Etiological spectrum and outcome of fever and inflammation of unknown origin. Does symptom duration matter?

OBJECTIVE: Evidence suggests that the symptom duration may affect the occurrence of certain fever (FUO) and inflammation (IUO) of unknown origin associated conditions. It is unclear if this could potentially guide diagnostic evaluations. We examined the association between symptom duration and diagnostic and prognostic outcomes in FUO/IUO. METHODS: We retrospectively analyzed a cohort of adult patients meeting criteria for FUO/IUO from a tertiary care center in Belgium between 2000 and 2019. The association between symptom duration and outcomes of interest were estimated by Cox proportional hazards models. RESULTS: Among 602 patients who met criteria for FUO/IUO (mean age 54 years, 43% female), 132 (22%) and 68 (11%) had symptoms for 3-12 months and >12 months, respectively. There were no significant differences in diagnosis or all-cause mortality between a symptom duration of <3 months and 3-12 months. In contrast, those who had a symptom duration of >12 months were less likely to receive a final diagnosis (aHR 0.42, 95% CI 0.30-0.60), in particular a diagnosis of infectious disorders (aHR 0.29, 95% CI 0.12-0.74), malignancies (aHR 0.11, 95% CI 0.03-0.46), and miscellaneous conditions (aHR 0.22, 95% CI 0.07-0.71), but no significant differences were seen in noninfectious inflammatory disorders (aHR 0.74, 95% CI 0.48-1.15) or all-cause mortality (aHR 0.55, 95% CI 0.19-1.54). CONCLUSIONS: The symptom duration may be used to guide the diagnostic workup among patients with FUO and IUO, in particular those with longstanding symptoms.

Rheumatic disorders among patients with fever of unknown origin: A systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic literature review and meta-analysis to estimate the proportion of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) cases that are due to rheumatic disorders and the relative frequency of specific entities associated with FUO/IUO. METHODS: We searched PubMed and EMBASE between January 1, 2002, and December 31, 2021, for studies with ≥50 patients reporting on causes of FUO/IUO. The primary outcome was the proportion of FUO/IUO patients with rheumatic disease. Secondary outcomes include the association between study and patient characteristics and the proportion of rheumatic disease in addition to the relative frequency of rheumatic disorders within this group. Proportion estimates were calculated using random-effects models. RESULTS: The included studies represented 16884 patients with FUO/IUO. Rheumatic disease explained 22.2% (95%CI 19.6 - 25.0%) of cases. Adult-onset Still's disease (22.8% [95%CI 18.4-27.9%]), giant cell arteritis (11.4% [95%CI 8.0-16.3%]), and systemic lupus erythematosus (11.1% [95%CI 9.0-13.8%]) were the most frequent disorders. The proportion of rheumatic disorders was significantly higher in high-income countries (25.9% [95%CI 21.5 - 30.8%]) versus middle-income countries (19.5% [95%CI 16.7 - 22.7%]) and in prospective studies (27.0% [95%CI 21.9-32.8%]) versus retrospective studies (20.6% [95%CI 18.1-24.0%]). Multivariable meta-regression analysis demonstrated that rheumatic disease was associated with the fever duration (0.011 [95%CI 0.003-0.021]; P=0.01) and with the fraction of patients with IUO (1.05 [95%CI 0.41-1.68]; P=0.002). CONCLUSION: Rheumatic disorders are a common cause of FUO/IUO. The care of patients with FUO/IUO should involve physicians who are familiar with the diagnostic workup of rheumatic disease.

Dengue: current state one year before WHO 2010-2020 goals.

BACKGROUND: Dengue is a possibly life-threatening human mosquito-borne viral infection widely spread in peridomestic (sub)tropical climates. The global incidence has expanded rapidly in the last decades, with 40% of the world's population currently at risk. To date, no anti-viral treatment other than supportive care exists. In 2015, the first and only dengue-vaccine, CYD-TDV, received marketing authorization. OBJECTIVES: To present the current understanding of dengue in terms of epidemiology, transmission, pathogenesis, disease management and prevention. To illustrate the knowledge gaps that remain to be filled in order to control dengue and achieve the WHO 2010-2020 goals. METHODS: An updated systematic review (2009-2019) was carried out. The databases Pubmed, Embase and The Cochrane Library were searched along with WHO and CDC guidelines. RESULTS: In total, 39 articles were included. Contemporary climatic and economic factors significantly contributed to the emergence of epidemic dengue. Unfortunately, CYD-TDV failed to meet safety and efficacy demands. New vaccination approaches are in the pipeline along with innovative vector-control strategies. Current anti-viral drug research focuses on repurposing drugs in addition to specific anti-dengue strategies that interfere with viral replication. CONCLUSION: The lack of understanding dengue pathogenesis and immunology has hampered the development of an effective vaccine. Recent research has provided new insights into the therapeutic and prophylactic approach. Implementation of complementary methods to control disease burden are required considering the socio-economic impact of this rapidly emerging global disease.

Efficacy and safety of canakinumab treatment in schnitzler syndrome: A systematic literature review.

BACKGROUND: Schnitzler syndrome is a rare autoinflammatory disorder characterized by chronic urticarial rash and a monoclonal gammopathy, accompanied by intermittent fever, bone pain, and arthralgia or arthritis. Canakinumab is a fully human monoclonal anti-interleukin-1ß (IL-1ß) antibody proven to be effective in IL-1 driven autoinflammatory disorders. METHODS: We systematically searched PubMed and Embase to include all types of studies on canakinumab treatment in Schnitzler syndrome published until March 16, 2020. RESULTS: Since 2011, 7 publications have been reported on canakinumab treatment in 34 patients with Schnitzler syndrome. The cumulative follow-up was 253 months, and 5 studies had a follow-up duration of 12 months or more. A complete response during treatment was reported in 58.6% of patients; all other patients had a partial response. Two hundred and seven adverse events were reported in 23 patients. Infection (n = 79) was the most common adverse event. One patient died from sepsis due to atypical mycobacterial infection. CONCLUSION: Based on the results of the current systematic review, canakinumab is an effective long-term treatment with a favorable safety profile in patients with Schnitzler syndrome.