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