We present a 60-year-old man with a history significant for ulcerative colitis requiring total colectomy, primary sclerosing cholangitis requiring liver transplant, chronic renal insufficiency, hypertension, psoriasis, and spondyloarthritis manifested by nearly fused sacroiliac joints, enthesopathies, bursitis, and severe stiffness. He had excellent control of arthritis symptoms on infliximab (5 mg/kg Q6 weeks) but self-discontinued in 2013 for insurance reasons.
In July 2014, he received another infliximab infusion secondary to worsening joint pain. One week later, he began to develop shortness of breath, diffuse joint swelling and aches, and general malaise. Nine days after his infusion, he presented to the Emergency Department with severe joint pain in all major joints. He was afebrile, tachycardic (100 s bpm), and hypertensive (140 s-160 s/100 s mmHg). Knee arthrocentesis showed noninflammatory fluid without crystals. Labs were remarkable for white blood cell (WBC) count of 17.1 K/muL (neutrophils 86%), creatinine stable at 2.38 mg/dL, C-reactive protein (CRP) elevated to 4.2 mg/dL (reference < 0.6 mg/dL), total bilirubin elevated to 1.9 mg/dL, and alkaline phosphatase elevated to 208 IU/L. Notably, procalcitonin (PCT) was 118 ng/mL (reference range < 0.05 ng/mL). He was empirically treated with hydration and antibiotics and subsequently began to improve (PCT 56 ng/mL on hospital day (HD) 4). On HD 3, transthoracic echocardiogram (TTE) showed small pericardial effusion and no vegetation. No source of infection was found. Blood, joint fluid, stool, and nasal and urine cultures were negative; urinalysis was unremarkable; viral titers and bacterial serologies were negative; and chest X-ray was unremarkable. Rheumatologic studies were also unremarkable, including C3, C4, ANA, anti-dsDNA, cryoglobulins, and extractable nuclear antigens. He was discharged from the hospital five days after admission and instructed to complete a course of antibiotics. Nine days after discharge, he was again admitted for progressive shortness of breath and recumbent chest pain. Inflammatory labs were elevated as follows: PCT 0.57 ng/mL, CRP 5.3 mg/dL, and Westergren sedimentation rate 82 mm (reference range < 15 mm). TTE following computer tomography on admission showed a moderate-to-large pericardial effusion (Figure 1) with echocardiographic evidence of cardiac tamponade.
Pericardiocentesis was performed and 480 mL of hemorrhagic fluid was drained. Bacterial, tuberculosis, and fungal cultures of pericardial fluid were all negative and no organisms were seen on gram, acid fast bacillus, or fungal stains. Cytology was negative for malignancy. Blood cultures were negative. Anti-histone antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibody were negative. The patient was started on steroids 60 mg per day, and repeat TTE the next day showed interval decrease in pericardial effusion size. The pericardial drain was pulled the next day and he was discharged home. TTE 2 months after infusion revealed only trace pericardial effusion.
Five weeks after infliximab infusion, anti-infliximab serum antibodies were strongly positive (628,550 ng/mL with reference < 22 ng/mL). Due to absence of documented infection or other identifiable causes of pericardial effusion and in light of highly elevated antibodies against infliximab, it was felt that an immune reaction to anti-TNFalpha therapy was responsible. He was able to taper off high-dose steroids without issue. Two years later, the effusion has not recurred, but he has struggled to manage his joint symptoms without anti-TNFalpha therapy.