Vasculitis crioglobulinémica de rápida evolución / Rapidly evolving cryoglobulinemic vasculitis

Las vasculitis se manifiestan por la inflamación de los vasos sanguíneos, afectando desde los capilares hasta los vasos de mayor tamaño. El compromiso dermatológico por vasculitis comprende desde casos leves, que generan compromiso superficial, hasta úlceras y necrosis de diferentes tejidos. La crioglobulinemia se caracteriza por la presencia de crioglobulinas séricas, que precipitan a temperaturas menores a 37 ºC. Se pueden asociar a enfermedades infecciosas (destacándose la infección por virus de hepatitis C, VHC), inmunomediadas y linfoproliferativas. La vasculitis en contexto de crioglobulinemia se produce por depósitos de inmunocomplejos en capilares, arteriolas, y arterias de pequeño y mediano calibre. El tratamiento consiste en tratar la causa subyacente y modular la respuesta inflamatoria. Se presenta el caso clínico de un varón de 50 años, con historia de hepatitis B crónica, que manifestó isquemia aguda y crítica de ambas extremidades, documentándose vasculitis crioglobulinémica con mala evolución.

Vasculitis is manifested by inflammation of the blood vessels, affecting from the capillaries to the largest vessels. Dermatological compromise due to vasculitis ranges from mild cases that generate superficial involvement to ulcers and necrosis of different tissues. Cryoglobulinemia is characterized by the presence of serum cryoglobulins, which precipitate at temperatures below 37 degrees Celsius. It is associated with infectious, immune-mediated, and lymphoproliferative diseases, especially infection by the hepatitis C virus. Vasculitis in the context of cryoglobulins is produced by immune complex deposits in capillaries, arterioles, and small and medium-sized arteries. Treatment is based on treating the underlying cause and modulating the inflammatory response. We present the case of a 50-year-old man, with a history of chronic hepatitis B, who presented acute and critical ischemia of both extremities, documenting cryoglobulinemic vasculitis with poor evolution.

Vasculitis crioglobulinémica por hiperviscosidad y formación de criogel como debut de mieloma múltiple. Caso clínico / Cryoglobulinemic vasculitis due to hyperviscosity and cryogel formation as the onset of multiple myeloma. Report of one case

Multiple Myeloma (MM) is characterized by a clonal expansion of plasma cells in the bone marrow. These cells typically produce a monoclonal immunoglobulin, and its symptoms arise either from plasma cell infiltration in several organs, or secondary to the presence of a monoclonal protein peak. Symptoms can be summarized by the acronym CRAB (hypercalcemia, renal failure, anemia and bone lesions). Sometimes, in the setting of a protein secreting monoclonal gammopathy, formation of cryoglobulins develops. Cryoglobulins are plasma proteins that precipitate at low temperatures, forming a cold - induced precipitate at small vessels, causing a wide range of clinical manifestations. We report a female consulting for ulcers lasting 2 months in the left foot associated with purpuric lesions in both lower limbs. Protein electrophoresis showed a monoclonal peak in the gamma region. Bone marrow aspirate showed 27% of plasma cells with kappa chain restriction by cytometry. The presence of cryoglobulins was confirmed. The patient was treated with dexamethasone and bortezomib, with a progressive healing of lower limb lesions and disappearance of cryoglobulins. She was discharged in good conditions.

Hepatitis C-related membranoproliferative glomerulonephritis in the era of direct antiviral agents / Glomerulonefrite membranoproliferativa relacionada à hepatite C na era dos agentes antivirais diretos

Abstract Membranoproliferative glomerulonephritis (MPGN) is the most typical Hepatitis C virus (HCV)-associated glomerulopathy, and the available data about the utilization of direct-acting antivirals (DAA) in HCV-associated glomerulonephritis is inadequate. We evaluated the renal and viral response in two cases of HCV-related MPGN; the first caused by cryoglobulinemia while the second was cryoglobulin-negative. Both patients received immunosuppression besides DAA in different regimens. They achieved partial remission but remained immunosuppression-dependent for more than 6 months after DAA despite sustained virological response, which enabled safer but incomplete immunosuppression withdrawal. Both patients were tested for occult HCV in peripheral blood mononuclear cells and found to be negative. Hence, the treatment of HCV-related MPGN ought to be according to the clinical condition and the effects of drug therapy. It is important to consider that renal response can lag behind the virological response.

Resumo A glomerulonefrite membranoproliferativa (GNMP) é a glomerulopatia associada ao vírus mais típico da hepatite C (HCV), e os dados disponíveis sobre a utilização de antivirais de ação direta (AAD) na glomerulonefrite associada ao HCV são inadequados. Avaliamos a resposta renal e viral em dois casos de GNMP relacionados ao HCV; o primeiro causado por crioglobulinemia, enquanto o segundo era negativo para crioglobulina. Ambos os pacientes receberam imunossupressão além de AAD em diferentes esquemas terapêuticos. Eles alcançaram remissão parcial, mas permaneceram dependentes da imunossupressão por mais de 6 meses após os AAD, apesar da resposta virológica sustentada, que permitiu a retirada da imunossupressão mais segura, mas incompleta. Ambos os pacientes foram testados para HCV oculto em células mononucleares do sangue periférico e deram resultados negativos. Portanto, o tratamento do GNMP relacionado ao VHC deve ser de acordo com a condição clínica e os efeitos da terapia medicamentosa. É importante considerar que a resposta renal pode ficar aquém da resposta virológica.

Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy / Remissão de doença hepática e renal a longo prazo induzida pelo HCV após terapia antiviral de ação direta

Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.

Hepatitis A Virus Infection Associated with Cryoglobulinemic Vasculitis

Atypical symptoms, especially immune complex disorders, areuncommonly reported with hepatitis A virus (HAV) infection. Wereport an 8-year-old child who contracted HAV infectioncomplicated by cryoglobulinemic vasculitis, and responded wellto oral steroids. HAV infection may be considered in the etiologyof cryoglobulinemia in children.

Vasculitis crioglobulinémica con compromiso renal y síndrome de Sjögren / Cryoglobulinemic vasculitis with renal involment and Sjögren's syndrome

La vasculitis crioglobulinémica es una vasculitis de vasos pequeños que se da en presencia de crioglobulinas séricas. Las crioglobulinemias mixtas son las más frecuentes y se asocian a infecciones crónicas, típicamente al virus de la hepatitis C, así como a enfermedades linfoproliferativas y autoinmunes, más a menudo al síndrome de Sjögren. Las manifestaciones clínicas incluyen púrpura de los miembros inferiores, neuropatía periférica, artralgias y glomerulonefritis. La presencia de vasculitis crioglobulinémica en el contexto de un síndrome de Sjögren es marcadora de peor pronóstico. Presentamos el caso de una paciente con vasculitis crioglobulinémica con compromiso cutáneo y renal, que condujo al diagnóstico de un síndrome de Sjögren primario. (AU)

Cryoglobulinemic vasculitis is a small-sized vasculitis that occurs in the context of serum cryoglobulins. Mixed cryoglobulinemias are the most frequent and are associated with chronic infections, typically hepatitis C and autoimmune diseases, most commonly Sjögren's syndrome. Clinical manifestations include purpura of lower limbs, peripheral neuropathy, arthralgias and glomerulonephritis. The presence of cryoglobulinemic vasculitis in the context of Sjögren's syndrome is a marker of poor prognosis. We present the case of a patient with cryoglobulinemic vasculitis associated to cutaneous and renal involvement that led us to the diagnosis of primary Sjögren's syndrome. (AU)

A Peripheral Smear Finding Beyond Cells: Cryoglobulins in a Case of Lymphoplasmacytic Lymphoma

A well prepared peripheral smear is an indispensable requisite for the diagnosis of hematological disorders and in some situations, non-hematological diseases. Here, we present the typical hemogram and peripheral smear findings of circulating cryoglobulins that led to the unraveling of the underlying lymphoproliferative disorder. A 51-year lady presented with symptoms of anemia since four months. Her hemogram showed anemia and leucopenia with flagging of platelet count. Peripheral smear at room temperature revealed marked artefactual changes in red blood cells including fragmentation. The morphology was better appreciated after incubating the sample at 37°C and showed normocytic normochromic RBCs, thrombocytopenia with a few lymphoplasmacytic cells and amorphous pinkish material in the background. Bone marrow examination showed near total replacement of marrow spaces by lymphoid cells positive for CD20 and CD138 and was diagnosed as lymphoplasmacytic lymphoma. Cryoglobulins can thus cause a range of laboratory artefacts which need to be recognized, warranting further search for possible underlying etiologies.

A Peripheral Smear Finding Beyond Cells: Cryoglobulins in a Case of Lymphoplasmacytic Lymphoma

A well prepared peripheral smear is an indispensable requisite for the diagnosis of hematological disorders and in some situations, non-hematological diseases. Here, we present the typical hemogram and peripheral smear findings of circulating cryoglobulins that led to the unraveling of the underlying lymphoproliferative disorder. A 51-year lady presented with symptoms of anemia since four months. Her hemogram showed anemia and leucopenia with flagging of platelet count. Peripheral smear at room temperature revealed marked artefactual changes in red blood cells including fragmentation. The morphology was better appreciated after incubating the sample at 37°C and showed normocytic normochromic RBCs, thrombocytopenia with a few lymphoplasmacytic cells and amorphous pinkish material in the background. Bone marrow examination showed near total replacement of marrow spaces by lymphoid cells positive for CD20 and CD138 and was diagnosed as lymphoplasmacytic lymphoma. Cryoglobulins can thus cause a range of laboratory artefacts which need to be recognized, warranting further search for possible underlying etiologies.

Crioglobulinemia: relação entre hepatite C e glomerulonefrite / Cryoglobulinemia: link between hepatitis C and glomerulonephritis

A Hepatite C é um problema de saúde mundial. Uma associação entre infecção pelo vírus da hepatite C (HCV) e crioglobulinemia mista com doença renal tem sido descrita, sendo a glomerulonefrite membranopoliferativa (GNMP) tipo I o acometimento renal mais comum. A GNMP é frequentemente associada com a crioglobulinemia mista tipo II. Esse relato de caso objetiva descrever fatores clínicos dos pacientes com crioglobulinemia mista, a qual é uma manifestação extra-hepática da infecção por HCV, assim como discutir a sua fisiopatologia e tratamento, baseado no relato de caso. (AU)

Hepatitis C is a public health concern worldwide. An association of hepatitis C virus (HCV) infection with mixed cryoglobulinemia and renal disease has been described, and type I membranoproliferative glomerulonephritis (MPGN) is the most common. MPGN is often associated with type II mixed cryoglobulinemia. This case report aimed to describe the clinical features of patients with mixed cryoglobulinemia, a major extrahepatic manifestation of HCV infection, and to discuss its pathophysiology and treatment of HCV infection based on the case report. (AU)

Crioglobulinemia tipo III en el lupus eritematoso sistémico

La crioglobulinemia es una enfermedad caracterizada por la precipitación a bajas temperaturas de unas inmunoglobulinas séricas llamadas crioglobulinas. El depósito de estas proteínas en la vasculatura de diversos órganos condiciona un cuadro de vasculitis de vasos pequeños y medianos, con daño tisular y disfunción del órgano comprometido, como veremos en el siguiente caso que trata de una paciente de 35 años de edad con manifestaciones cutáneas, dolores articulares, caída del pelo y psicopatías de 2 años de evolución llega a nuestro centro con deterioro importante de su estado clínico y psicológico, diagnosticándose un lupus eritematoso sistémico acompañado de una crioglobulinemia mixta tipo III presentando complicaciones de difícil manejo, después de 3 meses de tratamiento inmunosupresor la paciente mejora su cuadro clínico

Cryoglobulinemia is a condition characterize by precipitation at a low temperature of a serum globulins call cryoglobulins. The accumulation of protein in the vessels of several organs leads to a condition of smalls and medium vessels vasculitis, with tissue damage and failure of the compromise organ. The present case describes this disease in a 35-year-old female patient with arthralgia, cutaneous symptoms hair loss and worsening psychopathy. She is remitted to are service with progressive deteriorating clinical and psychological status, diagnosing a lupus erythematosus and a cryoglobulinemia type III. This patient had, at the time of the diagnosis, hard to treat complications

Research advances in hepatitis C virus-related renal injury and its treatment / 临床肝胆病杂志

Hepatitis C virus (HCV) is a blood-borne virus transmitted through contact with blood and blood products,and it is a major cause of liver cirrhosis and hepatocellular carcinoma.Many epidemiological studies have confirmed the association between HCV infection and renal disease.Membranoproliferative glomerulonephritis associated with mixed cryoglobulinemia is the most common type of HCV-related renal disease manifesting as nephropathy or nephritic syndrome,proteinuria,hematuria,and reduced glomerular filtration rate.The treatment of HCV-related renal disease includes antiviral therapy,B cell clearance,and non-specific immunosuppressive therapy.At the same time,the launch of rnew antiviral drugs has brought hope to the patients who cannot tolerate conventional regimens.This article reviews the research advances in epidemiology,clinical manifestations,pathogenesis,and treatment of HCV-related renal injury.

Correlação entre a síndrome antifosfolipídica e a crioglobulinemia: série de quatro casos e revisão da literatura / The correlation between antiphospholipid syndrome and cryoglobulinemia: case series of 4 patients and review of the literature

Resumo Introdução: A crioglobulinemia é uma vasculite de pequenos vasos mediada por imunocomplexos que normalmente envolvem a pele, os rins e os nervos periféricos. A síndrome antifosfolipídica (SAF) é um transtorno da hipercoagulabilidade autoimune que provoca trombose dos vasos sanguíneos. Pode se manifestar como um distúrbio microtrombótico que afeta múltiplos órgãos, denominado SAF catastrófica. Objetivo: Esta série de casos objetiva descrever os desafios de diagnóstico e tratamento que surgem quando esses dois graves transtornos estão presentes simultaneamente no mesmo paciente. Métodos: Foram descritos quatro pacientes internados em nosso hospital em decorrência de danos graves a múltiplos órgãos mediados pela vasculite crioglobulinêmica com SAF concomitante. Resultados: As manifestações clínicas incluíram úlceras de perna, livedo reticular, insuficiência renal e neuropatia periférica. As etiologias sugeridas para a combinação de síndromes foram a hepatite C, o lúpus eritematoso sistêmico e a doença mieloproliferativa retal associada a linfoma de zona marginal tipo células B. Todos os pacientes foram tratados com anticoagulantes, altas doses de corticosteroides, rituximabe, gamaglobulinas intravenosas e troca de plasma. Conclusão: A rara associação entre a SAF grave ou catastrófica e a crioglobulinemia deve ser considerada por médicos que atendem pacientes com isquemia ou necrose de múltiplos órgãos.

Abstract Background: Cryoglobulinemia is an immune-complex-mediated small vessel vasculitis that classically involves the skin, kidneys and peripheral nerves. Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder which causes blood vessel thrombosis. It can present as a multi-organ microthrombotic disorder which is called catastrophic APS. Objective: In this case series we aim to describe the diagnostic and management challenges that arise when these two severe disorders simultaneously present in the same patient. Methods: We describe four patients who were admitted to our hospital due to multi-organ life threatening damage mediated by cryoglobulinemic vasculitis with concurrent APS. Results: Clinical manifestations included leg ulcers, livedo reticularis, renal failure, and peripheral neuropathy. Suggested etiologies for the combined syndromes were hepatitis C, systemic lupus erythematosus and myeloproliferative disease rectal maltoma. All of our patients were treated with anticoagulation, high-dose corticosteroids, rituximab, intravenous gammaglobulins and plasma exchange. Conclusion The rare association of severe or catastrophic APS with cryoglobulinemia in patients should be considered by physicians who treat patients with multi-organ ischemia or necrosis.

Clinical and laboratory features of rheumatic autoimmune disease associated cryoglobulinaemia / 中华风湿病学杂志

Objective To investigate the clinical and laboratory features of autoimmune disease (AID) associated cryoglobulinaemia. Methods From April 2010 to May 2014, thirty threc patients with AID in Peking University Peopleˊs Hospital were tested positive for cryoglobulin. Their clinical and laboratory features were analyzed retrospectively. T test, Mann-Whitney U test, Chi-squaretest and Fisherˊs exact test were used for statistical analysis. Results Among the 33 patients, 26 were female, 7 were male, the average age was (47 ± 17) years old (range 12-75 years old). The spectrum of autoimmune diseases included, in order, systemic lupus erythematosus (SLE), Sj?grenˊs syndrome (SS), multiple myositis/dermatomyositis, rheumatoid arthritis (RA), systemic sclerosis (SSc), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, antiphospholipid syndrome and primary biliary cirrhosis. SLE and SS accounted for 84.8% (28/33) in tpatients with cryoglobulinaemia. In patients withSLE, cryoglobulinaemia occurred at 2.0 (1.0-12.0) years after disease onset, and cryoglobulinpositive patients had more frequent renal involvement (71% vs 40%, P=0.004), positive anti-RNP (56% vs21%, P=0.007) and ACL (53% vs 8%, P=0.000). However, among patients with SS, cryoglo-bulinaemia occurred at 11.0 (4.0-18.0) years after disease onset, and cryoglobulin positive patients had higher rheumatoid factors (RF) [1 170 (230.00, 2 800.00) U/ml vs 57.80 (20.00, 230.50) U/ml, U=-0.002, P=0.001], IgM [3.54 (1.83, 4.34) g/L vs 1.17 (0.81, 2.26) g/L , U=0.016, P=0.014] and lower complement C3 [0.58 (0.33, 0.68) g/L vs 0.81 (0.67, 0.98 g/L), U=0.004, P=0.003] and C4 [0.06 (0.03, 0.12) g/L vs 0.16 (0.12, 0.22), U=0.017, P=0.016]. Conclusion Autoimmune disease complicated with cryoglo-bulinaemia is not uncommon in clinical practice, in which SLE and SS account for the leading two causes. Patients with positive anti-RNP and/or ACL are positively associated with cryoglobulinaemia. renal involvement of SLE is increased by the presence of cryoglobulin.

HCV Extrahepatic Events: Cryoglobulinemic Syndrome – A Case Report in an Over-70-Year Old Patient.

Mixed Cryoglobulinemia (MC) is the most severe among the extrahepatic manifestations of hepatitis C virus. It is a circulating immune disease due to a virus-induced proliferative disorder of B lymphocytes, mainly involving low and medium-sized vessels. Diagnosis of cryoglobulinemia is based upon the presence in the serum of immunoglobulins which may reversibly precipitate at temperature inferior to 37°C. Presentation of Case: In the present paper we report an interesting case of a 72-year-old man with MC. The two main findings in MC are vasculitis and neuropathic syndrome. Cryoglobulinemic syndrome is characterized by purpura, which is one of the earliest and common clinical manifestations in over 80% of the cases. In this case report the neurological picture is represented by severe sensorimotor polyneuropathy, characterized by burning dysesthesia and lack of sensitivity and strength in the limbs. Discussion and Conclusion: The therapeutic approach to the patient with cryoglobulinemic syndrome should be tailored to the clinical characteristics of the patient and the degree of disease activity. The present clinical picture occurring with severe neurological impairment may be included among the most severe forms of the disease.

Influence of experimental conditions on the test results of cryoglobulin / 中华检验医学杂志

Objective This study was to observe the effects of different test conditions on the qualitative and quantitative detection of cryoglobulin .Methods We prepared 5 blood samples of different types of cryoglobulinemia . We detect the cryoglobulin qualitatively and quantitatively at different temperatures (37 ℃and room temperature of 20-25 ℃), and with different observation time (3 days and 7 days) and with different amount of blood (5 ml and 20 ml) .Further we will categorize the type of cryoglobulin and detect the components of cryoglobulin by immunofixation electrophoresis ( IFE) and other laboratory tests.Results (1) Blood samples from two groups were clotting and the serums were separated at 37 ℃ and room temperature respectively , and cryoglobulins of two groups were all qualitatively positive . Quantitative detection of cryoglobulins showed that the concentrations of cryoglobulins of room temperature group are lower than that of 37℃group;(2) Compared with 7 days, observing for only 3 days may lead to false-negative results in qualitative detection of cryoglobulin , and concentrations of cryoglobulin are also decreased;(3) Compared with 20 ml blood sample,5 ml blood sample is not enough for qualitative and quantitative detection of cryoglobulins .It may lead to false-negative results;(4) After purification, IFE and other laboratory tests can be used to categorize the types and find the components of cryoglobulins .Such examinations are helpful for finding the potential causes of cryoglobulinemia .Conclusions The positive of serum cryoglobulin is a key indicator of cryoglobulinemia .Detection of cryoglobulin can be affected by temperature, observed time and the blood volume for measurement .In addition, IFE and other laboratory tests are helpful for finding the type and the components of cryoglobulin .

Essential Cryoglobulinemia Presenting as Polyneuropathy and Cerebral Infarction

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.

Status of circulating immune complexes, IL8 titers and cryoglobulins in patients with dengue infection.

Dengue, a serious viral infection caused by the mosquito vector, Aedes aegyptii, affects about 390 million people annually from more than 125 countries across the globe. However, until now, there is no reliable clinical or laboratory indicator to accurately predict the development of dengue severity. Here, we explored critical pathophysiological determinants like IL8, circulating immune complex (CIC) and cryoglobulin in dengue-infected patients for identification of novel dengue severity biomarker(s). Totally, 100 clinically suspected dengue cases were tested by NS1 ELISA and MAC ELISA for dengue virus aetiology. For control, 49 healthy volunteers were included. Blood profiling (complete hemogram and liver function test) of patient population were done using automated cell counter and standard auto analyzer based biochemical analysis. Serum CIC was quantified by PEG precipitation. Serum cryoglobulins were estimated by Folin assay. Levels of serum IL-8 were assessed by standard sandwich ELISA kits. Patient CIC were further characterized by SDS Gel electrophoresis. Forty per cent of the cases tested positive, of which 11 patients had severe clinical manifestation. The mean ±SEM of cryoglobulin concentration for DHF, DF, and HC were 1.30±0.31, 0.59±0.08 and 0.143±0.009 μg/μl, respectively. Thus, DHF and DF patients have shown 9- and 2.2-fold increase in cryoglobulin levels; and 18- and 5-fold increased CIC, respectively compared to HC patients. The mean ±SEM of CIC-PEG index for DHF, DF and HC were 491±41.22, 146±14.19 and 27.98±2.56, respectively. Raised levels of IL8 titers were also found in all 11 DHF patients. Peak levels of CIC, cryoglobulin and IL8 titers were associated with thrombocytopenia. SDS PAGE analysis of CIC from DHF revealed the presence of at least six protein bands that were not observed in samples from DF and HC. Prediction efficacy of IL8, CIC and cryoglobulin for DHF was determined using the receiver operator characteristic curve (ROC). The area under the curve was 1.00 for IL8, 0.99 for CIC and 0.74 for cryoglobulins. Overall, the results suggest that CIC, IL-8 and cryoglobulins may serve as important laboratory parameters to monitor dengue infection progression.

Early onset mixed cryoglobulinemia in hepatitis C.

Cryoglobulinemia is one of the most common forms of extrahepatic manifestation of chronic hepatitis infection. The phenomenon is generally seen after several years of chronicity predominantly in the female population resulting in arthralgias, purpuras, and other symptoms, due to vasculitis. Here we present a case of incomplete mixed cryoglobulinemia Type III (as per Brouet’s classifi cation) in a young boy aged 13 years who presented with an unusual symptom of pruritus. Diagnosis was confi rmed by cryoprecipitation test followed by immunofi xation. We aim to highlight the diffi culty in diagnosis of this rare case/presentation, important investigation pitfalls and how to avoid them.

Vasculite crioglobulinêmica em portador do vírus da hepatite C-relato de caso / Cryoglobulinemic vasculitis by hepatitis C- Case report

Objetivo: relatar um caso de vasculite crioglobulinêmica com diagnóstico sorológico de Hepatite C crônica. Relatode caso: paciente do sexo masculino, 63 anos, apresentando manchas difusas pelo corpo. O quadro evoluiu para osurgimento de petéqueas e úlceras em MMII, polineuropatia sensitiva padrão em bota, associação a sinais e sintomasconstitucionais, como febre, anorexia, artralgia e mialgias. Exames sorológicos detectaram infecção pelo vírus daHepatite C e crioglobulinemia. Após ser submetido à pulsoterapia com metilprednisolona, seguida de três sessõesde plasmaférese, sem melhora significativa, optou-se por instituir terapia com anticorpo monoclonal anti-CD20(Rituximabe). O paciente recuperou-se e recebeu alta hospitalar. Considerações Finais: a associação entre hepatiteC e crioglobulinemia ainda é subdiagnosticada, por isso, o profissional de saúde deve atentar para suas manifestaçõesclínicas, uma vez que o tratamento varia de acordo com a gravidade do acometimento clínico. Neste caso, o uso doRituximabe mostrou benefício no tratamento da vasculite criglobulinêmica causada pelo vírus da hepatite C comacometimento cutâneo-articular e pulmonar, sem resposta às terapias prévias.

Objective: Report a case of cryoglobulinemic vasculitis in a patient with hepatitis C infection. Case report: Male,63 years, with spots throughout the body, which developed into petechiae and ulcers over the years, associated withsensitive deficit, and overall signs and symptoms, such as fever, anorexia, atralgias and myalgias. Serological testshave detected chronic hepatitis C and presence of cryoglobulinemia. After pulsotherapy with methylprednisolone and11 sessions of plasmapheresis without satisfactory results, we opted to perform therapy with anti-CD20 monoclonalantibody (Rituximab). The patient recovered after therapy and was discharged. Final Thoughts: The associationbetween hepatitis C and cryoglobulinemia is still underdiagnosed and therefore health professionals should be awareof its symptoms. Treatment varies according to the severity of clinical impairment. In this case, the use of Rituximabshowed benefit for the treatment of criglobulinêmica vasculitis caused by the hepatitis C virus with cutaneousarticularand pulmonary involvement, unresponsive to prior therapies.

Síndrome de hiper IgE, una enfermedad poco frecuente en edad adulta: Reporte de un caso / Hyper-immunoglobulin E syndrome: Report of one case

The Hyperimmunoglobulin E syndrome (HIES) is a rare sporadic or autosomal dominant immune and connective tissue disorder characterized by chronic eczema, cutaneous abscesses, pneumonias, invasive infections, high levels of Immunoglobulin E, primary teeth retention and bone abnormalities. We report a 24-year-old male with a history of cutaneous abscesses and esophageal candidiasis. He was admitted due to a left gluteal cellulitis. During the fifth day of hospitalization he presented a distal necrosis of the fourth finger of the right hand. Laboratory results showed high levels of IgE and positive cryoglobulins. The patient was discharged and was admitted again five days later with a new gluteal abscess. IgE levels were even higher. Applying Grimbacher scale, the diagnosis of Hyperimmunoglobulin E syndrome was reached.