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A Wolf in Infection's Clothing: The Difficulties of Discerning Systemic Lupus Erythematosus from Its Infectious Sequelae

Published:February 03, 2015DOI:https://doi.org/10.1016/j.amjmed.2015.01.017
      To the Editor:
      Systemic lupus erythematosus is notorious for its heterogeneous clinical presentations. Additionally, infections can not only precipitate lupus flares but also develop as complications of therapy.
      • Navarra S.V.
      • Leynes M.S.
      Infections in systemic lupus erythematosus.
      We report on a patient who initially presented with lupus masquerading as a diarrheal illness that delayed her diagnosis, followed by readmission with multiorgan disease due to immunosuppression-related disseminated cytomegalovirus infection mistaken for central nervous system involvement of lupus.
      A 58-year-old South Asian woman was admitted with 2 months of cramping abdominal pain, 4 to 5 watery bowel movements daily, and intermittent fevers. Testing revealed elevated creatinine (1.7 mg/dL from 1.1 mg/dL) and a white blood cell count of 5.98 × 103/mm3 (716 lymphocytes/mm3). Results of a Clostridium difficile toxin polymerase chain reaction were positive, and the patient underwent oral vancomycin therapy, with improvement in her diarrhea.
      She had a concurrent annular rash over her cheeks and forearms, however, which did not fit the picture of C. difficile infection. Furthermore, her fevers persisted despite antibiotics. Subsequent urine studies revealed a urine protein/creatinine ratio of 8.09. Additional testing revealed an antinuclear antibody titer of 1:320, with positivity for anti-Smith and ribonucleoprotein antibodies, and low complement levels (C3: 56 mg/dL, and C4: 12 mg/dL).
      A renal biopsy (Figure) showed glomerular wire loops, “full house” immunofluorescence, and subendothelial and mesangial electron-dense deposits on electron microscopy, consistent with diffuse proliferative lupus nephritis. Skin biopsy showed interface dermatitis, consistent with subacute lupus. The patient was given methylprednisolone 1 g/d intravenously for 3 days, followed by prednisone 60 mg (1 mg/kg), hydroxychloroquine, and mycophenolate mofetil. She rapidly improved and was discharged home.
      Figure thumbnail gr1
      FigureImmunoflurescent staining of renal biopsy showing “full house” immunoglobulin and complement deposition. (A) IgM, (B) IgA, (C) IgG, (D) C3, (E) C1q, (F) kappa, (G) lambda.
      Two months later she returned with diffuse abdominal pain and melenic stools while taking 20 mg of prednisone daily and mycophenolate mofetil 500 mg twice daily. Her lipase was elevated at 992 U/L and white blood cell count decreased to 2.89 × 103/mm3 (144 lymphocytes/mm3). An abdominal computed tomography scan was consistent with pancreatitis, and esophagogastroduodenoscopy revealed a clean-based duodenal ulcer.
      Her mental status declined, with febrile episodes to 38.5°C, creatinine worsened to 2.3 mg/dL, and echocardiography showed depressed left ventricular systolic function with an ejection fraction of 15%-20% (previously normal). Cytomegalovirus polymerase chain reactions from the serum and cerebral spinal fluid were positive with levels of 116,000 IU/mL and low-level DNA detection, respectively. Mycophenolate was held, and she was initiated on ganciclovir. Her cytomegalovirus viral load gradually decreased, becoming undetectable 3 weeks later. The patient clinically improved, with mental status and renal function gradually returning to baseline; repeat echocardiography showed a normalized ejection fraction. She was discharged to a chronic care facility.
      Distinguishing between lupus and infection can be difficult, because fevers and signs of systemic inflammation are often present in both, underscoring the importance of maintaining a broad differential diagnosis and considering the entire clinical picture.
      Although some clinical or laboratory findings–such as a depressed white blood cell count or markedly elevated erythrocyte sedimentation rate with relatively suppressed C-reactive protein–are suggestive of systemic lupus erythematosus, diagnosing lupus ultimately requires ruling out infection, medication effects, and other autoimmune disease.
      • Navarra S.V.
      • Leynes M.S.
      Infections in systemic lupus erythematosus.
      • Gaitonde S.
      • Samols D.
      • Kushner I.
      C-reactive protein and systemic lupus erythematosus.
      Cytomegalovirus infections are a particularly important consideration, because they occur with greater propensity among patients with lupus and can similarly present with multisystem dysfunction.
      • Zhang J.
      • Dou Y.
      • Zhong Z.
      • et al.
      Clinical characteristics and therapy exploration of active human cytomegalovirus infection in 105 lupus patients.
      Conversely, clinical signs atypical for a suspected infection, or poor clinical response to targeted antimicrobial therapy (as was the case with our patient's initial presentation) should prompt broader consideration of noninfectious causes.
      The diagnostic quandary of fevers in lupus can be difficult, with appropriate management predicated on maintaining a broad differential with constant re-evaluation as dictated by changes in the patient's clinical status.

      References

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        • Leynes M.S.
        Infections in systemic lupus erythematosus.
        Lupus. 2010; 19: 1419-1424
        • Gaitonde S.
        • Samols D.
        • Kushner I.
        C-reactive protein and systemic lupus erythematosus.
        Arthritis Rheum. 2008; 59: 1814-1820
        • Zhang J.
        • Dou Y.
        • Zhong Z.
        • et al.
        Clinical characteristics and therapy exploration of active human cytomegalovirus infection in 105 lupus patients.
        Lupus. 2014; 23: 889-897