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Aseptic abscess (AA) syndrome is a rare type of inflammatory disorder involving polymorphonuclear neutrophils (PMNs), often associated with inflammatory bowel disease (IBD). This study sought to describe the clinical characteristics and evolution of this syndrome in a large cohort. We included all patients included in the French AA syndrome register from 1999 to 2020. All patients fulfilled the criteria outlined by André et al. in 2007. Seventy-one patients were included, 37 of which were men (52.1%), of a mean age of 34.5 ± 17 years. The abscesses were located in the spleen (71.8%), lymph nodes (50.7%), skin (29.5%), liver (28.1%), lung (22.5), and rarer locations (brain, genitals, kidneys, ENT, muscles, or breasts). Of all the patients, 59% presented with an associated disease, primarily IBD (42%). They were treated with colchicine (28.1%), corticosteroids (85.9%), immunosuppressants (61.9%), and biologics (32.3%). A relapse was observed in 62% of cases, mostly in the same organ. Upon multivariate analysis, factors associated with the risk of relapse were: prescription of colchicine (HR 0.52; 95% CI [0.28-0.97]; p = 0.042), associated IBD (HR 0.57; 95% CI [0.32-0.99]; p = 0.047), and hepatic or skin abscesses at diagnosis (HR 2.14; 95% CI [1.35-3.40]; p = 0.001 and HR 1.78; 95% CI [1.07-2.93]; p = 0.024, respectively). No deaths occurred related to this disease. This large retrospective cohort study with long follow up showed that AA syndrome is a relapsing systemic disease that can evolve on its own or be the precursor of an underlying disease, such as IBD. Of all the available treatments, colchicine appeared to be protective against relapse.

Objective: An international multidisciplinary initiative, jointly supported by the American College of Rheumatology and European Alliance of Associations for Rheumatology, is underway to develop new rigorous classification criteria to identify patients with high likelihood of antiphospholipid syndrome (APS) for research purposes. The present study was undertaken to apply an evidence- and consensus-based approach to identify candidate criteria and develop a hierarchical organization of criteria within domains., Methods: During phase I, the APS classification criteria steering committee used systematic literature reviews and surveys of international APS physician scientists to generate a comprehensive list of items related to APS. In phase II, we reviewed the literature, administered surveys, formed domain subcommittees, and used Delphi exercises and nominal group technique to reduce potential APS candidate criteria. Candidate criteria were hierarchically organized into clinical and laboratory domains., Results: Phase I generated 152 candidate criteria, expanded to 261 items with the addition of subgroups and candidate criteria with potential negative weights. Using iterative item reduction techniques in phase II, we initially reduced these items to 64 potential candidate criteria organized into 10 clinical and laboratory domains. Subsequent item reduction methods resulted in 27 candidate criteria, hierarchically organized into 6 additive domains (laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic) for APS classification., Conclusion: Using data- and consensus-driven methodology, we identified 27 APS candidate criteria in 6 clinical or laboratory domains. In the next phase, the proposed candidate criteria will be used for real-world case collection and further refined, organized, and weighted to determine an aggregate score and threshold for APS classification., (© 2020, American College of Rheumatology.)

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management., (© 2020 by The American Society of Hematology.)

The increasing number of bacteria-related problems and presence of trace amounts of phosphate in treated wastewater effluents have become a growing concern in environmental research. The use of antibacterial agents and phosphate adsorbents for the treatment of wastewater effluents is of great importance. In this study, the potential applications of a synthesized polyaniline (PANI)-zirconium dioxide (ZrO 2 ) composite as an antibacterial, phosphate adsorbent and anti-corrosion material were systematically investigated. The results of an antibacterial test reveal an effective area of inhibition of 14 and 18 mm for the Escherichia coli and Staphylococcus aureus bacterial strains, respectively. The antibacterial efficiency of the PANI-ZrO 2 composite is twice that of commercial ZrO 2 . In particular, the introduction of PANI increased the specific surface area and roughness of the composite material, which was beneficial to increase the contact area with bacterial and phosphate. The experimental results demonstrated that phosphate adsorption studies using 200 mg P/L phosphate solution showed a significant phosphate removal efficiency of 64.4%, and the maximum adsorption capacity of phosphate on the solid surface of PANI-ZrO 2 is 32.4 mg P/g. Furthermore, PANI-ZrO 2 coated on iron substrate was tested for anti-corrosion studies by a natural salt spray test (7.5% NaCl), which resulted in the formation of no rust. To the best of our knowledge, no works have been reported on the synergistic effects of the PANI-ZrO 2 composite as an antibacterial, anti-corrosion, and phosphate adsorbent material. PANI-ZrO 2 composite is expected to be a promising comprehensive treatment method for water filters in the aquaculture industry and for use in water purification applications.

Objective: To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin-associated periodic syndromes (CAPS)., Methods: We retrospectively recorded the articular and muscular symptoms of patients with CAPS followed up in French hospitals. Data were presented as frequencies or the median (range), and patient groups were compared using chi-square test, Fisher's exact test, and Mann-Whitney test., Results: The study included 133 patients (33 children), 20 with familial cold autoinflammatory syndrome, 88 with Muckle-Wells syndrome, 22 with chronic infantile neurologic, cutaneous, articular syndrome, and 3 with unclassified CAPS. The median age was 35 years (range 0-78 years) at the time of the study, 1 year (range 0-41 years) at symptom onset, and 23 years (range 0-58 years) at diagnosis. The disease was sporadic in 17% of the patients. Cutaneous symptoms predominated at onset (77%), followed by articular symptoms (30%). The p.Thr348Met and p.Arg260Trp NLRP3 mutations were significantly associated with the presence and absence of articular symptoms at onset, respectively. During followup, 86% of the patients had musculoskeletal symptoms, 88% had arthralgia, and 58% had arthritis, but only 9% had joint destruction. Tendinopathies occurred in 21.5% of the patients, tender points in 16.5%, and myalgia in 33%. Only 3 patients had typical knee deformities. Radiographs were rarely obtained. Except for bone deformities, osteoarticular symptoms occurred at similar frequencies in the different CAPS phenotypes., Conclusion: Joint manifestations were frequent in all CAPS phenotypes. Bone deformities were rare. Musculoskeletal manifestations varied within given families but tended to worsen over time., (© 2015, American College of Rheumatology.)

Objective: Transforming growth factor-β is considered to play a key role in the process of fibrosis in systemic sclerosis (SSc) and in the development of regulatory T cells (Treg) and pro-inflammatory Th17 T cells producing interleukin 17 (IL-17) and IL-22. The authors therefore postulated that SSc could be characterised by a marked Treg/Th17 imbalance. Previous works did not distinguish between the different subsets of Treg and the non-regulatory FoxP3(+) cells leading to inconsistent results., Methods: Combined phenotypic and functional analysis of Th17 cells and FoxP3(+)CD4 T cells, discriminating activated Tregs and resting Tregs from non-regulatory FoxP3(+) T cells, in blood and skin of SSc patients., Results: In early disease stages, there is a decreased proportion of activated Tregs. A concomitant resting Treg deficit becomes more apparent with disease progression. Active and diffuse forms of the disease are characterised by a relatively higher proportion of all FoxP3(+) subsets, including non-regulatory T cells. No peripheral or local IL-17 amplification was observed. However, the authors found significantly increased IL-22 transcription levels in SSc lesional skin, as compared with healthy skin. Cytofluorometry confirmed the existence in SSc patients and controls of a distinct subset of T cells producing IL-22 in the absence of IL-17., Conclusion: SSc pathogenesis does not appear to be linked to IL-17-, but rather to IL-22-producing cells with skin-homing potential and a concomitant quantitative Treg defect. Active and diffuse forms of the disease are associated with a FoxP3 signature. Altogether, our data depict a status of regulatory/pro-inflammatory T cell imbalance in SSc.

Objective: Independent replication with large cohorts and metaanalysis of genetic associations are necessary to validate genetic susceptibility factors. The known tumor necrosis factor (ligand) superfamily, member 4 gene (TNFSF4) systemic lupus erythematosus (SLE) risk locus has been found to be associated with systemic sclerosis (SSc) in 2 studies, but with discrepancies between them for genotype-phenotype correlation. Our objective was to validate TNFSF4 association with SSc and determine the subset with the higher risk., Methods: Known SLE and SSc TNFSF4 susceptibility variants (rs2205960, rs1234317, rs12039904, rs10912580, and rs844648) were genotyped in 1031 patients with SSc and 1014 controls of French white ancestry. Genotype-phenotype association analysis and meta analysis of available data were performed, providing a population study of 4989 patients with SSc and 4661 controls, all of European white ancestry., Results: Allelic and genotypic associations were observed for the 5 single-nucleotide polymorphisms (SNP) with the subset of patients with SSc who are positive for anticentromere antibodies (ACA) and only a trend for association with SSc and limited cutaneous SSc. Rs2205960 exhibited the strongest allelic association in ACA+ patients with SSc [p = 0.0015; OR 1.37 (1.12-1.66)], with significant intra-cohort association when compared to patients with SSc positive for ACA. Metaanalysis confirmed overall association with SSc but also raised preferential association with the ACA+ subset and strongest effect with rs2205960 [T allele p = 0.00013; OR 1.33 (1.15-1.54) and TT genotype p = 0.00046; OR 2.02 (1.36-2.98)]., Conclusion: We confirm TNFSF4 as an SSc susceptibility gene and rs2205960 as a putative causal variant with preferential association in the ACA+ SSc subphenotype.

Introduction: Pemetrexed is approved to treat non-small cell lung cancer and has an overall favorable toxicity profile. A case of pemetrexed-induced cutaneous adverse events (CAE), i.e., periorbital edema with conjunctivitis and edema of the limbs, leading to severe fluid retention, was diagnosed in our unit. The aim of this study was to evaluate the incidence and risk factors for CAEs., Methods: Patients treated with pemetrexed were identified from a prospective cohort. To detect pemetrexed-associated CAEs, questionnaires were answered by patients and the referring oncologist., Results: Included were 107 patients treated with four cycles or more of pemetrexed. Pemetrexed-induced CAEs were observed in 37 of 107 (35%) total patients (TPs) and 25 of 47 (53%) alive patients (APs). Conjunctivitis was the most frequent CAE: 27 of 107 (25%) in TPs and 21 of 47 (44%) in APs. Periorbital edema occurred in 16 of 107 (15%) TPs and 14 of 47 (30%) APs. Limb edema was present in 14 of 107 (13%) TPs and 12 of 47 (25%) APs. Only two cases of CAE influenced pemetrexed treatment. No significant differences in age, body surface area, smoking status, and performance status were detected. Patients with CAE had more cycles of pemetrexed (7 versus 5.5; p = 0.028). In univariate and multivariate analyses, gender ratio was statistically different (p = 0.031): 48% (12/25) of women in the CAE group versus only 18% (4/18) in the control group., Conclusion: Pemetrexed induces frequent conjunctivitis, peripheral edema, and edema of the limbs. Female gender seems to be an independent risk for CAE. CAEs are frequently disabling and symptomatic treatment should be proposed.

Background: BANK1 and BLK B-cell genetic markers have been reproducibly and convincingly found to contribute to susceptibility to systemic sclerosis (SSc)., Objectives: To determine whether other B-cell genetic markers including CD19, CD20, CD22 and CD24 polymorphisms affect susceptibility to SSc in the European Caucasian population., Methods: A case-control study was performed in 900 patients with SSc and 1034 healthy controls. Among the whole SSc population, 304 (34%) had the diffuse cutaneous subtype, 551 (61%) had the limited cutaneous subtype, 732 (81%) were positive for antinuclear antibodies , 331 (37%) were positive for anticentromere antibodies and 228 (25%) for the topo-isomerase I. Genotyping has been performed for CD19 rs35979293, CD19 rs2904880, CD20 rs7126354, CD20 rs3802954, CD20 rs105146, CD20 rs4939364, CD22 rs10406069, CD22 rs10413500, CD22 rs10419538, CD22 rs34826052 and CD24 ins-del polymorphisms., Results: Genotype frequencies were at the Hardy-Weinberg equilibrium in the control population for all the SNPs investigated and observed frequencies were very similar to those expected in the European population. Allelic and genotypic frequencies for all these tested SNPs were found to be similar in SSc patients and controls. Moreover, subphenotype analyses in particular for subgroups having the diffuse cutaneous subset or topo-isomerase I positive antibodies, which are the most associated with BANK1 variants, did not detect any difference between SSc patients and controls., Conclusions: These results obtained through a large cohort of European caucasian patients with SSc do not support the contribution of CD19, CD20, CD22, CD24 variants to the genetic susceptibility of SSc.

Introduction: Accumulating evidences show that shared autoimmunity is critical for the pathogenesis of many inflammatory rheumatic conditions. Specific phenotype could arise from specific genes, and/or combination of genetic factors and environment. Systemic sclerosis (SSc) belongs to connective tissue disorders and recent data have highlighted strong associations with some autoimmunity genes shared with other autoimmune diseases., Objectives: To determine whether novel risk loci associated with rheumatoid arthritis (RA) may confer susceptibility to SSc. Single nucleotide polymorphism from CCL21, CD244 and CDK6 were tested for association., Methods: SNPs harbouring association with RA, CCL21-rs2812378, CDK6-rs42041 and CD244-rs6682654 were genotyped in a cohort of 1031 SSc patients and 1014 controls. All individuals were of European Caucasian origin., Results: The three polymorphisms were in Hardy-Weinberg equilibrium in the control population and allelic frequencies were similar to those expected in European populations. Allelic and genotypic frequencies for these three polymorphisms were found to be similar in SSc patients and controls. Moreover, sub-phenotype analyses in particular for subgroups having diffuse subcutaneous subtype, specific auto-antibodies or fibrosing alveolitis did not detect any difference between SSc patients and controls., Conclusions: These results obtained through a large cohort of European Caucasian SSc patients do not support the implication of CCL21, CD244 and CDK6 genes in the pathogenesis of SSc although these genes were recently identified as RA susceptibility genes.

The Kaposi sarcoma-associated herpesvirus (KSHV)-DNA level was determined in samples from 71 patients with Kaposi sarcoma (KS), 28 patients with multicentric Castleman disease (MCD), and 8 patients with primary effusion lymphoma (PEL). KSHV-DNA levels were higher in patients with active KS or MCD than in those with KS or MCD in remission. Among patients with active disease, the highest KSHV-DNA levels were observed in effusion fluid samples from patients with PEL (7.2 log(10) copies/150,000 cells), followed by blood samples from patients with MCD and PEL (4.86 and 3.83 log(10) copies/150,000 cells, respectively), and the lowest levels were observed in blood samples from patients with KS (2.63 log(10) copies/150,000 cells). Determining the KSHV-DNA level may be useful in diagnosing KSHV-associated disease and for following up patients with KS when the development of MCD or PEL is suspected.

Objective: To determine whether pulmonary arterial hypertension (PAH) is a prognostic factor for mortality in diffuse cutaneous systemic sclerosis (dcSSc), independent of interstitial lung disease (ILD)., Methods: ILD was diagnosed by high-resolution computed tomography and PAH (pulmonary arterial systolic pressure [PASP] > or =45 mm Hg) by echocardiography. All patients with ILD underwent testing for total lung capacity (TLC), forced vital capacity (FVC), and diffusing capacity for carbon monoxide., Results: Eighty-six patients with dcSSc (mean age at diagnosis 44.5 years) were followed up for a median of 72.5 months. ILD was found in 52 patients (60%) and PAH in 18 (21%). ILD was associated with PAH in 15 patients. Seventeen patients died (19.8%), 9 of whom had PAH (P = 0.001) and 10 of whom had ILD (P = 0.99). By multivariate analysis, age at SSc diagnosis and PAH were the only independent predictors of death (hazard ratio [HR] 1.057, 95% confidence interval [95% CI] 1.009-1.109, P = 0.020 and HR 4.09, 95% CI 1.47-11.5, P = 0.007, respectively). Mean TLC and mean FVC were similar in ILD patients with and those without PAH (P = 0.71 and P = 0.40, respectively). Among ILD patients, age at SSc diagnosis and PAH were again the sole predictors of death (HR 1.073, 95% CI 1.003-1.149, P = 0.042 and HR 5.07, 95% CI 1.09-23.8, P = 0.038, respectively). Twenty ILD patients received at least 6 monthly pulses of intravenous cyclophosphamide (CYC). In CYC-treated patients with PAH (n = 8), PASP increased significantly during the CYC regimen (mean +/- SD 55 +/- 14.5 mm Hg; P = 0.015 versus baseline), while TLC remained stable during the same period., Conclusion: These results indicate that, independent of ILD, PAH is a major prognostic factor for survival in dcSSc.

We report the case of a 52-year-old male heart transplant recipient with a persistent localized subcutaneous infection by Scedosporium apiospermum. This form differs from the most common mycetoma by the absence of granules. The patient showed multiple nodules on the right hand that were surgically removed. Concomitantly, he received oral itraconazole, but the infection persisted for two years, and several surgical interventions were necessary to eradicate the infection. Our case demonstrates that a medical approach alone may be not sufficient to cure this fungal infection., (Copyright John Libbey Eurotext 2003)

Compared with other side effects induced by thalidomide, amenorrhea has been relatively poorly investigated although it was first reported in 1989. The aim of this study was to determine the prevalence of amenorrhea in consecutive women treated with thalidomide in our institution from 1995 to 1999. During that period, 21 women received thalidomide associated with progestin contraception. Their clinical and biological data were retrospectively reviewed. Data concerning their genital life were systematically checked by phone with a simple questionnaire. Transient secondary amenorrhea occurred in 5 women (24%) treated for refractory cutaneous lupus erythematosus (4 cases) or complex aphthosis (1 case). The link between thalidomide and amenorrhea was suggested by the resumption of menses 2 to 3 months after drug withdrawal, recurrence of amenorrhea after reintroduction of thalidomide (1 case) and high serum levels of pituitary gonodotrophins. Amenorrhea secondary to ovarian failure is frequently observed in women treated with thalidomide. Its precise mechanism remains to be elucidated.