Case Presentation: A
67-year-old woman with a five-year history of rheumatoid arthritis,
characterized by arthritis and positive rheumatoid factor, had been on
leflunomide treatment for four consecutive years. She was referred to the
nephrology department on July 10, 2023, due to declining kidney function and
nephrotic syndrome (edema, serum albumin 2.5 g/dl, proteinuria/creatinine ratio
6.1 g/g, serum creatinine 1.28 mg/dl). She presented with fatigue, hair loss,
and joint pain. She also had a history of hypertension, treated with enalapril
10 mg every 24 hours. Upon initial evaluation, vital signs were stable.
Physical examination revealed malar rash, swan-neck deformity of the right
index finger, and lower limb edema. There was no evidence of dry skin, dry
eyes, or conjunctival changes. Laboratory tests showed anemia, with positive
antibodies for ANA, anti-DNA, anti-SSA, anti-SSb, and anti-CCP, a VSG of 62
mm/hr, and C3/C4 levels of 22 and 3.3, respectively. Serum and urine
electrophoresis were negative. Urinalysis indicated 100 red blood cells per
high-power field, oval fat bodies, and fat droplets.
Renal biopsy revealed
membranoproliferative glomerulonephritis due to immune complexes with active
focal extracapillary proliferation, eight of eighteen glomeruli with global
sclerosis, diffuse mesangial expansion with global proliferation, irregular, folded,
laminated, and duplicated basement membranes with interposed cells, four
glomeruli with endocapillary hypercellularity with leukostasis and
karyorrhexis, and five glomeruli with cellular and fibrocellular crescents.
Hypertrophic and vacuolated podocytes were observed. The interstitium showed
areas of fibrosis and approximately 25-30% cortical tubular atrophy. Two
glomeruli were designated for direct immunofluorescence, showing intense
positive staining for C3, IgG, IgM, IgA, and C1q, kappa, and lambda, with a
granular, global, and diffuse pattern in the glomerular basement membranes,
mesangium, and subendothelium. Findings were consistent with a diagnosis of
lupus nephritis (LN) class III + V.
Serum creatinine increased to
2.08 mg/dl, and the patient was hospitalized for three boluses of 500 mg
methylprednisolone every 24 hours. Cyclophosphamide was planned but was in
short supply, so rituximab (1 g on days 0 and 15) and mycophenolate mofetil (1
g every 12 hours) were initiated. Prednisone was continued at 1 mg/kg/day with
a taper to 5 mg/day by week 11. Renin-angiotensin system blockade with
irbesartan 150 mg every 12 hours, dapagliflozin 10 mg every 24 hours, and
hydroxychloroquine 200 mg every 24 hours were administered as antiproteinuric
measures. Monthly follow-up showed a proteinuria/creatinine ratio of 0.60 g/g
at the third month, with C3/C4 levels increasing to 36 and 15, respectively.
The patient remains in remission, with the last creatinine level at 1.99 mg/dl.
Discussion: The prevalence of
"rhupus" among SLE patients varies from 0.09% to 9.7%. In the two
most recent and extensive studies, prevalence rates of 1.3% and 1.4% were
observed. These differences can be attributed to variations in inclusion criteria
and diagnostic approaches, likely resulting in an underdiagnosis of
"rhupus." SLE is a chronic condition primarily affecting young women,
and approximately 35% of individuals diagnosed with SLE will exhibit signs of
lupus nephritis (LN) at the time of diagnosis. The optimal diagnosis is based
on a renal biopsy with histopathological findings demonstrating
glomerulonephritis mediated by immune complexes, characteristic of LN.
Late-onset SLE represents a specific subgroup, with no defined age limit, but
it is often considered to occur after the age of 50. SLE and RA have
substantially different immunopathogenic mechanisms, with RA primarily
associated with a Th1 immune response and SLE associated with a Th2 immune
response. In patients with "rhupus," various factors likely explain
the overlap, such as the polarization of senescent T cells, the human leukocyte
antigen (HLA) complex, and hormonal factors. Inflammatory markers, such as PCR
and VSG, increase more in patients with "rhupus." Anti-CCP antibodies
are highly specific (95-98%) and sensitive (70-80%) for RA, playing a crucial
diagnostic role in "rhupus." In the case we are discussing, the
patient exhibited late-onset SLE with LN and a diagnosis of RA with an elevated
VSG and positive anti-CCP, leading to the diagnosis of "late-onset
rhupus."