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SAN ANTONIO
BRAIN HEALTH
MEDICINE

Update on Systemic Lupus Erythematosus

By Pendleton Wickersham, MD

ystemic Lupus Erythematosus (SLE) is a complex multisystem 2. Standard Immunosuppression: Glucocorticoids are used for
autoimmune disease frequently encountered in clinical medicine, flares at the lowest effective dose for the shortest duration possible
Sboth in initial diagnosis and long-term management. Its hetero- due to long-term toxicities. The EULAR guidelines recommend
geneity presents ongoing diagnostic and therapeutic challenges. This 5mg of prednisone daily as the maximum safe dose. New data
update highlights both key areas of progress and important clinical suggests that corticosteroids increase cardiovascular risk in
reminders. lupus patients independently of other factors. Mycophenolate
mofetil (MMF), methotrexate (MTX), leflunomide (LFN)
Diagnostic Considerations and azathioprine (AZA) remain key steroid-sparing agents,
While the 2019 EULAR/ACR classification criteria are intended particularly in visceral disease such as lupus nephritis.
primarily for research, the use of a positive ANA as an entry criterion Cyclophosphamide is reserved for severe, life-threatening organ
followed by weighted clinical and immunologic domains does reflect involvement.
current clinical thinking. The clinician must consider many diverse 3. Biologics & Targeted Therapies: Much as has occurred in other
presentations with myriad symptoms including fatigue, fever, mouth rheumatologic diseases, biologics are becoming the standard of
and nasal sores, rash (especially photosensitive), arthritis, serositis, care for the treatment of patients with moderate to severe SLE. The
cytopenia, nephritis and neuropsychiatric manifestations. A high landscape of biologic treatment options is expected to expand dra-
index of suspicion is crucial, especially in young women presenting matically over the next five to 10 years. Current treatment options
with vague multisystem complaints. Key autoantibodies beyond ANA include:
testing include anti-dsDNA (suggesting nephritis risk), anti-Sm (highly • Belimumab (Anti-BLyS/BAFF): Approved for non-renal
specific), antiphospholipid antibodies (associated with thrombosis SLE and, more recently, for lupus nephritis in combination
and pregnancy morbidity) and anti-Ro/SSA and anti-La/SSB (often with standard therapy. Belimumab targets B-cell activation
associated with photosensitive rash). and survival. Potential risks of therapy include serious infec-
tion, malignancy, infusion reactions and depression.
Pathophysiology Insights Driving Therapy • Anifrolumab (Anti-Type I IFN Receptor): A significant
Research continues to underscore the central role of the Type I advance directly targeting the IFN pathway. Approved for
interferon (IFN) pathway in SLE pathogenesis. Overproduction of moderate-to-severe SLE (non-renal) in patients inadequately
Type I IFNs drives immune dysregulation, autoantibody production controlled on standard therapy, anifrolumab offers another
and subsequent tissue damage. This understanding has directly led to option for patients with persistent disease activity, particular-
targeted therapies. ly those with prominent skin and joint involvement. Potential
risks of therapy include serious infection (especially viral) and
Therapeutic Landscape Evolution infusion reactions. Malignancy risk is not completely known
1. Hydroxychloroquine (HCQ): HCQ remains a foundational but trials suggest minimal risk.
therapy, which is crucial for nearly all SLE patients, regardless • Voclosporin (Calcineurin Inhibitor): Approved specifically
of severity. It can improve skin and joint manifestations, reduce for active lupus nephritis in combination with MMF and low-
flare rates, lower organ damage accrual, decrease thrombotic risk, dose steroids. Voclosporin provides rapid reduction in protein-
and improve survival. Dose optimization (ideally ≤5 mg/kg actu- uria by stabilizing podocytes and inhibiting T-cell activation.
al body weight/day) and regular ophthalmologic screening to Potential risks include elevated blood pressure and decreased
exclude retinal toxicity are essential. renal function as well as serious infections.

30 SAN ANTONIO MEDICINE • June 2025