Robin Dhote

Acquired hemophilia due to factor VIII inhibitors in 34 patients

BACKGROUND Acquired hemophilia is a rare disease caused by the development of auto-antibodies against factor VIII. SUBJECTS AND METHODS We studied the characteristics and outcomes of 34 patients (19 women and 15 men) with acquired hemophilia from 1980 to 1997. RESULTS The mean age of the patients was 61 years (range, 22-93 years). An underlying disease was observed in 18 (53%) patients: 5 patients had cancer, 4 an autoimmune disorder, 2 a dermatologic disorder, 3 asthma, 3 were postpartum, and 1 had an adverse reaction to ampicillin. Factor VIII level was <5% in 30 (90%) patients; factor VIII antibodies were elevated (>10 Bethesda units) in 23 (69%) patients. Bleeding requiring transfusions was reported in 25 (75%) patients. Human factor VIII was given to 14 patients and porcine factor VIII to 5. Six patients received prothrombin complex concentrates and one desmopressin. Several immunosuppressive treatments were used, mainly corticosteroids, cyclophosphamide, and intravenous immunoglobulin. Bleeding stopped in all but one patient within 2 weeks. Most patients achieved complete remission, although two relapses were observed subsequently. CONCLUSION This large study helps to clarify the presentation and clinical course of acquired hemophilia. Prospective studies are needed to determine the efficacy of treatment.

Detection of myocardial involvement in patients with sarcoidosis applying T2-weighted, contrast-enhanced, and cine magnetic resonance imaging: initial results of a prospective study.

Purpose To assess myocardial magnetic resonance imaging (MRI) findings in sarcoidosis. Methods Cardiac assessment was prospectively performed in patients with sarcoidosis and included physical examination, electrocardiogram, echocardiography, thallium-201 myocardial scintigraphy, and coronary angiography if coronary disease was suspected. T2-weighted black-blood single-shot and inversion recovery fast spin echo, functional gradient echo, and T1-weighted gadolinium-DTPA-enhanced cardiac MRI examinations were performed in 40 patients while other cardiac disease was excluded. Results Results of the MRI images were normal in cardiac-asymptomatic stage I or Lofgren syndrome patients (n = 4). Among the patients with cardiac-asymptomatic multiple organ sarcoidosis, 17 of 31 patients (54%) had MRI myocardial abnormalities similar to those observed in five patients with cardiac symptoms: nodular peripheral increased intramyocardial signal intensity on both T2-weighted and contrast-enhanced images (n = 5), focal or patchy increased signal on contrast-enhanced images with or without myocardial thickening (n = 10), and focal increased signal only on T2-weighted images with or without myocardial thinning (n = 2). Focal contractility abnormalities were noticed in nine patients. Conclusions These preliminary results emphasize the occurrence of subclinical myocardial MRI abnormalities in patients with ongoing systemic sarcoidosis.

Population-Based Prevalence Study of Behçet's Disease : Differences by Ethnic Origin and Low Variation by Age at Immigration

OBJECTIVE To estimate the prevalence of Behçets disease (BD) in a multiethnic population living in France, with particular focus on disease risk among immigrants. METHODS The study was conducted in a county in the Paris metropolitan area that is home to 1,094,412 adults (ages > or =15 years), of whom 26% are of non-European ancestry. Patients with BD living in this area during 2003 were identified using 3 sources (hospitals, community physicians, and the National Health Insurance database), and diagnoses were verified using the International Study Group criteria. Standardized, year-2003 prevalence rates were computed for the overall population and for each ethnic group. Stratified prevalence rates according to age at immigration to France were calculated to investigate the relationship between age at immigration and BD risk. RESULTS Seventy-nine subjects fulfilled our search criteria. The overall prevalence per 100,000 adults was 7.1 (95% confidence interval [95% CI] 3.5-14.4), and the prevalence for populations of European, North African, and Asian ancestry was 2.4 (95% CI 0.6-7.2), 34.6 (95% CI 24.4-47.5), and 17.5 (95% CI 10.7-27.2), respectively. Within the migrant population of either North African or Asian ancestry, BD prevalences were similar for residents born in France, residents <15 years old at immigration, and residents > or =15 years old at immigration. CONCLUSION Our findings indicate that the prevalence of BD among immigrants of North African or Asian ancestry is significantly higher than that in the European-origin population, and comparable with rates reported from North Africa and Asia. Moreover, our results suggest that BD risk is not related to age at immigration. These findings support the hypothesis that BD has a primarily hereditary basis.

The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study.

In European multicenter study, we aimed to describe the real-life hydroxychloroquine use in APS patients during pregnancy and determine its benefit in refractory obstetrical APS. We analyzed the outcome of pregnancies treated by hydroxychloroquine in patients with APS or asymptomatic antiphospholipid (aPL) antibodies carriers. Thirty patients with APS with 35 pregnancies treated by hydroxychloroquine were analyzed. Comparing the outcome of pregnancies treated by the addition of hydroxychloroquine to previous pregnancies under the conventional treatment, pregnancy losses decreased from 81% to 19% (p<0.05), without differences in the associated treatments. The univariate analysis showed that the previous intrauterine deaths and higher hydroxychloroquine amount (400mg per day) were the factors associated with pregnancy outcome. Considering 14 patients with previous refractory obstetrical APS (n=5 with obstetrical and thrombotic primary APS and n=9 with purely obstetrical APS), all with previous pregnancy losses under treatment (aspirin with LMWH in 11 cases and LMWH in 3 cases), the addition of hydroxychloroquine resulted in live born babies in 11/14 (78%) cases (p<0.05). Our study shows the benefit of hydroxychloroquine addition in patients with refractory obstetrical APS and raises the need of prospective studies to confirm our preliminary study.

Autoimmune diseases in HIV-infected patients: 52 cases and literature review

OBJECTIVES 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. DESIGN 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. RESULTS The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. CONCLUSION In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use.

Efficacy of Biological-Targeted Treatments in Takayasu Arteritis Multicenter, Retrospective Study of 49 Patients

Background— The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-&agr; antagonists and tocilizumab) in patients with Takayasu arteritis. Methods and Results— This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20–55 years] treated by tumor necrosis factor-&agr; antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1–5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%–99%) over the biological treatment period compared with 58.7% (43.3%–79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-&agr; antagonists and tocilizumab. After a median follow-up of 24 months (2–95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. Conclusion— This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.Background— The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis. Methods and Results— This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20–55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1–5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P =0.006) and a trend toward fewer immunosuppressants drugs used before biologics ( P =0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [ P <0.05] and 15 versus 7.5 mg [ P <0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%–99%) over the biological treatment period compared with 58.7% (43.3%–79.7%; P =0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2–95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. Conclusion— This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile. # CLINICAL PERSPECTIVE {#article-title-34}

Cyclic sciatica. A manifestation of compression of the sciatic nerve by endometriosis. A case report.

Study design A case of cyclic sciatica secondary to ovarian cyst endometriosis is presented. Objectives To report the clinical description and magnetic resonance imaging aspects of cyclic sciatica. Summary of Background Data Endometriosis of the sciatic nerve is rare, but must be included in the differential diagnosis of sciatic mononeuropathies. Methods The authors report a new case of a woman whose cyclic sciatica was caused by an ovarian cystic endometriosis lesion. Results Magnetic resonance imaging was described as hyper‐ and hypointense on T1‐weighted sequences, and hyperintense on T2‐weighted sequences at the sciatic notch. Conclusion Magnetic resonance imaging may permit a specific diagnosis of this unusual cause of sciatica by showing a hemorrhagic mass in the region of the sciatic nerve. Early recognition is necessary to prevent permanent damage to the sciatic nerve.

Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: A french multicenter study

The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5years (range: 1.6-35). Two patients developed Waldenströms macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.

Incidence and predictors of urotoxic adverse events in cyclophosphamide‐treated patients with systemic necrotizing vasculitides

OBJECTIVE To assess hemorrhagic cystitis and urinary tract cancer incidence and predictors in cyclophosphamide (CYC)-treated patients with systemic necrotizing vasculitis (SNV). METHODS The French Vasculitis Study Group database, which contains longitudinal data on SNV patients, was searched for urinary tract cancer and/or hemorrhagic cystitis occurrences in patients diagnosed as having Wegeners granulomatosis (WG), microscopic polyangiitis, Churg-Strauss syndrome, or polyarteritis nodosa. The observed incidence of urinary tract cancer was compared to the expected incidence in the general population by calculating standardized incidence ratios (SIRs). Relationships between urinary tract cancer and/or hemorrhagic cystitis and 10 variables, including CYC dosage and administration route, were investigated by survival analyses for a nested subgroup of patients for whom detailed information on CYC exposure was available. RESULTS Among the 805 patients observed over 4,230 patient-years (mean followup 5.3 years), 22 cases of hemorrhagic cystitis and 7 of urinary tract cancer were identified in 27 patients. The SIRs for urinary tract cancer were 5.00 for all patients with SNV (P = 0.001) and 5.96 for patients with WG (P = 0.03). Based on 467 patients with detailed CYC information, cumulative CYC dose (hazard ratio [HR] for 10-gm increments 1.09; P = 0.03), ever-oral CYC administration (HR 5.50; P = 0.001), and WG (HR 2.96; P = 0.01) independently predicted urinary tract cancer and/or hemorrhagic cystitis. According to univariate analyses, smoking (ever) (HR 8.20; P = 0.02) and a prior hemorrhagic cystitis episode (HR 5.20; P = 0.046) significantly predicted urinary tract cancer. CONCLUSION Our findings indicate that CYC treatment of SNV is associated with a 5-fold higher risk of developing urinary tract cancer. Urotoxicity risk in SNV is associated with the cumulative CYC dose and its oral administration, and might be higher in WG.

Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20 pregnancies

OBJECTIVES To describe pregnancies of women with systemic necrotizing vasculitides (SNVs), i.e. PAN, WG, Churg-Strauss syndrome (CSS) or microscopic polyangiitis (MPA), followed over the past 15 years at four French centres. METHODS Retrospective analysis of women whose SNV appeared during pregnancy or who became pregnant after SNV diagnosis. RESULTS Among the 12 women identified, one experienced rupture of pancreatic artery microaneurysms at 27 weeks revealing PAN, leading to surgical haemostasis and caesarean delivery. Eleven others started 19 pregnancies after SNV diagnosis (8 in four WG, 6 in three CSS, 1 each in three PAN and 2 in one MPA); 14 conceived during vasculitis remission. Two ended in first-trimester abortions, four miscarried; the remaining 13 pregnancies yielded 14 live newborns (1 twin pregnancy), with 7 pre-term births. Life-threatening complications occurred during 3 of these latter 13 pregnancies and required caesarean delivery. The twin pregnancy (in a CSS patient with initial vasculitis-related cardiac involvement, but in remission at conception) was complicated by transient maternal cardiac failure at 32 weeks. One WG patient with vasculitis-related renal damage developed thrombotic microangiopathy-associated renal impairment at 32 weeks, and another WG patient had severe pneumonia at 37 weeks. Other pregnancies were uneventful or with minor vasculitis manifestations. CONCLUSION Pregnant SNV patients should be monitored closely, because miscarriages and pre-term births are not uncommon. Pregnancy does not seem to have a major impact on vasculitis activity. However, life-threatening manifestations can occur, especially in patients with vasculitis-related cardiac or renal damage.