Seborrheic Dermatitis as a Potential Trigger of Central Centrifugal Cicatricial Alopecia: A Review of Literature

Abstract

Central centrifugal cicatricial alopecia (CCCA) is a common form of scarring alopecia that affects the crown or vertex of the scalp as centrifugally spreading patches of permanent hair loss. The etiology of CCCA is uncertain. Genetic predisposition, autoimmune diseases, infections (bacterial and fungal), and other idiopathic factors have all been explored as potential risk factors for the development of CCCA. Seborrheic dermatitis (SD) has been identified in a number of studies as the most common concurrent hair disorder seen in patients with CCCA. The high prevalence of SD in African American women and its association with long-term inflammation of the scalp may increase the likelihood of a connection between SD and other inflammatory conditions of the scalp in this population. Since it has frequently been discovered as a concomitant diagnosis in patients with CCCA, we hypothesize that a history of SD may play a role in the pathogenesis of CCCA.

Introduction

Central centrifugal cicatricial alopecia (CCCA) is a common form of scarring alopecia that affects the crown or vertex of the scalp as centrifugally spreading patches of permanent hair loss [1]. It is the most common cause of cicatricial alopecia in black women with a mean age of onset of 36 years. The etiology of CCCA is uncertain. Its presence nearly exclusively in women of African descent has prompted speculation on the precise etiology. One of the initial theories postulated was a substantial association between CCCA and various hair care products used by black women, such as chemical relaxers, hot combs, as well as traction-inducing hairstyles [2]. Over time, this ideology was abandoned upon observation of the manifestation of CCCA in women who were not using such hair products [3]. Genetic predisposition, autoimmune diseases, infections (bacterial and fungal), and other idiopathic factors have all been explored as potential risk factors for the development of CCCA [4, 5].

In addition to these proposed etiologies, co-existing disorders with CCCA have been investigated. Some studies have found a statistically significant prevalence of certain conditions such as diabetes mellitus type 2, uterine leiomyomas, and bacterial scalp infections among patients with CCCA [6, 7]. However, seborrheic dermatitis (SD) has been identified in a number of studies as the most common concurrent hair disorder seen in patients with CCCA.

The high prevalence of SD in African American women [8] and its association with long-term inflammation of the scalp [9] may increase the likelihood of a connection between SD and other inflammatory conditions of the scalp in this population. Since it has frequently been discovered as a concomitant diagnosis in patients with CCCA, we hypothesize that a history of SD may play a role in the pathogenesis of CCCA.

Methods

A review of the literature was conducted using PubMed and Google Scholar. The keywords searched included “central centrifugal cicatricial alopecia” and “seborrheic dermatitis.” This review included all research articles published from 2000 to 2021. A total of 25 articles were selected based on relevance to the topic of exploration. Articles were included if they directly addressed the epidemiology, etiology, pathophysiology, and co-occurrence of both CCCA and SD. Articles that either did not explore the information of interest on these two disorders or did not contain data on common co-diagnoses were excluded.

Results

SD was found to co-exist with CCCA in a number of studies (Table 1). SD was identified as the leading concurrent diagnosis among the subjects in a retrospective chart review of 69 patients with CCCA and a coexisting diagnosis in another case series (13/25; 52%) [10]. Kyei et al. [6] report co-occurrence of SD in 24% of total subjects in yet another study of CCCA patients. A more recent study reported a medical history of SD in roughly 60% of CCCA subjects with both early and advanced-stage disease [11]. In another study which was histologically evaluating multifactorial alopecia, SD was also found to be the highest concurrent disorder (18/34; 52.9%) with alopecia [12].

Table 1.

Demographics of all study patients

Author	CCCA Subjects, n	Patients with SD, n	Family history of alopecia	Mean age of subjects	Severity	History of traumatic hair practice	Clinical inclusion criteria	Histopathologic inclusion criteria	Exclusion criteria
Shah & Alexis 2010 [10]	69	13/25 (52% of patients with a concurrent diagnosis)	15/27 (56% of CCCA subjects with available data)	42.4	37/48 (77% of subjects noted symptoms) and 11/48 (23% of subjects were asymptomatic)	64/64 (100% of subjects with available data ≥ traumatic hair practice)	No information − photographs were used for clinical correlation	(1) Premature inner root sheath desquamation; (2) perifollicular inflammatory infiltrate, predominantly lymphocytic; (3) perifollicular fibrosis or concentric perifollicular lamellar fibroplasia; (4) perifollicular granulomatous inflammation and/or hair shaft foreign-body giant cells; and (5) decreased follicle density and/or fibrotic tracts -Not all hair follicles had to be affected and not all histopathologic criteria had to be present for diagnosis	No information
Kyei et al. 2011 [6]	52	80/326 (24.4% of total participants)	No data	49.7	CHLGs 3–5	Chemical relaxer-286/310 (91% of respondent) Hot comb-13/310 (44% of respondents)	NAHRS central standardized central scalp alopecia photographic scale used − CHLG of 0 − normal hair; a CHLG of 1–2 − possibly early CCCA, androgenetic alopecia, or telogen effluvium; and a CHLG of 3–5–probable CCCA	No information	History of alopecia areata, lupus, and/or other hair loss pattern that was consistent with either of these types of hair loss.
Suchonwanit et al. 2016 [11]	38	22/38 (57.9% of CCCA subjects)	8/38 (21% of CCCA subjects) 5/22 (22% of early CCCA subjects) 3/16 (16% of advanced CCCA subjects)	45.8	Early stage − 22/38 (57.9% of CCCA subjects) Advanced − stage CCCA − 16/38 (42.1% of CCCA subjects)	Relaxer − 37/38 (97.4% of CCCA subjects) Hot comb − 32/38 (84.2% of CCCA subjects)	Grouped according to a photographic scale of central scalp alopecia (early stage CCCA for grades 1 and 2 and advanced-stage CCCA for grades 3–5)	Clinical findings of hair loss on the crown and/ or vertex of the scalp with the absence of follicular ostia, plus all of the following histological features: (i) premature desquamation of the inner root sheath; (ii) perifollicular fibrosis and/or lichenoid lymphocytic infiltration; and (iii) compound follicular structures and/or follicular scars. I	No information
Wohltmann et al. 2016 [12]	84	18/34 (52.9% of patients with alopecia and non-alopecia concurrent diagnosis)	No data	No data	No data	No data	None	1. Premature desquamation of the inner root sheath. 2. Concentric lamellar fibroplasia of affected follicles. 3. Eccentric epithelial atrophy. 4. Perifollicular inflammation	No information

CHLG, central hair loss grade; NAHRS, North American Hair Research Society.

Discussion

SD is a relatively common dermatological condition characterized by scaling, inflammation, and pruritus, most often of the scalp, face, chest, axilla, and groin [9]. Malassezia species have been identified as an aggravating factor in SD and various other pruritic skin conditions [13, 14]. It is believed that the symptomatology of SD results from the plethora of Malassezia species on the scalp due to its boost of the production of interleukin- (IL-) 8 [15, 16].

Furthermore, the Malassezia microbes contain lipase, which breaks down human sebum triglycerides into free fatty acids precipitating scalp irritation and inflammation that leads to pruritus [17, 18, 19]. Despite the high prevalence and chronicity of SD, there is no FDA-approved treatment for this condition. The mainstay of treatment of SD is long-term application of topical antifungals to decrease the Malassezia burden and subsequent inflammatory response as well as short-term use of topical corticosteroids and other immunomodulators like calcineurin inhibitors to alleviate the inflammation, pruritus, and erythema [20]. A highly potent and selective phosphodiesterase type 4 inhibitor, roflumilast, is currently undergoing phase 3 trials for immunomodulatory management of the inflammation and pruritus caused by SD and, if approved, will be the first FDA-approved treatment for SD [21]. Antifungals for SD management are often used in CCCA. In a retrospective review of treatment results of patients with CCCA, subjects receiving antidandruff shampoo had a better improvement in disease severity compared to those who did not (0.0 vs. 0.5; p = 0.42). However, there was no statistically significant difference in pre- and post-treatment severity scores [22]. More studies are needed to determine if anti-SD shampoos can positively impact the disease course of CCCA.

CCCA is also frequently associated with scalp pruritus [23, 24]. In one study, an association was found between the disease severity of CCCA and cowhage-induced itch [25]. In addition, like SD, CCCA is associated with scaling. Follicular scales were found to be a classic dermoscopic finding in majority of the CCCA patients (68%) in a cross-sectional study [26], while SD is associated with interfollicular and perifollicular scales [27]. There have also been several case reports of patients with long-standing scalp psoriasis, another inflammatory and pruritic papulosquamous dermatosis of the scalp, that progressed to cicatricial alopecia [28]. Since CCCA causes scalp pruritus and the disease severity is associated with the intensity of the itch and chronic inflammation, there is a chance that SD and other pruritus-inducing scalp conditions may play a role in its causation.

Furthermore, there are two types of scarring alopecias: primary and secondary (SSA). In primary scarring alopecias, the hair follicle is the main target of the inflammatory process as seen in diseases like chronic cutaneous lupus erythematosus, lichen planopilaris, classic pseudopelade of Brocq, and CCCA. In SSA, the destruction of the hair follicle is not the primary pathological event but rather a result of exogenous factors like trauma (e.g., traction, burns, radiation) or endogenous inflammatory and infiltrative processes (e.g., pemphigus vulgaris sarcoidosis and scleroderma) [29, 30]. Chronic SD may be a potential contributor, exacerbating etiology of CCCA or an endogenous inflammatory etiology of SSA.

Conclusion

Identifying the etiologies and risk factors for the development and progression of CCCA is an important step toward improved management of the condition. Some of the limitations of analyzing the association between SD and CCCA include low number of available studies, lack of information about how SD was managed in study subjects, selection bias, low subject numbers, retrospective and cross-sectional designs of the studies. Given the evidence for a possible association between CCCA and SD, we suggest a large-scale prospective investigation of this patient population that includes complete medical history, hair care practices, specific measures of disease progress, and lifetime management of their SD. This might help increase knowledge about the role of SD in CCCA and encourage more research in this area. If causation is established, aggressive management of SD in patients at risk of CCCA may reduce the disease incidence, severity, and its psychological burden on patients.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding was received for this study.

Author Contributions

Chiagoziem Ogbonna: substantial contributions to the acquisition, analysis, or interpretation of data for the work; drafting the work and revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Nwanneka Okwundu: substantial contributions to the design of the work; acquisition, analysis, or interpretation of data for the work; drafting the work and revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Amy J. McMichael: substantial contributions to the conception, design, analysis, and interpretation of data for the work; revising the work critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding Statement

No funding was received for this study.