These Antibiotics Just Aren’t Working: Fever of Unknown Origin and an Uncommon Culprit

Kajol Patel MD, WellStar MCG Health Department of Neurology; Nicholas Fuchs BBA Medical College of Georgia; Alexander Warner MD, WellStar MCG Health Department of Internal Medicine; Derek Backer MD MPH, WellStar MCG Health Department of Internal Medicine

Background: Fever of unknown origin (FUO) is defined as a periodic temperature of at least 38.4°C lasting longer than 3 weeks, with a diagnosis remaining uncertain after 1 week of evaluation. The potential etiologies of FUO are diverse, which adds to the challenge of determining the cause. We report a case of FUO that ultimately led to the diagnosis of a very rare cause of fever in adults: Adult-onset Still’s disease (AOSD). Cases like this pose a diagnostic dilemma due to the hesitancy to withhold antimicrobials in the presence of a persistent fever. However, despite the lack of an accepted standard workup for FUO, a thorough and methodical evaluation increases the likelihood of arriving at a treatable diagnosis.

Case Description: A 41-year-old female with a past medical history of psoriatic arthritis presented to the hospital after more than 2 weeks of undulating fevers and bilateral leg pain. She has a past history of psoriatic arthritis and a remote history of IV drug use reportedly in remission. She had previously been treated with antibiotics but no source was clearly identified. Her review of systems included pertinent positives such as odynophagia, salmon colored rash which worsened with the fevers, polyarthralgia, and negatives such as lack of cough or shortness of breath, diarrhea, or dysuria. She had a neutrophilic leukocytosis, markedly elevated CRP and ESR, and markedly elevated ferritin. After ruling out alternatives such as bacteremia, endocarditis, occult abscess, thrombosis or other connective tissue diseases, it was noted that the patient fulfilled 3 major and 4 minor Yamaguchi criteria and the diagnosis of Adult-onset Still’s Disease was made.

Case Discussion: Adult-onset Still’s disease is a very rare cause of fever of unknown origin. Its symptoms include inflammatory arthralgia, a salmon-colored rash, sore throat, lymphadenopathy, and hepatosplenomegaly. AOSD is estimated to occur in 0.16-0.4 per 100,000 persons. Due to its rarity and symptom overlap with other conditions, diagnosing AOSD can often take several months. This case highlights AOSD as a rare but debilitating cause of FUO. If left untreated, AOSD can lead to significant morbidity and irreversible organ damage. Our case demonstrates the importance of conducting an exhaustive evaluation for alternative causes of FUO before initiating steroids or disease-modifying antirheumatic drugs. When the correct therapy is initiated, the response can be both dramatic and rewarding.