A middle-aged man presented with asymptomatic multiple grouped papules present bilaterally symmetrically on the face. Histopathology revealed peri-follicular, predominantly B-cell lymphoid aggregates with germinal center formation and occasional tingible body macrophages. Immunohistochemistry for Bcl-2 was positive in the peripheral mantle zone while sparing the follicle center, suggesting a reactive lymphoid follicle. Clinical differential diagnosis of facial papules can be broad, encompassing sarcoidosis, granulomatous rosacea, lupus miliaris disseminatus faciei, acneiform eruption, and eruptive benign appendageal tumors, among others. We report a rare case of pseudolymphoma clinically presenting as multiple facial papules, diagnosed through combined histopathological and immunohistochemical evaluation.

Systemic lupus erythematosus (SLE) may overlap with Sjögren's syndrome (SS), leading to complex systemic involvement, including neurological and pulmonary manifestations. We report a 60-year-old woman with a 10-year history of SLE-SS overlap presenting with headaches and bilateral visual impairment. Hydroxychloroquine (HCQ) had been discontinued 4 months prior due to HCQ-related optic neuropathy confirmed on optical coherence tomography (OCT). Ophthalmologic evaluation revealed bilateral optic neuritis. Immunological testing showed high-titre antinuclear antibodies (ANAs) in both serum (1:640) and cerebrospinal fluid (CSF) (1:320), with positive anti-dsDNA, anti-SSA/Ro52, anti-Sm/RNP, and anti-ribosomal P antibodies. CSF analysis was normal, without pleocytosis, hyperproteinorrhachia, oligoclonal bands, or intrathecal IgG synthesis (IgG index 0.61). Brain MRI showed non-enhancing periventricular demyelinating lesions, and thoracic CT revealed bilateral bronchiectasis. The patient received intravenous methylprednisolone (500 mg/day × 3 days) followed by oral corticosteroids, with leflunomide added as an immunomodulatory agent given the overlap syndrome context, resulting in a favourable clinical outcome. The absence of intrathecal immunoglobulin synthesis and oligoclonal bands supports blood-brain barrier dysfunction rather than a primary demyelinating process, highlighting the diagnostic challenge in SLE-SS overlap. ANA detection in CSF may serve as a supportive marker for neuropsychiatric lupus (NPSLE) in overlap syndromes.

Salinity and water deficit are known to impair biomass production and affect the regulation of physiology and metabolism. The impact of irrigation frequency and salinity levels on biomass production, physiological, and antioxidant responses in Sarcocornia (Megadim ecotype) and Arthrocaulon macrostachyum (AM) was investigated. Plants were subjected to irrigation intervals of 2, 6, and 10 days and salinity levels of 50, 150, and 250 mM NaCl for Sarcocornia, and 150 and 250 mM for AM. Frequent irrigation significantly increased plants' biomass across salinity treatments, with the highest biomass under 250 mM NaCl in AM and at 150 and 250 mM in Megadim. Under 6- and 10-day irrigation, 150 mM NaCl maintained higher biomass than lower or higher salinity levels. In Megadim, biomass decreased by 28.9-43.8%, 23.1-42.7%, and 37-56.2% at 50, 150, and 250 mM NaCl, respectively, under six- and ten-day irrigation. Similarly, AM biomass declined by 32.3-59% at 150 mM and 58.1-79.4% at 250 mM NaCl. AM showed higher levels of flavonoids, polyphenols, radical-scavenging activity (RSA), oxygen radical absorbance capacity (ORAC), and protein levels, especially with 6-day irrigation. Megadim showed higher polyphenol, RSA, and ORAC under frequent irrigation at 150-250 mM NaCl, while flavonoids peaked under 10-day irrigation, and polyphenol, RSA, and ORAC peaked at 50 mM NaCl with 6-day irrigation. Photosynthetic pigments, total soluble solids, and electrical conductivity increased under 10-day irrigation, whereas anthocyanins, relative water content, and malondialdehyde were highest under frequent irrigation. Overall, irrigation frequency regulated salinity responses, with frequent irrigation enhancing biomass production and moderate water limitation improving antioxidant capacity.

Rheumatoid arthritis (RA)-related pleural disease is an uncommon but serious extra-articular complication that can closely mimic empyema. Rheumatoid pleural effusions are exudative, with low pH, markedly reduced glucose, and elevated lactate dehydrogenase (LDH), and the fluid may appear green and frankly purulent, a constellation that overlaps substantially with infected parapneumonic effusion, particularly when cultures are negative. We report a 66-year-old woman with a 22-year history of seropositive, erosive, nodular RA who presented with recurrent right-sided pleural effusions and progressive dyspnea over three years. She was initially diagnosed with empyema following a presumed ruptured pleural-based pulmonary abscess. Pleural fluid was an exudate with elevated LDH (1,364 U/L), low glucose (45 mg/dL), and a lipid profile consistent with a chronic pseudochylous effusion, and repeated bacterial, mycobacterial, and fungal cultures were sterile. Video-assisted thoracoscopic surgery (VATS) with pleural and lung biopsies demonstrated findings characteristic of RA-related lung disease, including fibrinous pleuritis, follicular bronchiolitis, and a usual interstitial pneumonia (UIP) pattern. Because the lung remained trapped by a fibrous peel, staged thoracotomy with decortication and parietal pleurectomy was performed, and immunosuppression was escalated from leflunomide to rituximab. Detailed long-term follow-up data were not available for inclusion in this report. This case illustrates that in a patient with established RA, an exudative, culture-negative, purulent-appearing pleural effusion should raise suspicion of rheumatoid pleuritis before empyema. Early recognition, alongside continued exclusion of infection, may reduce diagnostic delay and the need for extensive thoracic surgery.

Disease-modifying antirheumatic drugs (DMARDs) are immune-modifying agents that have shown efficacy in improving response rates and reducing infusion reactions associated with uricase therapy for uncontrolled gout by inhibiting anti-drug antibody (ADA) formation. However, increased gout flare rates following initiation of uricase therapy remain a concern, impacting patient quality of life and treatment adherence. Gout flares are an acute inflammatory reaction to monosodium urate crystals, driven by inflammasome activation. As such, it is possible that DMARDs could impact gout flare risk. In this hypothesis-generating narrative review, we have synthesized mechanistic data investigating the effects of the DMARDs methotrexate, mycophenolate mofetil, azathioprine, leflunomide, and sirolimus on mechanisms involved in gout flare such as NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation. The mechanisms by which DMARDs inhibit ADA formation appear to be distinct from those that may affect gout flares, but these may exist in balance with one another to form a distinct pharmacological profile for each agent. Paradoxically, preclinical evidence suggests that DMARDs may sometimes induce NLRP3 inflammasome activation, particularly at higher doses. We suggest that individual DMARDs' effect on inflammatory pathways relevant to gout flare may vary depending on the pathophysiological context and differences in their pharmacological profiles. Therefore, the inflammatory consequences of combining DMARDs with uricase therapy are likely to be specific to the individual agent. Understanding the mechanistic profile of each DMARD is key to optimizing both immunogenicity management and flare outcomes in patients receiving uricase therapy for uncontrolled gout.

Leflunomide, a disease-modifying antirheumatic drug (DMARD) employed for the treatment of rheumatoid arthritis, generally holds a reputation for safety. However, it occasionally induces severe adverse reactions, including acute liver failure, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and hemophagocytic lymphohistiocytosis (HLH). This report details the case of a 46-year-old female who developed these complications shortly after commencing leflunomide therapy, manifesting severe cutaneous adverse reactions, severe drug-induced liver injury with Grade I hepatic encephalopathy, and subsequently HLH. Her clinical journey underscores the critical need for vigilance and prompt management in patients showing signs of severe drug-induced reactions. Following the HLH-94 treatment protocol, her condition improved significantly, highlighting the efficacy of immediate and appropriate intervention. This case not only exemplifies the potential severe complications associated with leflunomide but also illustrates the life-saving potential of early diagnosis and treatment in cases of drug-induced HLH and DRESS syndrome. This case contributes to the literature by underscoring the complexities of managing rare but severe side effects of commonly used medications.

Per- and polyfluoroalkyl substances (PFASs) are globally detected in humans, yet regional variations in PFAS exposure remain insufficiently characterized. Herein, by utilizing target and nontarget analysis with machine learning, differences in PFAS exposure were assessed based on 1088 serum samples of the population from SX, GD, HeB, and HuB regions in China. Nontarget analysis identified 49 PFASs, among which bis(trifluoromethane)sulfonimide (Ntf2), C8 per- and polyfluoroalkyl ether carboxylic acid, C12 hydrogen-substituted polyfluoroalkyl (linear) carboxylic acid, 8:2 fluorotelomer unsaturated carboxylic acid, 1-hydroxy-6:2 fluorotelomer sulfonic acid, haloxyfop, and leflunomide were reported in human serum for the first time. Target analysis indicated total PFAS concentrations of 9.4, 17, 25, and 29 ng/mL in the SX, GD, HeB, and HuB regions, respectively, with compositional profiles differing in the proportions of specific PFAS classes. Machine learning classifiers achieved an accuracy of 0.89 in distinguishing samples from the four regions, revealing significant interregional disparity. Furthermore, PFNA, Ntf2, PFOA, and 6:2 Cl-PFESA were identified as distinctive exposure biomarkers for SX, GD, HeB, and HuB, respectively, each being closely associated with local industrial activities. Overall, this study elucidates the region-specific characteristics of human PFAS exposure in China, providing a scientific basis for regionally tailored health risk assessment and pollution control strategies.

This study aimed to evaluate treatment patterns, adverse events, and drug discontinuations associated with conventional synthetic (csDMARDs), biologic, and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD). A retrospective cohort study was conducted on 264 RA patients with CKD, followed between 2015 and 2025. Renal function was assessed using estimated glomerular filtration rate (CKD-epidemiology collaboration) and categorized according to Kidney Disease Improving Global Outcomes guidelines into stages 3 to 5. Demographic data, laboratory parameters, comorbidities, medication history, and all drug-related adverse events were collected. Severe adverse events were defined as those requiring hospitalization, causing drug discontinuation, or resulting in death. Comparisons among CKD stages were performed using chi-square, Fisher exact test, analysis of variance, or Kruskal-Wallis tests as appropriate. Of 264 patients, the median age was 65 years, and 73.9% were female. Hypertension and diabetes were the leading comorbidities and major contributors to CKD etiology. Use of nephrotoxic csDMARDs (methotrexate, leflunomide) and nonsteroidal anti-inflammatory drugs (NSAIDs) decreased with advancing CKD, whereas glucocorticoid use increased. Toxicity from methotrexate, leflunomide, and NSAIDs rose significantly across renal stages (P < .05 for all). In contrast, adverse event rates for biologic disease-modifying antirheumatic drugs and targeted synthetic disease-modifying antirheumatic drugs did not differ significantly between CKD stages (all P > .05). No renal function-dependent increase in severe adverse events was observed for biologic or targeted therapies. In multivariable analysis, younger age, longer RA disease duration, higher baseline estimated glomerular filtration rate, and higher baseline Disease Activity Score 28-erythrocyte sedimentation rate were independently associated with the occurrence of any adverse event. While csDMARD and NSAID toxicity increase progressively with renal impairment, biologic and targeted synthetic agents maintain a stable safety profile across CKD stages.