Systemic lupus erythematosus: SAQ

This girl has childhood-onset systemic lupus erythematosus. The combination of the malar rash sparing the nasolabial folds, painless oral ulcers, photosensitivity, a non-erosive symmetrical arthritis, autoimmune haemolytic anaemia with a positive direct antiglobulin test, thrombocytopenia, and lymphopenia, together with a strongly positive antinuclear antibody, high-titre anti-dsDNA, and low complement C3 and C4, is diagnostic of active multisystem lupus in an adolescent girl. The active urinary sediment with blood and protein mandates renal biopsy because the histological class of lupus nephritis determines the induction strategy. [1]

Question 1 (10 marks)

Outline the EULAR/ACR 2019 classification criteria for systemic lupus erythematosus and apply them to this patient. [1]

A complete answer states that the 2019 European League Against Rheumatism and American College of Rheumatism criteria are a weighted additive system. The mandatory entry criterion is a positive antinuclear antibody at any time, which this girl meets with a strongly positive titre of 1 in 1280. After the entry criterion is satisfied, weighted points are summed across clinical and immunological domains, and classification requires a cumulative score of 10 or more points, with each criterion counted once and the highest within a domain taken, and a more likely alternative explanation excluded. [1]

Applying the criteria to this patient: the malar rash is acute cutaneous lupus, scoring 6 points in the mucocutaneous domain; the joint pains reflect joint involvement, scoring 6 points in the musculoskeletal domain; the autoimmune haemolysis with a positive direct antiglobulin test scores 4 points in the haematological domain (the thrombocytopenia and lymphopenia also belong to this domain but only the highest, the haemolysis at 4, is counted); the low C3 and C4 together score 4 points in the complement subdomain; and the anti-dsDNA antibody scores 6 points in the SLE-specific antibody domain. The clinical and immunological contributions easily exceed the threshold of 10 points, confirming the classification. A candidate should also mention that the planned renal biopsy, if it shows class III or IV lupus nephritis, would classify lupus regardless of the point total via the biopsy shortcut. [1]

The candidate should briefly contrast the 2019 system with the older criteria: the 1997 American College of Rheumatology criteria require at least four of eleven criteria, and the Systemic Lupus International Collaborating Clinics 2012 criteria require at least four of seventeen criteria including at least one clinical and one immunological criterion. This demonstrates the expected familiarity with all three systems and their lineage. [2]

Question 2 (10 marks)

Describe the stepwise management of this patient, including the role and monitoring of hydroxychloroquine. [4]

A strong answer frames management as a stepwise ladder with the goals of controlling disease activity, preventing organ damage from both the disease and its treatment, and preserving growth, development, and quality of life. The foundation, recommended for every patient, is hydroxychloroquine at 5 mg per kg per day, using the lesser of the weight-based dose or 400 mg per day. Hydroxychloroquine reduces flares, improves survival, protects against renal and cutaneous relapse, reduces thrombosis, and is safe in pregnancy, so it should be started immediately. [4]

Because hydroxychloroquine can cause a bull's-eye maculopathy, screening for retinopathy is mandatory. The candidate should describe a baseline ophthalmology assessment including colour vision, visual fields, and optical coherence tomography within the first year of treatment, followed by annual screening after five years of therapy, or sooner in higher-risk patients such as those on higher doses, with renal impairment, or taking tamoxifen. The 2016 American Academy of Ophthalmology recommendations codified this weight-based dosing and screening schedule, and the candidate should quote the 5 mg per kg per day dose and the baseline-then-annual-after-five-years schedule. [3]

For this patient's active organ-threatening disease (haemolysis and probable nephritis), the next steps are glucocorticoids and steroid-sparing immunosuppression. Acute haemolysis is treated with intravenous methylprednisolone pulses (30 mg per kg per dose, maximum 1 g, daily for 3 days) followed by oral prednisolone (0.5 to 1 mg per kg per day, maximum 60 mg per day) tapered as quickly as the disease allows. For the nephritis, induction uses mycophenolate mofetil (target 2 to 3 g per day) or low-dose Euro-Lupus cyclophosphamide (500 mg every 2 weeks for 6 doses) with glucocorticoids; mycophenolate is preferred over cyclophosphamide first-line in children because cyclophosphamide is gonadotoxic. The candidate should add that the renal biopsy class will refine the induction choice, and that belimumab or anifrolumab are reserved for refractory disease. [4]