A 27-year-old woman, a schoolteacher, comes to the clinic with 3 months of fatigue, joint pain, and a facial rash. The rash is red, slightly raised, and spreads across both cheeks and the bridge of her nose. It worsens after sun exposure.

Her wrists, finger joints, and knees ache and are stiff in the morning, easing as the day goes on.

For the past 2 weeks, she has had sharp central chest pain that is worse when she breathes in deeply. She has lost 3 kg without trying, and her hair has thinned. She has had no recent infections and has not started any new medications.

Past Medical History: None

Medications: None

Allergies: None known

Social History: No tobacco, alcohol, or drug use. Not pregnant; she has a copper IUD and no plans for pregnancy in the immediate future (1-2 years), but she’d like to have kids after that.

Family History: Mother has rheumatoid arthritis.

Vital Signs: Temperature 99.1°F, heart rate 82 bpm, respiratory rate 16 bpm, blood pressure 132/86 mmHg, oxygen saturation 98% on room air. Body weight 60 kg.

Physical Exam: Red rash across the cheeks and nose. No oral ulcers. Lungs clear. Mild synovitis of the wrists and finger joints (PIPs), no deformity. No leg swelling. Neurological exam normal.

See image below. (Representative photograph of the lesion).

Laboratory tests:

After considering alternative causes of her findings, you diagnose her with SLE.

A. Prednisone 20mg daily, followed by a taper, guided by clinical response

B. Naproxen plus weekly methotrexate with folic acid supplementation

C. Naproxen plus colchicine with treatment duration guided by clinical response

D. Naproxen plus mycophenolate, titrated according to response and tolerability

Choose your answer now before moving on.

She has active lupus in three places: the skin, the joints, and the pericardium. There is no current evidence of organ or life-threatening disease. There is no clinical evidence of nephritis; she has mild leukopenia and borderline anemia with a normal platelet count; and her nervous system is normal. This question tests the ability to match treatment strength to the clinical picture.

Start hydroxychloroquine promptly unless contraindicated. The 2025 ACR guideline, the ACR's first guideline on overall SLE management since 1999, strongly recommends hydroxychloroquine for every patient with lupus unless contraindicated. Its long-term average daily dose goal is 5 mg/kg or less. At 60 kg, 300 mg daily is exactly 5 mg/kg.

Hydroxychloroquine is not fast-acting, so patients need a bridge for active symptoms. For lupus pleuritis or pericarditis, the guideline conditionally recommends starting with an NSAID, colchicine, or both, with a low threshold to add a steroid, rather than starting with a steroid alone. This fits her presentation. An NSAID also treats her arthritis while hydroxychloroquine takes effect. Her normal kidney function supports NSAID use, provided you assess gastrointestinal, cardiovascular, and drug-interaction risks; use gastroprotection during the anti-inflammatory NSAID course.

Her rash needs sun protection alongside hydroxychloroquine; a brief course of low-potency topical steroid or a topical calcineurin inhibitor can be used on the face. Reassess her pericarditis within 1–2 weeks, sooner for worsening chest pain, dyspnea, or syncope. Early review matters: if the pericarditis is not improving, add a short course of oral prednisone after reassessment. This is not an automatic failure of the plan.

A. Prednisone as the initial additional systemic treatment

A short course is clinically plausible and may be appropriate when symptoms warrant rapid control or NSAIDs and colchicine are unsuitable. However, the ACR conditionally favors an NSAID, colchicine, or both for initial lupus pleuropericarditis treatment, with a low threshold to add glucocorticoids. In this untreated patient without stated contraindications, C more closely follows that sequence. A is less preferred here, but it is not an inherently incorrect lupus treatment.

B. Naproxen plus methotrexate

This is a plausible approach to persistent inflammatory arthritis, and methotrexate may also help refractory skin disease. But she has not yet had a trial of hydroxychloroquine and initial symptomatic treatment. Starting methotrexate now prioritizes longer-term joint and skin control over the guideline-preferred initial approach to her active serositis. It becomes a stronger option if the arthritis persists or recurs.

D. Naproxen plus mycophenolate

Low complement, anti-dsDNA positivity, and activity in several systems can make broader immunosuppression tempting. Those findings alone do not establish nephritis or organ-threatening disease. Mycophenolate can be appropriate for persistent or recurrent extrarenal disease, including serositis, but this patient has not yet failed initial treatment. C is the more proportionate starting regimen; escalate based on clinical response.

In lupus, the diagnosis tells you to start hydroxychloroquine unless contraindicated. Everything else depends on which organs are active and how badly. Treat each one at its own intensity, use the least toxic drug that works as a bridge, and think of steroids as a short bridge, not the foundation.

Do not routinely stop hydroxychloroquine solely because lupus is well controlled. In a randomized trial of 47 patients with stable lupus, those switched to placebo were 2.5 times more likely to flare within 24 weeks (16 of 22 vs 9 of 25). The 2025 ACR guideline conditionally recommends continuing it indefinitely, even in remission, with reassessment for toxicity, contraindications, and patient preferences.

Dose by real weight, not ideal weight. The American Academy of Ophthalmology recommends a maximum of 5 mg/kg/day of real body weight, which predicts retinal risk better than ideal weight. The 2023 EULAR lupus recommendations use the same target. For our 60 kg patient, that is 300 mg daily. A flat 400 mg daily would be 6.7 mg/kg for her.

Risk increases with dose and duration. In a 2023 cohort of 3,325 screened long-term users, the estimated 15-year cumulative incidence of retinopathy was 2.7% at doses of 5 mg/kg/day or less, vs 11.4% at 5-6 mg/kg/day and 21.6% above 6 mg/kg/day; most cases were mild. These observational estimates are not individual predictions. Kidney disease, tamoxifen use, and older age at treatment initiation also increase risk.

The updated AAO screening schedule (2025 revision, published in 2026) recommends obtaining a baseline fundus examination, OCT, and a fundus autofluorescence (FAF) soon after starting treatment. Annual OCT and wide-pattern FAF are recommended, but may be deferred during the first 5 years if significant risk factors are absent. Visual fields and multifocal electroretinography are confirmatory tests. Screen all patients for both parafoveal and pericentral damage. Retinal toxicity is generally irreversible; advanced disease can progress after the drug is stopped.

When a higher dose is acceptable: The 2025 ACR guideline allows short courses of 5 to 6.5 mg/kg/day when starting treatment, during periods of incomplete control, or in pregnancy, with a long-term average of 5 mg/kg or less. This is an individualized specialist decision, not a routine dose increase in pregnancy.

Pericarditis that keeps coming back despite hydroxychloroquine, NSAIDs, colchicine, or steroids: the 2025 ACR guideline conditionally recommends adding mycophenolate, azathioprine, or a biologic rather than more steroids alone. The panel's preferred biologic for predominant pleuropericarditis is IL-1 blockade, though evidence in lupus is mostly indirect.

Arthritis that persists on hydroxychloroquine: Start with methotrexate, mycophenolate, or azathioprine, with a low threshold to add or switch to belimumab or anifrolumab. The guideline notes that in a randomized trial of overall extrarenal SLE activity, not a trial powered to compare arthritis-specific responses, patients on mycophenolate had higher remission rates and fewer side effects than those on azathioprine.

Steroid dependence: for stable, controlled SLE in patients taking more than 5 mg/day, the guideline strongly recommends tapering prednisone to 5 mg/day or less within 6 months, and ideally stopping it. If the taper fails, start or step up an immunosuppressant, not a higher daily steroid dose. EULAR's 2023 update says the same: start immunosuppressants or biologics promptly so steroids can be tapered.

The rule underneath all three: for ongoing activity in any organ despite initial therapy, the ACR panel strongly recommends escalating treatment rather than continuing the same plan.

Check antiphospholipid antibodies. The 2025 ACR guideline includes them in routine screening for every lupus patient, because they raise the risk of certain complications and change treatment decisions. They matter even more if she plans to become pregnant later.

Choose the next drug with pregnancy in mind. If she later needs a conventional immunosuppressant, maybe for skin and joint disease, the guideline lists methotrexate and mycophenolate, but prefers azathioprine when pregnancy is planned. Methotrexate and mycophenolate are teratogenic and require effective contraception and a planned switch before conception. This is why the case states she has no current plan for conception.

Plan pregnancy around quiescent disease. The ACR reproductive health guideline encourages pre-pregnancy counseling, conception during a period of inactive disease on pregnancy-compatible medications, and effective contraception until then. Check anti-Ro/SSA and anti-La/SSB once before or early in pregnancy, and assess antiphospholipid antibodies; these results guide pregnancy counseling and monitoring.