A 74-year-old Ecuadorian man who smoked 3 cigarettes a day for a year but quit 15 years prior presented to the Emergency Department (ED) with four days of a productive cough that did not improve with azithromycin. His medical history included hypertension and cataracts. He worked at a clothing factory for years. The body mass index was 24.9 kg/m2. Physical examination showed a blood pressure of 154/86 mmHg, pulse of 115 beats/minute, respiration rate of 18/min, oxygen saturation of 95% on ambient air, and temperature of 101 F. Pulmonary auscultation on hospital admission revealed decreased bilateral breath sounds in the lower lung fields. A chest radiograph showed a large rounded opacity in the superior segment right lower lobe and bibasilar patchy infiltrate. The results of laboratory studies revealed a white blood cell count of 16,000/mul with 82.7% neutrophils and 8% lymphocytes, hemoglobin of 11.9 g/dl, and platelet count of 250,000/mul. Blood and urine cultures yielded no growth, and his acute symptoms of fever and cough subsided with ceftriaxone plus azithromycin. He was discharged home three days after admission. However, his productive cough recurred. More than a month later, computed tomography (CT) scan of the chest revealed multiple, approximately 16.4-28.6 mm, enlarged nodes in the mediastinum and hila, diffuse septal thickening, and multiple ill-defined patchy ground glass opacities with a lower lobe predominance (Figure 1). On transthoracic echocardiography, the systolic pressure of the pulmonary artery was 33 mmHg with normal ejection fraction. The rheumatoid factor was negative, and the antinuclear antibody was positive at 1 : 80 with a homogeneous pattern. The patient was readmitted (2 months after the first episode) due to pleuritic chest pain and dyspnea on exertion. Radiography of the chest revealed bilateral prominent lung interstitial markings particularly in the left perihilar areas, and he was empirically covered for hospital-acquired pneumonia with vancomycin and piperacillin/tazobactam. More than a month later, his C-reactive protein (CRP) was <5 mg/l. He was lost to follow-up for five months but returned complaining of xerophthalmia, and artificial tears provided relief. He was again lost to follow-up for another five months and then noted to have weight loss of 25 pounds over 6 months. Follow-up chest CT findings more than a year after his initial admission included worsening septal thickening and ground glass opacities. Transbronchial lung biopsy demonstrated mild thickening of interstitial septae and increased infiltration by lymphocytes, macrophages, and plasma cells (Figure 2) consistent with LIP. No malignant cells were seen.
Then, he developed bilateral metacarpophalangeal swelling and pain and swelling. To treat LIP, he was started on oral prednisone at a dose of 20 mg/day (0.25 mg/kg). His joint symptoms improved markedly. A laboratory workup was positive for the SSA antibody, and he was diagnosed with Sjogren's syndrome. His CRP was elevated (191 mg/l) and complement levels were low (C3 and C4, 40 mg/dl and 1 mg/dl, respectively). He tested negative for anti-SSB, anti-Jo-1, anti Scl-70, anti-neutrophil cytoplasmic, and anti-double-stranded DNA antibodies. Pulmonary function testing did not show obstructive dysfunction. His postbronchodilator forced expiratory volume in one second (FEV1) was 3 liters (126% predicted), total lung capacity (TLC) was 5.48 liters (104% predicted), and diffusion capacity for carbon monoxide (DLCO) was 17.8 ml/min/mmHg (82% predicted). The patient complained of dry mouth, which improved with pilocarpine. He was lost to follow-up for four months, during which time he discontinued prednisone after five months. Then, he developed anterior uveitis which was treated successfully with topical prednisolone acetate. A follow-up chest CT scan more than a year after oral prednisone was first started showed bibasilar and lingular interstitial fibrotic changes, decreased prominence of associated interlobular septal thickening and ground glass opacity, and a decrease in the size of the lymph nodes. Prednisone 20 mg/day was resumed and slowly tapered over three months. A month after prednisone was tapered to 10 mg, he presented to the ED with oral mucosal bleeding. His vital signs were unremarkable. Physical examination was significant for a bloody oral cavity, bruises on the right arm and legs, and scattered petechiae on the chest and lower legs. Laboratory tests were remarkable for a platelet count of 2000/mul. Peripheral smear did not show schistocytes. CT head was negative for acute hemorrhage. Further labs, including liver function, lactate dehydrogenase, and vitamin B12 levels, were normal. Hepatitis C antibody, hepatitis B surface antigen, and human immunodeficiency virus were negative. No obvious drug-related causes of thrombocytopenia were identified. Blood and urine cultures were negative. A diagnosis of ITP secondary to Sjogren's syndrome was made. A bone marrow biopsy was not done.
The patient was started on prednisone at 80 mg/day (1 mg/kg/d) and received a total of 12 units of platelet transfusion. He was given intravenous immunoglobulin (IVIG) at 1 g/kg/d for two days. His platelet count improved to 84,000/mul by the sixth day, and oral bleeding resolved. The patient was discharged home, but he was unable to continue the prednisone because the prescription was accidentally not transmitted to the pharmacy. After five days, he was readmitted with oral mucosal bleeding. The platelet count was found to be 3000/mul. He received IVIG at 1 g/kg/d and IV methylprednisolone 62.5 mg twice a day. By the fifth day, his platelet count was 178,000/mul. He was discharged on prednisone 80 mg/day, and it was uneventfully tapered off over four months. He was also started on hydroxychloroquine for musculoskeletal pain. His latest platelet count around six months after the last admission was 254,000 cells/mul.