Acta Dermato-Venereologica 99-3CompleteContent

331 SHORT COMMUNICATION A Case of Interstitial Lung Disease and Autoimmune Thyroiditis Associated with Ustekinumab Seon Gu LEE, Ji Hae AN, Dong Hyun KIM, Moon Soo YOON and Hee Jung LEE* Department of Dermatology, Bundang CHA Medical Center, CHA University School of Medicine, Seongnam 13496, Korea. E-mail: derma97@ gmail.com Accepted Nov 14, 2018; E-published Nov 14, 2018 Biologics have been increasingly used to treat psoriasis over the past decade (1). Biologics have shown excel- lent results in the treatment of psoriasis due to their great target specificity (2). Ustekinumab is a fully hu- man monoclonal antibody with high specificity for the interleukin (IL)-12/23 p40 subunit. The safety profile indicates that up to 5 years of ustekinumab treatment is generally favourable and no evidence of cumulative end organ toxicity has been shown (1, 2). To the best of our knowledge, no cases of ustekinumab-associated autoimmune thyroiditis and only one case of interstitial lung disease (ILD) associated with ustekinumab have been reported (3). CASE REPORT A 68-year-old Korean woman with a 10-year history of plaque psoriasis visited our clinic. Her medical history was significant for osteoarthritis of the knee. Her psoriasis was treated with narrow- band ultraviolet B (NBUVB) for 2 months, oral methotrexate (MTX) 7.5–15 mg weekly for 6 months, and cyclosporine 200 mg daily for 8 months, none of which were effective. Ustekinumab 45 mg was used initially and 4 weeks later, followed by 45 mg every 12 weeks. PASI score reduced dramatically to less than 4 after the third injection. After the fifth injection of ustekinumab, the patient reported dyspnoea and interstitial lung disease (ILD) was diagnosed based on chest computed tomography (CT) (Fig. 1A). Newly developed reticulonodular opacity in both lungs was shown compared with initial chest X-ray (Fig. 1B, C). Diffuse enlarge- ment of the thyroid gland was also found on chest CT. In thyroid function tests, increased T3 level (2.29 ng/ml; normal 0.6–1.81) and decreased thyroid stimulating hormone (TSH) (<0.008 µIU/ ml; normal 0.35–5.5) were noted. TSH receptor antibody and anti-thyroid peroxidase (anti-TPO) were all positive and anti- thyroglobulin antibody was equivocal. High uptake of radioactive iodine was also shown. Based on these findings, Graves’ disease was diagnosed and the patient was started on methimazole. After the diagnosis of ILD and Graves’ disease, the use of ustekinumab was discontinued. Respiratory symptoms improved slightly and thyroid hormone levels including autoantibodies were also nor- malized within 3 months after discontinuation of ustekinumab. Thyroid hormone levels including autoantibodies remain normal even after stopping methimazole. DISCUSSION The incidence of ILD associated with biologics is un known and most cases were due to anti-tumour necrosis factor (TNF)-α agents (4, 5). Many cases of ILD associa- ted with anti-TNF-α agents occurred in patients who were previously prescribed MTX, which has traditionally been associated with the development of drug-induced ILD (5, 6). When TNF-α is suppressed, apoptosis of infiltrating inflammatory cells cannot occur and inflammatory cells persist in the lung, resulting in ILD (6). ILD as an ad- verse effect of anti-TNF-α agents alone in patients with psoriasis has also been reported in the literature, but it is unclear whether anti-TNF-α agents significantly increase the risk of ILD (7). There were no reports of ILD and autoimmune thyroi- ditis in large-population studies evaluating the efficacy and safety profile of ustekinumab in moderate to severe psoriasis (1, 2). Only one case of ILD in a patient with psoriasis treated with ustekinumab has been reported. A 60-year-old man who had a history of taking cyclosporine and infliximab for psoriasis was diagnosed with ILD after 2 years of ustekinumab treatment (3). IL-12, a target cytokine of ustekinumab, has shown anti-fibrotic activity by increasing interferon (IFN)-γ production in vivo in mice (8). Other in vivo studies Fig. 1. (A) Honeycombing and intralobular interstitial thickening on chest computed tomography (B) Initial chest X-ray showed no active disease. (C) Peribronchial and reticulonodular opacity in both lungs was developed after the fifth injection of ustekinumab. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3084 Acta Derm Venereol 2019; 99: 331–332

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