Autoinflammatory Conditions May Increase Risk of Adverse Drug Reactions

Abstract

In this case report, we will describe a patient who has been diagnosed with cryopyrin associated autoinflammatory syndrome (CAPS), with a history consistent with familial cold autoinflammatory syndrome (FCAS). The patient experienced drug reactions to multiple treatments highlighting how autoinflammatory conditions may increase the risk of drug reactions in patients.CAPS is a rare genetic autoinflammatory condition caused by gain of function mutation in NLRP3 leading to the activation of the cryopyrin inflammasome which causes release of many cytokines including IL-1β. Patients experience systemic symptoms involving the musculoskeletal, nervous system, and cutaneous systems. This patient is a 32-year-old female with no past medical history who presented with symptoms of recurrent cold urticaria, arthralgias, and frequent conjunctivitis since she was 15 years old. Her father and brother also experienced similar symptoms. Patient’s genetic testing revealed a pathogenic variant in the NLRP3 gene (Variant c1322C>T (p.Ala441Val)) consistent with CAPS. The patient was initially treated with canakinumab, a monoclonal antibody to IL-β, the cytokine implicated in CAPS. During the three months of therapy, the patient’s symptoms abated, however, she experienced increased bruising and heavier menstrual cycles. Her laboratory testing at the time revealed a stable platelet count of 157 000 µL (106 000 µL prior to treatment) and stable hemoglobin level of 11.6 g/dL (10.9 g/dL prior to treatment). Due to her significant symptoms, canakinumab was discontinued and she was trialed on Anakinra, an IL-1 receptor antagonist. After a week of daily injections, the patient developed bullous urticaria at the injection site. Skin biopsy of the lesions confirmed the presence of eosinophils within the dermis consistent with a drug eruption to Anakinra. Currently, the patient is trialing Rilocept, a dimeric fusion protein that prevents IL-β signaling, with close monitoring for any adverse effects.The immune modulation which occurs in patients with autoinflammatory conditions may predispose them to various adverse drug effects. This could be explained by the cytokine up-regulation which causes increased sensitization to various other inflammatory pathways including histamine and coagulopathy pathways. This case highlights the need for further research about drug reactions in autoinflammatory conditions.