Nakajo-Nishimura syndrome/proteasome-associated autoinflammatory syndrome (NNS/PRAAS) is a hereditary autoinflammatory disease. Clinically, NNS/PRAAS is characterized by periodic fever, skin rash, partial lipo-muscular atrophy, and joint contractures. Among PRAAS, NNS, is genetically characterized by a homozygous founder variant in the proteasome subunit beta type 8 (PSMB8) gene encoding an inducible proteasome component β5i. To establish an in vivo animal model recapitulating NNS/PRAAS, we generated mice harboring this founder variant. In Psmb8[G201V/G201V] mice, the immature β5i subunit was increased and 20S proteasome activity was significantly reduced in the spleen, whereas 26S proteasome activity was preserved and ubiquitin accumulation was not apparent. Compared with wild-type mice, Psmb8[G201V/G201V] mice exhibited a shortened lifespan and, as they aged, showed less weight gain and adipocyte shrinkage with interstitial macrophage infiltration and cytokine production/activation. The mutant mice also manifested significantly lower proportion of T cells in total splenocytes, with higher CD4[+] and lower CD8[+] T cell proportions. Psmb8[G201V/G201V] mice shared some characteristic autoinflammatory and progeroid phenotypes as observed in NNS/PRAAS patients, although their proteasome defect pattern was distinct. Thus, Psmb8[G201V/G201V] mice should be useful not only for investigation of NNS/PRAAS pathogenesis but also for examining the clinical effect of candidate drugs on NNS/PRAAS and related diseases.

Monkeypox disease, now commonly referred to as mpox, was once considered a geographically restricted zoonotic disease but has emerged as a global public health concern. The 2022 multinational outbreak marked a turning point, with notable shifts in transmission dynamics, affected populations, and clinical manifestations. Classical cases typically involve fever, lymphadenopathy, and a centrifugal vesiculopustular rash; however, recent outbreaks have revealed atypical presentations, including genital and perianal lesions, minimal or absent prodromal symptoms, and asynchronous rash evolution. These variations have complicated early clinical recognition and may contribute to delayed diagnosis and onward transmission. This review synthesizes current evidence on the evolving epidemiology of mpox, highlights differences between endemic and non-endemic outbreaks, and describes the full spectrum of typical and atypical clinical features. It also assesses diagnostic approaches, including molecular and point-of-care techniques, and evaluates the efficacy and limitations of current and emerging vaccines, such as JYNNEOS and ACAM2000. Future priorities include improving global surveillance, refining case definitions, expanding diagnostic access, and ensuring equitable vaccine distribution. Understanding the expanding clinical and epidemiological profile of mpox is essential for timely diagnosis, containment, and preparedness against future outbreaks.

Adult-Onset Still's Disease is a rare systemic auto-inflammatory disease that remains a diagnosis of exclusion. We present a 27-year-old female with no chronic medical conditions with recurrent cyclical fevers, neck mass, joint pain, and a newly diagnosed pregnancy. After extensive work up, the patient was found to fulfil the Yamaguchi criteria of AOSD. The patient was treated with oral steroids and infliximab for the remainder of her pregnancy.

We present the case of an HIV-positive patient with fever, arthralgia and maculopapular exanthema following a stay in Thailand, in whom acute chikungunya infection was serologically confirmed. Treatment was purely symptomatic, as no specific antiviral therapy is available. In view of the increasing number of cases in tropical endemic areas, but also in regions close to the borders of our neighbouring countries, and the steady spread of the tiger mosquito in Switzerland, tropical viral infections such as chikungunya, dengue and Zika are becoming increasingly important for clinical practice in Switzerland.

Background: Lymph node biopsy is an important means of etiologic diagnosis for patients with fever of unknown origin (FUO) and lymphadenopathy. However, it is an invasive procedure and may yield negative results. It is worth exploring which kinds of patients could benefit most from lymph node biopsy. Methods: FUO patients (n = 242) who had lymphadenopathy and underwent lymph node biopsy were enrolled into this retrospective single-center study. Clinical manifestations were documented and risk factors suggestive of an underlying positive lymph node biopsy (providing diagnostic clues) and lymphoma were analyzed. Results: The etiologies were as follows: infectious disease in 10 (4.1%) cases, connective tissue diseases in 51 (21.1%) cases, neoplastic diseases in 57 (23.6%) cases, other diseases in 28 (11.6%) cases, and unknown diagnosis in 96 (39.7%) cases. A total of 88 patients (36.4%) were diagnosed through lymph node biopsy. The following four independent risk factors were found to be related to positive lymph node biopsy: male gender (OR 2.471; 95% CI 1.158-5.270; p = 0.019), no rash (OR 3.531; 95% CI 1.595-7.816; p = 0.002), shape index of the lymph node (OR 8.566; 95% CI 1.035-70.915; p = 0.046), and hypoalbuminemia (OR 3.370; 95% CI 1.470-7.728; p = 0.004). Later, 146 patients with a confirmed diagnosis (including 57 cases of lymphoma and 89 cases of non-lymphoma) were included in the analysis of lymphoma-related factors. Age older than 45 years (OR 8.663; 95% CI 3.045-24.647; p < 0.001), no rash (OR 4.946; 95% CI 1.646-14.859; p = 0.004), serositis (OR 3.588; 95% CI 1.137-11.318; p = 0.029), abnormal blood flow of the lymph node (OR 3.025; 95% CI 1.034-8.848; p = 0.043), abnormal central lymph nodes (OR 6.546; 95% CI 1.721-24.898; p = 0.006), focal lesions in the spleen (OR 13.386; 95% CI 2.067-86.706; p = 0.006), and serum lactate dehydrogenase (LDH) > 250 U/L (OR 3.885; 95% CI 1.111-13.584; p = 0.034) were independent risk factors for lymphoma. Conclusions: Lymph node biopsy is a valuable diagnostic procedure for patients with FUO and lymphadenopathy. For male patients without rash, more rounded lymph nodes, and hypoalbuminemia, we strongly recommend lymph node biopsy. Age older than 45 years, no rash, serositis, abnormal blood flow of the lymph node, abnormal central lymph nodes, focal lesions in the spleen, and serum LDH > 250 U/L are risk factors suggesting an underlying lymphoma, and multi-site biopsy should be considered if necessary.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology, characterized by fever, arthralgia, rash, and leukocytosis. Severe disease may be complicated by macrophage activation syndrome (MAS), a life-threatening hyperinflammatory state marked by cytopenias, hyperferritinemia, and multiorgan involvement. Renal manifestations in AOSD are uncommon and varied. We report the case of a 22-year-old Nigerian male who fulfilled the Yamaguchi criteria for AOSD and presented with features consistent with MAS, including cytopenias, hyperferritinemia, hypertriglyceridemia, and transaminitis. He also developed acute kidney injury with significant proteinuria. Renal biopsy demonstrated features consistent with membranoproliferative glomerulonephritis (MPGN). The patient was successfully treated with pulsed corticosteroids followed by oral steroids and tacrolimus, resulting in clinical and biochemical improvement. This case highlights the diagnostic complexity of AOSD complicated by MAS, particularly in the presence of atypical renal involvement. Early recognition and prompt initiation of immunosuppressive therapy are essential to improving outcomes.

Legionnaires' disease is a severe form of pneumonia most commonly caused by Legionella pneumophila serogroup 1. While primarily affecting the lungs, extrapulmonary manifestations such as hyponatremia, renal dysfunction, and hepatic involvement are well described. In contrast, cutaneous manifestations are rare and remain poorly characterized. We report the case of a 62-year-old immunocompetent man with a history of chronic alcohol use and active smoking who presented with fever, dyspnea, and productive cough. On admission, he was febrile (38.5°C), tachycardic, and had crackles over the right lower lung field. Laboratory evaluation revealed hyponatremia (132 mmol/L) and markedly elevated inflammatory markers (CRP 480 mg/L, procalcitonin 41 ng/mL). Chest imaging demonstrated right lower lobe pneumonia. Initial empiric therapy with amoxicillin-clavulanate was started. Within 48 hours, the patient developed acute respiratory failure requiring intubation and ICU admission. Urinary antigen testing confirmed Legionella pneumophila infection, and antibiotic therapy was switched to levofloxacin and spiramycin. The course was complicated by severe ARDS (PaO2/FiO2 ratio 100) requiring prone positioning, and septic shock requiring vasopressors. On day 9 of hospitalization (seven days after targeted therapy initiation), the patient developed a diffuse, non-pruritic erythematous maculopapular rash with targetoid lesions, involving the trunk and limbs, with palmar involvement and petechiae at the ankles, without mucosal involvement. A drug eruption was initially suspected; however, skin biopsy showed mild interkeratinocytic edema with superficial lymphocytic infiltrate and rare keratinocyte necrosis, without eosinophilia or features of toxidermia. Direct immunofluorescence and PCR testing for herpes simplex virus and Mycoplasma pneumoniae were negative. These findings supported a diagnosis of erythema multiforme (EM) secondary to Legionella infection. The rash resolved spontaneously without specific treatment. The patient improved clinically, was extubated on day 12, weaned off vasopressors by day 10, and discharged on day 20 after completing antibiotic therapy. This case illustrates a rare presentation of Legionnaires' disease complicated by EM. Recognition of this association is important, as cutaneous findings may mimic drug reactions and lead to inappropriate modification of effective antimicrobial therapy. This report contributes to the limited literature describing dermatologic manifestations of Legionella infection and underscores the need for clinical awareness of this uncommon presentation.

Elderly-onset dermatomyositis (DM) is associated with an increased risk of malignancy. Serology supports clinical phenotyping of DM and risk assessment for malignancy, but malignancy cannot be completely excluded by serology alone. T-cell lymphomas can rarely mimic DM or coexist with established DM, posing an important diagnostic pitfall. An 82-year-old woman presented with fever, polyarthralgia, rash, and interstitial lung disease. Myositis autoantibodies assessed by immunoblot were positive for anti-PM/Scl-100 and anti-Mi-2. Aldolase was elevated, and skin biopsy findings were compatible with DM. Computed tomography showed interstitial lung disease and mild bilateral inguinal lymphadenopathy, while the inguinal lymph node biopsy suggested reactive lymphadenitis. She was diagnosed with DM and treated with oral prednisolone. During tapering, she rapidly developed systemic deterioration with severe thrombocytopenia and marked elevations in lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor, raising suspicion for lymphoma-associated hyperinflammation. Bone marrow aspirate ultimately revealed peripheral T-cell lymphoma, not otherwise specified, with bone marrow involvement. A literature review identified 16 reported cases, including ours, of T-cell lymphoma either "mimic" DM or "coexisting" with established DM. 7 cases were classified as mimic and 9 as coexisting. These cases suggest that repeat tissue evaluation, particularly of skin lesions, may be critical in atypical or treatment-refractory cases. Our case highlights that even a DM phenotype with autoantibodies generally considered less strongly associated with malignancy does not exclude occult lymphoma in elderly patients.