.121 and diffuse AA—a diffuse decrease in hair density over the entire scalp (Figure 2. If categorized by extent of involvement. (a) Front view showing loss of hair on scalp. longer duration. before the appearance of the patches.9). ophiasis-bandlike AA—hair loss in temporo-occipital scalp. reticular AA—reticulated pattern of patchy hair loss. and greater probability of a positive family history of AA. the following forms are seen: patchy AA—round or oval patches of hair loss (most common). alopecia totalis: 100% loss of scalp hair. and eyelashes. The clinical presentation of alopecia areata is subcategorized according to pattern or extent of the hair loss. and alopecia universalis: 100% loss of hair on scalp and body (Figure 2. HLA studies suggest this early-onset group of severe AA patients are a genetically distinct group. some patients describe paresthesias. .6 Alopecia universalis for 1 year in a 3-yearold girl. indicating very active disease.8). eyebrows.
This patient complained of burning on the patch before the hair fell out. (f) The AA patch may be red. (e) Another peach-colored patch of AA. Patients frequently present with just a patch. (b) A single large circular patch totally devoid of hair ‘bare as a baby’s bottom’. .Alopecia areata 31 Figure 2.7 Alopecia areata circumscripta. (a) A single small circular patch. (d) The color of an AA patch may be peach. (c) The patch may be skin-colored with broken-off hairs.
He has not had any other spots for over a decade. (i) Simultaneous circumscript alopecia in mother and son.) (h) Circumscript patches can be very constant and persistent. (Courtesy of Dr Harvey Lui. 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.
(c) Ophiasis (d) Simultaneous ophiasis in mother and daughter.Alopecia areata 33 Figure 2. . (f) Early diffuse A A with no distinct patches. (g) Advanced diffuse AA. mimicking androgenetic alopecia. (e) Sisapho—the diametric opposite of ophiasis.8 Clinical forms of AA based on pattern: (a) Patchy alopecia areata in multifocal areas. (b) Reticulated patches in AA.
Any hair-bearing surface can be affected. including eyelashes and eyebrows. trachyonychia (longitudinal striations resulting in sandpaper appearance). Most patients present with the limited patchy type that is easily camouflaged. many or all the nails.9 Clinical forms of AA based on extent: (a) Alopecia areata with its characteristic circular patches. Both regrowth in one site and extension of the alopecia on another site may be seen at the same time in the same patient.122 depending on how diligently it is looked for. onychorrhexis (superficial splitting of the nail extending to the free edge). (b) Alopecia totalis affecting 100% of the scalp. The reported incidence of onychodystrophy in AA ranges from 10 to 66%. followed by repigmentation.34 Hair Loss: principles of diagnosis and management of alopecia Figure 2. Where there is hair. Changes may be seen in one. thinning or thickening . there can be alopecia areata! Beard AA is very common. The dystrophy may precede. Beau’s lines (grooves through the nail matching that of the lunula’s margin). coincide or follow resolution of the AA. Pitting with an irregular pattern or in organized transverse or longitudinal rows. affecting the limbs or the thorax area. Nail dystrophy may be associated with AA.12). Frequently AA preferentially affects pigmented hair. (c) Alopecia universalis in an adult affecting all hairs on the body. as well as body AA. The initial regrowth in AA is frequently white.11). and only the white hairs remain (Figure 2. (Figure 2.10 and 2.
10 Extracranial AA: (a) AA affecting just the eyelash. (d) AA affecting the dorsa of the arms. (c) AA affecting the chest.Alopecia areata 35 Figure 2. . (e) A A affecting just the lateral portion of the leg. (b) AA affecting one eyebrow.
13). (pseudomycotic). Prognosis The only predictable thing about the progress of the AA is that it is unpredictable. 7–10% . (a) Random patches on the beard area. (c) Extensive AA of the beard. onychomadesis (onycholysis with nail loss). partial or non-existent.11 Alopecia areata of the beard is very common. but not affecting the great head of dreadlocks. koilonychia (concave dorsal nail plate). Patients usually present with several episodes of hair loss and hair regrowth during their lifetime. punctate or transverse leukonychia and red spotted lunula may be associated with AA. The recovery from hair loss may be complete. However.36 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (b) The characteristic peach color on an A A of the beard. The majority of patients will regrow their hair entirely within one year without treatment.123-128 (Figure 2.
Alopecia areata 37 Figure 2.82. vitiligo and alopecia areata. a young age of onset. extensive hair loss and ophiasis. The white hair regrowth proves the diagnosis had always been AA. Poor prognostic indicators are atopy. nail dystrophy. (b) and (c) White regrowth on the side of the scalp.12 White hairs. (d) White regrowth in an area of previous ophiasis. a positive family history of AA. can eventually end up with the severe chronic form of the condition.129 . the presence of other immune diseases. (a) Hair regrowth in a young child who had been diagnosed as a case of trichotillomania.
tinea capitis and pseudopelade (Figure 2. non-inflammatory tinea .14). traction alopecia. the differential diagnosis is usually between telogen effluvium. androgenetic alopecia (AGA). (f) AA and vitiligo in the same person. and purely telogen in telogen effluvium. Patients with AGA usually demonstrate the typical predictable pattern of balding. Differential diagnosis Clinically. hair loss is generalized over the whole scalp.38 Hair Loss: principles of diagnosis and management of alopecia (e) Circumscript AA. and shedding is not prominent. In telogen effluvium. triangular temporal alopecia. However. whereas in AA it is usually patchy. pressure-induced alopecia. usually. The pull test is usually negative in AGA. In trichotillomania and traction alopecia twisted and broken hairs are frequently evident. sparing white hairs. trichotillomania. In tinea capitis. Hairs that are shed are either telogen or dystrophic anagen in AA. (g) White moustache in a vitiliginous area in the patient illustrated in 12f. there is an inflammatory component.
(c) Koilonychia present in AA. (a) Trachyonychia. . and red-spotted lunula on the fingernails. (b) Red-spotted lunula on the toenails.Alopecia areata 39 Figure 2.13 Nail changes and alopecia areata. (d) and (e) Severe nail dystrophy in AA.
which may be difficult to see on a shiny smooth scalp. (d) Morphea mimicking AA. (c) AA may be linear and mimic morphea. (b) Temporal triangular alopecia can mimic AA. It is crucial to look for the presence of follicular ostia.14 Differential diagnosis of AA.40 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (a) This is an early case of biopsy-proven diffuse AA which can be difficult to differentiate from telogen effluvium. (e) & (f) AA .
(j) & (k) Pseudopelade mimicking AA. (h) Simulaneous trichotillomania in a mother and daughter. .Alopecia areata 41 mimicking AGA in a female patient. Note the loss of follicular ostia. but usually has a significant scarred component to it. (i) Broken hairs in trichotillomania. (g) Trichotillomania. which can easily mimic AA. (l) Post surgical pressureinduced alopecia can appear like AA.
Histologically. the most common cause of tinea capitis is Microsporum canis. A biopsy may occasionally be necessary to distinguish TTA from AA. oval or lancet-shaped patch of non-scarring alopecia overlying the fronto-temporal suture. much of this published work has involved patient . Lesions present as a triangular. Evaluating efficacy is most difficult. They cause blisters and erythema. See above for histologic differentiation of noncicatrizing alopecias. There is controversy as to whether the lesions are present at birth or acquired later in life. There is a paucity of studies that distinguish AT/AU from patchy AA. the treatment of AA is very difficult.11%. Temporal triangular alopecia (TTA) may mimic AA. Although this may seem crude. Most published studies for AA have been small. and there are no consistently reliable treatments. Pressure-induced alopecia131–134 (PIA) may also mimic AA. The lifetime incidence of TTA is 0. Bateman. and patchy AA may be difficult to differentiate from pseudopelade. 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.135 Diffuse AA can be especially difficult to diagnose clinically from other non-cicatrizing alopecias. While the FDA has never approved any drug for AA. This lack of stratification of patient population can have a profound influence on evaluating therapeutic efficacy. 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. mustard and black pepper. some current treatment regimens have similar objectives. this does not mean that there are no effective treatments. A KOH preparation and fungal culture may be necessary to distinguish noninflammatory tinea capitis from AA. Despite the advance of medicine over the last 200 years. In order to prove efficacy with sufficient power and statistical significance. especially for patchy AA. some of the fundamental principles in the treatment of AA remain unchanged. Unfortunately. Woods light examination may help if the patient is in or has been in an area where the fluorescent tineas predominate. There is great difficulty in evaluating the literature on treatment modalities for alopecia areata. peribulbar lymphocytic infiltrates are not present.130 This is ten times less frequent than AA. but again. as there is so much variability as to baseline patient populations and the terms ‘successful regrowth’ or ‘responders’. which does fluoresce. In British Columbia. as it is so unpredictable and frequently improves on its own. A 4 mm punch biopsy may be necessary to make a definitive diagnosis in some cases. Occasionally in AA. There is no question that AT/AU is a distinct prognostic and therapeutic group. there is usually some scarring with PIA. Treatment Modern therapy for AA is best appreciated within a historical framework. Look for the characteristic scaling in tinea capitis.136 in the 1800s. turpentine. Clinically. Half-head studies are very powerful. Usually the history of coma or surgery is present. He advocated the use of ointments prepared with oil of mace. and results can be skewed by this more difficult and severely affected population. and an immunologic patient response to modify the perifollicular immunologic milieu. large patient populations are necessary.42 Hair Loss: principles of diagnosis and management of alopecia capitis may be most difficult to distinguish from AA.
However. Scalp biopsies from 15 untreated AA patients showed a twofold increase in unoccupied GCR. meaning being able to abandon one’s wig or cap. It is of paramount importance that dermatologists should be knowledgeable and conscious of this important segregation when evaluating modalities in the treatment of AA. These abnormalities may explain why patients with AA show a varied response in hair area growth when treated with glucocorticoids.139 Topical corticosteroids Fluocinolone. all treatments are palliative. some biochemical abnormalities relating to steroid chemistry have been discovered in AA patients by Sawaya and Hordinsky. This suggests that patients with AA have abnormalities in type 2 GCR activation because of abnormal calcium-calmodulin metabolism. topical. but do not prevent further spread of the condition. and thus hormone binding to GCR. all results are skewed and will probably show ineffectiveness. Corticosteroids The main mechanism of action is immunosuppression. Fiedler145 believes that a combination of 0. it is important to ascertain clearly what the authors have defined as a ‘responder’. The terms ‘responder’ and ‘successful regrowth’ are not used in the same way from one study to another. facilitating collaboration.05% betamethasone dipropionate in 22%. and measuring the extent of scalp involvement. comparison of data.137 These guidelines highlight the fact that AT and AU are considered a separate entity from AA. and the motivation level of the patient. All local treatments may help the treated areas. This suggests suppressed cellular transcription. Price and Khoury144 have not had success with topical steroids.139 They showed that patients with AA have abnormalities in glucocorticoid receptors (GCR) for type 2 binding. It was found that low concentrations of calmodulin stimulate a cytosol kinase. The new Alopecia Areata Investigational Assessment Guidelines are helpful in establishing criteria for selecting and assessing patients for clinical studies of AA. topical immunotherapy. At the present time. with 5% minoxidil in 27% and with 5% minoxidil and 0. Otherwise.138 All treatment plans for patients depend on three major factors: the extent of scalp involvement. intralesional and systemic steroids. She reports that quality of response in severe recalcitrant AA was fair to good after 16 weeks of treatment with placebo in 13%. Most dermatologists consider successful regrowth to be cosmetically acceptable regrowth. At present. owing to the chronic nature of AA. .Alopecia areata 43 populations with a preponderance of AT/AU.141 halcinonide142 and dexamethasone in a penetration-enhancing vehicle have been reported to have some success. This suggests a synergistic benefit of using both modalities. and not curing the condition. minoxidil and photo-chemotherapy are available for the treatment of AA.05% betamethasone dipropionate cream and minoxidil may be more beneficial than either alone. only controlling the problem. anthralin. When comparing studies.140. The Guidelines help us to evaluate what is ‘successful regrowth’. slowgrowth cellular processes. Treatment guidelines for AA have been published by the American Academy of Dermatology. any mode of treatment may require long periods of usage.143 Only one of these studies was performed in a double-blind controlled manner. In addition.05% betamethasone dipropionate in 56%. and must be separated out in order to determine the efficacy of any trichogenic agent. This receptor is found to influence long-term. the age of the patient. with 0.
(d) Best position for injecting eyebrows: patient lying flat.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. .15 Intralesional corticosteroid injections for AA. (c) Same patch after 2 months of injections.
(g) Atrophy secondary to injection with triamcinolone acetonide 40 mg/ml. Initial regrowth is often seen in 4–8 weeks. with the next set in between areas of regrowth.Alopecia areata 45 (e) Injection of eyebrows with triamcinolone 2. which is at least 4–8 times what is recommended.3 mg/ ml. for scalp A A. Treatments .5–5. we inject a concentration of 5 mg/ml with a maximum total of 3 ml of triamcinolone acetonide. 146 Shapiro. Injections are performed every 4 weeks.146 For circumscribed AA. (f) Regrowth in eyebrow area after 4 weeks.5 mg/ml for a total of 0. A weaker concentration of 2. Price146 prefers 10mg/ml.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 0.151 and Thiers152 prefer triamcinolone acetonide.149 Mitchell and Krull.5 mg/ml is used for the beard area and the eyebrows.129 Whiting. Concentrations of triamcinolone ac- etonide vary from 2. Price. Shapiro149 prefers 5 mg/ml.1 ml per site.5 ml per eyebrow. intradermal corticosteroids remain the therapeutic standard. Triamcinolone acetonide is administered with a 0. At the University of British Columbia Hair Clinic.0 mg/ml diluted either in xylocaine or sterile saline. Bergfeld prefers 2.150 Bergfeld.5–10. Whiting150 prefers 5–10 mg/ml. Intralesional corticosteroids Intralesional corticosteroid injection is first-line therapy for adult patients with less than 50% of scalp involvement.0 mg/ml151 and Thiers152 prefers 3. Porter and Burton148 demonstrated response rates of 64% using triamcinolone acetonide and 97% using the less soluble and more atrophogenic triamcinolone hexacetonide. approximately 1 cm apart.
5% lidocaine and 2. or too superficial (intraepidermal). Ferrando et al. After 6 months of treatment. leading to uniformity in treatment applications. 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. They are not routinely used.5% prilocaine in a cream) in a thick layer with occlusion 1 hour prior to injection can be used.16). (a) & (b) Striae in a patient with alopecia universalis who had been on systemic steroids for 1 year. if there is no response. because of side-effects. because these patients may lack adequate corticosteroid receptors in the scalp. This disposable device has some advantages.153 recently published a paper on the use of a multi-injection plate for intralesional corticosteroid injection of patchy AA.139 (Figure 2. However. Systemic steroids Systemic corticosteroids are frequently effective in the treatment of AA. and they do not alter the long-term prognosis (Figure 2. and therefore likely to produce pain if the procedure is not performed gently. in that it permits the simultaneous injec- tion in 5–7 different points at a fixed distance. this cream can be difficult to use on the hairy scalp. Abdulkareen et al. discontinue. The 27 gauge needles are large. and an extensive alopecic area can be treated in a shorter period of time.154 recently showed success . are repeated every 4 to 6 weeks. With this method there is only one painful stimulus instead of five to seven. Children under 10 years of age are not usually treated with intralesional steroids owing to the local pain at the injection sites. Topical anesthesia cream (2.15). The main sideeffect is minimal transient atrophy. but their use is controversial.16 The chronic use of systemic steroids for AA can have significant side-effects. This can be prevented by avoiding injections that are too great in volume per injected site.46 Hair Loss: principles of diagnosis and management of alopecia Figure 2. One disadvantage is the needle calibre. intralesional corticosteroids.
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 .
181 Concerns have been raised about the safety of DNCB. anthralin into the eyes. (a) 27-year-old female with AA for 8 months. Careful dissection of the mechanism by which contact dermatitis is able to suppress alopecia areata is important. Therefore. but their safety profile is unacceptable to most dermatologists. (b) Baseline. but less than the treated side.. Systemic steroids may be the most effective modality. right side. to protect treated skin against sun exposure.99.19 Anthralin for alopecia areata. untreated side. and thus allow hair to regrow. (c) 4 months of treatment: left (treated) side showing regrowth. extreme caution must be used with DNCB. The immunomodulating effect of the topical sensitizers is supported by .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. and serum half life is 4 hours. Dinitrochlorobenzene Rosenberg and Drake178 first reported regrowth of hair in two patients following application of DNCB. a decrease in the peri-bulbar CD4+/CD8+ lymphocyte ratio. DNCB is rapidly absorbed after topical application. because it may be possible in the future to mimic the effect on the dermatitis by providing specific cytokines or specific inhibitors of cytokines. Excretion is primarily renal. Immunogens may interfere with the initial or continued production of proinflammatory cytokines by the follicular keratinocytes.177 and a shift in the position of the T-lymphocytes away from perifollicular areas to the interfollicular area and dermis. Weisburger et al.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.180. (d) 4 months of treatment: right (untreated) side showing regrowth. Baseline. The mechanism of action of topical immunotherapy is unclear. (e) Unilateral preferential regrowth of hair with anthralin on the C3H/ HeJ mouse on the treated half. clothes and linens (Figure 2. The issue of DNCB safety is controversial. treated with anthralin 1 % cream for 1 hour daily. 178 Happle has proposed the concept of antigenic competition.Alopecia areata 51 Figure 2. and to be aware of staining of the treated skin.182 Stobel and Rohrborn183 and Summer and Goggelman184 found DNCB to be mutagenic in Salmonella typhimurium in the bacterial plate incorporation assay (Ames assay).19). left side. The overall efficacy of DNCB treatment for AA has been investigated and has varied from 25% to 89%. with 53% recoverable in the urine. There was clearly unilateral preference for the treated side. squaric acid dibutyl ester (SADBE) and diphenylcyclopropenone (DPCP).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. (f) Marked redness can occur from anthralin. Kratka et al. Three contact sensitizers have been used extensively in alopecia areata—dinitrochlorobenzene (DNCB).
198 Furthermore. This would clearly affect any benefits of a contact allergen. it loses its stability in the presence of water. resulting in loss of all regrown hair.4%. Case et al. In 8/ 107.201 Efficacy in alopecia has varied from study to study. adenopathy. They concluded that the two associated therapies showed an impaired efficacy because of the inhibition of the SADBE action by PUVA.202 showed a response rate (on 139 patients) of 50.52 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. Two-thirds of the initial responders no longer responded to the SADBE. auto-eczematization. urticaria and tolerance. 187 Flowers et al.195 also treated children. a paradoxical regrowth of hair on the untreated side of the scalp was seen. Micali et al. Tolerance can sometimes be reversed with cimetidine 300 mg orally three times a day for 3–4 weeks. PUVA impairs Langerhans cells. SADBE has been shown to be Amesassaynegative.197 used SADBE in combination with PUVA on three patients and did not find increased efficacy with combined treatment.0% was reached without producing an adequate dermatitis. with subsequent relapses over the long term. is used only rarely in industry. defined as a required continuous increase in DPCP concentration until a concentration of 2. with excellent or satisfactory results. a tolerance phenomenon was seen.196 showed only minimal signs of terminal hair regrowth in 3/17 patients and do not recommend the use of SADBE in AA. Tosti et al.189 showed excellent responses in 11/26 (52%) of cases. However. This phenomenon is known as castling. is not found in the natural environment and does not react with other chemicals. but also as an immunomodulator in the treatment of melanoma200 and warts. Giannetti and Orecchia191 reported a good response in 5/26 cases. 188 found SADBE to be effective in 4/8 cases.199 It is an ideal immunogen in that it is a strong topical sensitizer.193 reported a 68% (13/19) success rate in a half-head study. Barth et al. and thus inhibits induction and elicitation of allergic contact dermatitis. PUVA also results in a systemic immuno-suppression through direct or indirect (via interleukin-1) stimulation of prostaglandins (PGE2). Orecchia et al. In 3/107. The purity of DNCB samples is also an issue.129 Squaric Acid Dibutyl Ester Happle achieved good results in 70% of patients treated with topical squaric acid dibutyl ester (SADBE). lifetime subcutaneous injections of squaric acid into ICR/Ha Swiss mice resulted in a low incidence of tumors at the injection site.192 showed a 49% success rate in 73 cases with over 50% scalp involvement.186 Side-effects of DNCB include a marked blistering reaction. Diphenylcyclopropenone Diphenylcyclopropenone (DPCP) has been used not only in the treatment of alopecia areata. Certain chloronitrobenzenes that are known mutagens are possible contaminants in preparations of DNCB. equaling that of control animals. Van der Steen et al. with an initial success rate of 30% (10/33). 30 relapsed and were resistant to further therapy. Of 107 who showed a unilateral response. No mutagenic contaminants were detected on gas chromatography-mass spectrometry. Caserio190 showed a success rate of 28% (4/14 cases). Chua et al. with the effect of an efferent lymphatic blockade. . Orecchia194 has used SADBE in children under 13 and showed a 32% (9/28) chance of cosmetically acceptable regrowth.
205 reported further results with DPCP on a larger series of patients. Gordon et al. with 33% showing complete regrowth.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. MacDonald-Hull et al. It appears those with AT/ AU and an early age of onset are prognostically a separate group. Berth-Jones and Hutchinson213 showed only an 18% response rate over 6 months.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. showed efficacy in only 1/26.211. and must be stored .219 It is therefore recommended that all DPCP samples be purified as described by van der Steen et al. Orecchia and Rabiossi212 also had a success rate of 1/26. Hatzis et al. 60. with complete regrowth in 30.Alopecia areata 53 MacDonald-Hull and Norris203 reported 29% (8/28) of patients had a cosmetically acceptable result. MacDonald Hull et al. Those patients with a younger age of onset are less likely to respond.218. with no significant difference in response with inosine pranobex (inosiplex). DPCP is degradable upon exposure to light. Using the survival analysis model.9%. This fits well with Colombe et al’s8 data that this group is a distinct sub-population of AA. They found that 7 of 19 (37%) showed no hair loss after treatment had been stopped for 6 months. Regarding children. A lag period of 3 months was present between initiation of therapy and detection of the first clinical response. Monk209 showed cosmetically acceptable results in 33% (6/18). Pericin208 showed that in 68 patients.6% showed a response. The only prognostic indicator correlated with response was extent of the condition.210 showed satisfactory regrowth in 24% (11/45). DPCP is not mutagenic in the Ames test. A cosmetically acceptable endpoint was obtained in 17. Of 78 patients.4% of subjects with 100% hair loss. although 53% developed patchy alopecia and 10% lost all hair that had re-grown. Six months after treatment was discontinued three of the four children with complete regrowth maintained their hair. In 1991.9%. In 68%. the presence of atopy and nail changes were not correlated to response. and teratogenicity and organ toxicity could not be detected in the hen’s egg test or in the mouse teratogenicity test. Ashworth et al.207 showed that 38% of 48 patients responded to DPCP with cosmetically acceptable regrowth.216 Analysis on serum and urine samples following application of at least 0.217 Commercial DPCP may contain a precursor.214 showed that topical 5% minoxidil solution combined with DPCP showed no benefit over DPCP alone.3% of subjects with 75–99% hair loss. The authors felt that eliciting an allergic reaction was an integral part of successful treatment resulting in hair growth. MacDonald-Hull and Cunliffe204 studied post-therapy relapse rates within 6 months after treatment. Wiseman et al. the appearance of the scalp 6 months later was cosmetically acceptable.1% of subjects with 50–74% hair loss. dibromoketone. 70.5 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. and 100% of subjects with 25–49% hair loss.215 treated 12 children aged 5–15 years. Shapiro et al. that is positive in the Ames test. Duration of condition. 25 (32%) showed complete regrowth of hair. Factors affecting response were clearly extent of condition and age of onset. the cumulative patient response at 32 months was 77. These data suggest that diphencyprone is not absorbed following application to the skin. 88.
(e) The physician or nurse must wear gloves when . (b) Intermediate concentrations may be necessary.0001–2. (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.54 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (a) Standard diphencyprone (DPCP) tray concentrations varying from 0.20 Topical immunotherapy for alopecia areata.
k. (g) Cotton swab is dipped directly into the bottle.Alopecia areata 55 handling the bottles. (f) After the application. (h) An area that has been sensitized one week before with a 2% solution. If the swab needs to be remoistened. Only unilateral application is performed until hair regrowth is seen on one side. an eyedropper is used to saturate the swab. (i) and (j) One coat is painted is the anteroposterior direction. gloves must be removed carefully from the inside out. . Another coat is painted in the lateral direction.
DPCP is compounded in an acetone base and stored in opaque bottles to protect the solution from photodegradation. The wearing of a hairpiece or scarf is sufficient. Intermediate concentrations may be necessary. 3. We periodically check the DPCP for purity with high-pressure liquid chromatography. These swabs are constructed with long wooden applicator sticks and cotton balls. and the possible failure to respond. A commitment is made to return for weekly treatments for at least 24 weeks.0001%. the use of a barrier cream and double gloving is helpful. because of the risk of sensitization of staff administering the treatment. Although not routinely used. 0. As Peret and Happle220.56 Hair Loss: principles of diagnosis and management of alopecia in amber bottles. If the person administering the DPCP develops eczema. The transition from 0. Scalp/hair should not be washed in the 48 hours following treatment. A low-potency topical corticosteroid is given to the patient for mild inflammatory reactions post-treatment. 0.20). Post-treatment guidelines for the patient include: 1. The physician must be notified of severe reactions. The . 1.05% and 0.221 suggest. Safety precautions must be implemented when handling DPCP. A local ethics committee should be asked for consent. If the swab needs to be remoistened. 4.1% to 1.5%.25% strengths for sensitive patients. For adults with more than 50% scalp hair loss. At the University of British Columbia. or topical anthralin. followed by a moist towel. 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. The patient is encouraged to meet with and observe other patients undergoing treatment. The standard DPCP tray for AA includes the following concentrations: 0.0% and 2%. We use DPCP on patients with less than 50% hair loss only if all other modalities have failed. Patients must be warned that the induction of an allergic contact dermatitis is a desired side-effect. DPCP is dissolved in acetone and stored away from the staff in the fridge in a special container. because we have found that the shelf life after opening is approximately 6 months.01%. 2. an eye-dropper is used to saturate the swab and prevent contamination. to eradicate all traces of the DPCP. topical minoxidil 5% solution in combination with topical corticosteroids. The scalp must be protected from all sources of light. 0. the lack of sufficient toxicologic data. Spills should be wiped up immediately using a dry towel. Gloves must be worn and caution used to prevent the DPCP from coming in contact with the skin of the staff member.222 The DPCP solution is applied to the scalp using a thick cotton swab that has been dipped into the bottle.001%. patients should be thoroughly informed about the experimental character of the treatment. such as intralesional corticosteroids. DPCP is used at the University of British Columbia Hair Clinic as follows: Prior to commencing treatment.5% solution of DPCP (Figure 2. the chance for regrowth. A gown covering the arms should be worn and laundered after each treatment session.1%. it has occasionally been necessary to use 0. and one that is necessary for a good result. the possible side-effects. topical immunotherapy with DPCP is our treatment of choice at the University of British Columbia Hair Clinic. 0. There is a report in the literature where DPCP treatment had to be abandoned in a clinic owing to the large number of staff becoming sensitized to DPCP. risks and benefits are carefully reviewed with all patients and an informed consent is signed. All bottles are dated on first use.0% is best bridged with a 0.
(b) 12 weeks of unilateral DPCP treatment. (f) 5 years of intermittent treatment. . (a) baseline. (c) 24 weeks of unilateral treatment. (e) 1 year of treatment.21 40-year-old female with an 18-year history of alopecia involving 99% of the scalp. (d) 30 weeks of treatment of the left side and 6 weeks on the contralateral side.Alopecia areata 57 Figure 2.
as well as the area where the tape for the hairpiece is applied. This can be confusing when attempting to titrate the patient to the correct dosage. cotton is wound around the stick to make a firm swab approximately three times the thickness of an average cotton-tipped applicator (Figure 2. Titration must be conducted carefully. a 0. The nape of the neck is a very sensitive area that will react when other parts of the scalp do not. (c) 24 weeks of DPCP treatment. it is difficult for the patient to continue wearing a hairpiece. we do not apply any solution until the following week. showing some white regrowth. If there is a marked reaction. Two coats are applied.0001% solution is applied to half the scalp. We avoid application on to the nape of the neck.22 Ophiasis in a 43-year-old female of 2 years’ duration. After 1 week. if no reaction or only a mild to moderate reaction is observed. Once the patient commits to DPCP treatment. DPCP is left on the scalp for 48 hours and then washed off. Cotton-tipped applicators do not retain enough moisture to paint the scalp adequately. Patients return for weekly visits until hair growth is established. an initial sensitizing dose of 2% DPCP is administered to a 4×4 cm circular area on the occipital region of the scalp. because severe reactions can discourage the patient and preciptate discontinuation of treatment. The patient must protect the scalp from light with a cap. .58 Hair Loss: principles of diagnosis and management of alopecia Figure 2. the first coat in an anteroposterior direction and the second coat in a lateral direction. If this area becomes irritated.20). (a) baseline. (b) 12 weeks of DPCP treatment.
Concentrations vary (0. DPCP is reapplied to the same half of the scalp.0001%.23 Unilateral treatment with DPCP. Intralesional corticosteroid is injected once monthly. 0. Each week when the patient returns.0%.01%.24 Delayed DPCP response.5%. (b) Both sides were then subsequently treated. the severity of reaction and the presence of any hair growth are assessed. Once hair growth is established one one side. 0. The following week. Figure 2. 0. The concentration is adjusted individually on the basis of the severity of the previous reaction.20).Alopecia areata 59 wig or scarf during this period of time. or a low tolerable eczema. 2. 1. on the treated side for 36–48 hours after application. These refractory areas can be injected once monthly.1%. It is better to be cautious than to be very aggressive and cause a severe reaction. (a) She returned to the clinic after treatment had been discontinued for 6 months with a unilateral response on the treated side. the other side is treated (see Figure 2. 0.001%. The tolerance to the discomfort from the eczema varies with patients. as DPCP is degraded when exposed to light.05%. . The aim is to maintain erythema and pruritus. showing circular areas refractory to treatment. Figure 2. The patient had been treated unilaterally for 6 months without a response.0%). with full regrowth. DPCP is applied weekly for 3 weeks out of every month. It is important to listen to your patients. 0.
(c) Complete regrowth with treatment. (a) Unilateral eczematous response one week after application. No application for 1 full week with a lower concentration applied the following week.25 Treatment of eyebrows with DPCP. . Figure 2.26 Eczematous eruptions from DPCP. (b) Marked bulla formation is possible. This reaction is too strong. (b) Baseline before treatment in a 40-year-old female with no eyebrows for 18 years. (a) Position used to apply DPCP to eyebrows.60 Hair Loss: principles of diagnosis and management of alopecia Figure 2. Eyes are well shielded.
(g) Contact dermatitis to remote areas. (f) Frontal unilateral edema and eczema.(e) The neck area is a common area for a bad reaction. .Alopecia areata 61 (c).(d).
(b) The same patient.and hyperpigmentation (‘dychromia in confetti’) after 24 weeks of treatment in an East Indian patient. Figure 2.and hyperpigmentation in an African-American patient. (d) Vitiligo on the back of the neck. .62 Hair Loss: principles of diagnosis and management of alopecia Figure 2. (c) Hypo.27 Lymphadenopathy occurs in 100% of patients.28 Pigmentary changes with DPCP: (a) Hypo. with most pigmentary changes resolved.
(f). Once full regrowth has occurred (Figures 2. . the frequency of treatment is gradually reduced.Alopecia areata 63 If patients have discontinued treatment because of intolerable effects. it is difficult to get them to resume therapy. (g). The requirement for (e) Vitilgo on half of the scalp in a patient who had been applying DPCP at home. The strength can always be increased later when the patient becomes familiarized with the treatments. 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. then every third week for 4 weeks. using the rule of four: treatment is adminstered every other week for 4 weeks. and so on. One patient was able to discontinue treatments for 4 years before she experienced any hair loss.21 and 2.22). Maintenance requirements vary with individuals and commonly range from biweekly to bimonthly treatments. (h).
The psoralen is administered either topically or orally. and we may abandon topical immunotherapy and proceed to another modality of therapy. Contact urticaria. At our clinic.223 Shah et al. such as hyperpigmentation. They consistently grow new hair in more areas and do not seem to lose hair. We have had a few patients that we identify as ‘slow growers’. but ocular toxicity is avoided.224 a combination of both referred to as ‘dyschromia in confetti’225 and vitiligo226–229 have been reported. Burns are more likely to occur with topical therapy. DPCP is contraindicated in pregnancy. most of the scalp regrows hair except for a few small areas refractory to DPCP. with gradual new growth in multiple areas. Another phenomenon we have seen is the ‘initial non-responder’. This is best done at the end of the treatment. although teratogenicity has not been demonstrated.222 report the risk to medical and nursing staff. and usually respond well (see Figure 2. 230. Pigment changes (Figure 2. hypopigmentation. and the swab should be minimally moist. Vitiligo is more common in AA patients.64 Hair Loss: principles of diagnosis and management of alopecia maintenance therapy illustrates the palliative nature of the treatment. .25).29). 232 and erythema multiforme233 have also been reported. However. If the patient has not responded by 52 weeks. These resistant areas are treated with intralesional triamcinolone acetonide 5 mg/ml once monthly. we consider the patient unlikely to respond. Extreme caution must be used.27) in the neck behind the ears. 234 (see Figure 2. All female patients are counselled to use reliable birth control while on DPCP. All six pregnancies have produced normal children. and because vitiligo has a tendency to koebnerize on to inflamed skin. growth was obtained (Figure 2. and is followed in 1 hour or 2 hours with UVA irradiation. Within 2 years of stopping treatment.23). and discontinue treatment. DPCP has been used with success to treat eyebrows. six women have become pregnant while on DPCP therapy. after the scalp has been treated (see Figure 2.234 It may effect T cell function and antigen presentation. one must be very cautious about rapid extension of vitiligo in an AA patient who already has the condition. autoeczematization. and possibly inhibit local immunologic attack against the hair follicle by depleting Langerhans cells. with gradual increase in UVA dosage. Treatments are administered two to three times a week. Side-effects include eczema (Figure 2. These patients initially do not respond. Extreme caution should be exercised when treating patients of dark pigmentation. Upon recommencing treatment.231 severe dermographism. a small number of individuals have returned with hair growth only on the orginally treated side. The process of complete regrowth is lengthy. DPCP therapy was immediately halted once our clinic was informed. In certain responders. despite all the warnings on the informed consent form. the eyes shielded with gauze.24). The patient should be lying flat. we do not ever give DPCP to the patient for self-application. Consort dermatitis to spouse/partner has also been reported. Vitiligo is a relative contraindication for treatment with topical immunogens. we have had patients that have taken 41 weeks to see unilateral regrowth.223 severe blistering and lymphadenopathy (Figure 2.28).26). Photochemotherapy (PUVA) The mechanism of action of PUVA on AA is believed to be a photoimmunologic action. Because of the possible side-effects. Regrowth of hair will take at least 12 weeks.
(a) Baseline before PUVA.61 (Figure 2.3%) and good regrowth in 2/22 (9%). Claudy and Gagnaire 235 used systemic PUVA with total body irradiation and showed a success of rate of 70%. Mitchell and Douglas234 used a combination of topical 0. with median time to relapse being 10 weeks. Whole body treatment did not produce significantly better hair growth.1 joules/cm2. Cyclosporin Systemic cyclosporin has been shown to have some benefit in AA.Alopecia areata 65 Figure 2.60. No significant differences were seen. (b) After 1 year of PUVA.239 Today’s concern about PUVA and its promotion of all types of skin cancer. Larko and Swanbeck236 studied 40 patients with systemic PUVA. but only 20% experienced a full regrowth. Relapses were frequent. owing to the side-effect profile.237 studied 41 patients with oral 8-MOP and whole body irradiation. the high recurrence rate following .1% 8-methoxypsoralen (8-MOP) and UVA and showed excellent regrowth in 8/ 22 (36. He was unresponsive to 24 weeks of topical immunotherapy with DPCP. including melanoma.30). Almost all the patients available for follow-up experienced relapse when PUVA was tapered.238. Only 10% relapsed after 6–12 months. and local 8-MOP plus local UVA irradiation. comparing whole body irradiation and scalp irradiation only. Lassus et al. Mean total UVA exposure for responders was 171. Thirty-five percent experienced hair regrowth.29 PUVA therapy in alopecia areata: a 22-year-old patient with extensive alopecia affecting 95% of his scalp for 2 years. There was a response rate of almost 50% in each group. He still has refractory patches that are amenable to intralesional corticosteroid therapy. The major problem with PUVA therapy is the high relapse rate that frequently sets in after tapering the treatment. 240 together with the need for long-term therapy in AA. with a mean total number of treatments of 47. As with systemic corticosteroids. make PUVA therapy less than satisfactory.
(d) 5 months of therapy.66 Hair Loss: principles of diagnosis and management of alopecia Figure 2. extent of alopecia and motivation for treatment. (a) Mechanism of action by inhibiting the Th response to the 1 hair follicle. Treatment plan Therapeutic selection for AA depends on patient age. The patient had to discontinue therapy owing to serum transaminase changes and cholesterol elevation. Gilhar et al. discontinuation of the treatment. (b) A 28-year-old male with alopecia universalis for 2 years.242 could not prove any cosmetic benefit from topical cyclosporin with concentrations of 10%. The dermatologist should first discuss all therapeutic options and outcomes. this treatment is simply not practical in AA.241 and De Prost et al.30 Cyclosporin in alopecia areata. (c) 3 months of systemic cyclosporin (4 mg/kg/day) and prednisone 5 mg/day. the long treatment periods and the inability to change the ultimate prognosis of the disease. al- .
Vera H. while in adults other options to be considered include intralesional corticosteroids or immunotherapy. A practical treatment algorithm for the treatment of AA is the University of California. If there is no response after 3–4 months. corticosteroids and anthralin are considered in children of less than 10 years of age.31 University of California at San Francisco-University of British Columbia Treatment protocol for alopecia areata (permission granted by Drs Jerry Shapiro. lowing the patient to become an active member of the therapeutic team.Alopecia areata 67 Figure 2. as many AA patients will regrow their hair without treatment.Price. 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. San Francisco—University of British Columbia Alopecia Areata Treatment Protocol (see Figure 2. Firstly. Topical therapies with minoxidil. However. the following options are offered. we always offer the patient the option of no treatment. For those with less than 50% scalp hair loss. and Harvey Lui). Patients are divided into those less than 10 years of age and those over 10 years of age. First-line therapy for scalp AA is intralesional corticosteroid injections into the alopecic patches. we will add a minoxidil 5% solution twice daily and a superpotent corticoster- .31). most of our patients are well-motivated and want treatment.
68 Hair Loss: principles of diagnosis and management of alopecia Figure 2.0% cream applied for up to 1 hour daily combined with topical minoxidil 5% solution applied twice daily.32). A scalp prosthesis should be available to all patients with more than 50% scalp involvement. topical immunotherapy is discontinued. Use of eyeliner or alopecia masking lotion (Figure 2. our first line is topical immunotherapy with DPCP. If there is no response by 52 weeks. It should be emphasized to the patient that a prosthesis does not imply permanent hair loss. (c) Net meshes that are typical. oid cream such as clobetasol propionate applied 30 minutes after the minoxidil in addition to the monthly injections. Other options that can be offered to the patient are systemic PUVA.33) can give the AA . minoxidil 5% solution. Scalp prostheses come in an assortment of net linings that are light. another option is short-contact anthralin therapy with anthralin 1. If there is no benefit. short-contact anthralin and superpotent topical steroids.32 Scalp prostheses come with different linings that are light and allow air to circulate. but having one on hand is comforting for episodes of extensive hair loss. For those patients with more than 50% scalp involvement. (a) A lining that will allow one’s own natural hair to be pulled through. and can give great satisfaction to a majority of patients. (b). and cool and allow air to circulate (see Figure 2.
and the dermatologist needs to become familiar with sup- Figure 2. patient considerable camouflage.194. He has a small patch of alopecia areata. Those older than 10 years are treated with the same protocols as adults.33 Camouflage with eyeliner. port groups and suppliers of hairpieces. Children: Therapeutic modality choices depend upon patient age. Physicians need to take the time to address the psychological needs of their patients. For some patients. (b) Camouflage with eyeliner.34). (a) The patient is a 23-year-old who likes his hair short. Dermatography of eyebrows is a technique that can be recommended for AA patients with prolonged eyebrow loss243 (Figure 2. In those younger than 10 years intralesional corticosteroids are avoided and topical immunotherapy is not implemented. support groups play an important role in the overall therapeutic strategy. The ultimate therapeutic plan is developed through team interaction between the patient. the patient’s family and the physician.195 For those under 10 years of age. giving the illusion of hair in the area.Alopecia areata 69 Figure 2. exploring the impact of alopecia on the patient’s emotional . although several European studies have demonstrated efficacy and safety in children as young as 5 years.34 Dermatography: a semi-permanent tattoo for the eyebrows. therapeutic options include minoxidil alone or in combination with a mid-potency topical corticosteroid or anthralin.
8.org) offers patients and physicians information... The role of this therapy in the treatment of AA holds great potential for the future. Profile of alopecia areata: a questionnaire analysis of patient and family. J Invest Dermatol Symp Proc. 96(5):67S–100S. Muller R. Khoury E. HLA class II alleles in longstanding alopecia totalis/alopecia universalis and long-standing patchy alopecia areata differentiate these two clinical groups. Alopecia areata. 1996. 4(3):197–254. Gene replacement therapy based on current genetic studies may eventually allow lasting correction of abnormal gene expression. Arch Dermatol. Alopecia areata: an evaluation of 736 patients. Bethesda.H. 1992. Colombe B. 33(5 Pt 1):757–64. et al. 1995. videos for children to take to school and information about support groups..H. 1995.Y. and Koo J. Heritable factors distinguish two types of alopecia areata.H.W. The eventual discovery of cytokines specific for hair growth promotion in topical immunotherapy will offer more focused treatments. Price V.V.W. Other biotechniques to interrupt the peptide-antigen or T-cell receptor are being evaluated. Physicians are welcome to attend. light-emitting diode arrays). Maryland. safety profiles and outcomes. Rodent models currently available have become an important part of therapeutic research.W. Shellow W. 3. 14(4):679–89.. It is imperative that the physician spend sufficient time with the patient. 1963. Third International Research Workshop on Alopecia Areata. November 7–8. 6. and Colombe B.W.D. Khoury E. 1999. 2. 1991. The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis. research updates. J Invest Dermatol.alopeciaareata. J Am Acad Dermatol. 4(3):216–19. 104(5 Suppl):1S–45S.E. 9. California 94901–3853. References 1. 5. and Lou C. which are present in many large cities in the USA and Canada. The National Alopecia Areata Foundation (710 C Street. Outlook for the future for alopecia areata treatments New therapeutic directions for alopecia areata will involve specifically targeted immunomodulatory agents. San Rafael.S. and Price V. Edwards J.. Lou C. 1995. Price V. The National Alopecia Areata Foundation (NAAF) has an annual convention for patients and their families. 4. just as one would with a patient who had recently been diagnosis as diabetic.L. Price V.70 Hair Loss: principles of diagnosis and management of alopecia well-being. bimonthly newsletters. .L. 1999. Maryland. 1990. sources for scalp prostheses. Colombe B. 2nd International Research Workshop on Alopecia Areata. Colombe B. including brochures. October 25–26. penpals for children. Newer immunomodulators specific for CD4 or CD8 and IL-2 receptors may further enhance treatments. J Invest Dermatol. Suite 11.W. HLA class II antigen associations help to define two types of alopecia areata. Int J Dermatol. 31(3):186–9..H. involving new photosensitizers and novel non-UV light sources (lasers. 88:290–7. Bethesda. 1994. www. 7.. J Invest Dermatol.D. and this is often the turning-point for them in terms of coping with the condition. J Invest Dermatol. has the potential to immunomodulate. Phototherapy beyond PUVA. A workshop. Dermatol Clin. It is the role of dermatologist to explain the diagnosis and inform the patient of all the therapeutic options. 104(5 Suppl):4S–5S.
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4-dinitrobenzene depletes glutathione in rat skin and is mutagenic in Salmonella typhimurium. 1980.M. 1979. 117(7):384–7. 1984. and Smith R. J Am Acad Dermatol. 35(1):52–6.L. Klein H. Buchner U. Contact allergy as a therapeutic tool for alopecia areata: application of squaric acid dibutylester. Topical treatment of alopecia areata. Arch Dermatol.. Testing of twenty-one environmental aromatic amines or derivatives for longterm toxicity or carcinogenicity. Arch Dermatol. 114(11):1629–31. Chua S. 115(10):1254–5. 193.G..B.S. Hehir M. 266(3):315–18.A. Happle R. 1981. 1985.L.. Irritant versus allergic contact dermatitis for the treatment of alopecia areata. 174. 10(3):447–50. and Buys C... 188. Treatment of alopecia areata with squaric acid dibutylester. and Rohrborn G.. J Invest Dermatol. et al.. 182. Morhenn V.H. and du Vivier A. and EchternachtHapple K. and Spielvogel R. 278(3):214–8. Arch Dermatol. 184. Mutagenic and cell transforming activities of 1-chlor-2. 187. 1980. Goerz G. Daman L. Anthralin therapy for alopecia areata.K. 123(11):1491–3.4dinitrobenzene (DNCB) and squaricaciddibutylester (SADBE). and Drake L. 45(4):307–14... 1980. 9(4):554–7. 185. Happle R. Inhibition of a Langerhans cell-mediated immune response by treatment modalities useful in psoriasis. 24(9):606–7. Cebulla K. 1978. Topical squaric acid dibutylester therapy for alopecia areata: a double-sided . J Environ Pathol Toxicol.. 267(1):109–14.K. 186. Arch Dermatol Res. 4(3):385–7. Arch Dermatol. 1987.C. Weisburger E.. 114(7):1036–8. Russfield A. 176. Case P.. Cicero R.B.J. 1983. Plewig G. 161(5): 289–97. Flowers F. Micali G.L. Treatment of alopecia areata with squaric acid dibutylester. Int J Dermatol. 1979.. Arch Toxicol. Summer K. Dermatologica. 123(8):1036–41. 1983.. 2(2):325–56. Arch Dermatol. Homburger F.J. 167(5):280–2. 81(1):23–7. 173.. Kalveram K. 1978. Kaplan J. Dinitrochlorobenzene: influence on the cytochrome P-450 system and mutagenic effects. and Orecchia G. Arch Dermatol Res.. Wilkerson M. Mitchell A. Mitchell A. l-chloro2.78 Hair Loss: principles of diagnosis and management of alopecia 171.. Int J Dermatol.. Nasca M. Buchner U.G. 1986. Strobel R. Weissman I. 1996. and Braun-Falco O...A.E. Fenske N. 190..J. Antigenic competition as a therapeutic concept for alopecia areata. Alopecia areata treated with DNCB. 175. 264:123. and Pullara T. 183. Fiedler-Weiss V.H. Wilkin J. 1987. Evaluation of anthralin in the treatment of alopecia areata.W. 1982. Vizethum W. 181. 1979. Nelson D. and Strobel R. 1978. Arch Dermatol Res. Leahy M.P. 179.B. Schmoeckel C. Caserio R. and Ang C.J. et al. 191. 178. 192. et al. 30(6):733–6. Clinical experience on the treatment of alopecia areata with squaric acid dibutyl ester. J Am Acad Dermatol.. Topical immunotherapy changes the composition of the peribulbar infiltrate in alopecia areata.M. 172. Topical squaric acid dibutylester therapy for alopecia areata. Dermatologica.. 189. and Sapuppo A.C.J. 1980. Happle R. Orenberg E.. Kratka J. Cutis.. 1979. Treatment of alopecia areata with dinitrochlorobenzene. Dinitrochlorobenzene therapy for alopecia areata. Topical therapy of alopecia areata with squaric acid dibutylester. et al.. and Macher E. 180. Happle R. Arch Dermatol.A. Swanson N. Rosenberg E. 77(1):91–3. 1983.. 177. Treatment of alopecia areata by anthralin-induced dermatitis. and Goggelmann W. Giannetti A.K.A..R. et al. Contaminants of dinitrochlorobenzene. Slazinski L. Swanson N. Goh C. Clin Exp Dermatol.A. Arch Dermatol Res. Mutat Res.
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Vitiligo complicating diphencyprone sensitization therapy for alopecia universalis [letter]. 179(3):137–8.. and Tron V. Berth-Jones J. 1991. 222. Treatment of alopecia areata. 199(2):198. New York: Springer Verlag. C. Ho V.. Steijlen P..H.Erythema multiforme-like eruptions: a rare side effect of topical immunotherapy with diphenylcyclopropenone. J Am Acad Dermatol. Pepall L.G. Shah M. Duhra P. pathogenesis and topical immunotherapy]. Alopecia areata in children: response to treatment with diphencyprone. 12(4):644–9. 1988. Topical photochemotherapy for alopecia areata. 133(3):496–7. Hatzis J.. 1993. 225. 1989. 229. 74(4):312–3. Br J Dermatol. 218. 123(3):415–16.M. Tosti A. Tan J. Connor T.M. 227..C. 21(3):196–7. Steijlen P. Allergy. Perret C. 1989. 1989. Lewis P.. Hazards in the use of diphencyprone. Contact Dermatitis.E. et al. and Foulds I. Diphencyprone is not detectable in serum or urine following topical application. 40(1):110–12. Shapiro J. Persistent vitiligo induced by diphencyprone [letter]. 1990. Severe urticarial reaction to diphenylcyclopropenone therapy for alopecia areata. 1994. Dermatologica. Acta Derm Venereal. Severe dermographism after topical therapy with diphenylcyclopropenone for alopecia universalis. Tosca A. and Happle R. 42(4):212–15. 29(5 Pt 1):729–35. 217. p. and Happle R. Wilkerson M. 231.C. Gross E. Nameda Y. 24(2 Pt 1):253–7. Dermatologica. 215. Perret C. 128(4):518–20. Mitchell A. Br J Dermatol. and Toribio J. and Stock J. Van der Steen P. 228. Dermatologica. and Bardazzi F. 1984. ed. J Am Acad Dermatol. Diphenylcyclopropenone: examination for potential contaminants.K.. Arch Dermatol.. Fernandez-Redondo V.80 Hair Loss: principles of diagnosis and management of alopecia 214. 2000. Florez A... 1987. and Hutchinson P. Henkin J.. 2000. J Am Acad Dermatol. 216. Assessment of diphenylcyclopropenone for photochemically induced mutagenicity in the Ames assay. 1995..M. 134(6):1153.J. 125(2):164–8. Orecchia G.. 17(4):606–11. Br J Dermatol. and Arase S. and Douglass M. Henkin J. Zaun H. 221.. In Hair and Hair Diseases.. Henderson C. et al.A. Br J Dermatol. Treatment of chronic severe alopecia areata with topical diphenylcyclopropenone and 5% minoxidil: a clinical and immunopathologic evaluation. 232. Van der Steen P. 55(2): 202–3. ‘Dyschromia in confetti’ as a side effect of topical immunotherapy with diphenylcyclopropenone.. Ned Tijdschr Geneeskd. Mc Burney A. and photochemical stability. [Alopecia areata. Treatment of alopecia areata with diphenylcyclopropenone [see comments]. 11(5 Pt 1): 802–7. 234.A. and Ilchyshyn A. Hazards in the use of diphencyprone [letter] [see comments]. Diphenylcyclopropenone: an important agent known to cause depigmentation [letter. and Cunliffe W. 180(1):5–7.. comment]. van Baar H. 1999.M.S. Contact Dermatitis. and Happle R. 224. J Am Acad Dermatol. 1991.... Guerra L. and Wilkin J.H. comment]. Gourgiotou K. and Happle R. 1999. Hull S.R. Gomez-Centeno P. 1985.M. 1996. Takiwaki H. and Messenger A. 233. 223.M. and Savin R..M. Alam M. 219. 1990.G.J.Happle. Dermatology. Contact urticaria during topical immunotherapy. 529.. 177(3):146–8. Wilkerson M. 133(25):1256–60. Perret C.. Perret C. 1992. . 220.O.Vitiligo and topical allergens [letter.M.G. 1990. Orecchia G. and Perfetti L. J Am Acad Dermatol. mechanisms of sensitization. Vitiligo as a reaction to topical treatment with diphencyprone [see comments]. 230. Skrebova N. 226. J Am Acad Dermatol.
totalis and universalis: audit of 10 years’ experience at St John’s Institute of Dermatology. and Hawk J. Larko O. and Etzioni A. Nichols K. Drost B. Lassus A. Acta Derm Venereal. 1995. Int J Dermatol. The PUVA Follow-Up Study [see comments]. PUVA treatment for alopecia areata—does it work? A retrospective review of 102 cases. Pillar T. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). 243. and Rogers S.. and Vakeva L.. Ijsselmuiclen O. and Gagnaire D. 37(8): 617–21. Photochemotherapy for alopecia areata. de Prost Y. Topical cyclosporin A in alopecia areata.R. 1998. 242. 60(2):171–2.. New Engl J Med. Gilhar A. Acta Derm Venereal. Teillac D. 69(3):252–3. 1997.E. Claudy A. 1980. 63(6):546–9.. Br J Dermatol. Dermatography as a new treatment for alopecia areata of the eyebrows. and Swanbeck G..Alopecia areata 81 235.S. Johansson E. 238. Stern R. et al. 161(5):298–304.H.. PUVA treatment of alopecia totalis. 239. 1980.. Van der Velden E. et al. et al.M. 241. 129(1):42–4. Healy E.H.L. Lancet. Dermatologica.. Br J Dermatol. 1989.. Placebo-controlled trial of topical cyclosporin in severe alopecia areata [letter]. PUVA treatment for alopecia areata. 336(15):1041–5. 1993. 1986. Acta Derm Venereal. 236. 133(6):914–18. 240. Kianto U.T. 1983...L. Paquez F. Taylor C. 237. PUVA treatment of alopecia areata partialis. 2(8510):803–4. . and Juvakoski T.
it can have a significant psycho-social impact for patients. This shortening of anagen and subsequent miniaturization of hairs leads to decreased scalp coverage. Complete permanent regression is unlikely. clinical features and state of the art medical management of AGA. Asians and Inuits. As its name implies. 4–6 This chapter will highlight the pathogenesis.3 polygenic. It is still controversial what becomes of these miniaturized follicles. Genetic factors The exact inheritance pattern of AGA is still debated.3 Androgenetic alopecia: Pathogenesis. minoxidil. and least frequent in Amerindians.17. It is believed to be most likely autosomal dominant. After puberty. AGA involves both genetic and hormonal factors.1).19 and inherited from either parent.18 These finer small vellus-like hairs of varying lengths and diameters are the hallmark of AGA (Figure 3. with progressive shortening of the anagen phase occurring over many cycles. clinical features and practical medical treatment 16 Introduction Androgenetic alopecia (AGA) is by far the most common cause of hair loss. in AGA the number of follicles per unit of area remains the same. less so in Africans.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. However. androgens trigger a series of events within these genetically-programmed hair follicles.21 .1–3 Although it is a medically benign condition.1. Pathogenesis Knowledge of the patho-physiology of AGA is essential in understanding the mechanism of action of current therapeutic agents. predominantly of the fronto-parietal scalp. that transform terminal to miniaturized follicles. spironolactone and estrogen (personal observation). We are only beginning to understand the different factors underlying AGA.19 The gene frequency appears to be most common in Caucasians. A MIM entry that begins with the number one indicates an autosomal dominant inheritance. since cases of severely advanced balding male to female transsexuals have experienced considerable regrowth using finasteride. The following is a summary of the current knowledge on AGA pathogenesis.20 The McKusick Mendelian Inheritance in Man (MIM) number for AGA is 109200.7– The hair cycle is altered.
Eleven had two generations of families with both parents affected. and 46% of the brothers were bald if the father was not bald. whereas the genotype Bb requires higher amounts of androgen. Fifty-six per cent of bald men had bald fathers. Some previous work on the genetics of AGA dates back to 1919. This observation is quite interesting. They present very credible arguments . although no formal study has been performed.1 In androgenetic alopecia. there is miniaturization of coarse terminal hairs into small vellus-like hairs with each subsequent cycle. in affected individuals. Salomon25 felt that AGA is inherited through multifactorial or conditioned dominance via an autosomal dominant gene of variable expressivity. 24 three generations and 3 four generations involved. The genotype bb may remain sub-clinical in both sexes. There was an association of increasing amounts of chest hair. Osborn22 stated that AGA was a sex-limited autosomal dominant trait similar to the inheritance of horns in sheep.26 Kuster and Happle. He studied 119 males with AGA. The authors concluded that this was consistent with an autosomal dominant gene. and women who presented with AGA were homozygotes only. in that Shapiro has noted the same trend in increased body hair distribution in a disproportionately large number of his balding male patients. A family has been described in which common baldness with early onset occurred in females only. 66% of the brothers were bald if the father of the proband was also bald. 65 had two generations. but not back hair. Sixteen had no family history.84 Hair Loss: principles of diagnosis and management of alopecia Figure 3. 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. Harris24 found that of 117 men with AGA.19 favor a polygenic inheritance rather than a simple Mendelian model. She believed that men could be either homozygotes (BB) or heterozygotes (Bb).
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.41–43 further supporting the DHT requirement for AGA expression. type I and II. 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. epidermal and follicular keratinocytes. although this genetic change was not the primary cause of either condition. are both part of normal androgen metabolism and reduce testosterone (T) to dihydrotestosterone (DHT).30 Sreekumar et al.28 There was an association with one allele of the steroid metabolism gene CYP17. The X-linked mutation for adrenoleukodystrophy.Androgenetic alopecia 85 supporting multi-allelic inheritance.33 5a-reductase isoenzymes. lacking androgen receptors.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. the distribution of the balding patterns in the general population along a Gaussian curve of variation. but to a lesser extent in women.27.34 as well as in the epididymis. Hormonal factors A major determinant of AGA is intracellular androgen metabolism. Individuals with a genetic deficiency of 5a-reductase type II isoenzyme do not develop AGA. which involves two steroid-metabolizing enzymes (5a-reductase and aromatase) and androgen receptor pro- teins.28 The search for the gene continues. vas deferens. 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. with typical female AGA (unpublished personal observa- . and the fact that the risk increases with the number of relatives already affected. A recent case report by Orme et al. and sweat glands.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. and fetal genital skin. The high prevalence rate. which is correlated to premature AGA in men.34 The 5a-reductase type II isoenzyme is located mainly in the root sheaths of the scalp hair follicle33.35.34 Both type I and type II isoenzymes play an important role in AGA. Shapiro has seen a female teenager with androgen-insensitive syndrome. The 5a-reductase type I isoenzyme is located mainly in sebaceous glands. Other important factors may still remain to be discovered.1. 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.38–40 Women have 3. dermal papilla cells. Carey et al.27. seminal vesicles. 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.32.33 DHT levels are increased in balding scalp when compared to non-balding scalp.33 and this may explain why female AGA is usually less severe than male AGA.5 times less 5α-reductase (I and II) than men.0–3. showing that this pattern of hair loss is not necessarily androgen-dependent.33. may be a part of the polygenic spectrum of genes responsible for AGA.35–37 Both isoenzymes are increased in frontal balding follicles compared to occipital non-balding follicles. prostate.
rather than downsize. which can elicit a telogen effluvium. consisting of acute episodic phases with increased loss of telogen hair.33 The receptor levels were found to be 30% greater in balding frontal hair follicles than in nonbalding occipital follicles in both men and women with AGA. although hair density does decrease as they age further.2a) and as late as the age of 45 in both sexes.47 For many individuals. Women . 12% in one study showed a completely negative family history. 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. However. may unmask a tendency for AGA.13. alternating with periods when there is little shedding. This likewise helps explain why women with AGA usually retain their frontal hairline and have less hair loss than men with AGA. Paradoxically. they admit that it is impossible to distinguish male from female hair shaft miniaturization either clinically or histologically. The shedding may be seasonal in a small number of individuals.and post-menopausal states.33 Aromatase results in the conversion of T to estradiol and estrone.86 Hair Loss: principles of diagnosis and management of alopecia tion). Aromatase is significantly higher in the hair follicles of women. Dermis of the frontoparietal scalp is derived from the neural crest.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. Most cases start between the ages of 15 and 25.17. whereas dermis of the occipital/temporal scalp is derived from the mesoderm. and may have a protective effect on hair follicles. The explanation for this bifurcated action is not known. but the total receptor content is 40% less in women than in men.17 Studying the quail-chick model. Ziller46 found differences of embryonic origin of the dermis of the fronto-parietal scalp compared to the occipital scalp.25 Hair loss in women may be triggered by hormonal changes.47 Many men reach their maximum pattern by their forties. These events. These events within the follicle result in the transformation of terminal to miniaturized hair follicles on the scalp in AGA. AGA usually manifests at an early age and progresses slowly. Norwood and Lehr45 have proposed that female AGA may be a separate entity.8. The cytochrome P450 aromatase enzyme is also part of normal androgen metabolism.47 The clinical course is gradual. androgens upsize. in other androgensensitive areas such as the beard and mustache. the condition may seem stable for years. and therefore the resulting shift will lessen conversion of T to DHT. However. However. These findings are intriguing. Usually there is a positive family history.32. hair follicles at puberty. including starting or stopping the oral contraceptive pills and post-partum and peri. 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.33 Androgen receptor proteins (ARP) are found in the outer root sheath and dermal papilla fibroblasts of scalp hair follicles. Clinical features of AGA History Thinning of the hair can occur as early as the age of 12 (Figure 3.
017 men from Framingham. in the vast majority of women with AGA. cardiovascular disease. A contrast paper is placed in a parted area of the scalp.49–51 In one study there appeared to be lipoprotein and triglyceride level differences between males with vertex thinning and non-balding men. in 1956 and in 1962. Baldness was assessed twice.2 (a) Male androgenetic alopecia can appear early. Massachusetts. in a cohort of 2. 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. frequently indicates an androgen excess in the female patient. This is a 13-year-old boy showing frontotemporal thinning and hair miniaturization. (b) The presence of miniaturized hairs helps to confirm a diagnosis of AGA. The hair is then closely examined against this backdrop. must be questioned about the regularity of their periods and the presence or absence of hirsutism in an attempt to determine if hyperandrogenism is a problem. The cohort was followed for up to 30 years for new occurrences of coronary heart disease. standing for seborrhea. especially among men with hypertension or high cholesterol levels.53 assessed the relation between the extent and progression of baldness and coronary heart disease.50 with an increased risk for atherosclerotic and coronary heart disease in balding men. coronary heart disease death. Lotufo et al. SAHA syndrome. Extent of baldness was not associ- . hyperandrogenism is not a problem.52 showed that vertex pattern balding appears to be a marker for increased risk of coronary heart disease. and death due to any cause. alopecia. adjusting for age and other known cardiovascular disease risk factors. Herrera et al. The biologic mecha- nisms for this relationship are unknown.Androgenetic alopecia 87 Figure 3. However. hirsutism and acne. The relations between the extent and progression of baldness and the aforementioned outcomes were assessed using a Cox proportional hazards model.48 An increased risk for coronary artery disease has recently been correlated to vertex balding in men.
47 In some individuals. although there may be a mild increase in telogen hairs. such as atherogenesis.3–4.55 A total of 3. hypertension.5. extended follow-up. no association between coronary heart disease and androgenetic alopecia was found.7). AGA becomes a preoccupation.56 further hypothesize that AGA in men may predict other age-related pathological processes. coronary heart disease mortality (RR=3.8). Men with AGA had a consistently higher incidence of prostate cancer compared with those without AGA. and is blamed for all social and professional problems. when compared to age-matched controls. These authors suggest that men with early AGA might benefit from screening for cardiovascular risk factors and for insulin resistance. in which the alopecia is merely a symptom that the patient may clutch on to. with preservation of follicular ostia. Miniaturized vellus-like hairs can usually be seen with contrast paper placed over a part (Figure 3. In some women with AGA.8. in a study of 478 men.5 per 10. and occasionally in men.9–7. Psychoneurotic attitudes may ensue.5 vs 12. 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.54 This finding supports the hypothesis that early AGA could be a clinical marker of insulin resistance. Hawk et al. In terms of the pattern of hair loss.2b). women usually have less severe hair loss than men and .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. medical records and death certificates.4). A hair pull test is usually negative.88 Hair Loss: principles of diagnosis and management of alopecia ated with any of the outcomes.000 person years). and dyslipidemia in men with early onset of AGA (< 35 years).5–3. 95% confidence interval (CI) 1. AGA may unmask a psychological lability and/or psychiatric disturbance. On the other hand. that tend to remain clinically silent until they are advanced. including race and age. 95% CI 1. The investigators noted that the age-standardized incidence of prostate cancer was greater among men with baldness at baseline (17. thus limiting the effective power of their study. 95% CI 1. and national representative sampling. Incident cases of prostate cancer were identified by interviews. However. and all-cause mortality (RR =2. the amount of progression of baldness was associated with coronary heart disease occurrence (relative risk (RR)=2. and was similar regardless of the severity of baldness at baseline and was independent of other risk factors.4. The major strengths of this study included its prospective design. Prostate cancer was diagnosed in 214 subjects over 17–21 years of follow-up. 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. beginning at approximately 60 years of age. It was concluded that rapid hair loss may be a marker for coronary heart disease. The authors concluded that men with AGA had a 50% excess risk for clinical prostate cancer.4. large sample size. 56 Participants were followed from baseline (1971–4) through to 1992.47 Physical examination Hair loss is patterned and non-scarring. The adjusted relative risk for prostate cancer among men with any degree of baldness was 1. though only in involved areas of the scalp.
and usually in those with early-onset AGA.Androgenetic alopecia 89 Figure 3.3 In female AGA. In men. This generally occurs in those women with more advanced hair loss. The hair thinning is mostly on the crown. Olsen58 feels that 5% show a global decrease in scalp hair density. This pattern is recognized as the Ludwig pattern. ‘parting’) found in a woman without AGA. 97:247–54. most women present with an intact frontal hair line.8). diffuse hair thinning may be present (Figure 3. Shapiro feels that approximately 30% of women have a more global thinning. Ludwig Stage III is rare.4–3. Reproduced with permission from the British Journal of Dermatology 1977. and women affected may require an endocrine work-up if they show other signs of androgen excess.57 Ludwig Stage I is the most common pattern. ‘parting’) in the centro-parietal area with that in the occipital area. and is divided in 3 stages according to severity (Figures 3.4 (a) Ludwig classification of female AGA.9a and b). (b) The characteristically narrow division of bare scalp between areas of combed hair (‘part’. retain their frontal hairline (Figure 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’. there still remains a variance of hair density on the top of the scalp versus the sides or the back of the scalp. The presence of global thinning clearly decreases the chances of being a successful female hair transplant candidate. . Even with this diffuse loss.3). In a significant percentage of female patients with AGA. there is a frontal hairline recession associated with thinning or balding on the Figure 3.
8 Ludwig Stage III: Considerable loss of hair. improved on this pictorial classification. as before. 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. as in Figure 3.90 Hair Loss: principles of diagnosis and management of alopecia Figure 3.7 Mother (left) with Ludwig Stage II and daughter (right) with Ludwig Stage I. Figure 3. ‘parting’) is now considerably more evident than in Ludwig I. crown or vertex. 60 more than 25 years later. and is divided . 59 Norwood.5 Ludwig Stage I: A widening of the division of bare scalp between areas of combed hair (‘part’. Figure 3. This pattern is known as the Norwood-Hamilton pattern.10a and b.6 Ludwig Stage II: The width of the division of bare scalp (‘part’. Figure 3. She will also notice her ponytail diameter may be reduced one-third to one-half of what it used to be. Hamilton originally classified male AGA on the basis of fronto-parietal/fronto-temporal recession and vertex thinning. with certain individuals showing no recession and only vertex thinning. There are exceptions. ‘parting’) may be the first complaint of the female patient.
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 miniaturized hairs. with preservation of the ‘horseshoe’ of hair at the sides and back of the scalp. (a) Frontal view (b) Lateral view. Figure 3.18 Women can show the Norwood-Hamilton pattern. Figure 3. Figure 3.17 Norwood-Hamilton Stage VII.19 A female with AGA with a Norwood-Hamilton Stage V pattern.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.94 Hair Loss: principles of diagnosis and management of alopecia Figure 3.
frequently with an iden- . The other two diagnoses that may be difficult to distinguish are telogen effluvium and alopecia areata.21 Two male teenagers with the Ludwig Stage I pattern.22a A 40-year-old male with Ludwig Stage II. Norwood-Hamilton Stage VII in a 48-year-old father (right) and Ludwig Stage I occurring in his 20-year-old son (left). with an abrupt onset.23a). Figure 3. (a) A fourteen-year-old male with Ludwig Stage I.22b Patterns of hair loss can intermix within the same family and within the same sex. Figure 3.Androgenetic alopecia 95 Figure 3. Telogen effluvium is usually generalized (Figure 3. (b) A seventeen-year-old male with the Ludwig Stage I pattern. Both these entities are discussed at length in other chapters.
It is ex- . but usually not childhood.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.24). Onset is at any age. tifiable trigger. with over 60% presenting under the age of 20. (Figure 3. Onset is usually abrupt. with a positive pull test for both dystrophic anagen and telogen hairs.23c Patients with telogen effluvium frequently present with bag of hair to show the physician. Alopecia areata (AA) is usually randomly patchy. but can be generalized. Figure 3. with no bare patches. Figure 3. with remissions and relapses. There is thinning. This amount of hair loss would not be seen in AGA. Onset is at any age. This is unusual with AGA. The pull test is positive with telogen hairs. Shedding is prominent.96 Hair Loss: principles of diagnosis and management of alopecia Figure 3. Overlapping of AGA and alopecia areata can occur. Shedding is prominent.23d A 28-year-old female with telogen effluvium who kept a diary of hair loss for 5 years.
This may have great significance if one is contemplating hair transplantation surgery for AGA. The meticulous ‘unit area trichogram’ introduced by Rushton61 will also give information on hair density. or will have AA. If an AGA patient has a previous recent or remote history of AA. have.0 mm scalp biopsy with transverse sectioning is the best laboratory test to distinguish AGA from AA or telogen effluvium. However. have. (a) A 25-year-old female with female AGA with a 6-month history of a patch of AA. It is expected that almost 2% of patients with AGA have had. he or she must be warned that that it could recur after surgery. but also more information on hair density and inflammatory perifollicular changes. are very popular in Europe and are useful. Laboratory tests In men.24a and b Overlapping of AGA and alopecia areata (AA) can occur.7% of patients with AGA have had. (b) A 35-year-old male with AGA with a 3-month history of a patch of AA. pected that 1. the scalp biopsy will give the physician not only the same information with respect to anagen/telogen and terminal/vellus ratios. he or she must be warned that that it could recur after surgery. no laboratory work-up is necessary unless there is concomitant diffuse hair loss. However. The 4. or will have AA. In . involving the hair pluck.Androgenetic alopecia 97 Figure 3. recent or remote history of AA. If an AGA patient has a previous. This may have great significance if one is contemplating hair transplantation surgery for AGA. Standard trichograms. it requires special skill and is fairly labor-intensive.
In reticular dermis there are no vellus or vellus-like hairs. a free testosterone and dehydroepiandrosterone sulfate (DHEAS) test should be ordered. If one suspects an androgen excess. Catagen and telogen terminal hairs are noted as well (Figure 3. and vellus-like hairs are identified. Primary vellus hairs are small hairs.28).27).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 . Androgen levels should only be ordered in those women who appear clinically to have an androgen excess. vellus. The vast majority of women with AGA do not display hyper-androgenism. women.98 Hair Loss: principles of diagnosis and management of alopecia Figure 3. 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. because of the frequency of thyroid abnormalities and the difficulty of distinguishing AGA from telogen effluvium. telogen or miniaturizing hair shaft and bulb (Figure 3. In fat. Terminal hair bulbs predominate in anagen phase.) Horizontal sections show distinctive changes in papillary and reticular dermis and in the deeper subcutaneous sections.26). In papillary dermis. have a thin outer root sheath. This patterning is typical of scalp hair.25).62–64 (Stelae are the residual fibrous tracts that mark the upward migration of the catagen.29). and therefore an androgen work-up is not indicated. Usually. papillary dermis. this author recommends a routine thyroid stimulating hormone test (TSH).03 mm in diameter. Ferritin levels are also ordered routinely on menstruating females. and originate in the upper half of the dermis (Figure 3. as low iron levels can trigger a telogen effluvium that may mimic AGA.25a and b Stelae or fibrous streamers (FSt) commonly seen in AGA (courtesy of Dr Magdalena Martinka). only the Pathology The histologic features of AGA are similar in males and females. hairs on horizontal section are arranged in follicular bundles of 2–4 hairs with sebaceous glands and arrector pili muscle63 (Figure 3. Vellus and vellus-like hairs are less than 0. both terminal.
Note the prominence of the sebaceous glands (SG) when hairs are miniaturized (courtesy of Dr Magdalena Martinka). The difference of counts between papillary dermis and reticular dermis represents the number of . Figure 3.28 Follicular bundles with miniaturized hairs (courtesy of Dr Magdalena Martinka). Follicular counts vary from level to level.29 A close-up of a follicular bundle in AGA.26 Primary vellus hair (V) with a small hair shaft and small outer root sheath (ORS) (courtesy of Dr Magdalena Martinka). In the reticular dermis the number is usually reduced to 35. and in the fat is usually around 30. indicating true miniaturization (courtesy of Dr Magdalena Martinka).Androgenetic alopecia 99 Figure 3. Normally. Figure 3. Figure 3. deeper anagen terminal hairs are present (Figure 3.27 Secondary vellus hair (V) with small hair shaft and large outer root sheath (ORS).30). showing a vellus hair (V) and a telogen hair (T). in the upper papillary dermis counts are usually around 40–50.
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
increasing hair growth. Thirty-three men received finasteride 1 mg daily and 33 received placebo for 48 weeks. The hair weight study demonstrated that treatment with finasteride 1 mg provides continued maintenance and improvement of hair growth over 96 weeks. 76 using the phototrichogram method. In this study. After 1 year of therapy. While improvement for finasteride-treated men compared to baseline was greater at 24 months. 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. investigator. 136 postmenopausal women (41–60 years of age) with AGA received finasteride 1 mg/day or placebo. Patients were randomized to receive either finasteride 1 mg daily or placebo for 48 weeks. the difference between the group treated with finasteride and the placebo group continued to increase throughout the 5 years of the study. double-blind. Finasteride was generally well tolerated. After 96 weeks. 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. Treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47%. significant differences between finasteride and placebo were seen with small numbers of subjects. or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. At 6week intervals.75 Van Neste et al.74 In a study of hair weights done by Price. In the extension study. Sixty-six men aged 18–40 years with Norwood-Hamilton Stage III and IV were enrolled in a randomized. Macrophotographs were taken to measure total as well as anagen hair counts in a 1 cm2 target area of the scalp. This study enrolled 212 men age 18–40 years with AGA. The study was extended for 48 weeks for a total of 96 weeks. blinded ratings of standardized photographs by an expert panel. patient and investigator assessments. leading to a net improvement in hair count of 277 hairs (31%) for men treated with finasteride compared with placebo after 5 years. In .. the total hair weight showed a statistically significant increase from baseline weight in the finasteridetreated subjects. provided direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. All hair samples were weighed in a single session by a technician who was blinded to patient. hair in a marked site was handclipped using a magnifying light. patient. Based on hair counts. multicenter trial. Finasteride may show improvement in older men. Efficacy was evaluated by scalp hair counts. Similarly. double-blind. placebo-controlled. and photographic assessments did not demonstrate any improvement in slowing hair thinning. 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. compared with 25% on placebo. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period.79 In this 1-year. 26 men continued to receive finasteride 1 mg and 23 men remained on placebo. there was no significant difference in the change in hair count between the finasteride and placebo groups. and histologic analysis of scalp biopsy specimens.Androgenetic alopecia 103 in up to 90% of men. randomized. visit number and treatment. 78. A study of finasteride in 136 postmenopausal women with AGA showed no benefit compared with placebo.77 A 2-year study in balding men between the ages of 41 and 60 years is ongoing. placebocontrolled study.
1%). Cyproterone acetate: Cyproterone acetate (CPA) is a potent progestin and an androgen receptor antagonist.40. and side-effects occur in less than 2% of patients. 80 Ninety per cent of circulating finasteride is bound to plasma proteins and can cross the blood-brain barrier. gynecomastia and feminization.80 Finasteride does not affect the cytochrome P450 metabolizing enzyme system.8% decreased ejaculate volume (0.8% vs 2.4% placebo). 1. The effect on prostate volume and serum PSA in this young population without benign prostate hypertrophy was small and reversible upon discontinuation of the drug. and therefore caution should be taken in patients with liver function abnormalities.1 A recent study by Overstreet et al.17 Exposure to semen of men who are taking finasteride does not pose a risk to a pregnant woman’s male fetus.80 but there is a risk that finasteride exposure during pregnancy may cause hypospadias in the developing male fetus. Asia and Canada. We also advise the patient’s family doctor to double the PSA value while patients are taking finasteride. The risk of teratogenicity in humans has not been directly evaluated. The bioavailability after oral intake is 65%. but may be too low for female AGA. with or without food. Women who are or potentially may be pregnant should not take finasteride or handle crushed or broken tablets. although regrowth is quite rare in this author’s experience. It may have some effect on stabilization of hair loss.80 Dosage does not need to be adjusted in case of renal insufficiency. decreased libido.17 Diane-35 contains 2 mg of CPA. . and are reversible upon cessation of treatment. This is adequate for the treatment of acne. CPA is an effective treatment for hirsutism and acne. CPA is available in Europe.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.40.73.80 Finasteride is metabolized in the liver. They are suitable only in women and are contraindicated in men because of side-effects such as impotence.40 Side-effects will subside spontaneously in 58% of those who decide to continue the treatment. it is recommended a baseline PSA be taken for older men prior to initiation of therapy with finasteride.7% placebo) and 0.80 Finasteride tablets are coated to prevent contact with the active ingredients during manipulation. on a regular schedule.83–85 There are no large controlled clinical studies in AGA with CPA.81 confirmed that finasteride 1 mg daily for 48 weeks did not effect spermatogenesis or semen production in men aged 19– 41 years.8% decreased libido (1. but there is a statistical difference when all side-effects are considered together (3.72 There was no significant difference from the placebo group for each of these side-effects taken alone.82 At the University of British Columbia Hair Research and Treatment Centre.72 Side-effects include 1.81 Finasteride can decrease PSA levels by 50% in older men. finasteride 1 mg/day taken for 12 months did not increase hair growth or slow the progression of hair thinning.3% erectile dysfunction (0. and no drug interactions have been reported.83. Androgen-receptor blockers (ARP inhibitors) Systemic ARP inhibitors decrease both T and DHT by binding to the androgen receptor.80 Finasteride is well tolerated.3% placebo).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. This was confirmed by histologic analysis on 94 women with AGA. but not in the United States.
97 Minoxidil is converted to minoxidil-sulfate. but it has been used worldwide by many dermatologists for many years. Biologic response modifiers Minoxidil Minoxidil (Rogaine™) was the first agent shown to promote hair regrowth.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.98.17 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.93 but appear to have little effect on stimulating regrowth. . Estrogens are weak 5a-reductase inhibitors.1 It has been shown to have a direct mitogenic effect on epidermal cells both in vitro and in vivo. Minimal increases in serum potassium may occur.66 Since one of its sideeffects is hypertrichosis. They also inhibit secretion of luteinizing hormonereleasing hormone (LH-RH) by the hypothalamus. a double-blind. thus opposing the entry of calcium into cells.92 but Spironolactone rarely offers the benefit of hair regrowth. reducing androgen synthesis by the gonads. Both solutions are available without a prescription in the United States.17 Spironolactone: Spironolactone is an aldosterone antagonist.99 Minoxidil was approved for men by the FDA as a 2% solution in 1988 and as a 5% solution in 1997. breast tenderness and loss of libido.95 Another possible mechanism of action is the opposition to intracellular calcium entry. Small open trials have shown some clinical effect in AGA.91. It is a competitive inhibitor of androgen receptor protein binding. and 200 mg per day is usually required. Calcium normally enhances epidermal growth factors (EGF) and inhibits hair growth. menstrual irregularity.90 It also depletes the cytochrome P450 enzyme (CYP 450) complex. It does not appear to have either a hormonal or an immunosuppressant effect. although no controlled studies have been done.Androgenetic alopecia 105 Side-effects include depression. weight gain.89. Its exact mechanism of action is still unclear.90 Spironolactone is effective mostly for hirsutism. and interferes with the translocation of this complex into the cell nucleus. Clinically. It is a piperidinopyrimidine derivative that is used orally as an antihypertensive drug. 95 plucked anagen hair bulbs from men applying minoxidil show a significant increase in proliferation index as measured by DNA flow cytometry.85. which is a potassium channel agonist and enhances potassium ion permeability. which weakly inhibits androgen biosynthesis in the adrenal glands.94 Minoxidil increases duration of anagen and enlarges miniaturized and suboptimal hair follicles. and its anti-androgenic effect is only mild. estrogens may help to maintain the status quo and to slow the progression of AGA. The 5% solution has not yet been approved for women. placebo-controlled trial. For women. thereby reducing circulating free T. Estrogen mediated: Estrogens increase levels of sex hormone binding globulin (SHBG).96 It has also been shown to prolong the survival time of keratinocytes in vitro.98 This would decrease EGF and subsequently enhance hair growth.85 The drug is less effective in female AGA. The main side-effect is menstrual irregularities. In men with AGA. nausea.97.84. a topical solution was developed to treat hair loss. Local vasodilatation does not seem to play a major role in hair growth. but are uncommon. Topical and oral estrogens have been used in women with AGA. the 2% solution was approved in 1991.89.
1 The major increase is usually seen within the first 4 months of therapy.100 Clinically. found that topically minoxidil solutions of both 2% and 5% were significantly more effective than a placebo lotion or no treatment. double-blind placebo-controlled study of 256 women between the ages of 18 and 45 with AGA. finasteride or the combination that is having the effect. he will not know whether it is either minoxidil. In a multi-center. the best mode of application is to divide it into 5 parts and apply 5 drops to each part. if one starts both medications simultaneously in a male patient.5% increase was found with the 2% solution compared to 1.103 In a multicenter. approximately 30–35% of patients.9% with placebo. One millilitre of minoxidil solution must be used twice daily.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.1 Minoxidil should be used for one full year before its efficacy is assessed. and combination therapy. where it is ineffective and thus wasted. regardless of the extent of the affected area.17 Patients must be told that minoxidil solution is a scalp lotion. Minoxidil can be used for either frontal or vertex scalp thinning. Therapeutic efficacy is evaluated by patient satisfaction and physician comparison with a baseline photograph.106 Hair Loss: principles of diagnosis and management of alopecia using hair weight measurements. The spray applicator is not recommended.65 The 5% solution produced a 35% increase in hair weights. For someone with moderate amounts of hair. physicians must rely mostly on the patient’s impression. 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. one study of 32 weeks used hair weights to assess efficacy. . compared to 25% with the 2% solution. In patients with very early AGA. while both the placebotreated men and the untreated men had an approximately 6% decrease in hair weight per year. For some patients.108 The increase in density is mostly due to miniaturized hairs that are converted into terminal hairs rather than a de novo regrowth. Practically. is a reasonable option. loss of hair is evident once treatment with topical minoxidil is discontinued. not a hair lotion. In those cases. every day in order to be effective.108 Twicedaily application is needed for efficacy.101–107 The rapid loss of hair weight after treatment confirms its trichogenic effects.104 The hair loss becomes stabilized after the initial period of regrowth.65 In women. Thus. this may not be an issue. showed moderate to dense regrowth as assessed by hair counts using macro-photographs. 63% who applied 2% topical minoxidil solution twice daily showed minimal to moderate regrowth using hair counts in macrophotographs for assessment. Minoxidil application halted hair loss over the 96 weeks. and a 42. topical minoxidil solution must be continued indefinitely.109 One study in the stump-tailed macaque showed additive benefit in using both minoxidil and finasteride. For those male patients already using minoxidil and wanting to switch to finasteride. since most of the sprayed solution will be applied on the hairs. if affordable. it is hard to appreciate any regrowth or hair loss because of the great hair density. double-blind study involving 2294 men between the ages of 18 and 50.110 but there are no data on this combination therapy in humans. 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. applying 2% topical minoxidil solution twice daily.17 No more than 2 ml should be applied every day.
If such an event occurs.Androgenetic alopecia 107 Figure 3. (a) Frontal view. and side-effects are mainly dermatologic.80 Accidental ingestion of topical minoxidil could lead to serious adverse effects. the concentration should be lowered to 2%. and is usually not a problem in men. (b) Lateral view.1.1. but in humans data are lacking.80 There is no evidence of teratogenicity in rats and rabbits. because it will cause burning and irritation. but it is possibly either through a systemic effect or via a transfer of .17.80 It is metabolized in the liver and excreted in the urine.3 to 4. minoxidil itself causes an allergic contact dermatitis. they should stop the treatment until all symptoms have resolved. Studies have not shown any change in blood pressure or any other hemodynamic effect.80 Minoxidil is secreted in human milk.5% reaches the systemic circulation. The percentage of minoxidil that is absorbed is eliminated within 4 days. and may be slightly higher with the 5% solution. but minoxidil solution should be used with caution in patients with cardiovascular disease. Facial hypertrichosis (Figure 3. thoroughly rinse the eyes with cool tap water.111–113 Incidence of scalp irritation is approximately 7% with the 2% solution. If they again develop dermatitis on the second trial. probably due to the propylene glycol in the vehicle.17 Occasionally. Each ml of the 5% solution contains 50 mg of minoxidil.103 Minoxidil should not be used by pregnant or nursing women. and the treatment may have to be discontinued altogether.80 If patients experience an irritant contact dermatitis due to the 5% solution.32 Hypertrichosis of the face can occur in women using topical minoxidil solution. The maximum oral daily dose for the treatment of hypertension is 100 mg.80. The most frequent side-effect is an irritant contact der- matitis. Patients will be unlikely to develop a tolerance to this side-effect.17 It is not clear yet why the hypertrichosis occurs.103 Contact with any mucosal surface (usually the eyes) should be avoided.32) may occur in 3–5% of women.80 Only 0. Minoxidil is poorly absorbed after topical application on normal intact skin.80 The effects of concomitant occlusion or abnormal skin are unknown 80 .80 Topical minoxidil solution is very safe.
For women with Ludwig stage III.17 They must either be mixed using generic powder forms or be applied as separate treatments.17 Those women who.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. 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. during the day. then it is continued for as long as hair loss is perceived to be important to the patient. and sides of the face. Patients should be reassured on the cosmetic appearance of hairpieces.025% tretinoin and 0. making this combination an impractical option for most patients. prior to treatment.33. already have mild hirsutism are more likely develop this side-effect. Rogaine® and Retin-A®. the irritation of tretinoin is not always well tolerated. hirsutism. In women with stage I or II hair loss. 3. Tretinoin Tretinoin (all-trans-retinoic acid) is a biologic response modifier. or hair transplantation if the patient has a good occipital scalp donor area. If there is any sign of virilization (i.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. a hairpiece is suggested. In addition. Rogaine® must be applied every morning and night and Retin-A ® during the day.116 However.114 It promotes angiogenesis115 and increases percutaneous absorption by affecting the fluidity and the lipid composition of cell membranes. Even though there seems to be some benefit in using the combination.17 It affects mostly the forehead. most patients are not compliant with the need for an extra application . serum testosterone and dehydroepiandrosterone-sulfate (DHEAS) tests should be ordered and referral to an endocrinologist may be indicated.34. topical therapies are usually ineffective.5% minoxidil. severe acne. If ongoing hair loss is detected after 1 year. as they can give excellent results.108 Hair Loss: principles of diagnosis and management of alopecia the drug. Hair transplantation in female AGA will be discussed in Chapter 4. menstrual irregularities. topical 5% minoxidil solution is offered and continued for 1 year (Figures 3. and it is most appreciated when they are given a few options. are incompatible and become ineffective if compounded in the same solution. Hypertrichosis is totally reversible upon discontinuation of the drug. formulated using generic powder forms. Hyper-androgen excess should be checked by history and physical examination. Treatment of AGA in women Many factors must be considered in the treatment of AGA. A partial hairpiece may also give a natural and satisfying appearance. An algorithmic approach to AGA in women. is presented in Figure 3. structured about the Ludwig classification.35). patients may be offered androgen blockade with CPA or spironolactone. It is a potent cell mitogen that promotes and regulates epithelial cell growth and differentiation. If patients respond to treatment. Patients often need guidance as to where to get hairpieces.17 Thorough hand-washing after each use may minimize irritation and possibly hypertrichosis in other body areas. or infertility). malar areas. For those with more advanced hair loss and a poor donor area. the proprietary products.e. seborrheic dermatitis.
is outlined in Figure 3.36. MD).38). the final decision is based on many factors. preference for topical or systemic therapy. such as the extent of hair loss. Vera H. then patients are counseled to continue with treatment for as long as they feel hair loss is im- . MD. An algorithmic approach to male AGA.37).Androgenetic alopecia 109 Figure 3. the presence or absence of miniaturized hairs. structured around the Norwood- Hamilton classification. In those with less severe hair loss and numerous miniaturized hairs. Treatment of AGA in men For men.Price. Therapeutic efficacy is evaluated at 1 year (Figure 3. patient age. If evaluation reveals stabilization or regrowth.33 An algorithmic approach on the treatment of female AGA: UCSF-UBC Treatment Protocol for androgenetic alopecia in women (courtesy of Jerry Shapiro. financial considerations and patient expectations. medical therapeutic options include finasteride or minoxidil (Figure 3. MD and Harvey Lui.
medical therapy is unlikely to work. with narrowing of her part/ parting.35 A 53-year-old female with AGA (a) before topical minoxidil solution.34 A 40-year-old female with AGA (a) before topical minoxidil solution.110 Hair Loss: principles of diagnosis and management of alopecia Figure 3. In those with more advanced hair loss and few miniaturized hairs. and a surgical approach or a hairpiece is recommended. If ongoing hair loss occurs despite treatment.110 and can be prescribed to very motivated patients. Figure 3. Studies are currently under way evaluating the effect of finasteride on the number of hair transplantation sessions. and (b) after 6 months of use of topical minoxidil. Combination therapy with both finasteride and minoxidil has been shown to have additive hair regrowth effects in a balding stump-tail macaque model. showing marked improvement. portant to them. It is . showing marked improvement. then a surgical approach or a hairpiece should be discussed. and (b) after 8 months of topical minoxidil solution.
36 An algorithmic approach on the treatment of male AGA: the UCSF-UBC Treatment Protocol for androgenetic alopecia in men (courtesy of Jerry Shapiro. MD and Harvey Lui.Price. MD. . MD).Androgenetic alopecia 111 Figure 3. Vera H.37 A good candidate for medical treatment of male AGA (note the presence of miniaturized hair). Figure 3.
This author recommends finasteride on all patients undergoing hair transplants if they are Stage IIIV–V pre-transplantation (Figure 3.39). patient impressions . likely that the combination of the two will reduce the number of sessions.112 Hair Loss: principles of diagnosis and management of alopecia Figure 3.38 A 24-year-old male with AGA (a) before the use of finasteride 1 mg/day and (b) one year later. and what methods can be used to determine treatment success or failure? First. A 33-year-old male with AGA (c) before the use of finasteride 1 mg/day and (d) after 11 months of therapy. showing improvement. showing improvement. Patient monitoring How is response to therapy assessed.
not have a digital set-up with a stereotactic device. In men. Expectations are largely dictated by the extent of hair loss. those . each patient has digital photography taken at a standardized distance and position (Figure 3. USA) is ideal as a means for monitoring patients. serial part diameters can be taken from the same areas of the scalp with each visit. 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. showing significant improvement. This patient felt he did not need another transplant session. Matching therapy to patient expectations are determined. Figure 3. (b) The same individual 12 months after the use of finasteride 1 mg/day. Finally. New Jersey. but do give a general impression of the kind of coverage present at baseline.40 Digital photography with a stereotactic device (Canfield Scientific. Both patient and physician should realize that these uncontrolled snapshots are not accurate. many patients are often unreliable and unsatisfied with subjective estimates. He was considering another session. The photograph is reviewed with the patient at each follow-up and compared to current hairgrowth status.40). the last transplant four years before the photo.Androgenetic alopecia 113 Figure 3. Ideally. If one does Patient expectations are an important factor when discussing therapeutic options and goals. Photographs do not need to be taken annually. The key features to distinguish between are prevention and regrowth. Unfortunately.
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
97(3):247–54.E. et al. In European Academy of Dermatovenereology Annual Meeting. Whiting D. J Am Acad Dermatol. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Stoner E. Br J Dermatol. Menefee E. et al. Hordinsky M. Fiedler V. 1977. and Mortimer C. Hamilton J. Inc. Finasteride in the treatment of men with frontal male pattern hair loss [see comments].A. Dermatol Ther. 37(3): 375–8. and Strauss P..J. The clinical development of a 5 alpha-reductase inhibitor. 41(4):550–4. South Med J..L.S. Transverse microscopic anatomy of the human scalp.H.I. 109(4):429–37.Androgenetic alopecia 117 55. on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. 1979.. a 5 alpha-reductase inhibitor. Ann NY Acad Sci. Cancer Epidemiol Biomarkers Prev. 1993. 1992. 356(9236): 1165–6. 41(5 Pt 1):717–21. Drake L.T. 1999. 71. Bruskewitz R. J Steroid Biochem Mol Biol. 60. The effect of finasteride in men with benign prostatic hyperplasia. 2000. Rushton H. 2000. E.A. et al. 1975. ed. Olsen E. The effect of finasteride.C. 64..A.. 1951. 79(3):703–6. Price V. 327(17):1185–91. Sanchez M. a type 2 5 alpha reductase inhibitor in men with male pattern hair loss. Male pattern alopecia and coronary artery disease in men. 1990. et al.. Changes in hair weight and hair count in men with androgenetic alopecia. Propecia: New Clinical Data—Five Year Experience. Disorders of Hair Growth. New Engl J Med. 69.. Whiting D. 1983. Roberts J. 1984. 68.D. Oct 2000. Male pattern baldness: classification and incidence. J Clin Endocrinol Metab. Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the first National Health and Nutrition Examination Survey. Norwood O.H. 1999. 53:708–28. Clinical dose ranging studies with finasteride. 57. Dallob A. Patterned loss of hair in men: Types and incidence. Headington J. 4(3):282–4. 1994. Semin Cutan Med Surg. Whiting D.C. Breslow R. and Kaufman K. Br J Dermatol. 65.. 72.. The unit area trichogram in the assessment of androgen-dependent alopecia. Unger W. 257–279. 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. after 66. J Invest Dermatol Symp Proc. 17(4):276–83. 1999.T. 1998. 101(4):455–8. pp. 1999. 8:24–33.. 1993 Oct. Gormley G.. et al. New York: McGraw-Hill.. 1999. 56. 29(4):554]. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia [published erratum appears in J Am Acad Dermatol. 61. Stoner E. The Finasteride Study Group [see comments]. 40(6 Pt 1):930–7. 62.T. Lancet.. 9(5):523–7. 70. Leyden J. 63. and Graubard B.. application of 5% and 2% topical minoxidil. Arch Dermatol. 68(11):1359–65. Miller B. Hawk E.. Cooke N. Sawaya M. J Am Acad Dermatol. 73. Dunlap F.. . Scalp biopsy as a diagnostic tool in androgenetic alopecia. Geneva. 67. J Am Acad Dermatol. androgenetic alopecia as a marker of insulin resistance [letter] [in process citation]. 58. Abstract..C. Olsen. Ludwig E. 59. 74. finasteride. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. 28(5 Pt 1):755–63. Novel agents for the treatment of alopecia. A basis for a morphometric approach to disorders of the hair follicle. Sadick N. or no treatment. Br J Dermatol. James K. Waldstreicher J. 41(4):555–63. 1998. J Am Acad Dermatol. placebo.. J Am Acad Dermatol. 120(4): 449–56. 1994.
162(4):1295–300. Fertil Steril. and Ruedi B.C.. 1996. J Steroid Biochem.. 42:317. Presentation at European Academy of Dermatology.. 9(1):1–13. 161(2): 124–32. 81(6):558–60. Br J Dermatol 2000. 1984. J Invest Dermatol. et al. hirsutism and virilism.H. 78(3):405–8.H. 1983.. Orfanos C.M. 1988. 77. 1991.. and Gillette J. Roberts J. Br J Urol. Van Neste D. and Schell H. Baden H. J Soc Cosmet Chem. Fuh V. 1980. Leo-Rossberg I. Lobo R. Langer P. Roberts J.M. J Invest Dermatol. 91. comment]. 35(11): 770–8. and Kubilus J. J Am Acad Dermatol. 43(2): 200–5. Shaw J. J Invest Dermatol. and Matz H. Finesteride increases anagen hair in men with androgenetic alopecia. Gould J. Use of cyproterone acetate (CPA) in the treatment of acne. 1975. 112(1):124–5. The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women. Local therapy of androgenetic alopecia with 17 alphaestradiol. Treatment of hirsutism.. A controlled. Namer M. 2000. 86.M. . Changes in hair weight in men with androgenetic alopecia after taking finasteride. Horm Metab Res. and Braf Z.. 1985. Int J Dermatol. 94.A. Brenner S. Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration. 160(6):398–404.. Minoxidil stimulates mouse vibrissae follicles in organ culture [letter. Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia. 76.. The effects of finasteride on post-menopausal women with androgenetic alopecia.L. Matzkin H. Dermatologica. Price V. 9(4):342–50. 92. Br J Dermatol... Brussels. Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. 95. 96. Serafini P. and James K. Hordinsky M.118 Hair Loss: principles of diagnosis and management of alopecia 75. Effect of minoxidil on cultured keratinocytes. 1999..J.R.L. Burckhardt P. 1999. 1996.M. J Urol.. Canada. et al. with cyproterone acetate. 84. Canadian Pharmacists Association Monography. Price V. 38(12):928–30. Oral spironolactone therapy for female patients with acne. 99(1):40–7. 1977. and Cunliffe W. Pharmacology and potential use of cyproterone acetate. Kan H. Rushton H. 88. 89. Effective medical treatment of common baldness in women.. Belgium.. acne and alopecia 87. 1999. hirsutism or androgenic alopecia [letter].L. 1999. randomized doubleblind study. 1991. Antiandrogen therapy in dermatology. 254(5): 1726–33. 90. Quantitative assessment of spironolactone treatment in women with diffuse androgen-dependent alopecia. et al. Studies on the destruction of adrenal and testicular cytochrome P-450 by spironolactone. In Compendium of Pharmaceuticals and Specialties (CPS) 34th Edition.H. 96(2):295–6. Minoxidil and Finasteride. 83.. Kiesewetter F. et al. Ekoe J. Requirement for the 7alphathio group and evidence for the loss of the heme and apoproteins of cytochrome P-450. Effect of finasteride on free and total serum prostatespecific antigen in men with benign prostatic hyperplasia. 79.C. 93. Guenthner T. Khoury E. Shoupe D.. Clin Exp Dermatol. Int J Dermatol.W. Meckies J. 1985.. J Biol Chem. 1992. Menard R. 1980. Neumann F. 80.. et al.E. Olsen E. et al. Dermatologica. Price V. et al.H. 43(5): 768–76.P. Amsterdam. 85. Mortimer C.H.. 81.. Burke B. Ottawa. Abdel-Salam M. In Hair Workshop. 6(6):827–36. Improvement in androgenetic alopecia in 53–76-year-old men using oral finasteride.. and Vogels L. 1979. 31(4B):719–29. Clinical applications of antiandrogens.. Hammerstein J.. 78. 82. 1998. Price V. 143(4):804–10. J Steroid Biochem.. Barak M. Rushton D. Overstreet J.H.
15(4 Pt 2):880–3. DeLong E. Minoxidil’s action in hair follicles. 95(6): 683–7. 108. 890–3. J Clin Endocrinol Metab. Terezakis N. Powell S..H. 109. Topical minoxidil in the treatment of androgenetic alopecia in women. 104. Mulholland M. Cutis. Wilson C. 1991. and Pinnell S. 99. Ohtsuyama M. 481. J Am Acad Dermatol. Topical tretinoin for hair growth promotion. J Am Acad Dermatol. 101.R. Contact dermatitis in reaction to 2% topical minoxidil solution. Quantitative estimation of hair growth. 1985. 1985. J Am Acad Dermatol.S.S.R.A.. 16(3 Pt 2):688–95.. Bardazzi F.. 114.L. and George M. Roche N.. Five-year follow-up of men with androgenetic alopecia treated with topical minoxidil. Dermatol Clin. Sporn M. DeLong E. 14(4):595–607.. . 15(1): 34–6. 1994. 74(2):345–50.A. 1992. Epidermal effects of retinoids: supramolecular observations and clinical implications. 96(5): 73S–74S. et al. Whole hair follicle culture. Buller T. J Am Acad Dermatol.. Olsen E. ed. 24(4):661–2. Weiner M. and DeLong E. 1995. Androgenetic alopecia in the female. Treatment of androgenetic alopecia with topical minoxidil solution.S..L. 116.S. Hair loss with minoxidil withdrawal [letter]. and Weiner M. 1987. and Kealey T... Long-term follow-up of men with male pattern baldness treated with topical minoxidil. Olsen E. J Invest Dermatol.R. and Muller E. 1987. 115. et al. 15(4 Pt 2):797–809..A. Price V. Hair growth effects of oral administration of finasteride. Shull K. Contact Dermatitis.M. 1991.J. 1990. p. 110. 13(4):275–6.A. 35:53. DeVillez R.. Natural history of androgenetic alopecia. a steroid 5 alpha-reductase inhibitor.R.A. et al. Amsterdam: Elsevier Science. Elias P. Kidwai B. Topical minoxidil in male pattern baldness: effects of discontinuation of treatment. Mechanism of action of retinoids.D. 106. Walkden V...Androgenetic alopecia 119 97. V. Lancet. J Am Acad Dermatol.. 98.. 340(8819):609–10. et al. 1992. Olsen E. et al. Amara I.R. DeLong E. 1990. Olsen E. J Am Acad Dermatol.S. 13(2 Pt 1):185–92. 22(4):643–6... 130(3):303–7. Olsen E. 111. J Am Acad Dermatol. 102. 1986.. Ebner H.E. Philpott M.A. Topical minoxidil in early male 107. Diani A.R. In Hair Reseach for the Next Millennium. Roberts A. and Weiner M. Olsen E.J. Arch Dermatol. Treatment with 2% topical minoxidil solution.P. Bazzano G.B. 100.A. Contact Dermatitis. Buhl A. 1991. 105.. 1986. 1996.B. 112. Clin Exp Dermatol.A.Van Neste. alone and in combination with topical minoxidil in the balding stumptail macaque. 15(4 Pt 2):756–64. Contact dermatitis to minoxidil. Res Staff Phys. Weiner M.. androgenetic alopecia in women: effect of minoxidil. and Galen W. 1990. De Padora M. Tosti A. Olsen E. J Am Acad Dermatol. Allergic contact dermatitis from minoxidil..R. 113. Sanders D. 32(5):316–17. 48(3):243–8.P. 103.S. 1996. J Invest Dermatol. pattern baldness. Minoxidil sulfate effect of internal calcium of cell in the epidermis and epidermal appendages. I. and Menefee E. 1986.A. 17(1):97–101. Weiner S. 1989.
(c). . These follicles can be transplanted anywhere on the same individual and will produse coarce terminal hairs for the lifetime of the individual.1 Hair transplantation two decades ago: (a). This patient requested laser hair removal to remove his grafts from twenty years ago. These hairs are unlikely ever to become vellus-like. Figure 4. Note the unnatural corn-row tufting of hair surgery performed in the 1960s and 1970s.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. (b). (d).
4). and these are discussed thoroughly elsewhere.2 Donor area is chosen in the occipital portion of the scalp.3 Donor area at the back of the scalp is trimmed. The chapter will deal solely with hair transplantation. This is termed donor dominance of the grafts. The field of hair transplantation has changed markedly within the past 10 years (Figure 4.122 Hair Loss: principles of diagnosis and management of alopecia Figure 4. The advent of (1) strip harvesting for the donor area. (2) the introduction of finer. 4. The donor site The selected donor area is initially trimmed (Figures 4. There are many differing approaches to 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. Figure 4. more natural-appearing grafts.3 It has been shown that tumescent anesthesia significantly reduces the total . Figure 4.2.1).3) and anesthetized using the tumescent technique (Figure 4. and is the basis for the success of hair transplantation.4 Donor area is injected with tumescent anesthesia. This anesthetic approach was first developed for patients undergoing liposuction.1. as this is the most commonly performed surgical procedure for androgenetic alopecia (AGA). and (3) the use of slits for the recipient area have revolutionized the field of hair transplantation.
2. It is important to keep this in mind when harvesting strips. and as a result are less likely to be later transected. If an excision is too deep.5b). thus decreasing bleeding. Constant monitoring of the angle is necessary. number of milligrams of lidocaine required and maximizes the vasoconstrictive benefits of epinephrine.5 (a) Multiple-bladed knife is prepared. This increases skin turgor in the area and allows easier visualization and excision of the donor area. Approximately 6–7 injections are performed with an action pump syringe and a 25 gauge needle into the trimmed occipital area. A mandatory period of 20 minutes is required for the anesthetic to have its full effect in terms of anesthesia and vasoconstriction. The hair follicle with its dermal papilla usually extends to a depth of 4–6 mm. it can cause unnecessary harm to underlying arteries and veins. Tissue more than 1 mm below the dermal papilla is not necessary for transplanting. If the angle is not precise there will be considerable follicular transection and subsequent follicular wastage. (b) The blades are angled in the direction of the hairs. If the angle is not pre- .4% sodium bicarbonate solution and 0.5 ml of 8. repeat injections of anesthesia are given to the patient’s donor area. and varies from 100 to 120 degrees.5a and 4.4 A solution prepared by adding 25 ml of 2% lidocaine without epinephrine. Strip harvesting has truly replaced the older punch-harvesting methods. This angle is crucial and varies from 100 to 120 degrees. Harvesting with strips as opposed to punches allows for more efficient harvesting and better cosmesis.Surgical management of androgenetic alopecia 123 Figure 4. Any curly hairs will also become more ‘straightened’ with this increased turgor. This angle is crucial. Any ‘hot spots’ that are not completely anesthetized can be further anesthetized with small amounts of 2% lidocaine. A multi-bladed knife with #10 Personna blades is angled parallel to the hair shafts (Figures 4. Just before excision.4 ml of 1:1000 epinephrine is added to a 250 ml IV bag of saline.
The width of each strip varies for each individual. Figure 4. This will usually yield 1100–1350 grafts on average.5 mm strips taken for a total width of 1 cm.25 mm are removed with a regular session or four strips of 2. 4. The surgical defect will range from 6.0 cm in width. This is done meticulously.25 mm each for a total of 6.5 mm for a megasession. 4. Small bleeders can be cauterized or tied off with 3–0 Vicryl absorbable sutures. the strips will usually be longer and wider.8). three strips of 2. .6. with avoidance of any kind of ‘sawing’ motions. This will yield an average total of 600–800 grafts. For an average megasession involving considerably more harvesting. Most strips are 12–16 cm in length. For an average regular session. The strips are released at the ends with a V shape and from underlying tissue with a #15 Figure 4. After the stab incision.7. Strips vary in size depending on whether it is a regular or a megasession.75 mm-1.75 mm width are excised.8 Strips are removed with a V shape at the ends. at the University of British Columbia (UBC) Hair Clinic.124 Hair Loss: principles of diagnosis and management of alopecia Figure 4.6 Strips are excised from the donor area. so as not to harm the lower portions of the follicle as well as not injure any underlying blood vessels. Usually three strips of 2. cise there will be considerable follicular transection and subsequent follicular wastage. blades are maintained at a constant depth. with four 2. Personna scalpel blade (Figures 4.7 Strips are released from the rest of the scalp with a #15 blade. Length is usually 10–14 cm.
hair density. Alternatively. This particular Asian patient did not mind the keloid. Keloids can subsequently be treated with intralesional corticosteroid.9). usually with a diameter of 1–2 mm (Figure 4. However. The donor site is sutured with blue nylon 3–0 Novafil. and it was not discovered until he returned two years later for his subsequent second session. However.9 The surgical defect is closed with a continuous stitch.10 (a) The scar 6 months after the procedure.Surgical management of androgenetic alopecia 125 Figure 4. as it was well camouflaged by his donor hair. We have found that sutures are more confortable than staples for the patient. certain centers have found the exactly the opposite. AfricanAmericans in particular usually have a lower scalp follicular density and frequently require a greater total width of strips. Larger areas of alopecia will require greater coverage and thus larger strips. He did not inform our center of this complication. leaving only one final scar. wider strips are necessary. ethnicity and scalp elasticity.5 The resulting scar is linear. (b) A rare complication of the donor area is the formation of a keloid. . and as a result prefer closure by a continuous suture (Figure 4. and just use staples. which is more commonly seen in African-Americans or Asians. If donor follicular density is low.10). These scars can be excised at subsequent sessions. another scar can be created above or below the previous Figure 4. the total width of strips removed will be lessened. The size of the strips taken varies according to how much area needs to be covered. if an individual’s scalp is too tight.
During preparation. and include keloid formation (Figure 4.11 Strips are placed on a tongue depressor and are sectioned with a #10 blade into smaller grafts. grafts are grouped according to size and density on Petri dishes on ice (Figures 4. Complications in the donor are very rare. hair without matrices. The recipient area In the frontal area. The most obvious advantage of using these small grafts is the elimination of tufting reminiscent of the old grafts. Positioning the hairline is critical. facial framing is frequently what the patient wants. and must be discussed at length with the patient. All of this is camouflaged nicely by the patient’s hair. one.10b) wound dehiscence. This is performed by meticulous dissection of the strips with a #10 Personna blade and fine jewelers’ forceps (Figure 4.14). Excessive amounts of fat. 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). which must have a prerequisite length of 2 cm.11). Because of the natural appearance of the small grafts. and any scar tissue (especially from a previous transplant) is removed (Figure 4.126 Hair Loss: principles of diagnosis and management of alopecia Figure 4. This is drawn in before the surgery. Stough has presented guidelines. and paresthesias. Figure 4.6 At .13 and 4. the patient is not committed to have to continue through many sessions to get that final natural look. leaving only 1 mm of fat underneath the follicle. Appropriate magnification is necessary to perform this. It is essential that during this whole process strips and grafts are not permitted to dry out and are well moistened with saline.12 Much of the fat is trimmed away.12).
14 The grafts are grouped on to Petri dishes according to the number of hairs per graft. the UBC hair clinic we mark an area 8–11 cm midline above the glabella and create a curved. On lateral view. . Figure 4.15b). the area marked is always parallel to the ground and on the flat portion of the scalp (Figure 4.13 Grafts are subdivided into micrografts containing single hairs (bottom) or minigrafts with single follicular bundles of 2–3 hairs (top).Surgical management of androgenetic alopecia 127 Figure 4. Figure 4.15 (a) and (b). bell-shaped hairline (Figure 4.15a). The hairline is drawn onto the recipient area.
18 (a) and (b). Figure 4. The recipient area is anesthetized with a field block of 2% lidocaine with a mandatory 20-minute waiting period to maximize vasoconstriction.17 Slits into the recipient area are made with an Ellis 1. the hair direction is planned. They are directed parallel to the direction of the hair. Figure 4.0 mm spear tip on a handle (Figure 4.17).18).16 On the vertex of the scalp. Those with pre-existing hair may only need 2 .16).5 mm between the slits laterally and 1 mm anteriorly or posteriorly (Figure 4.5 mm or 2. Usually we allow 1. the area is marked as to hair direction prior to the surgery (Figure 4. Slits are made with an Ellis 1. On the vertex. Slits are made into the recipient area.5–2.5 or 2 mm spear tip. The majority of patients get satisfactory cosmetic results with 3 sessions of slit grafting in a totally bald area.128 Hair Loss: principles of diagnosis and management of alopecia Figure 4.
sessions. The hairs in the grafts are aligned with . a zone of approximately 300 pure micrografts is created. The remaining minigrafts are placed behind this frontal zone. Planting into the slits is done meticulously with jewelers’ forceps (Figures 4. Figure 4. A megasession increases coverage. 600–900 total grafts are transplanted.19 and 4. In the frontal area. Figure 4.19 Grafts are placed on to the fingers of the nurses.20 Grafts are placed into slits with jewelers’ forceps. usually covering 30–50% of the anterior portion of the scalp.21 (a) and (b). Special care is taken not to harm any of the grafts.Surgical management of androgenetic alopecia 129 Figure 4. with a total of 1100–1400 grafts.20). For a regular session. and allows the placement of grafts into the anterior portion as well as the vertex of the scalp. Scalp after placement of grafts.
after one week virtually all crusting will have disappeared.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. Patients are warned of a telogen effluvium that can occur with the transplanted grafts as well as with pre-existing recipient hair. Patients leave the office with a moist dressing covering the donor and recipient areas (Figure 4. With appropriate postoperative care and daily shampooing.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. This would logically reduce the number of sessions necessary. The average patient with marked hair loss will receive on the average 3 sessions (Figures 4. Patients must wait for up to six months to see the full benefits of a hair transplant.130 Hair Loss: principles of diagnosis and management of alopecia Figure 4. Patients are warned appropriately and are told to expect it.39a and 3. Finasteride and hair transplants the appropriate angle and direction fitting directly into the slits.22). (See Figures 3. The grafts can be flush or slightly elevated above the surrounding tissue (Figures 4. especially with megasessions.21a and 4. There also is a possibility of regrowth as well as in the patient illustrated in Fig.23–4. This allows the transplanted hair to grow in visibly and allows us to visualize where to put the new set of grafts. Facial edema beginning 48 hours after the procedure and lasting for 5 days is certainly common. . 3. Finasteride may stabilize any further thinning of pre-existing hair in the recipient area.25). then this becomes a bonus for the patient. A regular session will usually take 5–6 hours. The dressing is removed the next day.36. We frequently recommend our male patients with pre-transplant Norwood-Hamilton Stages III–V to take finasteride 1 mg daily. Graftcyte® dressings are placed over the recipient area. If the facial edema does not then happen. We perform repeat sessions after a minimum of six months between sessions. A megasession may take 6–8 hours to complete.21b). It is best for patients to take one week off work.22 Post-operative dressing covering donor and recipient area. Forehead swelling is treated with the frequent application of ice-packs and upright positioning (at at least a 45 degree angle) for one week while sleeping. A full working schedule and exercise can be resumed 1 week after the procedure.
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 . Two years later. It is area. after four regular sessions. Figure 4. A 40-year-old male prior to hair transplant. the occipital donor area may be affected. 1 year later. (b). Hair transplantation in Women Because AGA in women may be more diffuse. (b). Atleast 30% (in the author’s experience) have significant thinning in the donor area and are not good candidates.Surgical management of androgenetic alopecia 131 Figure 4.23 (a). important to choose the appropriate fe- male surgical candidate. A 27-year-old male prior to hair transplant.24 (a). after two regular sessions.
Micro-grafting. (b). and will feel that her situation has worsened significantly compared to her pre-transplant state. (d). (c). as its results are cosmetically very natural. Conclusion Hair transplant surgery has become very popular. 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. then she will be prepared emotionally. she is not a candidate for hair transplant surgery. Side view after hair transplant. Two megasessions and a regular session and 3 years later.132 Hair Loss: principles of diagnosis and management of alopecia Figure 4.25 (a). mini-grafting and strip harvest- . daily. A 43-year-old male prior to hair transplant. In such cases the patient will experience effluvium of both the transplanted hair and her preexisting hair. but frequently will still occur even then. Side view of the same patient before hair transplant. If she is not able to accept this fact.
The tumescent technique for liposuction surgery. Missouri: Mosby. dermabrasion.Stough. 1996: St Louis. Stough D.P. Determination of hairline placement. pp. 2. . St Louis.Klein. 1995. Unger W. 16(3 Pt 2):685–7. 1st edn. In Hair replacement surgical and medical. 425–9. J Dermatol Surg Oncol 1992. 3rd edn.Stough. Use of topical minoxidil as a possible adjunct to hair transplant surgery. Missouri: Mosby. Hair Transplantation. 5. St Louis. New York: Marcel Dekker. D. Stough D.D. and soft tissue reconstruction. 7. Hair replacement surgical and medical. Kassimir J. In Hair replacement surgical and medical. Am J Cosmet Surg 1987. D. 139–49. 4. 3. Klein J. ed. Stough D. Use of the tumescent technique for scalp surgery. 4:263–7.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. A pilot study. J Am Acad Dermatol 1987. 6.A. References 1. The donor site. pp. 1996. Coleman W. and J. 1996. ed. Missouri: Mosby. 18(2):130–5.J. Combination medical therapy with systemic finasteride or topical minoxidil solution may certainly add to the cosmetic result.
Even if they do notice it. a brief transitional catagen phase of two weeks leads to a metabolically inactive resting telogen phase. A drug-induced alopecia can certainly unmask a tendency for androgenetic alopecia and accelerate the miniaturization process of AGA. barely noticeable shedding. The work-up for any patient with hair loss must include a thorough drug history. Drugs that cause alopecia The true incidence of drug-related alopecia is hard to determine accurately. Female androgenetic alopecia (AGA) poses a real problem. and will detect any inflammatory process. the axillary and pubic regions and the body may also be involved. One must understand the basic mechanisms of hair growth and cycling in order to understand drug-induced hair loss. Subtle cases can be difficult to detect. which lasts 4–8 years. The pattern of hair loss is almost always diffuse.5 Drug-induced alopecia Drugs can affect hair by causing alopecia. Practicing dermatologists make the diagnosis infrequently. Following anagen. The scalp follicle passes through a growing. and it is possible that many patients may lose small amounts of hair and never realize it. although the eyebrows. The scalp itself is usually unremarkable. from complete baldness to slight. A scalp biopsy with obligatory transverse sectioning will give you the anagen-telogen ratio and the terminalvellus ratio. This is all reviewed in detail in Chapter 1. except in rare instances. but it is also true that they rarely see the vast majority of such patients—those receiving chemotherapy. because it is very prevalent and can co-exist with diffuse alopecia. metabolically active phase known as anagen. Drug-induced alopecia is usually confined to the scalp. Some drugs can cause a severe drug-induced lichenoid eruption of the scalp. Repeated questioning may be necessary because of forgetfulness or ignorance. Drugs are capable of producing a wide spectrum of alopecia. This will help rule out AGA and alopecia areata. The telogen phase lasts for three . as well as helping to confirm an anagen or telogen effluvium. the loss of hair is considered to be trivial. This chapter will review which drugs have been implicated in hair loss and explore the mechanisms of how pharmaceutical agents can alter hair cycling and structure. and so may go unreported or may be reported without adequate documentation. Certain laboratory tests such as scalp biopsy and blood work can be helpful in ruling out other causes of alopecia. Each human scalp follicle produces hair cyclically and behaves independently of neighboring follicles.
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. but may result from changes in keratin production or changes in the hair cycle.4 The resultant hair contains fewer cells per unit length. Follicles are susceptible to noxious agents.1) Cytostatic drugs Any drug that affects cell division can alter hair growth. The intensity of damage to the cortex of the hair shaft depends on the drug dosage and the duration of its administration. namely bone marrow and mucous membranes. The duration of anagen and telogen phases. precipitation of catagen. especially . and 1% in catagen. 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. resulting in hair shaft damage. are more likely to be affected by drugs than the regions of the body with the lowest percentage of anagen follicles. Only the actively dividing matrix cells of anagen hairs are affected by cytostatic drugs. Hair loss developing weeks to months after drug intake may be due to hair matrix effects. The hair breaks at the point of constriction. Almost 90% of scalp follicles are in anagen.3. Drug-induced alopecia usually involves pharmaceutical alteration of the cycling process. in the clinical setting. while catagen and telogen follicles are relatively safe. impede hair cortex formation and cause an anagen effluvium in almost 100% of patients. Direct effects include anagen growth interruption. Cytostatic drugs suppress hair matrix cell mitosis. the most common mechanism by far for drug-induced alopecia is the precipitation of catagen.136 Hair Loss: principles of diagnosis and management of alopecia months. For this reason anagen hair matrix is highly susceptible to noxious events. such as the eyebrows and eyelashes. If one excludes anti-mitotics. and the predominant effect may depend on the dose and timing of the administration. the percentage of hairs in anagen and telogen phases. Hair loss occurring a few days after drug intake indicates an effect on hair matrix cells. and disturbed keratinization. Anagen effluvium (Table 5. 10% in telogen.1). An example of such a dilemma is highlighted by Reeves and Maibach. and the density of the follicles will account for the varying severity of alopecia in different areas of hair growth. During the anagen phase. with hair fall beginning in 7–14 days (see Figure 5. Combined therapy with two or more anti-mitotic agents has a greater effect than a larger dose of only one agent. There are two mechanisms of drug-induced alopecia—direct and indirect effects. A large single dose that strongly suppresses mitosis produces a sharp point-constriction. is thin and breaks easily. A spectrum of changes seems to occur. because many diseases for which drugs are administered also produce a precipitation of catagen. usually when they are actively growing. after which the club hair is shed as the hair follicle initiates a new cycle. A small single dose will produce constriction of the hair shaft. In some cases. such as the scalp and beard. there is confusion. Of course. Continued treatment with a smaller constant dose produces a slow decrease in hair shaft diameter to a tapered point. The regions of the body with highest percentage of anagen hairs. Scalp follicles are in differing phases of the hair cycle and are randomly scattered over the scalp.
1 Anagen effluvium. fluorouracil. Figure 5.Drug-induced alopecia 137 Table 5. Note the marked hair loss over the entire scalp. bleomycin. cytarabine. vinblastine and dactinomycin. cyclophosphamide. Alopecia most commonly occurs with the use of doxorubicin (adriamycin). vincristine. daunorubicin. bleomycin and hydroxy-carbamide. Drugs that may aggravate alopecia when used in combination chemotherapy include chlorambucil.1 Drug-induced anagen effluvium46 in-patients subjected to multiple cycles of chemotherapy. hair loss may be almost complete. methotrexate. (a) posterior view (b) lateral view . thiotepa. A 33-year-old female with lymphoma on dacarbazine. doxorubicin and vinblastine. chlormethamine (mechlormetha- mine).
and cisplatin. thiotepa. Immediate anagen release probably characterizes most drug-related events. 6-mercaptopurine and methotrexate. melphalan. Etretinate may cause SA. antitumor antibiotics. 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. All follicles in telogen may be susceptible. DAR is probably associated with postpartum hair loss and oral contraceptives. All areas affected by anagen effluvium had normal hair growth after the medication was discontinued. Colchicine Colchicine. If anagen is decreased by 50%. The five types are as follows: 1. nitrosoureas. characterized by a prolonged anagen rather than cycling normally into telogen. Hairs were dystrophic and broken off 1–2 cm above the scalp. hydroxyurea. It may persist for 1–3 months.5 Colchicine can produce diffuse hair loss in 1–10% of cases. There is some good evidence that topical minoxidil solution may effect IMR. Delayed anagen release (DAR). Immediate telogen release (IMR): normal telogen. is shortened to just a few days. busulfan. carmustine. as the affected follicles are promptly stimulated to cycle into anagen. Immediate anagen release (IAR).9 of these types are related to events in anagen and two related to telogen. Hair loss is dose-dependent. Those drugs that are S phase-specific include cytosine arabinoside. ifosfamide. Most of the cytotoxic agents are not phase-specific: these include alkylating agents (cyclophosphamide. if sufficient are involved. The M phase of mitosis is affected greatly by vincristine and vinblastine. which may last 4–12 weeks.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. 4. Cimetidine has also been implicated as causing DAR. The mode of action is due to metaphase arrest. 5. 2.8 Vasopressin Vasopressin. 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. and may be reversible even if the drug is continued. 3.10 Three . a vasoconstrictor and anti-diuretic pituitary hormone. dacarbazine). Shortened anagen (SA) occurs when the anagen phase is significantly decreased in time.6 Harms7 reported a case of diffuse alopecia that occurred after 2 months of colchicine therapy. procarbazine. characterized by a relatively short onset—usually 3– 5 weeks. the clinical sign of increased shedding will be found. has been reported to cause alopecia by causing an anagen effluvium from cutaneous infarcts. Follicles that would normally complete a longer cycle by remaining in anagen prematurely enter telogen. there is a corresponding doubling of telogen hairs. has anti-mitotic activity operating through failure of spindle formation. Cells with the highest rates of division are affected earliest. used in the treatment of gout.
Anti-coagulants All forms of anti-coagulants may induce hair loss. No drugs have been implicated with this mechanism conclusively. TE .Drug-induced alopecia 139 Table 5. which occurs during treatment of thyrotoxicosis.2).2–5. appears to be related to drug dosage. Anti-thyroid drugs Reversible alopecia is a constant finding in iatrogenic hypothyroidism. Anti-thyroid drugs that may produce telogen effluvium include iodine. propylthiouracil. and carbimazole. Telogen effluvium is frequently associated with hair dryness and brittleness. and tends to be more frequent in women (Figure 5. The following list of drugs have been implicated as causing telogen effluvium (Tables 5.2 Drug-induced telogen effluvium (incidence less than 1 %)46 fallout on the scalp.5) occurs in more than 10% of patients. but reports of delayed-onset shedding with drug treatment might be a result of DTR. methylthiouracil. These include heparin and coumarins.
11 Headington feels it is due to immediate anagen release. this mechanism is less likely. doses ranged from 0. However. Hypothyroidism (commonly) and thyrotoxicosis (rarely) have been described in patients on lithium therapy. with serum lithium assays between 0.4 Drug-induced telogen effluvium (incidence of more than 5%)46 Psychopharmacologic medications Lithium Hair loss is a possible adverse effect of lithium carbonate.5 g/ day. 23% described their hair as also becoming straighter.140 Hair Loss: principles of diagnosis and management of alopecia Table 5.13 About 20% of patients on long-term lithium therapy.3 Drug-induced telogen effluvium (incidence of 1–5%)46 Table 5. who had high lithium levels.4 to 1.18 A 3year survey of lithium-treated subjects reported a 12% incidence of alopecia.4 Meq/L.5 and 1. but not established. In most reports. and may be noticed within weeks or years after commencing therapy. A correlation between hair loss and lithium blood level and/or dosage is suspected.12–17 A review described 101 cases of lithiumrelated hair loss in over 25 years of use. since this drug is known for its ability to affect the thyroid gland. and both conditions may manifest with hair . in those patients in whom the onset of the hair loss may take years.19 Patients on lithium who develop alopecia must undergo a thyroid function assessment. reported hair thinning.
Drug-induced alopecia 141 Table 5.5 Drug-induced telogen effluvium (exact incidence unreported)46 .
22 This is probably coincidental.0% reported frequency.21 There is a case report of alopecia areata occurring during lithium therapy. (c) Pathology of telogen effluvium. despite a documented decrease in serum amounts of zinc and copper caused by both medications. with a slightly increased width of hair-part. (b) Lateral view.29 Carbamazepine and VPA possibly have different mechanisms of hair loss. but usually dosage reduction leads to regrowth of hair in individuals with valproate-associated alopecia.28 A threefold dose reduction of 200 mg/day helped one female patient. lished whether alopecia is dose-related.20.6% and 6%.18 With a reported incidence of 1. A 63-year-old female on warfarin showing general shedding.26 Valproate Carbamazepine Valproic acid (VPA).23. A review of the literature mentions 643 cases of valproateinduced alopecia. once ingested.142 Hair Loss: principles of diagnosis and management of alopecia Figure 5. dissociates in the gastrointestinal tract into a salt or ionic form.2 Telogen effluvium.24 Patients on VPA who develop hair loss tend to have a high valproate blood concentration. showing a disproportionate number of telogen hairs.30 Some individuals may have an . Hair loss is not as marked as in anagen effluvium. (a) Top view. illustrating marked thinning on the temporal area.18 with a 0. changes. VPA and divalproex (a stable combination of valproate sodium and valproic acid) may cause hair changes.5%–12.25 It is not completely estabThere are 177 documented cases of carbamazepine-induced alopecia.27. valproate.
Sometimes alopecia may develop 1.36 Other anti-psychotics/anxiolytics Haloperidol.33 and paroxetine in 30 subjects 18 The majority of these have a typical pattern of reversible diffuse alopecia. and thus decrease zinc levels. as well as zolpidem. telogen loss subsides despite continuing treatment. It occurs 1–24 months after treatment.35 In another case. imipramine.38–40 Low zinc levels can cause hair loss. Females are more commonly affected.42 . Fluoxetine is the most frequently prescribed anti-depressant. All TCA versions have been implicated with alopecia: amitriptyline. There is no relationship between dosage and time of onset or severity of hair loss. Serotonin reuptake inhibitors Several serotonin reuptake inhibitors can also cause hair loss on rare occasions.31 However. with a 2–6 month latency period.34. Significant recovery is seen after 4–8 months from the time use of the solution is discontinued.18 Sertraline has been reported in 46 instances.41 Tricyclic/tetracyclic antidepressants A few instances of diffuse hair loss associated with tricyclic antidepressants (TCA) have been documented.5 years following fluoxetine introduction. but also extends to eyelashes and eyebrows. a fluoxetine-induced alopecia was still evident 1.31 Interferons Telogen effluvium occurs in 20–30% of patients treated with interferons. The utilization of lowdose estrogen contraceptives is only occasionally associated with this effect. Oral contraceptives Telogen hair is lost 2–3 months after discontinuation of treatment with oral contraceptives. Beta-blockers may have a direct toxic effect on the hair follicles. olanzapine and respiridone have been documented as causing hair loss.5 years after drug discontinuation. and protriptyline. This sideeffect is reversible once medication is terminated. Clonazepam is one exception. Captopril can also cause hair loss. owing to the estrogens. nortriptyline.31 The tetracyclic antidepressant drug maprotiline and trazodone may also result in hair loss.32. despiramine.Drug-induced alopecia 143 increased genetic predisposition to medicinal alopecias. Antihypertensive agents Several anti-hypertensive agents are known to cause hair loss.37 This is believed by Headington to be a delayed anagen release. and with this there are 725 documented cases. particularly in those patients with renal disease. Anxiolytic medicines of the barbiturate and benzodiazepine classes. amoxapine.31 Buspirone is also associated with hair loss on rare occasions. In some cases. Topical ophthalmic beta-blockers Topical ophthalmic beta-blockers can cause hair loss. It may form a complex with zinc. Pathogenesis is probably similar to that in post-partum hair loss. none of the monoamine oxide inhibitors are known to cause alopecia. doxepin. Hair loss is not confined to the scalp alone. generally do not result in alopecia.10 There is prolongation of the anagen phase.
More research may further clarify drug-induced hair-loss issues. loss of hair color and ichthyosis. The package insert for accutane mentions hair loss. an informed patient and physician should discuss the risks and benefits of continuing. 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. with subsequent disturbed keratinization. Intrafollicular thinning. 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 . there is surge of ‘telogen release’. Diffuse hair loss is commonly observed during soriatane treatment. fatigue. joint pains and weakness. Acute poisoning produces hair loss in 10 days.144 Hair Loss: principles of diagnosis and management of alopecia Keratin production interference Thallium Thallium is no longer used as a drug. It certainly can be offered to the patient. unmanageable. with muscle aches. which is what is more commonly seen with other drugs. and offer new therapeutic recommendations. which has been withdrawn from the market because of cataract induction. can cause significant alopecia. stopping or changing the dose or medication. Retinoid-induced alopecia has a later onset and is almost always reversible. dry. just like any telogen effluvium. keratinization. Minoxidil tends to maintain hairs in anagen and convert telogen hairs into anagen hairs more quickly. with evident alopecia occurring in about 20% of patients. rather than an immediate anagen release. Triparanol. Available evidence indicates that thallium inhibits the utilization of cystine in the production of the keratin molecule. Cholesterol is a component of cellular lipids. However. Hair losses of several months’ to years’ duration. the negative implications of stopping or changing the regimen also need to be considered. Thallium ingestion produces changes in the matrix cells.31 How to manage druginduced alopecia In cases where an effective therapeutic agent causes alopecia and no appropriate alternative can be found. It is due to a shortened anagen release. loosely anchored hairs. breakage of the hair shaft and the induction of telogen is seen in thallium alopecia. The advantages and disadvantages of maintaining the drug must be reviewed. Decisions are based on alternative medications and hair loss severity and its emotional impact. During the early conversion of telogen to anagen hairs. Similarly. and its synthesis and metabolism are essential for the production of normal epidermal structures. have been reported in chronic thallium intoxication. Patients may temporarily Retinoids Soriatane and accutane can produce brittle. Such choices are especially difficult when the offending agent is otherwise effective. but may be ingested accidentally in rodent poisons or contaminated foods. along with ataxia. accumulation of air bubbles in the hair shaft.
1965. as the alopecia is usually reversible. Ahmad S. 18(10): 461–5. shedding telogen hairs and subsequently replacing them with the more desired anagen hairs. 20. 1982. 21. For drug-induced anagen effluvium.K. et al. 1994. The impact of lithium in South-west Scotland. 116(4):347–61. Thyroid disorders in lithiumtreated patients. Br J Dermatol. Harms M.T. Semin Oncol. Ann Intern Med.S. Int J Clin Pharmacol Ther Toxicol. Australas J Dermatol. 9th edn. Drugs and alopecia. 14:23. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Yassa R. 8(3):183–5. Br J Dermatol. pp. [Cutaneous side effects of antitumor chemotherapy]. Klotz U. Ann Clin Psychiatr.G. Molinoff P. 2. 1980. 25. I.D.I.. Davis R. Drug-associated alopecia. J Affect Disord. 107(1):124–5. McKinney P. A cutaneous side effect of lithium: report of two cases. and Schweizer C. Ann Dermatol Venereal.T. 1979. Alopecia areata during lithium therapy. 47(2): 332–72. Mortimer P. 24. Telogen effluvium. 647–9. 6. and Dawber R. Finkenbine R.A.L. Washington DC: Horizon Books. 148:752.G. Kusumi Y. Br J Psychiatr. 7. Orwin A. The use of cooling scalp devices is still controversial. 1984. Dis Nerv Syst. and Steck W. 15. 1986. and Mortimer P. Reeves J.44. Blankenship M. Patients should be warned of this temporary setback. and Woods D. 19. Hair loss following lithium therapy [letter]. 1985. 34(3): 149–58. A case report. 1971. and Morrison D. 129(3):356–63. Eustace D. 1998.. alopecia. Alopecia and hair changes following colchicine therapy.J. Hair loss in the course of lithium treatment: a report of two cases. Int Drug Ther News. Maceyko R.D. and Maibach H. Dunagin W.F. Hair loss and lithium. 23. New concepts and review [see comments]. topical minoxidil 5% solution has been reported to work. J Am Acad Dermatol. 91(6):930. Can J Psychiatr. Clinical toxicity of chemotherapeutic agents: dermatologic toxicity. 14. Valproic acid. Cimetidine and alopecia [letter]. 1980.H. 1983. Drug. . 1988. Alopecia and mood stabilizer therapy. New York: McGraw-Hill. 506–17. 108(4):503–4. Santonastaso P. Delaunay M. Pillans P. Some chemical influences on hair growth and pigmentation. 18. 28(2):132–3.45 References 1. 1994. Br J Psychiatr.. Demographic and clinical findings. Rook A.Drug-induced alopecia 145 (for the first month of minoxidil application) experience more hair loss. 32(12):853–4. and DeVane C. Headington J. Int J Dermatol.. 11. 24(3):100–4. 17. 5. Jefferson J. Gen Hosp Psychiatr. 13. 77:115–29. Inc.43 We rarely need to use it. 3.P. 8. and Freinkel N. 4. and McTavish D. Lithium-induced reaction [letter]. and Ananth J. 146:70–4. 10(1):46–8. 1972. 1983.L. 106(3):349–52. Dawber R. 1993. Arch Dermatol. Valproic acid in childhood epilepsy: anticonvulsive efficacy in relation to its plasma levels. Br J Dermatol. 12. 1979. 1983. 1982. Hautarzt.P. Kirov G.and chemical induced hair loss. Lithium and hair loss. 23(9):603–4. 9. 1996. 10. 50(1):33–40.. 31(1):111–13. Silvestri A. McCreadie R. Limbird L. Hair growth and alopecia in hypothyroidism.. 31(3):161–3. 1989. Int J Dermatol. and neuropathy. 16. Freinkel R. Vasopressin-associated cutaneous infarcts. 1996. 1995. Hair loss during lithium treatment [letter]. 9(1): 14–22. Arch Dermatol. and Paggiarin D. 22.P. Drugs. Vidimos A. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Peters D. 1983. J Hardman.
Hosking G.. 31. 46. Smit A. Brodin M. 1996. Duvic M. 45(3):549–51.J. Moroji T. New York: The Parthenon Publishing Group. 1999. 36(6):766–71. Naylor S. J Clin Psychopharmacol. Katsimbri P. Clinical and pharmacokinetic observations on sodium valproate—a 5-year follow-up study in 100 children with epilepsy. Ikeda M.. Br J Psychiatr. A multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy.F. Two cases of hair loss after sertraline use.. 38. 327(11):765–71. 5(3):571–9.. Telogen effluvium due to recombinant interferon alpha-2b. 264 Group [see comments]. and Major L. Hoorntje S. 1982. Bourgeois J. Bardazzi F. Physiologic skin changes in pregnancy.M.B. 1992. 30. Henriksen O. 1991. 44. The Department of Veterans Affairs Epilepsy Cooperative Study No..J. Dev Med Child Neurol. 2000. 34(3):196–7.. and magnesium in hair and serum of epileptics. Severe hair loss associated with fluoxetine use [letter]. 39. and Johannessen S.. Leaker B. 33.J.J. 14(6):866. Mattson R. et al. [Prevention of cytostatic-related hair loss by hypothermia of a hairy scalp using a cooling cap]. New Engl J Med. and Donker A.. JAMA. 1990. Am J Psychiatr. Alopecia possibly secondary to topical ophthalmic beta-blockers [letter]... Biol Psychiatr. 184(2):124–5. Ross R. Maruyama K.D. 148(3):392.. 1984. 37(2):97–108. The Paediatric EPITEG Collaborative Group. 1995..ethanol-induced gastric lesions in rats. Effects of long-term anticonvulsant therapy on copper. A randomized trial of minoxidil in chemotherapy-induced alopecia. et al. 1991. Ogilvie A. Physician Desk Reference. Dermatology. and Ellis C. Aust NZ J Med. 16(1):91–2. Koizumi J..A.I. 2000. Nobuhara Y. 18(1):62–6. et al. Hair loss during fluoxetine treatment [letter].F. Kiser J. 40. 29.. Jenike M.6-bis(1H-pyrazol-1yl)pyrimidine and related compounds on HCI. Nephron. and Easter D. Montvale.A. Lancet. Litt J.. Drug-related alopecia. Lemak N. 35. 263(11):1493–4. Zinc deficiency during captopril treatment.J. Hair loss associated with fluoxetine [letter]. Millennium edn. and Menacker S. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Acta Neurol Scand. 45. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. Schweiz Med Wochenschr. Cramer J.J. J Clin Psychopharmacol. Goldhirsch A. (ed. Fraunfelder F. Verity C. Drug eruption reference manual.H. Misciali C.. Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation. et al. . Tosti A. 1987. Gupta S.146 Hair Loss: principles of diagnosis and management of alopecia 26. Cytoprotective effects of 4. 28. Chem Pharm Bull (Tokyo).M.A. J Am Acad Dermatol.A. 1992. 1996. 27.C. 65(5):504–23. 1984. Dermatol Clin. J Am Acad Dermatol.. 159:737–8. et al. Wong R. and Collins J.. Valero V. and Pavlidis N. 1997.S. 43. Meyer S. Eur J Cancer. 1982. 112(16):568–71..T. Brodkin E. 1992. 41. 32. zinc. Bamias A. Suzuki T. 342(8884): 1423. 1983. 36. McDougle C.N. 10(6):929–40.. and Whitworth J. 35(1):74–8.. 42. 37. Alopecia associated with captopril treatment [letter].). NJ: Medical Economics. 1998.. et al.T. 31(6):571–81. 1993.. 34.
and must be questioned on taking history. such as interferons a and ?.3.7. Metabolic imbalances.8 There may be aggravating factors.2 Endogenous pyrogens. Rooth and Carlstrom10 noted hair loss. and low plasma protein. is not total and is usually reversible.6 Telogen effluvium: acute and chronic Telogen effluvium (TE) is discussed at length in Chapter 5 as it relates to medications. blood loss. as a result. Fever. may cause an immediate anagen release (IAR) as described by Headington.9 Loss is more marked in the frontal and temporal regions. .6 After parturition. which augments metabolic demands. It can be quite severe. and may continue for several months. there is a delayed anagen release.5 Acute telogen effluvium secondary to a known cause Fever Fever can cause alopecia 8–10 weeks after the bout. such as psycho-physical trauma. and. Postpartum During pregnancy anagen is prolonged. as described by Headington. such as those described below. edemas and weakness in 20 obese patients on a 200 calorie diet or on a total fast. However. Obese adolescents sometimes inflict on themselves a diet of salads and fruits lacking in protein. may slow down matrix proliferation. would probably impair the ability of the rapidly multiplying follicular matrix cells to proliferate normally.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. Increased hair loss may occur 1–4 months after childbirth. Full recovery is usual in 4–12 months. but may be generalized (see Figure 6.1). Telogen effluvium tends to be less severe in subsequent pregnancies. TE can occur as a result of a systemic disturbance.5. percentages of anagen hairs increase during pregnancy from 84% in the first trimester to 94% in the final trimester.4 Crash dieting/hypo-proteinemia Acute voluntary starvation in young women is not uncommon. 1 Follicles enter catagen and then telogen. This also can lead to hair loss. but these changes were prevented by the addition of a small amount of protein. It is never total. 2 Interferons a and ? have been shown to decrease epithelial proliferation and to affect follicular matrix cells directly.8.
(a) Side view. showing fronto-temporal thinning. It is possible that telogen effluvium from iron deficiency may unmask an underlying androgenetic alopecia.16 (see Figure 6. the two not infrequently occur together.1 A 30-year-old female presenting with a one-month history of abrupt diffuse hair shedding commencing 6 weeks after the birth of her last child. showing a widening of the central part. A thorough history regarding weight gain.148 Hair Loss: principles of diagnosis and management of alopecia Figure 6. This is clearly different from the patchy alopecia occurring after localized pressure from surgery.12 of women with diffuse alopecia13.14 Because androgenetic alopecia and iron deficiency are both common conditions in women. Thyroid influences There is no consistent correlation between the degree and duration of hypothyroidism and the severity of hair loss. Major interventions and prolonged anesthesias Blood loss and surgery with prolonged anesthesia may cause telogen effluvium15. Patients usually respond to thyroxine replacement11 unless the problem has been of very long duration and some follicles have atrophied.2). and energy level is important. Iron deficiency even in the absence of anemia (low hemoglobin) has also been reported by Hard. cold tolerance. (b) Top view. with regrowth after 4 months.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% . Severe thyrotoxicosis can also cause diffuse alopecia of the scalp. Desai and Roaf17 report telogen effluvium in a patient after prolonged surgery. The hair loss is diffuse.
2 35-year-old female with a 6-week history of abrupt diffuse hair shedding commencing 8 weeks after bowel surgery. It has been suggested that disturbed liver metabolism of cystine and methionine may be related to alopecia. particularly with Crohn’s disease. (a) Side view.19 This kind of hair loss is also referred to as ‘toxic telogen effluvium’. cirrhosis or fatty liver. showing thinning of the central part. brittle and sparse with chronic renal disease. The liver is the major site of amino acid inter-conversion. hepatic disease and malabsorption Hodgkin’s disease may present with telogen effluvium as its first sign. including pubic or axillary hair.15 Scalp hair can become dry. He found increased telogen counts in 34 patients and evident hair loss in 11. renal failure. Hepatic disease has been reported to be associated with diffuse alopecia. Malignant disease.20.21 There may thinning of body hair. Zaun 22 studied 53 patients who had either hepati- tis. 9 Inflammatory bowel disease has been reported to be associated with hair loss. malabsorption should be investigated. displaying a significant widening of the parting.23 .Telogen effluvium: acute and chronic 149 Figure 6. (c) Occipital view.22 When sparse hair and growth retardation are associated with chronic frequent loose pale and bulky stools. showing marked thinning. (b) Top view.
. increased parting widths over the entire scalp and increased telogen shedding. showing a disproportionate number of telogen hairs on transverse section (courtesy of Dr Magdalena Martinka).15. it is a source of anxiety to her. frequently with a positive pull test.27 They describe a ‘not uncommon condition’ presenting with transitory episodes of shedding lasting several weeks with no apparent cause. 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. There is literature that does support the notion of psychogenic telogen effluvium. CTE contrasts with classic acute telogen effluvium by its persistence and its tendency to fluctuate for a period of years. with or without a recognizable initiating factor. and depression Acute anxiety or depression may cause a telogen effluvium.3 A histological transverse section of chronic telogen effluvium. Obviously. Females present with a diffuse thinning. They considered Figure 6. Diffuse cyclic hair loss in women was first described by Guy et al.24.25 but the paucity of reports suggests that it is uncommon. 195126 this to be a physiological phenomenon. The onset is usually abrupt. Chronic telogen effluvium of unknown cause in the female patient ‘Woman is herself constantly doing something to her hair. The degree of shedding is usually severe in the early stages. The typical patient is a ‘vigorous otherwise healthy woman’ who presents with diffuse hair loss that is cyclic and reversible.29 CTE is not uncommon. 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. A modern term for this condition. Women who present with this type of hair loss frequently are upset and want a satisfactory explanation for their problem. acute anxiety. and the hair may come out in handfuls.28. reduction in pony tail diameter.150 Hair Loss: principles of diagnosis and management of alopecia Psychological stress.’— CBerg. coined by Whiting. would be Chronic Telogen Effluvium (CTE). in 1959.2 Medications These are discussed extensively in Chapter 5. It is a form of diffuse hair loss affecting the entire scalp for which no obvious cause can be found. Patients are particularly troubled by Frequently encountered in dermatological practice is the woman who presents with chronic diffuse hair loss of unknown cause.
Typically this occurs in 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.3). further studies with double-blinded placebo controls analyzing the single and combinational benefits of supplemental iron and topical minoxidil solution for CTE are needed. the amount of shed hair here is greater than that in androgenetic alopecia. Nutritional supplements (except for iron when indicated) are not recommended. However. while miniaturized hairs are not a feature of the disorder. Sufficient nutrition is obtained in a normal diet. (3) Top up ferritin levels to greater than 30 µg/1.31 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. in those women who have a genetic predisposition to androgenetic alopecia (AGA). and hair will not necessarily grow back to the same density as before. CTE is usually reversible. However. hair thinning is usually discrete which contrasts to the intense emotional overtones brought about by this situation. Trueb et al. and fear total baldness. In certain cases of CTE. and correlates better with emotional upset than with actual hair loss. With the exception of bitemporal recession. Repeated reassurance that the condition does not cause complete baldness is necessary. We have found that topical minoxidil solution is beneficial in maintaining hairs in anagen and increasing conversion of hairs from telogen to anagen. Scalp biopsies show an increase percentage of telogen hairs (see Figure 6. laboratory testing may often show ferritin levels below the normal male reference range of 25–30 µg/l. The patient should be monitored every 4–6 months with repeat ferritin levels until they have reached this threshold level. CTE does appear to be self-limiting in the long run. Usually normal reference levels for women are considerably lower.Telogen effluvium: acute and chronic 151 the continuing hair loss. 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. This may initially lead to the differential diagnosis of psychogenic pseudoeffluvium. No apparent cause can be found. and involving the entire scalp area in increased shedding of telogen hair. (4) Topical minoxidil 5% solution twice daily.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 6.30 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. .31 The normal ferritin levels for men and women differ in most laboratories. Owing to the synchronization of the hair cycle. (2) Make sure you have ruled out any underlying cause of telogen effuvium. as a large number of the ‘normal control’ group are menstruating women. CTE may unmask their AGA. Scalp dysesthesia or a sensation of pain in the hair (trichodynia) is an accompanying symptom in a significant proportion of cases. as one must temporarily shed more telogen hairs to increase the eventual percentage of anagen hairs. large amounts of zinc in supplements (> 25 mg/day) may affect iron absorption adversely. Overlap with androgenetic alopecia and/or psychogenic pseudo-effluvium is not uncommon.3). There is evidence that the taking of excessive and unnecessary supplements could actually induce telogen effluvium. starting abruptly without a recognizable initiating factor. Patients must be warned that initially there may increased shedding with topical minoxidil solution.31 For example.
Freinkel R.K. Williams R.152 Hair Loss: principles of diagnosis and management of alopecia References 1. Post operative (pressure) alopecia. 1989. 16. Post partum alopecia. Berg C. 22. Hair growth and alopecia in hypothyroidism. Acta Derm Venereol. R. 81:34.. 3. p. 136–66.L.Carlstrom. 24. Karassik R. 1980. 1985. A. Arch Klin Exp Derm. Arch Dermatol.C. Headington J. Skelton J. Zaun H. The normal trichogram of pregnant women. Ramsay I. Rushton D. Br J Dermatol. 1963. 81:83–5. Dis Colon Rectum. 18. 1973. 1963. Alopecia after ileal pouchanal anastomosis. Kligman A. Effects of alpha and beta interferons on cultured human keratinocytes..S. The unconscious significance of hair.Roaf.George and J. 32(6):457–65. Satyaswaroop and P. Acta Med Scand 1970. Telogen effluvium as a sign of Hodgkin disease. Telogen effluvium. 14. 123(2):187–97.G. Blackwell Scientific Publications: Oxford. 87:609. 1947. J Invest Dermatol.N.T. 8. Camacho F. Rooth G. New concepts and review. E. J Clin Endocrinol Metab.Rudolph and J. Anesth Analg. F.. James K. [Dermatological changes in patients receiving long-term hemodialysis].R.Olsen. Diffuse alopecia: telogen hair loss. . metabolic and chemical influences on the follicular cycle. Pergamon Press: Oxford. J R Soc Med. and Gilchrest B. 106(3):349–52. 1960. 7. Wachstumsstorungen der kopfhaare als folge von hepatopathien. 63(1):83–4. J Invest Dermatol. 9. 1984. Thyroid and adrenal interrelations with special reference to hypotrichosis and axillairis in thyrotoxicosis. McGraw-Hill.Rao. Arch Dermatol.I.: New York. and E. 187(6): 455–63.Shanon. Hard S. and S. Crohn’s ileocolitis presenting as chronic diffuse hair loss. 21.Nerette. Tabibzadeh.. Scoggins R. 241–252. 1972. Non-anemic iron deficiency as an etiologic factor in diffuse loss of hair of the scalp in women. J Clin Endocrinol Metab. Lubach D. 83:175–98. Aula Medica Group SA: Madrid. 13. Abel R. 1997. Arch Dermatol. Dahlin P. Desai S. 67(1):131–8. ed. 1960. Arch Dermatol. Thompson J.. 1959. and Y. Klein A. 1969. Lynfield Y.A. 1969. In Diseases of the hair and scalp. Inc. Arch Phys Med Rehabil. 1989. Fiedler V. Diffuse cyclic hair loss in women. 203. Pathologic dynamics of human hair loss.J. Schiff B. ed.W.Leyden. 15. Yaar M. 108(5):702–3. Diffuse alopecia: Endocrine.D. 1951.Camacho. 2. In Advances of biology of the skin.P. 41:357. S. 17. 82(5):303–4. Schnipper L. Telogen effluvium: hair loss after spinal cord injury. Alopecias due to telogen effluvium. Pecoraro V. W. Antiproliferative effect of interferon-gamma in human endometrial epithelial cells in vitro: potential local growth modulatory role in endometrium. 10. 6. 129(3):356–63. Arch Dermatol.A. pp. 20. Biochemical and trichological characterization of diffuse alopecia in women. pp. J. 25. 1966. Rook A.Freinkel.. 403–9. 26. Arch Dermatol.E. Cutaneous manifestations of hyperlipidemia and uraemia. In Trichology: diseases of the pilosebaeous follicle. 1984. 1993.C. 1993. 5. Therapeutic fasting. 27. Effect of pregnancy on the human hair cycle. 4. 1961. 7:52. and N.H. 1991. In Disorders of hair growth. 65(8): 485–6. 1988. P.Montagna. ed. 85(1):70–4. 31(2):82–5. ed. 43:562–9. Arch Dermatol. 11. 23. Postgrad Med 1967. et al. Telogen effluvium after anesthesia and surgery. J Obstet Gynecol. 35: 323–7. Hautarzt.. Study of postpartum alopecia. Schattner A. pp. London: George Allen & Unwin Ltd. 235:386–93. 12. 94:125.S. Guy W. 19.Rook. 1990..
Chronic telogen effluvium: increased scalp hair shedding in middleaged women.M. Clin Dermatol.A. 2000. and D. Whiting D. Hautarzt. 1996. Van Neste D. 35(6): 899–906.A.Telogen effluvium: acute and chronic 153 28. Hair problems in women. J Am Acad Dermatol. Trueb R. 1996. 30. 15(1):113–25. Chronic telogen effluvium. . [Idiopathic chronic telogen effluvium in the woman]. Whiting D.H.Rushton. Dermatol Clin. 29. 51(12):899–905. 31.J. 14(4):723–31. 1997.
7 Cicatricial (scarring) alopecias Introduction Cicatricial (scarring) alopecia represents a diverse group of diseases characterized by lack of follicular ostia (Figure 7. histological or proposed pathogenic criteria. The terms cicatricial and scarring are used interchangeably.2 Clinically. there is a permanent upper portion of the hair follicle and a non-permanent lower portion. because the location of the inflammatory infiltrate is crucial in determining irreversibility of alopecia. Figure 1.1 Lack of follicular ostia is the hallmark sign of scarring hair loss. If the inflammation is located within the permanent portion. Classification Classification schemes for cicatrizing alopecias have been based upon clinical. Scarring alopecias are true trichologic emergencies. then a cicatrizing alopecia is more likely to occur. catagen. (see Chapter 1. The non-infectious inflammatory scarring alopecias include chronic cutaneous lupus erythematosus (CCLE).1. As the hair cycles through anagen. particularly around the stem cells of the bulge area and the infundibulum. Follicles can be saved from irreversible damage if this peribulge infiltrate can be controlled. in the vicinity of the non-permanent portion. and telogen. a scarring alopecia is unlikely to develop. A basic knowledge of follicular anatomy is important in the understanding of scarring alopecias. . while FD presents with pus- Figure 7. lichen planopilaris (LPP) and folliculitis decalvans (FD). When the inflammation is located deep.1) and irreversible alopecia. These cells migrate down into the hair follicle.8). scarring alopecias are categorized as either inflammatory or non-inflammatory. and subsequently differentiate into the various layers of the hair follicle. CCLE and LPP are characterized by keratotic follicular papules. Follicular stem cells are located in the bulge area where the arrector pili muscle inserts into the follicles.
156 Hair Loss: principles of diagnosis and management of alopecia tules. The non-inflammatory scarring alopecias are pseudopelade of Brocq (PP) and follicular degeneration syndrome. is preferable. This site should be representative of active disease (primary lesion). Scarring alopecias can also be classified as primary or secondary. The punch is placed parallel to the direction of the hairs and inserted to the depth of the bevel.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. developmental abnormalities. This pathologically based classification system assists the clinician both in therapeutic decision-making and in gaining a better patho-physiological understanding of these disorders.0 nylon suture. The blue suture allows for easier recognition and differentiation from hair during suture removal 7 to 10 days later. and folliculitis decalvans. CCLE. The area is marked with a red marker. Secondary scarring alopecias result from events outside the follicular unit that impinge upon and eventually eradicate the follicle.4 This grouping includes pseudopelade. Sarcoidosis and morphea are examples of secondary scarring alopecias. because this is the location of terminal anagen hair bulbs. These conditions are centered on the crown or vertex and progress in a roughly symmetrical pattern. Special stains. follicular degeneration syndrome. In these cases. Two 4 mm punch biopsies are performed. preferably with a positive pull test and a paucity of follicular orifices. A second scheme. and neoplastic infiltrates. A less cosmetically important site. such as PAS and elastin. such as the posterior scalp. centrifugal scarring alopecia (CCSA). may also be requested. the hair follicle is the primary target of destruction. The lymphocytic-mediated disorders include CCLE. and FD are primary alopecias. PP. with disease activity limited to the peripheral zone surrounding the alopecic zone. Pressure is then applied to the biopsy site with a cotton applicator that may be saturated with aluminium chloride. the hair follicle is simply an ‘innocent bystander’. . based upon pathology. Follicular destruction is not the primary event. In primary scarring alopecias. Lymphocytic-mediated cicatricial alopecias Clinical features The three most common lymphocytic-mediated cicatricizing alopecias are CCLE. The hair in the biopsy site is clipped. dissecting cellulitis. and PP. and lidocane with epinephrine is infiltrated into the area. LPP and PP. The biopsy site is then closed with a blue 4. The biopsy should include the subcutaneous fat. 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. The biopsy for cicatrizing alopecias A scalp biopsy is crucial in the diagnosis of a cicatrizing alopecia. while the neutrophilic mediated conditions include FD. classifies the cicatrizing alopecias according to inflammatory infiltrate cell type: lymphocyte or neutrophil. First. a biopsy site is selected. Ten minutes is then allowed to take advantage of the vasoconstrictive effect of the epinephrine. and acne keloidalis. LPP. LPP. genetic disorders.
Cicatricial (scarring) alopecias 157 Figure 7. More than half these patients had scalp involvement at the onset of the condition. However.5 A published report6 of 89 patients with CCLE showed that 34% had scalp involvement. (d). 35 per cent (30/86) had scarring alopecia. (a) and (b). In 10% of patients with CCLE. (c).8 Age of .1 years.2 Chronic cutaneous lupus erythematosus of the scalp. the scalp was the most prominent finding. In a smaller study by Callen. Follicular hyperkeratosis occurring centrally within a plaque of lupus erythematosus. A 60-year-old female with frontal scalp involvement. an ANA is recommended for all patients with CCLE. 7/17 patients (41%) with CCLE had cicatricial scalp involvement.7 This common involvement of the scalp is intriguing. because the scalp is a relatively light-protected area. A 23-year-old female with painful erythematous atrophic plaques.7 In three out of the seven. Very few patients (< 10%) who present with CCLE ever progress to systemic LE. 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. scalp involvement may be the sole manifestation of LE.
In 1915.3g).9 who described the association of lichen planus with follicular keratotic lesions. Clearly.2d). There is a spectrum of LPP. Occasionally drugs such as gold14 or mepacrine (atabrine)15 can trigger scalp lichen planus and cause irreversible hair loss. edematous plaques. Follicular hyperkeratosis is present at the periphery of the plaques. Of all patients who have lichen planus. normal anagen hairs can easily be pulled out of the scalp. LPP is usually an insidious process evolving over several years. Seven per cent had either axillary or groin involvement. A clinical triad of classic plaquetype lichen planus.3b and 7.13 LPP accounts for 30–40% of scarring alopecias. Patients present with erythematous plaques of alopecia. Scalp lesions begin as erythematous papules or irregular small scaly plaques. a series of 807 patients showed that only 10 (< 1%) had scalp involvement. The term lichen planopilaris was first introduced in 1895 by Pringle. Tufted folliculitis consisting of several hair shafts emerging from a single ostium can also . Hypopigmentation and depigmentation begin to appear. 7. As the lesion expands. Lesions typical of lichen planus do not occur on the scalp. 7% nail involvement. and a female predominance (2:1) has been noted. It usually occurs between 30 and 70 years of age. A prominent thickened and adherent scale may develop.2). Central atrophy and telangiectasia eventually become prominent. These lesions slowly progress to large erythematous. and alopecia of the scalp or other hairy areas has been described. the oral mucosa and the nails must be examined.3a).3e. These keratinous plugs are from the follicular openings. a clue to help distinguish CCLE from LPP (Figure 7. white atrophic scarred alopecic plaques will predominate over their inflammatory precursors.3j). At this point patients may experience loss of hair. owing to torsional within the hair follicle.3i and 7. with a predilection for areas of greater hair density. a characteristic feature of the scarring alopecias. and ulcerations may even develop (Figure 7. with its extent not clearly apparent unless the scalp is shaved (Figures 7. the central erythema fades and the surface flattens.11 It was felt 40 years ago that one had to have this triad to make a diagnosis of LPP. and scarring develops. atrophy. There is also increased curliness of hairs in scarred areas. and represent follicular hyperkeratosis. Graham-Little10 described folliculitis decalvans et atrophicans or follicular scalp lesions resulting in cicatricial alopecia associated with follicular keratotic lesions at other sites.3h. In addition.3f. rather than centrally (Figures 7. The whole skin surface.12 showed that 50% of their series of 45 patients with scalp LPP had strictly scalp involvement only. which when removed reveals keratinous plugs on its under-surface. 27% mucous membrane involvement and 40% glabrous skin involvement. and anagen hairs can be extracted with gentle hair-pulling. This view is limited. Mehregan et al. and fails to account for the majority of intermediate cases. such as the occipital scalp in men with AGA (Figures 7. spinous or acuminate lesions. With continued spread of the disease.3c). large. Pruritus and tenderness are often a prominent feature. 7.158 Hair Loss: principles of diagnosis and management of alopecia onset of scalp CCLE is usually at between 20 and 60 years of age. These two presentations are now considered variants of lichen planus. Follicular hyperkeratosis is more active in the center of a plaque. 7.3d). patients with scalp lichen planus should be followed up to assess whether lichen planus develops elsewhere (Figures 7. This initial alopecia induced by follicular inflammation is potentially reversible. telangiectasia and follicular hyperkeratosis (Figure 7. LPP may be very widespread.
(b) and (c) LPP affecting the spared areas of male androgenetic alopecia. (d) Ulcerative lesion of LPP of the scalp. (c) Burnt out LPP. (a) Follicular hyperkeratosis at the periphery of erythematous alopecic areas. (e) Extensive case of LPP at the back of the scalp.Cicatricial (scarring) alopecias 159 Figure 7. (b) Showing active inflammation.3 Lichen planopilaris (LPP). .
. showing marked involvement of much of the scalp. Close-up after the head has been shaved.160 Hair Loss: principles of diagnosis and management of alopecia (f) and (g). (i). (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. Tufting of hairs in LPP. (k). (h). This fits well with GrahamLittle disease.
Scarring hair loss affecting central portion of the scalp. (c).4 Pseudopelade of Brocq (a). (b) A 5year-old with pseudopelade (Brocq). (e) An 8-year-old boy with scattered pseudopelade (Brocq).Cicatricial (scarring) alopecias 161 Figure 7. . (d).
(i) PP affecting the area most affected by androgenetic alopecia and mimicking androgenetic alopecia.162 Hair Loss: principles of diagnosis and management of alopecia (f) and (g) PP progressing over 10 years in a 40-year-old male. (h) PP affecting the area spared by androgenetic alopecia. (j) pp affecting tne beard area. .
it is now believed to represent an idiopathic disorder unrelated to trauma or hair cosmetics.4i).4a and 7.3k).17–19 Kossard has described an entity occurring in postmenopausal women presenting with perifollicular erythema along the marginal hairline.4j). overlaps significantly with PP with marked non-inflammatory cicatricial alopecia on the top of the scalp in black patients.20 PP presents with small. 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. Pseudopelade refers to ‘like alopecia areata but not alopecia areata’. There is controversy as to whether PP is a distinct entity or is effectively the same as end-stage CCLE or LLP.4f and 7.16 There is a variant of LPP. extension of the process takes place only very slowly (Figures 7. In pseudopelade (Brocq). in some cases. Pelade is the French word for alopecia areata (AA).4b). PP is usually asymptomatic and without inflammation. the follicular ostia are not present while in AA they are most certainly present. His group described 94/142 (66.5). 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. Occasionally the pattern of hair loss of PP can mimic androgenetic alopecia as described by Zinkernagel et al.6%) in the age range of 11–20.19 Histological findings were indistinguishable from LPP.26 Although initially thought to be a consequence of hair-care practices.Cicatricial (scarring) alopecias 163 occur in LPP (Figure 7. The parietal and vertex areas of the scalp are primarily involved (Figures 7. Indeed. asymmetrical.19c. Occasionally there may be erythema and mild pruritus. A form of central centrifugal scarring alopecia in African-Americans. usually of adulthood. after 15– 20 years the patient may still be able to arrange his/her hair to conceal the patches effectively. As with other cicatrizing alopecias. ivory porcelain white patches devoid of follicular units. and occurs because the infundibular epithelium of damaged follicles often heals so as to cause the formation of a common large infundibulum. Braun-Falco et al. End-stage LPP or CCLE may mimic an early pseudopelade (Brocq) as discussed below. This has been classically described as ‘footprints in the snow’.4b-e). producing a frontal fibrosing hair loss extending to the temporal and parietal hair margins. However. In 1885.25. post-menopausal frontal fibrosing alopecia. The course is often protracted and prolonged. In the majority of cases. reported an incidence of 4/ 142 (4.20. .. Brocq of Paris described what later became known as Pseudopelade19a. irregular. extension occurs more rapidly. also known as follicular degeneration syndrome (FDS). However.21 Detailed studies by Braun-Falco et al. Occasionally PP may affect the beard area and not just the scalp (Figure 7.4g).22 strongly support the idea that pseudopelade can exist as a distinct entity. Eyebrow loss was described in 13/16 women. and exceptionally there may be almost total baldness after 2 to 3 years. anagen hairs are easily extracted. PP is an idiopathic disorder. This is known as polytrichia.2%) patients with PP without any previous underlying condition. PP in children has been described. Tufting is common as an endstage phenomenon in many scarring alopecias. This author has seen at least 3 cases in children under the age of 10 (Figures 7.23 The course is extremely variable. Brocq subsequently admitted that this term does confuse the Iiterature 19b.24 and the diagnosis of PP may be missed (Figure 7.35%) cases of PP under the age of 11 and nine patients (9.
164 Hair Loss: principles of diagnosis and management of alopecia Figure 7. (d) Close-up of patient illustrating lack of follicular ostia. (b) Close-up showing obliteration of follicular ostia. (c) Black male with significant alopecia.5 Central centrifugal scarring alopecia (follicular degeneration syndrome) in African-Americans. (a) Black female with significant alopecia. .
First. a thickened basement membrane zone and an increased dermal mucin helps support the diagnosis of CCLE. Other features include loss of sebaceous epithelium and marked perifollicular lamellar fibrosis. and fibrosis (Figure 7. Some clinical pearls can be helpful in establishing a diagnosis (Figure 7. . a superficial and deep perivascular and periadnexal lymphocytic infiltrate. while a peripheral distribution is seen in LPP. Pigment incontinence is present. Perifollicular inflammation is most severe at the level of the infundibulum.7 Pathology of lupus erythematosus showing peri-adnexal and perivascular lymphocytic infiltration with follicular hyperkeratosis. the most likely diagnosis is PP if the scarring alopecia is non-inflammatory. if follicular hyperkeratosis is present.8). Direct immunofluorescence demonstrates granular deposits of C3 of IgG distributed along the dermal-epidermal junction. Pigment incontinence is present. but may extend down the length of the follicle. Finally. The presence of a focally thinned epidermis.7). and inflammatory cells may invade the follicular epithelium.Cicatricial (scarring) alopecias 165 Figure 7. a central localization tends to occur in CCLE. Inflammation affects the upper portion of the follicle. if pustules are present. with a characteristic perifollicular interface dermatitis (Figure 7. loss of sebaceous epithelium.6).6 Algorithm for diagnosis of major non-infectious scarring alopecias. Second. then FD is the most likely diagnosis. Pathology The histopathology of CCLE reveals follicular vacuolar interface changes.1 Figure 7. The lymphocytic infiltrate of LPP is lichenoid.
Pigment incontinence is less evident than in LE or LPP.166 Hair Loss: principles of diagnosis and management of alopecia Figure 7.) Perivascular and peri-eccrine infiltrates are usually not present.9 Numerous hairs exiting from one infundibulum which clinically appears as polytrichia or tufted folliculitis. Special staining techniques may help in establishing a diagnosis of a scarring alopecia. (b) and (c). As PP progresses. the epidermis becomes atrophic.8 (a). There may also be tufted folliculitis in the upper portion of the epidermis (Figure 7.) . (Courtesy of Dr Magdalena Martinka. In the early stages. Pathology of lichen planopilaris displaying the characteristic follicular lymphocytic interface dermatitis. a peri-infundibular lymphocytic infiltrate is present beneath a normal epidermis. Direct immunofluorescence may demonstrate grouped globular IgM cytoid bodies in follicular epithelium. (Courtesy of Dr Magdalena Martinka. and sebaceous glands and hair follicles are obliterated. while in LE and LPP the quantity of elastin is significantly dimin- Figure 7. The end stage of PP is characterized by marked scarring and the absence of an inflammatory infiltrate. rete ridges vanish. The pathology of PP depends on disease duration.9). Direct immunofluoresence is negative. Elastin staining demonstrated normal or abundant elastic tissue in PP. as in LE.
A potassium hydroxide preparation and/or culture will help confirm the diagnosis. However.11 Neutrophilic infiltrate in folliculitis decalvans. the co-existence of LPP and CCLE Figure 7. Tinea capitis can be scarring. (Courtesy of Dr Magdalena Martinka. 7. there are reported cases of scarring alopecia in severe scalp psoriasis. The lymphocytic scarring alopecias can certainly be difficult to tell apart from each other. and will be described below. An algorithmic approach to the pathology of scarring alopecias is presented in Figure .28 Inflammatory changes in the infundibular area of the follicle in psoriasis may disrupt follicular stem cells and result in scarring alopecia. but again there is no follicular plugging or atrophy. Keratoacanthomas and squamous cell carcinomas can mimic hypertrophic lupus erythematosus.10 dividing entities into lymphocytic.) ished.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. Early CCLE and LLP can look quite similar. Folliculitis decalvans is neutrophilic-mediated (Figure 7.versus neutrophilic-mediated. In addition.Cicatricial (scarring) alopecias 167 Figure 7.11). Differential diagnosis Scalp psoriasis has the presence of follicular ostia and the lack of follicular plugging and atrophy.10 Algorithm for pathological assessment of major noninfectious scarring alopecias.
and disease severity. This is summarized in algorithmic form in Figure 7.10. the severity of symptoms. 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. Triamcinolone 10 mg/ml.29 Differentiating clinical and histopathological features of lymphocytic scarring alopecias are discussed above and are summarized in Figures 7. The goals of treatment are to arrest the cicatrizing process.6 and 7. patient age. decrease follicular inflammation and prevent further fibrosis. has been reported. injected with a volume of 0. The severity is determined by the rapidity of the progression of the condition. can halt further spread of the condition and reduce symptoms of itch and burning. the degree of inflammation.12 Algorithmic approach to treatment of lymphocytic-mediated scarring alopecias. and the extent of scalp involvement. . Figure 7.12. Injections are performed once monthly.168 Hair Loss: principles of diagnosis and management of alopecia Figure 7.13 Injecting intralesional cortisone into the surrounding hairy areas of scarring alopecia.1 ml/injection for 20 injections. Treatment The treatment of scarring alopecia depends on three variables: diagnosis.
A pull test is conducted with each visit. double therapy with topical and intralesional corticosteriods is initiated. If the alopecia is very severe. then prednisone is added at 1 mg per kilogram per day and tapered over two months. intralesional corticosteroid and topical corticosteroid. then hydroxychloroquine.14 and 7.15 Lichen planopilaris: the patient from Figure 7. If improvement is not noted after six months. rapidly progressive.3d with previous ulcerative LPP improved markedly with hydroxychloroquine. can be initiated and then tapered once improvement is detected. triple therapy is immediately initiated with intralesional steroid. ultra-potent topical corticosteroid and hydroxychloroquine. Increasing the number of hairs. 2 ml of 10 mg per ml. Again. very inflamed and symptomatic. Intralesional corticosteroid. If there is less than 10% scalp involvement. If the alopecia is rapidly progressive. The prednisone provides bridge therapy. which can serve as a primary target in scarring . than other treatments can be attempted. When a pull test is negative for over two years and alopecia is clinically stable.30 is added for a minimum of six months (Figures 7. therapy is tapered once improvement is acheived. Dapsone (100 mg/day)34–37 and thalidomide (100 mg/day)38–40 are other alternatives.31–33 at doses of 1 mg per kg per day. showing marked improvement after 1 year of hydroxychloroquine 200 mg twice daily. inflamed. 200 mg twice a day. If the patient is not responding within eight weeks to this double therapy. and therapy is continued for six to twenty-four months until the pull test is negative. Isotretinoin.Cicatricial (scarring) alopecias 169 Figure 7. then a systemic steroid is also administered for eight to twelve weeks. Figure 7. is administered to scarring areas once every four weeks (Figure 7. If there is more than 10% scalp involvement. Premature transplantation may actually aggravate the condition.2c.14 Lupus erythematosus: the patient from Figure 7. monthly intralesional corticosteroid injections and topical superpotent corticosteroid ointment twice daily. and an ultra-potent topical corticosteroid is applied twice daily.13).15). then scalp reduction and/or hair transplantation are further options. and symptomatic. because of a delay in the therapeutic effects of hydroxychloroquine.
pruritus or burning if the condition is remotely still active. most evident after the scalp has been shaved. showing much improvement. Figure 7.17 Folliculitis decalvans in a 17-year-old female. (a) Marked erythema and folliculitis. by retaining unaffected hairs in anagen for a longer period of time. many clinicians feel that topical minoxidil.41 . topical minoxidil solution for scarring alopecias. Although there are no controlled trials for Figure 7. enables the overall density to be better than that of untreated individuals. (b) After 6 months of isotretinoin 1 mg/kg/day.16 Folliculitis decalvans in a 30-year-old male.170 Hair Loss: principles of diagnosis and management of alopecia Figure 7.18 Tufted folliculitis in dissecting cellulitis. may cause the patient to become more symptomatic with increased inflammation. alopecias. The use of topical minoxidil is controversial. showing hair shafts embedded within the skin.
Neutrophil-mediated cicatricial alopecias The neutrophil-mediated cicatricial alopecias. such as FD. high-dose isotretinoin for a prolonged course is recommended. that controlling the inflammation for these individuals is more important than salvaging the hair.Cicatricial (scarring) alopecias 171 Figure 7. such as topical fusidic acid. are considered an abnormal immune response to the normal scalp flora.44 Dissecting cellulitis can present as a boggy cystic inflammatory process (Figure 7.44 For severe dissecting folliculitis. . Dissecting cellulitis of the scalp with characteristic boggy cysts.19 (a). (b).18). as the disease progresses. Follicular-based pustules develop in successive crops (Figure 7. however. rifampin and fusidic acid.44 Topical therapy can also be added.43. itch and burning.45–49 Patients may be so symptomatic with discomfort. fibrosis is prominent. Hair shafts are occasionally embedded within the scalp (Figure 7. the pathology demonstrates a neutrophilic folliculitis (Figure 7. 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.43 Systemic fusidic acid may also have some benefit.16). cloxacillin.11). Laser-assisted hair removal50 may help for this subset of patients. Patients present with round patches of alopecia with overlying erosion. cephalosporins. The therapeutic strategy for the neutrophilmediated cicatrizing alopecias is targeted at anti-staphylococcal therapy with systemic erythromycin.19). Close-up of boggy cysts.17) Tufted folliculitis is a feature frequently seen in FD (Figure 7. scale or crust.42 In the early stages.
J Am Acad Dermatol. 97. H.Burge. 60(6):299–300. 11.172 Hair Loss: principles of diagnosis and management of alopecia Conclusion The scarring alopecias are trichological emergencies. 10.A.Papa and A.P. 12(2 Pt 1):278–88. 1996. Newton R. London: The Society. Pringle J. Mehregan D. laboratory. Hot comb alopecia.. Muller. .M..L. An accurate diagnosis is arrived at through a careful clinical and histo-pathological assessment.Solomon and D. Burge S. 1997. A. Réchèrches sur 1’alopecie atrophiante. Headington J. 14. Ann Int Med.. 18. 84:179. Lupus. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. 20. Silver H. Woods B. 1949. 2000. 40(2):77–83. 1992. T. de Berker D. Lichen pilaris spinulosus. Paris Vol.Solomon. Dean D. 1905. Follicular lichen planus (lichen planopilaris). 1968. Dermatol Clin. 136(2):235–42. Arch Dermatol Syph. Arch Dermatol. Hautarzt. Callen J. comment].. Postmenopausal frontal fibrosing alopecia. 1992. 1915. 6. 21(2):97–109. 130(6):770–4.. 19b. 209.. 17. 118(6):412–6. Annales de Dermatologie et de Syphiligraphie.Wilkinson. Lichen planopilaris: clinical and pathologic study of forty-five patients. Freese T.R.T. 5(3):603–18. J Am Acad Dermatol.Lee and B. 6.P. 1992. 9. 2. 7. LoPresti P. 67: 346–54. 4. Br J Dermatol. Clinical and laboratory findings in seventeen patients.M. 8. Sperling L. 1982. M.. 1961. A new look at scarring alopecia [editorial.Ahn. Clinical observations of atypical lichen planus and related dermatoses due to atabrine toxicity. 13.Hwang and S. Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus.A. Journal of Cutaneous and Venereal Diseases 1885..F. 15.. and Dawber. P648. 19c. 130(11):1407].C. Arch Dermatol. Chronic cutaneous lupus erythematosus. Kossard S. R. et al.R. Arch Dermatol. 1994. Br J Dermatol. 1985. 1997. C. Braun-Falco O. 19a. M. 1987. 3:49. 2. Kossard S. Callen J.W. Hebert A. 17:77–102. and Solomon A. 1994. therapeutic. Brocq L. 12. Altman J. Wilson C. Templeton S. Doin.A. 31: 1078. In Transactions of the St John’s Hospital Dermatological Society.M.Bergner and G.Van Hale. J Am Acad Dermatol. Pseudopelade in Traite elementaire de dermatolgie Practique. The sequelae of chronic cutaneous lupus erythematosus. Br J Dermatol. Lee W. Frontal fibrosing alopecia in a postmenopausal woman.. Heilgemeir. S.M. Brocq L. varieté psuedopelade. The variations and course of lichen planus.Dissaneyeka and S. 1. Little E.P. 1(3):181–6. 1989.S. 1953. and S. Scarring alopecia in a pattern distribution [published erratum appears in Arch Dermatol 1994 Nov. Scarring alopecia in discoid lupus erythematosus. Arch Dermatol. Clinical. Dermatol Clin.Alopecia. [The Brocq pseudopelade—a disease picture or disease entity]. 98(3):234–8. 36(1):59–66. Cicatricial alopecia.S. 27(6 Pt 1):935–42. 1968. 27: 183–5. Arch Dermatol. Whiting. Feder A.A. Cutis.K.P.Kligman. and A. An aggressive multiplemodality therapeutic approach is often necessary to gain disease control.M. 3. Scarring alopecia. Brocq L. 19. Lichen post-aurique. and prognostic examination of 62 patients. 16. 14(4):773–82.C.. References 1.. Folliculitis decalvans et atrophicans: Report of a case.R. Scarring alopecia: a classification based on microscopic criteria. 5. J Cutan Pathol. 126(4):307–14.
1989.J.E. 24.G.L. Skelton H. 35. 30. London: Martin Dunitz Ltd. F.A. 108(4):461–6. 129(12):1548–50.Camacho.L. Singh Y. 2000. 26.O. 29. 1998. 2000. and A. Arch Dermatol. 24(1):49–52. et al. 37.E. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? [see comments]. Bulengo-Ransby S. 44. Messenger.Headington. In Hair and its disorders. and management. Adya C. Madani S. 1990. 1993. Happle R. and J. 22.Reymann.W. The follicular degeneration syndrome in black patients. 1986. 36. 23. pathology. 138(5):799–805. Hasper M. Wright A. 27(3):147–52.. Dawber R. Shornick J. Holm A.. Successful treatment of hypertrophic lupus erythematosus with isotretinoin. 130(6):763–9.A. Annessi G.M. 70(2):156–9. 8:631–40.F. 1982. 128(1):68–74.. 1(6):351–6.. Sperling L.Gatter.S. 31. Br J Dermatol.C.Klokke. Bowers K. biology. Vena G. Lupus. 1983. and J. 1991. 25. Dapsone in the treatment of cutaneous lupus erythematosus. Elastic tissue in scars and alopecia. Br J Dermatol. Acta Derm Venereol. Abeck D. Dermatologica 1986.. Verma K.K. Bonsmann G. Long-lasting response to combined therapy with fusidic .F. Warschaw K.J. Treatment of refractory cutaneous lupus erythematosus. and A. R.. 17(2 Pt 2):364–8.Kerdel. 1990. Knop J. pp..M. Acta Derm Venereol. and W. 17(5):305–6.L. 1992. McMeekin T. 1992.. N. 140(2):328–33. McCollough M. 1992. Powell J. and R. ‘Hot comb alopecia’ revisited and revised. and P.K. 3rd and Smith K. Braun-Falco O. Rothe M.Trueb. Duna G.. J Am Acad Dermatol.G.C.Cash. 2000. 172(1):18–23. 136(2): 205–11...C. 21(1): 99– 115. [Use of oral isotretinoin in the treatment of cutaneous lupus erythematosus].. Arch Dermatol. 1999. Update of minoxidil treatment of hair loss. Imai S.F.Piette. 34. Chronic cutaneous lupus erythematosus treated with thalidomide. J Assoc Physicians India.Trotter and J.Korting and O. J Am Acad Dermatol.J. 42(5 Pt 2):895–6. Dapsone in cutaneous lesions of SLE: an open study. histopathological and immunopathological studies in six patients. and F. C. Follicular degeneration syndrome in men. J Cutan Pathol.. 167–76. Arch Dermatol.G. M. Clin Exp Dermatol.T. 27. 33. Lindskov R.Shapiro. 39. 1992. and F.M. 1983. Mixed lichen planus-lupus erythematosus disease: A distinict entity: Clinical.A. ed. Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus. Arch Dermatol. Isotretinoin for refractory lupus erythematosus.P. Treatment of cutaneous lupus erythematosus. 42. 62(4):321–4. H. Thalidomide in the treatment of chronic discoid lupus erythematosus. Zinkernagel M. Tufted folliculitis of the scalp: a distinctive clinicohistological variant of folliculitis decalvans [see comments]. et al. What is pseudopelade? Clin Exp Dermatol.. and Bergfeld W. Green S. Pseudopelade of Brocq in beard area.Sau. and Schmoeckel C.Braun-Falco.Coviello and G.Cicatricial (scarring) alopecias 173 21. J Am Acad Dermatol. 1995. 172(4):214–7.Angelini. 32. Dermatologica. Pseudopelade of Brocq. Dawber R.Parke. Pseudopelade of Brocq in a child [see comments].Formica and A. et al..N.. Elston D. 124(6):311–15.Dawber and K. Scarring alopecia in psoriasis.L. 1994. 38. 43. Sperling L.J. 40(11): 735–6. 41. J Am Acad Dermatol.M..H. Folliculitis decalvans.. et al.M. Folliculitis decalvans including tufted folliculitis: clinical. 40. Br J Dermatol. 2000. Vanderhorst J. histological and therapeutic findings. G Ital Dermatol Venereol.. 1987. Rheum Dis Clin North Am. 28. and Gaspari A. 23(5 Pt 1):944–5.
1992. Scerri L. Br J Dermatol.. Resolution with combination therapy..C. Action of isotretinoin in acne rosacea and gram-negative folliculitis.R.. 1982. Ross. 48. 45. Ann Dermatol Venereal. Dissecting cellulitis of the scalp: response to isotretinoin. and B. 6(4 Pt 2 Suppl): 766–85. [Perifolliculitis capitis abscedens and suffidiens.Williams.Srolovitz.B.. Acta Derm Venereal.Wolff. 47. 1996. 1994.. Plewig G. J Dermatol Surg Oncol. Dissecting folliculitis of the scalp. 128(10):1329–31.Billick and H. Price V. Chui C. . Delaporte E. A case report of combined treatment using tissue expansion.C.. radical excision. and isotretinoin.Antonyshyn and J.174 Hair Loss: principles of diagnosis and management of alopecia acid and zinc. 1999. 1992. Arch Dermatol. Dubost-Brama A. 49. H.. 18(10):877–80.. J. Berger T. Alfandari S.H. R. 1992. J Am Acad Dermatol.Allen. Efficacy of isotretinoin].M. Bachynsky T. O. 134(6): 1105–8..B. 46. Dermatol Surg. Perifolliculitis capitis abscedens et suffodiens. 25(1):34–7. et al.Nikolowski and H. 50. and Zachary C.G. 72(2): 143–5.H. 121(4):328–30. Shaffer N.T. Recalcitrant scarring follicular disorders treated by laser-assisted hair removal: a preliminary report.
tretinoin and 108 animal models. 49–51. 91f. telogen effluvium and 139 antidepressants. 69 anti-coagulants. 40–1f Down’s syndrome and 20f. 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. AA and non-AA 25–7 anthralin 43. AA see alopecia areata acne 16. 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. 19–81. 42 amitriptyline 143 amoxapine 143 ANA see antinuclear antibodies examination anagen effluvium 134. 10. alkaline phosphatase activity and 3 anagen-telogen hair ratio 12. tricyclic/tetracyclic 143 antihypertensive agents 143 antinuclear antibodies (ANA) examination 16. 68. 114 androgen receptor blockers (ARP inhibitors) 104–5 androgen receptor proteins (ARP) 85 androgenetic alopecia (AGA) 10t. 88. 163 AGA and 96–7 autoimmune disorders and 21 of beard 34. 157 antitumor antibiotics 138 anxiety. 47. vitiligo and 37f alopecia areata circumscripta 31–2f Alopecia Areata Investigational Assessment Guidelines 43 alopecia masking lotion 68 alopecia totalis (AT) 30. 156 adrenoleukodystrophy. telogen effluvium and prolonged 148 angiogenesis. 34f. iron deficiency 16 anesthesias. 21 emotional stress and 24 etiology of 19 extent of hair loss 30. 34f. 16.Index Note: References to figures are indicated by ‘f’ and references to tables by ‘t’. 134 androgen blockade 102–4. 151. 48. 155 anagen phase. 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. 136–8. hair loss and 139 anti-psychotics/anxiolytics 143 anti-thyroid drugs. telogen effluvium and acute 150 . 83–119. 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. premature male AGA and 85 adriamycin (doxorubicin). 16. 89f. 134 anemia. 36f clinical features of 28–36 cyclosporin in 66f cytokines and 24 differential diagnosis of 38–42. 42 alopecia universalis (AU) 30. 137f drug-induced 137t anagen (growing) hairs 6. 27. 143 see also hair loss alopecia areata (AA) 9.
105–8. alopecia areata of 34. 98 catagen-telogen hair ratio 101 cell-mediated immunity 22–4 cellulitis 156 central centrifugal scarring alopecia (CCSA) 156. alopecia areata of 34 body hair. thinning of 149 bulge area. 27. 155–72 algorithm for diagnosis for 165f inflammatory 155 lymphocytic 167 pathology algorithm 167f cimetidine. 26 calcitonin gene-related peptide 25 captopril 143 carbamazepine. 138 cyclosporin 65–6 cyproterone acetate (CPA) 101. stem cells of 5. alopecia and 142–3 carbimazole 139 cardiovascular disease 87 carmustine 138 castling. clues for 21–4 baldness coronary heart disease and 87 drugs and 134 patterns in population 85 prostate cancer and 88 beard. 23 autoimmune polyglandular syndrome 21. DPCP and 52 catagen 134. 69 cortisone. injection of intralesional 168f coumarins 139 Cox proportional hazards model 87 Crohn’s disease 149 cyclophosphamide 137. alopecia induced by 136 circumscript alopecia 32f circumscript alopecia areata 38 clindamycin 171 clobetasol propionate 68 clofibrate 144 clonazepam 143 cloxacillin 171 colchicine 138 corticosteroids 43–7. 17. 108 cysts. 48 biologic response modifiers 101. 150 dermal acid mucopolysaccharides 167 dermographism. 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. 16. 167 chronic telogen effluvium (CTE) 150. severe 64 despiramine 143 dexamethasone 43 . 114 bitemporal recession 91. 98. 136. boggy 171f cytarabine 137 cytochrome P450 aromatase enzyme 86 cytokines. 98. 36f Beau’s lines 34 beta-blockers 143 betamethasone dipropionate 43. 151 cicatricial (scarring) alopecias 10t. 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. 22 autoimmunity. 155 buspirone 143 busulfan 138 C3H/HeJ mice 25. 156. 108 delayed anagen release (DAR) 138 delayed telogen release (DTR) 138 depression 9. 157 histopathology of 165 vs LPP 158. 155 atherogenesis 88 autoeczematization 64 autoimmune diseases 21.176 Index arrector pili muscle 5. 155 catagen hairs 6. 104–5. 151 bleomycin 137 body.
in women 150 dihydrotestosterone 85 dinitrochlorobenzene (DNCB) 51–2 diphenylcyclopropenone (DPCP) 26. 140t. 109. 151 fever. 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. 88. planting of 129 hair loss 9. 148 diffuse alopecia areata 30. 133 hair transplants and 130 and minoxidil combination therapy 110 fluocinolone 43 fluorouracil 137 fluoxetine 143 follicular bundles. 170f. positive pull test 96 dystrophic hairs. 158. with miniaturized hairs 99f follicular degeneration syndrome (FDS) 156.Index 177 diabetes mellitus 22 dibromoketone 53 diffuse alopecia 16. 158 pattern in a family 95f prevention of 101. 16. loss of 144 hair cortex 4. 136 hair counts 13. 17 divalproex 142 dopaquinone 6 Down’s syndrome. 11f . alopecia areata and 20f. alopecia and 137 drug-induced alopecia 134–46 anagen effluvium 137f. 113 severity of 148 see also alopecia hair matrix cell mitosis 136 hair removal. 163. 164f follicular hyperkeratosis 58. 155 follicular scalp lesions 158 follicular stem-cell gene therapy 114 follicular stem-cells 155 folliculitis. 170f. counts of 12 dystrophy. 6 abnormalities of 15 quality of 10. 103 hair cycling. 51. 143. 5. 165 follicular ostia 10. 33f diffuse cyclic hair loss. 52–64. 102–4. 156. DPCP and 64 elastin staining 156. checking for presence of 15 eczema. 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. 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. 170f erythema multiforme 64 estrogen. 21 doxepin 143 doxorubicin (adriamycin). 171 folliculitis decalvans (FD) 155. 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. 166 eosinophils 27 epidermal growth factors (EGF) 105 erythema 163. 167. 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. laser-assisted 171 hair shafts 2. levels of 98. 141t Dundee experimental bald rat (DEBR) 25 dyslipidemia 88 dysmorphobia 9 dystrophic anagen hairs. tufted 166. alopecia and 147 finasteride 101.
144 keratinocytes. 121–2f. disturbed 136. women with 108 Ludwig Stages I–III 90f lupus erythematosus 22. 87. 108 Hodgkin’s disease 149 hormone modifiers 101. 148 isotretinoin 169. 87. 88 hyperthryoidism 9 hypertrichosis 108 hypertrophic lupus erythematosus 167 hypo-proteinemia 147 hypopigmentation 64. 156. AGA and 85 intralesional corticosteroids 67. 22. 155. telogen effluvium and 139 iron deficiency 16. responsiveness to 21 inflammatory bowel disease 149 infundibulum 1. 12 abrupt diffuse 148f. 108 hyper-insulinemia 88 hyperpigmentation 64 hypertension 47. 4. 158. 5 Kaplan-Meier survival analysis 53 keloids 125 keratin 4 keratinization. 140. 158 hypopituitarism 85 hypothyroidism 9. 64 lymphocytic-mediated cicatricial (scarring) alopecias 156–70 treatment algorithm 168f M phase drugs 138 . 102–5 Hox genes 26–7 human leukocyte antigens (HLA) 19–21 Huxley’s layer 2. 4. 171 isthmus 1. 110. 5 hen’s egg test 53 heparin 139 hepatic disease 149 hirsutism 16. 149f physiological 6 hair thinning 9. 169 intramuscular corticosteroid therapy 47 iodine. 108. 101 hairs light-microscopic examination of 13–16 miniaturization of 27. 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. 5. 98. 151 hair transplants 101. 158 lichenoid eruption 136 lithium 140–2 Ludwig pattern. 169f chronic cutaneous scalp 157f luteinizing hormone-releasing hormone (LH-RH) 105 lymphadenopathy 62f. stages of 89 Ludwig Stage I pattern. study of 103 hair-growth promoters 101 hair-specific antibodies 23 hairpieces 69. 136. 159– 60f. 89. 169 complication of donor area 126 finasteride and 130 male 113f. 4. 158–63. 5 hyaluronic acid 3 hydroxycarbamide 137 hydroxychloroquine 169 hydroxyurea 138 hyper-androgenism 16. 147 immediate telogen release 138 immunosuppressive therapy. 148 iatrogenic hypothyroidism 139 ICAM-1 27 ichthyosis 144 ifosfamide 138 imipramine 143 immediate anagen release 138. 5 insulin-resistance-associated disorders 88 interferons 143 intracellular androgen metabolism. 69. 163 inner root sheath (IRS) 2. 83 halcinonide 43 haloperidol 143 Henle’s layer 2. in teenagers 95f Ludwig Stage III. 169f cicatricial alopecia 10t pathology of 166f peripheral distribution 165 lichen planus 17. abnormal 24 keratoacanthomas 167 keratotic follicular papules 155 leflunomide 26 lichen planopilaris (LPP) 155.178 Index hair shedding 9.
105–8. 109 and hair transplants 130 hypertrichosis of the face and 107f topical 133. 138 methylprednisolone 47 methylthiouracil 139 mice. 47–8. 11f. 101. 58f ophiasis inversus (sisapho) 30. 4 melanin 3. 138 men AGA treatment options 101 frontal hairline recession 89 vertex balding in 87 mepacrine (atabrine). 161f. 88 olanzapine 143 onychorrhexis 34 ophiasis 33f. 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. 109 Norwood-Hamilton pattern 90. pulsed oral 47 pressure-induced alopecia (PIA) 38. 17f non-inflammatory cicatrizing alopecias 155 nortriptyline 143 Norwood-Hamilton classification 92. 5 papular atrichia 85 paroxetine 143 PAS stain 156 patchy alopecia areata 30. endogenous 147 quail-chick model 86 5α-reductase 85 . 16. 42 procarbazine 138 Propecia 102. intravenous methylprednisolone 47 pustules 156 PUVA therapy see photochemotherapy pyrogens. 93 minoxidil (Rogaine) 43. hair loss and 158 6-mercaptopurine 138 mesenchymal-derived dermal papilla 86 methotrexate 137. 166 psycho-physical trauma 147 psychogenic pseudoeffluvium 151 psychopharmacologic medications 140–3 pull-tests 10. 6 melanocytes 6. alopecia areata and 34. 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. 169 pulse therapy.Index 179 McKusick Mendelian Inheritance in Man (MIM) 83 Major Histocompatibility Complex (MHC) 19 malignant diseases 149 maprotiline 143 mechlormethamine 137 medulla 2. 163. 163 pseudopelade (PP) 38. 156. 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. 33f. 156. 170 use of betamethasone dipropionate and 48f monoamine oxide inhibitors 143 morphea 156 mouse teratogenicity test 53 myasthenia gravis 22 nail dystrophy. 147 prednisolone. therapy and 113–14 peri-infundibular lymphocytic infiltrate 166 perifollicular interface dermatitis 165 pernicious anemia 22 pheomelanin 6 photochemotherapy (PUVA) 64–5. 93. 37 National Alopecia Areata Foundation (NAAF) 19. hairless 26 micro-grafting 132 Microsporum canis 42 mini-grafting 132 miniaturized hairs 88. 24–5 melphalan 18. 104 propylthiouracil 139 prostate cancer. AGA and incidents of 88 protriptyline 143 pruritus 158. 42 patient. history of 9 patient expectations. 33f oral contraceptives 143 oral cyclosporine 22 outer root sheath (ORS) 2. 37.
33f skin diseases. 16. 10t. 10t. 148 thyroid screening 9 thyroid stimulating hormone test (TSH) 98 thyrotoxicosis 139. 69 topical ophthalmic beta-blockers 143 trachyonychia 34 traction alopecia 10t. acne) syndrome 87 Salmonella typhimurium 51 sarcoidosis 156 scalp cellulitis of 171f physiology of 1–8 scalp biopsies 14–15f. 134. 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. intralesional and systemic 43 stress alopecia areata and emotional 24 telogen effluvium and psychological 150 striae. 27. 138 thyroid dysfunction 16 thyroid function assessment 140 thyroid influences 21. 142f acute and chronic 147–53 alopecia areata and 27. 105. 51–64. 167 topical immunotherapy 43. 16. 4f syphilitic alopecia 27. 98. 27. 25 support groups 69 suprabulbar area 1. 156 scalp irritation. 108 squamous cell carcinomas 167 squaric acid dibutyl ester (SADBE) 26. 151. hair loss and 144 thiotepa 137. 28. alopecia. 28 systemic diseases 136 systemic erythromycin 171 targeted follicular gene therapy 114 telangiectasia 158 telogen effluvium 9. 96f.180 Index renal failure 149 respiridone 143 reticular alopecia areata 30. 33f Retin-A 108 rifampin 171 Rogaine see Minoxidil S phase-specific drugs 138 SAHA (seborrhea. cicatricial alopecias and 163 tyrosine 6 ulcerative colitis 22 valproic acid (VPA) 142 vasopressin 138 . 38 triparanol 144 tufting. alopecia and severe 136 Smyth chicken model 25 soriatane 144 spironolactone 101. 155 cross-section of 8f positive pull test 96 temporal triangular alopecia (TTA) 42 terminal-vellus hair ratio 27. 38. 134 testosterone 85 thalidomide 169 thallium. systemic steroids and 47 substance P (SP) expression 24. 52 steroid-metabolizing enzymes 85 steroids systemic 22. minoxidil and 10 scalp lesions 158 scalp prostheses 68f scalp psoriasis 167 scalp reduction 169 scarring alopecia see cicatricial alopecia sebaceous epithelium. 140 tinea capitis 9. 46–7 topical. 51. hirsutism. evaluation of 16 sex hormone binding globulin (SHBG) 105 short-contact therapy 49 shortened anagen (SA) 138 sisapho 30. 95 differential diagnosis 38. 134 drug-induced 139–44 pathology of 28 types of 138–9 in women 86 telogen hairs 6. loss of 165 seborrheic dermatitis 100 serotonin reuptake inhibitors 143 sertraline 143 serum ferritin. 28.
98. 108–9 Woods light examination 42 zolpidem 143 . 138 vincristine 137. 64 women AGA in 88. 91f finasteride and 104 hair loss in 86 hair transplantation in 131–2 treatment of AGA in 101.Index 181 vellus hairs 6. 138 vitiligo 63f. 99f vellus-like hairs 7f vertex pattern balding 87 vertex thinning 90 vinblastine 137. 89f.