Recent trends in the distribution of causative diseases of fever of unknown origin

Abstract

Fever of unknown origin is a challenging diagnostic problem and the aim of this research was to analyze trends in the distribution of its causative diseases. This retrospective study makes a comparison between two different clinical series of patients from two different periods: 227 from period 1 (1998-2002) and 602 from period 2 (2008-2012). There were fewer infections (31.72% vs.16.45%) and more miscellaneous causes (5.29% vs. 13.12%) in the period 2 series, whereas no significant differences in autoimmune diseases, malignancies and undiagnosed cases were found. Adult onset Still's disease and lymphoma occupied the largest proportion in autoimmune diseases (75.00%) and malignancies (89.81%), respectively. Interestingly, the autoimmune diseases group, instead of infections, was found to be the leading category of the causative diseases in fever of unknown origin, which is contrary to previous reports. Further, adult onset Still's disease and lymphoma were suggested to be valued more highly in view of the large and rising proportions found in this study. These trends could support the diagnosis and treatment of fever of unknown origin better in the future.

Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells

“…A key role of fever in the immune system is to stimulate the innate immune system, such as release of neutrophils in periphery, production of cyto-kines and nitric oxide from macrophages or dendritic cells, promotion of leukocyte trafficking, and enhancement of their phagocytic, bacteriolytic, cytolytic or antigen presentation functions (Evans et al, 2015;Hasday et al, 2014). Fever is also a shared clinical symptom in many autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, adult-onset Still's disease, rheumatic fever, and inflammatory bowel disease (Limper et al, 2010;Shang et al, 2017). Fever can be observed at both early and active stages of autoimmune diseases, and $20% of patients with clinical fever of unknown origins are diagnosed later with autoimmune diseases (Limper et al, 2010;Shang et al, 2017), suggesting a possible pathogenic role of fever in autoimmune diseases.…”

“…Fever is also a shared clinical symptom in many autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, adult-onset Still's disease, rheumatic fever, and inflammatory bowel disease (Limper et al, 2010;Shang et al, 2017). Fever can be observed at both early and active stages of autoimmune diseases, and $20% of patients with clinical fever of unknown origins are diagnosed later with autoimmune diseases (Limper et al, 2010;Shang et al, 2017), suggesting a possible pathogenic role of fever in autoimmune diseases.…”

Positron emission tomography and reframing vasculitis as a spectrum of disease when investigating a patient with a fever of unknown origin

“…Recent data suggest that autoimmune inflammatory disorders are increasingly found to be the leading cause of fever of unknown origin, confirming this 2003 recommendation 10. Temporal artery biopsy is the gold standard of diagnosis for giant cell arteritis, but false negatives occur due to the presence of ‘skip’ lesions 7.…”

Microenvironmental influences on T cell immunity in cancer and inflammation

“…Temperatures also vary widely in response to several physiological and pathophysiological mechanisms. Systemically, fevers can arise in many diseases and are a common side effect in bacterial and fungal infections, blood borne cancers like lymphoma, and a variety of autoimmune and inflammatory diseases, such as Adult-Onset Stills Disease [ 36 ]. While fevers are responsible for systemically increased temperatures, localized temperature changes are also common in damaged and inflamed tissue regions and have long been recognized.…”