FFA4 inhibits bleomycin-induced pulmonary fibrosis in mice by suppressing IL-33.

Spontaneous spinal CSF leaks: a rare variant exome sequencing study and functional analysis.

Association between autoimmune disease and obstructive sleep apnea in a pediatric population.

Pediatric dermatoses presenting as follicular papules are common entities encountered in clinical practice. These are a heterogeneous group of disorders of infectious or noninfectious origin that commonly present as regularly spaced, small papules with or without perifollicular inflammation. Inflammatory causes include follicular eczema, pityriasis rubra pilaris, lichen nitidus, follicular seborrheic dermatitis, keratosis pilaris and its variants, keratosis circumscripta, follicular psoriasis, lichen spinulosus, follicular lichen planus, follicular mucinosis, perforating folliculitis, follicular porokeratosis, and follicular dermographism. These conditions may arise due to filaggrin mutations, keratinization defects, autoimmunity, or microbial triggers. Nutritional causes include phrynoderma and scurvy, while connective tissue diseases such as dermatomyositis and chronic cutaneous lupus erythematosus are autoimmune. Additional categories include infectious, genetic, hormonal, environmental, frictional, malignant, nevus-related, iatrogenic, and idiopathic entities. An early and accurate diagnosis is essential for proper management and reducing disease-associated apprehension in children and/or their parents. This review attempts to describe the role of history taking and clinical examination, including morphology, location, pattern of distribution, and associated features, while dealing with a child with follicular-based papules. In addition, it delineates the role of dermoscopy and pathological examination in reaching a correct diagnosis. Furthermore, it describes the available treatment options and disease course of various follicle-based dermatoses.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that can occur as an idiopathic condition or in association with various systemic diseases. The association with Sjögren's syndrome (SS) is extremely rare, with only a few cases reported in the literature where PG developed in patients with established SS. We report the unique case of a 39-year-old female who presented with painful hemorrhagic bullae affecting the lower extremities, upper lip, and back, which rapidly evolved from nonpruritic papules. The patient also complained of arthralgia in small joints of both hands and had a history of dry mouth and eyes. Laboratory investigations revealed elevated inflammatory markers, positive antinuclear antibodies, and strongly positive anti-SSA/Ro and anti-SSB/La antibodies. Histopathological examination confirmed neutrophilic dermatosis compatible with PG. Schirmer's test was markedly positive, and salivary gland biopsy showed minimal inflammation, confirming the diagnosis of SS according to established classification criteria. The patient was initially treated with high-dose intravenous methylprednisolone and colchicine with good initial response. The patient showed excellent response with significant improvement in skin lesions and control of SS symptoms at a 3-month follow-up. This case highlights the importance of screening for underlying autoimmune connective tissue diseases in patients presenting with neutrophilic dermatoses.

Reply to Borie et al.: Is Sjögren's disease the overlooked connective tissue disease associated with a hypersensitivity pneumonitis pattern?

NIPT failure due to excessive chromosomal aberrations in an autoimmune pregnancy.

Trends in autoimmune rheumatic disease diagnoses before and after the COVID-19 pandemic in England: a population-based cohort study using OpenSAFELY.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is an important factor leading to a poor prognosis in connective tissue disease (CTD) patients. To analyze the clinical and imaging data of CTD-ILD patients, summarize their characteristics, and explore the diagnostic value of certain specific High Resolution Computed Tomography (HRCT) manifestations and their distribution patterns for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD). This study conducted a retrospective analysis of demographic data and HRCT findings from 384 patients with CTD-ILD. Using multivariable logistic regression, hierarchical analysis, and sensitivity analysis to compare data from the IIM-ILD group and other connective tissue disease-associated interstitial lung disease (OCTD-ILD) group, we summarized the imaging features and distribution of IIM-ILD, providing imaging clues for its recognition. The distribution of different imaging features differed between the IIM-ILD patients and the OCTD-ILD patients. This study found that nonspecific interstitial pneumonia (NSIP) located in the upper lung field, as well as organized pneumonia (OP) located in the middle and lower lung fields, are relatively significant characteristics that distinguish idiopathic inflammatory myopathies (IIM) from other connective tissue disease (OCTD) (the odds ratios (OR) were 2.51, 5.46, and 8.33, respectively, P < 0.001). If both NSIP in the upper lung field and OP in the lower lung field are present, diagnostic performance in differentiating IIM from OCTD will be further enhanced (sensitivity 55.90%, specificity 94.18%, accuracy 74.74%, OR 20.51, P < 0.001). This study indicated that for patients with CTD-ILD, specific HRCT manifestations could be used to distinguish IIM-ILD from OCTD-ILD, thereby assisting in clinical diagnosis. The coexistence of NSIP in the upper lung fields and OP in the lower lung fields would suggest a higher possibility of IIM-ILD.

Background. Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease characterized by immune dysregulation, vasculopathy, and progressive fibrosis of the skin and internal organs. Although SSc predominantly affects women, male patients may show a more severe disease phenotype, with higher morbidity and mortality. Case presentation. We describe four consecutive male patients with SSc managed at a tertiary rheumatology center between 2016 and 2024. The median age at presentation was 50.5 years (IQR 43.5–61). Three patients had limited cutaneous SSc and one had diffuse cutaneous disease. Pulmonary manifestations were prominent and included pulmonary thromboembolism, interstitial lung disease with a nonspecific interstitial pneumonia pattern, and echocardiographically suspected pulmonary hypertension. One patient developed scleroderma renal crisis with malignant hypertension and acute kidney injury and died despite aggressive management. Severe internal organ involvement occurred even in patients with limited cutaneous disease. SSc-specific autoantibody profiles were not available for all patients, which limits antibody–phenotype correlations. Conclusion. This case series illustrates the potentially aggressive and multisystem nature of SSc in male patients, with life-threatening pulmonary or renal complications. Early recognition and vigilant monitoring of organ involvement are essential to improve outcomes.

Secondary Raynaud's Phenomenon (RP) associated with connective tissue diseases (CTD) frequently presents as critical digital ischemia refractory to standard protocols. This review describes the clinical feasibility of a combined approach involving mechanical (surgical adventitial stripping) and chemical (Botulinum Toxin Type A [BTX-A] and/or prostanoid analogues) sympathectomy. We retrospectively reviewed four patients from tertiary centers in Mexico and Argentina presenting with severe refractory RP. Interventions involved periarterial digital sympathectomy augmented by intradigital BTX-A and/or intravenous (IV) prostanoids. Longitudinal clinical observations were recorded regarding pain reduction using the Visual Analog Scale (VAS), digital ulcer healing, and vascular imaging. Clinical remission was achieved in 3/4 patients. Case one healed a 0.5cm necrotic lesion following bilateral stripping and 80IU BTX-A. Case two, achieved complete tissue stabilization at 16-month follow-up; intraoperative angiography confirmed the immediate restoration of digital arch perfusion post-intervention. Case three, presented with a "late" capillaroscopy pattern, maintained a 60-month ulcer-free interval using 80IU BTX-A and Alprostadil. Case four involved 8/10 ischemic digits; the course was complicated by a radial artery thrombosis requiring a radio-radial venous graft bypass. This patient suffered a relapse with three new distal ulcers immediately following an administrative gap in Bosentan therapy. These hypothesis-generating findings suggest that multimodal sympathectomy is a feasible adjunctive strategy for limb salvage in refractory complicated secondary RP. Current literature enforces these findings supporting the notion for standardized dosing and stepwise approach for future research to support these hypothesis generating views.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by skin and internal organ fibrosis, vasculopathy and immune dysregulation. Skin fibrosis, commonly assessed using the modified Rodnan skin score (mRSS), remains a defining feature of SSc and is associated with disease severity and prognosis. However, conventional clinical assessment provides limited insight into the molecular heterogeneity underlying cutaneous involvement. Single-cell RNA sequencing and spatial transcriptomics have shown that SSc skin contains distinct fibroblast states, immune-stromal interactions and spatially organised fibrotic niches. These data challenge the view of cutaneous fibrosis as a uniform process and instead support a model in which different cellular and spatial programmes may contribute to clinically similar patterns of skin involvement. In this review, we synthesise findings from single-cell and spatial multi-omics studies of SSc skin published between 2021 and 2025, examine the extent to which molecular heterogeneity relates to clinical phenotype, and discuss the implications for cutaneous assessment, treatment-response heterogeneity and biologically informed patient subgrouping. Because skin biopsy is clinically accessible and can be repeated over time, it provides a practical setting in which these molecular observations can be studied. Whether they improve patient stratification, treatment selection or cutaneous outcome assessment will depend on prospective validation in larger and clinically well-characterised cohorts.

Janus kinase (JAK) inhibitors have emerged as a transformative therapeutic class across autoimmune diseases by targeting multiple cytokine networks implicated in inflammation and fibrosis. Beyond inflammatory arthritis, increasing evidence supports their potential efficacy in connective tissue diseases such as idiopathic inflammatory myopathies, systemic sclerosis, primary Sjögren's disease, and systemic lupus erythematosus. Through modulation of type I/II interferon and interleukin signaling, JAK inhibition exerts broad anti-inflammatory and antifibrotic effects, translating into clinical improvements in cutaneous, articular, and pulmonary domains. Early clinical trials and real-world data confirm meaningful responses in refractory disease, though randomized evidence remains limited. Overall, JAK inhibitors represent a promising, mechanistically grounded option for systemic autoimmune diseases, with ongoing studies expected to refine selectivity, indications, and long-term safety profiles.

This study aimed to evaluate the safety and efficacy of teclistamab, a T cell-redirecting bispecific antibody targeting B-cell maturation antigen, in a case series of severe autoimmune diseases. Data were retrospectively collected from patients with treatment-refractory systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), systemic lupus erythematosus (SLE), undifferentiated connective tissue disease (UCTD), or IgG4-related disease (IgG4-RD) who received 1 cycle of teclistamab at 5 European centres. Eighteen patients (72% women, median age 48.5 years, 10 SSc, 4 IIM, 2 SLE, 1 UCTD, and 1 IgG4-RD) with a median of 5 prior therapies and a median cumulative dose of 6.36 mg/kg teclistamab were included. The median follow-up was 5.1 months (range, 0.8-21.2 months). A total of 22 cytokine release syndrome episodes (16 grade 1 and 6 grade 2) occurred in 12 patients (67%). All patients developed severe hypogammaglobulinaemia, and 5 (28%) experienced severe infections. Two patients developed an inflammatory bowel disease-like colitis. Two patients with severe SSc-associated cardiac involvement died, 1 due to sudden cardiac death and the other following diffuse alveolar haemorrhage and heart failure. B-cell depletion was observed in all patients, accompanied by significant reductions in autoantibody levels. Teclistamab was associated with major clinical responses in 11 (61%) and minimal-to-moderate responses in 4 (22%) patients, despite discontinuation of immunosuppressive therapy. Teclistamab demonstrated the potential to induce treatment-free responses in refractory autoimmune disease, but clinically relevant safety events, including infections and fatal outcomes in patients with advanced cardiac involvement, highlight the need for careful patient selection and monitoring.

The diagnosis of connective tissue disease-associated interstitial lung disease (CTD-ILD) primarily relies on high-resolution computed tomography or lung biopsy, while several challenges persist in the clinical application of these modalities. This study aims to investigate the performance of lung ultrasound (LUS) in diagnosis of ILD in patients with CTD. Records from five electronic databases were screened and selected for eligible studies. Quality assessment of eligible studies was performed via Quality Assessment of Diagnostic Accuracy Studies-2. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve (AUC) of LUS was calculated. Sensitivity analyses, subgroup analyses and meta-regression were applied to identify sources of heterogeneity. Twenty-eight eligible studies were selected from 417 records, with a total of 2,196 participants (1,117 with CTD-ILD and 1,079 CTD patients without ILD). All studies reached moderate to high quality. LUS has shown good diagnostic performance in detecting CTD-ILD, with a sensitivity of 0.92, a specificity of 0.88 and an AUC of 0.96. Further stratified analyses suggested that good performance of LUS was also observed in diagnosing rheumatoid arthritis-associated ILD (sensitivity: 0.91, specificity: 0.90, AUC: 0.96) and systemic sclerosis-associated ILD (sensitivity: 0.96, specificity: 0.78, AUC: 0.94). Significant heterogeneity and publication bias was observed. Although LUS has shown good performance in diagnosing CTD-ILD, this approach does not yet justify routine application due to heterogeneity and publication bias. Further studies may focus on performance of LUS in other subtypes of CTD-ILD.

Congenital contractural arachnodactyly (CCA) is a rare, autosomal dominant connective tissue disease characterized by arachnodactyly, camptodactyly, multiple joint contractures, tall and slender habitus, crumpled ears, and scoliosis. It shares overlapping features with Marfan syndrome (MFS). This condition is caused by pathogenic variants in the fibrillin 2 (FBN2) gene. Currently, approximately 200 variants in FBN2 have been identified, with most of the variants located in the middle region of the gene (Exons 24–35). Here, we investigated the genetic etiology of CCA in two unrelated Chinese families. Whole‐exome sequencing (WES) identified a novel in‐frame deletion variant, NM_001999.4: c.4195_4209del, p.Trp1399_Gly1403del, in Exon 32 of FBN2 that was detected in all 3 affected patients but absent in 6 unaffected family members. The other novel missense variant in Exon 27 of FBN2 (c.3521G > A, p.Cys1174Tyr) was identified in an 8‐month‐old female patient who was diagnosed with CCA. This variant was verified to be inherited from her unaffected mother with low‐level mosaicism. Our study expands the mutation spectrum of FBN2 and provides insights into the genotype–phenotype relationship in CCA as well as a foundation for its genetic diagnosis, counseling, and management.

New Frontiers of Skin Ultrasound in Precision Medicine.

Risk of Pulmonary Aspergillosis in Tuberculosis Survivors: A Nationwide Population-based Study.

Mixed connective tissue disease (MCTD) is an autoimmune disorder characterized by overlapping features of multiple connective tissue diseases in addition to anti-U1-ribonucleoprotein (RNP) antibodies and Raynaud's phenomenon. A 53-year-old female patient with MCTD, interstitial pneumonia, and idiopathic thrombocytopenic purpura underwent partial tongue resection under general anesthesia. Perioperative management included steroid coverage and careful titration of the oxygen concentration. Although venous access was difficult, the anesthetic course was uneventful. MCTD can present perioperative challenges including pulmonary and cardiac complications, effects of long-term steroid use, and airway and cardiovascular disturbances. Safe anesthesia for patients with MCTD requires assessment of disease activity and severity across multiple conditions and individualized management accordingly.

Ear manifestations of connective tissue diseases: A dermatologic, histopathologic, and clinicopathologic review.