Successful treatment with upadacitinib for Sjögren's syndrome complicated by atopic dermatitis

Sjögren's syndrome is a chronic, multisystem autoimmune disorder, characterized by inflammation of the lacrimal and salivary glands, leading to dry eyes and dry mouth. Atopic dermatitis is a common chronic, recurrent, inflammatory skin disease. Upadacitinib, an oral Janus kinase (JAK) 1-selective inhibitor, has demonstrated its efficacy in treating several autoimmune and inflammatory diseases, notably in atopic dermatitis.1 We report a case of a patient with Sjögren's syndrome complicated by atopic dermatitis who showed obvious improvement with upadacitinib. A 40-year-old female patient presented to the Rheumatology Department in October 2023, reporting a symmetrical follicular rash on her both lower limbs (Figure 1A), accompanied by itching, fatigue, intermittent morning stiffness, and a reduced ability to clench her fists for 4 months. Laboratory tests revealed positive serum antinuclear antibody (1:640, speckled pattern, reference range: <1:40) and rheumatoid factor (82.3 IU/mL, reference range: 0–14.0 IU/mL), with the anti-SSA exceeding 500 RU/mL (reference range: 0–20 RU/mL) and the anti-SSB at 408 RU/mL (reference range: 0–40 RU/mL), elevated immunoglobulin (Ig) G (20.9 g/L, reference range: 7.0–16.0 g/L), normal IgE (25 IU/mL, reference range: <100 IU/mL), anti-Sm, anti-U1-RNP, anti-Jo-1, and anti-Scl-70 antibodies were all negative. Serum protein electrophoresis demonstrated the increases in γ-globulin (26.1%, reference range: 11.1%–18.8%). Ultrasonography of the salivary glands displayed irregular changes in both the parotid and submandibular glands (Figure 1C,D). The Outcome Measures in Rheumatology Clinical Trials scoring system rated these changes as 8.2 The patient presented with a documented penicillin hypersensitivity, and her son exhibited symptoms of anaphylactic rhinitis. Considering these clinical signs and laboratory findings, dermatologists and rheumatologists confirmed diagnoses of atopic dermatitis and Sjögren's syndrome, respectively. The European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score was 7. Tests for hepatitis B virus antigen and antibody, hepatitis C virus antibody and T-SPOT were all negative. Chest X-ray shows no abnormalities. The patient was prescribed topical halometasone, applied twice daily for 1 week. There has been no improvement in the rash, and the itching has become significantly more pronounced. Considering the moderate activity of the pruritus and rash, which greatly disrupts the patient's daily life, a combination therapy of hydroxychloroquine at 400 mg/day and upadacitinib at 15 mg/day was initiated. After 3 weeks' treatment, the patient displayed rapid alleviation of rash and pruritus on bilateral lower limbs (Figure 1B), with remarkable improvement in fatigue, morning stiffness, and joint movements. On February 28, 2024, the patient reported anti-SSB decreased to 292.66 RU/mL, rheumatoid factor dropped to 35.4 IU/mL, IgG 19.47 g/L, γ-globulin 24.1%. On April 9, 2024, the rheumatoid factor decreased to 28.8 IU/mL, IgG 17.35 g/L, γ-globulin 22.1%, ESSDAI score dropped to 1 and achieved Sjögren's Tool for Assessing Response (STAR) response 7 (STAR responder if score ≥5). During the treatment for atopic dermatitis, it was discovered that upadacitinib not only mitigated the atopic dermatitis symptoms but also led to a reduction in anti-SSB and IgG levels in the patient. Part of Sjögren's syndrome patients exhibit activation of the JAK-signal transducers and activators of the transcription (STAT) pathway.3 A case series involving 11 patients treated with baricitinib, a selective JAK 1/2 inhibitor, for patients with primary Sjögren's syndrome indicated improvements in symptoms of arthritis and rash, reductions were observed in IgG levels and in the Physician Global Assessment scores.4 Based on these findings, we preliminarily estimate that upadacitinib could be an effective treatment for Sjögren's syndrome. The JAK-STAT pathway, which plays a crucial role in several immune responses involved in the pathogenesis of atopic dermatitis, also appears significant in Sjögren's syndrome. Cytokines such as interleukin (IL)-2, IL-4, IL-6, IL-7, IL-9, IL-15, IL-21, and IL-22 mediate this pathway, leading to chronic inflammation.5 It has been shown that targeting the JAK-STAT pathway alleviates symptoms in atopic dermatitis, and similar benefits might be expected for Sjögren's syndrome,6 given the shared cytokine signaling pathways highlighted in Figure 1E. In summary, this case contributes new insights into the potential of JAK inhibitors in treating Sjögren's syndrome, and further research is needed to fully ascertain its efficacy profile. All the authors followed up the patient and collected the clinical data. Haojie Xu wrote the original draft, the other authors edited it, Yin Su treated the patient and obtained her written consent, and all the authors approved the final version. The study was supported by a grant from the Major Research Plan of the National Natural Science Foundation of China (92374101 to Prof. Yin Su). Figure 1E was created with BioRender.com. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article. Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research.