Development and validation of the AF score for diagnosis of adult-onset Still's disease in fever of unknown origin.

Objective: To develop and validate a diagnostic score to identify adult-onset Still's disease (AOSD) in fever of unknown origin (FUO). Methods: A single center, retrospective case-control study of inpatients with FUO from January 2018 to December 2021. Using clinical and laboratory data from 178 cases with AOSD and 486 cases with FUO, we developed an AOSD/FUO (AF) score with a Bayesian Model Averaging approach. AF score and Yamaguchi's criteria were evaluated by sensitivity, specificity, accuracy, and positive/negative predictive value for diagnosis of AOSD in developmental and validation samples. Results: Persistent pruritic eruptions (PPEs) in patients with rashes was higher in AOSD group than FUO group (52.3% vs 7.4%; P < 0.01). PPEs yielded a specificity of 97.5% and a sensitivity of 44.9%. AF score = PPEs × 3.795+Evanescent rash × 2.774+Serum ferritin × 1.678+Myalgia × 0.958+Neutrophil count × 0.185+Platelet count × 0.004. A cut-off value ≥ 5.245 revealed the maximizing sensitivity of 88.7% and specificity of 95.8% in discriminating AOSD from FUO in the validation group. And AF score improved the accuracy from 82.6% to 93.3% compared with Yamaguchi's criteria. Conclusions: We developed and validated a new score which can identify AOSD in FUO with higher classification accuracy than Yamaguchi's criteria. Future multi-centric prospective studies need to be designed to confirm the diagnosis value of AF score.

Dermatologic Manifestations of Noninflammasome-Mediated Autoinflammatory Diseases.

Autoinflammatory diseases (AIDs) arise from disturbances that alter interactions of immune cells and tissues. They give rise to prominent (auto)inflammation in the absence of aberrant autoantibodies and/or autoreactive T cells. AIDs that are predominantly caused by changes in the inflammasome pathways, such as the NLRP3- or pyrin-associated inflammasome, have gained substantial attention over the last years. However, AIDs resulting primarily from other changes in the defense system of the innate immune system are less well-studied. These noninflammasome-mediated AIDs relate to, for example, disturbance in the TNF or IFN signaling pathways or aberrations in genes affecting the IL-1RA. The spectrum of clinical signs and symptoms of these conditions is vast. Thus, recognizing early cutaneous signs constitutes an important step in differential diagnoses for dermatologists and other physicians. This review provides an overview of the pathogenesis, clinical presentation, and available treatment options highlighting dermatologic aspects of noninflammasome-mediated AIDs.

Acute Myocarditis Revealing Adult-Onset Still's Disease.

A 34-year-old man presented with fever, palpitations, maculopapular rash, pharyngitis, left cheilitis, and bilateral gonalgia. High-sensitivity troponin I concentration was 4,900 ng/l. Transthoracic echocardiogram revealed reduced global longitudinal strain. Cardiac magnetic resonance imaging showed acute myocarditis. Adult-onset Still's disease was diagnosed, and treatment with intravenous corticosteroids and tocilizumab was initiated. (Level of Difficulty: Beginner.).

Clinical manifestations and treatment outcomes in prurigo pigmentosa (Nagashima disease): A systematic review of the literature.

BACKGROUND: Prurigo pigmentosa (PP) is a rare inflammatory dermatosis characterized by pruritic erythematous papules that coalesce to form a reticulate pattern. PP is often misdiagnosed, and patients are treated with ineffective therapies. Although the majority of reports about PP are from East Asia, patients of all backgrounds can be affected. OBJECTIVES: To perform a systematic review of reported PP cases with the purpose of summarizing the clinical presentation and treatment of PP. METHODS: MEDLINE and Embase were searched for original articles describing PP. We identified 115 studies from 24 countries representing 369 patients to include in the analysis. RESULTS: Of the 369 patients included in the analysis, the mean age was 25.6 years (range: 13-72 years) with 72.1% (266 of 369) female. Risk factors or aggravating factors were described in 52.3% (193 of 369) of patients and included dietary changes (25.5%, 94 of 369), friction (8.4%, 31 of 369), sweat (7.6%, 28 of 369), and ketonuria (5.1%, 19 of 369). Of those patients who experienced PP following dietary changes, 40.4% (38 of 94) started a ketogenic diet. Minocycline monotherapy was the most frequently prescribed treatment for PP (20.9%, 77 of 369), achieving complete resolution in 48.1% (37 of 77) of patients. CONCLUSIONS: PP is sometimes associated with ketogenic diets and can be effectively managed with oral tetracyclines.

Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19.

BACKGROUND: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). METHODS: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n = 17), severe (n = 40) and critical groups (n = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 µg/L vs. 501.90 µg/L, p < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP. CONCLUSION: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19). MÉTODOS: Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROC (receiver operating characteristic). RESULTADOS: La cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 µg/L vs. 501,90 µg/L, p < 0,01). La concentración de ferritina guardó una correlación positiva con otras citoquinas inflamatorias tales como interleucina (IL)-8, IL-10, proteína C reactiva (PRC) y factor de necrosis tumoral (TNF)-α. El análisis de regresión logística demostró que la ferritina era un factor predictivo independiente de la mortalidad intrahospitalaria. En especial, el grupo de ferritina alta estuvo asociado a una mayor incidencia de la mortalidad, con un valor de odds ratio ajustado de 104,97 [intervalo de confianza (IC) del 95% 2,63-4.185,89; p = 0,013]. Además, el valor de ferritina tuvo una ventaja de capacidad discriminativa en el área bajo la curva ROC (AUC) de 0,822 (IC 95% 0,737-0,907] superior al de procalcitonina y PRC. CONCLUSIÓN: El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

State of care for patients with systemic autoinflammatory diseases - Results of a tertiary care survey.

BACKGROUND: Systemic autoinflammatory diseases (SAIDs) are rare debilitating disorders of which there is limited awareness and a significant delay in diagnosis. There is no uniform approach in the diagnosis and treatment of these disorders and the real life state of SAID patient care is poorly characterized. The aim of this study was to obtain data on the epidemiology, state of care and the perception of physicians who are involved in the care of SAID patients. METHODS: We performed a questionnaire-based survey and contacted 134 university departments of dermatology, pediatrics, rheumatology and other SAID departments of tertiary care in German-speaking countries. RESULTS: A total of 37 departments participated in the survey. The majority of departments managed both adult and pediatric patients with a variety of monogenic and polygenic/acquired SAIDs. For monogenic SAIDs such as cryopyrin-associated periodic syndromes (CAPS) and familial Mediterranean fever (FMF), the diagnostic and treatment strategies were similar among the departments. The diagnostic work-up included inflammatory markers and genetic testing, the first line treatment interleukin-1 (IL-1) blockers for CAPS and colchicine for FMF. For polygenic/acquired SAIDs, we observed a significant heterogeneity in diagnostic and therapeutic approaches. As a major unmet need, diagnostic delay was identified with a median time to diagnosis of 2 (range 1-5) years. The overall state of care for SAID patients was rated to be excellent or good by only 12% of departments, and to be poor or non-sufficient by 40% of departments. CONCLUSION: This study demonstrates a high need to improve the state of care and to harmonize diagnostic and treatment strategies for SAID patients.

Pulmonary arterial hypertension secondary to adult-onset Still's disease: Response to cyclosporine and sildenafil over 15 years of follow-up.

Adult onset Still's disease (AOSD) is an autoimmune disease characterized by systemic inflammation and is a rarely reported cause of pulmonary arterial hypertension (PAH). We describe the clinical course of a 40-year-old woman who presented with PAH 19 months after a diagnosis of AOSD. Sildenafil and immunosuppressive therapy with cyclosporine resulted in clinical and hemodynamic improvement with long-term survival 15 years after her initial presentation of AOSD. We review the literature for published cases of PAH due to AOSD and discuss the potential mechanisms relating inflammatory diseases and PAH.