Alopecia Areata: The Clinician and Patient Voice

Topical corticosteroids are the mainstay of treatment in patients younger than 10 years old or in patients unable to tolerate intralesional steroid injections.^10,17 Typically, they are less effective than intralesional corticosteroids and are used in conjunction with other treatments in less severe disease. As with intralesional corticosteroids, adverse effects involve skin changes. High-potency corticosteroids under occlusion can, however, be effective even in severe disease, even though they are not recommended in children due to the risk of sys-temic absorption.²¹

Oral corticosteroids can be used in the short-term treatment of AA,¹⁷ with a 6-week course showing significant benefit in mild-to-extensive AA.²² Pulse administration is recommended over continuous administration.²³ However, the benefit is not durable, with significant relapse rates after discontinuation.¹⁷ Also, long-term use of oral corticosteroids is limited by their adverse effects, including suppression of the pituitary-adrenal axis, effects on bone growth or integrity leading to osteoporosis, ocular changes, and worsening of hypertension or diabetes. Because oral corticosteroids have a long history of use, the danger is that clinicians may become comfortable using them. Clinicians should always consider their long-term adverse effects and ensure that patient safety is not compromised.  

Minoxidil, topical or oral, is often used as adjuvant therapy for AA to promote hair growth.^10,17  Topical and oral forms have been shown to be effective in stimulating hair regrowth; they are, however, less effective in severe AA. But in a recent case study of treatment-resistant alopecia universalis, co-administration of oral minoxidil with a JAK inhibitor (tofacitinib) appeared to improve the patient's SALT score from S5 (100% hair loss) to S2 (35% hair loss).²⁴ Adverse effects of topical minoxidil are usually mild, including scalp itching and dermatitis.¹⁷ Hypertrichosis, lightheadedness, fluid retention, tachycardia, and headache are potential adverse effects of oral minoxidil.¹⁰ 

JAK inhibitors are the newest class of treatments for AA, with oral baricitinib being approved for use in adults with severe AA,²⁵ others in development (ie, ritlecitinib, deuruxolitinib), and several being used off-label or in clinical studies (ie, tofacitinib, ruxolitinib, and brepocitinib). The IFNgamma- and IL-15-driven activation of cytotoxic T cells that contributes to AA pathophysiology is mediated in part by JAK, and JAK inhibition has been shown to reverse the effects of AA.²⁶ Oral, topical, and sublingual modes of delivery are being investigated. Current data suggest that oral formulations are the most effective, while the topical form lacks efficacy.^27,28 Compared to controls, oral formulations have a higher response rate (defined as 50% improvement in SALT score) (risk ratio of 6.86).²⁷ 

With respect to baricitinib in phase 3 trials of patients with SALT scores greater than or equal to 50, 36 weeks of treatment led to improved SALT scores of less than or equal to 20 in 36% to 39% of patients using 4 mg and in 19% to 23% of patients using 2-mg doses compared with 3.3% to 6.2% of patients using placebo.²⁹ Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more commonly reported with baricitinib than with placebo. As a drug class, JAK inhibitors, including baricitinib, have a black box warning for serious infections, malignancy, major adverse cardiovascular events, and thromboembolic events.^10,25 These events are rare in patients with AA, and clinicians should discuss with their patients the efficacy and side effects of this new treatment option to reach a shared decision.³⁰ 

Topical immunotherapy, diphenylcyclopropenone (DPCP) or squaric acid dibutyl ester (SADBE) may be used to induce contact dermatitis of the scalp and can modify the cytokine profile. This treatment is effective in approximately 30% of patients, including patients with severe AA.³¹ 

Medical therapy: Do not delay treatment for AA. Spontaneous remission may occur, more so with localized disease involving < 25% of the scalp, but generally, mild-to-moderate disease should be treated with topical agents, while moderate-to-severe disease is treated with systemic therapies. Current treatments for AA are limited by their unsatisfactory efficacy and adverse event profiles. The newer JAK inhibitors have better efficacy and are generally safe, at least in the short term, but have a relapse rate of 54% with discontinuation.²⁷ Therefore, therapies with increased long-term efficacy and safety are needed. 

Supportive therapy: Alopecia areata is associated with significant psychological burden requiring consideration of psychological interventions and access to support groups when developing treatment strategies. Further, treatment response with current therapies takes time. For example, while waiting for hair regrowth, patients require wigs and other camouflaging agents to conceal hair loss. Improved access to these agents, as well as counseling for coping strategies, is needed.