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J Allergy Clin Immunol Glob
J Allergy Clin Immunol Glob
The Journal of Allergy and Clinical Immunology: Global
2772-8293
Elsevier

S2772-8293(24)00119-X
10.1016/j.jacig.2024.100323
100323
Case Report
Successful treatment of the dupilumab-induced psoriatic dermatitis/arthritis and atopic dermatitis with a JAK inhibitor: A case report and literature review
Tsunoda Misuzu MD a
Adachi Takeya MD, PhD jpn4156@me.com
abcd∗
Nakajima Yuuri MD a
Yatomi Yoshihiro MD a
Shimizu Tomoko MD, PhD a
Nakasute Katsuki MD a
a Department of Dermatology, National Hospital Organization Saitama Hospital, Saitama, Japan
b Department of Dermatology, Keio University School of Medicine, Tokyo, Japan
c Keio Allergy Center, Keio University Hospital, Tokyo, Japan
d Department of Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
∗ Corresponding author: Takeya Adachi, MD, PhD, Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku Tokyo 160-8582, Japan. jpn4156@me.com
05 8 2024
11 2024
05 8 2024
3 4 10032312 2 2024
16 4 2024
28 4 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Dupilumab-induced psoriatic dermatitis and arthritis in a patient with atopic dermatitis were effectively managed with upadacitinib, highlighting the use of Janus kinase inhibitors as a possible treatment for biologic therapy side effects.

Key words

Dupilumab
psoriasis
psoriatic arthritis
atopic disease
upadacitinib
Abbreviations used

AD Atopic dermatitis

JAK Janus kinase
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pmcThe advent of biologics targeting cytokines has significantly transformed the treatment landscape for chronic immune-mediated inflammatory diseases such as atopic dermatitis (AD) and psoriasis. Although these therapies are generally safe and effective, cytokine-based therapeutic manipulation can cause immune system side effects, complicating the course of treatment and the selection of subsequent therapies. We encountered a case of dupilumab-induced psoriasis-like dermatitis and psoriatic arthritis in a patient with AD that was effectively managed with the Janus kinase (JAK) inhibitor upadacitinib. Here, we report this case and the associated clinical features, along with 9 previously reported cases of patients treated with JAK inhibitor for coexistence of AD and psoriasis during treatment with biologics.

A 25-year-old-man with childhood-onset AD had been taking dupilumab biweekly, with complete resolution of the eruption. Two years after initiation of dupilumab, he presented with well-demarcated scaly erythematous lesions predominantly on his trunk and extremities (Fig 1, A-C), prompting referral to our department. A skin biopsy sample from his upper arm revealed parakeratosis, intracorneal microabscess, acanthosis, and lymphocyte infiltration in the upper dermis (Fig 1, D-F), which was indicative of psoriatic dermatitis. Two and a half years after the plaques appeared, the patient also developed nail symptoms followed by widespread joint pain in his left shoulder, knees, ankles, and bilateral Achilles tendons along with swelling of the toes. Despite a normal level of C-reactive protein and normal erythrocyte sedimentation rate, as well as negative autoimmune serology, including anticyclic citrullinated peptide antibody and rheumatoid factor, bone scintigraphy revealed a diffuse increase in radiotracer uptake in the left sacroiliac joint, left sternoclavicular joint, ankles, and foot (Fig 1, G), which was consistent with psoriatic arthritis. There was no apparent history of inflammatory bowel disease or bacterial enteritis that would have caused suspicion of reactive arthritis classified as spondyloarthritis. The diagnosis of dupilumab-associated psoriatic dermatitis and arthritis was established on the basis of clinical and histopathologic features and the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria (confirmed inflammatory articular disease with 4 points [current psoriasis, rheumatoid factor negativity, and psoriatic nail dystrophy]).1 After discontinuation of dupilumab, cyclosporine (300 mg daily) was administered but did not alleviate the patient’s AD symptoms. Subsequently, his psoriatic symptoms were managed with an anti–IL-17A mAb (ixekizumab, 80 mg, biweekly after an initial dose of 160 mg), but his AD worsened. Administration of an oral corticosteroid (prednisolone, 15 mg daily) was followed a month later by baricitinib (4 mg daily), resulting in a partial response. Therefore, upadacitinib (30 mg daily) was introduced and continued, after which the skin lesions and joint symptoms improved significantly without recurrence.Fig 1 Clinical, histopathologic, and bone scintigraphy findings. A-C, Well-demarcated erythematous scaly plaques appear on the arm. D-F, A skin biopsy sample reveals acanthosis with rete ridge elongation. Hematoxylin and eosin staining; scale bar = 500 μm. (D), parakeratosis and a thin granular layer (150 μm) (E), and dilated capillaries and lymphocytic infiltrates (300 μm) (F). G, Bone scintigraphy shows increased radiotracer uptake in joints.

The coexistence of AD and psoriasis, 2 distinct chronic inflammatory skin diseases, has occasionally been observed, albeit in a small percentage of patients. The literature suggests that approximately 2% of individuals with AD may also present with psoriasis and vice versa, highlighting the complex interplay between these conditions.2 The advent of biologics has markedly improved the treatment outcomes for both diseases by targeting specific cytokines. Nonetheless, this therapeutic strategy introduces potential immunologic side effects, including the paradoxic reaction of psoriatic symptoms originally intended to be treated.3 A noteworthy concern with biologic therapy is the occurrence of immunologic side effects owing to cytokine manipulations. Indeed, it has been reported that 6% of patients treated with IL-17 inhibitors developed AD-like eczematous lesions.4 This immunologic shift between TH17 and TH2 cells may inversely contribute to the development of psoriatic dermatitis and psoriatic arthritis during biologic therapy for AD, as in our case.5

Another challenge of treatment with biologics is that once side effects develop as a result of cytokine manipulation, they persist even after discontinuation of the biologics, making it difficult to select an appropriate subsequent therapy.5 The overlap and exacerbation of AD and psoriatic dermatitis and/or arthritis, as observed in our case, highlights the complexities involved in managing such conditions when they coexist and are severe enough to require biologic agents. Indeed, in our case, 1 or both symptoms persisted despite the use of alternative biologics until a significant response had been achieved with the JAK inhibitor upadacitinib. The effects of JAK inhibitors extend to various members of the JAK/STAT signaling pathway, which may have contributed to effective suppression of both AD and psoriasis symptoms in our patient. Notably, upadacitinib primarily targets JAK1, potentially exacerbating TH1/TH17 cell responses in another case.6

The published literature on biologic-induced coexistence of AD and psoriasis was retrieved from PubMed in February 2024. We identified 5 case reports involving 10 patients (7 males and 3 females aged 12-58 years) who were given JAK inhibitors for psoriatic symptoms during biologic therapy for AD (including our patient) or for AD-like eczematous lesions during treatment of psoriasis with biologics (Table I).4, 7, 8, 9, 10 In all, 3 patients received an anti–IL-4Ra mAb for AD, 2 patients were treated with an anti–TNF-α treatment, 3 were given an anti–IL-17 treatment, and 2 were treated with an anti–IL12/23p40 mAb for psoriasis, without apparent bias in the development of immunologic side effects by cytokine type. In 4 of the 7 patients (57%) for whom information was available, the interval from biologic administration to the onset of adverse effects was 6 months or longer. Various alternative therapies, including biologics (70%) and immunosuppressive agents such as cyclosporin, methotrexate, or oral corticosteroids (60%), were tried before resorting to JAK inhibitors. The transition to JAK inhibitor therapy sometimes took several months after initial biologic therapy, suggesting that the patients had difficulty choosing alternative therapies. A total of 8 patients were treated with upadacitinib, 1 was treated with baricitinib, and 1 was treated with tofacitinib as JAK inhibitors; all of them responded by 16 weeks. These results emerged as an effective strategy for treatment with JAK inhibitors for patients who did not respond to or could not tolerate other biologics or immunosuppressive agents.Table I The characteristics of patients who developed psoriatic lesions and atopic lesions treated with JAK inhibitors

Report /year	Age (y)	Sex	Original diagnosis	Initial biologic	Adverse events induced by biologics	Interval between initial biologic initiation and adverse event onset (wk)	Interval between adverse event onset and JAK inhibitor initiation (wk)	Previous systemic treatments with partial response	Successful treatment with a JAK inhibitor (dose)	Time to response with a JAK inhibitor (wk)	
De Stefano et al (2022)7	49	M	AD	Dupilumab	Psoriasis arthritis	12	20	Secukinumab, MTX, corticosteroid	Baricitinib (4 mg/d)	8	
Patruno et al (2022)8	58	F	AD	Dupilumab	Psoriatic dermatitis	6	NA	Cyclosporine, MTX, corticosteroid	Upadacitinib (30 mg/d)	4	
Tang et al (2023)4	24	M	Psoriasis	Secukinumab	AD-like eczematous lesions	3	NA	NA	Tofacitinib (NA)	NA	
Gargiulo et al (2023)9	12	M	Psoriasis without arthritis	Ustekinumab	AD-like eczematous lesions	72	16	Dupilumab	Upadacitinib (15 mg/d)	16	
	39	M	Psoriasis without arthritis	Brodalumab	AD-like eczematous lesions	24	NA	Cyclosporine	Upadacitinib (15 mg/d)	16	
	50	F	Psoriasis with spondyloarthropathy	Ustekinumab	AD-like eczematous lesions	NA	NA	Secukinumab apremilast, MTX, salazopyrin	Upadacitinib (15 mg/d)	4	
	42	F	Psoriasis	Adalimumab	AD-like eczematous lesions	NA	16	Secukinumab, dupilumab, MTX	Upadacitinib (30 mg/d)	16	
Yi Ch'en et al (2023)10	50	M	Psoriasis	Secukinumab	AD-like eczematous lesions	NA	48	Tildrakizumab, ixekizumab, dupilumab	Upadacitinib (15 mg/d)	1	
	45	M	Psoriasis	Certrizumab	AD-like eczematous lesions	24	12	Dupilumab	Upadacitinib (15 mg/d)	8	
Our case (2024)	25	M	AD	Dupilumab	Psoriatic dermatitis and arthritis	96	128	Ixekizumab, baricitinib, cyclosporine, corticosteroid	Upadacitinib (30 mg/d)	16	
F, Female; M, male; MTX, methotrexate; NA, not applicable.

In conclusion, our observations underscore the importance of recognizing and addressing the unique challenges associated with the management of AD and psoriasis, particularly in the context of biologic therapy. The successful use of JAK inhibitors in treating the side effects of cytokine manipulation offers valuable insights into the potential of these agents to fill a critical therapeutic gap for patients with complex, overlapping dermatologic conditions.

Disclosure statement

Partially supported by the Scientific Research Fund of the 10.13039/100009647 Ministry of Health , Labour, and Welfare, Japan (grant 21FE2001), Japanese Society for the Promotion of Science Grants-in-Aid for Scientific Research Program (grant 22K16268), and the Japanese Agency for Medical Research and Development (grant 23ek0410090 [to T.A.]).

Disclosure of potential conflict of interest: T. Adachi has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie GK, Eli Lilly Japan KK, Sanofi KK, Novartis Pharma KK, Maruho Co, Ltd, and Jansen Pharmaceutical KK. The rest of the authors declare that they have no relevant conflicts of interest.

Declaration of generative AI and AI-assisted technologies in the writing process: During the preparation of this work, we used ChatGPT 4.0/OpenAI (Microsoft Corporation, Redmond, Wash) to improve language and readability. After using this tool/service, we reviewed and edited the content as needed and take full responsibility for the content of the publication.

Consent to publish: We obtained informed consent from the patient for this study.
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