Prognostic value of automated assessment of interstitial lung disease on CT in systemic sclerosis.

OBJECTIVE: Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning-based algorithm enabling automated quantification of ILD on HRCT in patients with SSc. METHODS: We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc. RESULTS: We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73-111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004). We constructed a risk prediction model that showed good discrimination for 10-year mortality (c index 0.789). Adding the automated quantification of ILD significantly improved the model for 10-year survival prediction (P = 0.007). Its discrimination was only marginally improved, but it improved prediction of 2-year mortality (difference in time-dependent area under the curve 0.043, 95% CI 0.002, 0.084, P = 0.040). CONCLUSION: The deep-learning-based, computer-aided quantification of ILD extent on HRCT provides an effective tool for risk stratification in SSc. It might help identify patients at short-term risk of death.

Anti-PM-Scl antibodies-positive patients encompass three different groups with distinct prognoses.

OBJECTIVE: To help identify homogeneous subgroups among patients with anti-PM-scleroderma-antibodies (PM-Scl-Abs) positive auto-immune diseases regardless of diagnostic classifications. MATERIAL AND METHODS: This multicentric (four hospitals) retrospective study collected all consecutive patients (from 2011 to 2021) with positive testing for anti-PM-Scl-Abs in a context of CTD. Subgroups of patients with similar clinico-biological phenotypes were defined using unsupervised multiple correspondence analysis and hierarchical clustering analysis of the features recorded in the first year of follow-up. RESULTS: One hundred and forty-two patients with anti-PM-Scl-Abs were evaluated and 129 patients were included in the clustering analysis and divided into three clusters. Cluster 1 (n = 47) included patients with frequent skin thickening, digestive involvement and interstitial lung disease (ILD) with non-specific interstitial pneumonia (NSIP). They were more likely to develop progressive fibrosing ILD. Cluster 2 (n = 36) included patients who all featured NSIP with frequent organizing pneumonia-associated pattern and mechanic's hands. This subgroup had increased risk of relapse and ILD was characterized by a good functional outcome. Cluster 3 (n = 46) was characterized by predominant or isolated musculoskeletal involvement and frequently matched UCTD criteria. Although very frequent among anti-PM-Scl-Abs positive patients, muscle involvement was less discriminating compared with skin thickening and ILD pattern to classify patients into subgroups. CONCLUSION: Anti-PM-Scl-Abs associated auto-immune diseases are segregated into three subgroups with distinct clinical phenotype and outcomes. Skin thickening and NSIP are determinant predictors in segregation of theses populations.

Determination of four homogeneous subgroups of patients with antiphospholipid syndrome: a cluster analysis based on 509 cases.

OBJECTIVE: APS is a heterogeneous disease with different phenotypes. Using an unsupervised hierarchical cluster analysis, we aimed to determine distinct homogeneous phenotypes among APS patients. METHODS: We performed an observational, retrospective study of APS patients enrolled in the French multicentre 'APS and SLE' registry who met the Sydney classification criteria. The clustering process involved an unsupervised multiple correspondence analysis followed by a hierarchical ascendant clustering analysis; it used 27 variables selected to cover a broad range of APS clinical and laboratory manifestations. RESULTS: These analyses included 509 patients, mainly women (77.8%). Mean (s.d.) age at APS diagnosis was 36.2 (14.6) years, and mean follow-up since diagnosis 10.3 (8.5) years. This hierarchical classification cluster analysis yielded four homogeneous groups of patients: cluster 1, mostly with venous thromboembolism without any associated autoimmune disease; cluster 2, older, lowest proportion of women, history of arterial events, and/or with migraines, arterial hypertension, diabetes mellitus, or dyslipidaemia; cluster 3, younger, highest proportion of women, associated SLE or other autoimmune diseases, and a history of venous thromboembolism or pregnancy morbidity; and cluster 4, mainly with a history of catastrophic antiphospholipid syndrome, aPL-associated nephropathy, and pregnancy morbidity, with frequent triple positivity and more deaths (16.7%). CONCLUSIONS: Our study applied an unsupervised clustering method to distinguish four homogeneous APS patient subgroups that were predominantly venous; arterial; associated with SLE or another autoimmune disease; and arterial microthrombotic. Heterogeneous pathophysiological mechanisms may explain these findings.

Induction failure in granulomatosis with polyangiitis: a nationwide case-control study of risk factors and outcomes.

OBJECTIVE: To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy. METHODS: We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment. RESULTS: We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone. CONCLUSION: In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.

Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges.

BACKGROUND: Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. METHODS: We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). RESULTS: No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (-15.9%; 95% CI, -29.4 to -2.5) compared with the PLEX not recommended group (-4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. CONCLUSIONS: PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.

IgA vasculitis in patients with inflammatory bowel disease: new insights into the role of TNF-α blockers.

OBJECTIVE: The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. METHODS: We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. RESULTS: Forty-three cases were included. IBD [mainly Crohn's disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4-15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19-56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). CONCLUSIONS: This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse.

Efficacy and safety of treatments in cutaneous polyarteritis nodosa: A French observational retrospective study.

BACKGROUND: Cutaneous polyarteritis nodosa is a form of medium-sized vessel vasculitis. Despite a disabling and prolonged course, data on treatment efficacy and safety remain scarce. OBJECTIVES: We aimed to describe treatment efficacy and safety in patients with cutaneous polyarteritis nodosa. METHODS: This multicenter retrospective, observational study, recorded clinical and biologic data together with treatments received. The primary outcome was the rate of complete response at month 3. Secondary outcomes assessed drug survival and safety. RESULTS: We included 68 patients who received a median of 2 therapeutic lines (interquartile range, 1-3). Overall, complete response was achieved in 13 of 42 (31%) patients with colchicine, 4 of 17 (23%) with dapsone, 11 of 25 (44%) with glucocorticoids (GCs) alone, 1 of 9 (11%) with nonsteroidal anti-inflammatory drugs, 11 of 13 (84%) with GCs+azathioprine, and 7 of 15 (47%) with GCs+methotrexate. GCs+azathioprine had the best drug survival (median duration, 29.5 months; interquartile range, 19.5-36.0). Response at month 3 was decreased with peripheral neurologic involvement (odds ratio, 0.19; 95% confidence interval, 0.03-0.81; P = .04). Overall, the rate of treatment-related adverse events was 18%, which led to the discontinuation of treatment in 7% of patients. LIMITATION: Retrospective study. CONCLUSION: Colchicine seems to confer good benefit-risk balance in cutaneous polyarteritis nodosa without peripheral sensory neuropathy. GCs+azathioprine seem the best treatment in the event of relapse.

P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4/heme-dependent manner.

Hemolytic diseases are frequently linked to multiorgan failure subsequent to vascular damage. Deciphering the mechanisms leading to organ injury upon hemolytic event could bring out therapeutic approaches. Complement system activation occurs in hemolytic disorders, such as sickle cell disease, but the pathological relevance and the acquisition of a complement-activating phenotype during hemolysis remain unclear. Here we found that intravascular hemolysis, induced by injection of phenylhydrazine, resulted in increased alanine aminotransferase plasma levels and NGAL expression. This liver damage was at least in part complement-dependent, since it was attenuated in complement C3-/- mice and by injection of C5-blocking antibody. We evidenced C3 activation fragments' deposits on liver endothelium in mice with intravascular hemolysis or injected with heme as well as on cultured human endothelial cells (EC) exposed to heme. This process was mediated by TLR4 signaling, as revealed by pharmacological blockade and TLR4 deficiency in mice. Mechanistically, TLR4-dependent surface expression of P-selectin triggered an unconventional mechanism of complement activation by noncovalent anchoring of C3 activation fragments, including the typical fluid-phase C3(H2O), measured by surface plasmon resonance and flow cytometry. P-selectin blockade by an antibody prevented complement deposits and attenuated the liver stress response, measured by NGAL expression, in the hemolytic mice. In conclusion, these results revealed the critical impact of the triad TLR4/P-selectin/complement in the liver damage and its relevance for hemolytic diseases. We anticipate that blockade of TLR4, P-selectin, or the complement system could prevent liver injury in hemolytic diseases like sickle cell disease.

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

BACKGROUND: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters. METHODS: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology. RESULTS: Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36-0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group. CONCLUSION: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.

A French cohort of patients with giant cell arteritis: glucocorticoid treatment and its associated side effects.

OBJECTIVES: Giant cell arteritis (GCA) is the most common primary large-vessel vasculitis. Glucocorticoids (GC) therapy remains the standard of care for GCA despite frequent side effects (SEs). However, treatment modality changes, prophylactic treatment of osteoporosis, or vaccinations might have decreased the frequency of GC-related SEs. This study aims to describe GCA treatment and GC-related SEs in a recent cohort. METHODS: Patients with a diagnosis of GCA between May 2009 and March 2018 were included in this multicentric retrospective study. Characteristics of patients, treatment modalities and GC-related SEs were collected and analysed. Risk factors associated with the occurrence of SE were studied. RESULTS: We analysed the files from 206 patients (153 women, 53 men; median age 74 years). Median follow-up was 34 months. Patients received GC for a median of 25 months, starting at 0.7 mg/kg/day, with tapering to 5 mg/day after 11 months follow-up. Flares occurred in 83/201 (41%) patients. Among the 132 patients who stopped GC, 29 (22%) experienced a relapse. SEs occurred in 129 (64%) patients: bone fractures and infections in 13% each and hypertension onset in 9%. Age >75 years, treatment duration >2 years, past medical history of diabetes were risk factors associated with GC-related SEs. CONCLUSIONS: Flares occur in 41% of patients during GC withdrawal. As much as 64% of patients had treatment related SEs. An age> 75 year and a past medical history of diabetes were predictive of SEs during follow-up.

Acute paraplegia due to schistosomiasis: an uncommon cause in developed countries.

We present a case of a young African migrant from Guinea-Conakry presented to a French emergency department with burning pain in both feet for 2 days. The symptoms progressed to limb paraparesis with sphincter disorders. A magnetic resonance imaging (MRI) scan showed a hyperintense spinal cord lesion without contrast enhancement extending from the T6 vertebrae to the conus medullaris. Cerebrospinal fluid exam (CFE) showed an isolated hyperproteinorachia (0.61 g/l). Schistosomiasiss serology was positive and a rectal biopsy showed a schistosoma egg surrounded by an inflammatory reaction with granulomatosis. After steroid and antihelminthic therapy, accompanied by intensive physical therapy, the patient had an improved neurological neurological outcome.

Precipitating factors of catastrophic antiphospholipid syndrome: the role of anticoagulant treatment in a series of 112 patients.

BACKGROUND: The prevention of catastrophic antiphospholipid syndrome (CAPS), a rare complication of antiphospholipid syndrome (APS), is a major goal. OBJECTIVES: We analyzed its precipitating factors, focusing on anticoagulation immediately before CAPS episodes. METHODS: We retrospectively analyzed patients in the French multicenter APS/systemic lupus erythematosus database with at least 1 CAPS episode. Then we compared each patient with known APS before CAPS with 2 patients with non-CAPS APS matched for age, sex, center, and APS phenotype. RESULTS: We included 112 patients with CAPS (70% women; mean age, 43 ± 15 years). At least 1 standard precipitating factor of CAPS was observed for 67 patients (64%), which were mainly infections (n = 28, 27%), pregnancy (n = 23, 22%), and surgery (n = 16, 15%). Before the CAPS episode, 67 (60%) patients already had a diagnosis of APS. Of the 61 treated with anticoagulants, 32 (48%) received vitamin K antagonists (VKAs), 23 (34%) heparin, and 2 (3%) a direct oral anticoagulant. They were less likely than their matched patients with APS without CAPS to receive VKA (48% vs 66%, p = .001). Among those treated with VKA, 72% had a subtherapeutic international normalized ratio (ie, <2) versus 28% in patients with APS without CAPS (p < .001). Finally, excluding pregnant patients (n = 14) for whom we could not differentiate the effect of treatment from that of pregnancy, we were left with 47 cases, 32 (68%) of whom had recently begun a direct oral anticoagulant, planned bridging therapy, or had VKA treatment with international normalized ratio <2. CONCLUSION: These results strongly suggest that suboptimal anticoagulation management can trigger CAPS in patients with thrombotic APS.

Cutaneous Involvement in Catastrophic Antiphospholipid Syndrome in a Multicenter Cohort of 65 Patients.

Importance: Catastrophic antiphospholipid syndrome (CAPS) is a severe, rare complication of antiphospholipid syndrome (APS), but cutaneous involvement has not yet been adequately described. Objective: To describe cutaneous involvement during CAPS, its clinical and pathological features, and outcomes. Design, Setting, and Participants: This cohort study was a retrospective analysis of patients included in the French multicenter APS/systemic lupus erythematosus register (ClinicalTrials.gov: NCT02782039) by December 2020. All patients meeting the revised international classification criteria for CAPS were included, and patients with cutaneous manifestations were analyzed more specifically. Main Outcomes and Measures: Clinical and pathological data as well as course and outcome in patients with cutaneous involvement during CAPS were collected and compared with those in the register without cutaneous involvement. Results: Among 120 patients with at least 1 CAPS episode, the 65 (54%) with skin involvement (43 [66%] women; median [range] age, 31 [12-69] years) were analyzed. Catastrophic antiphospholipid syndrome was the first APS manifestation for 21 of 60 (35%) patients with available data. The main lesions were recent-onset or newly worsened livedo racemosa (n = 29, 45%), necrotic and/or ulcerated lesions (n = 27, 42%), subungual splinter hemorrhages (n = 19, 29%), apparent distal inflammatory edema (reddened and warm hands, feet, or face) (n = 15, 23%), and/or vascular purpura (n = 9, 14%). Sixteen biopsies performed during CAPS episodes were reviewed and showed microthrombi of dermal capillaries in 15 patients (94%). These lesions healed without sequelae in slightly more than 90% (58 of 64) of patients. Patients with cutaneous involvement showed a trend toward more frequent histologically proven CAPS (37% vs 24%, P = .16) than those without such involvement, while mortality did not differ significantly between the groups (respectively, 5% vs 9%, P = .47). Conclusions and Relevance: In this cohort study, half the patients with CAPS showed cutaneous involvement, with a wide spectrum of clinical presentations, including distal inflammatory edema. Skin biopsies confirmed the diagnosis in all but 1 biopsied patient.

The Clinical Spectrum and Outcome of Uveomeningitis: A Comprehensive Analysis of 110 Cases.

PURPOSE: Uveitis can be associated with meningitis (uveomeningitis) and the inflammation shared with the central nervous system. We aimed to describe the characteristics and outcome of uveomeningitis. METHODS: We retrospectively analyzed 110 consecutive adult patients with uveomeningitis. RESULTS: The main causes of uveomeningitis were Vogt-Koyanagi-Harada (31%), syphilis (16%), sarcoidosis (12%), Behçet's disease (7%), and multiple sclerosis (5%). Sixteen percent of uveomeningitis remained of undetermined origin. Compared to etiology-matched uveitis without meningitis, patients with uveomeningitis were younger, had more frequent neurological manifestations, and had more frequent abnormal cerebral magnetic resonance imaging findings. In contrast, no ocular feature upon examination was significantly associated with the presence of meningitis. Patients with uveomeningitis were more frequently treated with immunosuppressants but uveitis relapse and systemic complications did not differ between groups. CONCLUSION: Uveomeningitis is associated with a limited spectrum of diseases. Meningitis does not seem to impact ocular and extraocular outcomes. Therefore, lumbar puncture should be performed on an individual basis during the diagnostic workup of uveitis.

Presentation, Diagnosis, and Management of Subglottic and Tracheal Stenosis During Systemic Inflammatory Diseases.

BACKGROUND: Subglottic stenosis (SGS) and tracheal stenosis (TS) are characterized by a narrowing of the airways. The goal of this study was to describe the characteristics and prognosis of nontraumatic and nontumoral SGS or TS. RESEARCH QUESTION: What are the inflammatory etiologies of SGS and TS, and what are their characteristics and prognosis? STUDY DESIGN AND METHODS: This multicenter, observational retrospective study was performed in patients with SGS or TS that was neither traumatic nor tumoral. RESULTS: Eighty-one patients were included, 33 (41%) with granulomatosis with polyangiitis (GPA) and 21 (26%) with relapsing polychondritis (RP). GPA-related stenoses exhibited circumferential subglottic narrowing in 85% of cases, without calcifications. In contrast, RP-related stenoses displayed anterior involvement in 76%, in a longer distance from vocal cords (4 cm), with calcifications in 62%, and extension to bronchi in 86%. Other diagnoses included bullous dermatoses (n = 3), amyloidosis (n = 3), sarcoidosis (n = 2), and Crohn's disease (n = 2); the remaining stenoses (n = 15) were idiopathic. SGS/TS was the initial manifestation of the disease in 66% of cases, with a median interval from stenosis to disease diagnosis of 12 months (interquartile range, 0-48 months). Despite the use of glucocorticoids in 80%, combined with methotrexate in 49%, endoscopic procedures were required in 68% of patients. Relapses of stenoses occurred in 76% without any difference between causes (82% in GPA, 67% in RP, and 75% in idiopathic SGS/TS). Three patients died due to the stenosis, two of RP and one of GPA. INTERPRETATION: These data show that GPA and RP are the two main inflammatory diseases presenting with SGS/TS. GPA-related stenoses are mostly subglottic and circumferential, whereas RP-related stenoses are mostly tracheal, anterior, and calcified with a frequent extension to bronchi. Relapses of stenoses are common, and relapse rates do not differ between causes. Diagnosis and management of SGS/TS require a multidisciplinary approach.

IgA vasculitis with underlying monoclonal IgA gammopathy: innovative therapeutic approach targeting plasma cells. A case series.

OBJECTIVE: There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV. METHODS: We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT. RESULTS: Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events. CONCLUSION: This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV.

Lymphocyte Immunophenotyping and CD4/CD8 Ratio in Cerebrospinal Fluid for the Diagnosis of Sarcoidosis-related Uveitis.

Background: This study aimed to assess the diagnostic relevance of CD4/CD8 ratio in cerebrospinal fluid (CSF) for the etiological diagnosis work-up of uveitis.Methods: We consecutively included patients who were referred to our department for the diagnostic workup of intermediate and/or posterior uveitis. Etiological diagnoses were established in a blind manner regarding CD4/CD8 ratio.Results: Fifty-two patients were included. A diagnosis of ocular sarcoidosis was made in 15 (29%) patients, 21% had another determined diagnosis while 50% remained of undetermined origin. Median CD4/CD8 ratio in CSF was 4.57 (IQR 3.39-5.47) in ocular sarcoidosis, 1.74 (1.60-3.18) in uveitis due to other determined cause (P = .008), and 2.83 (2.34-3.54) in those with uveitis of undetermined origin (P = .007). CD4/CD8 ratio >3.23 was associated with a diagnosis of ocular sarcoidosis.Conclusion: Determination of CD4/CD8 ratio in CSF can be useful for diagnosis work-up since a CD4/CD8 ratio >3.23 in CSF is associated with ocular sarcoidosis.

Evaluation of the severe preeclampsia classification criterion for antiphospholipid syndrome in a study of 40 patients.

BACKGROUND: The criteria for antiphospholipid syndrome (APS) include severe preeclampsia and/or placental insufficiency leading to preterm delivery before 34 weeks of gestation, but this APS manifestation has been rarely studied. Thus, we report a series of severe preeclampsia occurred in patients with APS. METHODS: We retrospectively analysed data of women with APS (Sydney criteria) who experienced severe preeclampsia with delivery before 34 weeks' gestation between 2000 and 2017 at five French internal medicine departments and one Italian rheumatology unit. RESULTS: The 40 women had a mean age of 30.5 ± 4.6 years at their first episode of preeclampsia; 21 were nulligravid (52.5%), 12 (30%) had already been diagnosed with APS, and 21 (52.5%) had a triple-positive antiphospholipid (aPL) antibody test. Preeclampsia occurred at a median gestational age of 25.5 weeks (IQR 23-29). It was associated with HELLP in 18 cases (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), catastrophic APS in 3 (7.5%), and foetal and neonatal death in 11 and 15 cases. Overall, 14 (35%) children survived, born at a median gestational age of 31 weeks. Among other APS criteria, 16 women (40%) experienced at least one thrombosis, 17 (42.5%) an intrauterine foetal death, and 19 (47.5%) at least one episode of HELLP during follow-up (median 5 years, IQR = 2-8). None had three or more consecutive miscarriages. Notably, 12 women (30%) had systemic lupus erythematosus. CONCLUSIONS: Severe preeclampsia led to high mortality in the offspring. Almost half of these women experienced other APS features, but not three consecutive miscarriages.

Characteristics and risk factors for poor outcome in patients with systemic vasculitis involving the gastrointestinal tract.

BACKGROUND: Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype. AIMS: This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis. METHODS: Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death. RESULTS: Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29-7.34), performance status (OR 1.40, 1.05-1.87), use of morphine (OR 2.51, 0.87-7.24), abdominal guarding (OR 3.08, 1.01-9.37), ileus (OR 2.29, 0.98-5.32), melena (OR 2.74, 1.17-6.42), increased leukocytes (per G/L, OR 1.05, 1.00-1.10), low hemoglobin (per g/dL, OR 0.80, 0.71-0.91) and increased CRP (log mg/L, OR 1.21, 0.94-1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well. CONCLUSIONS: Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death.