Central centrifugal cicatricial alopecia

INTRODUCTION — Central centrifugal cicatricial alopecia (CCCA) is a type of cicatricial (scarring) alopecia that presents as an area of permanent hair loss on the crown or vertex of the scalp that expands centrifugally (picture 1A-D). Clinical signs of inflammation (eg, inflamed papules, pustules, erythema, or scale) or symptoms (eg, scalp pain, tenderness, or itching) may accompany the hair loss. Women of African descent represent the most common population affected.

Data on the treatments for CCCA are limited, and treatment of the condition is largely guided by expert opinion. Local corticosteroid therapy and oral tetracyclines are well-accepted pharmacologic interventions for CCCA. Although uncertainty remains about the role of hair care practices in the development of CCCA, minimization of practices that can be damaging to the hair and scalp often is recommended.

The clinical manifestations and diagnosis of CCCA will be reviewed here. Other forms of cicatricial and noncicatricial alopecia are reviewed separately. (See "Evaluation and diagnosis of hair loss", section on 'Classification'.)

TERMINOLOGY — The terminology for the condition characterized by central scalp hair loss that is now called "central centrifugal cicatricial alopecia" has evolved over time:

●1968 – The term "hot comb alopecia" is proposed by the authors of a published series of 51 African American women with scarring alopecia involving the central scalp based upon a theory that permanent hair loss resulted from thermal damage to the scalp during use of a hot comb (a specialized metal comb that is heated and used to straighten hair) [1].

●1992 – Replacement of the term "hot comb alopecia" by the term "follicular degeneration syndrome" is proposed based upon a study of 10 African American women with cicatricial hair loss of the central scalp that found histologic evidence of follicular degeneration but did not find a clear association between cicatricial hair loss and a history of hot comb use [2].

●1993 – The term "chemically induced cosmetic alopecia" is proposed by the authors of a London-based retrospective study of eight women of Afro-Caribbean origin based upon the theory that cicatricial alopecia occurred secondary to chemical hair straightening agents [3]; this term did not proceed to widespread use.

●2000 – The term "central centrifugal scarring alopecia" (CCSA) is suggested for hair loss demonstrating the following features: central scalp hair loss, chronic and progressive disease with eventual "burnout," roughly symmetrical expansion with most active disease at the periphery, and both clinical and histologic evidence of inflammation in the active peripheral zone [4]. The authors proposed that the conditions known as follicular degeneration syndrome, pseudopelade (not classic pseudopelade of Brocq), folliculitis decalvans, and tufted folliculitis were all manifestations of CCSA.

●2001 – A workshop on cicatricial alopecia sponsored by the North American Hair Research Society proposed replacement of the term "scarring alopecia" with "cicatricial alopecia," resulting in the change of "central centrifugal scarring alopecia" to "central centrifugal cicatricial alopecia" [5]. The participants also classified central centrifugal cicatricial alopecia as a form of primary lymphocytic cicatricial alopecia. (See "Evaluation and diagnosis of hair loss", section on 'Classification'.)

EPIDEMIOLOGY — Well-designed, population-based studies to clarify the epidemiology of central centrifugal cicatricial alopecia (CCCA) are lacking, precluding precise estimates of the prevalence and incidence of the condition [6]. Based upon data from case reports, case series, and cross-sectional studies, CCCA predominantly affects adult women of African descent with hair that grows in a tightly curled or kinked configuration and appears to be relatively common in this population. Examples of studies that have attempted to identify the prevalence of CCCA include:

●A study of 233 African American women recruited from attendees of a health and beauty symposium and church meetings in the southeastern United States found extensive central scalp hair loss (a finding that suggests but is not exclusive to CCCA) in 6 percent in the studied population [7].

●A study of Black adults in South Africa recruited from churches, community organizations, and hostels found a prevalence of physical findings consistent with CCCA in 3 percent of all women, including 7 percent of 191 women over the age of 50 years, 1 percent of 241 women aged 25 to 50 years, and none of 129 women aged 18 to 25 years, suggesting increasing prevalence with age [8]. Signs of CCCA were not diagnosed in any of the 267 adult male participants. A study of 564 schoolchildren (ages 6 to 21) in South Africa performed by the same authors did not find physical signs consistent with CCCA in children [9].

●A study of 326 African American women in Cleveland, Ohio, recruited for participation from two churches and a health fair found a prevalence of physical findings consistent with "probable CCCA" in 17 percent of the 310 women without a history of alopecia areata or lupus [10]. The relatively high rate of CCCA suggested by this study compared with other reports may have been related to selection bias due to the method of recruitment (patients were recruited via advertisement for a hair study).

The lack of a biopsy to confirm a diagnosis of CCCA complicates the interpretation of the results of the above studies, as there are other potential causes of central scalp hair loss, including the relatively common condition female pattern hair loss. Additional data are needed to clarify the epidemiology of CCCA. (See 'Differential diagnosis' below.)

Although the South African study described above documented no cases of CCCA in men [8], the occurrence of CCCA in Black men has been documented in case reports [11-13].  

Well-documented cases of CCCA in non-Black patients have not been published in the peer-reviewed literature.

PATHOGENESIS — The pathogenesis of central centrifugal cicatricial alopecia (CCCA) is not fully understood. One possible theory is that premature desquamation of the inner root sheath (figure 1) might serve as a critical predisposing factor that leads to a damaging sequence of events. This theory is outlined below [2]:

●Premature desquamation of the inner root sheath develops in a predisposed individual (picture 2).

●As a result of the premature loss of the inner root sheath, the hair shaft presses against the softer outer root sheath, eventually resulting in follicular rupture and a subsequent inflammatory response; alternatively, the premature desquamation of the inner root sheath may facilitate descent of environmental insults, such as chemical relaxers or bacteria, into the lowermost portion of the follicle, inciting inflammation and follicular damage. (See 'Etiology' below.)

●The nonspecific, intense, inflammatory cascade composed of acute and chronic inflammatory cells leads to the destruction of the follicular epithelium in the lower infundibulum and isthmus of the hair follicle, and destruction of the stem cell region of the follicular bulge leads to an inability of the follicle to regenerate (picture 3).

●A follicular scar (a column of connective tissue visible on histologic examination) develops at the site of the follicle (picture 4).

Follicles that are not destroyed by the inflammatory process may heal in a cluster with similarly affected adjacent hairs, resulting in the formation of a common infundibular syncytium surrounded by a zone of fibrosis.

A second theory, favored by the author, is that CCCA may represent a fibroproliferative disorder (FPD). FPDs, like CCCA, are characterized by persistent, low-grade inflammation and irritation that results in end-stage fibrosis [14]. Unlike other scarring alopecias, patients with CCCA often have minimal visible inflammation on the scalp, even in instances when hair loss is active. Some studies have noted an increased risk of fibroids in patients with CCCA [15]. (See 'Etiology' below.)

Additionally, a separate study showed an increased expression of fibroproliferative genes, including those implicated in other FPDs [16]. In this study, gene chip microarray was performed on five patients with biopsy-proven CCCA with biopsies taken from affected and unaffected scalp. Genes implicated in other FPDs were shown to be selectively upregulated and overlapped substantially with other well-known FPDs, most notably idiopathic pulmonary fibrosis and fibroids. This latter finding was consistent with a prior study noting a clinically significant increased rate of fibroids in women affected with CCCA [15].

ETIOLOGY — The cause of central centrifugal cicatricial alopecia (CCCA) is unknown. An association between hair care practices and the development of CCCA has not been proven. Whether CCCA is a heritable condition is also unclear.

Hair care practices — Over the years, associations between CCCA and various hair care practices commonly used by Black women have been proposed, including use of specialized metal combs for hair straightening (hot combs), chemical relaxers, and traction-inducing hair styles (eg, braids and hair weaves). However, the few studies that have explored the relationships between CCCA and hair styling practices have been subject to various forms of bias and have not been performed with sufficient scientific rigor to either prove or disprove a role for these practices in the pathogenesis of CCCA. In particular, an initial theory that this form of alopecia was exclusively a result of hot comb use was discarded after recognition of the condition in women who were not using hot combs or had never used hot combs [1,2].

One study that reported a relationship between traction-inducing hairstyles and CCCA is a survey study of patients seen at a single academic medical center in which 51 African American women with a clinical and pathologic diagnosis of CCCA and 50 African American women without CCCA were asked to recall their hair grooming practices [17]. Although the study found that women with CCCA were more likely to have used hair weaves and cornrow or braided hair styles with artificial hair extensions than women without CCCA and that women with CCCA were more likely to report a history of uncomfortable pulling or tenderness on the scalp from hair weaves or braided hairstyles with extensions, a causative relationship cannot be confirmed based upon these findings. One potential confounding factor is that women with hair loss secondary to CCCA might be more likely to wear braids or weaves in an attempt to camouflage hair loss.

The results of studies evaluating the relationship between chemical relaxer use and CCCA have varied. The survey study of African American women described above did not find statistically significant associations between CCCA and chemical relaxer use or hot comb use [17] nor did a study of 326 African American women volunteers that based a diagnosis of "probable CCCA" on physical examination findings alone [10]. In contrast, the authors of a study of 39 women who presented to a university-based clinic for hair loss in Nigeria (including 20 women with cicatricial alopecia) suggested an association between chemical relaxers and CCCA based upon a finding that women who reported prolonged and frequent use of chemical relaxers were more likely to have features of cicatricial alopecia on physical examination than those who reported lesser use [18]. In addition, the acute development of scarring alopecia in patients who developed persistent discomfort after application of a chemical relaxer has been reported [19].

Genetics — Evidence supporting a heritable component to CCCA, such as a South African study that suggested an autosomal dominant inheritance pattern with partial penetrance and reports of familial cases, have stimulated efforts to identify the genetic factors that contribute to CCCA [20,21]. A study utilizing whole exome sequencing and other techniques to investigate the molecular basis of CCCA found an association between CCCA and loss-of-function mutations in PADI3 [22]. PADI3 encodes peptidyl arginine deiminase type III (PADI3), an enzyme that mediates modification to proteins important for normal hair shaft formation, such as trichohyalin. Mutations in PADI3 are proposed to lead to protein misfolding, contributing to impaired expression and functioning of the enzyme.

Among 58 patients with CCCA analyzed in the study, 14 (24 percent) had at least one of six identified PADI3 mutations. In addition, the study found reduced expression of PADI3 in scalp biopsy specimens from patients with CCCA, and a post-hoc analysis found a higher prevalence of PADI3 mutations in patients with CCCA than in a control group of women of African ancestry.

The absence of PADI3 mutations in many of the patients with CCCA suggests that other factors, both genetic and environmental, also play a role. Further studies are necessary to clarify the genetic basis of CCCA.

Other — A study of 326 African American female volunteers found a significantly greater prevalence of type 2 diabetes and bacterial scalp infections in women with CCCA than women without CCCA [10]. In addition, the authors of a survey study of 38 women with CCCA suggested an association with androgen-related disorders based upon a relatively high prevalence of acne, facial hair, and irregular menses in the study population [23]. An association with uterine leiomyomas has also been suggested by a single institution study including 447 women with CCCA and over 16,000 controls [15]. In this study, the prevalence of uterine leiomyomas was higher among women with CCCA than those without CCCA (14 versus 3 percent; odds ratio 4.68, 95% CI 3.57-6.12). Furthermore, a study suggests an overlap in gene expression patterns between CCCA and uterine fibroids (see 'Pathogenesis' above). However, further study is also needed to confirm these associations.

CLINICAL MANIFESTATIONS — Central centrifugal cicatricial alopecia (CCCA) begins as a subtle patch of partial hair thinning on the midline of the crown of the scalp or vertex of the scalp (ie, posterior portion of the crown or hair whorl zone) (picture 1A). With the passage of time, the severity of hair loss increases and the zone of involvement widens in a centrifugal fashion [23]. Although the crown/vertex is most typically involved in a symmetrical fashion, atypical distributions of hair loss have been reported [24]. Because most patients seek out medical care several years after they first note hair loss, clinicians seldom encounter truly "early" disease [25].

Hair loss from CCCA always is most severe in the center of the expanding patch (picture 1B). Careful examination will reveal loss of follicular ostia between residual hair shafts (a clinical finding characteristic of cicatricial alopecia), although sweat ducts remain intact. Magnification with a dermatoscope is valuable in confirming this finding. In addition, confetti-like or blotchy hyperpigmentation and hypopigmentation are often seen, especially in severe cases (picture 1C). Perifollicular erythema and tufted hairs also may be present.

The degree of visible active inflammation, as evidenced by perifollicular erythema and scaling, follicular papules, or pustules, is highly variable from one patient to another. A majority of patients with CCCA present with seemingly noninflammatory disease resembling common balding. Rarely, patients may exhibit papulopustular disease (picture 1D).

Some patients with CCCA note scalp symptoms localized to the area of involvement, including pain, tenderness, itching, or other dysesthesias [2,25]. However, most patients will be asymptomatic, even in the presence of extensive hair loss.

Unexplained hair breakage may be an early sign of CCCA. A retrospective study of nine patients who presented with hair breakage unaccompanied by pruritus, erythema, or scalp tenderness found histologic findings consistent with CCCA in five of the eight patients with histologic samples adequate for complete evaluation [26]. Of the remaining three patients, two showed only premature desquamation of the inner root sheath (a finding suggestive of early CCCA), and one had normal biopsy findings.

HISTOPATHOLOGY — The very earliest histologic abnormality that can be appreciated in central centrifugal cicatricial alopecia (CCCA) is premature desquamation of the inner root sheath (PDIRS), a feature that usually can be found in at least some of the follicles sampled (picture 2) [2,27]. PDIRS is not unique to CCCA and can be detected in other forms of inflammatory cicatricial alopecia, especially when follicles are severely inflamed or damaged [27,28]. However, when noninflamed or only slightly inflamed follicles demonstrate PDIRS, this feature is very characteristic of CCCA.

In the zone of alopecia, follicles with PDIRS eventually develop eccentric thinning of the follicular epithelium at the level of isthmus and lower infundibulum. In concert with this finding, affected follicles develop perifollicular concentric lamellar ("onion skin") fibroplasia and perifollicular lymphocytic inflammation, again most prominent in the isthmus and lower infundibulum (picture 5).

Although CCCA was classified as a lymphocytic cicatricial alopecia in the North American Hair Research Society workshop on cicatricial alopecia based upon the frequent detection of a lymphocyte-predominant infiltrate in this disorder [5], other types of inflammatory cells can be present, particularly in patients with inflammatory disease demonstrating papules, pustules, tufting of hairs, or confluent erythema (picture 3). Histology of papular or pustular areas will usually show a mixture of acute and chronic inflammatory cells, with varying proportions of neutrophils, histiocytes, lymphocytes, and plasma cells. In contrast, if less-inflamed skin at the border of the affected area is sampled, the predominating histologic findings will be the follicular changes and perifollicular lymphocytic infiltrate observed in more typical cases of CCCA.

Unlike discoid lupus erythematosus and lichen planopilaris, clear-cut vacuolar interface alteration of the follicular epithelium is not found in affected follicles in CCCA. In addition, artifactual clefting between follicular epithelium and stroma is seen only when the follicular epithelium becomes markedly thinned and inflamed. This contrasts with lichen planopilaris, in which epithelial/stromal clefting is an early histologic finding.

DIAGNOSIS — Suspicion for a diagnosis of central centrifugal cicatricial alopecia (CCCA) should arise in a patient with clinical findings of a centrifugally expanding area of alopecia on the central scalp, especially when the patient is a woman of African descent. There are no established criteria for the diagnosis of CCCA. The diagnosis is made when the sum of clinical and histologic findings are more consistent with CCCA than other forms of alopecia.

Patient history and physical examination — For all patients presenting with hair loss, a careful patient history is an important component of the patient evaluation. The history can be very helpful for ruling out other hair disorders and narrowing the differential diagnosis. In general, patients should be asked about the duration of hair loss, progression of hair loss, associated symptoms, medical disorders, medications, dietary changes, and hair care practices. The approach to interviewing patients with hair loss is reviewed in detail separately. (See "Evaluation and diagnosis of hair loss", section on 'Patient interview'.)

In particular, because of the potential for a role of hair care practices in the development of CCCA, a thorough history of hair care practices should be obtained and documented. We inquire about current and prior use of chemical hair relaxers, permanent waves, braided styles (with or without extensions), hair weaves (both sew-in and glued), and heat techniques for straightening hair (eg, hot combs or flat irons).

The physical examination should include a careful examination of the hair and scalp in which both the hair shafts and the scalp skin are carefully examined. Hairpieces and hair extensions should be removed to allow for a thorough examination. Although CCCA is limited to the scalp, performing a full skin examination at the time of initial evaluation also is recommended to aid in the detection of physical findings suggestive of a different hair disorder. (See "Evaluation and diagnosis of hair loss", section on 'Physical examination'.)

In sum, history and physical examination findings that support a diagnosis of CCCA include:

●Hair loss largely confined to the central crown and/or vertex of the scalp.

●A fairly symmetrical zone of alopecia, with most severe hair loss in the center and partial hair loss at the periphery.

●Symptoms such as itching or tenderness largely confined to the zone of hair loss.

●Loss of follicular ostia (a finding consistent with scarring alopecia) evident on visual inspection or dermoscopic examination.

●The patient is a person of African descent.

Not all of these features are evident in all patients with CCCA. In some patients, scarring may be difficult to appreciate on clinical examination, and others may be asymptomatic. Centrifugally expanding central scalp hair loss is the only essential physical finding.

Additional study is necessary to determine the relevance of the findings of a small retrospective study that suggested that unexplained hair breakage in a localized area on the central scalp may be an early sign of CCCA. Our detection of this finding triggers further evaluation with a biopsy. (See 'Clinical manifestations' above and 'Biopsy' below.)

It is important to recognize that more than one form of alopecia may account for hair loss. As examples, nonscarring hair loss related to female pattern hair loss or telogen effluvium may occur concurrently in patients with CCCA [29]. A careful patient history and physical examination can help to identify such patients.

Biopsy — A biopsy is recommended to support a diagnosis of CCCA because it helps to confirm the presence of scarring and aids in identifying features that distinguish CCCA from other cicatricial alopecias. Histologic findings that support CCCA include permanent loss of follicles, premature desquamation of the inner root sheath, concentric lamellar fibroplasia at the level of the follicular isthmus and lower infundibulum, perifollicular chronic inflammation, and the absence of vacuolar changes at the epidermal basal cell layer. (See 'Histopathology' above.)

The site for the biopsy should be chosen carefully to optimize the likelihood of identifying diagnostic findings. The most dependable biopsy site is a location at the periphery of the area of alopecia. The biopsy site should not be completely devoid of hair. Papules and pustules should be avoided. Some dermatopathologists prefer to receive two biopsy specimens when evaluating alopecia to allow for examination of tissue in both vertical and horizontal sections; however, we find that a single biopsy specimen sectioned horizontally usually is sufficient for the diagnosis of CCCA.

In patients in whom hair loss is due to more than one cause, the biopsy site may demonstrate findings of CCCA and another form of alopecia. Not uncommonly, miniaturization of hair follicles is noted, suggesting that female pattern hair loss also is present.

Dermoscopy — The findings of a retrospective study that compared 153 dermoscopic images of CCCA in 51 women with biopsy-proven CCCA and 30 dermoscopic images from 10 patients with other forms of scarring alopecia suggest that dermoscopy may assist with the diagnosis of CCCA [30]. Dermoscopic examination revealed a peripilar white halo in 94 percent of patients with CCCA and was highly specific for the diagnosis of CCCA. In addition, visualization of a peripilar white halo on dermoscopic examination of the biopsy site correlated with the detection of perifollicular concentric fibrosis on histologic examination. Further study will be useful for clarifying the role of dermoscopy in the diagnosis of CCCA (table 1). (See "Overview of dermoscopy of the hair and scalp".)

DIFFERENTIAL DIAGNOSIS — Other nonscarring and scarring hair loss disorders share clinical features with central centrifugal cicatricial alopecia (CCCA). The physical examination and biopsy results are usually sufficient for distinguishing these disorders from CCCA:

●Discoid lupus erythematosus – Discoid lupus erythematosus (DLE) is a form of cicatricial alopecia that commonly affects the scalp (picture 6). Active disease typically demonstrates erythematous, scaly plaques and follicular plugging. Marked pigmentary alteration often occurs in sites of DLE, resulting in hypopigmented, hyperpigmented, or depigmented macules and patches. The classic histologic findings of DLE differ from those of CCCA and include interface dermatitis, a superficial and deep lymphocytic infiltrate, and thickening of the basement membrane. (See "Overview of cutaneous lupus erythematosus", section on 'Discoid lupus erythematosus'.)

●Lichen planopilaris – Lichen planopilaris a form of cicatricial alopecia that is characterized by perifollicular erythema, perifollicular scale, and multiple smooth alopecic patches (picture 7). Like CCCA, the crown of the scalp is a common site of involvement. The histopathologic findings, including an interface dermatitis, wedge-shaped hypergranulosis, and follicular plugging, distinguish lichen planopilaris from CCCA. (See "Lichen planopilaris".)

●Female pattern hair loss – Female pattern hair loss is a nonscarring form of hair loss that results in reduced hair density on the frontal scalp and crown of the scalp (picture 8). The key feature that distinguishes female pattern hair loss from CCCA is the absence of scarring, a finding suggested by the retention of visible follicular ostia. Biopsy can be useful to distinguish these conditions; histologic examination of a site of female pattern hair loss will reveal an increased number of miniaturized hair follicles. (See "Female pattern hair loss (androgenetic alopecia in females): Pathogenesis, clinical features, and diagnosis".)

Additional hair loss disorders that should be considered in the differential diagnosis are trichotillomania, a compulsive hair-pulling disorder that may result in bizarre configurations of alopecia (picture 9), and alopecia areata, a nonscarring form of alopecia that most commonly presents as well-defined, round patches of complete hair loss (picture 10). (See "Alopecia areata: Clinical manifestations and diagnosis".)

TREATMENT — The goals of treatment of central centrifugal cicatricial alopecia (CCCA) are to promote hair regrowth, to arrest or slow disease progression, and to reduce symptoms. Although some hair regrowth can occur in sites of alopecia secondary to CCCA, hair will not regrow from follicles that have been permanently damaged by the disease process. Thus, initiating treatment in the early stages of disease is critical for maximizing the likelihood of successful treatment.

Overview — Due to a lack of data on the efficacy of treatments for CCCA, support for various treatments is largely derived from the recommendations of clinicians experienced in the treatment of hair and scalp disease. Local corticosteroid therapy and oral tetracyclines, both well-tolerated therapies with anti-inflammatory properties, are well-accepted and commonly used first-line treatments for CCCA. The approach to treatment reviewed here reflects our approach to CCCA. Other approaches to treatment may be reasonable.

In general, the response of CCCA to local and systemic therapies is slow. At least six months of treatment usually is required to assess the efficacy of a particular treatment. Once a satisfactory response is obtained, treatment can be slowly tapered as tolerated. Subsequently, patients should be followed periodically for recurrence of active disease.

Patient selection — Patients who are most likely to benefit from pharmacologic treatments for CCCA are those with active disease. Findings that suggest disease activity include:

●Ongoing progression of hair loss

●Signs of inflammation (erythema, papules, pustules) visible on physical examination

●Evidence of active inflammation on biopsy

●Symptoms of scalp pain, tenderness, itching, or other dysesthesias

Patients with end-stage disease that is no longer active (ie, none of the above findings are present) are unlikely to benefit from treatment [31].

Patients who present for treatment of CCCA often present with a strong desire to induce regrowth of lost hair in addition to a desire to prevent further hair loss and minimize symptoms. Because no treatment can regenerate hair follicles that have been destroyed by the disease process, long-standing disease with a large area of involvement seldom achieves much regrowth of hair. A careful discussion with the patient about the expected results will help to avoid unrealistic expectations for treatment. The discussion should be performed in a sensitive and empathetic manner because for many patients hair loss is a psychologically distressing condition.

First-line therapy — Our first-line therapy for CCCA consists of anti-inflammatory therapies that are usually well tolerated by patients. For patients with mild involvement (small, nondisfiguring area of hair loss, slow progression, and minimal clinical signs of inflammation), we typically begin treatment with a topical corticosteroid alone or combined with intralesional corticosteroid therapy. For patients with more extensive disease, we usually add an oral tetracycline to these therapies. (See 'Local corticosteroids' below and 'Oral tetracyclines' below.)

In addition to pharmacologic interventions, we encourage our patients with CCCA to avoid or reduce potentially harmful hair care practices. We generally advise that patients avoid or minimize chemical or thermal styling, as this damages healthy hair and makes it more difficult to camouflage hair loss. (See 'Behavioral interventions' below.)

Local corticosteroids — Although data on the efficacy of topical or intralesional corticosteroid therapy for CCCA are limited [32,33], use of these agents often is recommended [11,13,34-36]. We typically treat patients with topical corticosteroid therapy and use intralesional corticosteroid injections as an adjunctive treatment for those patients who demonstrate prominent clinical signs of inflammatory disease (ie, papules, pustules, and/or erythema).

An initial response to local corticosteroid therapy is usually prompt (within a few weeks), but it may take several months for complete control (resolution of symptoms, resolution of signs of inflammation, and cessation of progression of hair loss) to be achieved. A 14-week, uncontrolled study (n = 30) in which women with early CCCA applied clobetasol 0.05% emollient foam once daily found improvement in pruritus, pain, tenderness, erythema, and scale after treatment [33]. In addition, histopathologic examination revealed reductions in severe inflammation and perifollicular edema.

Patients are instructed to apply a high-potency topical corticosteroid (groups 1 or 2 (table 2)) daily to the affected area and the periphery. The patient's preference for a vehicle should be considered. While some patients prefer a topical corticosteroid in an ointment form, others may prefer a gel, foam, or solution. The potency of the topical corticosteroid can be tapered once the patient achieves satisfactory improvement. We usually continue some degree of topical corticosteroid therapy (eg, three times weekly) for at least one year because our experience is that relapse commonly occurs when treatment is abruptly discontinued.

When we supplement topical corticosteroids with intralesional corticosteroid injections, we perform intralesional corticosteroid therapy every six to eight weeks for up to six months, injecting triamcinolone acetonide (5 to 10 mg/mL with lidocaine 1% without epinephrine used as a diluent) into all areas of hair loss, with special focus being given to periphery of the area of alopecia.

Cutaneous atrophy is a potential adverse effect of topical and intralesional corticosteroid therapy that may be more likely to occur with intralesional corticosteroid therapy. When this occurs, we discontinue injections until atrophy resolves (usually several months). Other adverse effects of topical and intralesional corticosteroid therapy are reviewed in greater detail separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects' and "Intralesional corticosteroid injection", section on 'Adverse effects and pitfalls'.)

Oral tetracyclines — In addition to local therapy with topical and intralesional corticosteroids, we treat most patients who exhibit more than very mild manifestations of CCCA with an oral tetracycline-class antibiotic (eg, doxycycline, minocycline) based upon the anti-inflammatory properties of these agents. Our patients with mild disease who fail to respond to local corticosteroid therapy alone are also given a trial of antibiotic therapy. We usually treat adults with CCCA with 100 mg of doxycycline administered once daily. Other authors have utilized doses of 100 mg twice daily [31].

Combination therapy with local corticosteroid therapy and an oral tetracycline is continued until all clinical signs of active disease have resolved. Once this has been achieved (typically two to six months), the potency of the topical corticosteroid is gradually reduced, and the dose of the oral antibiotic is decreased (usually by 50 percent) [11]. Treatment is discontinued once the disease has been quiescent for a full year. If signs or symptoms of active inflammation recur, we restart treatment immediately.

Oral tetracyclines are usually well tolerated [37]. Common adverse effects include photosensitivity, headaches, and gastrointestinal distress.

Behavioral interventions — Although there remains a lack of clarity regarding the contribution of hair care practices to the development of CCCA, many authors recommend modification of hair care practices in patients who are diagnosed with the disease. We agree with the following approach described by other authors [34]:

●Discontinue use of chemical relaxers if feasible

●If the patient cannot discontinue use of chemical relaxers, institute the following measures:

•Have chemical relaxers applied by a professional hair stylist

•Apply a "base" (usually a petrolatum derivative) to the entire scalp prior to application of the chemical relaxer

•Space chemical relaxer sessions as far apart as possible, usually no more frequently than every 8 to 10 weeks (a measure often colloquially referred to as "stretching relaxers")

•Apply relaxers for the minimum amount of time necessary to achieve straightening

●Avoid styles that induce excessive traction on hair follicles (eg, cornrows and braid or weave extensions)

It is important to emphasize to patients that these interventions are unlikely to result in the cessation of hair loss. However, minimizing damaging treatment ensures optimal health of the remaining hair, which can help with camouflaging active areas of hair loss.

There are no studies that have investigated the benefit of adding antifungal shampoo to the treatment regimen. However, some clinicians include therapeutic shampoos containing zinc pyrithione, ketoconazole, or ciclopirox in treatment regimens. This may minimize the possibility that underlying seborrheic dermatitis contributes to exacerbation of symptoms (pruritus or scale). In keeping with the theory that CCCA may represent a fibroproliferative disorder (FPD), some dermatologists recommend aggressive treatment of seborrheic dermatitis, as even minor inflammation may spur further fibrosis.

Refractory disease — Patients who fail to respond to standard therapy with local corticosteroids and tetracyclines may be given trials of treatments that have been effective for other forms of cicatricial alopecia. The efficacy of these agents specifically for CCCA has not been studied. Concern for adverse effects supports the use of these drugs as second-line therapies rather than first-line therapies:

●Hydroxychloroquine – Hydroxychloroquine is an antimalarial drug with immunomodulatory properties that is commonly used for lichen planopilaris and discoid lupus erythematosus [38-40]. Hydroxychloroquine is typically given at a dose of 200 mg twice daily [41]. Adverse effects of hydroxychloroquine include gastrointestinal side effects and ocular toxicity. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Adverse effects' and "Antimalarial drugs in the treatment of rheumatic disease", section on 'Monitoring for toxicity'.)

●Immunosuppressants – Mycophenolate mofetil and cyclosporine are occasionally used for CCCA that fails to respond to standard therapy due to their immunosuppressive properties [41]. Due to the potential for serious adverse effects, hydroxychloroquine generally is tried prior to considering immunosuppressive therapy. Given the side effect profile and low likelihood of results, we rarely use immunosuppressants. (See "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases", section on 'Adverse effects' and "Pharmacology of cyclosporine and tacrolimus".)

Other therapies — Topical tacrolimus ointment is an additional treatment option that has been suggested for use in CCCA as an alternative to topical corticosteroids [42]. The efficacy of tacrolimus for this indication has not been evaluated.

Use of minoxidil has been proposed by some authors based upon the concept that the drug may help to prolong the anagen (growth) phase of hair follicles and may treat concomitant male or female pattern hair loss when present [31]. The author routinely uses minoxidil for patients with CCCA, particularly in those patients who appear to have concomitant female pattern hair loss complicating their presentation.

Compounded 10% topical metformin appeared effective in two patients with CCCA [43]. This cream can be applied once daily to affected areas on the scalp. Metformin has been shown to reverse fibrosis in mouse models of idiopathic pulmonary fibrosis through increased expression of adenosine monophosphate kinase [44]. The gene regulating expression of this enzyme was found to be diminished in patients with CCCA.

Cosmetic interventions — Cosmetic measures, such as hair styling techniques, wigs, hair pieces, hair powder, hair color, and other interventions that assist in camouflaging hair loss, can be very useful for patients with hair loss secondary to CCCA [45]. A cosmetologist with experience in dealing with patients with hair loss can be a valuable resource.

Hair transplantation is an option to restore hair within areas of alopecia [46]. Because of concern about a poor outcome, hair transplantation is not recommended prior to the resolution of disease activity.

PROGNOSIS — In our experience, most patients with central centrifugal cicatricial alopecia (CCCA) are able to achieve improvement in symptoms and a halt to progression of hair loss with treatment. In addition, our experience suggests that a select group of patients may be able to achieve hair regrowth with standard treatment. The disease may be more difficult to control in patients with more advanced disease, though at least partial improvement usually can be achieved.

CLINICIAN AND PATIENT SUPPORT — The Cicatricial Alopecia Research Foundation (CARF) is a helpful resource for clinicians and patients. The foundation offers a website with information and links to local support groups and national conferences.

SUMMARY AND RECOMMENDATIONS

●Central centrifugal cicatricial alopecia (CCCA) is a form of cicatricial (scarring) alopecia that presents with centrifugal spread of hair loss that begins on the crown or vertex of the scalp. Most patients diagnosed with CCCA have been women of African descent with hair that grows in a tightly curled configuration. However, men may also be affected. (See 'Epidemiology' above.)

●A variety of alternative terms were used to refer to CCCA in the past. Examples include hot comb alopecia, follicular degeneration syndrome, chemically induced cosmetic alopecia, and central centrifugal scarring alopecia. (See 'Terminology' above.)

●The pathogenesis of CCCA is not well understood, and the inciting factors are unclear. One theory suggests that premature desquamation of the inner root sheath of hair follicles is a precipitating event (picture 2). Another emerging theory is that CCCA may represent a fibroproliferative disorder (FPD), and this theory is supported by gene chip microarray data. Although certain hair care practices that can be damaging to the hair and scalp have been proposed as inciting factors for CCCA, a relationship between hair care practices and CCCA remains to be proven. In a subset of patients, mutations in the PADI3 gene may contribute. (See 'Pathogenesis' above and 'Etiology' above.)

●CCCA usually begins as a subtle patch of partial hair thinning on the crown or vertex of the scalp. Over time, the zone of hair loss expands in a centrifugal pattern, with the most severe hair loss remaining in the center (picture 1A-D). Clinical signs of inflammation, such as papules, pustules, erythema, and scale, may or may not be present. The presence of pain, itching, tenderness, or other dysesthesias in the involved area is variable. (See 'Clinical manifestations' above.)

●A diagnosis of CCCA should be suspected in patients who present with centrifugally expanding hair loss on the central scalp, particularly when the patient is a woman of African descent. Because other forms of alopecia may clinically resemble CCCA, performance of a scalp biopsy is recommended to confirm the diagnosis. (See 'Diagnosis' above and 'Differential diagnosis' above.)

●Data are limited on the treatment of CCCA, and there are no established treatment guidelines. Support for the various treatment options for CCCA is primarily derived from the recommendations of clinicians experienced in the treatment of hair and scalp disease. (See 'Treatment' above.)

●For patients with mild CCCA (small area of hair loss, slow progression, and minimal clinical signs of inflammation), we suggest initial treatment with a high-potency topical corticosteroid (Grade 2C). For patients with more extensive disease (or with mild disease that fails to respond to corticosteroid therapy alone), we suggest the addition of an oral tetracycline-class antibiotic to this regimen (Grade 2C). Our experience suggests that intralesional corticosteroid injection may be a useful adjunct to these therapies, particularly in patients with visible signs of inflammation. (See 'First-line therapy' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Leonard C Sperling, MD, who contributed to an earlier version of this topic review.