Central Centrifugal Cicatricial Alopecia

Article Author:
Sarah Gabros
Article Editor:
Sadia Masood
Updated:
6/16/2020 8:28:46 PM
PubMed Link:
Central Centrifugal Cicatricial Alopecia

Introduction

Central centrifugal cicatricial alopecia (CCCA) is a unique form of scarring alopecia that clinically presents as patches of permanent hair loss on the vertex or crown of the scalp, and spreads centrifugally.[1] This type of hair loss is associated with signs and symptoms of inflammation. It is a common condition that usually affects women of African descent, and it runs in families.[2]

There is limited data available about the treatment of CCCA The treatment modalities include topical and systemic corticosteroids and oral tetracyclines with limited response. The prognosis of the disease varies, and it widely depends upon the duration and nature of the disease.[3]

Etiology

The cause of central centrifugal cicatricial alopecia is not clear. There are various theories about the etiology of CCCA. One hypothesis suggests that there is a strong association between CCCA and different hair care products used by black women, like chemical relaxers, hot combs, and various traction inducing hairstyles.[4] Over some time, this concept was discarded upon recognition of the problem in women who were not using these various hair products. Literature suggested that environmental and genetic factors also play some role in the etiology.[5]

Current evidence does not support these various theories. The etiology of central centrifugal cicatricial alopecia is multifactorial. Various other suggested causes include infections, autoimmune disease, or genetic factors. It could be idiopathic, but still, more studies needed to clarify this concept.[6]

Epidemiology

Central centrifugal cicatricial alopecia is very common among middle-aged women of African ancestry with hairs that grow in curled or kinked configuration with a prevalence of 3% to 6%. It is the most frequent cause of alopecia in African Americans. It is uncommon in men and children. The mean age of onset of the disease in women is 36 years.[5]

Currently, there is no well documented published evidence about the involvement of CCCA in the nonblack population.[7]

Pathophysiology

The pathophysiology of central centrifugal cicatricial alopecia is still not well understood. A study by Sperling and colleagues identified cytokeratin 75 expressions in unaffected and affected tissues.[1] Cytokeratin 75 is usually expressed in the hair follicle that lies between inner and outer root sheaths. They had reduced expression of the keratin, occurring more prematurely (below the isthmus) within the affected follicles of central centrifugal alopecia in comparison with normal follicles. Although, they also identified that this expression in unaffected follicles in cases of central centrifugal alopecia was not different from the normal follicles, which suggest that cytokeratin 75 expressions can only express the premature desquamation of inner hair root sheath (PDIRS). As a result, the hair shaft presses against the outer root sheath that results in a mild inflammatory response, which leads to the rupture of the follicle. PDIRS can promote the descent of various environmental threats, like bacteria or chemical relaxers, into the lower follicle, leading to inflammation and follicular damage, but it is not involved directly in the pathogenesis of CCCA.[1]

Another theory suggested that CCCA may be a fibroproliferative disorder (FPD). These FPDs are characterized by persistent irritation and mild inflammation, which leads to end-stage fibrosis. Further immune histochemical studies are needed to identify other suspected acquired or heritable mutations that predispose certain particular populations to CCCA.[8]

Histopathology

The histologic finding found in early cases is premature desquamation of inner root sheath (PDIRS), but it is not specific to central centrifugal cicatricial alopecia as it is also present in other primary scarring alopecia, where the follicle is damaged due to severe inflammation. However, when slightly inflamed or non-inflamed follicles demonstrate features of PDIRS, then it is suggestive of CCCA. Early histologic changes show perifollicular lymphocytic infiltrate with perifollicular fibroplasia. These inflammatory infiltrates typically extend from lower follicular infundibulum to the upper part of the isthmus. Few cases present with a reduction of terminal hair follicles. Later stages are associated with follicular epithelium destruction and retention of fragments of hair shaft along with granulomatous inflammation. This is followed by follicular epithelium being replaced by connective tissue, and tufting/polytrichia of hair follicles (fusion of infundibulum). Histologically, it resembles the early stages of folliculitis keloidalis (FK) and advanced stage of lichen planopilaris.[9]

Lichen planopilaris presents with superficial perifollicular fibrosis, infundibular inflammation, and destruction that leads to free hair shafts in the dermis, which is similar to central centrifugal alopecia, but it is differentiated by the presence of vacuolar lichenoid dermatitis with epidermal cytoid bodies and peri-infundibular hypergranulosis. There may also be dyskeratosis with perifollicular lymphocytic inflammation. In frontal fibrosing alopecia, there is a gradual progressive hair follicles loss with lymphohistiocytic infiltration and lamellar fibrosis around the isthmus and lower infundibulum.[2]

History and Physical

History and findings of a clinical examination-that help to diagnose central centrifugal cicatricial alopecia include:

  • CCCA usually starts at the vertex of the scalp.[10]
  • It progresses centrifugally, usually in a symmetrical fashion.
  • The scalp is soft on palpation. 
  • There can be mild hyperpigmentation seen around the hair follicles.[11]
  • The affected patch of alopecia slowly blends with the surrounding normal scalp. 
  • There may be mild burning, tenderness, or itching confined to the area of hair loss.
  • Islands of unaffected hairs with polytrichia can be seen within affected areas.

Evaluation

A suspicion of central centrifugal alopecia should be considered in every case of alopecia involving the vertex in female patients of Afro-Caribbean descent.[12]. The trichoscopy shows perihilar white halos, loss of follicular openings, disrupted pigmented network, irregularly distributed pinpoint white dots, and individual broken hair follicles. The hair shaft quality can be assessed by checking the hair length, diameter, and breakage. The blunt tip of hair with broomstick ends suggest breakage or trichorrhexis nodosa. Longitudinal splitting of the distal end of hair and trichoptilosis are suggestive of hair damage secondary to heat or chemical processes.

A hair pull test needs to be performed to rule out telogen effluvium. This is a test usually yields 2 to 5 telogen hairs on pulling 50 to 100 hairs in a normal adult, but it may be increased up to 3 to 5 times in telogen effluvium. Signs of hyperandrogenism like acne, hirsutism, prolongation of menstrual cycles, and obesity need to be noted as they are associated with female pattern hair loss.[13] A serum total and free testosterone dehydroepiandrostenedione sulfate (DHEAS), prolactin levels, and luteinizing hormone, follicular stimulating hormone ratio helps in ruling out polycystic ovarian syndrome associated with female pattern hair loss.

An extreme elevation in androgens is suggestive of a virilizing tumor. Further, nutritional deficiencies need to be ruled out. This can be done by ascertaining the levels of vitamin D, serum iron, ferritin, and total iron-binding capacity. A baseline complete blood counts, renal function test, liver and thyroid function tests, syphilis serology, and antinuclear antibody screening helps in ruling out other minor causes of hair loss. An absence of hyphae in KOH mount from the scalp scraping may help in ruling out tinea capitis. Finally, two 4-mm punch biopsies (for vertical and horizontal sectioning) from the active margin of the alopecia may help in the confirmation of the diagnosis.[4]

Treatment / Management

Treatment aims include encouraging hair regrowth and preventing or halting the progression of the disease, but hairs will not regrow from permanently damaged hair follicles. Although there are no clear guidelines for the management of central centrifugal cicatricial alopecia, and most treatment options are only empiric, but it is imperative to start it early as it would reduce the chance of disease progression.[14]

The response of CCCA to various treatment modalities is slow. Anti-inflammatory therapy is often considered as the first-line treatment and is achieved with the use of topical steroids or intralesional triamcinolone acetonide. Lower concentration of topical steroids decreases the risk of hypopigmentation in people with dark skin. Antibiotics, both topical and systemic like doxycycline, are effective and need to be continued till improvement is seen (at least 2 to 6 months). The dose may be decreased and then gradually discontinued after a quiescent state for at least one year. Systemic anti-inflammatory treatments like mycophenolate mofetil, hydroxychloroquine, and cyclosporine have also been used in a few cases. Short courses of oral corticosteroids are ideal for cases with active inflammation. Vitamin D also has some effective role in management.[2]

Minimal hair grooming is recommended, even though the evidence is not sufficient. Haircare practices need to be modified, reduced or apply for a minimum time. However, excessive traction of hairs should be avoided. Symptomatic relief is achieved with the once-weekly use of mild shampooing.[3]

Differential Diagnosis

Central centrifugal cicatricial alopecia clinically resembles:

  • Female pattern hair loss: It is a form of non-scarring alopecia occurring after menopause or at puberty, associated with hyperandrogenism. The key feature to differentiate it from CCCA is the absence of scarring and the presence of visible follicular openings.[15]
  • Lichen planopilaris: It is a type of scarring alopecia, which is also indistinguishable in some cases. In contrast to central centrifugal cicatricial alopecia, lichen planopilaris presents with perifollicular erythema and follicular keratosis. Frontal fibrosing alopecia is another form of lichen planopilaris. It is characterized by facial papules and slowly progressive scarring alopecia of the scalp. It also affects the eyelashes, eyebrows, and other body parts.[16]
  • Tinea capitis: It is a fungal infective condition of the scalp and is differentiated by Wood's lamp examination, which emits bright green fluorescence with Microsporum and faint blue fluorescence with Trichophyton schoenleinii species. It presents both scarring and non-scarring alopecia.
  • Discoid lupus erythematosus: It is a form of scarring alopecia that usually affects the scalp. It appears as erythematous scaly plaques with follicular plugging along with pigmentary changes. The histological findings differentiate it from CCCA. Histopathology shows perivascular and peri adnexal lymphohistiocytic infiltrate and interface dermatitis.[16] The basal layer shows degenerative changes.
  • Pseudopelade of Brocq: It usually affects middle-aged and older women. It commonly presents as irregular patches of hair loss that usually begins at the vertex. The bald areas look like 'footprints in the snow.' Histopathology of the lesion shows thin epidermis with sclerotic dermis and streamers of fibrosis that goes up to the fat layer.[17]

Staging

A photographic scale has been in use for staging alopecia in African-American women. The central scalp alopecia scale used for African-American women helps assess the severity of the hair loss in central centrifugal cicatricial alopecia. It is graded on a scale of 0 to 5. The grade 0 suggests normal hair density and grade 5 suggestive of severe alopecia.[18]

Prognosis

The prognosis of central centrifugal cicatricial alopecia depends on the stage of the disease. Early diagnosis and standard treatment may be able to enhance hair regrowth.[19] The prognosis is not good in patients who present with more advanced disease, because late diagnosis and treatment may only prevent the progression of the disease as there is only a slight potential for hair regrowth due to scarring.[1]

Complications

The most common problems associated with central centrifugal cicatricial alopecia relate to late or misdiagnosis. It is a type of scarring alopecia, and thus it is difficult to restore the amount of hair already damaged. Symptoms usually vary from none to very disruptive and presenting with burning, itching, and tenderness. The aim of treatment is to preserve the remaining hairs and avoid the progression of the disease. It is crucial that the patient is clearly explained the severity of the condition and the available treatment options.

Deterrence and Patient Education

  • Patient education is essential in allaying anxiety associated with central centrifugal cicatricial alopecia, and well-informed patients can learn to be confident at managing their condition.
  • For the scarring stage, it requires emphasizing to the patient that there is no cure, but it can be well controlled and managed primarily.
  • It is important that patients should avoid hair practices that need heat treatment or that provide friction.
  • The regular use of hair relaxers should be avoided, as it leads to increased disease incidence.

Enhancing Healthcare Team Outcomes

  • Consider the impact of CCCA on psychosocial functioning and quality-of-life and remember that it may accompany psychological distress.[20]
  • The dermatologist and pharmacist can help to promote the appropriate use of topical corticosteroids and employ steroid-sparing alternatives.
  • Hair transplantation can be an effective strategy in patients with advanced disease, although there is a chance that scarring may reduce the survival rate of transplanted graft.
  • Patients with advanced disease need to be counseled about various camouflage techniques and hairpieces. These patients always need psychological support and may be encouraged to join various disease support groups.

References

[1] Flamm A,Moshiri AS,Roche F,Onyekaba G,Nguyen J,James AJ,Taylor S,Seykora JT, Characterization of the inflammatory features of central centrifugal cicatricial alopecia. Journal of cutaneous pathology. 2020 Feb 18;     [PubMed PMID: 32068905]
[2] Aguh C, Updates in our understanding of central centrifugal cicatricial alopecia. Cutis. 2019 Dec;     [PubMed PMID: 31939927]
[3] Araoye EF,Thomas JAL,Aguh CU, Hair regrowth in 2 patients with recalcitrant central centrifugal cicatricial alopecia after use of topical metformin. JAAD case reports. 2020 Feb;     [PubMed PMID: 32016152]
[4] Sundberg JP,Hordinsky MK,Bergfeld W,Lenzy YM,McMichael AJ,Christiano AM,McGregor T,Stenn KS,Sivamani RK,Pratt CH,King LE Jr, Cicatricial Alopecia Research Foundation meeting, May 2016: Progress towards the diagnosis, treatment and cure of primary cicatricial alopecias. Experimental dermatology. 2018 Mar;     [PubMed PMID: 29341265]
[5] Malki L,Sarig O,Romano MT,Méchin MC,Peled A,Pavlovsky M,Warshauer E,Samuelov L,Uwakwe L,Briskin V,Mohamad J,Gat A,Isakov O,Rabinowitz T,Shomron N,Adir N,Simon M,McMichael A,Dlova NC,Betz RC,Sprecher E, Variant {i}PADI3{/i} in Central Centrifugal Cicatricial Alopecia. The New England journal of medicine. 2019 Feb 28;     [PubMed PMID: 30763140]
[6] Anzai A,Wang EHC,Lee EY,Aoki V,Christiano AM, Pathomechanisms of immune-mediated alopecia. International immunology. 2019 Jul 13;     [PubMed PMID: 31050755]
[7] Akintilo L,Hahn EA,Yu JMA,Patterson SSL, Health care barriers and quality of life in central centrifugal cicatricial alopecia patients. Cutis. 2018 Dec;     [PubMed PMID: 30657802]
[8] Haskin A,Aguh C,Okoye GA, Understanding patient experiences with scarring alopecia: a qualitative study with management implications. The Journal of dermatological treatment. 2017 Jun;     [PubMed PMID: 27615549]
[9] Fernandez-Flores A, Use of Giemsa staining in the evaluation of central centrifugal cicatricial alopecia. Journal of cutaneous pathology. 2020 May     [PubMed PMID: 32065424]
[10] Miteva M,Tosti A, Central Centrifugal Cicatricial Alopecia Presenting with Irregular Patchy Alopecia on the Lateral and Posterior Scalp. Skin appendage disorders. 2015 Mar;     [PubMed PMID: 27172374]
[11] Griggs J,Trüeb RM,Gavazzoni Dias MFR,Hordinsky M,Tosti A, Fibrosing alopecia in a pattern distribution. Journal of the American Academy of Dermatology. 2020 Jan 8;     [PubMed PMID: 31926219]
[12] Su HJ,Cheng AY,Liu CH,Chu CB,Lee CN,Hsu CK,Lee JY,Yang CC, Primary scarring alopecia: A retrospective study of 89 patients in Taiwan. The Journal of dermatology. 2018 Apr;     [PubMed PMID: 29341216]
[13] Tan T,Guitart J,Gerami P,Yazdan P, Premature Desquamation of the Inner Root Sheath in Noninflamed Hair Follicles as a Specific Marker for Central Centrifugal Cicatricial Alopecia. The American Journal of dermatopathology. 2019 May;     [PubMed PMID: 30562220]
[14] Bolduc C,Sperling LC,Shapiro J, Primary cicatricial alopecia: Other lymphocytic primary cicatricial alopecias and neutrophilic and mixed primary cicatricial alopecias. Journal of the American Academy of Dermatology. 2016 Dec;     [PubMed PMID: 27846945]
[15] Rogers N, Imposters of androgenetic alopecia: diagnostic pearls for the hair restoration surgeon. Facial plastic surgery clinics of North America. 2013 Aug;     [PubMed PMID: 24017974]
[16] Callender VD,Wright DR,Davis EC,Sperling LC, Hair breakage as a presenting sign of early or occult central centrifugal cicatricial alopecia: clinicopathologic findings in 9 patients. Archives of dermatology. 2012 Sep;     [PubMed PMID: 22986858]
[17] Fernandez-Nieto D,Saceda-Corralo D,Jimenez-Cauhe J,Pindado-Ortega C,Erana I,Moreno-Arrones OM,Vano-Galvan S, Central Centrifugal Cicatricial Alopecia in a Fair Phototype Patient. International journal of trichology. 2019 Nov-Dec;     [PubMed PMID: 32030062]
[18] Fung MA,Sharon VR,Ratnarathorn M,Konia TH,Barr KL,Mirmirani P, Elastin staining patterns in primary cicatricial alopecia. Journal of the American Academy of Dermatology. 2013 Nov;     [PubMed PMID: 24035210]
[19] Eginli A,Dothard E,Bagayoko CW,Huang K,Daniel A,McMichael AJ, A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia. Journal of drugs in dermatology : JDD. 2017 Apr 1;     [PubMed PMID: 28403264]
[20] Pärna E,Aluoja A,Kingo K, Quality of life and emotional state in chronic skin disease. Acta dermato-venereologica. 2015 Mar     [PubMed PMID: 24978135]