Case Report. Cryoglobulin Hyaline-thrombi Associated Acute Jejunitis in A Patient with Type 2 Cryoglobulinemic Glomerulonephritis
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Abstract Introduction/Objective Only one prior case report indicates that mixed positive cryoglobulin in serum can be associated with intestinal vasculitis (Annals of Internal Medicine, 1974). Methods/Case Report We report a 63-year old man with history of positive serum cryoglobulin and hepatitis-C 4 years ago and membranoproliferative pattern of glomerulonephritis with possible cryoglobulin type of deposits by electron microscopy on renal biopsy. After treatment, his hepatitis C became negative. But he was recently found to have monoclonal IgM-kappa and positive cryoglobulin in his serum, and the concurrent renal biopsy showed membranoproliferative pattern of glomerulopathy with many hyaline-thrombi (eosinophilic vascular occlusions with no lamination, inflammatory cells or nuclear debris) in the glomerular capillary loops (Figure, left panel). Both immunofluorescent and electron microscopy confirmed a mixed IgG polyclonal and IgM monoclonal type 2 cryglobulinemic glomerulonephritis. The patient also developed abdominal pain and underwent intestinal endoscopy with biopsy. His jejunal biopsy revealed neutrophil infiltration into glands and surface epithelium, with superficial sloughed epithelial cells, consistent with acute jejunitis with features of ischemic etiology. In addition, hyaline-thrombi were identified in the submucosal vessels with surrounding vasculitis (Figure, right panel); the central part of thrombi was morphologically similar to that found in glomerular capillary loops. Therefore, we conclude that cryoglobulin associated hyaline-thrombi were the most likely etiology to cause the acute ischemic jejunitis in this patient. Results (if a Case Study enter NA) NA Conclusion NAKeywords:
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The technique of cryofiltration has been applied in the treatment of cryoglobulinemia. Good clinical improvement has been demonstrated accompanied by decreases of cryoglobulin levels. Three treatments in a week produced transient improvement of clinical symptoms and reduction of cryoglobulin levels. Follow-up treatments performed at adequate frequency and volume processed maintained relief of symptoms and serologic improvement. The cryofilter demonstrates good selectivity for cryoglobulin removal in cryogel, confirmed by electrophoretic analysis of both the cryogel filtrate from the cryofilter used clinically. Plasma cryofiltration appears to be a safe alternative to plasma exchange, requiring no replacement fluids.
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We present a case of type 1 cryoglobulinemia with an underlying hematological malignancy. Unusually, the entire unifying diagnosis was made on the basis of the renal biopsy. Initially, serum cryoglobulin was not identified; repeat samples were positive. It is important to note that there is a significant false-negative rate with laboratory testing for cryoglobulin, due, at least in part, to the specific conditions required for collection and processing. With that in mind, in all cases with strong clinical or histological evidence of cryoglobulin but negative testing, carefully repeated samples should be sent.
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An 81-year-old man was admitted to our hospital because of leg edema. Serological studies for anti-neutrophil cytoplasmic antibody (ANCA), anti-double stranded DNA antibodies, and antibodies to hepatitis C and B were negative. Severe hypocomplementemia was present and a cryoglobulin was detected with serum immunoelectrophoresis being positive for the immunoglobulin (Ig)M kappa type. The cryoglobulin was characterized by immunoelectrophoresis which showed that the protein was composed of polyclonal IgG and kappa-type monoclonal IgM. A diagnosis of essential type II cryoglobulinemia was made and the patient underwent a renal biopsy. The renal biopsy revealed endocapillary and mesangial cell proliferation with increased matrix. The resultant lobular appearance of the glomerulus and double contours of the basement membrane were indicative of membranoproliferative glomerulonephritis (MPGN). Immunofluorescence studies demonstrated granular staining in the capillary wall for IgG, IgA, IgM and C4 with little C3 deposition but no C1q. He was finally diagnosed with MPGN due to mixed cryoglobulinemia type II. MPGN with essential cryoglobulinemia type II without evidence of hepatitis C virus infection, like that found in the present case, is very rare.
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Cryoglobulinemia, a condition in which a protein or group of proteins in the blood precipitate on exposure to cold, may be associated with retinal vascular changes. This paper reviews the present knowledge of cryoglobulinemia and presents the eye findings which were present in one of three patients with cryoglobulinemia seen at the Veterans Administration Hospital in Philadelphia. In 1933, Wintrobe and Buell described a cold-precipitable globulin. Others repeated this observation, but not until 1947 was the term cryoglobulin used.4,7,13,16,22,49Lerner and Watson, in 1947, while studying the blood serums of 121 patients suffering from various diseases, found that there was a spontaneous precipitation of protein in 31 cases when the serum was cooled to 4 C.6They proposed the term cryoglobulin to describe the protein or group of proteins which have the characteristic of precipitation, or "gelifying," in the cold. The precipitated protein, which they regarded as a
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Pseudo-leukocytosis was found in a patient with essential cryoglobulinemia when leukocyte (WBC) counts were determined using a Model S Coulter Counter. The spurious leukocytosis was confirmed in additional patients with cryoglobulinemia and is thought to be due to particle formation between the cryoglobulin and fibrinogen. Markedly elevated leukocyte counts not confirmed by standard methods should alert the laboratory that a cryoglobulin may be present.
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Most patients with clinically significant cryoglobulinemia exhibit rheologic, vasculitic or constitutional findings. There are several unusual laboratory findings that suggest the possibility of unsuspected cryoglobulinemia. Specimen collection and laboratory processing errors can lead to inaccurate cryoglobulin evaluation. Recognition of these unusual laboratory manifestations and rigorous specimen collection, transport and processing will improve the diagnostic evaluation of patients with cryoglobulinemia.
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Cryoglobulinemia is an uncommon cause of renal disease and often occurs in patients with hepatitis C virus (HCV) infection. We report a case of membranoproliferative glomerulonephritis in a patient with cryoglobulinemia, which was not associated with HCV infection or any identifiable etiology.
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Membranoproliferative glomerulonephritis
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