Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1-INH-AAE versus C1-INH-HAE types I/II, respectively.

Mucosal-associated Invariant Cells are Deficient in Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease, characterized by fibrosis of the skin and other organs, vascular impairment and deficient immune responses. Mucosal-associated invariant T cells (MAIT) have been involved in various inflammatory and autoimmune diseases. The aims of this study were to determine the frequencies of MAIT cells in the blood of patients with systemic sclerosis (SSc) and to compare their distribution in different types of SSc. Blood samples from patients with SSc and healthy controls were examined by flow cytometer to analyse the frequencies of MAIT and γδ T cells. We demonstrate that in SSc the frequencies and absolute numbers of MAIT and γδ T cells are significantly reduced in comparison with healthy controls. MAIT and γδ T cells did not correlate with C-reactive protein, BNP, pulmonary involvement or median skin fibrosis scale, steroid amount or disease duration. In addition, MAIT and γδ T cells decrease did not stratify with gender, interstitial lung disease or active digital ulcers. Functional studies are necessary to determine the signification of MAIT cells decrease in systemic sclerosis.

Hereditary angioedema with normal C1 inhibitor and factor XII mutation: a series of 57 patients from the French National Center of Reference for Angioedema.

Hereditary angioedema (HAE) is a rare disease associated with either a quantitative or qualitative deficiency in C1-inhibitor (C1-INH) or normal C1-INH. HAE with normal C1-INH is associated in 20% of cases with mutations in the gene for factor XII (FXII) or FXII-HAE. A recent review described 41 families, including 14 German and 15 Spanish families. We have constructed a register of French patients and their characteristics. A national survey was launched through the French National Center of Reference for Angioedema (CREAK) to study the clinical, biological and therapeutic characteristics of patients with HAE linked to a mutation of FXII gene. Fifty-seven patients were identified from 24 different families. In most cases they were young women (mean age at diagnosis: 31 years, mean age at first symptom: 21 years, female/male ratio: 76%). Twenty-one per cent of the patients experienced angioedema attacks only during pregnancy or when on oestrogen contraception. Sixty-three per cent had attacks at all times, but they were more severe during these same periods. Male carriers of the mutation were more frequently asymptomatic than females (P = 0·003). C1-INH concentrate and icatibant were both effective for treating attacks. The prophylactic use of tranexamic acid led to a 64% decrease in the number of attacks. This is one of the largest series reported of HAE patients with FXII mutation. The therapeutic management appeared to be identical to that of HAE with C1-INH deficiency.

Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels.

OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.

Subcutaneous phaeohyphomycosis caused by Exophiala spinifera in a European patient with lymphoma: a rare occurrence case report and literature review.

Exophiala spinifera is a dematiaceous fungus responsible for rare skin infections presenting as phaeohyphomycosis or chromoblastomycosis which has been primarily reported in tropical and subtropical areas (Asia, South and North America). We report the first case of E. spinifera phaeohyphomycosis in a European patient. The phaeohyphomycosis was limited to the skin, involving the finger of an immunocompromised patient presenting with a large B-cell lymphoma treated by R-mini-CHOP regimen. Remission was initially achieved by surgical excision; however, a local subcutaneous relapse required treatment with itraconazole. We performed a literature review of the 32 previously published cases of E. spinifera phaeohyphomycosis highlighting its clinical phenotype: disseminated infection with extracutaneous involvement and poor prognosis were reported in young patients, of whom some were recently associated with CARD9 mutations, whereas cases in older immunocompromised patients were limited to the skin and showed better prognosis. There is currently no standard treatment for E. spinifera phaeohyphomycosis; however, itraconazole, alone or in combination, allowed partial or complete response in 16 out of 20 cases.

Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients.

OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).

FDG-PET/CT findings in systemic mastocytosis: a French multicentre study.

INTRODUCTION: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined. METHODS: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data. RESULTS: Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells. CONCLUSIONS: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients.

Tranexamic acid as maintenance treatment for non-histaminergic angioedema: analysis of efficacy and safety in 37 patients.

Angioedema (AE) is a clinical syndrome characterized by localised swelling lasting several hours. The swelling is often recurring and can be lethal if it is located in the laryngeal region. Much progress has been made recently in the treatment of acute episodes, but no consensus has been reached on maintenance treatment. We have performed a national retrospective observational study to assess the use of tranexamic acid (TA) as maintenance treatment for non-histaminergic AE [hereditary AE (HAE) or idiopathic non-histaminergic AE]. Records for 64 cases were collected from 1 October 2012 to 31 August 2013; 37 of these were included (12 HAE with C1-inhibitor deficiency, six with HAE with normal C1-inhibitor and 19 idiopathic non-histaminergic AE). When treated with TA over six months, the number of attacks was reduced by 75% in 17 patients, 10 patients showed a lower level of reduction and 10 had the same number of attacks. In no instances were symptoms increased. No thromboembolic events were observed, and the main side effects were digestive in nature. Thus, TA, which is well tolerated and inexpensive, appears to be an effective maintenance treatment for some patients with HAE or idiopathic non-histaminergic AE.

Hereditary angioedema with F12 mutation: factors modifying the clinical phenotype.

BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1Inh) associated with the c.983C>A and c.983C>G mutations of the F12 gene (FXII-HAE) is a rare condition, and presents with highly variable clinical expression. On the basis of data gathered from a large carrier cohort, we assessed the modifiers affecting the clinical phenotype. METHODS: We analyzed clinical and biological data recorded from 118 mutation carriers (80 symptomatic and 38 asymptomatic), 58 noncarrier relatives from 40 families, and 200 healthy donors. Disease severity was scored in relation to frequency and location of edema, as well as age at disease onset. To predict FXII-HAE disease severity, we analyzed the biological phenotype [C1Inh, C4, spontaneous amidase, angiotensin-I-converting enzyme (ACE), aminopeptidase P (APP), and carboxypeptidase N/M (CPN)] by means of logistic regression (Akaike information criterion) and odds ratio (OR). RESULTS: Meaningful variables contributed to FXII-HAE, with the kinin catabolism enzymes ACE and CPN exhibiting a significant inverse relationship with disease severity (OR = 0.36, 95% CI 0.23-0.59, P < 0.001; OR = 0.58, 95% CI 0.36-0.91, P < 0.05, respectively). CPN activities were 37.5 (28.5-41.3) nmol/ml/min and 38.5 (32.8-45.6) for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 37.9 (30.5-43.7) nmol/ml/min for noncarriers. Angiotensin-I-converting enzyme activities were 58 (44-76) and 49 (35-59) nmol/ml/min for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 56 (49-66) nmol/ml/min for noncarriers. CONCLUSIONS: The FXII-HAE is associated with modifiers, for example kinin catabolism enzymes, ACE and CPN, different from those recognized in HAE with C1Inh deficiency.

Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

Benefits of progestin contraception in non-allergic angioedema.

BACKGROUND: Hereditary angioedema attacks can be induced or worsened by oral contraceptive containing oestrogens. OBJECTIVES: The purpose of this study was to assess the impact of progestin contraceptives on angioedema attacks. METHODS: We conducted a French retrospective, multi-centre study of progestin contraception in women with non-allergic angioedema, including hereditary angioedema type I, II and III and idiopathic angioedema. Patients were classified into four groups according to frequency of attacks. We evaluated the effects of progestin on the mean number of attacks and compared the number of patients in each group before and under progestin contraception. The influence of hormonal factors on the course of angioedema was also assessed. RESULTS: Fifty-five women were included: mean age was 32.1 years (16-52) and mean follow-up 32.4 months (SD:29). Fourteen women were classified as type I (25.4%), two as type II (3.6%) and 19 as type III (34%) and 20 were idiopathic (36%). Seventeen patients were taking a low dose progestin-only pill (POP), 24 antigonadotropic progestins (AGP) and 14 both successively. Total or partial improvement was observed in 81.8% (45/55) of the patients and more frequently in those on an AGP agent (34 patients, 89.5%) than on POP (19 patients, 61.3%) (P = 0.013). CONCLUSIONS & CLINICAL RELEVANCE: This is the first study evaluating the interest of antigonadotropic progestin contraception in a series of women with non-allergic angioedema. Progestins, especially antigonadotropic progestins, appear to convey a marked benefit in most cases. Antigonadotropic progestins could thus be recommended as adjuvant treatment in childbearing women with non-allergic angioedema.

[Hereditary angioedema and its new treatments: An update]. / Mise au point sur les angiœdèmes héréditaires et leurs nouvelles thérapeutiques.

Hereditary angioedema, with or without deficient C1 inhibitor level or function, is a rare disease characterized by recurrent attacks of noninflammatory subcutaneous and/or submucosal edema. It may be life-threatening and substantially affects quality of life. Attacks may be spontaneous or induced, in a setting of emotional stress, by infections or physical trauma, in particular. As the key mediator is bradykinin, this angioedema does not respond to the usual treatments of mast cell-mediated angioedema (antihistamines, corticosteroids, adrenaline), which is much more frequent. Therapeutic management of hereditary angioedema first consists in treating severe attacks with a selective B2 bradykinin receptor antagonist or a C1 inhibitor concentrate. The latter or an attenuated androgen (danazol) can be used for short-term prophylaxis. Therapeutic solutions conventionally proposed for long-term prophylaxis (danazol, antifibrinolytics [tranexamic acid], C1 inhibitor concentrate) vary in efficacy and/or pose problems of safety or ease of use. Kallikrein inhibitors (subcutaneous lanadelumab, oral berotralstat) recently made available as disease-modifying treatment constitute an important advance in long-term prophylaxis of hereditary angioedema attacks. The advent of these new drugs is accompanied by a new ambition for patients: optimize control of the disease and thereby minimize its impact on quality of life.

French national diagnostic and care protocol for Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis with a particular tropism for the coronary arteries. KD mainly affects male children between 6 months and 5 years of age. The diagnosis is clinical, based on the international American Heart Association criteria. It should be systematically considered in children with a fever, either of 5 days or more, or of 3 days if all other criteria are present. It is important to note that most children present with marked irritability and may have digestive signs. Although the biological inflammatory response is not specific, it is of great value for the diagnosis. Because of the difficulty of recognising incomplete or atypical forms of KD, and the need for urgent treatment, the child should be referred to a paediatric hospital as soon as the diagnosis is suspected. In the event of signs of heart failure (pallor, tachycardia, polypnea, sweating, hepatomegaly, unstable blood pressure), medical transfer to an intensive care unit (ICU) is essential. The standard treatment is an infusion of IVIG combined with aspirin (before 10 days of fever, and for a minimum of 6 weeks), which reduces the risk of coronary aneurysms. In case of coronary involvement, antiplatelet therapy can be maintained for life. In case of a giant aneurysm, anticoagulant treatment is added to the antiplatelet agent. The prognosis of KD is generally good and most children recover without sequelae. The prognosis in children with initial coronary involvement depends on the progression of the cardiac anomalies, which are monitored during careful specialised cardiological follow-up.

Efficacy of rituximab in primary Sjogren's syndrome with peripheral nervous system involvement: results from the AIR registry.

OBJECTIVE: To evaluate rituximab (RTX) in primary Sjögren's syndrome (pSS) with peripheral nervous system (PNS) involvement. METHODS: Patients with pSS and PNS involvement who were included in the French AIR registry were analysed. RESULTS: 17 patients (age 60 years (44-78 years); 14 were female) were analysed. Neurological improvement was noted in 11 patients (65%) at 3 months. Rankin scale decreased from 3 (1-5) to 2 (1-5), 2 (1-5) and 2 (1-6) after 3, 6 and 9 months (p=0.02). European Sjögren's Syndrome Disease Activity Index decreased from 18 (10-44) to 11 (5-20), 11 (5-29) and 12 (5-30) after 3, 6 and 9 months (p<0.05). RTX was effective in neurological involvement in 9/10 patients with vasculitis or cryoglobulinaemia (90%) (group 1) at 3 months and in 2/7 cases (29%) without cryoglobulinaemia and vasculitis (p=0.03). Rankin and European Sjögren's Syndrome Disease Activity Index scales decreased significantly in group 1. CONCLUSION: RTX seems effective in cryoglobulinaemia or vasculitis-related PNS involvement in pSS.

Why are people still dying of drug-susceptible TB in Paris in the 21st century?

BACKGROUND: Although the burden of TB is lower in France than in low-income countries, patients continue to die from TB in Paris. Our goal was to describe TB-related deaths and to identify associated risk factors.METHODS: We conducted a retrospective cohort study in two hospitals in Paris between 2013 and 2018. All patients with drug-susceptible TB were included and followed until end of treatment. The primary outcome was death. We performed univariate and multivariate analysis using Cox proportional hazard model.RESULTS: Of the 523 patients included, 362 were men (median age 37 years), of whom 24 patients died (4.5%). The final survival model concluded that age (HR 1.1 for each additional year), not living in one´s own accommodation (HR 5.9), being born in France (HR 8.0), being alcoholic (HR 4.2), having a history of cancer (HR 7.1) or meningeal or miliary TB (HR 8.2) were associated with a higher risk of death.CONCLUSION: The rate of TB-associated death is unacceptably high for a curable disease. To note, patients born in France were much more at risk of death than immigrants. We believe raising awareness among healthcare professionals is a potentially easy and efficient lever for improving care.

Syndrome de Cogan.

"Typical" Cogan's syndrome is defined as a non-syphilitic interstitial keratitis associated with audio-vestibular resembling Ménière's disease with a 2-year maximum delay between these 2 organ impairment. Cogan syndrome is classified as "atypical" in the absence of interstitial keratitis and the presence of other inflammatory eye manifestations, an audio-vestibular impairment different from typical Menière-like disease, or a delay longer than 2 years between eye and audio-vestibular manifestations. Constitutional signs and large-vessel vasculitis is also possible, mostly affecting the thoracic aorta. The presence of acute-phase reactants is common, but no specific laboratory tests are available. The prognosis is dominated by the audio-vestibular impairment and in particular the risk of deafness, while other complications especially vascular complications being rare. Treatment with glucocorticoids is usually necessary and the combination to other immunosuppressive therapies or biological-targeted drugs needs to be determined.

[Behçet's-like syndrome and other dysimmunitary manifestations related to myelodysplastic syndromes with trisomy 8]. / Syndrome de pseudo-Behçet et autres manifestations dysimmunitaires associées aux syndromes myélodysplasiques avec trisomie 8.

Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies which are also characterised by immune dysregulation. The impaired immune response is mainly due to T lymphocytes (CD8 and T regulatory cells) with increased cell apoptosis. MDS could be associated in some cases with various clinical dysimmune features; however, only MDS with trisomy 8 is correlated with particular clinical phenotype. The latter is mainly Behçet's-like disease which includes orogenital aphtosis, skin features and severe ulcerative digestive disease of ileocaecal distribution. Other clinical manifestations, such as arthritis or neutrophilic dermatosis, have been also described in MDS patients with trisomy 8. The dysimmune manifestations, and among them the Behçet's-like disease, do not impact the overall survival or the risk of progression to acute myeloid leukemia. Immunosuppressive and immunomodulatory therapies, and among them TNF-α inhibitors, are usually ineffective to control the dysimmune manifestations. Targeting the underlying clonal disease with specific therapies, such as azacitidine, seems to be the best strategy to control these disorders, even in MDS patients with low-risk disease.

[Periodic fever syndrome associated with mutations in the TNF type 1 receptor gene: A differential diagnosis of familial Mediterranean fever that should not be overlooked in patients of Mediterranean origin]. / Le syndrome de fièvre prolongée associée aux mutations du gène du récepteur au TNF de type 1 : un diagnostic différentiel de la fièvre méditerranéenne familiale à ne pas méconnaître chez les patients d'origine méditerranéenne.

INTRODUCTION: Tumor Necrosis Factor Type 1 Receptor Associated Periodic Syndrome (TRAPS) is a rare autosomal dominant autosomal autoinflammatory disease associated with mutations in the TNF type 1 receptor gene (TNFRSF1A). It is characterized by relatively long recurrent febrile seizures with an average duration of 7 days accompanied by arthralgia, myalgia, and usually a rash. In a patient of Mediterranean origin with recurrent fever, familial Mediterranean fever is the first diagnosis to be suspected by argument of frequency. METHODS: A retrospective observational study was conducted on patients from Mediterranean origin followed for TRAPS and included in the "Juvenile Inflammatory Rheumatism" (JIR) observational cohort in the national French autoinflammatory center. The age of onset of symptoms, age of diagnosis, number of years of wandering and treatments received were collected for each index case. RESULTS: Nine patients from 6 families of Mediterranean origin were included. A molecular diagnosis confirmed TRAPS in all patients. The median age at diagnosis was 26 years, the mean number of years of wandering was 17 years. The diagnosis of FMF was made first in all patients. AA amyloidosis revealed TRAPS in 2 patients. Colchicine was started without any efficacy in all cases. Five patients were treated with interleukin-1 inhibitory biotherapy with 100% efficacy. CONCLUSION: In a patient of Mediterranean origin presenting with recurrent febrile abdominal pain of AA amyloidosis, the first diagnosis to be suspected is FMF. Long relapses, dominant transmission, a non-Mediterranean relative, and the ineffectiveness of colchicine should evoke TRAPS.