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.

Parvovirus B19 and C-reactive protein in blood bank donors: implications for hygiene hypothesis research.

Exposure to certain environmental factors during childhood may influence the developing immune system, causing predisposing or protective effects toward development of autoimmune disorders. This study examines the hypothesis that past infection with parvovirus B19, a common childhood infection, is associated with altered levels of subclinical inflammatory activity in presumably healthy adults. Qualitative anti-parvovirus B19 IgG antibody and high-sensitivity C-reactive protein were determined in serum samples from adult blood bank donors. C-reactive protein values of B19 IgG-positive and B19 IgG-negative groups were compared. Analysis was performed on 282 blood bank donor serum samples. Among donors aged 17-49 years (n = 152), B19 IgG-positive samples (57.9%) were associated with significantly lower C-reactive protein levels compared with B19 IgG-negative samples (median C-reactive protein: 1.30 mg/l vs. 2.65 mg/l; p = 0.012 unadjusted (Mann-Whitney U-test); p = 0.014 adjusted for gender and age (logistic regression)). Among donors aged >49 years, median C-reactive protein levels were identical by B19 IgG status. The association of B19 IgG antibody with lower C-reactive protein levels in the serum of younger adults supports the hypothesis that infection in childhood may contribute long-term beneficial adaptive immune responses.