Drug-Induced Autoimmune Inflammatory Myositis in a Patient with Psoriatic Arthritis Receiving Biologic Therapy: A Case Report

Autoimmune inflammatory myopathies, also referred to as idiopathic inflammatory myopathies, are a heterogeneous group of immune-mediated muscle disorders characterized by muscle inflammation, proximal weakness, and elevated muscle enzymes. Contemporary classification extends beyond the traditional polymyositis–dermatomyositis spectrum to include immune-mediated necrotizing myopathy, antisynthetase syndrome, inclusion body myositis, and overlap myositis, each with distinct clinical and serological features. Drug-induced autoimmune myositis is an increasingly recognized entity, particularly in patients receiving biologic and targeted immunomodulatory therapies, which may disrupt immune homeostasis and trigger inflammatory muscle injury. The authors report the case of a 34-year-old male with psoriatic arthritis on multiple biologic and targeted therapies who presented with acute proximal muscle weakness and markedly elevated creatine phosphokinase levels (2,071 U/L), along with raised inflammatory markers. Vascular causes were excluded on imaging. Based on clinical and biochemical findings, a diagnosis of autoimmune inflammatory myositis was established. The onset of myositis occurred several years after COVID-19 vaccination, making a causal association unlikely. In contrast, the patient’s prolonged exposure to immunomodulatory therapies supports a drug-induced etiology. The patient demonstrated clinical improvement following immunosuppressive treatment. This case underscores the importance of recognizing autoimmune inflammatory myositis as a potential complication of biologic therapy and highlights the need for early diagnosis and vigilant monitoring in patients receiving long-term immunomodulation

Key Points: 1. Although uncommon, autoimmune inflammatory myositis is a clinically significant adverse event that has been reported in association with biologic and targeted immunomodulatory therapies used for inflammatory rheumatic diseases, making early recognition essential.

2.This case report describes a patient with psoriatic arthritis who developed autoimmune inflammatory myositis after prolonged sequential exposure to multiple biologic and targeted therapies, highlighting the diagnostic challenge of distinguishing drug-induced myositis from disease progression and other potential causes.

3. In patients receiving long-term biologic or targeted therapy who present with new-onset proximal muscle weakness and markedly elevated creatine phosphokinase levels, clinicians should consider drug-induced autoimmune inflammatory myositis in the differential diagnosis and undertake prompt evaluation and appropriate management. INTRODUCTION Autoimmune inflammatory myopathies (AIM), collectively referred to as idiopathic inflammatory myopathies, are a group of heterogeneous immune-mediated disorders characterized by chronic muscle inflammation, progressive weakness, and elevated muscle enzymes.1-3 Advances in clinical, serological, and histopathological understanding have led to a shift from the traditional classification of polymyositis and dermatomyositis to a more refined categorization that includes dermatomyositis, immune-mediated necrotizing myopathy, antisynthetase syndrome, inclusion body myositis, and overlap myositis.2-4 These subtypes are distinguished by specific autoantibodies, clinical features, and patterns of organ involvement, reflecting diverse underlying immunopathogenic mechanisms.5 The role of environmental triggers, including infections and medications, has been increasingly recognized in the development of autoimmune myositis.2,6 Drug-induced autoimmune inflammatory myositis has emerged as an important clinical entity, particularly with the expanding use of biologic agents and targeted synthetic disease-modifying antirheumatic drugs.6 These therapies, including IL-17 inhibitors and JAK inhibitors, modulate immune pathways but may paradoxically disrupt immune tolerance and precipitate autoimmune phenomena.2,6 Psoriatic arthritis is a chronic inflammatory condition frequently managed with such therapies.7-9 While these treatments have significantly improved disease outcomes, their long-term immunological effects may contribute to rare but clinically significant complications, including inflammatory myopathies.4,6,7 In this report, the authors describe a case of autoimmune inflammatory myositis in a patient with psoriatic arthritis receiving multiple biologic therapies, highlighting diagnostic challenges and the importance of recognizing drug-induced etiologies in the modern therapeutic era. EPIDEMIOLOGY Autoimmune diseases are a major contributor to increased mortality among middle-aged individuals, with incidence rates varying by condition.3 Myositis, characterized by muscle inflammation, most commonly occurs between age 45–64 years.3 Gender differences have been observed, with women more frequently affected by polymyositis and dermatomyositis, and men more commonly diagnosed with inclusion body myositis.3 In patients with psoriasis, myositis affects approximately 1.32 per 1,000 individuals.10 The presence of other autoimmune conditions, psoriatic arthritis, and prior use of anti-TNF-α therapies may elevate the risk of developing myositis in this population.7-10 Approximately 7,000 new cases of myositis are diagnosed annually in the USA, with a greater incidence observed in certain demographic groups.3 CASE PRESENTATION A 34-year-old man presented to the Department of Rheumatology at a tertiary care hospital in Hyderabad, India, with acute onset of severe pain and swelling in the left lower limb, accompanied by progressive difficulty in walking that eventually required wheelchair assistance. He had a known history of psoriatic arthritis (diagnosed), and had been treated with multiple sequential biologic and targeted immunomodulatory therapies over the course of his disease. Following his diagnosis, the patient was initiated on secukinumab, which was continued for 4 years. He then received the Covishield™ (Serum Institute of India [SII], Pune, India) COVID-19 vaccine. After experiencing a subsequent flare of his psoriatic arthritis, secukinumab was discontinued, and treatment was switched to tofacitinib. Despite this change, the patient developed worsening joint symptoms and progression of psoriatic skin lesions 6 months later, prompting discontinuation of tofacitinib and re-initiation of secukinumab at a dose of 300 mg monthly. Six months later, recurrent synovitis and worsening cutaneous manifestations were noted, and apremilast was added to his treatment regimen. Owing to persistent disease activity, ixekizumab therapy was initiated 13 months later. The patient subsequently achieved stable clinical improvement throughout the rest of the year and the following year while receiving ixekizumab. However, 1 year and 3 months after ixekizumab therapy was initiated, he presented with acute proximal muscle weakness, markedly elevated creatine phosphokinase (CPK) levels, and clinical features suggestive of autoimmune inflammatory myositis. The complete chronology of the patient’s treatment course, disease progression, and onset of myositis is illustrated in Figure 1.

The treatment history demonstrated prolonged and sequential exposure to several biologic and targeted immunomodulatory agents over approximately 8 years. Notably, the onset of myositis occurred nearly 4 years after COVID-19 vaccination, whereas the patient had received long-term biologic therapy during the intervening period. This temporal relationship, together with cumulative immunomodulatory exposure, favored a biologic-associated or drug-induced etiology rather than a vaccine-associated mechanism. On physical examination, the patient was conscious, coherent, and oriented. His vital signs were stable, with a blood pressure of 130/80 mmHg, a heart rate of 88 beats per minute, and an oxygen saturation of 99% on room air. Local examination revealed tenderness, swelling, and increased warmth around the left knee, along with active psoriatic skin lesions. Neuromuscular examination demonstrated symmetrical weakness predominantly involving the proximal muscles of the lower limbs, including the hip flexors, hip extensors, quadriceps, and hamstrings (Medical Research Council [MRC] Grade 3/5), while distal lower limb and upper limb muscle strength remained preserved (Grade 5/5). The findings of manual muscle testing are summarized in Table 1.

The patient did not exhibit clinical features suggestive of specific inflammatory myositis subtypes. In particular, there was no history or examination finding consistent with Raynaud’s phenomenon, dysphagia, interstitial lung disease, nail-fold capillary abnormalities, or dermatomyositis-specific cutaneous manifestations other than the pre-existing psoriatic lesions. The initial differential diagnosis included cellulitis, deep vein thrombosis, and inflammatory myositis. Laboratory investigations demonstrated markedly elevated serum CPK levels of 2,071 U/L, an elevated C-reactive protein (CRP) level of 60.2 mg/dL, and a mildly increased aspartate aminotransferase (AST) level of 68 U/L. Leukocytosis was also present. A venous Doppler ultrasound examination of both lower limbs revealed no evidence of deep vein thrombosis. Based on the patient’s clinical presentation, physical examination findings, and biochemical evidence of muscle injury, a diagnosis of autoimmune inflammatory myositis was established. The laboratory findings are summarized in Table 2.