Dermatology MCQ - Inflammatory Dermatoses - Systemic lupus erythematosus management

A 28-year-old woman is diagnosed with systemic lupus erythematosus (SLE) based on the presence of a malar rash, polyarthritis, positive ANA, and anti-dsDNA antibodies. Her urinalysis is normal, and she has no other major organ involvement. In addition to advising strict sun protection, which of the following is the most appropriate initial long-term pharmacologic management for this patient?

A. High-dose oral prednisone (1 mg/kg/day)
B. Oral hydroxychloroquine
C. Oral cyclophosphamide
D. Oral mycophenolate mofetil
E. Intravenous rituximab

Correct Answer: B. Oral hydroxychloroquine

Explanation

The management of SLE is tailored to the severity and type of organ involvement. This patient has active but non-life-threatening, non-major organ disease (skin and joints).

• First-Line Therapy for Mild-Moderate SLE: Hydroxychloroquine (HCQ) is considered a cornerstone of therapy for all patients with SLE, barring contraindications. Its benefits extend beyond symptom control for skin and joints; it reduces disease flares, improves long-term survival, protects against organ damage, and has favorable effects on lipid profiles and thrombosis risk. It is the foundation upon which other therapies are added if needed.

Why other options are incorrect

• A. High-dose oral prednisone (1 mg/kg/day): High-dose corticosteroids are reserved for severe, life-threatening, or major organ manifestations of SLE (e.g., lupus nephritis, neuropsychiatric lupus, severe hemolytic anemia). Using them as initial long-term therapy for mild disease exposes the patient to significant long-term toxicities (e.g., osteoporosis, diabetes, cataracts, weight gain) unnecessarily. A short course of low-dose steroids may be used to control symptoms initially while HCQ takes effect, but it is not the preferred long-term monotherapy.

• C. Oral cyclophosphamide: This is a potent alkylating agent used for the most severe forms of organ-threatening lupus, such as diffuse proliferative (Class IV) lupus nephritis or severe central nervous system involvement. Its significant toxicity profile (including infertility, hemorrhagic cystitis, and malignancy risk) makes it inappropriate for mild disease without major organ involvement.

• D. Oral mycophenolate mofetil: Mycophenolate mofetil (MMF) is a first-line agent for the induction and maintenance therapy of proliferative lupus nephritis (Class III/IV). It is also used for other severe manifestations. It is not indicated as first-line treatment for SLE limited to mucocutaneous and articular disease.

• E. Intravenous rituximab: Rituximab, a B-cell depleting agent, is typically reserved for cases of SLE that are refractory to standard treatments like corticosteroids, antimalarials, and other immunosuppressants (e.g., MMF, azathioprine). It is not an initial therapy for a newly diagnosed patient with mild disease.

Key Associations for SLE Management

• General Principles: The goal of treatment is to control symptoms, prevent flares, and minimize organ damage while minimizing drug toxicity. Treatment is a spectrum:

  • Mild Disease (Arthritis, Rash, Serositis): Antimalarials (HCQ) are first-line. NSAIDs and low-dose corticosteroids may be used as bridge therapy.

  • Moderate-Severe Disease (e.g., Hematologic cytopenias, more severe serositis): Corticosteroids (moderate dose) are added, often with a steroid-sparing agent like azathioprine or methotrexate.

  • Major Organ Disease (Lupus Nephritis, CNS Lupus): High-dose corticosteroids plus a potent immunosuppressant like mycophenolate mofetil or cyclophosphamide are used for induction, followed by a maintenance agent like MMF or azathioprine.

• Role of Hydroxychloroquine: Beyond its immunomodulatory effects, HCQ is crucial for its ability to reduce the risk of disease flares and damage accrual. All patients should have a baseline ophthalmologic examination and annual screening after 5 years of use to monitor for the rare complication of retinal toxicity.

• Biologics: Belimumab, a monoclonal antibody that inhibits B-cell activating factor (BAFF), is approved for active, autoantibody-positive SLE (often with musculoskeletal and cutaneous involvement) in patients who have not responded adequately to standard therapy. Rituximab is used off-label for severe, refractory cases.

• Prognosis: The prognosis for SLE has improved dramatically over the decades. The 10-year survival rate now exceeds 90%. The leading causes of early mortality are active SLE and infections, while the leading causes of late mortality are cardiovascular disease and malignancy, highlighting the importance of managing traditional risk factors and minimizing long-term corticosteroid exposure.