Concurrent Refractory Atopic Dermatitis and Generalized Vitiligo Successfully Treated with Abrocitinib: A Case Report

Introduction

Atopic dermatitis (AD) is a common chronic inflammatory skin condition characterized by eczematous skin lesions, including erythema and papules.¹ AD is prevalent in 15–20% of children and 2–10% of adults.^2–4 AD is associated with recurrent eczematous lesions and intense pruritus, which severely affects patient quality of life, negatively impacting psychological and social well-being.

In China, vitiligo is a common mucocutaneous depigmentation disorder with a global incidence of 0.5–2%^5,6 and prevalence of approximately 0.54%.⁷ Cytotoxic CD8⁺ T cell-mediated killing of melanocytes is the main cause of vitiligo.⁸ Both AD and vitiligo belong to immune-mediated inflammatory skin diseases, and in some cases, clinical overlap may occur, with the severity of the disease showing correlation, complicating disease treatment.

Topical corticosteroid and calcineurin inhibitor therapies are widely used for the treatment of AD and vitiligo. However, these therapeutic agents are often slow acting and lead to various adverse effects, resulting in poor patient compliance. Biologics such as dupilumab and the Janus kinase(JAK) inhibitors such as topical ruxolitinib 1.5% cream that target aberrant immune responses are promising treatment options.^5,9–11 Given the immune overlap in the pathogenesis of AD and vitiligo and the treatment of AD patients with vitiligo remains a major challenge in clinical practice. Only a case report suggested that upadacitinib can be a preferred treatment option when AD and vitiligo coexist.¹² Herein, we report a case of refractory moderate-to-severe AD with generalized vitiligo that responded well to the JAK1 inhibitor abrocitinib.

Case Report

A 65-year-old male patient presented with generalized vitiligo that had been untreated for more than 30 years and was diagnosed with AD at another hospital more than 20 years ago. In May 2023, the patient visited our dermatology department for the first time because of poor response to repeated antihistamine treatment for AD. Physical examination revealed extensive erythema and papules with pruritus on the face, torso, and extremities. Additionally, large irregular vitiligo patches (skin lesions accounting for >50% of the body surface area) with blurred edges and white hair were observed on the head, face, neck, torso, and extremities. Consequently, the patient was diagnosed with moderate-to-severe AD (Scoring of Atopic Dermatitis [SCORAD] score: 70.6; Investigator Global Assessment [IGA] score: 3; Numeric Pain Rating Scale [NRS]: 8) and generalized vitiligo (vitiligo disease activity [VIDA] score=0; vitiligo area score index [VASI]=90%, facial VASI [FVASI]=1.5) (Figure 1a and d). The patient was treated with epinastine capsules (20 mg/day, qd, po), levocetirizine tablets (5 mg/day, qn, po) and betamethasone dipropionate cream (1 g/dose, bid, top).

Figure 1 Clinical photographs of a 65-year-old male patient with atopic dermatitis and generalized vitiligo who presented with extensive erythema, papules and vitiligo patches showing the initial and recent response to treatment in the course of his treatment: (a and d) atopic dermatitis and vitiligo lesions on the patient’s face, torso and extremities when admitted; (b and e) atopic dermatitis lesions receded partially but vitiligo lesions had no change after conventional therapies for 6 months; (c and f) atopic dermatitis lesions showed further recovery and vitiligo lesions revealed repigmentation after treatment with abrocitinib for 4 months.

However, after 2 months of treatment, the patient showed no signs of improvement in generalized erythema, papules, and pruritus ([SCORAD]: 70.6, [IGA]: 3, [NRS]: 8), and no change in generalized vitiligo lesions ([VIDA]=0, [VASI]=90%, [FVASI]=1.5). Subsequently, dupilumab (300 mg/dose, q2w, s. c.) was administered. After four months of treatment, erythema and papules were markedly alleviated in the lower extremities but were still severe in the torso ([SCORAD]: 53.8, [IGA]: 5, [NRS]: 6), and generalized vitiligo lesions remained unchanged ([VIDA]=0, [VASI]=90%, [FVASI]=1.5) (Figure 1b and e). The patient requested the discontinuation of dupilumab treatment.

After excluding contraindications (viral hepatitis, tuberculosis, tumor, and serious infection) and obtaining informed consent from the patient in December 2023, the treatment was modified to include abrocitinib (100 mg/day, qd, po). After a month of treatment, the patient’s erythema and papules on the torso and extremities were significantly abated with alleviated pruritus (([SCORAD]: 39, [IGA]: 3, [NRS]: 6) but no change in vitiligo lesions ([VIDA]=0, [VASI]=90%, [FVASI]=1). Thus, abrocitinib (100 mg/dose, qd, po) treatment was continued. In April 2024, erythema and papules significantly improved, and subjective itching symptoms disappeared ([SCORAD]: 18, [IGA]: 1; [NRS]: 1). In addition, significant improvement and repigmentation of vitiligo lesions on the face and body ([VIDA]=0, [VASI]=65%, [FVASI]=0) were observed (Figure 1c and f). At present, the patient is still receiving abrocitinib treatment (100 mg/day, qd, po). The clinical symptoms and medication regimens are shown in Figure 2.

Figure 2 Timetable depicting the time frame for the medication regimen and changes in lesions of a 65-year-old male patient with atopic dermatitis and generalized vitiligo. The medication regimens are shown on the left-hand side. On the right-hand side, the duration of each medication and the disease severity assessment of each subsequent visit are depicted by different coloured boxes which correspond to the month within the whole treatment. Abbreviations: FVASI, Facial vitiligo area score index; IGA, Investigator Global Assessment; NRS, Numeric Pain Rating Scale; SCORAD, Scoring of Atopic Dermatitis; VASI, vitiligo area score index; VIDA, vitiligo disease activity.

Discussion

Herein, we report a case of refractory moderate-to-severe AD with generalized vitiligo successfully treated with oral abrocitinib. Although previous studies have reported that abrocitinib can effectively treat AD, only a limited number of studies have evaluated its efficacy in the treatment of vitiligo. Therefore, our case confirms the therapeutic effect of abrocitinib in vitiligo and highlights its potential as a treatment option in patients with AD and vitiligo.

AD is a common chronic inflammatory skin disorder that is characterized by persistent itching. The development of AD primarily involves the activation of Th2 cells, which stimulate JAK/STAT signaling through the release of inflammatory cytokines such as IFN-γ, IL-4, IL-13, and IL-17, resulting in a cascade of inflammatory responses. In addition, abnormal Th1 and Th17 cell activation is associated with AD.¹³

Vitiligo is a chronic depigmentation disease dominated by a Th1 immune response. IFN-γ activates the JAK/STAT1 signaling pathway and Th1 cells. Activated Th1 cells secrete more IFN-γ, further affecting melanocytes and promoting the downstream release of CXCL9/10 via JAK/STAT-1 signaling in keratinocytes, eventually leading to the recruitment of CD8⁺ T cells to skin lesions and the destruction of melanocytes.^14–16

Previous studies have reported that patients with AD and patients with vitiligo have a higher risk of developing concurrent vitiligo and AD.^17,18 In addition, genome-wide association studies have shown substantial overlap between susceptibility loci for AD and Th1-mediated autoimmune conditions, demonstrating that Th1 cell activity is involved in the pathogenesis of both AD and vitiligo.¹³ Thus, the co-occurrence of AD and vitiligo may be attributed to the overlap in immune responses.

Abrocitinib is a JAK1 inhibitor approved by the FDA for the treatment of AD, which reduces the activity of various Th2 cytokines (such as IL-4 and IL-13) in AD by inhibiting JAK/STAT-1 signaling.¹⁹ Additionally, abrocitinib attenuates inflammation, and reducing damage to immune cells at the skin barrier. The most frequently reported side effects are gastrointestinal symptoms, acne and respiratory tract infections. Moreover, JAK inhibitors disrupt the intracellular signalling pathways responsible for the activation of immune cells and production of pro-inflammatory cytokines that are involved in the development of vitiligo.²⁰ Only topical ruxolitinib has been approved for the treatment of vitiligo in patients aged ≥12 years, indications for other JAK inhibitors such as tofacitinib, baricitinib use in the treatment of vitiligo are lacking. And only several cases explored abrocitinib’s use in vitiligo treatment.^21–23 In this case, we observed the significant improvement in AD and repigmentation of the vitiligo lesions after the treatment of abrocitinib, which confirmed the beneficial effects of abrocitinib in the treatment of AD and vitiligo.

This case report had some limitations. First, the sample size is small, further large-scale cohort studies are warranted to confirm the findings of this study. And long-term follow-up data is lacking, we still need to continue following up on the patient’s later condition.

Conclusion

Our report suggested significant improvement in refractory atopic dermatitis and generalized vitiligo after treatment with abrocitinib, and provided evidence for the potential of JAK inhibitors in the treatment of vitiligo, particularly in cases where other therapies have failed. In addition, further research and clinical trials are needed to validate the effectiveness and safety of abrocitinib.