1/315. Familial primary cryofibrinogenemia. BACKGROUND: To our best knowledge this is the second case ever described of familial primary cryofibrinogenemia (CFG). patients: A 29-year-old Moroccan female and two of her three children suffered from painful purpura, slow healing small ulcerations and edema of both feet during the winter season. Laboratory investigations revealed the presence of cryofibrinogen in their blood plasma. All three patients were otherwise healthy and no associated disease could be demonstrated. CONCLUSIONS: The diagnosis of CFG has to be considered in patients with livedo reticularis, edema, painful purpura and slow healing ulcera after cold exposure. Cryofibrinogen-precipitates in the blood plasma have to be determined. Because secondary CFG occurs much more frequently than the primary form, it is important to rule out associated diseases through extensive physical examination and laboratory investigations. This communication also stresses the importance of a through family history of patients with CFG. An autosomal dominant mode of inheritance is supposed. ( info) |
2/315. Diffuse recidivant alveolar hemorrhage in a patient with hepatitis c virus-related mixed cryoglobulinemia. A case of diffuse and recidivant alveolar hemorrhage is presented in a patient with hepatitis c virus-related type II mixed cryoglobulinemia with membranoproliferative glomerulonephritis. The patient was a 48-year-old white woman who suffered several outbreaks of pulmonary hemorrhage refractory to treatment with steroids, cyclophosphamide, azathioprine, plasmapheresis and interferon-alpha. The patient also presented persistent increased titers of immune complexes and rheumatoid factor with no histological hepatic alterations. Some considerations about evolution and treatment are given according to the updated physiopathology of this disease. ( info) |
3/315. interferon-alpha may exacerbate cryoblobulinemia-related ischemic manifestations: an adverse effect potentially related to its anti-angiogenic activity. The discovery of the strong association between hepatitis c virus (HCV) infection and the development of mixed cryoglobulinemia has motivated active testing of antiviral-directed alternative therapies. Several trials have demonstrated that classic cryoglobulinemia-associated manifestations improve with interferon-alpha (IFNalpha) treatment. Herein we report on 3 HCV-infected patients with severe cryoglobulinemia-related ischemic manifestations who were closely followed up during IFNalpha therapy. Clinical evaluations with special attention to ischemic lesions, liver function tests, and cryocrit determinations were serially performed. In addition to prednisone and immunosuppressive agents, the patients received IFNalpha at 3 x 10(6) units, 3 times per week for 2 months, 3 months, and 4 months, respectively. In all 3 patients, systemic features improved, liver function results returned to normal, and cryocrit values decreased. However, ischemic lesions became less vascularized and ischemia progressed, leading to transmetatarsal and subcondylar amputation, respectively, in 2 of the patients and fingertip necrosis and ulcer enlargement in the third. skin biopsies performed before IFNalpha therapy and after 2 months of IFNalpha therapy in the third patient showed a significant decrease in subepidermal microvessels. When IFNalpha was discontinued, the lesions finally healed. cryoglobulinemia-related ischemic lesions may worsen during IFNalpha treatment, presumably through a decrease in inflammation-induced angiogenesis. The anti-angiogenic activity of IFNalpha may delay the appropriate healing of ischemic lesions. ( info) |
4/315. Severe cold agglutinin disease and cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda cryoagglutinin. OBJECTIVE: To present a case of cold agglutinin disease/cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda antibody, and review the literature on the occurrence of this antibody in cold-induced disease and the clinical disease associated with it. methods: Cryoantibody characteristics were evaluated by cold precipitation. The antigen specificity of the monoclonal IgM lambda antibody was evaluated using techniques of selective red blood cell absorption. RESULTS: In our patient, we were able to identify an antibody with both cryoglobulinemic and cold agglutinin (cryoagglutinin) properties. This antibody was found to be monoclonal IgM lambda with specificity to the Pr2 antigen on red blood cells. CONCLUSIONS: Monoclonal IgM lambda anti-Pr is a rarely found cold agglutinin antibody. In this report we describe the clinical course of a patient who had this antibody, which not only agglutinated red cells in the cold but also had cryoglobulin properties. The clinical illness of this man was characterized by severe acrocyanosis and digital necrosis with eventual organ necrosis and death. We also review the literature on cold induced disease due to monoclonal anti-Pr IgM lambda antibody. Our patient was found to be unique among the reports reviewed. Our case is the first to report both cold agglutinin and cryoglobulinemic properties with the evaluation of the thermal amplitudes of these activities of the antibody. Also, unlike the lymphoproliferative malignancy observed in the cold agglutinin-associated disease in the other reports, our patient's disease was associated with a monoclonal B-cell expansion on the spectrum between benign monoclonal gammopathy and a low grade lymphoproliferative disorder. ( info) |
5/315. Intensive tandem cryofiltration apheresis and hemodialysis to treat a patient with severe calciphylaxis, cryoglobulinemia, and end-stage renal disease. This is the first report on tandem cryofiltration apheresis (CFA) and hemodialysis (HD). A 44 year old white man with Type II mixed cryoglobulinemia, hepatitis c virus (HCV), severe skin lesions, and end-stage renal disease (ESRD) on maintenance hemodialysis was air-transferred for CFA, which is only available at our medical center. The patient failed to respond to high dose steroids, immunosuppression, intravenous immunoglobulin (IVIG), and plasma exchange for the treatment of his cryoglobulinemia, and he failed alpha-interferon therapy for his HCV. On arrival, he was also found to have severe calciphylaxis secondary to ESRD with generalized, painful skin ulceration, necrosis, and penile gangrene. To treat both conditions, intensive, tandem CFA/HD was initiated. He received extensive wound care and surgical debridement. To prevent pressure ulcers and worsening of skin lesions, he was placed on the FluidAir (Kinetic Concepts Inc., San Antonio, TX) controlled air bed. The patient received 18 tandem CFA/HD treatments, and four extra HD treatments in one month. sodium citrate was used as an anticoagulant for the CFA procedure. His plasma cryoglobulin (CG) level dropped from 6,157 to 420 microg/ml, and his calciphylaxis also improved. The CFA effectively removed 93% of CG, without significant removal of IgG, IgM, IgA, albumin, and fibrinogen. No albumin or fresh frozen plasma (FFP) was required as replacement fluid for CFA. No citrate toxicity or evidence of complement activation with the cryofilter was observed. The entire CFA procedure time (3(1/2) hours) was considered. Intensive, tandem CFA/HD was performed in a critically ill patient with no apparent adverse consequences. ( info) |
6/315. Neurological manifestations of chronic hepatitis c. hepatitis c virus (HCV) infection is often associated with abnormal immunological responses. We describe four patients with vasculitic neurological signs and symptoms following HCV infection. A 56-year-old woman with HCV infection developed peripheral neuropathy characterized by asymmetric distal painful hypesthesia, dysesthesia and moderate motor weakness of the lower limbs. Serological examinations revealed cryoglobulinemia and low levels of complement c4. A biopsy of the sural nerve revealed vasculitic neuropathy. HCV infection associated immunomediated vasculitis was diagnosed. While steroid therapy was ineffective, treatment with interferon-alpha improved the neuropathy considerably without, however, eliminating HCV infection. A 62-year-old man with HCV infection developed peripheral sensory neuropathy. complement c3 was slightly diminished. Nerve biopsy revealed vasculitic neuropathy. A 71-year-old woman developed chronic symmetric sensomotor polyneuropathy. HCV hepatitis followed blood transfusions. cryoglobulins tested positive, consistent with type II cryoglobulinemia. Complements C3 and C4 were diminished. Inflammatory infiltrates in the sural nerve biopsy specimen led to the diagnosis of chronic vasculitic disorder. A 55-year-old woman with HCV infection developed vasculitis of the skin, connective tissue, visceral organs, and kidney, leading to hemodialysis. Neurologically she developed severe apathy and drowsiness, myoclonic jerks, exaggerated deep tendon reflexes, and positive pyramidal signs. magnetic resonance imaging of the brain showed diffuse increased signal abnormalities involving supra- and infratentorial white matter suggesting cerebral vasculitis. cryoglobulins were positive, complements C3 and C4 slightly diminished (54 mg/dl, 4.3 mg/dl). Supportive therapy resulted in neurological improvement. Treatment with interferon-alpha was discontinued because of agranulocytosis. In patients with peripheral neuropathy or signs of leucencephalopathy, a hepatitis c associated vasculitis should be considered in the differential diagnosis. ( info) |
7/315. Primary hepatic diffuse large B-cell lymphoma in a patient with chronic hepatitis c. Epidemiological and experimental data suggest that the hepatitis c virus infection might be associated with the development of distinct types of non-Hodgkin's lymphomas. Here, we report a case of a patient with chronic hepatitis c and type II mixed cryoglobulinemia, who developed a primary hepatic non-Hodgkin's B-cell lymphoma. A diffuse, large B-cell lymphoma was diagnosed based on morphological, immunophenotypical and molecular genetic findings. hepatitis c virus replication, as evaluated by strand-specific reverse transcriptase-polymerase chain reaction, was detected in the nonneoplastic liver, but not in the lymphomatous tissue. High grade non-Hodgkin's lymphomas, although rare complications, have to be considered as part of the spectrum of hepatitis c virus-related hepatic lesions. ( info) |
| BACKGROUND/AIMS: The dynamics of hepatitis c viremia after perturbation by plasma exchange was addressed in two infected patients with symptomatic cryoglobulinemia. This approach may offer an alternative to studying patients treated with antivirals in order to understand the dynamics of hepatitis c virion exchange among different compartments in vivo. methods: plasma exchange sessions were conducted every 24 h for 3 consecutive days; hepatitis c virus rna copy numbers were evaluated in sequential plasma samples collected before (-24, -12, -8, and 0 h) and at short intervals (at 1, 3, 6, and 12 h) after each session. RESULTS: After each plasma exchange session viremia dropped by 45.3-93.3% in patient 1, and by 60.5-72.7% in patient 2, paralleling (or, in some cases, exceeding) the amount of fluid exchanged. No mobilization of cell-free hepatitis C virus from extra-vascular sites was documented during the 2-h plasma exchange. The dynamics of hepatitis c viremia after each procedure was also evaluated. Pre-plasma exchange levels were restored within 3-6 h in both patients, and the mean doubling times of residual viremia were 4.6 h and 4.5 h for patients 1 and 2, respectively. CONCLUSIONS: The results, in agreement with recent evidence indicating that the turnover of hepatitis c virions is a highly dynamic process, extend previous evaluations by documenting that large amounts of newly-produced virions are introduced into the vascular compartment within a few hours of the drop in hepatitis c viremia caused by plasma exchange. ( info) |
| OBJECTIVE: hepatitis c virus (HCV) infection is associated with type II cryoglobulinemia. HCV is specifically concentrated in type II cryoglobulins and has been implicated in the cutaneous vasculitis associated with the disease. In contrast to HCV, a role for hepatitis G virus (HGV) in type II cryoglobulinemia has not been defined, although prevalences as high as 43% of HGV infections in type II cryoglobulinemia have also been reported. methods: We studied 34 patients with type II and 29 patients with type III cryoglobulinemia associated with HCV infection, 6 patients with essential mixed cryoglobulinemia (EMC; all with type II), 50 hospital control patients, and 125 normal individuals. serum HCV and HGV rna were detected by reverse transcription-polymerase chain reaction (RT-PCR). In coinfected sera, HCV and HGV were quantitated by competitive RT-PCR assays. One coinfected patient was studied longitudinally for 6 years. RESULTS: Two (5.9%) of 34 patients with HCV-infected type II cryoglobulinemia, none of 29 patients with type III cryoglobulinemia, and none of 6 patients with EMC were positive for HGV rna, for an overall prevalence of 3.0% in mixed cryoglobulinemia. None of the control populations were positive for HGV. No statistical difference was seen between the prevalence in patients with type II cryoglobulinemia and the other populations studied. In coinfected sera, HCV, but not HGV, was concentrated in cryoglobulins, and HCV, but not HGV, correlated with cryoglobulinemia in a longitudinal study. CONCLUSION: There is a low prevalence of coinfection with HGV in patients with mixed cryoglobulinemia and HCV infection in the united states. HCV is selectively precipitated by type II cryoglobulins in coinfected sera. HGV infection does not appear to have a role in mixed cryoglobulinemia. ( info) |
| We describe a case of type II mixed cryoglobulinemia, with monoclonal IgMkappa rheumatoid factor, associated with visceral leishmaniasis caused by leishmania infantum. Involvement of Leishmania antigen(s) in the formation of cryoprecipitable immune complexes was suggested by the fact that cryoglobulinemic vasculitis subsided after antiparasite therapy and that anti-Leishmania antibodies, as well as rheumatoid factor, were enriched in the cryoprecipitate. We observed 2 additional patients with visceral leishmaniasis and cryoglobulinemic vasculitis. All 3 patients had seemingly contracted leishmaniasis in italy, were hepatitis c virus negative, and were initially diagnosed as having autoimmune disorders. These findings indicate that Leishmania can be an etiologic agent of type II mixed cryoglobulinemia. This parasitosis should be taken into consideration in the differential diagnosis of vasculitides in endemic areas. ( info) |