Cryoglobulinemia is a rare medical condition defined by presence of cryoglobulins in serum and it may cause hyperviscosity syndrome or systemic vasculitis in variable organs including the skin, joints, liver, kidneys, lungs and nervous system. A vasculitic polyneuropathy or mononeuritis multiplex commonly occurs. However, central nervous system complications of cryoglobulinemia including stroke, encephalopathy and seizures are rarely reported. We represent a case of essential cryoglobulinemic vasculitis manifested as a sensorimotor polyneuropathy combined with an acute ischemic stroke attack.
Central Nervous System ; Cerebral Infarction* ; Cryoglobulinemia* ; Cryoglobulins ; Joints ; Kidney ; Liver ; Lung ; Mononeuropathies ; Nervous System ; Polyneuropathies* ; Seizures ; Skin ; Stroke ; Systemic Vasculitis ; Vasculitis

No abstract available.
Cryoglobulinemia* ; Gangrene* ; Monoclonal Gammopathy of Undetermined Significance* ; Paraproteinemias*

OBJECTIVETo summarize the clinical features of cryoglobulinemia.

METHODWe retrospectively analyzed the clinical data of 30 patients admitted to Peking Union Medical College Hospital from January 2003 to March 2013 due to cryoglobulinemia.

RESULTSThe average age was(53.8±11.9)years in these 30 patients(12 men and 18 women),among whom 22 patient(73.3%)developed infectious diseases including hepatitis B(n=11)and hepatitis C(n=11);in addition,3 hepatitis B patients and 1 hepatitis C patient also had malignancies. Four patients(13.3%)were accompanied with malignant lymphocytic proliferation diseases,and three(10.0%)with connective tissue diseases. The cause of disease was unclear in 5 patients(16.7%). The clinical manifestations varied due to the primary diseases;notably,20 patients(66.7%)had an onset of purpura rash,22(73.3%)and 19(63.3%)were accompanied with hypertension and chronic renal insufficiency,respectively. The severity of renal involvement was relevant with the increase of C reactive protein,erythrocytes,sedimentation rate,and IgM and the decrease of complements. Treatment should be directed at the primary diseases. Glucocorticoid and immunosuppressants were good choices for relieving renal involvement. Elderly, type 1 cryoglobulinemia,and poor renal function were associated with the poor prognosis.

CONCLUSIONSCryoglobulinemia is mainly seen in middle and elderly patients. It can often affect multiple systems,in particular the kidney. Inflammatory markers,IgM,and complements is related with the disease severity. Age,primary disease,and renal function are related with prognosis.

Aged ; Cryoglobulinemia ; diagnosis ; drug therapy ; pathology ; Female ; Hepatitis C ; diagnosis ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney ; pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

BACKGROUNDChronic hepatitis C virus (HCV) infection can affect multiple organ systems and cause a variety of extrahepatic manifestations (EMs). We sought to assess the constituent ratio of EMs in Chinese patients with chronic HCV infection and identify the clinical and biological factors associated with EM.

METHODSThe medical records of 297 patients with chronic HCV infection were analyzed and demographic and epidemiological information was collected. The diagnosis of chronic HCV infection was based on positive anti-HCV combined with a positive HCV-RNA or at least two times of elevated aminotransferases attributable to HCV infection. Patients with HBV and/or HIV coinfection, autoimmune hepatitis, and history of alcohol abuse were excluded.

RESULTSSixty-two percent (184/297) of the patients had at least one EM, including fatigue (29.4%), type 2 diabetes mellitus (28.2%), renal involvement (12.5%), lymphadenopathy (9.6%), fever (9.4%), thyroid dysfunction (8.1%), and arthralgia (7.4%). Neuropathy, sicca syndrome, B-cell lymphoma, Raynaud's phenomenon, and lichen planus were rare. The mean age of patients with EM was older compared with those without EM.

CONCLUSIONSEMs were common in Chinese patients with chronic HCV infection, particularly fatigue, type 2 diabetes, renal impairment, lymphadenophy, fever, and thyroid dysfunction. Older age was associated with EMs.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; China ; Cryoglobulinemia ; diagnosis ; etiology ; Diabetes Mellitus, Type 2 ; diagnosis ; etiology ; Fatigue ; diagnosis ; etiology ; Female ; Hepatitis C, Chronic ; complications ; physiopathology ; Humans ; Lymphatic Diseases ; diagnosis ; etiology ; Male ; Middle Aged ; Thrombocytopenia ; diagnosis ; etiology ; Young Adult

We report a 62-year-old woman with multiple myeloma associated with cryoglobulinemia accompanied by gangrene of the digits. She presented with generalized purplish net-like discoloration (livedo reticularis), which was more prominent in the lower extremities. Multiple small shallow ulcers with crusts were found in places. In addition, gangrene was observed in both ear helices, both index fingers, and several toes. The patient had monoclonal gammopathy consisting of IgG and kappa (3.95 g/dL), cryoglobulinemia, and bone marrow plasmacytosis (42%). A biopsy of a discolored skin patch on the lower leg revealed leukocytoclastic vasculitis. She was diagnosed with multiple myeloma associated with cryoglobulinemia. Immediate plasmapheresis halted the progression of the skin lesions and digital gangrene. Two cycles of thalidomide plus dexamethasone therapy led to a partial response. This case highlights the need to search for cryoglobulinemia and multiple myeloma when we see livedo reticularis or multiple skin ulcers with obscure causes.
Biopsy ; Bone Marrow ; Cryoglobulinemia ; Dexamethasone ; Ear ; Female ; Fingers ; Gangrene ; Humans ; Immunoglobulin G ; Leg ; Livedo Reticularis ; Lower Extremity ; Middle Aged ; Multiple Myeloma* ; Paraproteinemias ; Plasmapheresis ; Skin ; Skin Ulcer ; Thalidomide ; Toes ; Ulcer ; Vasculitis*

OBJECTIVETo determine whether patients infected with chronic hepatitis C (CHC) show a differential distribution profile of IL-28B polymorphisms according to the presence of concomitant cryoglobulinemia.

METHODSSixty-two consecutive CHC patients were enrolled in the study between December 2008 and December 2010. All patients received combination therapy of pegylated interferon alpha-2a (weekly, 180 g, subcutaneous injection) plus ribavirin (daily, 10to15 mg/kg body weight, oral) for 48 weeks, with individualized dosage adjustments according to the patient's clinical situation. Cryoglobulins were detected visibly by separation of cryoprecipitates in patient serum samples. Three IL-28B SNPs (rs8099917, rs12979860, and rs12980275) were detected by sequencing. Response to treatment was assessed by measuring serum levels of HCV RNA by quantitative PCR at baseline (prior to treatment initiation), during treatment (4 and 12 weeks after treatment initiation), end of therapy (48 weeks after treatment initiation), and post-treatment (24 weeks after end of therapy). The significance of between-group differences were assessed by the Chi-square and Fisher's exact tests.

RESULTSCryoglobulinemia was detected in 43.5% (27/62) of the CHC patients and showed a female bias (59.3% vs. males: 34.3%, P = 0.05). Compared to CHC patients without cryoglobulinemia, the CHC patients with cryoglobulinemia showed significantly higher levels of HCV RNA at baseline (5.64+/-1.20 vs. 6.37+/-0.67, P less than 0.05) but lower frequencies of the IL28B rs8099917 TT genotype (94.3% vs. 63.0%, P = 0.002), rs8099917 T allele (97.1% vs. 81.5%, P = 0.003), and rs12979860 C allele (94.3% vs. 83.3%, P = 0.048). CHC patients with cryoglobulinemia and having the rs8099917 TT, rs12979860 CC, or rs12980275 AA genotype achieved a higher rate of sustained virological response.

CONCLUSIONCryoglobulinemia in CHC patients is associated with a differential distribution of IL-28B polymorphisms, and certain polymorphisms may be related to anti-viral treatment response.

Adult ; Alleles ; Antiviral Agents ; therapeutic use ; Cryoglobulinemia ; blood ; complications ; Female ; Genotype ; Hepatitis C, Chronic ; blood ; complications ; drug therapy ; genetics ; Humans ; Interleukins ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; RNA, Viral ; blood

Cryoglobulinemia ; physiopathology ; Humans ; Male ; Middle Aged ; Peripheral Nervous System Diseases ; diagnosis ; etiology ; Serologic Tests ; Syphilis ; diagnosis

BACKGROUNDMixed cryoglobulinemia (MC) is one of the most common and severe symptoms in chronic hepatitis C patients. The aim of this study was to investigate whether mixed cryoglobulinemia is a factor associated with sustained virological response in chronic hepatitis C patients treated with combination therapy of pegylated interferon alpha-2a and ribavirin.

METHODSThis is a single-center study including 57 chronic hepatitis C patients who received combination treatments of pegylated interferon alfa-2a and ribavirin. Serum cryoglobulin was detected by cryoprecipitation prior to treatment. Serum hepatitis C virus (HCV) RNA levels were checked before treatment, during the fourth and 12th week of treatment, and during the 24th week after cessation of treatment. The genotype of HCV was determined at baseline. Logistic regression analysis was used to assess the factors associated with sustained virological response.

RESULTSTwenty-five patients were with MC (43.9%). Twenty-four weeks after cessation of antiviral treatment, sustained virological response achievement in MC(+) patients was significantly lower than that in MC(-) patients (32.0% vs. 75.0%, P = 0.001). Univariate Logistic regression analysis and multivariate Logistic regression analysis found that only MC (odds ratio: 6.375; 95% CI: 1.998- 20.343, P = 0.002) was negatively associated with sustained virological response achievement.

CONCLUSIONMC is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients treated with pegylated interferon alpha-2a and ribavirin.

Adolescent ; Adult ; Aged ; Cryoglobulinemia ; etiology ; metabolism ; Cryoglobulins ; metabolism ; Female ; Hepatitis C, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Ribavirin ; therapeutic use ; Young Adult

Cryoglobulinemia, first described by Wintrobe and Buell in 1933, is characterized by the presence of serum immunoglobulins that precipitate below 37degrees C and that dissolve on rewarming. Although the actual mechanism of cryoprecipitation and the etiology of cryoglobulinemia remains obscure, it is frequently associated with other systemic diseases, such as hepatitis C virus (HCV) infection, multiple myeloma, Sjogren's syndrome, B cell lymphoma, and systemic lupus erythematosus. No cases of cryoglobulinemia associated with B cell lymphoma have ever been published in the Korean medical literature, and few such cases have been reported in other countries. Herein, we report on a rare and interesting case of cryoglobulinemia developed in a patient with gastric diffuse large B cell lymphoma.
Cryoglobulinemia ; Hepacivirus ; Humans ; Immunoglobulins ; Lupus Erythematosus, Systemic ; Lymphoma ; Lymphoma, B-Cell ; Multiple Myeloma ; Rewarming ; Sjogren's Syndrome

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.
Antigens, CD5/*metabolism ; Antineoplastic Agents/therapeutic use ; B-Lymphocytes/immunology/metabolism ; Bone Marrow/pathology ; Cryoglobulinemia/diagnosis ; Cyclophosphamide/therapeutic use ; Diagnosis, Differential ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Female ; Glomerulonephritis/*diagnosis/pathology ; Humans ; Kidney/pathology ; Middle Aged ; Paraproteinemias/diagnosis ; Prednisolone/therapeutic use ; Vincristine/therapeutic use ; Waldenstrom Macroglobulinemia/*diagnosis/drug therapy/pathology