Fever of unknown origin (FUO) caused by multiple myeloma: the diagnostic value of the Naprosyn test.

Fever of unknown origin (FUO) remains a difficult diagnostic problem. The causes of FUO have changed over the years. Neoplastic disorders have now displaced infectious diseases as the most common cause of FUOs. Most neoplasms are associated with no or low-grade temperatures, with some important exceptions. Hypernephromas and lymphomas are neoplasms typically associated with high spiking fevers or may present as FUOs. Hematologic malignancies, that is, the acute and chronic leukemias, myeloproliferative disorders, and multiple myeloma, do not usually present with acute fevers or as FUOs. We present an elderly male patient who presented with an FUO, whose history is significant for multiple myeloma in remission. Differential diagnostic possibilities in this patient included plasma cell leukemia, relapse of multiple myeloma, secondary/superimposed malignancy, or opportunistic infection. The main differential diagnosis for his FUO was between neoplastic and infectious disorders. As part of the diagnostic workup, a Naprosyn test (naproxen 375 mg [by mouth] every 12 hours for 3 days) was used to differentiate neoplastic from infectious causes of FUO in this patient. The Naprosyn test was positive, which indicated a neoplastic explanation for the patient's FUO and eliminated, along with the infectious disease workup, an infectious explanation for his FUO. The patient's FUO was finally determined to be the result of a relapse of multiple myeloma and not of a secondary malignancy or malignant transformation of myeloma into plasma cell leukemia. We conclude the Naprosyn test remains a valuable diagnostic test to use to narrow differential diagnostic possibilities in patients with FUOs when a malignancy is a diagnostic consideration.