ANA-Negative Presentation of SLE in Man with Severe Autoimmune Neutropenia

Abstract

Background. Systemic lupus erythematosus (SLE) is a chronic, inflammatory, connective tissue disease that commonly affects the joints and a variety of organs due to an overactivation of the body's immune system. There is wide heterogeneity in presentation of SLE patients, including lung, central nervous system, skin, kidney, and hematologic manifestations. Case Presentation. We report a case of atypical manifestation of SLE in a 53-year-old man who presented with neutropenic fever. Physical findings of interest included oral ulcers on the lower lip, a malar-like rash across the bridge of the nose, and a discoid-like rash on extensor surfaces of the elbows and knees. Labs include ANC <100, weakly positive anti-dsDNA, negative ANA, ferritin 1237 ng/mL, low C3/C4, and positive direct Coombs' test. A thorough workup for infection and hematologic malignancy was negative. Two days after initiation of therapy with 25 mg IV solumedrol twice a day, the patient's daily fevers resolved. ANC drastically improved to 2000 after two weeks of steroid treatment. He was later found to have a high titer of anti-neutrophil antibodies. Discussion. Autoimmune leukopenia is a common presentation in SLE, occurring in 50–60% of patients. Severe autoimmune neutropenia is uncommon and may correlate with high anti-neutrophil antibody activity despite a negative ANA. As neutropenia is usually mild, there are currently no guidelines for therapy. For our patient, we started him on low dose IV solumedrol and found that he responded drastically to treatment. Given strongly positive nonspecific anti-neutrophil antibodies in the setting of a negative ANA noted in our patient, it is likely that there are other currently unknown antibodies associated with SLE which may correlate strongly with autoimmune neutropenia.

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

“…The presence of anti‐dsDNA in ANA‐negative SLE patients has been reported by others . These patients were reported to have more severe complications, including nephritis , dystrophic calcification , or severe autoimmune neutropenia . Thus, the detection of anti‐dsDNA antibodies even in ANA‐negative cases is still important and may aid in risk assessment for clinical complications.…”

A Case Report of Male Systemic Lupus Erythematous with Antinuclear Antibodies-Negative: A Challenging Diagnosis

“…ANAs have a sensitivity of 33.6%, while anti-dsDNA has a sensitivity of 57.1%, indicating that a significant portion of SLE cases may be missed based on these markers alone. Studies have suggested that a positive ANA may disappear in some SLE patients over time, with sensitivity dropping to 76% and positivity dropping from 98% to 71% in patients with established SLE [ 9 ]. Khajehdehi et al [ 10 ] reported a rare case of class III lupus nephritis in a male who developed clinical flare-up of SLE despite being ANA-negative.…”

“…Khajehdehi et al [ 10 ] reported a rare case of class III lupus nephritis in a male who developed clinical flare-up of SLE despite being ANA-negative. Zhao [ 9 ] suggested that more biomarkers may be associated with SLE, given the strongly positive nonspecific anti-neutrophil antibody in the setting of marker negativity.…”