Loose Granulomas Research Articles

Fatal Intra-Alveolar Hemorrhage After Rituximab in a Patient with non-Hodgkin Lymphoma

A 65-year-old male developed progressive dry cough and digital clubbing after starting rituximab-CHOP chemotherapy for non-Hodgkin lymphoma. A lung biopsy showed loose non-necrotic granulomas in a background of mild fibrosis and rare eosinophils, compatible with a drug-induced hypersensitivity pneumonia. Associated manifestations of this hypersensitivity reaction were a high eosinophil count, elevated serum levels of immunoglobulin E, and a skin rash consistent with pigmented purpuric dermatitis (Schamberg disease). Corticosteroids were marginally efficacious in treating this reaction. Few similar reactions have since been described, 2 of them ultimately fatal, but none was associated with pulmonary hemorrhage. A 2.5 : 1 ratio between the interstitial alveolar T4/T8 lymphocytes in our case is similar to the findings in methotrexate-induced pneumonitis and farmer lung disease. This report documents the serologic and immunohistologic findings associated with a pulmonary interstitial reaction to rituximab. A review of the pertinent literature is provided. The possible pathogenetic mechanisms, including the role of cytokines, cytotoxic T-lymphocytes and CD 20 positive T-cells in relation to the administration of rituximab are discussed.

Experimental paracoccidioidomycosis in high and low antibody responder mice of Selection IV-A.

High (H) and low (L) responder mice were selected for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). In this selection, the difference in antibody responsiveness between H and L lines (HIV-A and LIV-A mice, respectively) was shown to depend mainly on macrophage function. The more rapid catabolism of antigens by macrophages in L mice has been suggested as the main cause of the low antibody production. Due to this high macrophage activity, L animals have been described as more resistant than H animals to intracellular pathogens. These animals were utilized as an experimental model of paracoccidioidomycosis. HIV-A and LIV-A mice were infected with Paracoccidioides brasiliensis by the intravenous route. As expected, H mice were more susceptible to P. brasiliensis with a shorter survival time and higher levels of specific antibodies when compared to L mice. Contrasting with the survival time, the lungs, spleen and liver from H mice showed typical nodular granulomas containing epithelioid and giant cells and few fungi. On the other hand, in LIV-A mice, the lesions of these organs were characterized by looser granulomas with irregular borders and the presence of a large number of fungi. However, the adrenal gland showed different lesion patterns. In H mice these lesions were extensive and characterized by loose granulomas with numerous fungi, while in LIV-A mice the lesions were small and limited to the cortex. Moreover the HIV-A mice presented higher levels of serum corticosterone when compared to LIV-A ones. The higher susceptibility of H mice could be attributed to the extensive lesions of the adrenal glands. These results suggest the use of the H line from the IV-A Selection as an experimental model for further studies of adrenal involvement in paracoccidioidomycosis.

COLITIS IS COMMON IN CGD

99 Chronic Granulomatosis Disease (CGD) is due to abnormality of NADPH oxidase in variety of cells and tissues, which are inherited as either an X-linked or an autosomal recessive trait. Gastrointestinal involvement (GI) has been rarely described though abnormal cells are present in the gut. We have studied the colon of 7 consecutively presenting patients with CGD, five boys and two girls, who were diagnosed, from birth or up to 30 months of age. 2 had an autosomal variant and 5 were x-linked. They presented with anemia 7/7, failure to thrive 6/7, recurrent diarrhoea 5/7, bloody stools 3/7, constipation 1/7. The time between presentation and investigation of GI was 3 months to 5 ½ years. Colonoscopy showed a patchy erythema thoughout the colon with occasional ulceration. Colonic biopsies revealed in all patients a patchy pancolitis with irregular, flat epithelium, crypt distortion, reduction in their number, cryptitis and crypt abscesses. The lamina propria showed an increase in degranulating eosinophils and eosinophilic pigmented macrophages. The number of histocytes was augmented, sometimes forming loose granulomas. Granulomas were found only in the older patients. The vascular endothelium appeared plump and eosinophils could be seen trafficking through the vessel wall. In contrast eosinophils did not traffic through the surface epithelium. Staining with BODIPY-phalloidin demonstrated a disorganized sheath of f-actin around the crypts, with modification of their shape. The colitis in CGD is described as a rare finding, however in our study 7/7 patients had histopathological changes present in the colon and were anaemic. Although previously described as Crohn-like our findings suggest that in CGD there are specific histological hallmarks present. We suggest that colitis occurs in most if not all patients with CGD and that evaluation of the gastrointestinal tract should be part of the routine investigation of such children.