Systemic Lupus Erythematosus — Clinical Case

DCE Long Case

Patient profile

Ms L is a 29-year-old physiotherapist who presents to the rheumatology service with a two-week history of progressive leg swelling, frothy urine and rising blood pressure. [1]

Presenting concern: Over two weeks she has noticed progressive bilateral leg swelling, initially mild but now up to the knees, with frothy urine and increasing fatigue. Her general practitioner noted a blood pressure of 156 over 98 (previously 118 over 72) and referred her urgently. She has no chest pain, shortness of breath, haemoptysis or fever. She has noticed a recurrence of the facial rash she had at diagnosis three years ago, and joint pain in her wrists and fingers worse in the mornings. [1]

Past medical history:

• Systemic lupus erythematosus diagnosed 3 years ago, presenting with a malar rash, arthralgia, oral ulcers and fatigue. Confirmed by the 2019 EULAR/ACR criteria — positive ANA, anti-dsDNA 42 IU/mL, anti-Smith positive, low C3 (0.65 g/L) and C4 (0.08 g/L). No renal involvement at diagnosis (urinalysis normal). She has been in clinical remission on hydroxychloroquine 400 mg daily.
• One first-trimester miscarriage 18 months ago at 9 weeks gestation.
• Iron deficiency anaemia of chronic disease.
• No hypertension, diabetes or dyslipidaemia previously. [1]

Medications: hydroxychloroquine 400 mg daily, oral contraceptive pill (ethinyloestradiol and levonorgestrel) which she takes for cycle control. No over-the-counter medications or supplements. [1]

Family history: Mother with autoimmune thyroid disease. One maternal aunt with rheumatoid arthritis. No family history of lupus, renal disease or thrombophilia. [1]

Social: Lives with her partner of 5 years. Works full-time as a physiotherapist. Non-smoker. Alcohol 4 to 6 standard drinks per week. They wish to start a family in the next 12 to 18 months. She is a sun-lover and admits to inconsistent sun protection. [1]

Examination:

• Alert, comfortable. Temperature 36.9. Pulse 92 regular. Blood pressure 154 over 96. Respiratory rate 18. SpO2 99 per cent room air.
• Facial examination: a fixed erythematous rash over both cheeks and the bridge of the nose in a butterfly distribution, sparing the nasolabial folds. Patchy non-scarring alopecia at the temples. Two painless oral ulcers on the hard palate.
• Hands: symmetrical mild synovitis of the MCP and PIP joints bilaterally, with reducible ulnar deviation at the MCPs consistent with Jaccoud arthropathy. Periungual erythema. Livedo reticularis over the dorsum of both hands and forearms.
• Chest: clear breath sounds, no rub.
• Heart: normal heart sounds, no murmur or rub.
• Abdomen: soft, non-tender. Mild peripheral oedema to mid-shin bilaterally.
• Neurological: intact, no focal deficit. [1]

Investigations:

• Haemoglobin 105 g/L (normocytic); platelets 145; white cell count 3.8 with lymphocyte count 0.9 (lymphopenia); ESR 58 mm/h; CRP 8 mg/L (normal).
• Sodium 138; potassium 4.2; creatinine 124 micromol per litre (baseline 68, 2 years ago); eGFR 48 mL/min/1.73m squared.
• Albumin 28 g/L; total protein 58 g/L.
• Urine: protein 3 plus, blood 2 plus; microscopy shows dysmorphic red cells and red cell casts.
• Urine protein-to-creatinine ratio: 220 mg/mmol.
• ANA positive (homogeneous, 1:1280); anti-dsDNA 210 IU/mL (ULN 25, was 42 at diagnosis); anti-Smith positive; anti-Ro (SSA) positive; anti-La negative; C3 0.42 g/L (low); C4 0.06 g/L (low).
• Lupus anticoagulant positive; anticardiolipin IgG 55 GPL units (high); anti-beta-2 glycoprotein I positive (to be confirmed at 12 weeks).
• Coagulation: INR 1.0; aPTT 42 seconds (prolonged, does not correct on mixing study).
• Renal biopsy: ISN/RPS class IV (A/C) diffuse proliferative lupus nephritis — endocapillary hypercellularity in 70 per cent of glomeruli, wire-loop subendothelial deposits, cellular crescents in 25 per cent of glomeruli. Full-house immunofluorescence (IgG, IgA, IgM, C3, C1q). Activity index 12/24; chronicity index 2/12.
• Echocardiogram: normal left ventricular function, no pericardial effusion, no vegetations. [1]

Candidate's opening statement (SASPOP)

"This is Ms L, a 29-year-old physiotherapist with a known history of systemic lupus erythematosus who presents with a two-week history of progressive oedema, hypertension and frothy urine, representing an acute renal flare of class IV diffuse proliferative lupus nephritis — confirmed on biopsy with crescents in 25 per cent of glomeruli, a high activity index and a low chronicity index. Serologically, her anti-dsDNA has risen from 42 to 210 and both C3 and C4 have fallen, the classic signature of active lupus. She also has a newly identified antiphospholipid antibody profile — lupus anticoagulant positive, high-titre anticardiolipin and positive anti-beta-2 glycoprotein I — which, combined with her first-trimester miscarriage, is consistent with secondary antiphospholipid syndrome. She is anti-Ro positive, which has implications for any future pregnancy. Her main problems are: (1) active proliferative class IV lupus nephritis requiring urgent induction immunosuppression; (2) significant hypertension and proteinuria requiring RAAS blockade; (3) secondary antiphospholipid syndrome with implications for thrombosis and pregnancy; (4) accelerated cardiovascular risk from the combination of lupus, APS and chronic kidney disease; and (5) her desire to start a family, which constrains the choice of immunosuppressive agents. My priorities are to establish induction therapy within days, control her blood pressure, continue hydroxychloroquine, address the antiphospholipid syndrome, and plan a pregnancy-compatible long-term strategy." [1]

Structured problem list (numbered, prioritised)

1. Active class IV (A/C) proliferative lupus nephritis — crescentic, high activity index; requires urgent induction immunosuppression to prevent irreversible scarring and progression to end-stage kidney disease.
2. Hypertension and nephrotic-range proteinuria — blood pressure 154/96, urine PCR 220 mg/mmol; RAAS blockade and fluid management required to protect remaining renal function.
3. Secondary antiphospholipid syndrome — triple-positive with a clinical event (miscarriage); thrombosis risk and pregnancy implications; requires anticoagulation strategy.
4. Accelerated cardiovascular risk — SLE plus APS plus CKD makes her a high coronary risk; statin, blood pressure and lifestyle measures required.
5. Future fertility and pregnancy planning — desire to conceive within 12 to 18 months; mycophenolate (and any cyclophosphamide) must be reconciled with this; she is anti-Ro positive with congenital heart block risk.
6. Cumulative glucocorticoid and immunosuppression risk — infection, osteoporosis, avascular necrosis, diabetes; steroid-sparing strategy essential.
7. Psychosocial impact — chronic relapsing disease in a young woman planning a family; education, contraception counselling and shared decision-making. [1]

Integrated management plan

Step 1 — Urgent induction of lupus nephritis: [1]

Ms L has active proliferative class IV lupus nephritis with crescents and a rapidly rising creatinine. Delay causes irreversible scarring. Per the 2019 EULAR/ERA-EDTA recommendations and KDIGO 2021, I would commence induction immediately with: [1]

• Methylprednisolone 500 to 1000 mg intravenously daily for 3 days, followed by oral prednisone 0.3 to 0.5 mg/kg/day (approximately 25 to 30 mg daily), tapering to below 5 to 7.5 mg by 6 months.
• Mycophenolate mofetil as first-line, target 2 to 3 g/day (titrated up from 500 mg twice daily to minimise gastrointestinal effects). The ALMS trial established that mycophenolate is non-inferior to high-dose cyclophosphamide for induction, with response rates of 56.2 per cent versus 53.0 per cent [3]. Mycophenolate is preferred over cyclophosphamide here because of her future fertility — cyclophosphamide is gonadotoxic. If she had severe crescentic disease (over 50 per cent crescents) or rapidly progressive renal failure, I would prefer the Euro-Lupus low-dose cyclophosphamide regimen (500 mg IV every 2 weeks for 6 doses), which the Euro-Lupus Nephritis Trial showed was as effective as high-dose with fewer infections [4].
• Consider adding voclosporin (23.7 mg twice daily). The AURORA trial showed that voclosporin added to mycophenolate and rapidly tapered steroids increased complete renal response at 52 weeks to 41 per cent versus 23 per cent, with separation as early as 4 weeks [5]. Given her active crescentic disease and the need for rapid response, this is an attractive option I would discuss with her nephrologist.

Step 2 — Blood pressure and proteinuria control: [1]

I would start an ACE inhibitor (for example, ramipril 2.5 to 10 mg daily) or an ARB. RAAS blockade reduces intraglomerular pressure, reduces proteinuria, and slows progression to end-stage kidney disease. Target blood pressure below 130/80. I would monitor potassium and creatinine closely (a small rise in creatinine of up to 30 per cent on initiation is acceptable). I would counsel her on dietary salt restriction. A diuretic may be needed for the oedema. [1]

Step 3 — Continue hydroxychloroquine: [1]

Hydroxychloroquine 400 mg daily is continued. It reduces disease activity, flare frequency, renal recurrence, thrombosis and cardiovascular risk, and in anti-Ro positive women reduces the risk of congenital heart block in a future pregnancy. The LUMINA cohort showed hydroxychloroquine use is independently associated with improved survival [2]. I would arrange baseline ophthalmology including spectral-domain OCT and annual screening from 5 years.

Step 4 — Antiphospholipid syndrome management: [1]

She has triple-positive antiphospholipid antibodies with a clinical event (miscarriage), consistent with definite APS by the Sydney (2006) criteria [7] — to be confirmed with persistence at 12 weeks. Her immediate thrombotic risk is elevated by the nephrotic-range proteinuria (loss of antithrombin), immobility and active inflammation. I would:

• Stop the combined oral contraceptive pill immediately — oestrogen-containing contraception is contraindicated in APS due to thrombosis risk. Switch to a progestogen-only pill or intrauterine device.
• Start prophylactic low molecular weight heparin during her admission if she is immobile or has heavy proteinuria.
• For long-term thromboprophylaxis: aspirin 100 mg daily. If she were to thrombose, she would need lifelong therapeutic anticoagulation with warfarin (preferred over DOACs in triple-positive APS), target INR 2.0 to 3.0 for venous disease. I would be vigilant for catastrophic antiphospholipid syndrome.

Step 5 — Pregnancy planning (a major integrating theme): [1]

She wishes to conceive in 12 to 18 months. This must be reconciled with her immunosuppression:

• Defer conception until at least 6 months of renal quiescence — inactive urinary sediment, stable creatinine, proteinuria controlled. Premature pregnancy dramatically increases flare, pre-eclampsia and fetal loss risk.
• Switch mycophenolate to azathioprine (2 mg/kg/day) at least 3 months before conception — mycophenolate is teratogenic.
• Continue hydroxychloroquine throughout pregnancy — safe, reduces flares and congenital heart block risk.
• Anticoagulation in pregnancy — given her APS with pregnancy morbidity, prophylactic low molecular weight heparin plus low-dose aspirin once pregnant, through pregnancy and 6 weeks postpartum.
• Serial fetal echocardiography between 16 and 26 weeks given her anti-Ro positivity, to detect congenital heart block.
• Cyclophosphamide avoided because it is gonadotoxic and teratogenic — another reason mycophenolate is preferred for her current induction. [1]

Step 6 — Cardiovascular risk management: [1]

SLE is a coronary risk equivalent, amplified here by APS and CKD. I would start a statin (atorvastatin 20 to 40 mg), optimise blood pressure to below 130/80, encourage regular exercise and sun protection (photosensitivity), enforce smoking avoidance, and minimise cumulative steroid exposure. I would check a fasting lipid panel and HbA1c. [1]

Step 7 — Supportive and preventive care: [1]

• Pneumocystis prophylaxis (trimethoprim-sulfamethoxazole) while on moderate-dose steroids and mycophenolate.
• Bone protection (calcium, vitamin D, and a bisphosphonate if indicated on bone densitometry).
• Vaccinations up to date before intensifying immunosuppression (pneumococcal, influenza, hepatitis B, COVID-19, zoster recombinant); avoid live vaccines.
• VTE prophylaxis during admission given the nephrotic state and immobility.
• Education on sun protection, medication adherence, flare warning signs, and the importance of pre-pregnancy planning. [1]

Step 8 — Communication, follow-up and safety: [1]

I would sit with Ms L and her partner, with the rheumatology nurse specialist and a nephrologist. I would explain that she has a renal flare of her lupus that requires strong immunosuppression for several months, that the prognosis with modern therapy is good (5-year renal survival above 85 per cent with class IV disease treated aggressively), and that her wish to start a family is achievable with careful planning. I would explain the switch from mycophenolate to azathioprine before pregnancy, the continuation of hydroxychloroquine, and the aspirin and heparin plan for APS in pregnancy. I would address the emotional burden and offer psychology support. I would arrange close follow-up (every 2 to 4 weeks during induction, with monitoring of creatinine, proteinuria, complement, anti-dsDNA and full blood count) and document the shared decisions. [1]

Probing questions the examiner would ask

Q: She develops a fever and confusion on day 5 of her admission. How do you respond? [1]

A: "The cardinal rule is to exclude infection BEFORE attributing a neurological change to neuropsychiatric lupus and escalating immunosuppression. She is on mycophenolate and moderate-dose steroids, so she is significantly immunocompromised. Infection is more likely than active lupus. I would perform a full septic screen — blood cultures, urine culture, chest X-ray, and a lumbar puncture (after CT to exclude a mass) to exclude meningitis or encephalitis — start empiric broad-spectrum antibiotics, and hold further immunosuppression escalation until infection is excluded or treated. Only if infection is confidently excluded would I consider a neuropsychiatric lupus flare and treat with high-dose methylprednisolone and cyclophosphamide. The diagnosis of neuropsychiatric lupus is clinical — there is no single confirmatory test — and MRI may be normal. Giving more immunosuppression to a septic patient can be fatal, so this discipline is essential." [1]

Q: On the AURORA regimen, what is the complete renal response rate with voclosporin, and how does this compare with standard therapy? [1]

A: "The AURORA trial (Rovin et al, 2021) randomised 357 patients with active class III, IV or V lupus nephritis to voclosporin (23.7 mg twice daily) or placebo, added to standard mycophenolate and rapidly tapered low-dose steroids. The complete renal response rate at 52 weeks was 41 per cent with voclosporin versus 23 per cent with placebo — a significant improvement. Notably, the separation was evident as early as 4 weeks, reflecting the rapid proteinuria reduction that calcineurin inhibitors provide. Voclosporin is a novel calcineurin inhibitor that, unlike ciclosporin, does not require therapeutic drug monitoring and has a cleaner safety profile. For Ms L, with active crescentic class IV disease and a need for rapid response and steroid-sparing, adding voclosporin is a rational, evidence-based option I would discuss with her nephrologist [5]."

Q: Her chronicity index is low (2 out of 12). Why does this matter for your treatment intensity? [1]

A: "The activity and chronicity indices on the lupus nephritis biopsy guide the intensity of immunosuppression. The activity index (endocapillary hypercellularity, karyorrhexis or fibrinoid necrosis, cellular crescents, hyaline deposits) reflects active, potentially reversible inflammation — it justifies aggressive immunosuppression because the inflammation can be treated and the damage prevented. The chronicity index (glomerular sclerosis, fibrous crescents, interstitial fibrosis, tubular atrophy) reflects irreversible scarring that will NOT respond to immunosuppression. Ms L has a high activity index (12 out of 24) and a low chronicity index (2 out of 12) — meaning most of her renal injury is active and reversible, which strongly justifies aggressive induction to prevent transition to irreversible chronic damage. If her chronicity index were high (for example above 6 or 8), the benefit of aggressive immunosuppression would be much less, because much of the damage is already permanent. The activity-chronicity split is therefore central to the risk-benefit calculation of induction intensity." [1]

Q: How would you distinguish a lupus flare from pre-eclampsia if she were to become pregnant and develop hypertension and proteinuria? [1]

A: "This is a classic and difficult discriminator. Both cause hypertension, oedema, proteinuria and renal dysfunction in a pregnant lupus patient. Features favouring SLE flare over pre-eclampsia: active urinary sediment (dysmorphic red cells, red cell casts), falling complement (C3 and C4), rising anti-dsDNA, extra-renal lupus activity (rash, arthritis, oral ulcers), and a stable platelet count. Features favouring pre-eclampsia: raised serum urate, low platelets, abnormal liver function (transaminitis), hyperreflexia, and a low or falling placental growth factor with a high soluble fms-like tyrosine kinase-1. The single most discriminating finding pointing to lupus flare is a rising anti-dsDNA with falling complement. The distinction changes management fundamentally — delivery is the treatment for pre-eclampsia, while immunosuppression is the treatment for lupus flare. In practice, if there is genuine uncertainty, I involve the obstetric medicine and nephrology teams jointly and may treat empirically for both while awaiting the full serological picture." [1]

Q: She asks whether her future children will inherit lupus. How do you answer? [1]

A: "SLE has a polygenic and multifactorial inheritance pattern — there is an increased relative risk in first-degree relatives (about 8-fold higher than the general population), and a higher concordance in monozygotic than dizygotic twins (around 25 per cent versus 2 per cent), but the absolute risk to a child of an affected mother is low (around 5 to 10 per cent, much lower than the impression of a 'genetic disease'). Most children of mothers with SLE do not develop lupus. However, two specific antibody-mediated effects can affect the baby regardless of genetic risk: anti-Ro and anti-La antibodies cross the placenta and can cause neonatal lupus (transient rash, cytopenias, and most seriously congenital heart block), and antiphospholipid antibodies can increase pregnancy complications. I would reassure her that the genetic risk is modest, and focus the counselling on the modifiable factors — achieving disease quiescence before conception, continuing hydroxychloroquine, aspirin and heparin for APS, and serial fetal echocardiography for heart block surveillance because she is anti-Ro positive." [1]

Communication and shared decision-making

"I would sit with Ms L and her partner in a quiet room, with the rheumatology nurse specialist and a nephrologist. I would explain that her lupus has flared in the kidneys — the most serious organ — and that we need strong treatment for several months to bring it under control and prevent permanent kidney damage. I would explain the choice of mycophenolate over cyclophosphamide, framed around her wish to start a family — mycophenolate preserves her fertility while being effective, and we will switch it to a pregnancy-safe drug (azathioprine) before she conceives. I would reassure her that hydroxychloroquine, which she already takes, is one of the most important drugs for lupus and will continue through any pregnancy. I would explain the newly identified antiphospholipid antibodies, the implications for blood thinning in pregnancy, and the need to switch her contraceptive pill to a non-oestrogen method. I would be honest that the next few months will be demanding — frequent blood tests, possible side effects, and the discipline of waiting for disease control before pregnancy — but that the outlook with modern therapy is good, with the majority of patients achieving remission and successful pregnancies. I would offer psychology and social work support, and document the shared decisions." [1]

DCE Short Case — Hand and Face Examination in SLE

Instruction

"Examine this patient's hands and face." [1]

Systematic examination routine

1. End of bed — observe for facial rash, facial puffiness, hair changes, body habitus (Cushingoid from steroids), and hand deformities. Note walking aids and oxygen.
2. Face inspection — malar (butterfly) rash over cheeks and bridge of nose, noting whether nasolabial folds are spared (SLE) or involved (rosacea, seborrhoeic dermatitis). Check for discoid lesions (scarring, follicular plugging), oral ulcers (hard palate, buccal mucosa), and non-scarring alopecia.
3. Hands inspection — symmetrical arthropathy pattern (ulnar deviation, swan-neck deformities, reducible versus fixed), periungual erythema, nailfold capillary changes, livedo reticularis, vasculitic lesions, digital pulp infarcts, palmar erythema.
4. Hands palpation — synovial bogginess at MCP and PIP joints, warmth, squeeze test, assessment of caput ulnae and reducibility of deformities.
5. Movement and function — active and passive range of motion, grip, pinch, ability to make a fist, button and write.
6. Multisystem screen — eyes (episcleritis), chest (pleural or pericardial rub), heart (murmur of Libman-Sacks, pericardial rub), abdomen (splenomegaly), legs (oedema, vasculitic ulcers, livedo). [1]

Key physical signs the patient demonstrates (for this case)

• Malar rash in butterfly distribution sparing the nasolabial folds
• Pain-free oral ulcers on the hard palate
• Non-scarring alopecia at the temples
• Symmetrical reducible Jaccoud arthropathy (ulnar deviation, swan-neck deformities) with mild synovitis
• Periungual erythema and livedo reticularis on hands and forearms [1]

Presentation template

"I examined Ms L, a 29-year-old woman. On the face there is a fixed erythematous rash over both cheeks and the bridge of the nose in a butterfly distribution, critically sparing the nasolabial folds, consistent with the malar rash of systemic lupus erythematosus. There are two painless oral ulcers on the hard palate and patchy non-scarring alopecia at the temples. In the hands there is a symmetrical reducible deforming arthropathy with ulnar deviation at the metacarpophalangeal joints and swan-neck deformities, consistent with Jaccoud arthropathy — the deformities correct when she flattens her hand, indicating tendon and ligament laxity rather than joint destruction. There is mild synovial bogginess at the MCP and PIP joints. I also note periungual erythema and livedo reticularis over the dorsum of the hands and forearms. These findings are consistent with active systemic lupus erythematosus with possible associated antiphospholipid syndrome. I would confirm the diagnosis with ANA, anti-dsDNA, anti-Smith and complement levels, screen for renal involvement with urinalysis and proteinuria, and assess for antiphospholipid antibodies." [1]

Discussion questions

Q: What is the mechanism of the Jaccoud arthropathy and how does it differ from rheumatoid arthritis? [1]

A: "Jaccoud arthropathy is a non-erosive, reducible deforming arthropathy caused by inflammation-induced laxity of the tendons, ligaments and joint capsule — the deformities arise from soft tissue imbalance rather than joint destruction. Radiographs show no erosions, and the deformities (ulnar deviation, swan-neck, Z-thumb) reduce passively. This contrasts with rheumatoid arthritis, where proliferating pannus invades and destroys cartilage and bone, producing fixed, erosive, deforming change on radiographs. Jaccoud arthropathy is most associated with SLE but also occurs in rheumatic fever." [1]

Q: Why does the malar rash spare the nasolabial folds? [1]

A: "The sparing of the nasolabial folds is a characteristic feature of the malar rash of SLE and reflects the distribution of the underlying vasculopathy and photosensitivity — the UV-exposed convex surfaces of the cheeks and nose are affected, while the shadowed, sun-protected nasolabial folds are relatively spared. This single feature distinguishes the malar rash from rosacea and seborrhoeic dermatitis, both of which typically involve the nasolabial folds. Discoid lupus, in contrast, produces scarring lesions with follicular plugging and a carpet-tack sign, and can occur anywhere." [1]

Q: What does the livedo reticularis suggest in this patient? [1]

A: "Livedo reticularis — a mottled, net-like violaceous discolouration of the skin — in a patient with SLE is a cutaneous marker of antiphospholipid syndrome. It reflects disturbed dermal blood flow from microvascular thrombosis or vasculopathy. Its presence, combined with her positive antiphospholipid antibodies and miscarriage history, supports the diagnosis of secondary APS and reinforces the need for thromboprophylaxis and pregnancy-specific management. Livedo can also be a benign physiological finding in cold conditions, but in the context of SLE and known antiphospholipid antibodies it is clinically significant." [1]

Q: How would you interpret a renal biopsy showing a high chronicity index rather than a high activity index? [1]

A: "A high chronicity index (glomerular sclerosis, fibrous crescents, interstitial fibrosis, tubular atrophy) indicates irreversible scarring. Unlike a high activity index — which reflects active, potentially reversible inflammation and justifies aggressive immunosuppression — a high chronicity index means much of the damage is already permanent and will not respond to immunosuppression. In that situation, the benefit of aggressive induction is reduced, the risk-benefit balance shifts towards avoiding toxic immunosuppression that will not help, and the focus moves to blood pressure control, RAAS blockade, and preparation for the possibility of progression to end-stage kidney disease. This is why the activity-chronicity split on the biopsy report is so important in guiding treatment intensity and in counselling the patient on prognosis." [1]