Case Presentation: Patient is a 45-year-old female who presented to the ED for a 5 day history of abdominal pain, shortness of breath, inspiratory chest pain, and anemia (Hgb 6.2) discovered at an Urgent Care Center. She has no medical history, takes no medications, and does not use alcohol, tobacco, or drugs. She reports that she has always had constipation, that her hands and feet are frequently cold and “yellow,” and that her menstrual cycle has been irregular recently. Exam was significant for pallor, decreased breath sounds over right lower chest, abdominal distension and tenderness, and pale fingertips with a yellow hue. Pertinent labs include WBC 3.19, ESR 47, LD 330, Na 124, Cl 90, Ca 80, AST 57, and ALT 14. She also had a positive hepatitis C antibody, negative ANA, RF 51, C3 77, C4 7, and D-Dimer of 13.73. Urinalysis revealed large blood and 30 mg/dL protein.
CT abdomen/pelvis and CTA revealed moderate volume, low density ascites, large pericardial effusion, large right pleural effusion, and no evidence of PE. Initial differential included hepatitis C with mixed cryoglobulinemia, an autoimmune process, and malignancy. She underwent paracentesis, and the aspirate had many lymphocytes and rare lupus cells. Hep C viral PCR, cryoglobulins, repeat ANA, ENA, anti-CCP, anticardiolipin, and anti-beta2-glycoprotein were all negative. PTT lupus anticoagulant was prolonged to 50.2. She developed bilateral lower extremity edema, and her creatinine increased from 0.93 to 1.13. She underwent renal biopsy, which showed class III lupus nephritis. She began treatment with high dose prednisone and cyclophosphamide in an attempt to save her kidneys.
Discussion: The switch from using rodent tissue to the human Hep-2 cell line for ANA immunofluorescence has resulted in the near disappearance of ANA negative SLE. Though rare, these cases do exist, and treatment should follow the same algorithm as ANA positive SLE. Over time, some patients may become ANA positive, though historically most have remained ANA negative at follow up. ACR does not require the presence of autoantibodies to diagnose SLE if enough clinical criteria are met, so the index of suspicion for SLE should remain high if there is a convincing clinical picture for it regardless of laboratory findings.
Conclusions: Although ANA negative lupus previously comprised ~5% of SLE diagnoses in 1970s-80s due to poor sensitivity of immunofluorescence testing, it is now an extremely rare entity that may be unrecognized by younger physicians. It is important that physicians not eliminate the possibility of SLE on the basis of a negative ANA if there is convincing clinical evidence of such a diagnosis, as this could result in delayed treatment and irreversible organ damage.