Fever Of Unknown Origin – Differential Diagnosis

Definition: Fever of unknown origin is defined as a fever in which patient has a temperature of more than 101F (38.3 C ) on most of the days for at least 3 weeks duration of a single illness and the diagnosis is unclear despite 1 week of intense inpatient investigations.

The list of potential etiologies of FUO is vast but following can be considered:

1. Infection
In almost all reviews of FUO in pediatric patients , infection is the largest category. It is important to recognize uncommon manifestations of common disorders. About half of the localized infections involve the respiratory tract and a careful history and x-ray can confirm the diagnosis. Other locations that are sources of prolonged fever include urinary tract, bone and CNS. Look for clues to more generalized infections like epstein-barr virus , enteric fever, cat-scratch disease etc in which there may be evidence of multiple organ involvement.

2. Collagen or Connective tissue Disease
Juvenile rheumatoid arthritis may present with a long duration of fever before a diagnosis is established. Additional causes include Kawasaki disease, SLE, rheumatic fever and other vasculitic syndromes. Some of these diseases may produce additional physical findings but some patients have only atypical presentations with only a few manifestations of the disorder.

3. Neoplasia
Most common in this group are lymphoreticular malignancies ( e.g lymphoma. leukemia ). If there are any joint symptoms , there may at times be confused with JRA. Neuroblastomas and occasionally other sarcomas may also sometimes present with fever as the only major symptom.

4. Inflammatory Bowel Disease
This is an unusual cause of isolated FUO because other symptoms e.g diarrhea, weight loss, poor growth are usually present.

5. Miscellaneous
There are always rare causes not evident on an initial search. Examples are ectodermal dysplasia with poor thermal regulation, diabetes insipidus with dehydration and fever in infancy and central fever in patients with disordered thermoregulation. Another rare cause is so called inflammatory pseudo tumor usually found in the abdomen.

6. Pseudo FUO
This entity is likely much more common than true FUO because frequent , minor viral illness may be over interpreted. A careful recording of illness and overall function of child and family is necessary, including school attendance.

7. Periodic Fever
This is a separate entity in which fever is truly episodic, followed by normal times. This category includes periodic fever with apthous stomatitis, familial Mediterranean fever and variants. Many of these disorders are still under study.