Acute Coxsackievirus B3-induced meningo-cerebellitis in an immunocompetent adult patient.

We report an acute Coxsackievirus B3 (CVB3)-induced meningo-cerebellitis in an immunocompetent adult patient. CVB3 has a global distribution and is the most common Enteroviruses cause of myocarditis and sudden cardiac death. To our knowledge, CVB3 is exceedingly rare as causes of meningo-encephalitis in immunocompetent adults, whereas some cases have been reported in neonates due to perinatal acquired infections or in immunocompromised patients.

Dramatic decline in new HIV diagnoses in persons born in France in a large nationwide HIV cohort.

OBJECTIVES: As trends in new HIV diagnoses represent a measure of the HIV epidemic, we conducted a 6-year longitudinal study to evaluate the change in rates of new HIV diagnosis, stratified by birthplace, HIV risk groups and CD4 cell count at diagnosis in a large French multicentre cohort. STUDY DESIGN: We performed a retrospective cohort study using data from the mainland French Dat'AIDS cohort. METHODS: Data were obtained for subjects with a new HIV diagnosis date between 2013 and 2018. HIV diagnosis date was defined as the date of the first known positive HIV serology. RESULTS: Between 2013 and 2018, a total of 68,376 people living with HIV (PLHIV) were followed in the Dat'AIDS cohort; 9543 persons were newly diagnosed with HIV. The annual number of new HIV diagnoses decreased from 1856 in 2013, to 1149 in 2018 (-38.1%), P = 0.01; it was more pronounced among subjects born in France, from 858 to 484 (-43.6%), P < 0.01, than in those born abroad (-23.8%, from 821 to 626, P = 0.13). Among subjects born in France, the decrease over the period was -46.7% among men who have sex with men (MSM), -43.5% for heterosexual women and -33.3% for heterosexual men. CONCLUSION: Our findings show changes in HIV epidemiology in PLHIV born in France, with a decline around 40% in new HIV diagnoses, and a more pronounced decrease among MSM and heterosexual women. Our results support the long-term effectiveness of the antiretroviral therapy as a prevention strategy among the various tools for HIV prevention.

Cerebral venous thrombosis: a rare complication of herpes simplex encephalitis.

We report a case of classic HSE with early neurological relapse 7 days after onset of acyclovir treatment secondary to cerebral venous thrombosis (CVT). The development of CVT after meningoencephalitis has been described with neurotropic viruses such as HSV, HIV, or enteroviruses and also bacterial or fungal agents. CVT is probably the consequence of the inflammation secondary to these infections. A diagnosis of CVT, although rarely described, should be systematically suspected in patients with HSE who present no or only moderate improvement, or early relapse of symptoms despite adapted acyclovir treatment.

Progressive multifocal leukoencephalopathy despite immune recovery in a HIV/HCV co-infected patient.

In HIV patients, HCV co-infection has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Furthermore, PML has also been described in patients with cirrhosis, whether related to HCV infection or not. We describe here the case of a HIV/HCV co-infected patient with cirrhosis who developed PML despite HIV suppression and CD4 cell count above 250/mm3 for 2 years. Immunological studies performed at onset of PML and before HCV therapy showed a decrease in naïve CD4 cells (CD45RA+CCR7+CD27+ CD4+ T cells - 23% cells, i.e. 75/mm3) and NK lymphopenia with abnormal and activated NK cells (CD3- CD16+ and/or CD56+) (5% lymphocytes, i.e. 58/mm3, CD69 91%, NKp30 26%). This impaired immunity, possibly related to HIV infection, or HCV infection or cirrhosis, or a combination thereof, could have led to the development of PML.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

BACKGROUND: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people. OBJECTIVE: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage. METHODS: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort. Patients' characteristics were described at KS diagnosis according to ART exposure and to HIV-plasma viral load (HIV-pVL) (≤50 or >50) copies/mL. RESULTS: Among the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART-experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV-pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted-PI-based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis. LIMITATIONS: Data on human herpesvirus 8, treatment modalities for KS and response rate were not collected. CONCLUSION: Half of KS cases observed in the study period occurred in patients not on ART, reflecting the persistence of late HIV diagnosis. Factors associated with KS in patients on ART with HIV-pVL ≤50 cp/mL remain to be explored.

Effectiveness of an education health programme about Middle East respiratory syndrome coronavirus tested during travel consultations.

OBJECTIVE: We aimed to evaluate the level of knowledge of Middle East respiratory syndrome coronavirus (MERS-CoV) among Hajj pilgrims before and after an education health programme during international vaccine consultations in France. STUDY DESIGN: A cross-sectional study was performed in the consultation for travel medicine and international vaccination in Reims University Hospital between July 2014 and October 2015. METHODS: Consecutive adults (>18 years old) who attended for pre-Hajj meningococcal vaccination were eligible to complete an anonymous questionnaire with closed answers to evaluate their level of knowledge about MERS-CoV. To evaluate the effectiveness of the information given during the consultation, the same questionnaire was completed by the Hajj pilgrim before and after the consultation, where the information about MERS-CoV was provided. RESULTS: Among 82 Hajj pilgrim adults enrolled in the study, less than 25% were aware of the routes of transmission, symptoms and preventive behaviours to adopt abroad or in case of fever. Pilgrims had a higher rate of correct responses on each question at the time they completed the second questionnaire, as compared with the first, with 11 of 13 questions answered significantly better after delivery of educational information about MERS-CoV. However, although the rate of correct answers to the questions about routes of transmission, symptoms, preventive behaviours to adopt in case of fever and time delay between return and potential MERS-CoV occurrence increased significantly after receiving the information, the rates remained below 50%. CONCLUSION: Information given during travel consultations significantly increases the general level of knowledge, but not enough to achieve epidemic control.

No relationship between late HIV diagnosis and social deprivation in newly diagnosed patients in France.

OBJECTIVES: The aim of the study was to determine whether there is a relationship between social deprivation and time of HIV diagnosis in France. METHODS: Prospectively collected data from a multicentre database were used in the study. Patients with a first HIV diagnosis between 1 January 2014 and 31 December 2015 were selected from the database. Deprivation was measured using the European Deprivation Index (EDI), which is an ecological index constructed from the address of residence and based on the smallest geographical census unit, in which individuals are classified so as to be comparable with national quintiles. Time of diagnosis was classified as being at an early, intermediate, late, or advanced stage of disease. Age, gender, distance from home to HIV centre, most probable route of infection, and hepatitis B or C coinfection were considered in the analysis. Because of a strong interaction between gender and most probable route of infection, we constructed a 'population' variable: men who have sex with men (MSM), heterosexual men and women. RESULTS: Of 1421 newly diagnosed patients, 44% were diagnosed either late or at an advanced stage of disease, and 46.3% were in the highest deprivation quintile. Using multivariate logistic regression, 'population' [odds ratio (OR) 0.62 (95% confidence interval (CI) 0.48-0.78) for MSM compared with women] and age [OR 1.39 (95% CI 1.07-1.80), 1.72 (1.32-2.23) and 1.86 (1.40-2.47) for the second, third and fourth quartiles, respectively, compared with the first quartile] were found to be related to late diagnosis. EDI level was not related to late HIV diagnosis. CONCLUSIONS: 'Population' seems to be more relevant than EDI to define evidence-based interventions to limit late diagnosis.

Factors associated with deaths from suicide in a French nationwide HIV-infected cohort.

OBJECTIVES: People living with HIV (PLHIV) are at a higher risk of dying by suicide than the general population. Epidemiological data regarding determinants of suicide in PLHIV are scarce. The aim of this study was thus to study demographic, socio-economic, psychiatric history and immunovirological characteristics associated with death from suicide in the French multicenter Dat'AIDS cohort, from January 2000 to July 2013. METHODS: This was a nested case-control study. All deceased PLHIV during the study period who died by suicide and whose medical files could be checked were included as cases. Controls were selected using incidence density sampling. For each case, up to four controls were selected among all actively followed PLHIV at the index date (date of death of cases). Controls were matched for time from HIV diagnosis (5-year periods) and clinical centre. RESULTS: Seventy cases and 279 controls were included in the study. By multivariable analysis, the factors significantly associated with death from suicide were: not having children, active or substituted drug consumption, alcohol intake > 20 g/day or history of alcohol abuse, history of depressive disorder and/or of attempted suicide, and psychotropic drug intake. Conversely, age, gender, country of birth, positive HCV serology and HIV-related factors, such as AIDS status, use of combination antiretroviral therapy (cART), nadir and current CD4 counts and HIV viral load, were not significantly associated with the risk of death from suicide. CONCLUSIONS: In the cART era, HIV-related factors are not associated with a higher risk of suicide mortality. Suicide prevention measures should target PLHIV with the psychological morbidities observed in our cohort.

Ageing with HIV: do comorbidities and polymedication drive treatment optimization?

OBJECTIVES: The aim of the study was to describe the ageing HIV-infected population (> 50 years old) and their current antiretroviral therapy (ART), comorbidities and coprescriptions in France in 2013 and to compare them to the younger population. METHODS: A retrospective analysis of a prospectively collected database was performed. The characteristics of patients receiving ART as well as their current ART and their numbers of comorbidities and comedications at the censoring date (1 July 2013) were compared between patients ageing with HIV infection, patients who seroconverted while ageing, and younger patients. RESULTS: We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53-62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36-47 years). The ageing patients were more frequently male than the younger patients (77 vs. 65%). Among the ageing patients, 7025 were diagnosed with HIV infection before 2000 and represented a distinct group, the 'experienced ageing' group, by comparison with the 'recently diagnosed ageing' group. Triple therapy containing a boosted protease inhibitor was used in 28.2% of the patients (vs. 39% and 36% of the younger and "recently diagnosed ageing" groups, respectively); a nonnucleoside reverse transcriptase inhibitor in 27% (vs. 33% and 38%, respectively), an integrase strand transfer inhibitor (INSTI) in 9% (vs. 7% and 9%, respectively), and another regimen (fewer or more than three drugs) in 35.8% (vs. 21% and 16.5%, respectively). "Experienced ageing" patients typically had one or more comorbidities (62.1%) and were receiving at least one comedication (71%). Central nervous system (CNS) agents (prescribed in 44.6% of the "experienced ageing" patients) and antilipidaemics (in 44.2%) were the most frequently prescribed comedications. INSTIs were used in 23% of the population and were used significantly more often in patients with comorbidities and coprescriptions. For all comparisons, P < 0.0001. CONCLUSIONS: In ageing HIV-infected patients, especially those with a long history of HIV infection, comorbidities and coprescriptions are highly prevalent.

Comparative risk of failure of ABC/3TC or TDF/FTC based first-line regimens in patients with a high viral load.

OBJECTIVES: To compare the efficacy, in current clinical practice, of first regimens containing abacavir with lamivudine (ABC/3TC) or tenofovir with emtricitabine (TDF/FTC) in patients with baseline viral load ≥100,000 HIV-1 RNA copies/mL. METHODS: Using a prospective cohort, we selected all patients starting a first HIV regimen based either on ABC/3TC or on TDF/FTC. The propensity score (PS) method was used to limit the indication bias due to the observational nature of the data. Adjusting and weighting methods via PS were used to compare the effectiveness of a first regimen containing ABC/3TC or TDF/FTC. The primary outcome was treatment failure by month 12 (M12). RESULTS: Overall, 2781 patients started an antiretroviral (ARV) regimen with ABC/3TC or TDF/FTC each in combination with efavirenz, boosted atazanavir or boosted darunavir. Among the 2472 uncensored patients before M12, 962 (39%) had a baseline viral load ≥100,000 copies/mL of whom 294 were in treatment failure at or before M12. Our analyses showed no difference between ABC/3TC and TDF/FTC in the risk of treatment failure at M12 in patients starting an ARV regimen with a high viral load (≥100,000 copies/mL). CONCLUSIONS: Using a large prospectively collected cohort of patients seeking care in France, we found no evidence that ABC/3TC based regimens led to more failures than TDF/FTC based ones in patients with high baseline viral loads.

Factors associated with guideline-based hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients: role of comorbidities and physicians' perceptions.

OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

Chronic hepatitis delta cirrhosis cured by adapting PEG-IFNα-2a + tenofovir disoproxil fumarate treatment duration until HBsAg loss.

As the loss of HBsAg during treatment of chronic hepatitis delta (CHD) is mandatory for definitive clearance and durable response, the optimal target of therapy should be complete response (CR), defined as loss of HDV RNA and HBsAg, plus development of anti-HBs. The optimal treatment duration of CHD is not well established. We present 2 cases of patients with CHD cirrhosis who were treated with prolonged Peg-IFNα-2a + tenofovir disoproxil fumarate until HBsAg loss, and who achieved CR after 46 and 55 months of treatment respectively. A personalized approach and prolonged treatment duration determined by HBsAg loss may increase the likelihood of CR in CHD.

Severe transaminitis after interferon-ribavirin therapy in HIV/HCV-coinfected patients: influence of a sustained HCV response.

Chronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV-coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five-fold above the upper limit of normal in patients with normal baseline levels or >3.5-fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV-coinfected patients on HAART who had previously been treated for HCV infection. Median follow-up exceeded five years. Cox proportional hazards models were used. At baseline, 248 patients had been receiving antiretroviral therapy for a mean of 6.3 (± 3.2) years. Seventy-one patients (29%) had a sustained HCV viral response (SVR). During follow-up, 66 patients (26.6%) received a second course of HCV therapy and 29 (44%) of them had an SVR. Severe transaminitis occurred in 64 patients (26%). In multivariate analysis, no SVR (HR 33.33, 95% CI 4.54-222, P = 0.001) and stavudine-based therapy (HR 2.11, 95% CI 1.12-3.99, P = 0.018) remained significantly associated with severe transaminitis. A SVR to anti-HCV therapy is thus associated with a markedly reduced risk of severe transaminitis during antiretroviral therapy. Treatment of HCV infection should therefore be a priority in HIV-coinfected patients. Stavudine is associated with an increased risk of severe transaminitis.

Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients.

The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV-coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV-coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non-nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1-3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1-3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2-3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0-2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0-1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV-coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.

Short duration of post-amputation antibiotic therapy in diabetic foot patients with total resection of osteomyelitis.

BACKGROUND: Short duration of post-amputation antibiotic therapy (2-5 days) is recommended in patients with diabetic foot osteomyelitis after total resection of infected bone tissue. OBJECTIVE: To evaluate the long-term effectiveness of short-duration post-amputation antibiotic therapy in diabetic patients with total resection of osteomyelitis assessed by sterile bone bacteriological samples obtained from the resection margin. METHODS: The endpoint was the absence of osteomyelitis relapse at 6 months, defined as recurrence of osteomyelitis with the need for surgical revision and/or new bone antibiotic therapy. RESULTS: Among 15 patients included, 12 (80%) were cured without recurrence of osteomyelitis at 6 months, with a mean duration of antibiotic therapy of 8.3±5.9 days post surgery. This result is comparable to literature data, while all of them reported longer duration of antibiotic therapy and/or shorter follow-up. CONCLUSION: Short duration of post-amputation antibiotic therapy in diabetic patients with sterile bacteriological samples obtained from resection margin seems effective.

Major 5'terminally deleted enterovirus populations modulate type I IFN response in acute myocarditis patients and in human cultured cardiomyocytes.

Major 5'terminally deleted (5'TD) group-B enterovirus (EV-B) populations were identified in heart biopsies of patients with fulminant myocarditis or dilated cardiomyopathy suggesting that these 5'TD forms are key drivers of host-cell interaction in EV cardiac infections. To date, early emergence of EV-B 5'TD forms and its impact on type 1 IFN response during acute myocarditis remains unknown. Using quantitative RACE-PCR assay, we identified major EV-B 5'TD RNA populations in plasma or heart samples of acute myocarditis cases. Deletions identified within the 5' non-coding region of EV-B populations only affected secondary-structural elements of genomic RNA domain I and were distinguished in two major groups based on the extent of RNA structural deletions. Proportions of these two respective EV-B 5'TD population groups were positively or negatively correlated with IFN-ß levels in plasma samples of myocarditis patients. Transfection of synthetic CVB3/28 RNAs harboring various 5'terminal full-length or deleted sequences into human cultured cardiomyocytes demonstrated that viral genomic RNA domain I possessed essential immunomodulatory secondary-structural elements responsible for IFN-ß pathway induction. Overall, our results highlight the early emergence of major EVB-TD populations which deletions affecting secondary-structures of RNA domain I can modulate innate immune sensing mechanisms in cardiomyocytes of patients with acute myocarditis.

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis.

OBJECTIVE: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. METHODS: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. RESULTS: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels. CONCLUSION: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.

[Treatment of chronic hepatitis C in HIV-infected patients]. / Traitement de l'hépatite chronique C chez les patients co-infectés VHC-VIH.

Since the pivotal trials conducted over the last few years which have used the combination of pegylated interferon along with fixed low doses (800 mg/day) of ribavirin and have provided treatment for 12 months, regardless the kinetics of hepatitis C virus (HCV) viral load during therapy, great progress has been made in the treatment of chronic hepatitis C in HIV-infected patients. Results approaching those seen in HCV-monoinfected patients can be obtained with optimal dosages of ribavirin, extension of treatment beyond 48 weeks in the absence of rapid virologic response and/or in patients older than 40 years, with severe fibrosis (METAVIR score F3 or F4) and/or with high HCV viral load and with a better management of HIV treatment in order to avoid a negative interaction between HCV and HIV therapies (interaction between abacavir and ribavirin) and to improve the tolerance of HCV therapy (Didanosine should never be used with ribavirin, Zidovudine and Stavudine should be avoided when possible with ribavirin).

Rituximab treatment in seronegative autoimmune autonomic neuropathy and autoimmune autonomic ganglionopathy: Case-report and literature review.

BACKGROUND AND PURPOSE: Autoimmune autonomic ganglionopathy (AAG) is a rare disease with no well-established treatment. Until recently, AAG could be seropositive (50 to 60% of patients) or seronegative for ganglionic (α3-type) nicotinic acetylcholine receptor (Gα3NAChR) antibodies. In early 2018, the two forms of the disease were distinguished, separating seropositive from seronegative ones, designating this latter form "seronegative autoimmune autonomic neuropathy" (SAAN). Most described treatments are plasma exchange (PE) and intravenous immunoglobulin (IVIG). However in some cases with no or small benefit, other immunomodulatory therapies, such as rituximab have been reported. We report the case of a 24-year-old female patient successfully treated for SAAN with rituximab and steroids after IVIG and PE failure. We also provide a review of case-reports reporting rituximab treatment for both SAAN and AAG. METHODS: To identify articles reporting SAAN and AAG treatment with rituximab, we searched the PubMed database using the terms "autoimmune autonomic ganglionopathy", "autoimmune autonomic neuropathy" or "seronegative autoimmune autonomic neuropathy" and "rituximab". RESULTS: Including our patient, nine cases have been described in the literature (4 SAAN and 5 AAG). Rituximab had a significant positive effect in 2 out of 4 SAAN and all 5 AAG cases, used alone or in association with other etiologic treatments. CONCLUSION: Our study suggests rituximab (alone or in association with other treatments) could provide efficacy in both SAAN and AAG when PE and/or IVIG are not effective enough.