Déficits immunitaires primitifs et cytopénies auto-immunes de l’adulte

Although primary immunodeficiencies (PID) are typically marked by increased susceptibility to infections, autoimmune manifestations have increasingly been recognized as an important component of several forms of PID. Here, we discuss two forms of PID in which autoimmune cytopenias are particularly common and may be the first manifestation of the disease in adults: autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID). Approximately one fifth of patients with CVID develop autoimmune diseases, and immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AHA) are the most common. Since autoimmune cytopenias frequently precede the diagnosis of CVID, testing for immunoglobulin levels should be performed in patients diagnosed with AITP and AHA. Patients with CVID in association with autoimmune cytopenias have a “particular phenotype” with lower susceptibility to infection and higher susceptibility to autoimmune manifestations and, for patients with AHA, a more frequent development of splenomegaly and lymphoma. Corticosteroids and high doses of intravenous immunoglobulins (IVIg) seem to have the same efficacy as in idiopathic AITP and AHA. Splenectomy and rituximab are as effective as in idiopathic autoimmune cytopenias but are associated with an increased risk of severe infection and should, in our opinion, be considered only for those rare patients with “refractory diseases”. The course and outcome of autoimmune cytopenias is not affected by supportive IVIg therapy. Autoimmune destruction of blood cells affects over 70% of ALPS patients. The median age of first presentation is 24 months of age, but with increasing awareness of this condition, adults with autoimmune cytopenias are now being diagnosed more frequently. Testing for ALPS should therefore be considered in young adults with unexplained Evan's syndrome. Patients usually respond to immunosuppressive medications, including corticosteroids. Unlike many patients with idiopathic autoimmune cytopenias, the cytopenias in patients with ALPS typically do not respond to IVIg. After corticosteroids, the immunosuppressive drug that is the most studied in ALPS patients is mycophenolate mofetyl. Rituximab and splenectomy are relatively contraindicated in ALPS because of an increase risk of severe infection and should be reserved for patients who fail all other therapies.     

An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection

Hepatitis C virus (HCV) infection is emerging as a common and insidiously progressive liver condition. In more than one third of the cases, extrahepatic manifestations are seen in the course of the disease. Over the past decade, authors have reported membranous nephropathy, cutaneous vasculitis, idiopathic thrombocytopenic purpura, porphyria cutanea tarda and diabetes mellitus, among other extrahepatic manifestations of HCV infection. Recently, there have been a growing number of reports relating HCV infection to autoimmune cytopenias. Here, we report an unusual case of Coombs'-negative autoimmune hemolytic anemia (AHA) with severe autoimmune leukopenia and neutropenia, occurring simultaneously, in a patient with untreated hepatitis C infection. Mild cytopenias during chronic hepatitis C have been reported widely in the medical literature; however, severe cytopenias are seldom described and are usually seen only after or simultaneously with therapy.     

An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection

Hepatitis C virus (HCV) infection is emerging as a common and insidiously progressive liver condition. In more than one third of the cases, extrahepatic manifestations are seen in the course of the disease. Over the past decade, authors have reported membranous nephropathy, cutaneous vasculitis, idiopathic thrombocytopenic purpura, porphyria cutanea tarda and diabetes mellitus, among other extrahepatic manifestations of HCV infection. Recently, there have been a growing number of reports relating HCV infection to autoimmune cytopenias. Here, we report an unusual case of Coombs'-negative autoimmune hemolytic anemia (AHA) with severe autoimmune leukopenia and neutropenia, occurring simultaneously, in a patient with untreated hepatitis C infection. Mild cytopenias during chronic hepatitis C have been reported widely in the medical literature; however, severe cytopenias are seldom described and are usually seen only after or simultaneously with therapy.     

Hepatitis C virus-related thrombocytopenia: clinical and laboratory characteristics compared with chronic immune thrombocytopenic purpura

Thrombocytopenia can be a complication of hepatitis C viral (HCV) infection. However, there is little published data regarding the clinical and laboratory manifestations of HCV-related thrombocytopenia (HCV-TP) compared with adult chronic immune thrombocytopenic purpura (CITP). We reviewed the medical records for all patients evaluated for chronic thrombocytopenia by the Haematology Service between January 1996 and June 2000. All patients were screened for HCV infection at the time of initial diagnosis. Of 250 patients who fulfilled American Society of Hematology criteria for CITP, 76 (30%) were HCV seropositive. HCV-TP patients were older [mean age (+/-SD) 54.9 +/- 8 years vs. 40.3 +/- 8 years, P 相似文献   

Cytopénies auto-immunes associées au lymphome de Hodgkin : étude rétrospective monocentrique

IntroductionHodgkin's lymphoma (HL) is less common than non-Hodgkin lymphoma and is rarely associated with autoimmune cytopenia.MethodWe report a consecutive, monocentric and retrospective series of HL patients diagnosed with concomitant or subsequent autoimmune cytopenia over a period of 8 years.ResultsWe report 4 out of 84 HL patients (4.8%) diagnosed with autoimmune cytopenia (4 immune thrombocytopenia including 2 Evans’ syndromes). They were 4 males (average age 24 years for the 3 youngest, and one over 60 years old). Autoimmune cytopenia revealed lymphoma in 2 patients and occurred after HL treatment in the two other patients (5 and 36 months from the end of chemotherapy) without HL relapse. All cytopenias were resistant to conventional treatments (glucocorticoids, intravenous immune globulin, rituximab) and sensitive to chemotherapy when indicated for HL treatment.ConclusionIn our series, the predominance of males, a higher frequency of immune thrombocytopenia than autoimmune hemolytic anemia, the resistance to usual treatments and the efficacy of specific chemotherapy were consistent with the literature. Unexpectedly, patients were young and with nodular sclerosis morphology (vs. mixed cellularity) in 3 of 4 cases.     

Autoimmune cytopenia does not predict poor prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is characterized by an acquired immune defect that can cause autoimmune complications, including anemia and thrombocytopenia. We conducted an observational study of the epidemiology, clinical presentation and significance of autoimmune complications of CLL/SLL in 132 patients from a large population (>45,000 veterans), in which at least 90% of patients with CLL/SLL have been previously identified. Over a period of 12.5 years, 12 patients (9.1%) had autoimmune complications; of these, 6 (4.5%) had autoimmune hemolytic anemia (AIHA), 5 (3.8%) had immune thrombocytopenia (ITP), and 1 (0.8%) had pure red blood cell aplasia (PRBA). All 6 cases of AIHA had a positive direct immunoglobulin test for IgG and C3d. In 6 patients, CLL/SLL was an incidental finding at the time of presentation with autoimmune cytopenia. Nine out of 10 patients responded to immunosuppressive therapy, which was complicated by serious infection in 7 cases, one of which was fatal. The major cause of mortality in patients with autoimmune complications of CLL/SLL was secondary malignancy. Survival of patients with immune cytopenia was not significantly different from CLL/SLL patients without immune cytopenia. Among patients with anemia or thrombocytopenia, mortality was significantly higher in those with bone marrow failure compared to an autoimmune etiology. We show that in a non-referred population with a high incidence of CLL/SLL, autoimmune cytopenia can occur early in the natural history of the disease. These data suggest that the Rai and Binet classifications for CLL need to be modified for patients with autoimmune cytopenia. .     

An immunological syndrome featuring transverse myelitis, Evans syndrome and pulmonary infiltrates after unrelated bone marrow transplant in a patient with severe aplastic anemia

A patient with severe aplastic anemia underwent a matched unrelated bone marrow transplant, following which he developed a complex autoimmune syndrome. This featured transverse myelitis, immune mediated Coombs positive hemolytic anemia and immune thrombocytopenia (Evans syndrome), pulmonary infiltrates, eosinophilia, muscle pains and cramps and lichenoid dermatitis all of which may represent manifestations of graft-versus-host disease as they showed response to immunosuppression. Thus, although immune-mediated cytopenias after an allogeneic bone marrow transplant are rare, they should be considered as a possible cause of cytopenia in post-transplant patients.     

Hematologic complications of primary immune deficiencies

Primary immune deficiencies have an estimated overall incidence of 1 in 10,000 individuals. These disorders are diverse, depending on the specific immune functions involved, and lead to chronic or recurrent infections, inflammatory conditions, and a variety of autoimmune diseases. The most common autoimmune disorder is immune thrombocytopenic purpura (ITP), followed by autoimmune hemolytic anemia (AHA). While cytopenias are common in all the congenital immune diseases, they are particularly common in the antibody defects, common variable immunodeficiency and selective immunoglobulin A deficiency. In common variable immunodeficiency, ITP occurred in 7.6% of the patients and AHA in 4.8%. Treatment options include corticosteroids, intravenous immunoglobulin (i.v.Ig), anti-D, and splenectomy. Although the association between cytopenias and congenital immune deficiency is unclear, defects in T-cell regulation, cytokine defects, abnormal apoptosis, and abnormal production of immunoglobulins with autoimmune features are potential mechanisms.     

Mycophenolate mofetil in patients with hepatitis C virus infection

Diagnosis and treatment of hepatitis C virus (HCV) -related autoimmune features has become a clinical challenge in HCV-infected patients, in whom chronic liver disease associated with severe autoimmune features may contribute to a very poor prognosis. Both antiviral and immunosuppressive therapies, either alone or in combination, seem likely to have a key role. Based on the experience of mycophenolate mofetil (MMF) use in HCV patients receiving organ transplantation, this new immunosuppressive agent might represent a safe and effective therapeutic option to treat HCV-related extrahepatic features. Recent data are available for the use of MMF in HCV patients with autoimmune manifestations, mainly for autoimmune cytopenias and vasculitic features. MMF may be used as monotherapy or in association with other drugs for cases of HCV-related autoimmune diseases refractory or intolerant to common immunosuppressive treatments, allowing the reduction of the drug dosage and avoiding serious side effects.     

Pathogenesis, prevalence, and prognostic significance of cytopenias in chronic lymphocytic leukemia (CLL): a retrospective comparative study of 213 patients from a national CLL database of 1,518 cases

Utilizing the database of the Israeli CLL Study Group, we investigated the prevalence and prognostic significance of anemia and thrombocytopenia in patients with chronic lymphocytic leukemia (CLL). Of 1,477 patients, 113 had anemia and thrombocytopenia associated with “infiltrative” marrow failure, median survival of 41 and 86 months, respectively. Autoimmune cytopenias were diagnosed in 100 patients, autoimmune hemolytic anemia (AIHA) in 80, and immune thrombocytopenia (ITP) in 31, while 11 had both co-existent. Median survival of patients with AIHA and ITP, from CLL diagnosis, was 96 and 137 months, respectively, but 29 and 75 months from onset of cytopenia. Patients with AIHA from the time of CLL diagnosis had a significantly shorter survival than those without anemia (p?<?.0001). Survival was similar for patients with AIHA or anemia due to “infiltrative” bone marrow failure (p?=?.44). The presence of positive antiglobulin test even without hemolysis was associated with worse outcome. Overall survival of patients with ITP and those without cytopenias (p?=?0.94) were similar. In conclusion, laboratory or clinical evidence of AIHA has a significant negative impact on the survival of patients with CLL. Outcome for cases with ITP and patients without cytopenias was similar.     

Common variable immunodeficiency with autoimmune manifestations: study of nine cases; interest of a peripheral B-cell compartment analysis in seven patients

PURPOSE: Autoimmune manifestations (AIM) are associated to common variable immunodeficiency (CVI) in about 20 to 25% of the cases. This study presents the clinical, biological characteristics and the evolution of nine patients developing CVI and AIM. A peripheral B-cell compartment analysis has been performed in seven cases. METHOD: This multicenter retrospective study analyses nine patients, six men and three women, within a population of 32 CVI. RESULTS: The mean age was 27 years at the time of diagnosis of AIM and 30 years at the time of diagnosis of CVI. The diagnosis of AIM preceded the diagnosis of CVI in five cases. Thirteen AIM of different types were observed: autoimmune hemolytic anemia (AHA, 3), immune thrombocytopenic purpura (ITP, 2), Evan's syndrome (2), primary biliary cirrhosis (1), rheumatoid arthritis (1), alopecia totalis (1), myasthenia gravis (1). The peripheral B-cell compartment was investigated in seven patients: five patients with autoimmune cytopenia presented with a diminution of memory B cells (CD27+IgD-) and immature B cells (CD21-) levels; the patient with primary biliary cirrhosis and myasthenia gravis had only a diminution of memory B cells level; the last patient with ITP presented with a normal level of memory B cells. Five among the seven patients with autoimmune cytopenia required a specific treatment using corticosteroids, high dosages of intravenous immunoglobulin, then splenectomy after failure of the medical management, with severe infectious complications in one case. CONCLUSION: The association of AIM and CVI is not fortuitous. The most common AIM is autoimmune cytopenia. The peripheral B-cell compartment analyses show that a majority of patients have a defect in memory B-cells. Treatment regimens are not standardized and splenectomy increases the risk of infectious complications.     

Efficacy and safety of rituximab for systemic lupus erythematosus‐associated immune cytopenias: A multicenter retrospective cohort study of 71 adults

The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)‐associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE‐associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31‐48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6‐11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow‐up after the first injection of RTX was 26.4 months [14.3‐71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX‐induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE‐associated immune cytopenias.     

Efficacy and safety of rituximab in common variable immunodeficiency-associated immune cytopenias: a retrospective multicentre study on 33 patients

Patients with common variable immunodeficiency (CVID) are at high risk of developing immune thrombocytopenia (ITP) and/or autoimmune haemolytic anaemia (AHA). Given their underlying immunodeficiency, immunosuppressive treatment of these manifestations may increase the risk of infection. To assess efficacy and safety of rituximab in patients with CVID-associated ITP/AHA, a multicentre retrospective study was performed. Thirty-three patients, 29 adults and four children, were included. Patients received an average of 2·6 treatments prior to rituximab including steroids, intravenous immunoglobulin and splenectomy (21%). The median ITP/AHA duration at time of first rituximab administration was 12 months [range 1-324] and the indication for using rituximab was ITP (22 cases), AHA (n = 5) or both (n = 7); 1 patient was treated sequentially for ITP and then AHA. The overall initial response rate to rituximab was 85% including 74% complete responses. After a mean follow-up of 39 ± 30 months after rituximab first administration, 10 of the initial responders relapsed and re-treatment with rituximab was successful in 7/9. Severe infections occurred after rituximab in eight adults (24%), four of whom were not on immunoglobulin replacement therapy. In conclusion, rituximab appears to be highly effective and relatively safe for the management of CVID-associated severe immune cytopenias.     

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Background Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. DESIGN AND METHODS: One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20×10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. RESULTS: Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. Conclusions Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.     

Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre

Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency‐associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.     

Hepatitis C virus and arthritis

Arthritis is one of the several autoimmune disorders induced by HCV infection. There is not a specific clinical pattern of HCV-related arthritis, but two nonerosive subsets have more frequently been described: a RA-like polyarthritis and a less common mono-oligoarthritis involving medium-sized and large joints, often showing an intermittent course. This latter form is associated with the presence of serum cryoglobulins. Because of its variable characteristics, HCV-related arthritis must be considered in the differential diagnosis of many patients having inflammatory joint involvement. Antikeratin antibodies and possibly IgA RF can be useful in distinguishing between RA and HCV-related RA-like polyarthritis. In fact, these tests are highly specific in RA patients. In any case, the search for HCV antibodies should be more widely performed in the diagnostic approach to rheumatic diseases. An association between PsA and HCV infection has been described in the literature, but the authors were unable to confirm these data. Nonsteroidal anti-inflammatory drugs, hydroxychloroquine, and low doses of corticosteroids are the cornerstones of the treatment of HCV-related arthritis. An etiologic therapy with alpha-interferon and ribavirin is useful when required by hepatic or systemic involvement; such therapy could also be considered in selected cases of isolated arthritis that are unresponsive to other drugs. Few case reports described the onset of polyarthritis after the administration of alpha-interferon for HCV-related chronic hepatitis. This topic should be more accurately studied in the future to exclude a spurious association between the two events.     

Autoimmune cytopenia in chronic lymphocytic leukaemia: diagnosis and treatment

Autoimmune cytopenia, especially autoimmune haemolytic anaemia (AIHA), appears in 5-10% of patients with chronic lymphocytic leukaemia (CLL). In these patients, the prognosis is not as poor as in those cases in which the cytopenia is due to a massive bone marrow infiltration by the disease, and their treatment requires special considerations. For these reasons, the diagnosis of autoimmune cytopenia should be entertained in any patient with CLL presenting with cytopenia. In patients with autoimmune cytopenia and CLL, treatment is as for idiopathic autoimmune cytopenia, with most patients responding to corticosteroids. For patients not responding to corticosteroids, splenectomy is a reasonable treatment choice. Monoclonal antibodies and thrombopoietin analogues have shown enough activity to support their use, especially within clinical studies, in selected cases not responding to corticosteroids and before splenectomy. In patients with resistant immune cytopenia, the most effective treatment is that of the underlying CLL. Fear of fludarabine-associated AIHA is no longer appropriate in the age of chemo-immunotherapy. Finally, prospective studies are required to better identify the optimal therapy for these patients.     

Chronic lymphocytic leukemia and autoimmunity: a systematic review

Chronic lymphocytic leukemia is frequently associated with immune disturbances. The relationship between chronic lymphocytic leukemia and autoimmune cytopenias, particularly autoimmune hemolytic anemia and immune thrombocytopenia, is well established. The responsible mechanisms, particularly the role of leukemic cells in orchestrating the production of polyclonal autoantibodies, are increasingly well understood. Recent studies show that autoimmune cytopenia is not necessarily associated with poor prognosis. On the contrary, patients with anemia or thrombocytopenia due to immune mechanisms have a better outcome than those in whom these features are due to bone marrow infiltration by the disease. Moreover, fears about the risk of autoimmune hemolysis following single agent fludarabine may no longer be appropriate in the age of chemo-immunotherapy regimens. However, treatment of patients with active hemolysis may pose important problems needing an individualized and clinically sound approach. The concept that autoimmune cytopenia may precede the leukemia should be revisited in the light of recent data showing that autoimmune cytopenia may be observed in monoclonal B-cell lymphocytosis, a condition that can only be detected by using sensitive flow cytometry techniques. On the other hand, there is no evidence of an increased risk of non-hemic autoimmune disorders in chronic lymphocytic leukemia. Likewise, there is no epidemiological proof of an increased risk of chronic lymphocytic leukemia in patients with non-hemic autoimmunity. Finally, since immune disorders are an important part of chronic lymphocytic leukemia, studies aimed at revealing the mechanisms linking the neoplastic and the immune components of the disease should help our understanding of this form of leukemia.     

Hepatitis C virus syndrome: A constellation of organ-and non-organ specific autoimmune disorders,B-cell nonHodgkin’s lymphoma,and cancer

The clinical course of chronic hepatitis C virus(HCV)infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinicoepidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells nonHodgkin’s lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCVrelated thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients’ populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.     

Approach to the investigation and management of immune thrombocytopenic purpura in children

Childhood immune thrombocytopenic purpura (ITP) is typically a benign, self-limiting disorder occurring in young (<10 years of age) previously healthy children. More than 80% of such children enter a complete sustained remission within a few weeks to a few months of initial presentation, irrespective of any therapy given. The major concern is the small but finite (0.1 to 0.9%) risk of intracranial hemorrhage, which occurs in children with very low platelet counts (<20 x 10(9)/L), and is the justification for treatment to increase the circulating platelet count. Effective treatment strategies are single-dose intravenous immunoglobulin G (IVIgG; approximately 1 g/kg) and medium to high-dose corticosteroids, administered orally or parenterally. The necessity for initial bone marrow aspiration and hospitalization continues to be debated. In children with chronic ITP, defined by persistence of thrombocytopenia for > or =6 months, splenectomy should be considered for the relatively small subgroup with symptomatic, severe thrombocytopenia who have either failed an adequate trial (> or = 12 months) of primary therapy (IVIgG, intravenous anti-D, corticosteroids) or are intolerant of such therapy. Laparoscopic splenectomy is preferred over open splenectomy. Children who fail to respond to splenectomy ( < or = 20% of cases) should be evaluated for the presence of accessory spleens; their management is often difficult and must be individualized. In severe refractory cases, second-line therapies (such as azathioprine or vinca alkaloids) need to be considered. Secondary ITP in children is relatively rare and is sometimes associated with other autoimmune cytopenias (Evan's syndrome, ITP with autoimmune neutropenia). These cases often respond poorly to conventional medical therapies and response rates to splenectomy are considerably lower than in children with primary chronic ITP.