Approach To A Child With Recurrent Fever

Fever is one of the most common medical signs and is defined as a condition in which the body temperature elevates above the normal range of 36.5–37.5 °C (97.7–99.5 °F).

Recurrent fever: Recurrent fevers are defined as three or more febrile episodes in a six-month period, occurring at least seven days apart, with no causative medical illness. These episodes can occur at regular or irregular intervals.

Causes: Although the exact data is unknown the most common diagnosis associated with this fever pattern is PFAPA syndrome (i.e., periodic fever, aphthous ulcers, pharyngitis, and adenopathy).

PFAPA syndrome typically causes fevers every 4 weeks lasting 5 days. Parents will often be able to predict within several days the onset of the next fever attack.The syndrome usually occurs in children younger than five years who present with regular fevers and cervical adenopathy. Aphthous ulcers, which are usually small and relatively painless, are the symptom most likely to be missed. Children with PFAPA syndrome are well between episodes and relatively well even during episodes.

The other common cause of recurrent fever in children is cyclic neutropenia (CN).

Patients with cyclic neutropenia (CN) suffer from fevers lasting 4-5 days every 2-3 weeks, slightly more frequently than PFAPA patients. Interestingly, symptoms of PFAPA and CN are very similar including oral aphthae, cervical adenopathy, and pharyngitis.

Patients with malignancies can have recurrent fevers but these are typically not periodic and the child does not grow and develop normally between attacks.

Recurrent fevers that occur at irregular intervals have a lengthy differential diagnosis. Infectious causes can include viruses, bacteria, and parasites. Fever without any other sign or symptom is more common with viral infections than with bacterial infections. Fungal infections have not been reported to cause recurrent fevers in healthy children. Inflammatory or autoimmune diseases, including inflammatory bowel disease, juvenile rheumatoid arthritis, and Behçet’s disease, as well as hereditary periodic fevers, lymphoma, and factitious fever, should be considered. ESR testing is useful in distinguishing inflammatory from hereditary disorders.

Diagnosis: The diagnosis of recurrent fever depends on a good history, physical findings and the appropriate laboratory workup. The child who is otherwise well, with no unusual features on history or physical examination, needs only minimal laboratory testing. Blood should be drawn for a complete blood count (CBC) with differential and platelet count, ESR and CRP. A urine culture should also be obtained unless there are clear grounds for an alternative diagnosis.

The preferred method for the diagnosis of Cyclic Neutropenia is twice weekly complete blood counts with differentials. Patients with CN have episodic drops in neutrophil maturation which occur prior to onset of fevers and oropharyngeal symptoms. Therefore, examination of the absolute neutrophil count (ANC) at the time of fever attack is often normal. Up to 70% with CN have a definable mutation in the Elastase 2 gene.

Management: Children with normal initial evaluations and no additional signs or symptoms do not require further testing. Recurrent fevers with no defined underlying cause have a very favorable prognosis.

Oral corticosteroids can be effective in aborting attacks in patients with PFAPA. Daily cimetidine and colchicines can be used to prevent the occurrence of attacks but are only effective in a minority of children.

Tonsillectomy has proven to be almost curative in children with PFAPA. More than 90% of children with PFAPA experience complete resolution of fever attack within 6 months of the procedure. It is not clear as to why tonsillectomy results in such dramatic improvement.