Figure 71.1 Algorithm for assessing fever and polyarthritis. FUO = fever of unknown origin; SLE = systemic lupus erythematosus; JIA = juvenile idiopathic arthritis.
Age, sex, and geography are important clues. Gout is more common in men. Septic arthritis is more likely in the young, elderly, and immunosuppressed. Parasites and chikungunya fever should be considered in a traveler with fever and arthritis. Giant cell arteritis (GCA) is unlikely in patients less than 50 years old.
Acknowledge how and under what circumstances symptoms first manifest. Abrupt onset of symptoms, occurring in hours/days, may indicate infection or gout; whereas symptoms persisting for weeks or months suggest an autoimmune disease, chronic infection, or malignancy. Reactive arthritis (ReA) or parvovirus infection should be considered in a patient who initially presents with a viral illness then develops acute oligo- or polyarthritis.
Pattern of joint involvement
Observe the number, location, and symmetry of joint involvement. Monoarthritis is common in patients with ReA, septic arthritis, or gout. In contrast, patients who have diffuse symmetrical involvement (e.g., hands, wrists, shoulders, knees, ankles) are likely to have a chronic systemic disease such as systemic lupus erythematosus (SLE), chronic viral infections, or rheumatoid arthritis (RA). Spinal involvement may be a manifestation of tuberculous infections or a spondyloarthritis. Shoulder and hip girdle pain with high inflammatory markers should alert the clinician to polymyalgia rheumatica (PMR). The timing of joint involvement is also useful. Varying patterns of presentation have been described including: intermittent/episodic pattern with flares punctuated by periods of complete remission (e.g., gout, pseudogout, autoinflammatory diseases), additive pattern where symptoms begin with a few joints and progress to involve more joints with time (e.g., RA, SLE, hepatitis B, parvovirus), or migratory pattern where certain joints are affected for a time then remit, only to reappear elsewhere in other joints (e.g., gonococcal arthritis, acute rheumatic fever).
Fever is a nonspecific significant sign of systemic inflammation. It can also manifest in several patterns: continuous or sustained, intermittent, relapsing, or periodic (e.g., quotidian, tertian, quartan). Studies have examined the significance of fever pattern and found only a few fever curves convey any significance. Most drug reactions, vasculitides, and viral infections present with continuous fevers; the double quotidian fever curve with spikes twice a day has been associated with visceral leishmaniasis (kala-azar) and malarial infections. Patients with systemic-onset juvenile idiopathic arthritis (soJIA) or adult-onset Still’s disease (AOSD) display quotidian fever that is truly circadian, occurring at the same hour each day (usually late afternoon or evening). The magnitude of fever has not been shown to correlate with the degree of disease severity; however, infections should be higher in the differential diagnoses in patients with temperatures >102°F. Despite extensive research on the topic of fever and fever patterns, it remains unclear why certain diseases are associated with a particular fever pattern.
Differential diagnoses for polyarthritis and fever
Most causes of polyarthritis and fever can be classified into one of the following categories: infection, rheumatologic diseases (e.g., autoimmune, autoinflammatory, and crystalline diseases), and malignancies (Table 71.1). While literature reviews indicate infections account for the majority of fever of unknown origin (FUO), rheumatologic diseases and malignancies each account for about 20% to 25% of cases.
|Escherichia coli infections|
|Gonococcal and meningococcal infections|
|Human immunodeficiency virus|
|Chikungunya and other arboviruses|
|Atypical mycobacterial infections|
|Systemic lupus erythematosus|
|Vasculitis (e.g., MPA, GCA, GPA)|
|Adult onset Still’s disease (AOSD)|
|Systemic-onset juvenile idiopathic arthritis (SoJIA)|
|Muckle–Wells syndrome (MWS)|
|Familial Mediterranean fever (FMF)|
|Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)|
|Crystalline diseases (gout, CPPD, calcium hydroxyapatite)|
|Solid tumors +/− metastases|