Lupus Abstract:
Systemic lupus erythematosus (SLE) is a multisystem disease with a complex etiology which manifests in a multitude of manners. We present a case of lupus nephritis in a patient who developed complications of immunosuppressive treatment with eventual resolution of her nephritis following cure of her Nocardia brain abscess.
Key words:
Systemic Lupus Erythematosus, Lupus Nephritis, Nocardia, Immunocompromised
Background/Objective: Lupus nephritis occurs in 50% of patients with systemic lupus erythematosus (SLE) within the first year of diagnosis1. Multiple theories exist with regards to the pathophysiology of lupus nephritis to include immune complex deposition, autoantibody: self-antigen binding, and cross-reactivity of antibodies with renal parenchyma2. Prior studies have demonstrated the role of infective agents in the development of autoimmune disease. In concert with the gut microbiome, the skin microbiome is characterized by the presence of several micro-organisms influencing the innate and adaptive immune systems. We present a unique case of lupus nephritis in a 47 year old African American female who developed complications of immunosuppressive treatment with eventual resolution of her lupus nephritis following cure of her Nocardia brain abscess.
Case Report: A 47 year old female with no known history of SLE or renal disease presented with edema, proteinuria, and hypoalbuminemia consistent with nephrotic syndrome in June 2008. Serum serology was positive for anti-dsDNA >300IU/ml (0-4IU/ml), anti-SSA, anti-RNP, and anti-SM antibodies. Laboratory data also revealed hypocomplementemia C3 74mg/dl (82-167mg/dl), C4 4mg/dl (14-144mg/dl), low Ch50 <10mg/dl (31-60mg/dl), leukopenia, and anemia (See Tables 1 and 2 for complete biochemical evaluation). A renal biopsy was performed which revealed findings consistent with membranous lupus nephritis (Figure 1). Histopathology demonstrated “full house” staining on immunofluorescence and deposits in all compartments on electron microscopy. The biopsy results, coupled with the patient meeting EULAR criteria for SLE, met the diagnostic criteria for Class V Lupus Nephritis. Mycophenolate mofetil 1000mg BID and prednisone 60mg daily were initiated in July 2008.
In November 2008, she presented to her nephrologist with homonymous hemianopsia, headache, nausea, and vomiting. Renal function and serology were unchanged, and proteinuria was stable at 7.5 grams/24 Hours. Expedited MRI brain revealed abscesses in her right occipital lobe (Figure 2). Immunosuppression was immediately stopped and she was transferred to an outside facility for neurosurgical drainage. CSF cultures demonstrated growth of Nocardia asteroides. She was initiated on intravenous meropenem and oral linezolid for an interval of 3 months with transition to oral minocycline for a total antibiotic duration of one year. Her occipital lobe abscesses were resolved in March 2009 on follow up with her neurosurgeon.
Given the association of the intracranial abscess and immunosuppressed state, the mycophenolate mofetil and prednisone were not restarted. As the infection resolved, so did her proteinuria and positive serology studies except for anti-SSA. By June 2009, complement levels, nephrotic range proteinuria, anemia, and leukopenia had normalized (Table 3 and Figure 1). As of December 2019, the patient remained in complete remission with normal serology, including normalized anti-SSA (table 4).
Discussion: Systemic lupus erythematosus is a multisystem disease with a complex etiology. It can manifest in a multitude of manners affecting virtually every organ system with a highly variable clinical course2. Lupus nephritis is a common entity in patients with SLE and can be the initial presentation of this disease process.3 It is postulated that epigenetics plays a crucial role in the manifestation of this disease. Epidemiologic studies demonstrate the strongest association with cigarette smoking, crystalline silica exposure, oral contraceptives, and postmenopausal HRT but emerging research has proposed the role of infections in SLE, and other autoimmune disease, emergence.2,4,5 For instance, staphylococcus aureus is hypothesized to colonize at a higher prevalence in those with autoimmune disorders when compared to those without similar disorders4. Another example is seen in rheumatoid arthritis, as porphyromonas gingivalis bacterium has been postulated to play a central role in disease development due to its ability to induce citrullination4. Therefore it can be assumed that if the innate and adaptive immune system can modulate the resident microbiome then the opposite is also plausible. In the case presented above, it appears, despite grossly limited immunosuppression therapy, complete remission of her lupus nephritis was only obtained through chronic treatment of an underlying Nocardia asteroides infection. This suggests that bacterial infections could potentially play a crucial role in the pathophysiology of lupus nephritis in patients with SLE.
The authors confirm contribution to the paper as follows:
Study conception and design: Francis Essien D.O., Joshua Tate M.D.,
Data collection: Francis Essien D.O., Joshua Tate M.D., Wayne Latack M.D.
Analysis and interpretation of results: Francis Essien D.O., Joshua Tate M.D., Wayne Latack M.D.
Draft manuscript preparation: Francis Essien D.O., Joshua Tate M.D.
All authors discussed the results and contributed to the final manuscript