A Case of Angioedema and Urticaria in a Patient with Adult-Onset Still's Disease Receiving a TNF-alpha Inhibitor

Abstract

Abstract Background Adult-onset Still’s Disease (AOSD) is a rare multisystemic autoinflammatory disorder of unknown etiology usually affecting young adults and is characterized by spiking fever, polyarthritis and evanescent salmon pink rash. Recently, multiple new treatments including IL-1, IL-6, IL-17, and IL-18 inhibitors as well as TNF alpha inhibitors have been suggested for patients resistant to conventional glucocorticoid therapy. We present an unusual case of a patient who was diagnosed with AOSD and treated with infliximab. Treatment course was complicated by drug induced lupus, periorbital angioedema and urticaria. Case Presentation A previously healthy 20-year-old female presented with a 10-day history of recurrent fevers, rash, polyarthritis and an intermittent pink, patchy, non-raised rash on her arms, neck, and face. Physical exam revealed synovitis in her bilateral elbows, wrists, knees, and ankles. Workup was significant for ANA 1:80 (Negative < 1:80), ferritin > 4500 ng/ml (normal range 11-306.8), soluble IL-2R 2221 U/ml (normal range 45-1105), CRP 171.5 mg/L (normal range 1-10), ESR 23 mm/hr (normal range 0-20), and normal C3 and C4. She was diagnosed with adult Still’s disease and treated with glucocorticoids followed by methotrexate and plaquenil without resolution of her symptoms. Her treatment was escalated to infliximab 3 mg/kg to which she responded well. Eight months later, the patient developed periorbital swelling, malar rash, and eyelid rash. We suspected that the patient developed drug induced lupus and we discontinued Infliximab for Actemra infusions with improvement of her arthritis and rash. However, she continued to have episodes of urticaria with left upper eyelid swelling. Urticaria workup was remarkable for a low quantitative C1 esterase inhibitor, though previously normal. She was referred to allergy and was diagnosed with hereditary angioedema. Conclusions Drug-induced lupus is a well-recognized complication of TNF alpha inhibitor therapy. Although less commonly reported, angioedema and urticaria should also be recognized as potential complications. In these patients, treatment should be promptly discontinued to avoid life threatening complications such as laryngeal edema. Angioedema and urticaria are rare cutaneous manifestations of AOSD and recognition of this clinical variant is important in the differential diagnosis of unexplained angioedema.