Tofacitinib treatment in a severe pediatric alopecia areata: A case report and a literature review

Dear Editor,

Alopecia areata (AA) is a common autoimmune disease, which is characterized by non‐scarring hair loss and is liable to relapse. Pediatric AA is the most severe form of AA. Compared with adult AA, it is more likely to progress into complete hair loss on the scalp (alopecia totalis, AT) or complete scalp and body hair loss (alopecia universalis, AU). Currently, only few medical therapies are available for severe pediatric AA, which are not effective. In this article, we present a case report of a 6‐year‐old girl with severe AA, who had been effectively treated using the oral tofacitinib therapy. Besides, no relapse was observed after dose reduction with continued therapy. We also provide a brief review of global cases in which tofacitinib treatment was applied in pediatric AA. Tofacitinib can be applied at a minimum age of 4 years, and usually leads to hair growth in the first 3 months, while significant regrowth occurs after 6 months of continued therapy. In summary, tofacitinib could be a potential choice for children with alopecia areata in the future.

A 6‐year‐old girl, weighing 22 kg, was presented to our clinic in June 2021 due to hair loss for more than 2 months. The girl's mother found patches on her daughter's scalp 2 months earlier, which got bigger ever since. The girl had received intramuscular injection with betamethasone once but no obvious improvement was observed. The physical examination showed normal findings. Dermatological examination showed patches on her forehead, two temporal and occipital regions, with a patch area > 50%, positive hair‐pulling test, dents in nails, and Severity of Alopecia Tool (SALT) score of 85.5 (Figure 1). Dermoscopic inspection in the hair loss region showed yellow dots, broken hairs, and exclamation mark hairs. Laboratory tests, including complete blood cell count, liver or renal function, and antinuclear antibody spectrum, were normal. The patient was then diagnosed with severe AA. She was given 10 mg oral prednisone daily, topical halometasone, and 2% minoxidil solution twice a day. After 2 weeks of treatment, limited hair growth was observed in the patch region, which was accompanied with a new patch area, and the hair‐pulling test was positive. Unfortunately, the patient became depressed. Considering that depression might be a side effect of oral prednisone, we discontinued this therapy. We communicated with the patient's parents and obtained their consent to use tofacitinib. Then, the patient was given oral tofacitinib 5 mg a day, while continuing the usage of topical 2% minoxidil solution. After 3 months, the girl had more than 90% hair regrowth (Figure 2) and 70% improvement in the SALT score. The dose of tofacitinib was then reduced to 5 mg every other day. After 6 months, the hair completely regrew, and no relapse was observed. The patient's laboratory indicators, such as the complete blood cell count, liver or renal function, and electrolyte levels, showed normal values after 1 month of treatment and at follow‐up checks every 3 months. No adverse effects, such as infection or headache, were observed.

FIGURE 1.

Before starting tofacitinib.

FIGURE 2.

After 3 months of tofacitinib therapy.

Alopecia areata (AA) is a common autoimmune disease, which negatively affects the health and life quality of the patients, especially in children and adolescents. ¹ In the United States, the prevalence of the AA is 0.1%–0.2% in the general population, children constitute approximately 20% of patients with AA. ² Common methods to treat severe pediatric AA include topical, intralesional, or systemic application of glucocorticoids, topical minoxidil, and systemic immunosuppressives, such as methotrexate. ³ However, all these methods have multiple adverse effects and are liable to relapse. Hence, we still lack an effective treatment for severe pediatric AA.

Previous studies found that the pathogenesis of AA involves CD8⁺ T‐cells attacking hair follicles. A group of cytokines, including IFN‐γ and IL‐15, which dependent on the Janus‐activated kinase Singal transducers and activators of transcription (JAK‐STAT) pathway, further upregulate these CD8⁺ T‐cells, leading to self‐attack of the hair follicles. Besides, IL‐2, IL‐7, IL‐17, and IL‐21, which play an important role in the onset of AA, also depend on the JAK/STAT pathway. ⁴ Therefore, by blocking the JAK/STAT pathway, JAK inhibitors could promote the patients’ hair regrowth. Although this treatment is not officially approved, many clinical trials have verified its safety and efficacy in adult patients with AA. ⁵ However, only few studies introduced tofacitinib therapy for pediatric AA.

A recent pediatric case series by Leslie presented eight adolescents (aged 12–19 years) with AU, who did not benefit from all previous treatments. After 5–18 months of tofacitinib, they all had more than 50% hair regrowth. Craiglow discussed oral tofacitinib in 13 patients aged 12–17 years, among which 10 experienced full hair regrowth after 6.5 months of treatment. ⁶ Furthermore, Craiglow and King reported four patients aged 8–10 years with AA or AU, among which two experienced complete hair regrowth after 3 and 6 months of treatment, one had 62% hair regrowth after 6 months of treatment and one showed no obvious improvement. ⁷ Dai and Chen reported tofacitinib treatment of 2.5 mg per day in three children aged 4–5 years old with AA, among which two had more than 90 % hair regrowth after 12 months of treatment. At the 6 month of treatment, the tofacitinib dose was increased to 2.5 mg 4 days per week and 5 mg 3 days per week for the third patient, who showed full regrowth of eyebrows and eyelashes, and 50% hair regrowth was experienced at the 21st month of treatment. ⁸ Another case study reported a 6‐year‐old AU patient with nail damage, who experienced more than 50% hair growth after 3 months of oral tofacitinib 2.5 mg per day and complete hair regrowth after 6 months of therapy; the nails were improved as well. ⁹ The safety of tofacitinib treatment in children and adolescents is similar to what has been reported in adult patients. Common side effects, such as upper respiratory tract infections, headache, and gastrointestinal discomfort were reported and no new potential risks were found. ¹⁰

Based on above‐mentioned case reports, we suggest oral tofacitinib 5 mg twice a day to be a promising therapy for children and adolescents with AA (aged 8–17 years). In this treatment, hair growth occurs after 3 months of continued therapy, and evident hair regrowth (> 50%) appears after 6 months of treatment. For patients aged ≤ 6 years, more than 90% hair regrowth generally occurs after 6–12 months of oral tofacitinib 2.5–5 mg daily. While some studies pointed out that AA is liable to relapse after the cessation of therapy for 2.7 months, there is no literature about the maintenance or reduction of tofacitinib after complete hair regrowth. ¹¹ In this reported case, 5 mg tofacitinib per day was used for the 6‐year‐old patient, and more than 90% hair regrowth occurred after 3 months of treatment. No relapse was observed after dose reduction for another 6 months. This shows that tofacitinib treatment is a good option for severe pediatric AA, and dose reduction for maintenance does not only prevent recurrence, but also reduces the incidence of adverse effects.

In conclusion, oral tofacitinib treatment presents a new option for severe pediatric AA. However, further research is required to investigate its maximum effect, possibility of relapse after cessation of therapy, maintenance measures, and long‐term impact.

CONFLICT INTEREST STATEMENT

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

DATE AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.