|Year : 2019 | Volume
| Issue : 2 | Page : 78-82
Severe alopecia areata: Analysis of treatment outcome
Thamer Mubki1, Rasha Zainalabidin2
1 Department of Dermatology, College of Medicine, Al-Imam Mohammed Bin Saud Islamic University; Aesthetica Clinics, Riyadh, Saudi Arabia
2 Department of Medicine, Imam Abdulrahman Al Faisal Hospital; Derma Clinics, Riyadh, Saudi Arabia
|Date of Submission||18-May-2019|
|Date of Acceptance||28-May-2019|
|Date of Web Publication||30-Jul-2019|
Dr. Thamer Mubki
PO Box 230244, Riyadh 11321
Source of Support: None, Conflict of Interest: None
Problem Statement: Data on treatment options in severe alopecia areata (AA) are limited. All available therapies are currently off-label. Choosing the best therapy could be challenging.
Materials and Methods: Medical records of a cohort of 55 patients with severe AA, involving >40% of scalp, including totalis and universalis who were started on topical or systemic therapy, were reviewed for efficacy and safety data. Response to therapy was evaluated using changes in the validated Severity of Alopecia Tool (SALT). SALT50 was defined as 50% regrowth and was regarded as a treatment success.
Results: Thirty-two patients met the study inclusion criteria. Mean treatment duration was 11.4 months. 78% of patients had AA for >1 year. 41% had AA totalis/universalis. 53% achieved SAL50 using the described treatments. However, only 38% of AA totalis/universalis achieved SALT 50 as compared to 62% of patchy type (P = 0.148). SALT50 was achieved in 27% of patients using anthralin, 30% with diphenylcyclopropenone acetate, 28% with intralesional steroid injection, and 56% using tofacitinib. 55% of patients who used minoxidil 5% achieved SALT50 compared to only 40% of those who did not use it (P = 0.026).
Conclusions: Treatment of severe AA is possible. More than 50% of cases may respond to therapy. AA totalis/universalis may, however, respond less favorably than the patchy type. Tofacitinib, and possibly other Janus kinase inhibitors, is very promising therapies for severe cases. Minoxidil 5% solution was significantly associated with better response to therapies in severe AA cases.
Keywords: Alopecia areata, hair, Janus kinase inhibitors, tofacitinib
|How to cite this article:|
Mubki T, Zainalabidin R. Severe alopecia areata: Analysis of treatment outcome. Imam J Appl Sci 2019;4:78-82
| Introduction|| |
Alopecia areata (AA) is common nonscarring hair loss. Pathogenesis is immune-mediated with an acute-onset and self-limiting course in 67% of cases. However, 33% of AA cases may progress to chronic disease with multiple patches that relapse and remit over many years or even progress to AA totalis/universalis requiring different types of therapies. Choosing the best therapeutic option could be quite challenging for treating physicians, as there is no yet an Food and Drug Administration-approved therapy for AA. Current treatments are largely off-label and have variable success rates. Patient's age, disease severity, cost, and patient's compliance are among the most important factors influencing the treatment choice. Herein, we review the treatment outcomes and safety of a group of patients with severe AA including AA totalis/universalis treated at our specialized hair clinic, derma clinic, Riyadh, Saudi Arabia.
| Materials and Methods|| |
This is a cohort study, in which we examined the medical records database of 55 patients with severe AA who have been following in our specialized hair clinic, derma clinic, Riyadh, Saudi Arabia, from March 2016 to March 2019. The study was approved by the Institutional Board Committee.
The severity of AA was evaluated using the validated Severity of Alopecia Tool (SALT) as detailed in the AA Investigational Guidelines.
- SALT S3–S5 corresponding to 50%–100% scalp hair loss
- Age ≥18 years
- AA episode lasting >6 months at time of presentation
- Regular on treatment and follow-up for a minimum of 6 months.
The primary treatments used were anthralin 2% cream, topical immunotherapy using diphenylcyclopropenone acetate (DPCP), intralesional steroid injections (ILS), and tofacitinib citrate 5 mg BID. Minoxidil 5% solution was occasionally used as additional supportive therapy.
Anthralin 2% cream was used as a daily short-contact therapy. DPCP was used once per week and was washed off after 48 h in an escalating concentration from 0.0001 to 2% depending on tolerability of the patient's scalp. Triamcinolone acetonide was used in concentrations 2.5 mg–5 mg/ml, with a total dose up to 20 mg/month, single monthly intralesional injections. Tofacitinib citrate 5 mg tablet (Xeljanz) was used as twice daily. Patients were screened for hepatitis B, hepatitis C, and interferon gamma for latent tuberculosis before starting tofacitinib. Baseline complete blood count, liver function test, and lipid profile were also done.
Minoxidil 5% solution, 1 ml, was used as supportive therapy for some patients, twice daily application for men and once daily for women.
Treatments were used interchangeably between patients, and hence, patients who failed to respond to a given treatment after a minimum duration of 6 months were shifted to another treatment after a wash-out period of 2 months.
Treatment outcome was evaluated by calculating the percentage regrowth of scalp hair (SALT at baseline – SALT at follow-up)/SALT at baseline) × 100. SALT50 was defined as 50% regrowth. A Chi-square test with Yates continuity correction and Fisher exact test were used for comparisons, P < 0.05 was regarded as statistically significant.
| Results|| |
Thirty-two patients met the study inclusion criteria and were included in analysis. Treatment duration ranges from 6 to 28 months, mean 11.4 months. The group included 22 females and 10 males (female-to-male ratio 2.2:1) [Table 1]. 69% of patients had the first episode of AA before the age of 18 years. 78% of subjects had AA for more than 1 year and 39% had the disease for >5 years. 41% of patients had AA totalis/universalis, neither gender nor age of onset influenced developing more severe disease (P = 0.636, 0.548, respectively).
Nail involvement was observed in 22% of cases, and it was more prevalent in patients with AA totalis/universalis compared to patchy type (P = 0.008).
17 out of 32 patients (53%) achieved SAL50 using the described treatments. However, only 38% of AA totalis/universalis achieved SALT 50 as compared to 62% of the patchy type (P = 0.148) [Table 2].
|Table 2: Improvement measured as a change in Severity of Alopecia Tool score|
Click here to view
Out of 32 patients, 15 used anthralin, 27% of the latter achieved SALT50 [Table 3].
DPCP was used in 10 patients. SALT50 was achieved in 30% of treated patients. Patchy AA responded better than AA totalis/universalis (P = 0.049).
Eighteen out of 32 patients received ILS as the main mode of therapy. 28% achieved SALT50.
Nine out of 32 patients received oral tofacitinib. SALT50 was achieved in 56% of treated patients. Although AA totalis/universalis improved as good as the patchy type (P = 0.526), 2 out of 2 patients (100%) with patchy AA achieved SALT50 as compared to 3 out of 7 patients (43%) with AA totalis/universalis. 4 out of 5 (80%) patients who achieved SALT50 had AA for duration of <5 years (P = 0.147).
Minoxidil 5% solution was used as supportive therapy in 22 out of 32 patients. 55% of patients who used minoxidil achieved SALT50 compared to only 40% of those who did not use it (P = 0.026) [Table 4].
| Discussion|| |
AA is completely unpredictable disease with spontaneous remission ranging from 8% for extensive disease including AA totalis/universalis to 68% for limited patchy AA. Many treatment options have been described in the literature with variable success rates.
Anthralin (dithranol) cream in different concentrations (0.2%–3%) has been reported in the literature with variable response rates. Using anthralin (0.2%–0.8%), Schmoeckel et al. reported a “cosmetically good” hair regrowth in 75% of patients with patchy AA compared to 25% in AA totalis. Similarly, Deshpande et al. reported a regrowth of cosmetically acceptable hair in 75% of AA using anthralin 1.1% paste in combination with minoxidil 2%–5% solution. Ngwanya et al. used a higher concentration of anthralin up to 3% and achieved SALT50 in 61% and 37% of patients with mild and severe AA, respectively.
SALT50 was achieved in 23% of our patients with severe AA using anthralin 2%, with the mean treatment duration of 9 months.
ILS, mainly triamcinolone acetonide, is commonly considered the first-line treatment for limited patchy AA and as supportive therapy for more severe cases. Achieving SALT50 can be expected in 80% of patients with limited AA; however, less favorable improvement is commonly seen in more severe disease. In accordance with the latter, only 28% of our patients with severe AA achieved SALT50 using ILS as the main treatment after a mean duration of 9 months. Only mild local skin atrophy was reported in a few patients. Spacing treatment sessions and using a lower concentration (2.5 mg/ml) were sufficient to reverse atrophy.
DPCP has been considered as one of the main effective treatments for extensive AA. DPCP is commonly applied by the medical team in the clinic 2–4 times per week to avoid possible side effects that could possibly result from inappropriate application of the drug by patients. Poor patients' compliance is one of the main drawbacks of this treatment modality. Discontinuation of DPCP due to financial and temporal reasons has been reported to reach 36% in one study. Self-application of DPCP has been reported by Lee and Lee In the latter, AA patients have been shifted to home therapy after having the treatment in the clinic for at least 3 months with comparable efficacy and safety profile. Variable response rates (9%–87%) have been reported; however, a systematic review reported a mean response rate of 53.75 + 0.79%., One-third of our DPCP-treated patients achieved SALT50, indicating a positive medical response. Pruritus, blisters, depigmentation, and cervical lymphadenopathy are the most commonly reported side effects of DPCP. In our group, only mild pruritus in most cases and occasional blisters in two patients were reported.
Janus kinase (JAK) inhibitors are anti-inflammatory drugs that target both INF-gamma and interleukin-15 pathways leading to activation of hair follicle stem cells. Since the first report of Craiglow and King in 2014, a few more studies reported the effectiveness of JAK inhibitors in treating AA. Sixty-six AA patients, treated with Tofacitinib 5 mg twice daily (anti JAK1 and 3), were evaluated by Kennedy Crispin et al. In the latter, 64% responded to treatment and 32% achieved SALT50 after 3 months. Changes in SALT score were independent of age nor sex; however, patchy AA had a significant higher chance of improvement as compared to AA universalis. Similarly, Liu et al. reported 90 patients with severe AA. 42% of patients achieved SALT50. However, higher doses of tofacitinib; 10 mg twice daily or oral pulse prednisolone; 300 mg per month for 3 months were concomitantly given to nonresponders after 3 months of therapy with tofacitinib 5 mg twice daily alone. Ruxolitinib, a JAK1 and 2 receptor antagonist, at a dose of 20 mg twice daily resulted in hair regrowth in 75% of patients. Almutairi et al. compared ruxolitinib 10 mg twice daily to tofacitinib 5 mg twice daily in 80 patients with severe AA. About 84% and 78% of treated patients achieved SALT50, respectively, with no statistically significant difference between treatment modalities. Patchy AA showed a better response compared to AA totalis/universalis in both groups. In our sample, 56% of patients, treated with tofacitinib 5 mg twice daily, achieved SALT50 as compared to 32%–78% of treated patients in the latter studies,, and in accordance with other studies, however, our sample size is smaller, patchy AA and shorter disease duration seem to respond better than AA totalis/universalis or longer disease duration. Tofacitinib is generally safe and well tolerated. We did not encounter any side effects in our sample. However, minor side effects such as headache, mild and transient elevation in aspartate transaminase/alanine transaminase, mild increase in upper respiratory tract, and urinary tract infections have been reported in other studies.,
Minoxidil is commonly used as an adjunctive to other treatment modalities in AA. Stimulation of hair regrowth has been reported in AA patients. Minoxidil 3% solution, as adjunctive, was evaluated in patients with severe AA by a double-blind placebo-controlled trial. Hair regrowth was documented in 64% of treated patients as compared to 36% of those treated with placebo. On the other hand, minoxidil 3% solution failed to produce any statistically significant increase in hair regrowth compared to placebo when used as monotherapy in another study. In our study, use of minoxidil 5% solution twice daily as adjunctive was significantly associated with better response to therapies in severe AA cases.
| Conclusions|| |
It is possible to treat severe AA. More than 50% of cases may respond to therapy. AA totalis/universalis may, however, respond less favorably than the patchy type. Tofacitinib and possibly other JAK inhibitors are very promising therapies for severe cases. This study supports the use of minoxidil 5% solution as adjunctive to other treatments for AA.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cranwell WC, Lai VW, Photiou L, Meah N, Wall D, Rathnayake D, et al.
Treatment of alopecia areata: An Australian expert consensus statement. Australas J Dermatol 2019;60:163-70.
Strazzulla LC, Wang EH, Avila L, Lo Sicco K, Brinster N, Christiano AM, et al.
Alopecia areata: An appraisal of new treatment approaches and overview of current therapies. J Am Acad Dermatol 2018;78:15-24.
Olsen EA, Hordinsky MK, Price VH, Roberts JL, Shapiro J, Canfield D, et al.
Alopecia areata investigational assessment guidelines – Part II. National alopecia areata foundation. J Am Acad Dermatol 2004;51:440-7.
Tosti A, Bellavista S, Iorizzo M. Alopecia areata: A long term follow-up study of 191 patients. J Am Acad Dermatol 2006;55:438-41.
Schmoeckel C, Weissmann I, Plewig G, Braun-Falco O. Treatment of alopecia areata by anthralin-induced dermatitis. Arch Dermatol 1979;115:1254-5.
Deshpande D, Dhurat R, Saraogi P, Mishra S, Nayak C. Extensive alopecia areata: Not necessarily recalcitrant to therapy! Int J Trichology 2011;3:80-3.
Ngwanya MR, Gray NA, Gumedze F, Ndyenga A, Khumalo NP. Higher concentrations of dithranol appear to induce hair growth even in severe alopecia areata. Dermatol Ther 2017;30(4).
Tan E, Tay YK, Goh CL, Chin Giam Y. The pattern and profile of alopecia areata in Singapore – A study of 219 Asians. Int J Dermatol 2002;41:748-53.
Cotellessa C, Peris K, Caracciolo E, Mordenti C, Chimenti S. The use of topical diphenylcyclopropenone for the treatment of extensive alopecia areata. J Am Acad Dermatol 2001;44:73-6.
Lee S, Lee WS. Home-based contact immunotherapy with diphenylcyclopropenone for alopecia areata is as effective and safe as clinic-based treatment in patients with stable disease: A retrospective study of 40 patients. J Am Acad Dermatol 2018;78:599-6010.
Pratt CH, King LE Jr., Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers 2017;3:17011.
Jang YH, Jung HJ, Moon SY, Lee WJ, Lee SJ, Lee WK, et al.
Systematic review and quality analysis of studies on the efficacy of topical diphenylcyclopropenone treatment for alopecia areata. J Am Acad Dermatol 2017;77:170-20.
Craiglow BG, King BA. Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J Invest Dermatol 2014;134:2988-90.
Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, et al.
Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight 2016;1:e89776.
Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol 2017;76:22-8.
Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, et al.
Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight 2016;1:e89790.
Almutairi N, Nour TM, Hussain NH. Janus kinase inhibitors for the treatment of severe alopecia areata: An open-label comparative study. Dermatology 2019;235:130-6.
Price VH. Double-blind, placebo-controlled evaluation of topical minoxidil in extensive alopecia areata. J Am Acad Dermatol 1987;16:730-6.
Price VH. Topical minoxidil (3%) in extensive alopecia areata, including long-term efficacy. J Am Acad Dermatol 1987;16:737-44.
[Table 1], [Table 2], [Table 3], [Table 4]