Successful management of therapy-resistant chronic refractory atopic dermatitis and alopecia universalis with oral tofacitinib in a girl

Abstract

Background

The association between alopecia areata (AA) and atopic dermatitis (AD) is common. The association of both autoimmune diseases is an indicator of poor prognosis. We hereby discuss the off-label therapeutic role of tofacitinib as concurrent treatment for both the conditions and long-term safety data.

Case report

Herein we describe a 5-year-old girl with alopecia areata and atopic dermatitis refractory to combination therapy of methotrexate and atopic dermatitis, who was started on tofacitinib 5 mg once daily. Due to inadequate response, the dose was escalated to 5 mg twice daily. The child achieved complete hair regrowth except for the ophiasis pattern and complete clearance of AD. The child was maintained on tofacitinib for the long term due to the risk of flare of both conditions.

Conclusion

We emphasize the long-term safety of tofacitinib in dermatological conditions like AA and AD. There are minimal case reports of long-term efficacy and use of tofacitinib in concurrent conditions.

Keywords

atopic dermatitis alopecia universalis tofacitinib JAK-STAT inhibitors

Introduction

The association between alopecia areata (AA) and AD has been known for ages. The association of both autoimmune diseases is an indicator of poor prognosis. The U.S. FDA has approved abrocitinib (≥12 years), ritlecitinib (≥12 years), and upadacitinib (≥12 years) for atopic dermatitis (AD). For alopecia areata (AA), baricitinib (≥18 years) and ritlecitinib (≥12 years) have been approved. However, in countries where these agents are not available, such as India, we discuss the off-label therapeutic role of tofacitinib as a concurrent treatment option for both conditions, along with available long-term safety data.

Case

A 5-year-old girl from Eastern India presented to us in February 2019 with moderate atopic dermatitis (AD) and was taking 5 mg of oral prednisolone. She was on on-and-off oral prednisolone without complete remission before presenting to us. In view of this, she was started with oral cyclosporine. The timeline of her treatment is mentioned in Table 1 and suppl Figure 1. In December 2020, she developed alopecia universalis (AU), cyclosporine was stopped due to prolong use and was prescribed methotrexate, and later oral prednisolone was added. Her AD and AU were not controlled with methotrexate and oral prednisolone. In August 2022, she was prescribed oral tofacitinib 5 mg once daily (5 mg once daily for weight less than 45 kg, and twice daily for weight more than 45 kg) after normal baseline (hemoglobin: 12.6%, total leukocyte count: 4130/μL, platelets: 1,50,000/μL, creatinine: 0.3 mg/dL, total bilirubin: 0.6 mg/dL, alanine transaminase: 28 U/L, aspartate transaminase: 32 U/L, triglyceride: 130 mg/dL, chest x-ray: normal, urine routine microscopy: normal, serology of hepatitis B and C, human immunodeficiency virus was negative, and Mantoux test: 8 × 6 mm) investigations (Figure 1(a) to (d)). At the time of starting oral tofacitinib the child was vaccinated appropriately, her scoring atopic dermatitis (SCORAD) was 37.4, NRS itch was 10, the severity of alopecia tool (SALT) score was 100, and her children dermatology life quality index (cDLQI) was 24. After 6 months, SCORAD was 12.5, NRS itch was 8, SALT score was 34, and cDLQI was 20. The tofacitinib dose was escalated to twice a day in view of uncontrolled itching and flare-in atopic dermatitis. After twice dosing, the child’s SCORAD, NRS itch, SALT score, and cDLQI were 1.2, 2, 6, and 4, respectively. Reduction of SCORAD, SALT, cDLQI, and NRS scores was 98%, 94%, 67%, and 75%, respectively, after taking 1.5 years of tofacitinib. The alopecia improved, except for the occipital area, after taking 1 year of tofacitinib (Figure 1(e) to (h)). In addition, regrowth of hair in the occipital area was noted after 2 years (suppl Figure 2). The child and the parents did not report any side effects, and blood investigations (hemoglobin: 11% and 12%, total leukocyte count: 5130/μL and 4200/μL, platelets: 2,50,000/μL and 1,80,000/μL, creatinine: 0.34 mg/dL and 0.4 mg/dL, total bilirubin: 0.4 mg/dL and 0.6 mg/dL, alanine transaminase: 28 U/L and 32 U/L, aspartate transaminase: 30 U/L and 45 U/L, and triglyceride: 150 mg/dL and 160 mg/dL)were normal after 1 month and three-month follow-up visits. However no adverse events were reported by parents and child, and 3 monthly investigations of complete hemogram, liver and renal function tests, and fasting lipid profile were normal.

Table 1.

Summary of treatment history.

Month	Drug and dose	Remarks
February 2019–June 2019	Was started on cyclosporine 50 mg OD	• She was on oral prednisone 5 mg OD when presented to us
February 2019–June 2019	Prednisolone 5 mg OD	• Disease was under control during this period
July 2019–February 2020	Cyclosporine 50 mg BD	• The exacerbation of AD in June led us to increase the dose of cyclosporine and we tapered the dose of oral prednisolone and stopped
July 2019–February 2020	Prednisolone 2.5 mg OD	• AD remained in remission
March 2020–December 2020	Cyclosporine 50 mg OD	• AD remained in remission
January 2021–April 2021	Methotrexate 5 mg once/week (0.3 mg/kg/week)	• She developed alopecia universalis (AU)
January 2021–April 2021	Methotrexate 5 mg once/week (0.3 mg/kg/week)	• Cyclosporine tapered and stopped, and methotrexate was added
May 2021–October 2021	Methotrexate 5 mg once/week	• Partial improvement in AD
May 2021–October 2021	Methotrexate 5 mg once/week	• No response in AU
November 2021–July 2022	Methotrexate 10 mg once/week and oral prednisolone (0.25–0.5 mg/kg)	• Due to flare in AD, the methotrexate dose was increased, and oral prednisolone was given on and off
August 2022–April 2023	Oral tofacitinib 5 mg OD	• Due to a flare in AD and no response in AU, tofacitinib was started
August 2022–April 2023	Oral tofacitinib 5 mg OD	• Methotrexate and oral prednisolone tapered and stopped
May 2023–October 2023	Tofacitinib 5 mg BD	• The dose of oral tofacitinib was increased due to a partial response
November 2023–January 2024	Tofacitinib 5 mg OD	• AD, near-complete resolution
November 2023–January 2024	Tofacitinib 5 mg OD	• Complete regrowth of hair except the occipital area
February 2024–April 2024	Tofacitinib 5 mg alternate days	• AD resolved (100%)
February 2024–April 2024	Tofacitinib 5 mg alternate days	• Hair growth maintained, except occipital area
May 2024	Tofacitinib 5 mg OD	• Dose increased due to mild flare in AD
May 2024–February 2025	Tofacitinib 5 mg OD	• AD is under control
		• Occipital hair started regrowing from August 2024
		• Hair growth maintained, including in the occipital area

OD: once daily; BD: twice daily; AD: atopic dermatitis; AU: alopecia universalis.

Figure 1.

Depicts pre- (a, b, c, and d) and post-treatment (e, f, g, and h) improvement in SALT score with tofacitinib for 1.5 years.

Discussion

JAK-STAT (Janus kinase signal transducers and activators of transcription) pathway is the common pathway in both dermatological conditions. JAK activates the cytokine receptors that bind the transcription factor STAT, thereby increasing various inflammatory mediators. JAK-STAT inhibitors reduce the inflammatory cascade, such as interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, IL-21, and interferon (IFN)-γ.^1,2 Tofacitinib inhibits JAK-1/3 and STAT-6 pathways, thereby regulating IL-4, 5, 10, and 13 signaling linked in the pathogenesis of atopic dermatitis. Similarly, it regulates IFN-γ, IL-13, IL-15 expression, and cytotoxic CD8 + NKG2D + T cells expressed in AA patches. IL-13 has been linked as a common cytokine associated with the pathogenesis of both AA and AD.²

A systematic review involving 66 studies on the effect of JAK-STAT inhibitors in AD reported good responses in all cases with nil to mild adverse events. The adverse events reported include lymphopenia, diarrhea, nausea, flare of disease, and skin infection. Relapse of AD after discontinuation of therapy has been reported.² Similar to our case, tofacitinib (5 mg BD) was effective in a 22-year-old adult male with AA and AD who was refractory to topical steroids, phototherapy, methotrexate, and mycophenolate mofetil. The NRS has been reduced to 50% from 8 to 3, and complete hair regrowth was noted at the end of 10 months of therapy.³ Another report of overlap of AD and AA showed dramatic response to baricitinib after 4 to 7 months of therapy.⁴ In 6 patients aged between 18 and 55 years, tofacitinib was able to achieve a 54% average reduction of SCORAD at 1 to 3 months, and this reduction was maintained at 70% up to 29 weeks. The itch score decreased by 70% at 1 to 3 months of therapy and was sustained at 76% during 2 to 7 months.⁵

Huang et al., in 11 preadolescent patients, reported a 50% SALT score improvement in 64% of the cases with oral tofacitinib alone.⁶ Similarly, a 50% SALT score reduction was noted in 63.6% of cases with oral tofacitinib and oral minoxidil by Jerjen et al.¹ A retrospective study from India reported initial hair regrowth with oral tofacitinib within 3 months and a complete response within 6 months.⁷ In our case, the child started showing regrowth of hair in 3 months of follow-up, with near-complete response at 15 months, except for the occipital area and complete regrowth at 24 months. We also observed that while tapering tofacitinib 5 mg alternate days, there was exacerbation of atopic dermatitis, while hair regrowth was preserved with no relapse. Numerous studies have individually demonstrated the effectiveness of tofacitinib in treating AD or AA. Its efficacy in patients with both AD and AA is rarely reported. Nevertheless, this highlights its potential therapeutic role in this subset of patients.^3,6

Conclusion

In conclusion, we highlight the successful use of tofacitinib as a targeted therapy in a girl with concomitant therapy-resistant AD and AU. This is relevant in a country like India where baricitinib is not available and abrocitinib is too costly to afford.

Supplemental Material

Supplemental Material - Successful management of therapy-resistant chronic refractory atopic dermatitis and alopecia universalis with oral tofacitinib in a girl

Supplemental Material for Successful management of therapy-resistant chronic refractory atopic dermatitis and alopecia universalis with oral tofacitinib in a girl by Shreya K. Gowda, Bhini Ameta, Akash Agarwal, and Biswanath Behera in International Journal of Risk & Safety in Medicine

Footnotes

Consent to participate

Content was obtained as per departmental format from the guardian/parents.

Author contributions

SK and BB had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis and were responsible for the study concept and design. SK and BA drafted the manuscript. BB contributed to the critical revision of the manuscript for important intellectual content and supervised the study. All authors contributed to the acquisition, analysis, and interpretation of data.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

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

Data Availability Statement

Date will be available with the corresponding author shared when required; ethics review: not required for a single case, per journal policy.*

Supplemental Material

Supplemental material for this article is available online.

References

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Supplementary Material

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