What is the degree of fever and who has documented it

Normal body temperature is highest in children who are preschool aged. Several studies have documented that peak temperature tends to be in the afternoon and is highest at about 18-24 months of age when many normal children will have a temperature of 101 °F. It is important to document fever (usually in an office setting) prior to beginning extensive testing.

B. Is this truly fever of unknown origin (FUO)? Definition in adults is 2 weeks of outpatient fever and 1 week in hospital without a diagnosis. In children, variable definitions have been used. Generally, most clinicians would accept fever documented for more than 1 week in which initial cultures and other investigations fail to yield a diagnosis. This is quite different from fever without localizing signs (FWLS), which is a more common and acute disorder in pediatrics, often involving risks and outcomes of bacteremia (for further discussion, see Chapter 27, Fever, p. 132). Another key question is whether this is a "periodic" fever interspersed with wellness, pointing to additional possible diagnoses.

C. What symptoms does patient have now? At onset? Clues to diagnosis of FUO are often obtained from the history, including meticulous review of systems (eg, rashes, skin breaks, and GI complaints).

D. What testing has been done? Initial effort should be to ensure complete data collection (ie, cultures, laboratory work, x-rays, antibody titers).

E. Are there known exposures? In difficult cases patients and families may, with careful questioning, recall exposures (eg, insect or tick bites, animal contact, other children or adults with illness).

F. What treatment has been initiated previously? At times, prior treatment may mask the fever history, make cultures negative, suppress bacterial growth (eg, urine or throat), or be the source of fever in the form of a drug reaction.

G. Has patient traveled outside the country or to an endemic area? Certain areas are far more likely to be sources of individual illnesses (eg, Lyme disease, Salmonella infection), and a history of travel to these areas may provide valuable clues.

III. Differential Diagnosis. The list of potential etiologies of FUO is enormous, but with care, a systematic approach using key major screening tests and categories will prove useful.

A. Infection. In almost all reviews of FUO in pediatric patients, infection is the largest category, with a figure of at least 50% of all final diagnoses. It is important to recognize uncommon manifestations of common disorders (infectious mononucleosis with hepatitis or pneumonia) rather than unusual or uncommon infections, such as tularemia. About half of the localized infections involve the respiratory tract, and a careful history and x-rays may confirm this diagnosis. Other locations that are sources of prolonged fever include urinary tract, bone, and CNS. A random search for abscesses may not be warranted, but if patient has abdominal symptoms with FUO, a CT scan may be useful. Look for clues to more generalized infections (Epstein-Barr virus, enteric infection, cat-scratch disease, tuberculosis, and cytomegalovirus) in which there may be evidence of multiple organ involvement.

B. Collagen or Connective Tissue Disease. Juvenile rheumatoid arthritis may present with a long duration of fever before a diagnosis is established (ie, fever precedes evidence of joint or skin involvement). Additional causes include Kawasaki disease, systemic lupus erythematosus, rheumatic fever, and other vasculitic syndromes, such as Wegener granulomatosis. Most of these conditions produce additional physical findings, but patients with Kawasaki disease who are younger than 1 year of age may have "incomplete" or atypical presentations with only a few manifestations of the disorder.

C. Neoplasia. Most common in this group are lymphoreticular malignancies (eg, lymphoma, leukemia). If there are joint symptoms, these may, at times, be confused with juvenile rheumatoid arthritis. Neuroblastoma and occasionally other sarcomas may present with fever as the major symptom.

D. Inflammatory Bowel Disease. This is an unusual cause of isolated FUO because other symptoms (eg, diarrhea, weight loss, poor growth) are usually present.

E. 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 pseudotumor, usually found in the abdomen.

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

G. Periodic Fever. This is a separate entity in which fever is truly episodic, followed by "normal" times. This category includes periodic fever with aphthous stomatitis, pharyngitis (PFAPA) and familial Mediterranean fever and variants. Many of these latter disorders are being delineated using newer genetic techniques as well as by studying pathways of inflammation.

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