Systemic lupus erythematosus: Viva

Branch 1: Classification

The candidate should classify this as systemic lupus erythematosus using the 2019 European League Against Rheumatism and American College of Rheumatism criteria. The entry criterion is a positive antinuclear antibody at any time, which is met. The weighted score then exceeds the threshold of 10 points: acute cutaneous lupus (the malar rash) scores 6 in the mucocutaneous domain, joint involvement scores 6 in the musculoskeletal domain, low C3 and C4 together score 4, and anti-dsDNA scores 6 in the SLE-specific antibody domain. A strong candidate states that each criterion counts once, the highest within a domain is taken, and a more likely alternative must be excluded. [1]

If the examiner presses on the older criteria, the candidate should contrast the 2019 system with the 1997 American College of Rheumatology criteria (at least four of eleven criteria) and the Systemic Lupus International Collaborating Clinics 2012 criteria (at least four of seventeen, with one clinical and one immunological), demonstrating familiarity with the lineage and the move toward weighting by specificity. The candidate should also flag that the urinalysis abnormality mandates renal biopsy, and that a biopsy showing class III or IV lupus nephritis would classify lupus regardless of the point total via the biopsy shortcut. [1]

Branch 2: Mechanism

The candidate should explain that lupus begins with defective clearance of apoptotic cells, which release double-stranded DNA and nucleosomes that are normally sequestered. Persistent antigen exposure breaks tolerance, generating high-affinity autoantibodies such as anti-dsDNA (which correlates with activity and nephritis) and anti-Smith (the most specific marker of the disease). These form circulating immune complexes that deposit in tissue, activate the classical complement pathway, and consume C3 and C4, which is why low complement is the serological signature of active disease. [2]

A strong candidate then identifies the type I interferon pathway as the amplifier that sustains the loop. Plasmacytoid dendritic cells, activated by nucleic-acid-containing immune complexes, produce type I interferons that activate antigen-presenting cells, promote B-cell maturation, and upregulate the very pathways that generate more nuclear antigen. This feed-forward loop explains why lupus is chronic and relapsing, and it is the therapeutic rationale for anifrolumab, the type I interferon receptor antagonist established in the TULIP-2 trial. [4]

Branch 3: Treatment plan

The candidate should present the stepwise ladder. The foundation is hydroxychloroquine at 5 mg per kg per day (the lesser of weight-based or 400 mg per day) for every patient, with strict sun protection, vaccination, and cardiovascular and bone protection. Because of retinopathy risk, the candidate should describe baseline ophthalmology screening within the first year then annual screening after five years, as codified by the 2016 American Academy of Ophthalmology recommendations. [3]

For the active organ-threatening disease, the candidate adds glucocorticoids at the lowest effective dose for the shortest time, with intravenous methylprednisolone pulses (30 mg per kg, maximum 1 g) for the induction, followed by a prednisolone taper. Steroid-sparing immunosuppression follows: mycophenolate mofetil (target 2 to 3 g per day) or azathioprine for general and renal disease, with mycophenolate preferred over cyclophosphamide first-line in children to spare the gonads. For refractory disease, the candidate should name belimumab (a B-cell-activating factor inhibitor) and anifrolumab (the type I interferon receptor blocker). The candidate should close with the principle that infection must be excluded before escalating immunosuppression, and that a rising anti-dsDNA with falling complement is the serological signature of a flare. [2]