Fever of unknown origin (FUO) due to cyclic neutropenia with relative bradycardia

Fever of unknown origin (FUO) is the diagnosis associated with a variety of infectious, neoplastic, or rheumatic/inflammatory disorders. FUOs are associated with fevers of ≥ 101°F for ≥ 3 weeks that remain undiagnosed after intensive in-hospital or ambulatory investigation. Many FUOs caused by rheumatic/inflammatory disorders are particularly difficult to diagnose because of the lack of specific diagnostic tests for many of these disorders. Several causes of obscure rheumatic/inflammatory fevers with a genetic ethnic or geographic disposition can be eliminated by history alone. Among the obscure rheumatic/inflammatory causes of FUO is cyclic neutropenia. Cyclic neutropenia is a rare disorder that may occur with autosomally dominant transmission or sporadically. As a cause of FUO, cyclic neutropenia is exceedingly rare. The clinical diagnosis of cyclic neutropenia is made by recognizing fever cycle periodicity as multiples of 7 days, that is, most commonly at 21 or 28-day intervals. The severity of cyclic neutropenia symptoms varies; a severe attack may be preceded by 1 or more less-severe attacks. If cyclic neutropenia is suspected and attacks occur at 21 or 28-day intervals, then the clinician should try to relate leukopenia to symptoms. Patients with cyclic neutropenia may have myalgias, fever, pharyngitis, oral ulcers, or bilateral anterior cervical adenitis. Fever may be accompanied by a pulse-temperature deficit, that is, relative bradycardia, which may provide an additional clue to the diagnosis of cyclic neutropenia. The diagnosis of cyclic neutropenia is straightforward if leukopenia is present when the patient is symptomatic. With cyclic neutropenia, clinicians should keep in mind that neutropenia may precede the patient's symptoms by 3 to 5 days and a complete blood cell count should be obtained to detect neutropenia 3 to 5 days before episodes and at the onset of symptoms. We believe this is the first reported case of FUO caused by cyclic neutropenia with relative bradycardia.