Central Centrifugal Cicatricial Alopecia: Challenges and Treatments

doi:10.1016/j.det.2021.03.004

Dermatologic Clinics

Volume 39, Issue 3, July 2021, Pages 389-405

https://doi.org/10.1016/j.det.2021.03.004 Get rights and content

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Key points

•
Central centrifugal cicatricial alopecia (CCCA) is the most common form of primary scarring alopecia in women of African descent.
•
At the molecular level, an autosomal dominant mode of inheritance, mutations in protein PADI3, and upregulation of critical fibroproliferative genes have all been linked to patients with CCCA.
•
CCCA often occurs in the absence of clinical signs of overt inflammation and instead fibrosis is often the predominant feature.
•
The presence of a white/gray peripilar follicular

Prevalence

The true prevalence of CCCA has yet to be established; however, multiple studies have been conducted to explore the prevalence in different demographics. A study completed in 2011 sought to discern the prevalence of CCCA in African American women, where patients from the central/southeast United States were recruited and their hair loss evaluated through the use of a standardized photographic scale⁵ and questionnaire; the study concluded a prevalence of 5.6% in a study of 529 subjects.⁶^,⁷ A

Pathogenesis

The pathogenesis of CCCA is believed to involve a complex mixture of a multitude of factors including but not limited to genetic predisposition,¹³ variants in gene expression,¹⁴ ethnic hair care practices,¹⁵ and disruption of the balance between proinflammatory and anti-inflammatory factors. One study of 14 South African index families with 31 immediate family members found evidence to suggest that CCCA can be inherited in an autosomal dominant fashion.¹³

New research¹⁴ suggests that pathogenic

Associated findings

More recent literature has explored the possible connection between CCCA and systemic diseases. One study reported a statistically significant increase in the prevalence of diabetes mellitus type 2 among patients with CCCA, suggesting that CCCA may be a marker of metabolic dysregulation.⁸ A retrospective study reported that women with CCCA were found to have a nearly 5 times increased odds of having uterine leiomyomas compared with race-matched, age-matched, and sex-matched controls.¹⁷ This

Dermatoscopy

Dermatoscopy serves as a noninvasive diagnostic tool to elucidate specific findings seen in CCCA and to select the best sites for obtaining biopsy specimens. In a retrospective study, a highly sensitive and specific finding of a peripilar gray/white halo located around the emergence of hair follicles was observed in 94% of patients diagnosed with CCCA.¹⁸ Other reported dermatoscopic findings include honeycomb pigmented rete ridges and hypomelanotic dermal papillae, hair shaft variability,

Histopathology

Histopathologic analysis is useful in the diagnosis of CCCA and specific features can help distinguish CCCA from other scarring alopecias. The histopathology of CCCA is usually summarized by the presence of premature desquamation of the inner root sheath (PDIRS) at the level of the deep dermis with varying degrees of perifollicular lymphocytic inflammation around the infundibulum and isthmus that leads to follicular destruction and replacement of hair shafts with fibrosis.²⁰ PDIRS is such a

Clinical presentation

CCCA typically begins as an area of decreased hair density or hair breakage notably at the vertex of the scalp and expands peripherally (Fig. 1). In early stages, patients may report scalp pruritus or tenderness. The hair loss can progress insidiously, delaying diagnosis and treatment especially in asymptomatic patients. Advanced cases reveal impressive hair loss evidenced by a smooth, shiny scalp with loss of follicular ostia (Fig. 2). Hair breakage also can be a sign of early or occult CCCA,

Patient evaluation overview

When evaluating a patient with suspected CCCA, a thorough history should be obtained from the patient. Box 1 lists pertinent questions applicable to patients with suspected CCCA. Baseline photographs of the affected area(s) are important to evaluate the patient’s condition at subsequent follow-up visits. A detailed scalp examination using adequate lighting and a dermatoscope is necessary. Dermoscopy is essential in identifying the optimal site for a biopsy and narrowing the differential

General Guidelines

The general goals in treating CCCA are aimed at addressing symptoms at the earliest presentation, halting progression of disease, and establishing hair regrowth. These steps involve patient education, topical agents, systemic medications, and in some cases, procedural therapies. Discontinuation of hair grooming practices that promote fragility, tension, and trauma to the hair follicle is essential.³¹ It is also important to acknowledge the psychological impact that patients with CCCA may

The role of hair care practices

The differences in hair structure in patients of African ancestry compared with other ethnic backgrounds plays an important role when discussing treatments for CCCA. In its natural state, the African hair shaft tends to be elliptical or flattened in cross-section and spiral or tightly curled in its tertiary structure.³⁸ It is important to note that not all patients of African descent exhibit curly hair. African hair also exhibits more knots, broken hair shafts, and interlocking of hair shafts.⁵⁰

Challenges and solutions

Early CCCA can often be difficult to distinguish from the most common form of alopecia, which is AGA. Unfortunately, this can pose a major challenge and delay appropriate treatment. CCCA in men can present almost identical to AGA; however, the former usually presents at an earlier age, is symptomatic, and is restricted to the vertex, whereas the latter can have asymptomatic additional hair loss in the frontal or bi-temporal hairline or crown.¹² This highlights the importance in performing a

Summary

CCCA remains the leading cause of scarring alopecia in women of African descent. Although certain traumatic hairstyles play a contributory role, we now understand this is a much more complex disease process. Future research will hopefully identify the exact inheritance pattern of CCCA, other causal genes linked to CCCA, and systemic diseases that we should screen for in our patients diagnosed with CCCA. In addition, future clinical studies should explore possible therapeutic options that target

Clinics care points

•
CCCA is the most common form of primary scarring alopecia in women of African descent.⁴¹
•
At the molecular level, an autosomal dominant mode of inheritance,¹³ mutations in protein PADI3,¹⁴ and upregulation of critical fibroproliferative genes¹⁶ have all been linked to patients with CCCA.
•
CCCA often occurs in the absence of clinical signs of overt inflammation and instead fibrosis is often the predominant feature.³⁰
•
The presence of a white/gray peripilar follicular halo on dermoscopy is both

Disclosure

The authors have no disclosures to report.

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Cited by (17)

Proteomic Profiling of Central Centrifugal Cicatricial Alopecia Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation
2024, JID Innovations
Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a Th1 mediated inflammatory pathway, but in CCCA, the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalp in CCCA. A total of 5,444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA affected scalp, with upregulation of adaptive immune pathways (IGHG3, p=0.034; IGHG4, p=0.01; IGG1, p=0.026) and markers of fibrosis (ITGA1, p=0.016; SFRP2, p=0.045; TPM2, p=0.029; SLMAP, p=0.016), and downregulation of metabolic proteins (ALOX15B, p=0.003; FADS2, p=0.006; ELOVL5, p=0.007; FA2H, p=0.017; FAR2, p=0.011; SC5D, p<0.001). Our analysis revealed to our knowledge previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus suggesting unique mechanisms of disease in CCCA patients.
Treatment for central centrifugal cicatricial alopecia—Delphi consensus recommendations
2024, Journal of the American Academy of Dermatology
There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely.
To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA.
We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed.
In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus.
This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies.
Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.
Central centrifugal cicatricial alopecia in males
2023, Journal of the American Academy of Dermatology
Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia seen primarily in women of African descent but rarely reported in men. The etiology of CCCA is unknown, but genetic variants, type 2 diabetes mellitus, and bacterial infections may play a role.
We aimed to characterize the demographics, medical histories, and clinical findings of male patients with CCCA with the hypothesis that features may differ from women.
This was a case series of adult male patients with biopsy-confirmed CCCA seen at an academic dermatology department between 2012 and 2022.
In total, 17 males had a scalp biopsy and clinical findings consistent with CCCA. The average age was 43 years, and 88.2% of cases identified as Black race. Scalp pruritus was the most common symptom, and few patients endorsed high-risk hair care practices. None of the cases had diagnosis of type 2 diabetes mellitus, but 17.6% had history of latent tuberculosis, and 47.1% had a positive family history of alopecia. We observed 8 patients with atypical CCCA, and 29.4% had an overlapping scalp diagnosis.
This study is limited by the single center, retrospective design and small sample size.
It is important to consider CCCA in the differential diagnosis of alopecia in adult Black males.
Scarring Alopecia
2023, Dermatologic Clinics
Trichoscopy: An Update
2023, Actas Dermo-Sifiliograficas
La tricoscopia es una técnica sencilla y no invasiva que se puede realizar durante la consulta con un dermatoscopio manual o digital. Esta herramienta ha ganado popularidad en los últimos años, ya que la visualización e identificación de estructuras y signos característicos puede ser la clave en el diagnóstico de alopecias y enfermedades del cuero cabelludo. El enfoque de esta revisión es el estudio y actualización de los hallazgos tricoscópicos en las alopecias más frecuentes en la práctica clínica habitual.
Así pues, existen algunas alopecias como la alopecia areata, la tricotilomanía o la alopecia frontal fibrosante en las que los hallazgos con la tricoscopia resultan clave para su diagnóstico y seguimiento. El reconocimiento de estas estructuras distintivas puede ser de gran ayuda y, por ello, como dermatólogos debemos estar familiarizados con las mismas.
Trichoscopy is a simple, noninvasive office procedure that can be performed using a handheld or digital dermatoscope. This tool has gained popularity in recent years, because it provides useful diagnostic information for hair loss and scalp disorders by enabling the visualization and identification of distinctive signs and structures. We present an updated review of the trichoscopic features described for some of the most common hair loss disorders seen in clinical practice. Dermatologists should be familiar with these helpful features, as they can significantly aid the diagnosis and follow-up of numerous conditions, such as alopecia areata, trichotillomania, and frontal fibrosing alopecia.
A case of rapid progression of central centrifugal cicatricial alopecia after COVID-19 infection
2022, JAAD Case Reports
Citation Excerpt :
Hair loss begins at the vertex or crown of the scalp and spreads centrifugally over time. Patients often report associated symptoms of scalp burning, itching, tenderness, and scaling.6 Dermoscopy may be used to identify specific features of CCCA, including a peripilar gray/white halo around the emergence of the hair follicle, honeycomb pigmented rete ridges and hypomelanotic dermal papillae, perifollicular erythema, and hair breakage appearing as black dots on the scalp.6,7

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