Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Multiple cranial neuropathies following zoledronic acid infusion: a relationship? Clinical features and pathogenic discussion concerning a case.

The widespread use of bisphosphonates, especially in osteoporosis, has led to a greater number of reports of side effects. We describe for the first time a case of a 75-year-old female patient with a history of indolent sicca syndrome who developed multiple cranial neuropathies after zoledronic acid infusion. In this case, the elimination of the main causes of multiple cranial neuropathies, the chronology with zoledronic acid infusion, the absence of secondary complications of the Sjögren's syndrome, reported cases of similar peripheral nerve injuries with interferon infusions, the spontaneous remission of this multiple cranial neuropathy in parallel with the induced flu-like syndrome, argue for its iatrogenic origin, probably by a great release of inflammatory mediators in this particular background of primary Sjögren's syndrome.

Efficacy of anakinra for various types of crystal-induced arthritis in complex hospitalized patients: a case series and review of the literature.

BACKGROUND: There are few data on anakinra use after failure of conventional medications for crystal-induced peripheral arthritis and/or crowned dens syndrome among complex hospitalized patients. METHODS: We retrospectively analyzed the outcome of six patients affected with subacute crystal-induced arthritis who had received anakinra in second or third line therapy, including three patients with crowned dens syndrome and three others with gouty arthritis. Patients' comorbidities, reasons for anakinra use and associated drugs, and outcomes were recorded. RESULTS: All patients presented with elevated inflammatory syndrome, systemic symptoms with poly/oligoarthritis. Except for absolute contraindications, all patients were previously treated with full or decreased dose of NSAID, colchicine, and/or glucocorticoids, with unsatisfactory response. All three gouty patients exhibited complete responses in all acute involvements under anakinra within 3 to 5 days, including one of them who needed the reintroduction of colchicine treatment that was previously unsuccessful. Crowned dens syndrome patients, including two with pseudogout and one with subacute hydroxyapatite deposition disease, needed 9 to 11 days to achieve complete response. Tolerance to anakinra was good. CONCLUSION: In case series of complex hospitalized patients, anakinra showed good activity in crowned dens syndrome and associated crystal-induced peripheral arthritis, with longer treatment duration than in gouty arthritis.

[Survey of the management of moderate to severe active Graves' orbitopathy at 28 metropolitan centers of excellence in France]. / État des lieux de la prise en charge de l'orbitopathie dysthyroidïenne modérée à sévère active en France à partir de 28 centres experts métropolitains.

INTRODUCTION: This study investigates the management of Graves'orbitopathy (GO) in France, at 26 university medical centers (CHU) as well as the Rothschild Foundation and the Quinze-Vingts national eye hospital in Paris. METHODS: The 28 metropolitan university medical centers were contacted by telephone or e-mail. The authors devised a 5-item questionnaire that explored the scheduling of multidisciplinary meetings, the existence or lack of a dedicated Graves' consultation service, the place of hospitalization, and first- and second-line treatments. RESULTS: Eighty-nine percent of hospital departments had a dedicated service for patients with GO, with 36% organizing multidisciplinary meetings. Intravenous corticosteroid therapy is still used as first-line treatment, while mycophenolate is used much less (14.3%), despite the new EUGOGO (European Group on Graves' orbitopathy) 2021 recommendations. For second-line treatment, tocilizumab is most commonly used (64%). Teprotumumab is available in France only on a compassionate basis, and its use is limited (18%). CONCLUSION: This study highlights the variability in practices and the importance of a multidisciplinary approach, while calling for national standardization of practices. Despite disparities in the application of recommendations, the emergence of second-line treatments such as tocilizumab and teprotumumab indicates a steady evolution in therapeutic options, although obstacles in terms of accessibility and cost remain.

Melanoma-associated retinopathy treated with ipilimumab therapy.

Melanoma-associated retinopathy (MAR) is a rare autoimmune syndrome in patients with melanoma characterized by visual disorders. MAR is induced by the degeneration of bipolar cells of the retina and the presence of serum autoantibodies against retina proteins. Ipilimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 antibody, improves survival in previously treated patients with metastatic melanoma, but is responsible for a spectrum of immune-related adverse events. Administration of ipilimumab to patients with autoimmune diseases (such as MAR or vitiligo) is actually not recommended. We report a patient presenting with MAR occurring during a melanoma relapse. Surgery and chemotherapy had no effect on visual acuity and melanoma increased. In the absence of alternative antitumoral treatment, we focused on the vital prognosis and treated the patient with ipilimumab. Two years after the treatment the patient is free from new metastasis but has presented with exacerbation of vitiligo and MAR. In the very rare case of melanoma with autoimmune disease without a therapy option, ipilimumab could be discussed, taking into account the fact that it can be effective on tumor burden but can also increase autoimmunity.

Tocilizumab and COVID-19: Timing of administration assessment.

Recent evidence showed greater efficacy of tocilizumab (TCZ) in the subgroups of COVID-19 patients who presented with symptoms for less than 7 days and in those only receiving oxygen. We retrospectively analyzed a compassionate use cohort to determine the best timing for TCZ injection. We showed no association between the timing of injection after symptom onset and the efficacy of TCZ on mortality. We then investigated whether the oxygen level at the time of TCZ injection impacted the mortality rate. Our study finally suggested that TCZ could be less effective when oxygen requirement is >11L/min and we hypothesized that earlier administration could be associated with better outcome. However, randomized clinical trials are required to confirm this hypothesis.

Specific Follicular Helper T Cell Signature in Takayasu Arteritis.

OBJECTIVE: Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS: Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS: Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/ß TCR repertoire. CONCLUSION: We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.

Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients.

OBJECTIVE: To characterise major infectious complications and analyse potential risk factors in patients with Wegener granulomatosis (WG). METHODS: Data from 113 patients with WG (69 male) followed at least once between January 1984 and March 2006 in our internal medicine department, were analysed retrospectively. RESULTS: A total of 35 patients (mean (SD) age at WG diagnosis: 50.2 (13.05) years) developed 53 major infections. Infections were: bronchopneumonias (n = 19), herpes zoster recurrences (n = 9), cellulitis (n = 4), prostatitis (n = 4), spondylodiscitis and septic arthritis (n = 3), digestive tract infections (n = 2), Enterococcus faecalis or Staphylococcus aureus septicaemia (n = 2), viral hepatitis B reactivations (n = 2), post transfusion HIV infection with fatal cerebral toxoplasmosis, oesophageal candidiasis, disseminated herpes simplex and cytomegalovirus infection, cytomegalovirus retinitis, herpetic keratitis, herpetic stomatitis, Serratia sp. node suppuration and fever resolving under broad spectrum antibiotics (n = 1 each). Half of the major infectious episodes occurred within 3 years after WG diagnosis. Eight (7%) patients died, with two (2%) infection-related deaths. Patients diagnosed with WG before 1996 had a significantly higher rate of infection than those diagnosed later (48% vs 24%, p = 0.02). Cyclophosphamide and corticosteroids were independently associated with significantly higher risk of major infection (p<0.05 and <0.001, respectively). All patients treated since 1993 received antipneumocystosis prophylaxis. CONCLUSION: Cyclophosphamide and corticosteroids were associated with higher risk of infection. Despite systematic cotrimoxazole prophylaxis, major infections, mostly bronchopneumonias and herpes zoster recurrences, were still common in the course of WG.

Factors influencing influenza-vaccination in adults under immunosuppressive therapy for a systemic inflammatory disease.

OBJECTIVE: The aim of this study was to evaluate flu vaccination rates and influencing factors in patients with systemic inflammatory diseases. METHODS: All patients presenting with a systemic inflammatory disease and taking immunosuppressants, who were hospitalized or had consulted in our internal medicine department between January 2 and 31, 2006, were included in the study. The information concerning flu vaccination was collected with a standardized form. RESULTS: One hundred and thirty-seven patients (mean age 53.1+/-17.6years; 40 [29%] male patients) were included: 39 (28%) had received flu vaccination in 2005 including 14 (16.7%) of the 84 patients with no other indication for flu vaccination than IS-induced immunodepression and 25 (47.2%) of the 53 patients with other flu vaccination indication(s) (p<0.001). The most frequent reasons for non-vaccination were: absence of physician recommendation (58%), fear of adverse effects (35%) and concern on vaccine clinical effectiveness (5%). The vaccination rate was significantly higher (49%) among patients who remembered having received a voucher from the French National Health Insurance Agency versus 18% among those who did not (OR=4.2 [95%CI, 1.92-9.19] p<0.05). This correlation remained significant after adjustment for confounding factors in a logistic regression model. CONCLUSION: Influenza-vaccination coverage is low in patients receiving immunosuppressive therapy for systemic inflammatory diseases. We have to increase the influenza-vaccination coverage in this population.

Survival and prognosis factors in systemic sclerosis: data of a French multicenter cohort, systematic review, and meta-analysis of the literature.

BACKGROUND: Data on survival and prognosis factors in incident cohorts are scarce in systemic sclerosis (SStc). To describe survival, standardized mortality ratio (SMR), and prognosis factors in systemic sclerosis (SSc), we analyzed a multicenter French cohort of incident patients and performed a systematic review of the literature and meta-analysis. METHODS: A multicenter, French cohort study was conducted between January 1, 2000, and December 31, 2013. Patients were followed-up until July 1, 2016. A systematic review of the literature was carried out in MEDLINE and EMBASE up to July 2017. Meta-analysis was performed using all available data on SMR and hazard ratios of prognosis factors. RESULTS: A total of 625 patients (493 females, 446 lcSSc) were included. During the study period, 104 deaths (16.6%) were recorded and 133 patients were lost to follow-up. Overall survival rates at 1, 3, 5, and 10 years from diagnosis were 98.0%, 92.5%, 85.9%, and 71.7% respectively in the French cohort. Overall SMR was 5.73 (95% CI 4.68-6.94). Age at diagnosis > 60 years, diffuse cutaneous SSc, scleroderma renal crisis, dyspnea, 6-min walking distance (6MWD), forced vital capacity < 70%, diffusing capacity of the lungs for carbon monoxide < 70%, pulmonary hypertension (PH), telangiectasia, valvular disease, malignancy, anemia, and CRP > 8 mg/l were associated with a poorer survival after adjustment. Eighteen studies (11,719 patients) were included in the SMR meta-analysis and 36 studies (26,187 patients) in the prognosis factor analysis. Pooled SMR was 3.45 (95%CI 3.03-3.94). Age at disease onset, male sex, African origin, diffuse cutaneous SSc, anti-Scl70 antibodies, cardiac and renal involvement, interstitial lung disease, PH, and malignancy were significantly associated with a worse prognosis. Anti-centromere antibodies were associated with a better survival. CONCLUSIONS: Overall, our study highlights a high mortality rate in SSc patients and confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.

Concomitant association of giant cell arteritis and malignancy: a multicenter retrospective case-control study.

INTRODUCTION: Some studies suggest that there is an increased risk of malignancies in giant cell arteritis (GCA). We aimed to describe the clinical characteristics and outcomes of GCA patients with concomitant malignancy and compare them to a GCA control group. METHOD: Patients with a diagnosis of GCA and malignancy and with a maximal delay of 12 months between both diagnoses were retrospectively included in this study and compared to a control group of age-matched (3:1) patients from a multicenter cohort of GCA patients. RESULTS: Forty-nine observations were collected (median age 76 years). Malignancies comprised 33 (67%) solid neoplasms and 16 (33%) clonal hematologic disorders. No over-representation of a particular type of malignancy was observed. Diagnosis of GCA and malignancy was synchronous in 7 (14%) patients, while malignancy succeeded GCA in 29 (59%) patients. Malignancy was fortuitously diagnosed based on abnormalities observed in laboratory tests in 26 patients, based on imaging in 14 patients, and based on symptoms or clinical examination in the nine remaining patients. Two patients had a concomitant relapse of both conditions. When compared to the control group, patients with concomitant GCA and malignancy were more frequently male (p < 0.001), with an altered general state (p < 0.001), and polymyalgia rheumatica (p < 0.01). CONCLUSIONS: This study does not indicate an over-representation of any particular type of malignancy in GCA patients. Initial follow-up dictated by vasculitis may have led to an early identification of malignancy. Nevertheless, GCA male patients with an altered general state and polymyalgia rheumatica might more frequently show concomitant malignancies.

[Prevalence of macrovascular arterial involvement of the 4 limbs in systemic sclerosis: About a case series of 14 patients]. / Prévalence de l'atteinte artérielle macrovasculaire des 4 membres dans la sclérodermie systémique : à propos de 14 patients.

INTRODUCTION: Trophic disorders of the extremities are a common complication of systemic sclerosis (SSc), mainly related to microvascular damage. However, SSc seems to be a risk factor for premature athero-thrombotic disease that can affect the peripheral arteries, participate in the occurrence of trophic disorders and promote the occurrence of infectious complications. The objective of this study was to assess the prevalence of arterial disease of the limbs in SSc patients. METHODS: Consecutive inclusions in the context of a multidisciplinary consultation centered on disability of the hand with collection of clinical data [cardiovascular risk factors (CVRF), history of trophic disorders of ischemic origin, peripheral pulse palpation, Allen maneuver the upper (UL) and lower limbs (LL)], and hemodynamic data (flow recorded by Doppler in radial, ulnar, anterior and posterior tibial arteries, and measurement of systolic indices ankles). RESULTS: Fourteen patients were included (11 right-handers, 2 left-handers, 1 ambidextrous). The sex-ratio male/female was 0.27 and the average age of 58.1±10.4 years. The main CVRF were age and smoking. In the UL, 42.8% of patients had a history of trophic disorders, Allen maneuver was abnormal for 35.7% of the superficial palmar arch, 42.9% of ulnar pulse were not perceived and there was no recordable flow in 25% of ulnar artery. In the LL, 14.3% of patients had already presented trophic disorders toes, Allen maneuver was abnormal for 15.4% of the posterior tibial artery, 25.6% of posterior tibial pulse were not perceived and flow of 15.4% of posterior tibial arteries was pathological. CONCLUSION: The distal macrovascular disease preferentially affecting the ulnar and posterior tibial arteries with a high frequency to the UL and two times less at LL. The pathophysiology is unclear but it could be a proper manifestation of SSc. It seems necessary that SSc patients have a strict balance of their CVRF and a screening of macrovascular arterial lesions. There is also the question of the place of an anti-atherosclerotic therapy in these patients.

Concordance of Time-of-Flight MRA and Digital Subtraction Angiography in Adult Primary Central Nervous System Vasculitis.

BACKGROUND AND PURPOSE: 3D-TOF-MRA and DSA are 2 available tools to demonstrate neurovascular involvement in primary central nervous system vasculitis. We aimed to compare the diagnostic concordance of vessel imaging using 3D-TOF-MRA and DSA in patients with primary central nervous system vasculitis. MATERIALS AND METHODS: We retrospectively identified all patients included in the French primary central nervous system vasculitis cohort of 85 patients who underwent, at baseline, both intracranial 3D-TOF-MRA and DSA in an interval of no more than 2 weeks and before treatment initiation. Two neuroradiologists independently reviewed all 3D-TOF-MRA and DSA imaging. Brain vasculature was divided into 25 arterial segments. Concordance between 3D-TOF-MRA and DSA for the identification of arterial stenosis was assessed by the Cohen κ Index. RESULTS: Thirty-one patients met the inclusion criteria, including 20 imaged with a 1.5T MR unit and 11 with a 3T MR unit. Among the 25 patients (81%) with abnormal DSA findings, 24 demonstrated abnormal 3D-TOF-MRA findings, whereas all 6 remaining patients with normal DSA findings had normal 3D-TOF-MRA findings. In the per-segment analysis, concordance between 1.5T 3D-TOF-MRA and DSA was 0.82 (95% CI, 0.75-0.93), and between 3T 3D-TOF-MRA and DSA, it was 0.87 (95% CI, 0.78-0.91). CONCLUSIONS: 3D-TOF-MRA shows a high concordance with DSA in diagnostic performance when analyzing brain vasculature in patients with primary central nervous system vasculitis. In patients with negative 3T 3D-TOF-MRA findings, the added diagnostic value of DSA is limited.

Pulmonary embolism and deep jugular venous thrombosis resulting from compression by a lipoma.

Lipomas usually extend in subcutaneous tissues and rarely may be compressive. We report a case of neck lipoma resulting in jugular vein thrombosis and pulmonary embolism in a patient treated by clozapine. Clozpine may be considered an associated risk factor for thrombosis. This case suggests that performing a regional evaluation may be particularly important when thrombophlebitis occurs.

[Temporomandibular disorders and Ehlers-Danlos syndrome, hypermobility type: A case-control study]. / Dysfonction de l'appareil manducateur et syndrome d'Ehlers-Danlos de type hypermobile : étude cas-témoin.

INTRODUCTION: The Ehlers-Danlos syndrome, hypermobility type (EDS-HT) is a rare genetic disease. Diagnosis is based on a combination of clinical criteria described in the classification of Villefranche. Diagnosis is difficult to make because of the lack of specific clinical signs and the absence of genetic testing. The EDS-TH manifests itself manly by musculoskeletal pain and joint hypermobility. Temporomandibular disorders (TMD) are also reported. Our aim was to objectify the presence and to qualify the type of TMD associated with the EDS-HT in order to propose an additional diagnostic argument. MATERIAL AND METHODS: A prospective, monocenter case-control study, comparing a cohort of patients suffering from EDS-HT to a paired control group of healthy volunteers has been conducted. Clinical examination was standardized, including a general questioning, an oral examination and a temporomandibular joint examination following the TMD/RDC (temporomandibular disorders/research diagnostic criteria). RESULTS: Fourteen EDS-HT patients and 58 control patients were examined. The prevalence of TMDs (n=13; 92.9% vs. n=4; 6.9%; P=10(-11)) was significantly higher in the EDS-HT group. TMDs occurring in the EDS-HT group were complex, combining several mechanisms in contrast to the control group, where only one mechanism was found in all the patients (n=13; 92.9% vs. n=0; 0.0%). DISCUSSION: TMDs are strongly associated with RDS-HT. TMDs could therefore be used in the diagnosis of this disease.

[Efficiency and good tolerance of rituximab for idiopathic thrombocytopenic purpura revealing a 22q11 deletion syndrome]. / Efficacité et bonne tolérance du rituximab sur un purpura thrombopénique immunologique chronique révélant un syndrome de délétion 22q11.

INTRODUCTION: 22q11 deletion is a common genetic disorder which associates a polymalformative syndrome to dysimmune features. Autoimmunity and immune deficiency manifestations are often associated, resulting in a therapeutic challenge for this disease. CASE REPORT: We report a 28-year-old patient who presented with hemorrhagic manifestations leading to the diagnosis of severe thrombocytopenia (15,000/mm3), of both central and peripheral origin. Patient history, cardio-facial malformative syndrome, hypoparathyroidism and partial immune deficiency led to the molecular diagnosis of 22q11 deletion syndrome. After failure of polyvalent immunoglobulin infusions, rituximab alone allowed the increase of platelets to their usual level of 100-120,000/mm3 within 4 weeks and a complete clinical remission of the hemorrhagic syndrome, without any infectious complication after a 4-year follow-up. CONCLUSION: Rituximab may be an alternative to corticosteroid for the treatment of auto-immune manifestations associated with minor forms of 22q11 deletion syndrome without significant worsening of the immune deficiency.

Does the route of immunoglobin replacement therapy impact quality of life and satisfaction in patients with primary immunodeficiency? Insights from the French cohort "Visages".

BACKGROUND: IgG replacement therapy (IgRT) in primary immunodeficiencies (PID) is a lifelong treatment which may be administered intravenously (IVIg) or subcutaneously (SCIg), at hospital or at home. The objective of the VISAGE study was to investigate if route and/or place for IgRT impact patients' satisfaction regarding IgRT and quality of life (QoL) in real-life conditions. METHODS: The study enrolled PID patients at least 15 years old receiving IgRT for at least 3 months. Satisfaction and QoL were evaluated at enrollment and over a 12-month follow-up period by Life Quality Index (LQI) which measures 3 dimensions of satisfaction: treatment interference, therapy related problems and therapy settings (factors I, II and III) and SF-36 v2 questionnaire. RESULTS: The study included 116 PID patients (mean age 42 ± 18 years, 44 % males, 58 % with scholar or professional occupation) receiving IgRT for a mean of 8.5 ± 8.4 years. At enrollment they were receiving either home-based SCIg (51 %), hospital-based IVIg (40 %) or home-based IVIg (9 %). Patients exhibited a high degree of satisfaction regarding IgRT whatever the route and place for administration. LQI factor I was higher for home-based SCIg (86 ± 2) than for hospital-based IVIg (81 ± 3) and home-based IVIg (73 ± 5; p = 0.02 versus home-based SCIg); no difference was found for LQI factor II; LQI factor III was higher for home-based SCIg (92 ± 2) than for hospital-based IVIg (87 ± 5) and hospital-based IVIg (82 ± 3; p = 0.005 versus home-based SCIg). By contrast, every dimension of QoL was impaired. Over the follow-up period, 10 patients switched from hospital-based IVIg to home-based SCIg and improved LQI factor I (p = 0.004) and factor III (p = 0.02), while no change was noticed in LQI factors II and QoL. Meanwhile, no change in satisfaction or QoL was found in patients with stable route of IgRT. When asked on their preferred place of treatment all but one patient with home-based treatment would choose to be treated at home and 29 % of patients treated at hospital would prefer home-based IgRT. CONCLUSION: PID patients expressed a high degree of satisfaction regarding IgRT, contrasting with impaired QoL. In real-life conditions awareness of patient's expectations regarding the route or place of IgRT may be associated with further improvement of satisfaction.

Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome.

OBJECTIVE: To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). METHODS: A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. RESULTS: One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. CONCLUSION: In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.

Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.

Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ±â€Š14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ±â€Š1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.