Fu, Jennifer M.; Price, Vera H.
Cicatricial or scarring alopecia represents the last frontier of hair problems. This group of inflammatory disorders is characterized by permanent destruction of the pilosebaceous unit, leading to irreversible hair loss. However, like androgenetic alopecia and alopecia areata, two common nonscarring forms of hair loss, cicatricial alopecia is not hereditary, is not contagious, and typically occurs in your healthiest patients.
These disorders represent a particular challenge. They are rare, and much remains to be learned about disease pathogenesis and natural history. Of all new hair loss seen in patients in four major hair research centers, the annual incidence of lichen planopilaris (LPP), one of the most common cicatricial alopecias, ranged from 1.2% to 7.6% (Ochoa, King, & Price, 2008). Although the disorders are clinically distinct and have been well described, histopathology can only distinguish two main groups, those that are predominantly lymphocytic and those that are predominantly neutrophilic.
Cicatricial alopecia may occur as a primary or secondary process. In primary scarring alopecia, the hair follicle is specifically targeted for destruction by the inflammatory process. In secondary scarring alopecia, the hair follicle is an innocent bystander to injury from a nonfollicular process such as traction, infection, tumor, burn, or radiation. This article reviews the primary cicatricial alopecias.
The clinical hallmark of all cicatricial alopecia is the loss of follicular ostia. Other signs of acute or chronic inflammation, including perifollicular erythema, perifollicular scale, erythema, crusting, and pigmentary change may be present. Patients may report severe itching, pain, or burning discomfort or may be entirely asymptomatic. The distribution of the hair loss may be focal or diffuse. A pull test (a gentle but firm slow pull on a small cluster of 30-40 hairs from the scalp end to the distal end) in an affected area may yield anagen or growing hairs; this is a sign that the condition is active and requires treatment.
Until now, treatments for these disorders have not been able to alter the underlying disease process. Recent molecular studies, however, have begun to shed light on the mechanisms by which the pilosebaceous unit may be targeted and offer exciting possibilities for future treatments. More specifically, researchers studying the lymphocytic group of cicatricial alopecias have found decreased function of the peroxisome-proliferator-activated receptor gamma in the sebaceous gland, which leads to an abnormal processing and buildup of toxic lipids, which subsequently triggers inflammation and destruction of the hair follicle (Karnik et al., 2009).
The primary cicatricial alopecias are classified by the predominant inflammatory infiltrate observed on biopsy (Olsen et al., 2003). Although the individual clinical entities cannot be distinguished with light microscopy, the pathological findings can assist in your choice of treatment. Medical therapies for the cicatricial alopecias are generally grouped into those that are more selective for the lymphocytic group versus the neutrophilic group.
The lymphocytic group includes LPP, frontal fibrosing alopecia, central centrifugal cicatricial alopecia and pseudopelade of Brocq. Of note, although chronic cutaneous lupus erythematosus of the scalp is not a primary cicatricial alopecia but rather one entity within the autoimmune spectrum of lupus erythematosus, it shares many features with the lymphocytic cicatricial alopecias. As such, a discussion of its salient features is often included with this group. The neutrophilic group includes folliculitis decalvans and its milder subtype tufted folliculitis, and dissecting cellulitis. Finally, some patients present with end-stage findings with no residual inflammation (Figure 1).
APPROACH TO THE PATIENT
A scalp biopsy is the critical first step in the approach to a patient with cicatricial alopecia. If time is limited, prioritize getting a scalp biopsy and ordering laboratory tests. Pustules if present should be cultured. A more thorough history and clinical examination may be performed at the second visit, at which time the results of your biopsy, laboratory tests, and culture will be available to guide you. The scalp biopsy should be performed at the hair-bearing margin of an area of active disease. If your dermatopathologist is accustomed to looking at horizontal sections, then only one biopsy needs to be done. If your dermatopathologist prefers to look at both horizontal and vertical sections, then two 4-mm punch biopsies should be done.
There is no specific laboratory test for the cicatricial alopecias. The laboratory tests that are useful in evaluating any patient with hair loss (e.g., complete blood count, thyroid stimulating hormone, ferritin, and 25-hydroxy vitamin D) should be done to rule out other treatable problems, but they are not specificially relevant for cicatricial alopecia.
A thoughtful and comprehensive patient history should be taken. The hair loss may be patchy or diffuse. Hair loss in other areas may occasionally be noted. Patients with frontal fibrosing alopecia, for example, may also have eyebrow loss.
Patients may report a history of symptoms including severe itching, burning, and pain, or they may be entirely asymptomatic. Patients may have noticed scaling, crusting, or pustules. With few exceptions, the hair loss in cicatricial alopecia is permanent, making a history of regrowth unlikely. Past treatments should be recorded. In general, there are no family members with similar manifestations, except in central centrifugal alopecia, which may affect other family members.
WHAT THE PATHOLOGY REPORT SHOULD INCLUDE
Partnering with your local dermatopathologist is helpful to make sure that he or she provides you with information that can be key to the management of your patient. The following should be included in the pathology report:
1. What is the status of sebaceous glands? Diminished, absent, or normal?
2. Is there an inflammatory infiltrate?
3. Is it predominantly lymphocytic, neutrophilic, or plasmacytic?
4. How dense is the infiltrate? Mild, moderate, or dense?
5. Where is the infiltrate? Is it perifollicular, peri-infundibular, or peri-isthmic?
6. What proportion of follicular tracts is fibrotic or scarred?
GOALS OF TREATMENT AND THREE OUTCOME MEASURES
Once a diagnosis has been established, you and your patient should discuss expectations for treatment. The goals of management will be to alleviate symptoms and signs and arrest the progression of hair loss. It is crucial that your patient understand that in all but rare cases, hair regrowth will not be possible. Documentation of the following three outcome measures using a standardized patient flowchart enables efficient tracking of your patient's progress and response to treatment:
1. Severity of symptoms-itching, pain, and burning.
2. Clinical disease activity-perifollicular scale, perifollicular erythema, erythema, pustules, crusting, and positive pull test (number of anagen hairs/total).
3. Extent of hair loss-determined by patient self-report, review of photographs, clinical examination.
In general, these outcome measures are recorded at 3-month intervals.
Classic LPP presents as itchy, sometimes burning and painful patches of hair loss. Perifollicular scale and perifollicular erythema are typically seen at the hair-bearing margins of active patches (Figure 2). The center of the alopecic patch is bare without follicular ostia or inflammation. Up to 20%-50% of patients may have other cutaneous, mucous membrane or nail changes of lichen planus.
Frontal Fibrosing Alopecia
This cicatricial alopecia presents in a unique distribution. Patients have notable frontal hairline recession, which may progress to the sides of the scalp and even to the occipital hairline (Figure 3). Eyebrow loss frequently accompanies these findings and may begin before, during, or after the hairline recession. Frontal fibrosing alopecia tends to be less symptomatic than LPP.
Central Centrifugal Cicatricial Alopecia
Central centrifugal cicatricial alopecia is most often observed in women of African ancestry and first presents as a small flesh-colored patch of scarring hair loss at the vertex that spreads symmetrically and centrifugally (Figure 4). Even in the setting of active hair loss, patients exhibit few physical signs of inflammation and often are minimally symptomatic. The pathogenesis of central centrifugal cicatricial alopecia, whether associated with exogenous factors related to hair styling or grooming, remains controversial and is being studied. Hair breakage and traction alopecia may coexist with central centrifugal cicatricial alopecia and if present should be separately addressed.
Pseudopelade (Brocq) has been described as asymptomatic, white or flesh-colored, small, oval-to-round bare areas without follicular scaling or perifollicular inflammation (Figure 5). When characteristic, the presentation has been likened to "footprints in the snow.“ The main difference between pseudopelade (Brocq) and LPP is the absence of symptoms and signs in the former. Histology and treatment are the same.
Chronic Cutaneous Lupus Erythematosus
Chronic cutaneous lupus erythematosus is not a primary cicatricial alopecia but rather a cutaneous manifestation of the autoimmune spectrum of lupus erythematosus. The most common clinical subtype of chronic cutaneous lupus erythematosus is classic discoid lupus erythematosus (DLE). DLE differs from the primary scarring alopecias because it is potentially reversible if treated early, and the inflammation is not strictly folliculocentric but also vacuolar at the dermal-epidermal junction, periadnexal, and perivascular. Other characteristic findings such as follicular plugging, basement membrane thickening, mucin, and pigmentary incontinence may also be seen on biopsy. However, the clinical presentation of DLE may resemble some of the lymphocytic cicatricial alopecias, especially LPP. It is therefore important that clinicians be able to recognize and distinguish DLE. Patients may be quite symptomatic, reporting pruritus, stinging, burning, and tenderness. Physical examination typically shows active inflammation in the center of the alopecic patch, with follicular plugging, erythema, and scale. Older areas may exhibit telangiectasia and hypo- and hyperpigmentation. Nonscalp disease may also be present. Only 5%-10% of patients with DLE will develop systemic lupus erythematosus.
Folliculitis decalvans presents with follicular pustules, crusting, and marked inflammation. It is invariably painful and itchy. Large areas of hair loss result. It is postulated to result from an abnormal suppurative immune response to Staphylococcus aureus and other organisms.
Tufted folliculitis is a mild focal variant of folliculitis decalvans. In contrast to folliculitis decalvans, the hair loss in tufted folliculitis is usually minimal and occasionally demonstrates regrowth when treated (Figure 6).
Dissecting cellulitis may present alone or in conjunction with the other entities in the follicular occlusion triad (acne conglobata, hidradenitis suppurativa). It is most common in men with darker skin types. Physical examination demonstrates painful, boggy, suppurative nodules that may progress to sinus tract formation (Figure 7). It is thought to result from abnormal follicular keratinization and obstruction, leading to bacterial infection and eventual follicular destruction.
If there are symptoms and signs of ongoing inflammation, clinical evidence of activity, and progressive hair loss, treatment should proceed. For the lymphocytic group of cicatricial alopecias, hydroxychloroquine 200 milligrams twice daily or doxycycline 100 milligrams twice daily are first-line therapies (Chiang, Sah, Cho, Ochoa, & Price, 2010; Price, 2006). For hydroxychloroquine, a complete blood count, liver function tests, and a baseline eye examination should be performed; a glucose-6 phosphate dehydrogenase level is recommended in patients of African ancestry.
If disease progression continues after these two drugs, second-line therapies such as mycophenolate mofetil (0.5 g twice daily for 1 month then 1 g twice daily for 5 months; Cho et al., 2010) and cyclosporine (3 to 5 milligrams/kg/day or 100 mg three times daily for 3 to 5 months; Mirmirani, Willey, & Price, 2003) should be considered. Of interest, recently, the efficacy of pioglitazone, a peroxisome-proliferator-activated receptor gamma agonist more traditionally used in the treatment of Type 2 diabetes, was effective at a dose of 15 milligrams daily in one patient with treatment-resistant LPP (Karnik et al., 2009; Mirmirani & Karnik, 2009). Although we still start with more traditional therapies, be on the watch for more to come on this potentially exciting new class of medications.
Adjuvant therapy with intralesional triamcinolone acetonide (at a concentration of 10 mg/ml), high-potency topical corticosteroids, topical tacrolimus, topical pimecrolimus, and fluocinolone acetonide 0.01% scalp oil (Derma-Smoothe/FS) may provide additional benefit.
Treatment: Neutrophilic Group
Treatment for the predominantly neutrophilic-plasmacytic group of cicatricial alopecias hinges on the selection of an appropriate antimicrobial agent. In some cases, this may mean repeated cultures of pustules or hair bulbs from areas of disease activity. The most commonly cultured organism remains S. aureus (Powell, Dawber, & Gatter, 1999). Depending on the predominant pathogens and resistance patterns within a given community, therapies may include 10 weeks of cephalexin (500 mg four times a day), doxycycline (100 mg twice daily), clindamycin (300 mg twice daily), or ciprofloxacin (750 mg twice daily), either alone or in combination with rifampin (600 mg once a day for 10 days). It should be noted that although rifampin is indispensable for the treatment of both methicillin-resistant S. aureus and Streptococcus pyogenes when combination therapy is warranted, resistance develops quickly when this agent is used as monotherapy. Rifampin is also a potent inducer of the cytochrome P-450 oxidative system, and careful review of the patient's current medications is needed to rule out any clinically significant drug interactions such as with oral contraceptives and coumadin. If S. aureus is found, add mupirocin ointment intranasally once daily for 1 week and then once a month. After 10 weeks, the patient should be reassessed.
In dissecting cellulitis, microbial cultures are usually negative for pathogens. Isotretinoin is often effective, but the starting dose must be low (20 mg daily) to avoid exacerbation.
SUMMARY FOR THE PATIENT
For all cicatricial alopecias, it is essential that the clinician appropriately counsel the patient that the goals of treatment are to relieve symptoms and signs of inflammation and retard the spread of hair loss. Regrowth is generally not possible. However, the patient should be reassured that these disease processes have no effect on their general health, are mostly confined to the scalp, are not hereditary, are not contagious, and occur in an otherwise healthy population.
Chiang, C., Sah, D., Cho, B. K., Ochoa, B. E., & Price, V. H. (2010). Hydroxychloroquine and lichen planopilaris: Efficacy and introduction of Lichen Planopilaris Activity Index scoring system. Journal of the American Academy of Dermatology, 62(3), 387-392.
Cho, B. K., Sah, D., Chwalek, J., Roseborough, I., Ochoa, B., Chiang, C., et al. (2010). Efficacy and safety of mycophenolate mofetil for lichen planopilaris. Journal of the American Academy of Dermatology, 62(3), 393-397.
Karnik, P., Tekeste, Z., McCormick, T. S., Gilliam, A. C., Price, V. H., Cooper, K. D., et al. (2009). Hair follicle stem cell-specific PPARgamma deletion causes scarring alopecia. Journal of Investigative Dermatology, 129(5), 1243-1257.
Mirmirani, P., & Karnik, P. (2009). Lichen planopilaris treated with a peroxisome proliferator-activated receptor gamma agonist. Archives of Dermatology, 145(12), 1363-1366.
Mirmirani, P., Willey, A., & Price, V. H. (2003). Short course of oral cyclosporine in lichen planopilaris. Journal of the American Academy of Dermatology, 49(4), 667-671.
Ochoa, B. E., King, L. E. Jr., & Price, V. H. (2008). Lichen planopilaris: Annual incidence in four hair referral centers in the United States. Journal of the American Academy of Dermatology, 58(2), 352-353.
Olsen, E. A., Bergfeld, W. F., Cotsarelis, G., Price, V. H., Shapiro, J., Sinclair, R., et al. (2003). Summary of North American Hair Research Society (NAHRS)-sponsored Workshop on Cicatricial Alopecia, Duke University Medical Center, February 10 and 11, 2001. Journal of the American Academy of Dermatology, 48(1), 103-110.
Powell, J. J., Dawber, R. P., & Gatter, K. (1999). Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings. British Journal of Dermatology, 140(2), 328-333.
Price, V. H. (2006). The medical treatment of cicatricial alopecia. Seminars in Cutaneous Medicine and Surgery, 25(1), 56-59.
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