Progressive pericardial effusion during chemotherapy for advanced Hodgkin lymphoma

A 48 year-old man, previously in excellent health, presented with several weeks of diffuse pruritus and night sweats as well as a cervical mass unresponsive to antibiotics. A biopsy of the supraclavicular lymph node demonstrated CD30-positive, CD15-negative classical Hodgkin lymphoma (HL), nodular sclerosing subtype (Fig. 1). There was a normal cardiac silhouette and widened mediastinum on a chest X-ray performed at that time (Fig. 2a,b). A staging positron emission tomography/computer tomography (PET/CT) revealed extensive FDG-avid cervical, supraclavicular, mediastinal as well as periportal adenopathy. There was no lymphoma in the bone marrow biopsy, confirming the diagnosis of stage IIIB disease according to Ann Arbor classification. The white blood cell count was 6.6 3 10/L, absolute lymphocyte count 900 3 10/L, hemoglobin 13.6 g/dL, erythrocyte sedimentation rate 37 mm/h and albumin 4.0 g/dL. The patient was offered treatment with standard ABVD chemotherapy for six cycles, with a plan for interim reassessment after two cycles. The patient had advanced HL with two negative prognostic factors based on the International Prognostic Score, corresponding to a 67% chance of 5-year freedom from progression of disease and overall survival of 81% [1]. Despite superior results in advanced HL reported in the HD9 study with dose-escalated BEACOPP, [2] its adoption has been hampered by high rates of infertility, infections, and secondary leukemias [3]. Recent data suggest attenuated difference between BEACOPP and ABVD if stem cell transplantation is planned for the minority of patients experiencing a relapse [4]. This area remains a subject of intense controversy. Moreover, evidence of complete response by PET/CTafter two cycles of ABVD appears to confer excellent prognosis, even though decision-making based on such evaluation is still subject to prospective randomized trials. This paradigm underscores the focus on identifying the patients with good or poor outcomes with standard therapy rather than treating everyone with maximally aggressive protocols. Evaluation of cardiac function is recommended before administration of doxorubicin and the patient had an incidental negative stress echocardiogram 9 months before the lymphoma diagnosis, without evidence of decreased ventricular function or pericardial disease. Similarly, he had a normal pulmonary function test including diffusion lung capacity before receiving bleomycin. A complete clinical and radiographic response was confirmed at the time of 2-month interim restaging. There were no major side effects of chemotherapy except for Grade 2 neutropenia, aphtous ulcers, and toenail onchomycosis treated with oral terbinafine and nail avulsion. On the restaging PET/CT a moderate, circumferential pericardial effusion was noted, retrospectively present on the initial scan, without any fluorodeoxyglucose (FDG) activity in the pericardial sac. Since the patient had no respiratory or cardiovascular symptoms, therapy was continued as planned without interruption. During the last cycle of chemotherapy the patient reported transient bilateral swelling of the metacarpophalangeal joints and ankles. This was accompanied by a recurrent, atypical left-sided chest discomfort at rest and with exertion. There was no difference with position or respiration. He had no palpitations, dyspnea, dizziness, fever or night sweats, and no numbness or paresthesiae. No other musculoskeletal problems, recent travel, or tick bites were reported. Examination revealed normal vital signs with mild tachycardia (heart rate 89 beats per minute), no adenopathy or discernible edema in the hands, and only mild swelling of the ankles. Heart sounds were normal with no gallop, murmur, or rub. The symptoms subsided after a few days. Immediately after the last dose of chemotherapy, the lower extremity edema as well as cough and a steady left-sided chest discomfort recurred. The electrocardiogram (EKG) showed normal sinus rhythm at the rate of 84 beats per minute with a QRS interval of 90–110 msec (Fig. 2d). There were no classic ST or T wave changes seen in acute pericarditis. There was no diagnostic low voltage or electrical alternans to suggest a large, hemodynamically significant pericardial effusion. Cardiac troponin and creatinine kinase were repeatedly normal. A 2D echocardiogram revealed a circumferential pericardial fluid measuring up to 19 mm at end diastole consistent with moderate to large pericardial effusion (Fig. 2c). Early diastolic collapse of the right atrium was noted but no pericardial thickening or tamponade physiology. Chest X-ray confirmed enlargement of the transverse diameter of the heart with resolution of mediastinal adenopathy. The patient had a clinical syndrome of serositis with a progressive pericardial effusion. The electrocardiographic findings were non-specific. EKG findings in acute pericardi-