Central centrifugal cicatricial alopecia an approach to diagnosis and management

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1 Review Central centrifugal cicatricial alopecia an approach to diagnosis and management Pamela Summers, MD, MBA, Angela Kyei, MD, MPH, and Wilma Bergfeld, MD Cleveland Clinic, Department of Dermatology, Cleveland, OH, USA Correspondence Dr. Angela Kyei, MD, MPH 9500 Euclid Ave, A61 Cleveland OH USA Funding: Wilma Bergfeld is co-investigator of a study on Central Cicatricial Centrifugal Alopecia sponsored by the North American Hair Research Society and funded by Proctor and Gamble. Abstract Central centrifugal cicatricial alopecia (CCCA) occurs primarily in African American women and is the most common cause of scarring hair loss in this population. Since the mid 20th century, hair care practices of African American women have been associated with CCCA, although there is developing evidence that the etiology of CCCA may be multifactorial. Clinically diagnosing CCCA may be challenging because it can resemble female pattern hair loss, alopecia areata, lichen planopilaris, or telogen effluvium. Therapeutic options are limited, thus the goal of treatment is to prevent progression of disease because once scar formation occurs, it is irreversible. Drugs (generic US Trade Name): Tacrolimus Protopic Pimecrolimus Elidel Minoxidil Rogaine Ketoconazole Extina, Kuric, Nizoral A-D, Nizoral Topical, Xolegel Zinc pyrithione BetaMed [OTC]; Denorex Daily Protection [OTC]; DermaZinc [OTC]; DHS Zinc [OTC]; Head & Shoulders [OTC]; KeraCare Dry and Itchy Scalp [OTC]; Selsun Salon [OTC]; Skin Care [OTC]; T/Gel Daily Control [OTC]; Zincon [OTC]; ZNP Bar [OTC] Tetracycline Hydroxychloroquine Plaquenil Mycophenolate mofetil CellCept, Myfortic Cyclosporine Neoral, Sandimmune, Gengraf, Restasis Pioglitazone Actos Introduction Central centrifugal cicatricial alopecia (CCCA) occurs primarily in African American women and is the most common cause of permanent hair loss in this group. 1,2 Prevalence increases with age as women are most commonly affected in the late second or third decade of life, and many do not seek treatment until the hair loss is extensive and/or permanent. 2 4 In cicatricial alopecias, the hair follicle is destroyed and replaced by fibrous tissue. 5 In CCCA, hair loss begins at the vertex or mid scalp and slowly progresses centrifugally. 2 Histopathologically, the predominate inflammatory cellular infiltrate of CCCA is lymphocytic. 5 The etiology of CCCA is unclear; however, the hair care practices of African American women have been implicated since Since the early 20th century, African American women have used hot combs, heated metal combs that reach temperatures above 300 ªF, to temporarily straighten hair. 7 Later reports associate this type of scarring alopecia with other grooming techniques, such as the use of chemical relaxers and traction styles, 1457 ª 2011 The International Society of Dermatology International Journal of Dermatology 2011, 50,

2 1458 Review Central centrifugal cicatricial alopecia Summers, Kyei, and Bergfeld which include tight hair braids, ponytails, and sewn-in or glued hair weaves. 1,7 10 A survey developed by the North American Hair Research Society (NAMHRS) completed in Cleveland, Ohio, revealed that 28% of the 326 African American female participants have clinical evidence of CCCA. 11 Ninety-four percent of these women use chemical relaxers. In this cohort, there was an increased rate of adult acne, difficulty conceiving, bacterial skin infections, and diabetes mellitus (DM) type II, suggesting hair-grooming practices are not the only contributing factor to CCCA, but inflammatory, hormonal, and autoimmune processes may be confounding factors. 11 A defect in the peroxisome proliferator-activated receptor-gamma (PPAR-c) may have significance. 12 PPAR-c has a role in anti-inflammatory mechanisms and lipid metabolism in the pilosebaceous unit. A defect in PPAR-c has been implicated in the lymphocytic cicatricial alopecia lichen planopilaris (LPP), thus it can be speculated to have a similar role in CCCA. Thiazolidinediones are a class of medications used to treat type 2 DM by increasing the activity of the nuclear receptor PPAR-c and have been effectively used to treat LPP. 13 Potentially, a link between inflammation, DM, and CCCA may exist. Also, the cause of CCCA is multifactorial with genetics also contributing to the condition, as sisters of patients with CCCA are significantly more likely to have CCCA. 9,14 Theoretically, environment may have a role given sisters are raised with the same hair-grooming techniques. The role of the cosmetologists has not been explored in the etiology and management of CCCA. An unpublished survey of African American women found that of the 68.3% of women who relax their hair, 59.5% have the procedure completed by a cosmetologist. 11 Another survey found that the cosmetologist initially found the hair loss in 21% of those surveyed. 9 Thus, cosmetologists may be confounders in this disorder. When evaluating a patient, determining the type of hair loss can be challenging. While CCCA is a scarring alopecia, it clinically resembles the non-scarring alopecia of female pattern hair loss (FPHL) with subtle differences (Fig. 1). 8,15 Alopecia areata, LPP, or telogen effluvium may also be considered in the differential diagnosis. 8 There are several key factors that should be considered when trying to determine the correct diagnosis. These include a thorough clinical history, clinical exam, and laboratory evaluations. Below is a method for this process. consultation may not be indicative of CCCA, it is important to obtain all information to differentiate the reason for hair loss. An individual may have underlying CCCA mimicking FPHL, LPP, telogen effluvium, or alopecia areata. 8 Determining the onset and duration of hair loss is important. Age of onset for CCCA typically begins later in the second or third decade of life, while FPHL may begin at puberty or older. 2,3,16 A grooming history is necessary. For African American women, this includes asking about chemicals placed on the hair (relaxers, Jheri curl, color), heat applied to the hair, and hair brush used (boar bristle or wide spaced with smooth round tips). 14 Use of a boar bristle brush may contribute to hair breakage. History of use of hair weaves (sewn-in or glue-in) and hair braiding should be obtained. Inquire about breakage, decreased density, shedding, or bare areas of the scalp, as these events occur with varying etiologies such as trichorrhexis nodosum, telogen effluvium, or FPHL. Burning, scaling, tenderness, and pruritis are symptoms that may also be present, which could be indicative of seborrheic dermatitis or tinea capitis. 10,17,18 Tenderness and uncomfortable pulling have also been associated with CCCA. 9,10 Shampoo usage should be determined as it may debride scale and crust. Gynecological history, including menstrual cycle, pregnancy history or infertility, age at menopause, acne, and hirsutism may indicate androgen access, which is often Clinical history A complete history is essential in diagnosing women with hair loss (Table 1). While all questions asked in the initial Figure 1 CCCA International Journal of Dermatology 2011, 50, ª 2011 The International Society of Dermatology

3 Summers, Kyei, and Bergfeld Central centrifugal cicatricial alopecia Review 1459 Table 1 Clinical history Age of onset Styling and practice history (note frequency) Relaxers Permanent wave (e.g. Jheri curl, Ferm Ò, Wave Nouveau Ò ) Hair weaves (sewn-in or glue-in) Hair braiding (with and without extended hair) Hair coloring Heat applied to hair Hot comb Flat iron Curling iron Blow-dryer Hair brush used (boar bristle vs. plastic round tip) Hair breakage Percentage of density loss Bare scalp areas Symptoms Burning Scaling Tenderness Itching Shampoo Frequency Type of shampoo (e.g. ketoconazole) Gynecological history Last menstrual period Frequency of menstrual cycle Pregnancy history Infertility history Age of menopause History of acne History of hirsutism History of seborrheic dermatitis History of obesity History of autoimmune disease (e.g. DM, thyroid, lupus erythematosus) Medication history (new or change of medications, including 6 months prior to hair loss) Surgeries or major illnesses (include 6 months prior to hair loss) Nutritional history Red meat intake Crash diets Major life stressors Family history of hair loss DM, diabetes mellitus. associated with FPHL. 16,17 Medication history should include information six months prior to hair loss. Newlyprescribed medications, over-the-counter medications, history of oral contraceptives, and hormone replacement therapy should be included. It is important to note weight changes, illnesses, or surgeries that may have occurred in the recent past, including six months prior to hair loss, as they are associated with telogen effluvium. 17 Nutritional history, to determine low protein or low iron status, is important in vegetarians or crash dieters and is known to exacerbate FPHL. Elevated personal stress level may also contribute to hair loss through pro-inflammatory effects that negatively impact the hair follicle. 19 Obtain personal history of autoimmune disorders because DM, thyroid, and lupus erythematosus can present with hair loss. 20,21 Additionally, family history of hair loss should be obtained. 9,14,17 Clinical exam Hair pieces, weaves, or accessories should be removed to obtain an accurate assessment of the hair loss (Table 2). 14 Determine the pattern of hair loss as either localized or diffuse and assess the density of the hair. 16 The hair loss of CCCA begins near the vertex or mid scalp and slowly progresses centrifugally. 2,15 Signs of scarring, such as absence of follicular ostia, should be noted, preferably with a dermatoscope. In FPHL, visible follicular openings are present. If perifollicular erythema and follicular keratosis are present, then LPP should be considered. 14,16 A central scalp alopecia scale for African American women (Fig. 2) is useful to grade the hair loss. 20 Examination should include not only the scalp but all hair-bearing areas to ensure other forms of alopecia are not present. Signs of inflammation, including erythema, tenderness, as well as scale, should be noted. Follicular pustules or an active inflammatory border of the patch of hair loss may be present in early disease. 2 A Wood s light can be used to determine the presence of yeasts or dermatophytes. Many organisms of the Microsporum genus fluoresce bright green. 22 Of the Trichophyton genus, typically only T. schoenleinii appears as a faint blue. This is important as CCCA has masked as tinea capitis. 16,18,20 Dried soap, Table 2 Clinical exam Vital signs blood pressure, weight, note of body habitus Remove hair pieces, weaves or accessories Pattern of loss Location Localized Diffuse Density of hair Evaluate follicular ostia (examine with at least 2 magnification) Note erythema, scale and/or inflammation Wood s lamp Green fluorescence dermatophyte (typically Microsporum) Orange fluorescence Malassezia (Pityrosporum) Faint blue fluorescence Trichophyton schoenleinii Bright white dried soap, lint, ointments and scale Breakage (note length and diameter) Pull test Acne Evaluate all hair-bearing areas Note loss or hirsutism ª 2011 The International Society of Dermatology International Journal of Dermatology 2011, 50,

4 1460 Review Central centrifugal cicatricial alopecia Summers, Kyei, and Bergfeld 1a 2a 0 1b 2b lint, ointments, and scale can create bright white falsepositive findings. 17,22 Pin-point orange fluorescing would be indicative of the causative organism of Malassezia (Pityrosporum) in seborrheic dermatitis. 17 The quality of the hair shaft should be evaluated by assessing the breakage, length, and diameter. Blunt hair tips with broom stick ends may indicate breakage or trichorrhexis nodosa. 14,16 Hair damaged secondary to heat chemical processes may show trichoptilosis, or a longitudinal splitting of the distal end of the hair. 23 A pull test to determine if there is active shedding should be performed. 16,21,24 Pulling hairs in an adult without hair loss will typically yield 2 5 telogen hairs, with telogen effluvium exceeding this number by 3 5 times. 21 Signs of androgen excess, including hirsutism, acne, frequent seborrheic dermatitis, and obesity, should be noted as they can be associated with FPHL. Body habitus should be noted with weight assessment and blood pressure measurement, as obesity, hypertension, acne, and hirsutism are associated with polycystic ovarian syndrome. 25 Such significant findings are related to increased cardiovascular risks, which may result in referral to a physician who can assist with modifying these risk factors. Laboratory evaluation 3a 4a 5a Figure 2 Adapted with permission from the central scalp alopecia photographic scale in African American women. The correlation of hair loss patterns to probable clinical diagnosis is as follows (no histological confirmation): Pattern 0: normal hair density, no hair loss; Patterns 1 and 2: differential diagnosis would include early CCCA, FPHL and telogen effluvium (acute and chronic); Patterns 3 5: probable CCCA 14 3b 4b 5b Females being evaluated for CCCA should be assessed for triggers resulting in various forms of hair loss (Table 3). These include those that would lead to FPHL, such as androgen access, including serum total and free testosterone and dehydroepiandrostenedione sulfate (DHEA-S). 16,17 Extremely elevated androgen levels and presence of virulization may be a sign of a virulizing tumor. 26 If the total testosterone or free testosterone is elevated or if galactorrhea is present, assess a prolactin level. 26 Elevation of any of these may prompt referral to an endocrinologist for further evaluation. Hyphae can be detected through a potassium hydroxide scraping of scale and fungal culture completed if indicated to ensure it is not tinea capitis. 16 A Wood s lamp can also be used, as stated in the previous section, to check for dermatophytes and Malassezia (Pityrosporum). If bacterial infection is suspected, a bacterial culture should be obtained. 17 An antinuclear antibody level may be ordered if systemic lupus erythematosus is suspected. Screening for syphilis is recommended if the patient possesses risk factors. 16,17 Nutritional deficiencies should be identified. Iron deficiency is associated with FPHL as well as telogen effluvium, and can be screened by checking serum ferritin. 16,26 Vitamin D deficiency has been associated with alopecia in mice, and African-Americans are more likely International Journal of Dermatology 2011, 50, ª 2011 The International Society of Dermatology

5 Summers, Kyei, and Bergfeld Central centrifugal cicatricial alopecia Review 1461 Table 3 Laboratory evaluations Endocrine (androgen excess, pituitary dysfunction, thyroid disease) DHEA-S Testosterone level (free and total) Prolactin level TSH level Free thyroxine (T4) Microsomal antibody Infectious Fungal scraping and culture Bacterial culture Syphilis serology Autoimmune Antinuclear antibody Microsomal antibody Nutritional Ferritin level Vitamin D (25-hydroxyvitamin D) level Vitamin A level Zinc level Systemic (anemia, renal disease, liver disease) Complete blood count Comprehensive metabolic panel Two 4-mm punch scalp biopsies of an active edge Figure 3 Punch biopsy, 4 mm, H&E, 4 magnification, vertical section, demonstrating a reduction in terminal hair follicles, increased and widened fibrous tracts, perifollicular infundibular lymphocytic infiltrate, loss of sebaceous glands and hair follicles with fibrosis of the dermis DHEA-S, dihydroepiandrostenedione sulfate; TSH, thyroid-stimulating hormone. to have Vitamin D insufficiency. 27,28 Excessive vitamin A and zinc deficiency is also associated with alopecia. 24,29 A complete blood count and comprehensive metabolic panel should be checked to assess for anemia and renal and liver disease. 17 Thyroid function should be assessed as it is a frequent cause of hair loss. Two 4-mm punch biopsies of an active edge should be obtained to confirm diagnosis; one for horizontal and the other for vertical viewing histopathologically (Figs. 3, 4, and 5). In CCCA, a reduction in terminal hair follicles, increased and widened fibrous tracts, and perifollicular infundibular lymphocytic infiltrate would be present. In late stages, there is loss of sebaceous glands and hair follicles with prominent hyalinization or fibrosis of the dermis. 2,16,17 Treatment Treatment of CCCA is challenging as the goal is to stop progression of disease, rather than regrowth of hair, by administering anti-inflammatory agents (Table 4). 14 Once the hair follicle has been replaced by scar tissue, regrowth is not possible. Unfortunately, many patients seek treatment options after entering this stage of the disease. 2 Stress reduction techniques should be introduced and symptoms are used to guide treatments as they may be indicative of active disease. 14 Follow-up should occur every 3 4 months. Figure 4 Punch biopsy, 4 mm, H&E, 10 magnification, vertical section, demonstrating increased and widened fibrous tracts and perifollicular infundibular lymphocytic infiltrate Because hair-grooming techniques have been implicated in CCCA, discontinuation of potential damaging hair-grooming practices should be encouraged. This includes decreased heat to the scalp and modification of the application of chemical relaxers and permanent wave products. 7 Although there are conflicting data on women with CCCA in regards to its association with hair relaxer frequency application or scalp burns, 9,10 encourage the patient to base the scalp prior to relaxer, use a milder strength chemical relaxer, minimize duplicate application ª 2011 The International Society of Dermatology International Journal of Dermatology 2011, 50,

6 1462 Review Central centrifugal cicatricial alopecia Summers, Kyei, and Bergfeld Table 4 Treatment Stress reduction techniques Modify application and frequency of chemical relaxers and permanent wave products Avoid sewn-in or glued-in hair weaves Avoid tight hair braiding Avoid hair gels and sprays Intralesional triamcinolone acetonide Topicals High-potency corticosteroids Tacrolimus or pimecrolimus Others (may assist by treating concomitant conditions) Minoxidil Ketoconazole shampoo Zinc pyrithione shampoo Systemic Anti-inflammatory antibiotics (e.g. tetracycline) Hydroxychloroquine Mycophenolate mofetil Cyclosporine Thiazolidinediones (e.g. pioglitazone) Nutritional supplementation Biotin and zinc supplement Multivitamin Vitamin D supplement as needed Iron supplement as needed Wear natural hairstyle Camouflage techniques Wigs Color sticks Micropigmentation Hair transplant Support in collaboration with cosmetologist to previously relaxer-treated hair, and decrease frequency of relaxer touch-ups to decrease potential damage. Encourage avoidance of sewn-in or glued-in hair weaves and tight braiding of hair. Hardening gels and sprays should be avoided as they increase the hair s fragility. 7 Topical therapy may help with symptom alleviation or if dense perifollicular inflammation is present per biopsy. 14 High-potency topical corticosteroids, topical tacrolimus or pimecrolimus, and intralesional injections of triamcinolone acetonide have been used. Residual hair follicles may benefit from topical minoxidil by extending their anagen phase, which would also help FPHL if it is coexistent. 14 Inflammatory alopecias benefit from the use of zinc pyrithione and ketoconazole shampoos as they assist in the debridement of scalp scale. These shampoos and topical corticosteroids can also help with the treatment of concomitant microorganisms such as Malassezia (Pityrosporum) and seborrheic dermatitis. 17 In individuals with active spreading disease, antiinflammatory antibiotics, such as tetracycline mg daily, may slow disease activity. Antimalarials, such as hydroxychloroquine 200 mg twice daily, are Figure 5 Punch biopsy, 4 mm, H&E, 20 magnification, horizontal section, demonstrating perifollicular infundibular lymphocytic infiltrate antilymphocytic and are steroid-sparing agents that have been used. Medication guidelines should be followed prior to antimalarial administration. Recalcitrant active disease has been treated with mycophenolate mofetil or cyclosporine. 1,7,14 Nutritional optimization is potentially beneficial given that many nutritional deficiencies, such as biotin, zinc, and vitamin D, are associated with various forms of alopecia. 21,27 Treatment of infections secondary to dermatophytes or bacteria should be completed with antifungals or antibiotics, with the latter based on bacterial culture sensitivities. Natural hairstyles, as well as camouflaging techniques, are also an option. Camouflage techniques include wigs, color sticks or crayons, and/or micropigmentation. 7 Hair transplantation is an option, but should be done only if the inflammatory process has been controlled with medical therapy for at least one year. A scalp biopsy should be completed to prove cessation of inflammation. 7 CCCA is challenging for hair transplantation as the presence of scarring can decrease the transplanted graft survival rate. Also consider collaborating with the patient s cosmetologist as many African American women utilize them for routine services for hair care. Conclusion Central centrifugal cicatricial alopecia (CCCA) can often be a devastating disease as it results in permanent hair loss. The etiology remains unclear; however, current associations include hair-grooming techniques of women of African descent. Both clinical and histological information is needed for diagnosis. Early treatment can enhance regrowth, while late treatment prevents progression of International Journal of Dermatology 2011, 50, ª 2011 The International Society of Dermatology

7 Summers, Kyei, and Bergfeld Central centrifugal cicatricial alopecia Review 1463 disease and has limited regrowth potential. As we move forward, more studies are needed to further elucidate this disorder. Questions 1. Histopathological classification of CCCA is: a. lymphocytic b. neutrophilic c. non-specific d. mixed 2. Hair care practices associated with CCCA include: a. boar bristle hair brush use b. chemical relaxers c. hair coloring d. shampoo frequency 3. Which clinical finding would be more indicative of CCCA? a. decreased follicular ostia b. hirsutism c. positive pull test d. positive Wood s lamp examination 4. What would you suggest to a patient with CCCA? a. decrease the frequency of application of chemical relaxer b. increase the application strength of the chemical relaxer c. sewn-in hair weaves are preferred over glued-in hair weaves d. use hair gels instead of hair spray to style hair 5. The laboratory evaluation that would confirm diagnosis of CCCA is: a. antinuclear antibody b. potassium hydroxide preparation of scalp scale c. punch biopsy d. testosterone level 6. Which of the following medications has been used to treat CCCA? a. cyclosporine b. mycophenolate mofetil c. tetracycline d. all of the above 7. Select the laboratory value more likely to be found deficient in your patient with CCCA? a. vitamin A b. vitamin B12 c. zinc d. vitamin D 8. The medication more likely to assist in decreasing the progression of CCCA is: a. colchicine b. dapsone c. doxycycline d. itraconazole 9. In what age group does CCCA typically present? a. 1st decade of life b. 3rd decade of life c. 7th decade of life d. all of the above 10. Which of the following are hair options for patients with CCCA? a. color sticks b. hair transplant c. natural style d. all of the above References 1 Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol 2009; 60: Whiting DA, Olsen EA. Central centrifugal cicatricial alopecia. Dermatol Ther 2008; 21: Khumalo NP, Jessop S, Gumedze F, Ehrlich R. Hairdressing and the prevalence of scalp disease in African adults. Br J Dermatol 2007; 157: Khumalo NP, Jessop S, Gumedze F, Ehrlich R. Hairdressing is associated with scalp disease in African schoolchildren. Br J Dermatol 2007; 157: Mirmirani P, Willey A, Headington JT, et al. Primary cicatricial alopecia: histopathologic findings do not distinguish clinical variants. J Am Acad Dermatol 2005; 52: LoPresti P, Papa CM, Kligman AM. Hot comb alopecia. Arch Dermatol 1968; 98: Callender VD, McMichael AJ, Cohen GF. Medical and surgical therapies for alopecias in black women. Dermatol Ther 2004; 17: Sperling LC, Sau P. The follicular degeneration syndrome in black patients. Hot comb alopecia revisited and revised. Arch Dermatol 1992; 128: Gathers RC, Jankowski M, Eide M, Lim HW. Hair grooming practices and central centrifugal cicatricial alopecia. J Am Acad Dermatol 2009; 60: Nnoruka EN. Hair loss: is there a relationship with hair care practices in Nigeria? Int J Dermatol 2005; 44(Suppl 1): Kyei A, Bergfeld W. Identification of risk factors in the development of central centrifugal cicatricial alopecia in African American women. Accepted for presentation at the 6th World Congress for Hair Research, June 2010, Cairns, Australia. ª 2011 The International Society of Dermatology International Journal of Dermatology 2011, 50,

8 1464 Review Central centrifugal cicatricial alopecia Summers, Kyei, and Bergfeld 12 Karnik P, Tekeste Z, McCormick TS, et al. Hair follicle stem cell-specific PPARgamma deletion causes scarring alopecia. J Invest Dermatol 2009; 129: Mirmirani P, Karnik P. Lichen planopilaris treated with a peroxisome proliferator-activated receptor gamma agonist. Arch Dermatol 2009; 145: Fu JM, Price VH. Approach to hair loss in women of color. Semin Cutan Med Surg 2009; 28: Olsen EA. Female pattern hair loss and its relationship to permanent/cicatricial alopecia: a new perspective. J Investig Dermatol Symp Proc 2005; 10: Shapiro J. Clinical practice. Hair loss in women. N Engl J Med 2007; 357: Harrison S, Piliang M, Bergfeld W. An approach to hair loss in women. Cosmet Derm 2009; 22: Chiang C, Price V, Mirmirani P. Central centrifugal cicatricial alopecia: superimposed tinea capitis as the etiology of chronic scalp pruritus. Dermatol Online J 2008; 14: Arck PC, Handjiski B, Hagen E, et al. Indications for a brain-hair follicle axis (BHA) : inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P. FASEB J 2001; 15: Olsen EA, Callender V, Sperling L, et al. Central scalp alopecia photographic scale in African American women. Dermatol Ther 2008; 21: Olsen EA. Clinical tools for assessing hair loss. In: Olsen EA, ed. Disorder of Hair Growth: Diagnosis and Treatment, 2nd edn. New York, NY: McGraw-Hill Professional, 2003: Asawanonda P, Taylor CR. Wood s light in dermatology. Int J Dermatol 1999; 38: Whiting DA. Hair shaft defects. In: Olsen EA, ed. Disorder of Hair Growth: Diagnosis and Treatment, 2nd edn. New York, NY: McGraw-Hill Professional, 2003: Fiedler VC, Gray AC. Diffuse alopecia: telogen hair loss. In: Olsen EA, ed. Disorder of Hair Growth: Diagnosis and Treatment, 2nd edn. New York, NY: McGraw-Hill Professional, 2003: Lo JC, Feigenbaum SL, Yang J, et al. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: Olsen EA, Messenger AG, Shapiro J, et al. Evaluation and treatment of male and female pattern hair loss. JAm Acad Dermatol 2005; 52: Malloy PJ, Wang J, Jensen K, Feldman D. Modulation of vitamin d receptor activity by the corepressor hairless: differential effects of hairless isoforms. Endocrinology 2009; 150: Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, Arch Intern Med 2009; 169: Tosti A, Pazzaglia M. Drug reactions affecting hair: diagnosis. Dermatol Clin 2007; 25: Answers 1. a. 2. b. 3. a. 4. a. 5. c. 6. d. 7. d. 8. c. 9. b. 10. d. International Journal of Dermatology 2011, 50, ª 2011 The International Society of Dermatology