[Adult immune thrombocytopenia and thrombopoietin receptor agonist: Ten years later]. / Agonistes du récepteur de la thrombopoïétine et purpura thrombopénique immunologique de l'adulte : où en sommes-nous 10 ans après ?

Ten years after their licence in France, the use of the two thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, has deeply modified the landscape of immune thrombocytopenia (ITP) treatment. In this review, we summarise data on efficacy and safety of these treatments during ITP, as well as their use in clinical practice. Their place in therapeutic strategy, the recent description of persistant remission after discontinuation of TPO-RA, and future new thrombopoietic agents are also discussed. Their use has progressively increased and early use at a newly diagnosed stage of the disease is under evaluation. However physician have to keep in mind that thromboembolism rates appear to be higher with TPO-RA treatment in ITP patients at high risk of thrombosis, and that data from "real-life" studies with very long term follow up are not available. Finally, the cost of these treatments should also be evaluated in future therapeutic strategies comparisons.

Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage?

Immune checkpoint inhibitors (ICIs) are changing the treatments of many patients with cancer. These immunotherapies are generally better tolerated than chemotherapy, and their adverse events are immune-related mimicking autoimmune or inflammatory conditions. Although these immune-related adverse events mainly affect the skin, endocrine glands, digestive tract, joints, liver or lungs, all the organs can be theoretically affected, and the haematopoietic system is not spared. This review of the literature will focus on the haematological immune-related adverse events (Haem-irAEs). By reviewing the largest clinical trials of ICIs, we estimate the frequency of Haem-irAEs at 3.6% for all grades and 0.7% for grades III-IV. Frequency of Haem-irAEs of all grades was found to be higher with anti-programmed cell death 1 (4.1%) or anti-programmed cell death ligand 1 (4.7%) than with anti-cytotoxic T-lymphocyte-associated protein 4 (0.5%) (p < 0.0001). From the 63 cases with Haem-irAEs reported in the literature, the mean time to the onset was found to be 10 weeks after ICI initiation, and the large range for occurrence (1-84 weeks) and the regular incidence suggest that Haem-irAEs could occur at any time after ICI therapy. Among the 63 reported cases with Haem-irAEs, the distribution was immune thrombocytopenia (n = 18, 29%), pancytopenia or immune aplastic anaemia (n = 12, 19%), neutropenia (n = 11, 17%), haemolytic anaemia (n = 10, 16%), cytokine release syndrome with haemophagocytic syndrome (n = 7, 11%) and other Haem-irAEs including bicytopenia or pure red cell aplasia (n = 5, 8%). Haem-irAEs are generally highly severe adverse reactions with a mortality rate of Haem-irAEs reported to be 14% (9 deaths among the 63 cases reported). The more severe and life-threatening Haem-irAEs were both cytokine release syndrome with haemophagocytic syndrome and pancytopenia or aplastic anaemia. Haem-irAEs induced by ICIs are potentially life-threatening. By discussing their pathophysiological aspects and clinical picture, we propose in this review clinical guidelines for management.

[Hemophagocytic lymphohistiocytosis with granulomatosis and diffuse T-cell infiltration associated with disseminated Nocardiosis and pulmonary infection due to Streptomyces spp]. / Syndrome d'activation macrophagique associé à une granulomatose et une infiltration lymphocytaire T CD4 diffuse révélant une nocardiose disséminée et une infection pulmonaire à Streptomyces spp.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome frequently secondary to infectious disease, especially in immuno-compromised patients. We report a HLH secondary to disseminated nocardiosis and Streptomyces spp pulmonary infection. CASE REPORT: A 69-years-old women had recent subcutaneous nodules of the forearms and loins associated with peripheral neuropathy and pulmonary nodule of the right upper lobe. Cutaneous biopsy revealed granuloma. Cutaneous lesions worsened and the patient developed a HLH with probable cardiac and neurological involvement, associated with cutaneous granulomatosis and diffuse polyclonal lymphocyte proliferation. Nocardia PCR was positive in cutaneous biopsy. Pulmonary samples revealed Streptomyces in culture and Nocardia in PCR. The evolution under antibiotic treatment was favorable. CONCLUSION: Recent diagnosis of HLH without obvious etiology should lead to etiological investigation, including the search for infections with slow-growing bacteria such as Nocardia or Streptomyces spp.

NK cell compartment in the peripheral blood and spleen in adult patients with primary immune thrombocytopenia.

Immune thrombocytopenic purpura (ITP) is a disease characterized by antibody-mediated platelet destruction. The T- and B-cell subsets have been extensively studied in primary ITP, but the NK cell compartment has been less thoroughly explored. We investigated the NK cell receptor repertoire and the functionality of NK cells in the peripheral blood and spleen in patients with primary ITP. An immunophenotypic analysis of peripheral blood lymphocytes from patients revealed that the numbers of CD19+ B lymphocytes, CD4+ and CD8+ T lymphocytes and CD3-CD56+ NK cells were within the normal range. No major alteration to the expression of distinct inhibitory or activating NK cell receptors was observed. The functionality of NK cells, as evaluated by their ability to degranulate in conditions of natural cytotoxicity or antibody-dependent cell cytotoxicity (ADCC), was preserved in these patients. By contrast, these stimuli induced lower levels of IFNγ production by the NK cells of ITP patients than by those of healthy controls. We then compared the splenic NK cell functions of ITP patients with those of cadaveric heart-beating donors (CHBD) as controls. The splenic NK cells of ITP patients tended to be less efficient in natural cytotoxicity conditions and more efficient in ADCC conditions than control splenic NK cells. Finally, we found that infusions of intravenous immunoglobulin led to the inhibition of NK cell activation through the modulation of the interface between target cells and NK cells.

[Thrombosis during thrombopoietin receptor agonist treatment for immune thrombocytopenia. A French multicentric observational study]. / Thromboses sous agonistes du récepteur de la thrombopoïétine au cours du purpura thrombopénique immunologique. Étude rétrospective multicentrique en France.

INTRODUCTION: Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP. METHODS: We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. RESULTS: Overall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1-1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock). CONCLUSIONS: The thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae.

Is there still a place for "old therapies" in the management of immune thrombocytopenia?

New molecules such as rituximab or thrombopoietin receptor agonists (romiplostim and eltrombopag) have changed the management of immune thrombocytopenia. Therefore, old drugs which are less expensive and with a well-known benefit/risk ratio are being underused. We aim to define the place of dapsone, danazol, hydroxychloroquine and vinca-alkaloids at the era of targeted therapy in immune thrombocytopenia. With a response rate around 30% to 50%, dapsone is an interesting second-line therapy to be used just after corticosteroids. Patients with positive antinuclear antibodies can benefit from hydroxychloroquine with a 50% response rate. Because of its side effects, mostly virilization, danazol will be preferentially used in the elderly. Vinca-alkaloids could be temporarily used in patients that do not respond to intravenous immunoglobulins or to limit their use to avoid shortage periods.

[Retroperitoneal fibrosis in adults: Main characteristics and relevance of the diagnostic procedures based on a retrospective multicenter study on 77 cases]. / Fibrose rétropéritonéale de l'adulte : analyse descriptive et évaluation de la pertinence des examens complémentaires réalisés à visée diagnostique à partir d'une série rétrospective multicentrique de 77 cas.

INTRODUCTION: Retroperitoneal fibrosis (RPF) is a rare disorder characterized by the sheathing of retroperitoneal structures by fibro-inflammatory process. It can be either isolated or associated with an underlying disease or condition. In the absence of consistent and consensual approach, the objective of this study was to assess the relevance of diagnostic tests performed during the diagnostic work-up of RPF. METHODS: Seventy-seven patients were included in this retrospective multicenter study. The diagnosis of RPF was defined by the presence of a thickened circumferential homogeneous tissue unsheathing the infrarenal aorta, excluding peri-aneurysmal fibrosis and a clear evidence of a cancer. RESULTS: In 62 cases (80.5%), the RPF was considered as being primary or "idiopathic". Surgical (n=31) or CT-guided (n=9) biopsies of the RPF were performed in half of the patients showing some fibrotic or non-specific inflammatory lesions in 98% of cases. A bone marrow biopsy was performed in 23 patients leading to diagnosis of low grade B cell non-Hodgkin lymphoma in a single patient who also had a monoclonal gammopathy IgM. The systematic search for autoantibodies or serum tumor markers was of no diagnostic value. CONCLUSIONS: Although the diagnostic procedure was heterogeneous, no cause or associated disease was found in the majority of cases of FRP in this series. In the absence of any clinical or paraclinical evidence suggesting an underlying disease or any atypical features at presentation, a number of non-invasive tests (autoantibodies, tumor markers, bone scintigraphy) and also more invasive diagnostic tests (bone marrow and RPF biopsies) seem of little relevance.

Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects.

OBJECTIVES: The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. DESIGN: Systematic case-control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. PARTICIPANTS AND SETTING: A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14-26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain-Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. ANALYSIS: Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. RESULTS: Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5-1.5]. The individual ORs were 1.0 (95% CI 0.4-2.6) for ITP, 0.3 (95% CI 0.1-0.9) for MS, 0.8 (95% CI 0.3-2.4) for connective disorders and 1.2 (95% CI 0.4-3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain-Barré syndrome or thyroiditis. CONCLUSIONS: No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.

Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry.

OBJECTIVE: The risk of severe infection is a crucial factor in the assessment of the short-term risk:benefit ratio of biologic drugs in rheumatoid arthritis (RA). There is no increase in severe infections in RA patients treated with rituximab (RTX) in controlled trials, but this has not yet been assessed in daily practice. We undertook this study to investigate the occurrence of and risk factors for severe infections in off-trial patients using data from the AutoImmunity and Rituximab (AIR) registry. METHODS: The AIR registry was set up by the French Society of Rheumatology. The charts of patients with severe infections were reviewed. RESULTS: Of the enrolled patients, 1,303 had at least 1 followup visit at 3 months or later, with a mean ± SD followup period of 1.2 ± 0.8 years (1,629 patient-years). Eighty-two severe infections occurred in 78 patients (5.0 severe infections per 100 patient-years), half of them in the 3 months following the last RTX infusion. Multivariate analysis showed that chronic lung disease and/or cardiac insufficiency (odds ratio 3.0 [95% confidence interval 1.3-7.3], P = 0.01), extraarticular involvement (odds ratio 2.9 [95% confidence interval 1.3-6.7], P = 0.009), and low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6-15.2], P = 0.005) were significantly associated with increased risk of a severe infection. CONCLUSION: The rate of severe infections in current practice is similar to that reported in clinical trials. The risk factors for severe infections include chronic lung and/or cardiac disease, extraarticular involvement, and low IgG before RTX treatment. This suggests that serum IgG should be checked and the risk:benefit ratio of RTX discussed for patients found to have low levels of IgG.

[Immune thrombocytopenic purpura: pathophysiology and treatment]. / Purpura thrombopénique immunologique: physiopathologie et traitement.

Immune thrombopenic purpura (ITP) is an autoimmune disease characterized by a peripheral destruction of platelets. B lymphocytes play a key role but pathophysiology is more complex, involving humoral and cellular immunity associated with an inappropriate platelet production. The treatment of ITP is still based on uncontrolled studies. Prednisone and intravenous immunoglobulins remain the first line treatments. Splenectomy remains the best "curative" treatment for adults with chronic ITP. However, most patients are reluctant to undergo surgery and new treatments give promising results. Among them, rituximab and thrombopoietin receptor agonists could replace splenectomy in near future.

Vaccination in adults with auto-immune disease and/or drug related immune deficiency: results of the GEVACCIM Delphi survey.

INTRODUCTION: There are insufficient data regarding the efficacy and safety of vaccination in patients with auto-immune disease (AID) and/or drug-related immune deficiency (DRID). The objective of this study was to obtain professional agreement on vaccine practices in these patients. METHODS: A Delphi survey was carried out with physicians recognised for their expertise in vaccinology and/or the caring for adult patients with AID and/or DRID. For each proposed vaccination practice, the experts' opinion and level of agreement were evaluated. RESULTS: The proposals relating to patients with AID specified: the absence of risk of AID relapse following vaccination; the possibility of administering live virus vaccines (LVV) to patients not receiving immunosuppressants; the pertinence of determining protective antibody titre before vaccination; the absence of need for specific monitoring following the vaccination. The proposals relating to patients with DRID specified that a 3-6 month delay is needed between the end of these treatments and the vaccination with LVV. There is no contraindication to administering LVV in patients receiving systemic corticosteroids prescribed for less than two weeks, regardless of their dose, or at a daily dose not exceeding 10mg of prednisone, if this involves prolonged treatment. Out of 14 proposals, the level of agreement between the experts was "very good" for eleven, and "good" for the remaining three. CONCLUSION: Proposals for vaccine practices in patients with AID and/or DRID should aid with decision-making in daily medical practice and provide better vaccine coverage for these patients.

Characteristics and outcome of connective tissue diseases in patients with sickle-cell disease: report of 30 cases.

OBJECTIVES: To analyze the main characteristics of adults with sickle cell disease (SCD) and concurrent connective tissue disease (CTD). METHODS: A retrospective investigational study was performed. CTD was diagnosed according to standard international criteria. Severity of SCD was assessed by a clinical severity score. RESULTS: Thirty patients, 23 women (76%) and 7 men, with hemoglobin S/S (n = 25) or S/C (n = 5) SCD were included. The subtypes of CTD were rheumatoid arthritis (RA) (n = 15), definite systemic lupus erythematosus or "incomplete lupus" requiring treatment (n = 13), primary Sjögren's syndrome with central nervous system involvement (n = 1), and systemic sclerosis (n = 1). Twenty-five of the 30 patients (83%) received steroid treatment, and 15 (50%) received at least 1 immunosuppressive agent (methotrexate in 14 cases) to control CTD. Four RA patients were given antitumor necrosis factor (TNF)alpha and 1 was treated with rituximab without SCD exacerbation. After a median follow-up of 4.5 years [range: 6 months to 30 years] from CTD diagnosis, 11 of the 25 (44%) patients receiving steroids had at least 1 episode of severe infection (mostly due to Staphylococcus aureus or Escherichia coli). SCD exacerbated in 13 of the 30 (43%) patients after CTD onset; 12 of these patients were receiving prednisone and/or methotrexate. Six patients (20%) had died from sepsis (n = 2), stroke (n = 2), or acute chest syndrome (n = 2). CONCLUSIONS: CTD-related clinical manifestations and outcome were not particularly severe in patients with SCD. However, those with active CTD and undergoing steroid +/- methotrexate treatment had more serious SCD-related manifestations, a higher rate of severe infections, and an overall patient mortality rate of 20%. Thus, the management of patients with CTD and underlying SCD should consider the risk/benefit ratio of each treatment and steroid-sparing strategies should be implemented.

Vasculitis restricted to the lower limbs: a clinical and histopathological study.

BACKGROUND: Rare cases of vasculitis restricted to the lower limbs have been reported, but the characteristics, outcome and response to treatment of this entity are not well known. OBJECTIVE: To describe the clinical, complementary examinations and response to treatment of this rare entity in the first retrospective series, and to compare data with historical pooled cases. METHODS: Retrospective analysis of all biopsy-proven cases observed over a 10-year period in four French tertiary medical units. Diagnosis of vasculitis restricted to the lower limb required the absence of any clinical symptom and complementary test finding, suggesting major extramuscular visceral involvement. RESULTS: 11 patients were included. Vasculitis restricted to the lower limb was associated with disabling muscle pain of the calves. Fever was present in 50% of cases; ankle arthralgia in 50% and skin involvement in 40%. MRI was the cornerstone of the diagnosis, showing hyperintense signal in T2 weight and in T1 weight after gadolinium injection. MRI findings correlated well with clinical outcome and were useful in guiding biopsy. Muscle biopsy was consistent with a polyarteritis nodosa-type vasculitis in only 40% cases, whereas a leucocytoclastic vasculitis was seen for all other cases. Treatment with corticosteroids was effective in all cases, but there were relapses requiring immunosuppressive agents in 54% of cases. CONCLUSION: Vasculitis of the calf muscles must be considered for patients with calf pain and with a biological inflammatory syndrome.

[Hepatosplenic localization of cat scratch disease: two cases in immunocompetent adult patients]. / Atteinte hépatosplénique de la maladie des griffes du chat : à propos de deux observations chez l'immunocompétent.

INTRODUCTION: Cat-Scratch Disease (CSD) is a well-recognized benign cause of localized lymphadenopathy, which often recovers spontaneously. However systemic clinical presentations are described in immunodeficient adults (bacillary angiomatosis, bacillary splenitis) and are less common in immunocompetent ones. EXEGESIS: We report two cases of disseminated CSD in immunocompetent patients, presenting hepatosplenic nodules, associated in the second case with an endocarditis. CONCLUSION: Bartonella serology must be achieved in case of hepatosplenic nodules with fever. Treatment of disseminated CSD in immunocompetent adults is still empirical and recovery can occur without antibiotherapy when endocarditis is not associated.

[Burkitt's lymphoma in a patient with systemic lupus erythematosus treated with immunosuppressive drugs. A case report]. / Lymphome de Burkitt au cours d'un lupus systémique traité par immunosuppresseurs. A propos d'un cas.

INTRODUCTION: Neoplasia and lymphoproliferative disorders are sometimes reported in patients with systemic lupus erythematosus (SLE). However, the pathophysiological link between lymphoma and SLE is still a matter of debate. We report a new case of Burkitt's lymphoma occurring in a patient treated with immunosuppressive drugs for SLE. CASE REPORT: A 38-year-old woman with SLE treated for 10 years with immunosuppressive drugs was admitted for the rapid onset of multiple neuritis with cranial nerves palsy, without extra-neurological involvement. The cerebrospinal fluid was normal. A bone marrow biopsy revealed Burkitt's lymphoma. CONCLUSION: This is the third case reported of Burkitt's lymphoma occurring in SLE. Here we discuss the data of the literature and the possible pathophysiological links between Burkitt's lymphoma and SLE.

[Calciphylaxis: a rare differential diagnosis of systemic vasculitis]. / La calciphylaxie: un diagnostic différentiel rare de vascularite systémique à ne pas méconnaître.

INTRODUCTION: Calciphylaxis is a rare phenomenon of medium- and small-vessel calcifications leading to cutaneous necrosis mimicking vasculitis. CASE REPORT: A 75 year-old-woman with chronic renal insufficiency was admitted for extensive cutaneous necrosis of the limb. Diagnosis of vasculitis was made, but inspite of corticosteroid therapy, the condition of the patient was worsening. After cutaneous biopsy, the diagnosis of calciphylaxis was established. CONCLUSION: Calciphylaxis must be suspected in cases of cutaneous necrosis occurring in a patient with chronic renal failure. Treatment requires rapid normalization of phosphocalcic balance. It is a condition with high mortality.

[Characteristics of autoimmune hemolytic anemia in adults: retrospective analysis of 83 cases]. / Caractéristiques des anémies hémolytiques auto-immunes de l'adulte: analyse rétrospective d'une série de 83 patients.

PURPOSE: To describe the main characteristics and outcome of adult's acquired immune hemolytic anemias (AIHA). To analyse the relevance of the complementary tests performed for the search of an underlying disease. METHODS: Retrospective (1980-2000) monocentric study. INCLUSION CRITERIA: age above 16, AIHA defined by an hemoglobin level below 12 g/dl in men and 11 g/dl in women, with hemolysis and/or a positive direct Coombs test and/or the presence of cold agglutinins (threshold 1/500) and/or in the absence of any other cause. RESULTS: Eighty three patients included (56 women and 27 men), with a mean age of 56 years (+/- 22) at AIHA onset including: 72 patients (87%) with warm antibody AIHA and 11 (13%) with cold agglutinin disease. The mean follow-up was 48 months (median 22 months). Among the 72 patients with warm antibody AIHA, the specificity of autoantibodies was: IgG + complement (43%), IgG (32%) or complement alone (25%); cold agglutinins (titre from 1/60 to 1/512) were detected in 15 (20%) of the patients. Antinuclear antibodies were detected (threshold: 1/80) in 33% of the cases. Hypogammaglobulinemia on serum protein electrophoresis (SPE) was significantively associated with the presence of an underlying non-Hogkin lymphoma (NHL). The CT-scan of the the chest and abdomen which was performed in 50% of the patients, showed abnormalities other than a spleen enlargement in 25% of the cases. The medullar biopsy (MB) was abnormal in 7 of 26 cases (27%) but lead by itself to the diagnosis of NHL in a single case. Thrirty seven (51%) of warm antibody AIHA cases were finally considered to be "secondary" to an underlying disease namely: NHLs (n = 14), Hogkin's disease (n = 1) connective tissue disease (CTD) (n = 14), drug-induced AIHA (n = 3), miscellaneous (n = 5). In 6 out of 14 cases (43%) of NHL's associated AIHA, the onset of AIHA precedes the NHL from 22 to 66 months. The response rates to different therapeutic regimens did not significatively differ when "secondary" and "idiopathic" AIHA were compared. Overall, 13 patients (15.6%) died mainly from infectious complications (n = 5) or an underlying NHL (n = 5). CONCLUSIONS: In more than half of the cases AIHA are associated with an underlying disease and AIHA may precede the onset of a NHL for a long period. In the absence of a clinically apparent underlying disorder, testing for the presence of antinuclear antibodies, a SPE and a CT-scan must be systematic. Conversely, if no abnormalities are found, the relevance of a systematic MB at AIHA onset seems very low.

Intravenous immunoglobulin for adults with autoimmune thrombocytopenic purpura: results of a randomized trial comparing 0.5 and 1 g/kg b.w.

Since the first reports demonstrating the ability of a total dose of 2 g/kg body weight (b.w.) of intravenous immunoglobulin (IVIg) to increase the platelet count in patients with autoimmune thrombocytopenic purpura (AITP), the optimal dose has remained controversial. We report the results of a randomized study which compared two low doses of IVIg (0.5 g/kg b.w., group A, n = 19, and 1 g/kg b.w., group B, n = 18) in 37 adults with AITP and platelet count <50 x 109/l, in preparation for surgery or in a situation with a risk of bleeding. On day 4 the proportion of responses, defined by a platelet count > 80 x 109/l and at least twice the initial platelet count, was significantly higher in the group receiving 1 g/kg b.w. (12/18 in group B versus 4/19 in group A, P = 0.005). All but one of the day 4 responders had already responded on day 3. The daily changes in the platelet count from the beginning of IVIg treatment were larger in group B, with a significant difference relative to group A on day 3 (92 x 109/l in group B versus 50 x 109/l in group A, P = 0.03) and on day 4 (106 x 109/l in group B versus 55 x 109/l in group A, P = 0.03). Patients who had not responded by day 4 subsequently received 1.5 g IVIg/kg b.w. (group A) or 1 g IVIg/kg b.w. (group B). A response was observed in 11/13 initial non-responders in group A, and in 2/6 initial non-responders in group B. Finally, on day 8, the proportion of responders was 78% (29/37) in the entire group and was similar in the two subgroups. In conclusion, (1) initial treatment with 1 g/kg b.w. of IVIg appeared to be more effective than 0.5 g/kg b.w. in adults with AITP; (2) infusion of a low dose of IVIg did not jeopardize the efficacy of IVIg reinfusion; (3) some adults who did not respond to 1 g IVIg/kg b.w. responded to a higher dose.