Search Results (318)

Background/Objectives: Interleukin-6 is a key proinflammatory cytokine involved in the pathophysiology of Familial Mediterranean Fever (FMF). This study aimed to evaluate interleukin-6 levels and the interleukin-6 rs1800795 variant in pediatric FMF participants and to investigate their associations with clinical manifestations, laboratory findings, and Mediterranean fever (MEFV) mutation status. Methods: The research involved 69 pediatric FMF participants and 50 healthy children. Interleukin-6 levels, laboratory findings, and genotype distributions of the interleukin-6 rs1800795 variant were compared between FMF and control groups. Moreover, the relationship between interleukin-6 levels and clinical findings, MEFV mutation status, and laboratory parameters were evaluated in the FMF group. Results: In the FMF group, interleukin-6, serum amyloid-A (SAA), white blood cell count (WBC), neutrophil, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels were higher compared to the control group. In the FMF group, interleukin-6 levels showed a positive correlation with ISSF score, annual attack frequency, the number of concomitant symptoms, disease duration, SAA, CRP, and ESR. The allele and genotype distribution of the interleukin-6 rs1800795 variant was similar to those in the control and FMF groups. In the FMF group, interleukin-6 values were higher in patients with abdominal pain, fever, chest pain, or arthralgia compared to those without these symptoms. Interleukin-6 levels were higher in both homozygous and compound heterozygous subgroups compared to the heterozygous subgroup. Conclusions: Elevated interleukin-6 levels in symptomatic pediatric FMF patients and those with homozygous or compound heterozygous MEFV mutations suggest that interleukin-6 may reflect both clinical disease severity and MEFV mutation status. Full article

Background: The “doxycycline deficiency syndrome” is a colloquial term used in tropical Australia to describe the overlapping, non-specific findings seen in leptospirosis, Q fever, and the rickettsial diseases scrub typhus and Queensland tick typhus (QTT). A laboratory confirmed diagnosis is frequently delayed, however, early differentiation of these potentially life-threatening infections has important implications for clinical management. Methods: We examined consecutive laboratory-confirmed cases of leptospirosis, Q fever, and rickettsial diseases managed at a referral centre in tropical Australia. The patients’ symptoms, clinical signs and simple laboratory and radiology investigations at presentation were compared. Results: There were 111 cases of leptospirosis, 59 cases of Q fever, and 34 cases of rickettsial disease (17 cases of QTT and 17 of scrub typhus). Patients with leptospirosis had a shorter duration of symptoms and were more likely to have gastrointestinal symptoms, arthralgia, haemoptysis, hypotension, conjunctival suffusion and abnormal chest auscultation at presentation than patients with the other infections. They were more likely to have renal impairment and an elevated creatine kinase but less likely to have an elevated serum ferritin and serum lactate dehydrogenase. Patients with leptospirosis were more likely to have alveolar and multilobar changes on chest imaging. Patients with Q fever were more likely to have abnormal liver function tests at presentation but were more likely to have preserved renal function and normal chest imaging. Patients with rickettsial disease were more likely to have a rash, an eschar, lymphadenopathy and splenomegaly. Overall, 76/204 (37%) required ICU admission, of whom 56 (74%) had leptospirosis, but all 204 patients survived to hospital discharge. Conclusions: Leptospirosis, Q fever, and rickettsial diseases can have a similar presentation, but simple clinical, laboratory and imaging findings can help distinguish these infections and expedite their optimal management. Full article

Background: Chikungunya virus and dengue virus rank among the most clinically significant mosquito-borne pathogens worldwide, imposing substantial disease burdens in endemic regions. Despite their overlapping symptomatology, the diseases diverge markedly in prognosis. This disparity underscores the critical need for tools to differentiate these conditions and elucidate their distinct pathogenic mechanisms. Method: We conducted liquid chromatography–tandem mass spectrometry-based comparative metabolomic analyses to systematically compare plasma profiles from infected individuals. Results: We collected plasma samples from 26 chikungunya fever (CHIKF) patients, 49 dengue fever (DF) patients and 28 healthy individuals. Clinically, CHIKF patients exhibited a higher prevalence of rash (96.3% vs. 36.7%) and involvement of small joints, while DF patients showed prolonged fever and more severe hematological abnormalities. Metabolically, significant differences were observed in specific metabolites, such as eugenol sulfate, lysophosphatidylcholine (14:0/0:0), and piperine, which were dysregulated in both groups compared to healthy controls. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted unique metabolic perturbations in CHIKF, such as peroxisome proliferator-activated receptor (PPAR) signaling and mechanistic target of rapamycin complex (mTOR) pathways, suggesting potential mechanisms underlying CHIKV-induced arthritis. Conclusions: This study identifies distinct metabolic signatures and functional pathways associated with CHIKF and DF, offering a potential mechanism for differential diagnosis and therapeutic targets. The role of eugenol sulfate in modulating CHIKV-induced arthralgia is particularly promising, supported by its known anti-inflammatory properties. Full article

Background/Objectives: Psoriatic arthritis (PsA) affects up to 30% of psoriasis patients but remains underdiagnosed due to heterogeneous early manifestations. Existing tools rely on advanced imaging or biomarkers, limiting feasibility. This study aimed to develop a simple nomogram, using routinely available clinical features to identify patients with likely PsA. Methods: This multicenter cross-sectional study enrolled adult psoriasis patients from two tertiary hospitals (training: n = 884; validation: n = 690). PsA was diagnosed using the Classification Criteria for Psoriatic Arthritis (CASPAR) by rheumatologists and dermatologists who were blinded to each other’s assessments. Thirteen candidate predictors, including demographics, disease history, and lesion characteristics, were prespecified. Independent predictors were selected using least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable logistic regression. Internal validation used 1000 bootstrap resamples, followed by temporal–geographic validation. Performance was assessed using area under the curve (AUC), calibration plots, the Hosmer–Lemeshow test, decision curve analysis (DCA), and clinical impact curves (CIC). Sensitivity analyses included E-value analysis for unmeasured confounding and alternative model specifications. Results: Five independent predictors were identified: uveitis (odds ratio (OR): 5.23, 95% confidence interval (CI): 1.94–14.10), inverse lesions (OR: 1.65, 95% CI: 1.09–2.48), scalp lesions (OR: 2.97, 95% CI: 1.45–6.10), nail lesions (OR: 5.98, 95% CI: 3.69–9.68), and arthralgia (OR: 20.23, 95% CI: 13.14–31.13). The nomogram showed good discrimination (AUC: 0.885 training, 0.874 validation), with good calibration and clinical utility confirmed by DCA and CIC. Conclusions: This nomogram, integrating five clinically accessible predictors, offers a practical tool to identify psoriasis patients with likely PsA, supporting timely referral in tertiary dermatology outpatient settings. Full article

Background: Acute rheumatic fever (ARF) is a clinical syndrome triggered by group A streptococcal (GAS) infections and characterized by fever, carditis, and arthritis as its main manifestations. Diagnosis relies on the revised Jones criteria. We report a rare case of ARF diagnosed in Switzerland. Case Presentation: An 18-year-old woman presented to the emergency department five days after returning from a one-week stay in Egypt with intermittent fever and a transient sore throat, followed by migratory joint pain. Laboratory testing revealed leukocytosis, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Chest X-ray, urine analysis, and (travel-associated) pathogen-testing (Epstein–Barr virus, Cytomegalovirus, human immunodeficiency virus, Malaria, Dengue, Zika, Chikungunya) were unremarkable. Blood cultures remained negative. Initially, a viral respiratory infection was suspected and symptomatic treatment established. Days later the patient was re-evaluated due to persistent symptoms. Leukocyte count (Lc) and CRP further increased and subcutaneous nodules appeared. The antistreptolysin-O (ASO)-titer was elevated more than three times higher than the normal upper limit and proofed serological evidence of a preceding streptococcal infection (GAS throat culture had not been performed). ARF was diagnosed according to the Jones criteria. Treatment with amoxicillin and a high dose of acetylsalicylic acid (ASA) led to a rapid clinical improvement. Secondary prophylaxis with depot penicillin (benzathine penicillin G; 1.2 million units; once monthly) was initiated to prevent rheumatic heart disease. Conclusions: This case highlights a rare occurrence of ARF following travel to Egypt, with probable acquisition of group A streptococcal infection during the trip. It emphasizes consideration of ARF even in Western countries with low ARF-prevalence if clinical history is suggestive. Early recognition and initiation of antimicrobial and anti-inflammatory therapy is crucial to prevent cardiac involvement. To the best of our knowledge, this represents one of the first cases diagnosed in Switzerland in the past 20 years. Full article

Breast implant illness (BII) describes a constellation of systemic symptoms reported by some patients after breast implantation, including fatigue, cognitive dysfunction, arthralgia, myalgia, sicca symptoms, skin manifestations, and mood disturbance. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) provides a broader conceptual framework in which silicone and other biomaterials may contribute to immune dysregulation in susceptible individuals, although causality remains controversial and no validated diagnostic biomarker exists. This narrative review summarizes current evidence on BII and implant-related ASIA, focusing on epidemiology, clinical presentation, biological plausibility, diagnostic evaluation, explantation outcomes, and implant-associated complications. Proposed mechanisms include chronic foreign-body inflammation, silicone gel bleed and particulate migration, macrophage activation, inflammasome signaling, cytokine dysregulation, bacterial biofilms and biofilm-derived metabolites, adaptive immune activation, autoantibody formation, and host genetic susceptibility. The review also distinguishes BII/ASIA-like presentations from breast implant-associated anaplastic large cell lymphoma and other rare implant-associated malignancies. A practical multidisciplinary diagnostic and management algorithm is proposed to support structured assessment, red-flag triage, exclusion of alternative diagnoses, patient-centered counseling, and individualized decision-making regarding medical management and explantation. Full article

Objectives: Temporomandibular disorder (TMD) is a multifactorial condition that significantly affects patients’ quality of life. This study investigated the association between clinical, biopsychosocial, and genetic factors, including the MMP3 rs679620 polymorphism, and TMD in women from southern Brazil. Methods: A cross-sectional case–control study was conducted including 305 women, comprising 138 patients with TMD (disc displacement with or without reduction and arthralgia) and 167 controls without TMD symptoms. TMD was diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Clinical and biopsychosocial characteristics were evaluated, and the MMP3 rs679620 polymorphism was genotyped using real-time polymerase chain reaction (RT-PCR). Univariate and multivariate analyses were performed, with statistical significance established at p < 0.05. Results: Univariate analysis demonstrated significant associations between TMD and chronic pain (p = 0.002), somatic symptoms (p < 0.001), and depression (p = 0.007). Multivariate analysis identified pain preventing leisure activities, headache, ear ringing (tinnitus), and age as factors significantly associated with the presence of TMD. No significant association was observed between the MMP3 rs679620 polymorphism and TMD in the study population. Conclusions: Clinical and biopsychosocial factors were associated with the presence of TMD in this female population, whereas the MMP3 rs679620 polymorphism was not. These findings support the multifactorial nature of TMD and suggest that biopsychosocial factors may play a greater role than the genetic variant investigated in this population. Due to the cross-sectional case–control design, the observed associations should not be interpreted as evidence of causal relationships. Full article

Background/Objectives: Celiac disease (CD) is an immune-mediated enteropathy with gastrointestinal and extraintestinal manifestations. In primary care, recognition can be delayed when psychiatric symptoms, arthralgia, thyroid dysfunction, alcohol exposure, and liver-test abnormalities coexist. This case report describes a confounder-aware diagnostic approach to histologically confirmed CD in a patient with a multifactorial primary-care presentation. Methods: We report a single-patient, de-identified reflective case from routine family medicine practice, organized according to CARE case-report principles. Results: A woman in her early sixties with hypothyroidism and glaucoma presented with new low mood, anhedonia, somnolence, generalized anxiety, increased alcohol intake, poor appetite, weight loss, abdominal bloating, diarrhea, flatulence, and polyarthralgia. Initial investigations, including celiac serology obtained before gluten-free diet advice, showed mild anemia, marked hyperferritinemia, severe cholestatic and hepatocellular liver-test abnormalities, uncontrolled hypothyroidism, and strongly positive tissue transglutaminase IgA (>250 kIU/L; reference 0.0–14.9). Radiographs showed mild osteoarthritis and osteopenia without erosive arthropathy. Computed tomography excluded malignancy but showed severe diffuse hepatic steatosis and mild pancreatic atrophy. Mirtazapine was started at the index visit; after the initial laboratory results, gluten-free diet advice, alcohol-reduction counseling, and levothyroxine adjustment were undertaken. During the diagnostic episode, small-bowel biopsy demonstrated moderate-to-severe crypt hyperplastic villous atrophy with increased intraepithelial lymphocytes, and gastric biopsies showed no significant pathology; the histology was consistent with CD. Symptoms improved substantially. Longer-term objective follow-up showed persistent but improved celiac serology (tTG-IgA 49.4 kIU/L), normalization of thyroid-stimulating hormone, partial improvement in gamma-glutamyl transferase, which remained elevated, and a later iron-deficiency pattern with persistent anemia. Conclusions: This case supports targeted CD testing when anxiety or depressive symptoms occur alongside gastrointestinal symptoms, weight loss, arthralgia, hypothyroidism or documented thyroid autoimmunity, anemia, osteopenia, or liver-test abnormalities. Histology and repeat serology confirmed the diagnosis, but the psychiatric and hepatic manifestations still require cautious interpretation because hypothyroidism, alcohol exposure, steatotic liver disease, and simultaneous treatments also shaped the clinical course. Full article

Chikungunya virus (CHIKV), traditionally recognized as a mosquito-borne alphavirus that causes febrile illness and debilitating arthralgia, has increasingly been associated with atypical organ involvement, including respiratory manifestations. These observations raise important questions regarding whether respiratory symptoms reflect severe systemic disease or signal previously underappreciated respiratory exposure routes. This review aimed to synthesize current evidence on respiratory complications of CHIKV infection and to evaluate the plausibility of respiratory or aerosol-associated transmission. A systematic literature search of PubMed, EMBASE, and MEDLINE (Ovid) identified five eligible studies spanning clinical virology, outbreak surveillance, epidemiology, and experimental aerosol models. Across human studies conducted in India, Réunion Island, Puerto Rico, and Brazil, respiratory presentations—including pneumonia, dyspnea, and respiratory failure—were uncommon but consistently associated with increased hospitalization and mortality risk. Respiratory symptoms generally arose in the context of respiratory viral coinfections, systemic inflammation, or cardiopulmonary decompensation rather than primary viral tropism for the respiratory tract. Only one non-human primate study directly evaluated aerosol exposure, demonstrating that cynomolgus macaques could be infected via inhaled CHIKV, confirming biological plausibility but showing no evidence of enhanced respiratory pathology. Importantly, no epidemiologic data support human-to-human airborne or droplet transmission. Collectively, available evidence indicates that respiratory involvement serves as a marker of disease severity rather than a transmission route. Nonetheless, rare aerosol-acquisition events in laboratory settings underscore the need for continued vigilance, strengthened surveillance, and re-evaluation of respiratory risks as climate change and viral evolution expand CHIKV’s global footprint. Full article

Dengue remains a major public health challenge in Peru, where recurrent outbreaks show marked variation in clinical presentation. This systematic review and meta-analysis synthesized available evidence to quantify the frequency and variability of dengue manifestations in Peruvian patients and to identify clinically relevant patterns for early recognition. We systematically searched PubMed, Scopus, Embase, Web of Science, ScienceDirect, Google Scholar, Virtual Health Library, and Scielo for observational studies published between 1993 and January 2025. Two reviewers independently selected studies, extracted data, and assessed methodological quality. Pooled prevalence estimates with 95% confidence intervals (CIs) were calculated using random-effects models. Twenty-eight studies including 4418 patients were analyzed. The most frequent manifestations were fever (95%; 95% CI: 90–98%), headache (86%; 95% CI: 80–91%), malaise (82%; 95% CI: 71–91%), myalgia (69%; 95% CI: 58–79%), arthralgia (64%; 95% CI: 56–73%), and retro-orbital pain (56%; 95% CI: 47–66%). Gastrointestinal symptoms were also common, including nausea/vomiting (40%; 95% CI: 33–48%) and abdominal pain (33%; 95% CI: 21–45%), whereas hemorrhagic and severe manifestations were less frequent, such as hematemesis (6%; 95% CI: 2–10%), petechiae (6%; 95% CI: 2–10%), jaundice (3%; 95% CI: 1–7%), and melena (1%; 95% CI: 0–6%). Heterogeneity was high across most outcomes (I² generally >90%), suggesting substantial between-study variability. This heterogeneity is likely related to differences in geographic region, outbreak period, circulating serotypes, diagnostic methods, and case severity definitions across studies. These findings highlight a consistent core symptom profile of dengue in Peru while also demonstrating important clinical variability. This information may support earlier clinical suspicion, triage, and surveillance in endemic settings. However, pooled estimates should be interpreted cautiously given the high heterogeneity, moderate methodological rigor of included studies, and lack of individual-level data. Future analyses stratified by region, study period, and diagnostic method are needed to generate more clinically precise estimates. Full article

Dengue is a rapidly spreading mosquito-borne viral disease with increasing incidence in Europe, driven by international travel and climate-related expansion of Aedes mosquito habitats. Data on imported dengue in Central Europe remain limited. The aim of this study was to characterize clinical and epidemiological features of imported dengue infections in Austria and identify factors associated with dengue warning signs. A retrospective, single-centre observational study conducted from January 2013 to October 2024. We retrospectively analyzed 175 adults with confirmed travel-associated dengue treated in Vienna, Austria. Demographics, travel history, symptoms, laboratory values, and clinical outcomes were extracted from electronic records. WHO criteria were applied to classify dengue severity. Most infections were acquired in Southeast Asia (72.6%), particularly Thailand. Common symptoms were fever (97.1%), fatigue (97.1%), arthralgia (59.4%), and rash (53.8%). Dengue warning signs were observed in 16% of cases and associated with significantly prolonged leukopenia (p = 0.003), increased hospitalization rates (50.0% vs. 23.8%, p = 0.005), and higher frequencies of vomiting, abdominal pain, mucosal bleeding, and petechiae at first medical contact. Women reported rash, arthralgia, and retro-orbital pain more frequently, while men showed lower platelet counts. No cases of severe dengue or deaths occurred. Dengue should be considered in febrile returning travellers, particularly from Southeast Asia. The presence of warning signs predicts more complicated disease courses and should prompt closer clinical monitoring. These findings underscore the importance of awareness and preparedness for dengue in non-endemic European settings. Full article

Azathioprine-associated hypersensitivity syndrome is a rare, idiosyncratic, dose-independent reaction that typically develops within the first four weeks of therapy. The clinical presentation includes a broad spectrum of symptoms such as fever, gastrointestinal manifestations including abdominal pain, nausea, and vomiting, cutaneous involvement, arthralgias, myalgias, and organ dysfunction, particularly affecting the liver and kidneys. Laboratory findings typically include leukocytosis, neutrophilia, and elevated C-reactive protein (CRP), whereas eosinophilia is usually absent. To date, lymphadenopathy has not been described as a manifestation of this syndrome. In this report, we describe the case of a 75-year-old female patient who developed a probable azathioprine-associated hypersensitivity syndrome three weeks after treatment initiation and who, in addition to systemic manifestations of the syndrome, presented with bihilar and mediastinal lymphadenopathy, which may represent a previously unreported feature of this condition, and we discuss potential differential diagnoses. Full article

Mayaro virus (MAYV) is an emerging arbovirus from the Togaviridae family where inflammation plays a central role in disease development. As the cause of Mayaro fever, MAYV triggers strong production of pro-inflammatory cytokines, which can result in long-lasting arthralgia in affected individuals. Macrophages are both targets for viral infection and key regulators of inflammatory responses. Human monocyte-derived macrophages (MDMs) are susceptible to MAYV infection in vitro and support productive viral replication. With no approved antivirals or vaccines, finding host-directed therapies is an urgent priority. Cannabinoids are compounds with antiviral and immunomodulatory properties, suggesting potential against MAYV infection. Here, we examined the effects of cannabidiol (CBD) and the synthetic cannabinoid WIN 55,212-2 on MAYV-infected MDMs in pre- and post-treatment conditions. Cells and supernatants were collected at 6 and 24 h post-infection (h.p.i). To understand the mechanisms involved, transcriptomic and functional analyses were performed at 24 h.p.i in the post-treatment setting, focusing on inflammatory, antiviral, and endoplasmic reticulum (ER) stress pathways. WIN 55,212-2 post-treatment significantly decreased viral replication at 24 h.p.i without any direct virucidal activity and was independent of type I interferon activation or interferon-stimulated gene induction, instead being linked to the modulation of ER stress signaling. Specifically, WIN 55,212-2 increased IRE-1α RNase activity, promoting the alternative splicing of sXBP1, while the integrated stress response appeared central to its antiviral effect. Additionally, WIN 55,212-2 downregulated inflammation-related genes and altered cytokine and chemokine production, counteracting the strong inflammatory response caused by MAYV. Remarkably, it also exerted broader immunomodulatory effects independent of infection. Full article

Leptospirosis is among the most widespread zoonotic infections globally and is particularly prevalent in tropical settings, where it remains endemic. In Malaysia, the disease burden has increased markedly over recent decades. Severe leptospirosis can result in multi-organ dysfunction and death; however, early identification of patients at risk of a severe clinical course remains a significant challenge. This study aimed to determine independent clinical and laboratory predictors of severe leptospirosis among adults admitted to hospitals in northeastern Malaysia. A multicenter retrospective cohort study was conducted at two tertiary referral hospitals in Kelantan, northeastern Peninsular Malaysia, over a seven-year period. Adults with confirmed leptospirosis were categorised as severe or non-severe according to established clinical criteria. Group comparisons were performed using appropriate statistical tests, followed by multivariable logistic regression with internal bootstrap validation to identify independent predictors of severe disease. Of 525 patients included in the final analysis (mean age 38.1 ± 16.8 years; 65.5% male), 303 (57.7%) met criteria for severe leptospirosis and overall, in-hospital mortality was 6.5%. Common presenting symptoms (>30% of patients) included fever, myalgia, nausea, vomiting, and arthralgia. Independent predictors of severe disease identified on multivariable analysis were; age > 40 years, delayed hospitalisation (presentation after four days of symptom onset), T-wave changes on electrocardiography, conjunctival suffusion, hyponatraemia, prolonged prothrombin time, and elevated alanine aminotransferase (all p < 0.05). The predictive model demonstrated good discriminatory ability (AUC 0.794, 95% CI: 0.747–0.841). Severe leptospirosis is associated with distinct clinical and laboratory features at presentation. Early recognition of key risk factors—particularly older age, delayed presentation, and electrocardiographic abnormalities—may enable clinicians to stratify risk, initiate timely targeted interventions, and potentially reduce morbidity and mortality in this endemic setting. Full article

Chronic chikungunya disease (CCD) affects approximately 30–50% of infected individuals and is associated with persistent inflammatory arthritis, chronic pain, and long-term functional disability. We conducted a prospective observational cohort study including 584 patients with laboratory-confirmed chikungunya infection, evaluated between 3 and 12 months after acute infection, to better understand the natural history, risk factors, clinical presentation, and treatment patterns of CCD. Here, we present a cross-sectional analysis derived from this cohort. Older age, female sex, and higher body mass index were identified as major risk factors for CCD. Four distinct clinical phenotypes were identified: Axial (12.2%), defined by inflammatory axial pain regardless of peripheral manifestations; Oligoarthritis (18.1%), defined by fewer than four swollen joints; Polyarthritis (10.6%), defined by four or more swollen joints; and Pain without Swelling (70.4%), characterized by myalgia and/or arthralgia in the absence of objective inflammatory findings on physical examination. The axial phenotype could overlap with peripheral phenotypes, whereas oligoarthritis, polyarthritis, and pain without swelling were mutually exclusive categories. These phenotypes differed substantially in symptom burden and clinical impact. Patients with the Pain without Swelling phenotype had longer symptom duration, whereas Axial and Polyarthritis phenotypes were associated with greater functional impairment and higher disease burden. These findings reinforce the clinical heterogeneity of CCD and support the potential value of phenotype-based approaches for clinical management and future therapeutic research. Full article