Fever in Lupus Nephritis Flares
Yes, fever is a recognized constitutional manifestation of lupus nephritis flares, occurring in approximately one-third of patients experiencing disease flares, though infection must always be excluded as fever can also indicate superimposed bacterial infection in these immunosuppressed patients. 1, 2
Clinical Context and Frequency
Fever occurs as part of the constitutional symptoms during lupus nephritis flares in a substantial proportion of patients:
- Constitutional manifestations, including fever, occur in 40.6% of SLE flares during dialysis, with fever specifically documented in 34.3% of flare episodes 1
- In hospitalized SLE patients with fever, 60% of febrile episodes are attributed to active lupus alone, while 23% are due to infections 2
- Lupus nephritis flares are common, occurring in 27-66% of patients with SLE, and renal flares specifically occur in up to 45% of patients with lupus nephritis 3, 4
Critical Distinction: Lupus Flare vs. Infection
The most important clinical challenge is distinguishing fever from lupus activity versus superimposed infection, as this fundamentally changes management:
Features Suggesting Infection Rather Than Lupus Flare:
- CRP >50 mg/L strongly suggests infection rather than lupus activity, as SLE patients rarely have elevated CRP from lupus alone 4, 5
- Leukocytosis and neutrophilia are associated with infection 2
- Shaking chills suggest infection 2
- Normal or stable anti-dsDNA antibody levels favor infection over lupus flare 2
Features Suggesting Lupus Flare:
- Rising anti-dsDNA antibody titers correlate with disease activity and active renal disease 4, 6
- Low complement levels (C3/C4) are significantly associated with active renal disease 7, 6
- Presence of other lupus manifestations (hematologic abnormalities, particularly thrombocytopenia and leukopenia) 1
Diagnostic Approach When Fever Occurs
When a patient with lupus nephritis develops fever, you must simultaneously evaluate for both lupus flare and infection:
- Obtain inflammatory markers: ESR and CRP, with CRP >50 mg/L strongly favoring infection 5
- Check serologic markers: anti-dsDNA antibodies and complement levels (C3, C4) to assess lupus activity 6, 5
- Obtain blood cultures if infection is suspected 5
- Assess renal flare indicators: serum creatinine, urine sediment analysis, proteinuria quantification, and blood pressure 4, 7
- Look for red blood cell casts, white blood cell casts, or acanthocytes (≥5%) in urine sediment 7
Clinical Implications
Bacteremia carries significant mortality risk in SLE patients, resulting in fatal outcomes in one-third of infected patients 2. Therefore, err on the side of treating infection empirically while awaiting culture results in febrile patients with lupus nephritis, particularly those on immunosuppressive therapy.
Higher nonrenal SLEDAI scores before dialysis initiation predict increased risk of disease flares (HR 1.24,95% CI 1.12-1.36) 1, indicating that patients with more active extrarenal disease require closer monitoring.
Management Considerations
- Hematologic manifestations are the most common flare features (40.6%), particularly thrombocytopenia (31.2%) and leukopenia (21.8%) 1
- Treatment of lupus flares typically requires corticosteroids, with approximately one-third of patients requiring additional immunosuppressants such as cyclophosphamide or mycophenolate mofetil 1
- Continued follow-up and appropriate immunosuppressive treatment should be maintained even in patients on dialysis, as more than a quarter experience disease flares 1