Fever, rash, and positive Ehrlichia antibodies. Class IV-G(A) lupus nephritis.

A 21-year-old Asian woman presented with a waxing and waning course of low-grade fevers, malaise, pain in the small joints of her hands, a faint facial rash, and hair loss over a period of several weeks. Except for the findings mentioned above, her physical exam was unremarkable. Laboratory studies revealed leukopenia (2.5 × 103/μl), anemia (11.3 g/dL), and thrombocytopenia (100 × 103/μl). Antibody testing revealed positive direct antinuclear antibodies (1186 AU/ml), positive Antistreptolysin O titer (310 IU/ml), positive Epstein–Barr virus immunoglobulin IgG antibody (3186 AU/ml), positive Ehrlichia chaffeensis IgM (1:60) and IgG (1:512), and positive human granulocytic ehrlichiosis IgG (1:512) by indirect fluorescent antibody. Of note, IgM titers for Epstein–Barr virus and human granulocytic ehrlichiosis were negative. Human granulocytic ehrlichiosis testing was also negative. In the presence of multiple positive serologies, laboratory data, and some clinical features, the patient was presumptively treated for ehrlichiosis with a 14-day course of doxycycline. At a 4-week follow up, repeat Ehrlichia chaffeensis IgM and IgG titers were further elevated (1:1024 and 1:2048, respectively) and retreatment with minocycline was initiated. Due to drug intolerance the patient discontinued the treatment. A urinalysis revealed 3+ protein; 24 h urine protein measured 0.6 gm/day and in the following week increased to 1.7 gm/day. A renal biopsy was performed.

What is the renal biopsy likely to show?

The Diagnosis ∣ Class IV-G(A) lupus nephritis

Further clinical decline occurred and over the subsequent 2-week period, her presentation met the American College of Rheumatology criteria for a definitive diagnosis of systemic lupus erythematosus (SLE) (positive antinuclear antibody, positive anti-double-stranded DNA, malar rash, proteinuria, leukopenia, thrombocytopenia, and psychosis).

Renal biopsy (Figure 1 ) revealed diffuse proliferative lupus nephritis (ISN/RPS Class IV-G(A)) with activity index 10/24 and chronicity index 0/12 according to the National Institutes of Health criteria. Focal evidence of lupus vasculopathy was identified.

Figure 1

Renal biopsy showing diffuse proliferative lupus nephritis (ISN/RPS Class IV-G(A)) with focal evidence of lupus vasculopathy.

Ehrlichiosis and SLE have comparable features. Symptoms of ehrlichiosis include severe headache, myalgias, and fever. Confusion may also occur. Nausea, vomiting, and abdominal pain are uncommon and mild. Symptoms of SLE include fever, malaise, anorexia, fatigue, weight loss, myalgias, photosensitivity, alopecia. Cognitive dysfunction, headache, mood disorder, cerebrovascular disease, seizures, polyneuropathy, anxiety, and psychosis may also occur. On exam, patients with ehrlichiosis display a maculopapular rash and hepatomegaly. Lymphadenopathy is observed in less than 25%. Malar rash or discoid rash and symmetrical oligoarticular arthritis are seen in SLE. Lymphadenopathy is frequently observed; however generalized lymphadenopathy is rare. Laboratory findings in ehrlichiosis include positive serology, thrombocytopenia, and disseminated intravascular coagulation (in severe ehrlichiosis). In SLE, positive serology, leukopenia, lymphopenia, anemia, and thrombocytopenia have been well described.

Within 1 week of initiation of treatment with steroids and mycophenolate mofetil, Ehrlichia chaffeensis titers (IgM and IgG) were undetectable and titers to EBV IgM and IgG decreased (0.49 and 6.83 AU/ml, respectively). Within several weeks the patient's SLE entered remission.

This case report illustrates the importance of recognizing false-positive antibody titers in the presence of active SLE. In addition to Ehrlichia, false-positive antibodies to the following infectious etiologies have been reported in patients with SLE: syphilis, Lyme disease, hepatitis C, HIV, cytomegalovirus, and the severe acute respiratory syndrome virus. To our knowledge, this is the first reported association of false-positive Ehrlichia species antibodies in patients with SLE.