Alopecia areata

Published on 16/03/2015 by admin

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Alopecia areata

Sivanie Vivehanantha and John Berth-Jones

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Alopecia areata (AA) is a T lymphocyte-mediated autoimmune disease of the hair follicle. It is characterized by patchy hair loss developing in otherwise normal skin, with ‘exclamation mark’ hairs around margins of expanding areas. Most cases are limited to one or more coin-sized patches, but in severe cases there may be complete baldness of the scalp (alopecia totalis, AT) or of the entire body (alopecia universalis, AU). The alopecia is non-cicatrizing, and in most cases resolves spontaneously after a few months.

Management strategy

Leaving AA untreated is a reasonable option for many patients. Spontaneous remission often occurs, and no treatment has been shown to alter the long-term prognosis. Treatment can be time-consuming, uncomfortable, and potentially toxic, and relapse after treatment may be difficult to cope with. Many patients are distressed so psychological support can be helpful, and careful ‘management of expectations’ from treatment is important. Contact with other sufferers and support groups may also help.

The treatments listed as first line are the most consistently effective and safe; however, the response to any treatment is variable and depends largely on the extent and duration of the alopecia. This is one reason why the results of trials are often conflicting. Trials involving recent-onset patchy alopecia may have a high rate of spontaneous remission, whereas trials limited to severe long-standing disease that is resistant to treatment do not exclude efficacy in mild alopecia.

Intralesional corticosteroid injections are considered first-line treatment for adult patients when only one or two small patches of alopecia are present, but can be used on larger areas if patients can tolerate the discomfort. The authors most frequently use triamcinolone acetonide aqueous suspension (2.5–10 mg/mL) injected intradermally in multiple 0.05–0.1 mL doses, and do not inject more than 20 mg in total at one visit. Treatment is repeated at intervals of 4–12 weeks. A concentration of 2.5 mg/mL can be used on the eyebrow area. The main side effect is pitting atrophy which is usually transient.

Topical immunotherapy is the induction of contact allergy on the scalp. Contact sensitizers include dinitrochlorobenzene (DNCB; now considered potentially carcinogenic and therefore no longer used), squaric acid dibutyl ester (SADBE; this has limited stability), and diphencyprone (DPCP, diphenylcyclopropenone). The latter compound combines efficacy and safety with a practical shelf-life and has become the most widely used. DPCP can initially be applied as 2% lotion to a small area (2–4 cm2) of scalp until the site of application becomes pruritic and erythematous. Treatment is then continued over a larger area with weekly applications of lower concentrations, typically ranging from 0.001% to 0.1%. The lowest concentration that maintains mild erythema or pruritus should be used. Our patients usually have half of their scalp treated initially, until a favorable result means treatment can then be extended to the contralateral scalp. This is one of the best-documented therapies for AA, and is the one most likely to be effective in extensive long-standing disease. However, the timing of the response is quite unpredictable, so the authors treat patients for as long as they wish to continue. Relapse rates may be high. Side effects include regional lymphadenopathy and rarely autosensitization, resulting in generalized eczema or even an eruption resembling erythema multiforme. Vitiligo may develop, although this is usually confined to the treated areas. For this reason, sensitization therapy is best avoided in patients with pigmented skin types.

Topical corticosteroids have demonstrated efficacy in some studies of patchy AA, particularly those using potent steroids with occlusion. They are fairly inexpensive and practical to use, and the main side effect is transient folliculitis. Results are variable, however, and they do not appear to be very effective in AT or AU.

Topical prostaglandin analogues have been reported as effective in treating the eyelashes of patients affected with AU.

Irritants, including anthralin (dithranol) and retinoic acid, are safe and practical to use, although the evidence for their efficacy is limited. For patients with dark hair, anthralin has the advantage of camouflaging a pale area of scalp by staining it brown. Application needs to be frequent and at a fairly high concentration, as it needs to induce significant irritation to be effective. Retinoic acid is more practical for use in patients with fair hair.

Topical minoxidil is a safe treatment, but most studies have failed to demonstrate a response of cosmetic value in most patients.

Systemic corticosteroids are effective in some cases if high doses are used. However, AT, AU, and ophiasiform AA do not respond well and high relapse rates make this toxic treatment hard to justify. Given the level of emotional disturbance associated with alopecia, there is clearly a risk of encountering serious difficulty in withdrawing treatment.

Systemic cyclosporine and methotrexate also appear effective if given in high dosage, but the response is not maintained on cessation of therapy, and again it is difficult to justify use of such potentially toxic modalities.

Other less conventional treatments include PUVA, inosiplex, nitrogen mustard, lasers, topical bexarotene, topical azelaic acid, combination of simvastatin and ezetimibe, combination of topical garlic and topical steroids, cryotherapy, aromatherapy, onion juice etc.

Treatments that do not appear to be beneficial include topical imiquimod, topical tacrolimus, topical pimecrolimus, botulinum toxin type A, topical tri-iodothyronine ointment, photodynamic therapy, narrowband UVB, topical 5-fluorouracil, capsaicin and, so far, biologics.

Many patients find wigs an acceptable camouflage. Tattooing (dermatography) of the eyebrows may lead to a more socially acceptable image for some patients.

First-Line therapies

image Intralesional steroids A
image Topical immunotherapy B

Topical immunotherapy with diphenylcyclopropenone in the treatment of chronic extensive alopecia areata.

Sotiriadis D, Patsatsi A, Lazaridou E, Kastanis A, Vakirlis E, Chrysomallis F. Clin Exp Dermatol 2007; 32: 48–51.

In this prospective open clinical trial, 17 patients had either AA totalis (AAT) or AA universalis (AAU) and 24 had severe alopecia (>50% scalp involvement). After sensitization with DPCP 2% in acetone, progressively higher concentrations were applied once a week for a period of 6–12 months. Of the 41 patients, 38 (16 with AAT or AAU and 22 with extensive AA) completed therapy. Significant hair regrowth was observed in five patients with AAT or AAU (31.25%) and ten patients with extensive alopecia (45.4%). The above results were sustained in 66.6% of patients for a 12-month follow-up period.

Second-Line therapies

image Topical corticosteroids B
image Anthralin/dithranol B
image Retinoic acid B
image Topical minoxidil B
image Bimatoprost / Latanoprost eye drops (for eyelashes) B
image PUVA B

Latanoprost in the treatment of eyelash alopecia in alopecia areata universalis.

Coronel-Perez IM, Rodriguez-Rey EM, Camacho-Martinez FM. J Eur Acad Dermatol Venereol 2010; 24: 481–5.

A 2-year prospective, non-blinded, non-randomized, controlled study of 54 subjects with AAU and eyelash alopecia. The control group comprised ten subjects who received injections of 0.5 mg/cm2 of triamcinolone acetonide (TAC) in their eyebrows and 1 mg/cm2 of TAC injections in affected scalp. The treatment group included 44 subjects who received the same treatment as the control group in scalp and eyebrows, but they also applied a drop of latanoprost 0.005% (50 µg/mL) ophthalmic solution to their eyelid margins every night. In the treatment group, there was complete regrowth in 17.5%, moderate regrowth in 27.5%, slight regrowth in 30% and no response in 25%. No patients had cosmetically acceptable eyelash regrowth in the control group.

Third-Line therapies

image Systemic corticosteroids B
image Systemic cyclosporine C
image Oral minoxidil B
image Sulphasalazine B
image Methotrexate C
image Azathioprine C
image Inosiplex (inosine pranobex) B
image Nitrogen mustard C
image Dermatography B
image Cryotherapy B
image Pulsed infrared diode laser C
image Excimer laser C
image Topical bexarotene C
image Topical azelaic acid C
image Combination treatment of simvastatin and ezetimibe E
image Aromatherapy B
image Onion juice B
image Combination of topical garlic gel and topical betamethasone valerate B

Placebo-controlled oral pulse prednisolone therapy in alopecia areata.

Kar BR, Handa S, Dogra S, Kumar B. J Am Acad Dermatol 2005; 53: 1100–1.

Forty-three patients were randomized to receive oral prednisolone 200 mg weekly (23) or placebo (20) for 3 months. All patients had more than 40% scalp hair loss, or more than ten patches of AA, for more than 9 months. Eight of 23 in the treatment group showed more than 30% regrowth, compared to none in the placebo group. More than 60% regrowth occurred in only two patients, both within the treatment group. Side effects occurred in 55% of the treatment group, compared to 11% in the placebo group, although all were temporary.

Numerous reports of using systemic corticoids over the last 60 years in various doses and regimens indicate that high doses can be effective while treatment is continued. There is no convincing evidence of any change to the natural course of the disease when treatment is stopped.

Combination of topical garlic gel and betamethasone valerate cream in the treatment of localised alopecia areata: a double-blinded randomised control study.

Hajheydari Z, Jamshidi M, Akbari J, Mohammadpour R. Indian J Dermatol Venereol Leprol 2007; 73: 29–32.

In this double-blinded randomized control trial, 40 patients were divided into two groups of garlic gel and placebo. Garlic gel was rubbed on the alopecia patches under dressing and left for 1 hour, twice daily for 3 months in the garlic group. The same procedure was carried out in the control group with placebo gel. Both groups received topical corticosteroid (betamethasone cream 0.1% in isopropyl alcohol) twice daily. Good and moderate responses were observed in 19 (95%) patients in the group treated with garlic gel and one (5%) patient in the placebo group.

Undoubtedly the worst-smelling treatments!

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