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Central Centrifugal Cicatricial Alopecia: Overview of Disease and Management
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Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia, with a typical presentation of permanent, central scalp hair loss that progresses outward.1 The disease follows
an autosomal dominant inheritance pattern in 25% of cases.2 Mutations in the PADI3 gene responsible for encoding proteins involved in hair shaft development have also been linked to CCCA.3 Because the condition leads to permanent hair loss, it is imperative that clinicians have the tools necessary for early recognition and intervention to slow its progression and improve patients’ quality of life.
Epidemiology
The incidence of CCCA in the United States is estimated to be between 2.7% to 5.7%.4 CCCA most commonly affects African American adults, often in the second or third decade of life, with a female-to-male ratio of 3:1.2 However, the condition may also affect adolescents and has significant overlap with tinea capitis in this population.5
Pathophysiology
The exact cause of CCCA is unknown but a common hypothesis is that some environmental or physical insult leads to lymphocytic infiltration of the hair follicle triggered by the peroxisome proliferator-activated receptor gamma and transforming growth factor (TGF)-beta cascades.6 This response to insult may be more common in those genetically predisposed to the condition. On histopathology, active disease typically involves perifollicular fibrosis with CD3+/CD4+ lymphocytic infiltrate, peri-infundibular lymphocytic infiltrate, and reduced follicle density in affected patches.7 These histologic findings are often similar in lichen planopilaris (LPP), and these conditions often mimic one another.
Later stages of disease progression often do not show signs of inflammation and lymphocytic infiltration but instead are defined by increasing fibrosis. It has been proposed that individuals with lower levels of proliferator-activated receptor gamma within hair follicles may be at increased risk for TGF-beta driven fibrotic processes to encourage progression of disease.8 As both topical and injectable steroids remain the standard of care for CCCA, late disease progression with minimal inflammation poses a significant treatment challenge for clinicians.
Symptoms
There should be a high suspicion for CCCA in any African American patient presenting with central hair loss, particularly if symptomatic. Early disease is often characterized by hair breakage. Patients often describe itching, burning, pain, and possibly altered sensation within the region of hair loss. They may also describe the patch of hair loss expanding outward in a symmetric pattern.1 On examination, there may be areas of hyperpigmentation near hair follicles, which may represent active inflammation, and the scalp may be soft to palpation. Late disease progression may be characterized by shiny, smooth areas representing areas of fibrosis (Figure 1).9
Risk Factors
Discrepancies exist in the literature as to what factors put a patient at higher risk for developing CCCA. It was traditionally thought that tight hairstyles involving significant pulling and chemical hair relaxers were associated with CCCA development. In fact, the condition was initially described as “hot comb alopecia.”9 One study found the odds of CCCA development to be 12.37 times higher in individuals using chemical hair relaxers compared with women who did not (P < .001).10 Furthermore, another study showed that women who wore cornrows/braids had 1.6 times higher odds (P=.03) of developing CCCA, and women wearing sewn-in weaves had 2.8 times higher odds (P = .04) of developing CCCA when compared with women who did not.11 However, additional studies have shown no significant association between tight hairstyles with significant pulling or chemical hair relaxers and CCCA. Given these mixed results in the literature, clinicians should counsel patients on the discrepancies, so they may make the best decision for themself.
Comorbidities
Discrepancies also exist in the literature as to comorbidities that clinicians should be on the lookout for in patients with CCCA. Metabolic syndromes have been most frequently studied. One study found significantly higher rates of type 2 diabetes mellitus (T2DM) in patients with CCCA (OR=4.13, 95% CI 2.76-6.18, P<.05), with an additional study finding significantly higher CCCA severity in patients with T2DM (P=.043).12,13 Additionally, hyperlipidemia was shown to occur at much higher rates in patients with CCCA compared with control individuals.14 However, further work found no significant association between T2DM or hyperlipidemia with CCCA in studies with greater sample size.15 An additional comorbidity researched in association with CCCA was uterine fibroids, with one study finding that patients with CCCA had a 4.68 times higher risk of uterine fibroids (95% CI 3.57-6.12), whereas another found no significant association.16
To date, no clear comorbidities have been established in connection with CCCA. Clinicians should understand differences in results among studies and counsel patients on the unclear connection between their disease and metabolic syndromes and fibroproliferative disorders.
Treatment
Unfortunately, treatment of CCCA is difficult and options remain limited. Clinicians should consider a biopsy to confirm the diagnosis of CCCA and rule out other similar conditions, such as LPP or folliculitis decalvans (FD).5
Initial management should involve clinicians acknowledging the impact that CCCA often has on patients’ lives; many patients describe low self-esteem, relationships impacted by the condition, and feelings of hopelessness that their hair will never return.17 Additionally, although the evidence is mixed, many sources do suggest advising patients against heat/ chemical hair treatments.9 These hairstyles can be an important cultural practice for some and, therefore, the mixed evidence should be properly explained to patients so they can make their own informed decision. Finally, clinicians should evaluate patients for concurrent pattern alopecia, such as pseudofolliculitis barbae or FD, that commonly occur alongside CCCA.
Management of the initial phases of the disease, most often characterized by inflammation, typically involves high-potency topical steroids and/or intralesional steroid injections.17 For example, monthly injection of actively spreading lesion margins with 2.5 mg/ml triamcinolone acetonide for 6 months is recommended.18 Once the spread of the lesion has been stabilized with intralesional injections, patients can be instructed to apply topical steroids to the lesion 3 times a week and consider topical calcineurin inhibitors.9 Additionally, oral antibiotic regimens, such as doxycycline, minocycline, or tetracycline, can be initiated to help suppress inflammation in early stages, with goals to discontinue when inflammation has improved (20 mg–100 mg daily, with doxycycline monohydrate recommended at higher doses).19 Minoxidil 1.25 mg daily is often added to aid in hair growth, as it protects healthy hair follicles and may slow CCCA progression.20 Recent research has also suggested the potential benefit of topical metformin 10% cream daily to improve hair regrowth in CCCA patients.21 Furthermore, clinicians should consider the initiation of oral metformin in patients with suspected insulin resistance or confirmed prediabetes or diabetes. In patients with recalcitrant diseases, clinicians should consider reevaluating the diagnosis, performing an additional biopsy, or asking for a second opinion with a dermatopathologist well-versed in hair disorders.
In late CCCA progression, treatment is often extremely challenging. Given that there is usually little active inflammation in late fibrotic stages of disease, anti-inflammatory regimens often offer little to no benefit. In other fibrotic disorders, such as idiopathic pulmonary fibrosis, IL-13 blockers have shown promise in halting progression, and they may have a future role for CCCA.22 In patients without histologic evidence of inflammation, hair transplantation may be considered to treat late-stage disease. This treatment should be reserved for those with CCCA controlled for 9 months to a year.23 Surgical hair transplant represents the most definitive one-time cure, but higher failure rates occur if transplants are performed during active inflammation.10 Nevertheless, surgical intervention with hair transplantation shows positive results for the majority of CCCA patients.23 A proposed treatment algorithm is outlined in Figure 2.
Conclusion
CCCA is the most common scarring hair loss disorder in African American women, but current understanding of disease pathophysiology and management remains limited. CCCA should be considered in any woman presenting with central hair loss progressing outwards. Early intervention is of the utmost importance to prevent progressive, permanent hair loss and improve psychosocial outcomes in these patients. Initial treatment with topical and intralesional steroids is recommended, with the potential addition of minoxidil, hydroxychloroquine, or immunomodulatory therapy as second-line agents. Late-stage CCCA is difficult to treat because of its predominance of fibrotic changes, and future investigation surrounding the efficacy of antifibrotic therapy in recalcitrant CCCA is needed.
Maxwell Green is a fourth-year medical student in the department of medicine at Tulane University School of Medicine in New Orleans, LA. Aileen Feschuk is a fourth-year medical student at Memorial University of Newfoundland, St John’s, Newfoundland and Labrador, Canada. Dr Palmer is a resident in the department of internal medicine at Richmond University Medical Center in Staten Island, NY. Dr Valdebran is an assistant professor in the department of dermatology and dermatologic surgery at the Medical University of South Carolina in Charleston, SC.
Acknowledgment: The authors would like to thank Dirk Elston, MD, for his contributions and clinical image.
Disclosure: The authors report no relevant financial relationships.
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