CENTRAL CENTRIFUGAL CIcatricial

OBSERVATION Hair Breakage as a Presenting Sign of Early or Occult Central Centrifugal Cicatricial Alopecia Clinicopathologic Findings in 9 Patients Valerie D. Callender, MD; Dakara Rucker Wright, MD; Erica C. Davis, MD; Leonard C. Sperling, MD Background: Central centrifugal cicatricial alopecia is the most common form of cicatricial alopecia in African American women. Treatment options are limited and mostly aimed at halting further hair loss but rarely result in hair regrowth. Therefore, it is important to recognize early clinical signs, perform a confirmatory biopsy, and begin treatment promptly. We have observed that hair breakage may be a key sign of early central centrifugal cicatricial alopecia, and this association is not clearly described in the literature. Observations: Nine patients with hair breakage on the vertex with or without scalp symptoms underwent scalp biopsies as part of their evaluation. Of these, 8 had histologic samples adequate for complete interpretation: 5 specimens (63%) showed histologic changes typical of central centrifugal cicatricial alopecia, with 1 of these showing advanced end-stage changes of cicatricial alopecia. Two (25%) revealed premature desquamation of the inner root sheath as the sole finding suggestive of early central centrifugal cicatricial alopecia and 1 (13%) was normal. Conclusions: Although hair breakage can have multiple causes, early central centrifugal cicatricial alopecia must be considered in the differential diagnosis, particularly in women of African ancestry. Histologic evaluation may reveal early or late findings that can help establish the diagnosis. Arch Dermatol. 2012;148(9):1047-1052 Author Affiliations: Callender Dermatology and Cosmetic Center, Glenn Dale, Maryland (Drs Callender and Davis); Department of Dermatology, Howard University College of Medicine, Washington, DC (Dr Callender); Department of Dermatology, Henry Ford Hospital, Detroit, Michigan (Dr Wright); Mid-Atlantic Permanente Medical Group, Lutherville, Maryland (Dr Wright); and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (Dr Sperling). CENTRAL CENTRIFUGAL CIcatricial alopecia (CCCA) is a form of primary cicatricial alopecia that can result in the permanent destruction of hair follicles. It is the most common form of cicatricial hair loss among black women. 1,2 Typically, CCCA presents on the vertex of the scalp and can be divided into early (inflammatory) and late (scarring) stages of disease. 3 Although hair loss is permanent once the hair follicle is replaced with fibrous tissue, recognizing early stages of the disease and promptly initiating treatment may allow for hair regrowth and halt disease progression. 3,4 We have observed that a subset of women with CCCA initially present with hair breakage localized to the vertex. This finding suggested to us that hair breakage may be an early indicator of CCCA. Therefore, we studied 9 African American women who presented with scalp symptoms and hair breakage but with no or minimal hair thinning and underwent scalp biopsy performed as a part of their evaluation for alopecia and/or scalp symptoms. REPORT OF CASES The medical records of 9 patients who presented with hair breakage with and without pruritus, erythema, and scalp were retrospectively reviewed. Hair breakage was identified as discrete zones of abnormally short hair compared with the surrounding hair. The short hairs showed frayed distal tips on microscopic or dermoscopic examination. Information about medical history, current medications, hair grooming practices, and physical examination was noted. Archived histologic slides of 4-mm scalp biopsy specimens from the periphery of the involved area, obtained after patient consent, were reviewed. Tissue was sectioned vertically and horizontally exceptfor1specimen,whichwasonlysectioned vertically because of laboratory error, although adequate histologic examination could be performed. In addition, 1 patient s biopsysamplecouldnotbecompletelyevaluated because of inadequate sections for complete histologic study and was therefore excluded from interpretation. This study was approved by the institutional review board of Schulman Associates Inc. 1047

Table 1. Characteristics of the Study Patients Patient No./ Age, y a Symptoms and Signs 1/40 Severe scalp and itching 2/37 Scalp and itching 3/41 Scalp itching, dry and brittle hair only in crown area 4/41 Scalp itching and 5/35 Scalp itching and 6/50 Intense scalp burning Duration 8mo Estimated Area of Hair Breakage 7 7.5-cm area of hair breakage and decreased hair density on crown, hair lengths 0.5 vs 4.5 cm in other areas Histopathologic Diagnosis Normal; second biopsy 1 year later normal as well Description of HE Stain Normal biopsy; few normal vellus hairs 4 mo Not measured CCCA Vertical sections with 1 follicle show typical changes of CCCA and a follicular scar 4-5 y Not measured CCCA Vertical sections do not show any pathologic findings; however, transverse sections show naked hair shaft indicating follicular destruction, prominent PDIRS affecting several follicles, eccentric epithelial atrophy, and concentric lamellar fibroplasia of a few follicles 3mo 6mo 6mo 6 3-cm hair breakage on central crown with hair lengths of 0.5 cm vs 5 cm in normal areas 5 5-cm area of hair breakage at vertex, hair thinning 13 10-cm area of broken hairs 1-2 cm in length; uninvolved hairs approximately 13-15 cm in length Advanced CCCA CCCA Early CCCA PDIRS, eccentric epithelial atrophy, concentric lamellar fibroplasias, perifollicular chronic inflammation most prominent at the upper isthmus level, and follicular scars PDIRS, eccentric epithelial atrophy, concentric lamellar fibroplasias, perifollicular chronic inflammation most prominent at the upper isthmus level, and follicular scars PDIRS seen in horizontal sections; concentric lamellar fibroplasias and perifollicular chronic inflammation most prominent at the upper isthmus level, seen in vertical sections 7/53 None 5 y Not measured Normal with PDIRS Number and size of follicles normal; there is a single follicle showing evidence of PDIRS b 8/41 Scalp itching and hair bumps 9/45 Scalp itching and reported no hair growth 6mo 2 1-cm of hair loss and thinning with widened part from frontal scalp to vertex Normal with PDIRS A few follicles show PDIRS; otherwise, it is normal; second biopsy 1 y later again showed PDIRS Unknown Not measured Normal with PDIRS A few follicles show PDIRS; otherwise, it is normal Treatment Outcome Itching and burning stopped in a few months with no hair regrowth; lost to follow-up Regrowth at approximately 6-8 mo Regrowth in 10 mo Regrowth after approximately 4 mo but with continued occasional itching Regrowth in 6 mo Lost to follow-up Lost to follow-up Progression of hair loss for 2 y Lost to follow-up Abbreviations: CCCA, central centrifugal cicatricial alopecia; HE, hematoxylin-eosin; PDIRS, premature desquamation of the inner root sheath. a All patients are African American women. b Patient 7 had inadequate sectioning of specimen, so was not included in pathological interpretation and analysis. Table 1 presents the clinical information for the 9 patients. All patients were African American women with a mean (SD) age of 42.6 (5.8) years at initial presentation. Every woman had a history of chemical relaxer use. All but 1 patient had scalp symptoms, with the most common being pruritus in 7 patients (78%). Four patients (44%) had scalp. Three patients (33%) had evidence of localized vertex hair thinning but without obvious cicatricial hair loss. In 6 of the 9 patients (67%), the duration of disease was 8 months or less, with 1 patient presenting only 3 months after the start of symptoms. On examination, hair breakage occurred proximally on the hair shaft (0.5-2 cm from the scalp) in patches localized to the vertex (Figure 1 and Figure 2). Of the 8 biopsy specimens completely evaluated, 5 (63%) demonstrated histologic changes typical of CCCA, 1048

A B Figure 1. Patient 6. Patient has a large area of hair breakage with minimally decreased hair density and scarring. Histopathologic analysis revealed early changes of central centrifugal cicatricial alopecia. Figure 2. Patient 9. Patient had decreased hair density and hair breakage on the vertex of the scalp. Histopathologic analysis revealed premature desquamation of the inner root sheath of a few follicles but an otherwise normal scalp. Figure 3. Hematoxylin-eosin stained specimen from patient 6. A horizontal section through the deep dermis demonstrates early changes of central centrifugal cicatricial alopecia, namely, premature desquamation of the inner root sheath (note the 2 boxed follicles in A; magnified in B; original magnification 40 [A] and 200 [B]). but with varying degrees of severity. One showed more advanced end-stage changes of cicatricial alopecia with destruction of most of the follicles. Another demonstrated premature desquamation of the inner root sheath (PDIRS) and lamellar fibroplasia with perifollicular inflammation but had no evidence of follicular destruction (Figure 3 and Figure 4). The remaining 3 biopsy specimens showed the full complement of histologic findings typical of CCCA (Figure 5), including focal follicular destruction. The sole abnormality found in biopsy specimens from 2 patients (25%) was PDIRS; otherwise, the findings on these scalp specimens were normal. Only 1 patient had completely normal biopsy results (13%), and biopsy was performed again 1 year later. Allpatientswereempiricallyprescribedhigh-potencytopical corticosteroid foam or ointment nightly and corticosteroid shampoo weekly at the first visit. After biopsy results were obtained, patients received intralesional triamcinolone, 5 mg/ml every 4 to 6 weeks for approximately 1 to 3 sessions. Additional treatments varied based on the patient s clinical presentation, symptoms, and physician preference and included ciclopirox shampoo, zinc pyrithione shampoo, doxycycline hyclate, midpotency topical corticosteroid, minoxidil(2%-5%), and/or sulfur salicylic acid corticosteroid compound. As indicated in Table 1, 4 patients (44%) experienced hair regrowth, 1 patient s(11%) hair loss progressed, and 4 patients (44%) were lost to follow up. COMMENT LoPresti et al 5 first described CCCA as hot comb alopecia in 1968, when this type of scarring alopecia was 1049

A B A B Figure 4. Hematoxylin-eosin stained specimen from patient 6. Vertical section from a biopsy site adjacent to the one sampled in Figure 3. At the level of the lower infundibulum, eccentric epithelial thinning, concentric fibroplasia, and mild perifollicular chronic inflammation can be seen (original magnification 200 [A] and 400 [B]). thought to result from the hot liquefied petrolatum created by hot pressing comb use. The theory was that hot pressing oil descended into the follicle, causing chronic inflammation around the upper segment of the hair. Eventually, the external root sheath degenerated with subsequent destruction of the hair follicle and replacement with dense fibrous tissue. 5 The cause of scarring alopecia by hot combing has subsequently been debated. 1,6,7 Although the use of hot combs has significantly decreased over the years, the prevalence of scarring alopecia among black women has not seen a corresponding decrease. 1 In 1992, Sperling and Sau 6 performed a retrospective study on 10 women thought to have hot comb alopecia, but most did not have a significant history of hot comb use. Because of the poor correlation of hot comb use and onset and progression of the disease in these patients, the authors concluded that the use of hot combs may contribute to follicular damage only among women who may be predisposed to follicular damage but was not the single cause of this type of scarring alopecia. The term follicular degeneration syndrome replaced hot comb alopecia based on characteristic histologic findings. 1 However, in 2001, the North American Hair Research Society sponsored Workshop on Cicatricial Alopecia recommended use of the current term CCCA, which was intended to be more descriptive and encompass prior terms, such as follicular degeneration syndrome, hot comb alopecia, and pseudopelade, in African Americans. 8 Despite this descriptive term, CCCA remains an incompletely understood inflammatory process that can result in permanent hair loss involving much of the scalp. Histologically, CCCA demonstrates varying levels of inflammation, ranging from minimal to intense perifollicular lymphohistiocytic infiltration involving the infundibulum and isthmus, typically leading to replacement of terminal hair follicles with fibrous tracts. 9 In Figure 5. Hematoxylin-eosin stained specimens from patient 5. A, Two follicles sectioned at the level of the lower dermis show premature desquamation of the inner root sheath. B, At the level of the lower infundibulum, these follicles show concentric, lamellar fibroplasia and a moderate amount of perifollicular, chronic inflammation (original magnification 200). addition, PDIRS is observed, followed by eccentric atrophy of the outer root sheath epithelium, concentric lamellar fibroplasia, and subsequent hair granulomas. 2,6,10 Residual arrector pili muscles may remain within the resulting dense fibrosis. 10 Lamellar fibroplasia, PDIRS, and perifollicular inflammation are typical findings of CCCA. However, the presence of PDIRS in an otherwise histologically normal scalp specimen is highly suggestive of early CCCA, unlike other forms of scarring alopecia, where PDIRS is only associated with well-established, severe inflammation. 11 This particular finding is important in the pathogenesis of disease because it may predispose the affected follicles to external injury. 12 On clinical examination, erythema and scaling may indicate the presence of inflammation around hair follicles, and at any stage of the disease, patients may experience pruritus and/or scalp. 9 Our cases reveal that most patients experienced pruritus (78%) and scalp (44%). Early in the disease, the scalp may appear normal or exhibit hair breakage or decreased hair density in an area measuring only a few centimeters in diameter. 12 However, it may be difficult to obtain an accurate duration of symptoms due to the insidious 1050

Table 2. Differential Diagnosis of Hair Breakage Hair care products Chemical relaxers (straighteners) Permanents (curly perm) Hair dyes Styling products (gel, hair spray, spritz) Hair care practices Heat styling (eg, hot combs, blow dryer) Excessive brushing/combing Twisted hair styles Hair extensions (from traction or glue) Braids (using synthetic hair) Hair and scalp diseases Early central centrifugal cicatricial alopecia Seborrheic dermatitis a Tinea capitis Androgenetic alopecia b Eczema a Trichotillomania Alopecia areata (with hair regrowth) Systemic diseases Genetic disorders c Syphilis a Damage typically occurs secondary to increased manipulation from scratching. b Miniaturized hair seen with this disorder can mimic hair breakage. c Including argininosuccinic aciduria, trichothiodystrophy, monilethrix, and pili torti associated diseases. onset and slow progression of CCCA in many patients. Hair loss or breakage may be present for years before the patient notices the hair loss. 6 The location of hair breakage, particularly on the vertex, may also make it difficult for patients to notice the onset of hair loss. In fact, Gathers et al 7 found that 51 study patients with CCCA (21%) were first informed of their hair loss by a hairstylist. Most of our patients (67%) had symptoms for 8 months or less. One patient reported symptoms for only 3 months, but her biopsy specimen revealed advanced CCCA, which may be due to the long-term presence of relatively asymptomatic CCCA, unnoticed by the patient until the onset of more severe scalp symptoms or hair breakage. Hair breakage in our patients occurred in a welldemarcated area of the vertex with normal to decreased hair density and minimal to no clinical evidence of scarring. However, in most of our study patients, biopsies revealed a histologic spectrum of findings typical of CCCA. Hair breakage has not been previously reported as a common early clinical finding of CCCA but rather is usually associated with hair care products and practices, systemic diseases, or various scalp disorders (Table 2). In general, women of African descent may be particularly susceptible to hair breakage given the innate fragility of the hair shaft in this population. 13,14 In normal hair development, the cells of the inner root sheath (IRS) cornify before the central hair cortex that will form the hair shaft; thus, the IRS provides a rigid cylinder by which the developing hair shaft is molded and guided outward. 1,15 It is unclear why some patients with early CCCA develop hair breakage, but one could postulate that the lack of a complete IRS leads to disorderly packaging of the hair shaft, particularly the cuticle, causing instability and ultimately breakage. However, this theory would not explain why biopsy specimens from areas of hair Table 3. Clinical Evaluation in Early Central Centrifugal Cicatricial Alopecia Symptoms Scalp Itching Burning sensation Signs Difference in length of hairs on vertex compared with surrounding scalp Vertex or crown only vs patchy or diffuse With or without minimally decreased hair density Absence of hair shaft deformities Tests Negative pull test result a Scalp biopsy a A positive pull test result suggests the presence of proximal trichorrhexis nodosa. breakage in these patients show follicles with intact IRS as well. Whether chemical relaxers or styling with excessive heat causes CCCA remains to be determined; however, it is clear that these hair grooming practices can injure the hair shaft. 16-18 A population study by Kyei et al 19 found that patients with CCCA had a significant increase in the use of traction hairstyles (eg, braids and weaves), which can cause scalp folliculitis, than patients with less severe central hair loss. Thus, the difficulty in attributing hair breakage to early CCCA alone lies in determining the true causative factors because most of the women who develop CCCA also use traumatic hair care practices. On the other hand, not all women who use these traumatic hair care practices develop CCCA. Chemical relaxers, permanents, hair dyes, and heat styling can damage and weaken the hair shaft, whereas certain styling products, such as gels and hair sprays, lead to increased dryness and difficultly manipulating the hair, causing breakage. 13,14,20-22 However, in this study, hair breakage was localized to the exact areas of the scalp normally affected by CCCA, and the presence of CCCA was confirmed by biopsy in most of our cases. Chemical relaxers and permanents, on the other hand, are typically applied to the hair diffusely, and known chemically induced hair breakage is not solely limited to the vertex and often occurs in the anterior or posterior hairline or as several patchy areas on the scalp. 23 More clinical studies are needed to determine the mechanism of follicular abnormalities present in CCCA, which lead to hair shaft damage, and whether traumatic hair care practices also contribute to the development of this finding. Early recognition and treatment of CCCA may halt further progression of the inflammatory and destructive process. Table 3 lists the clinical evaluation that should be performed on patients whose clinical picture may be suggestive of early CCCA but have not yet manifested the characteristic signs of the disease. Physicians must maintain a high index of suspicion even in younger patients. In the study by Gathers et al, 7 more than 20% of patients with CCCA noticed some hair thinning or balding by 30 years of age. When CCCA is suspected, the diagnosis can most often be confirmed by biopsy. In our study, 5 of 8 patients (63%) with hair breakage in the vertex had histologic 1051

changes consistent with CCCA. In the 1 patient with a normal biopsy result, the clinical history and examination were suggestive of CCCA, and the negative result may be attributable to sampling error. Patients 8 and 9 showed a few follicles with PDIRS on histologic examination, which demonstrates the utility of confirmatory biopsy, especially in early disease, and further supports the concept that PDIRS may be the earliest pathologic finding in CCCA. In our cases, we did not find a correlation between duration of disease and severity of histologic inflammation. However, there may be sampling error because only a small portion of a much larger involved area is obtained with a 4-mm punch biopsy. Also, the number of patients in this study is too small to establish the presence or absence of any correlation with confidence. Although 8 of 9 patients had scalp symptoms and 3 had localized hair thinning of the vertex (without evidence of scarring), hair breakage appeared to be the most dependable clue to the underlying diagnosis of CCCA. The symptoms could be attributed to seborrheic dermatitis and the thinning to androgenetic alopecia. Therefore, the physician has to consider a more serious problem and perform a diagnostic biopsy. In summary, we have shown that it is important for physicians to include early CCCA in the differential diagnosis of hair breakage in the crown or vertex even in the absence of obvious scarring alopecia, particularly in patients of African ancestry. Simply advising patients to alter hairstyling habits is not sufficient and may prove to be ineffective. Early initiation of medical treatment will give these patients the greatest chance for halting disease progression and regrowing hair. Accepted for Publication: December 12, 2011. Correspondence: Valerie D. Callender, MD, Callender Dermatology and Cosmetic Center, Annapolis Road, Ste 315, Glenn Dale, MD 20769 (drcallender@callenderskin.com). Author Contributions: Drs Callender and Wright had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Callender and Wright. Acquisition of data: Callender and Wright. Analysis and interpretation of data: Callender, Wright, Davis, and Sperling. Drafting of the manuscript: Callender, Wright, Davis, and Sperling. Critical revision of the manuscript for important intellectual content: Callender, Wright, Davis and Sperling. Financial Disclosure: Dr Callender serves as a consultant, speaker, and researcher for Medicis, Galderma, and Stiefel. REFERENCES 1. Sperling LC, Solomon AR, Whiting DA. A new look at scarring alopecia. Arch Dermatol. 2000;136(2):235-242. 2. Whiting DA, Olsen EA. Central centrifugal cicatricial alopecia. 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