Introduction
Alopecia areata (AA), a common, immune-mediated, non-scarring form of hair loss, affects up to 2% of the general population in all ethnic-, sex-, and age-based groups.1 Besides patchy loss of head hair, AA may cause varying degrees of eyebrow, eyelash, pubic, and axillary hair loss. It can also cause nail dystrophy in severe cases. Baricitinib, an inhibitor of Janus kinase (JAK)1/2, has been approved for treatment of severe AA in adults by the Food and Drug Administration (FDA).2 However, there is still scanty clinical evidence for the use of JAK inhibitors in adolescents and pediatric patients with severe AA. The impairment of quality of life, urgent need for treatment, frequent relapses, and safety issues around medication make the treatment of adolescent and pediatric AA patients challenging.
Upadacitinib, a JAK 1 inhibitor, has been used to treat atopic dermatitis in patients aged 12 and older,3 despite its efficacy and safety in adolescents and pediatric patients with severe AA being unclear. Here, we report a case series of upadacitinib treatment of adolescents with severe AA and present the findings of a narrative review.
Materials and Methods
Adolescents with severe AA were recruited from the outpatient department of dermatology and completed 6 months of follow-up between November 2023 and December 2024. The inclusion criteria were as follows: (1) age from 12 to 17 years at the time of enrollment; (2) severe AA as evidenced by Severity of Alopecia Tool (SALT) scores over 50; (3) AA refractory to more than 3 consecutive months of at least one type of systemic therapy, including corticosteroids and immunosuppressive agents; and (4) patient strongly desirous of further treatment. The exclusion criteria were as follows: (1) contraindications to upadacitinib such as severe infection, tumor, thrombosis, and allergy; (2) aged less than 12 or over 18 years at the time of enrollment; (3) mild or moderate AA as evidenced by SALT scores less than 50; (4) no systemic therapy before initiation of a JAK inhibitor or treatment course less than 3 months; and (4) failure to attend for follow-up visits. All enrolled patients underwent full laboratory examinations, including antinuclear antibodies, thyroid function, plasma trace elements, immunoglobulin, ferritin, vitamin A, vitamin E, coagulation function, chest radiograph and screening for Hepatitis B virus and tuberculosis. All participants received upadacitinib 15 mg/day orally. SALT scores were used to assess AA severity and activity at monthly follow-ups. Adverse events were recorded during follow-up. The study was approved by the Ethics Committee of Peking Union Medical College Hospital, and complied with the Declaration of Helsinki. Written informed consent for publication was obtained from these patients’ legal guardians.
We conducted a literature review of the PubMed, Web of Science Core Collection database and Cochrane Library on 14th August 11, 2025. The search terms were ((alopecia areata) OR (alopecia totalis) OR (alopecia universalis)) AND (upadacitinib) AND ((Adolescent) OR (children) OR (pediatric)). Articles that met the following inclusion criteria were analyzed: (1) pediatric and adolescent patients; (2) patients with AA received upadacitinib treatment; and (3) papers written in English. The exclusion criteria were as follows: (1) adult patients who did not meet the age criteria.; (2) incomplete data; and (3) patient with comorbidities that cannot receive upadacitinib treatment. Two authors independently screened and extracted information from the articles.
Results
Case Series
This is a retrospective case series. The cohort of this case series comprised three adolescents with severe AA (Table 1). Their mean age was 16.33 years (range 15–17 years) and the median duration of disease 6 years (range 1–10 years). None of the patients in this case series had a family history of AA or personal history of atopic dermatitis, allergic rhinitis, or asthma. The immunoglobulin E concentrations of these three patients were all within the normal range. All three had severe AA, with a median SALT score of 86.67 (range: 73–100, all > 50). Besides severe loss of head hair, two of the patients also had loss of eyebrow, eyelash, pubic, and axillary hair; additionally, one had nail dystrophy. The disease of all three patients was refractory to at least one type of systemic therapy, prior treatment having included systemic corticosteroids (n=3), cyclosporine (n=1), glycyrrhizin (n=1), traditional Chinese medicine (n=1), and topical minoxidil (n=3).
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Table 1 The Demographic Data and Clinical Response for Upadacitinib Treatment in This Case Series
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All three participants had received upadacitinib treatment at 15 mg/day for 6 consecutive months (Figure 1). Regrowth of eyebrow and pubic hair occurred earlier than regrowth of head hair, regrowth of eyebrows and pubic hair occurring in the first and second months after upadacitinib treatment, respectively, whereas obvious regeneration of head hair occurred approximately 4 months after initiating upadacitinib treatment. The median SALT score dropped to 36.33 (range: 15–57), representing a reduction of 58.08%, after 6 consecutive months of upadacitinib treatment (Figure 2). Additionally, our patient’s eyelashes regrew later than their head, eyebrow, and pubic hair. However, there was no improvement in nail dystrophy after upadacitinib treatment. All participants in this case series tolerated upadacitinib treatment well. Mild acne was the most common adverse event, developing in all three participants and resolving in response to topical fusidic acid. No moderate or severe adverse events were reported during follow-up. Upadacitinib treatment was continued after 6 months’ treatment.
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Figure 1 The clinical manifestations for severe AA adolescent patients. (A) Patient 1 before treatment; (B) Patient 2 before treatment; (C) Patient 3 before treatment; (D) Patient 1 after 6 months of upadacitinib treatment; (E) Patient 2 after 4 months of upadacitinib treatment; (F) Patient 3 after 1 month of upadacitinib treatment.
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Figure 2 SALT score improvement before and after upadacitinib treatment.
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Literature Review
A total of seven papers were finally included after implementation of the inclusion and exclusion criteria.4–10 Reported details concerning upadacitinib for treatment of AA in adolescent patients are summarized in Table 2. Up to now, a total of 26 adolescents with AA, including the three in the present study, from five countries, comprising Canada, China, Korea, Italy, and Poland, have reportedly received upadacitinib treatment. The youngest reported patient with severe AA to receive upadacitinib treatment was 9 years old. This patient had significant regrowth of head hair after 3 months’ treatment and stopped upadacitinib treatment without relapse from the 5-month follow-up.9 The most commonly prescribed dosage of upadacitinib in adolescents with severe AA was 15 mg/day. Sporadic hair regeneration has been reported to occur as early as the second week after initiating upadacitinib treatment.9 However, the time of onset of hair regrowth in most reports is 4 to 6 weeks after initiating treatment4,6,8 and the longest period of treatment with upadacitinib is 12 months.5,10 Comorbidities in adolescents with severe AA receiving upadacitinib treatment have included atopic dermatitis (AD, n=10), vitiligo (n=1), thyroiditis (n=1), conjunctivitis (n=2), allergic rhinoconjunctivitis (n=1), Crohn’s disease (n=1) and eosinophilic gastroenteritis (n=1). Additionally, besides inducing significant regrowth of hair, upadacitinib treatment has contributed to improvements in AD, vitiligo, and Crohn’s disease. Our study provides more clinical data on response to upadacitinib treatment in adolescents with severe AA and without comorbidities. Overall, upadacitinib is a well-tolerated and safe treatment in adolescents with severe AA. Mild adverse events have been reported, including increased creatine phosphokinase (n=8), onset or exacerbation of acne (n=6), mild upper respiratory tract infection (n=1), and transient mild leukopenia (n=1). To our knowledge, severe adverse events have not been reported in adolescents with severe AA.
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Table 2 The Literature Review Concerning Upadacitinib for Treatment of AA In Adolescent Patients
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Discussion
A common autoimmune, non-scarring form of hair loss, AA has a slightly higher prevalence in pediatric and adolescent patients than in adults. It has been estimated that pediatric and adolescent patients with AA are more susceptible to autoimmune and metabolic disorders than are pediatric and adolescent individuals in general.11 AD is one of the most common comorbidities in pediatric and adolescent patients with AA.11 A systematic review found that topical corticosteroids and contact immunotherapy are the first and second commonly preferred treatments for pediatric and adolescent patients with AA.12 However, the management of refractory, severe, or frequently relapsing AA in adolescent is sometimes complex.
The inhibitory effect of Janus kinase–signal transducers and activators of transcription signaling pathways is responsible for the favorable efficacy of JAK inhibitors in the treatment of both severe AA and AD. Up to now, there has been limited clinical evidence for the efficacy and safety of JAK inhibitors in adolescent and pediatric AA patients with and without comorbidities such as AD. Atopic diathesis, atopic comorbidities, and high serum concentrations of immunoglobulin E have been identified as risk factors for developing AA, especially coexisting AD. The genetic polymorphism of interleukins 13 and 4 and infiltration of mast cells and eosinophils in skin biopsies of patients with severe AA, and favorable responses to antihistamine and dupilumab therapy suggest that the mechanisms of Th1 and concomitant Th2 involved in AA.13 Our literature review showed that most reported adolescents with severe AA who had received upadacitinib treatment had concomitant AD. In one patient, upadacitinib treatment induced both hair regrowth and improvement in symptoms of AD, as well as relief of vitiligo. Another patient showed relief of symptoms of Crohn’s disease after upadacitinib treatment. The three patients in our study did not have a history of atopic diseases or atopic diathesis and had normal serum concentrations of immunoglobulin E, providing clinical evidence for the therapeutic efficacy of upadacitinib in adolescents with severe AA without AD. All three of our participants, none of whom had atopic comorbidity, responded well to upadacitinib treatment. In these patients, regrowth of eyebrow and pubic hair occurred earlier than did regrowth of head hair, the latter becoming obvious approximately 4 months after initiating treatment. Upadacitinib at 15 mg/day was the most commonly used treatment in reported adolescents with severe AA. Notably, the SALT score of our Patient 3 was still over 50 after 6 months of treatment. We gave further consideration to increasing this patient’s upadacitinib dosage because he weighed 90 kgs. Although one reported 9-year-old patient had significant regrowth of head hair after 3 months’ treatment and stopped upadacitinib treatment without relapse at the 5-month follow-up,9 our patients needed to continue on upadacitinib treatment for more than 6 months.
A JAK 1 inhibitor, upadacitinib downregulates gamma-interferon signaling by inhibiting JAK activity, thereby preventing breakdown of hair follicles via immune mechanisms. Upadacitinib reportedly induced rapid regrowth of hair and significant improvement in quality of life in a retrospective study of 25 adults with AA.14 The FDA has approved upadacitinib for patients with atopic dermatitis aged 12 and older and provided more clinical and safety evidence to support its application in adolescents with severe AA aged from 12 to 17 years. One study has reported adverse musculoskeletal and skin events in male patients receiving upadacitinib treatment, whereas musculoskeletal issues, infections, and abnormal laboratory tests were prevalent and severe in female patients receiving upadacitinib treatment.15 According to our research and literature review, adverse reactions are mild in adolescents with severe AA receiving upadacitinib treatment. Increased creatine phosphokinase was the most common adverse event recorded in adolescents with severe AA treated with Upadacitinib, followed by onset or exacerbation of acne. Additionally, the adverse reactions did not differ significantly between sexes.
Two Phase III trials over 52 weeks have found that baricitinib, an inhibitor of JAK 1/2, is an effective treatment for AA.16 The FDA has approved the use of baricitinib in adults with severe AA. There are also case reports supporting the off-label use of baricitinib for treating adolescents with severe AA. Compared with baricitinib, upadacitinib has the following advantages in treatment of adolescents with severe AA. First, upadacitinib more strongly inhibits the effect of JAK1/STAT on transcription than does baricitinib.17 In some studies, upadacitinib has been used as conversion therapy for insufficiently effective responses to baricitinib treatment, indicating the significance of JAK 1 inhibition in management of AA.18,19 Second, upadacitinib has been approved by the FDA for treatment of atopic dermatitis in children aged 12 and older, and it has been demonstrated that it is safer than baricitinib in adolescents aged 12 to 17 years. Third, upadacitinib may have better therapeutic effects on comorbidities of AA. AD has been identified as a risk factor for developing AA and is one of the most common comorbidities in pediatric and adolescent patients with AA. Although various JAK inhibitors have shown some efficacy in the management of AD, a network meta-analysis concluded that upadacitinib is the optimal option according to short-term studies.20 Further research is needed on the efficacy and safety of baricitinib and upadacitinib in the treatment of adolescents with severe AA.
This study has several limitations. First, as a retrospective case series, future randomized controlled trials with larger sample sizes are warranted to confirm the efficacy and safety of upadacitinib in adolescents with severe AA. Second, while the follow-up period exceeded 6 months, longer-term evaluation is required to comprehensively assess the treatment’s sustained efficacy. Moreover, systematic assessment of disease recurrence following treatment discontinuation should be conducted in subsequent studies.
Conclusion
In conclusion, in the present study, we found that upadacitinib at 15 mg/day is an effective and safe treatment option for adolescents with severe AA, both in those with concomitant AD and vitiligo, but also in those without comorbidities. However, further long-term follow-up is warranted.
Acknowledgments
The study was approved by the Ethics Committee of Peking Union Medical College Hospital, and complied with the Declaration of Helsinki. Written informed consent for publication was obtained from these patients’ legal guardians.
Funding
Beijing Key Clinical Specialty Construction Project; National Key Clinical Specialty Project of China.
Disclosure
The authors report no conflicts of interest in this work.
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