PARANEOPLASTIC VASCULITIS AND COEXISTENT TROUSSEAU'S SYNDROME SECONDARY TO PANCREATIC CARCINOMA

Abstract

To the Editor: An 81-year-old man was admitted with a 3-week history of cough, yellow sputum, hemoptysis, and shortness of breath. He had a history of bilateral branch retinal vein occlusions, pulmonary embolism, epistaxis (before warfarin), thrombophlebitis, raised prostate-specific antigen with negative biopsy, chronic pancreatitis, and bronchiectasis. He never smoked, and his medications were prazosin, nifedipine, and warfarin. On admission, he was febrile (38°C), tachypneic, and hypoxic (pressure of oxygen=7.21 kPa). He had left basal crepitations, and otherwise the examination was unremarkable. Blood tests indicated anemia (hemoglobin 12.3 g/dL), neutrophil leucocytosis (11.5 × 109/L), raised C-reactive protein (>250 mg/L), and normal renal and liver function. His international normalized ratio was 3. Chest x-ray showed a left pleural effusion and underlying volume loss. He was treated with antibiotics. His fever settled, and dyspnea improved, although the hemoptysis persisted. The warfarin therapy was changed to low-molecular-weight heparin, which was maintained throughout his admission. Cultures of sputum, urine, and blood were all negative. One week later, he developed a palpable purpuric rash with a leukocytoclastic vasculitic appearance on both legs and arthralgia. Although his C-reactive protein had fallen to 110 mg/L, his erythrocyte sedimentation rate was 98 mm/h, and he had microscopic hematuria and proteinuria. The following investigations were negative or normal: antinuclear antibody, antiglomerular basement membrane antibody, serum electrophoresis, hepatitis B and C, and human immunodeficiency virus serology. His prostate-specific antigen was 20.5 μg/L; CA19-9 was not raised. He had a positive c-antineutrophil cytoplasmic antibody (ANCA) with positive proteinase 3 antibody at 24 Au/mL (range 0–10). A skin biopsy was not done. The following tests revealed no evidence of malignancy: bronchoscopy and biopsy, pleural fluid and urine cytology, upper and lower gastrointestinal endoscopy, cystoscopy, and prostate biopsy. Computerized tomography (CT) of the thorax and abdomen showed a focal, low soft-tissue-density mass within the liver consistent with metastasis; bowel gas obscured the pancreas, and the prostate was enlarged (Figure 1). Computed tomography (CT) scan of liver showing soft-tissue-density mass consistent with metastasis. He was started on prednisolone and methotrexate (stopped once results of the CT scan were available), and his purpura disappeared, and inflammatory markers returned to normal. A liver biopsy was planned, but the patient died suddenly after a respiratory arrest. Postmortem examination revealed pulmonary embolism secondary to a deep vein thrombosis. A moderately differentiated adenocarcinoma of the pancreas was found, with liver and peritoneal metastases. Paraneoplastic vasculitis associated with solid tumors is rare. In a review,1 only 36 of more than 200 patients who had simultaneous cancer and vasculitis had a solid tumor, the majority had hematological malignancy. Bronchogenic carcinoma is the cancer most frequently associated with vasculitis.2, 3 ANCA is usually negative in secondary vasculitis. There are few reports of ANCA-associated paraneoplastic vasculitis.4 Only two previous reported cases of pancreatic carcinoma and vasculitis could be found, and both were associated with Wegener's granulomatosis.5, 6 Diagnosis of vasculitis in this patient was based on the clinical picture, with involvement of skin and possibly kidney (hematuria) and lung (hemoptysis). The history of epistaxis and retinal vein occlusions raises the possibility of Wegener's granulomatosis with positive c-ANCA. The role of the patient's medications, including antibiotics, in the vasculitis is unlikely, because drug-induced vasculitis is usually ANCA negative. This patient had pancreatic carcinoma, which is also associated with Trousseau's syndrome. The development of recurrent superficial thrombophlebitis characterizes this syndrome. Thrombi may occur in the arterial or the venous system. Patients typically have thromboembolic phenomena that are manageable with heparin-based anticoagulation,7-9 but these conditions are unresponsive to warfarin.7 This syndrome is most commonly associated with solid tumors of the adenocarcinoma type. Pancreatic tumors, especially those of the body or tail, seem to be associated with the highest risk of this syndrome.10 This patient had thrombophlebitis and a pulmonary embolism some months before admission, for which he was on warfarin. He also had a history of retinal vein occlusions. He was taking low-molecular-weight heparin during his admission, which should have been more effective than warfarin and a suitable alternative to unfractionated heparin.8, 9 No case report has been found of paraneoplastic vasculitis caused by pancreatic carcinoma and Trousseau's syndrome in the same patient. In summary, a patient with a solid neoplasm, c-ANCA positive paraneoplastic vasculitis, and Trousseau's syndrome is presented. Because malignancy is associated with ANCA-positive vasculitis, it should be considered as part of the differential diagnosis in patients presenting with vasculitis. Diagnosis is important, because immunosuppressive regimens have the theoretical risk of provoking malignancy or its dissemination. Financial Disclosure: None. Author Contributions: Both authors were equally involved in the writing of this letter. Sponsor's Role: None.