Primary myelofibrosis in a patient who developed primary biliary cirrhosis, autoimmune hemolytic anemia and fibrillary glomerulonephritis

Abstract

Dear Editor, We report a patient with primary myelofibrosis (PMF) who developed primary biliary cirrhosis, autoimmune hemolytic anemia, and fibrillary glomerulonephritis (FGN). A 67-year-old woman was referred to our institution in November 1999 because of asthenia and nocturnal sweats associated to PMF, which was diagnosed in September 1996. In June 1998, high liver enzymes, circulating antimitochondrial antibodies, and a liver biopsy disclosed primary biliary cirrhosis. She had a history of arthralgia, positive latex test, xerosthalmia, and xerosthomia. On admission, she presented with hepatosplenomegaly, moderate thrombocytosis, mild anemia, elevated leukocytes and 6% circulating blasts. Leukocyte alkaline phosphatase score was very low, karyotype was normal, no bcr-abl translocation was detected, and high lactic dehydrogenase levels were found. Bone marrow (BM) aspiration yielded a dry tap and BM biopsy disclosed megakaryocyte and myeloid hyperplasia, diffuse increase in reticulin fibers with osteosclerosis. Progressive splenomegaly was noted. In January 2000, the patient was medicated with hydroxyurea except during 2002 when she received thalidomide 50 mg/day plus prednisone for only 4 months because of lack of response and development of marked basophilia and polyneuritis. She had severe anemia with low levels of erythropoietin but did not respond to erythropoietin. In November 2003, an immunophenotype showed 10% circulating blasts of myeloid lineage with monocytoid features. In February 2004, she was admitted because of classic autoimmune hemolytic anemia with positive direct Coomb’s test. Reduced total complement level, homogenous positive antinuclear factor, and Sm B, Sm D, and RNP-A antinuclear antibodies were also detected. She received red cells transfusion and prednisone with favorable response and a dramatic decrease in spleen size. Two weeks later, she presented with nephrotic syndrome characterized by non-selective proteinuria, 8 g/day, and decreased renal function. Renal biopsy disclosed Congo red-negative fibrillar deposits, characteristic of FGN, which were confirmed by electron microscopy (Fig. 1). Immunofluorescence microscopy revealed granular staining for IgG, IgM inside the glomeruli, and IgG, IgA in the tubular deposits. Urine IgG and IgA, lambda and kappa light chains were detected by immunoelectrophoresis. JAK2V617F mutation yielded negative results. In December 2005, she had 32% circulating blasts. In April 2006, an immunophenotype with 47% of blasts supported the diagnosis of acute myelogenous leukemia-M0. She died of sepsis. The presence of several immunologic disorders in this patient and partial improvement of PMF features with Ann Hematol (2008) 87:1019–1020 DOI 10.1007/s00277-008-0516-6