Systemic Sclerosis — Written Clinical Reasoning

SAQ 1 — Systemic sclerosis with pulmonary arterial hypertension, refractory Raynaud and GI disease (20 marks, 30 minutes)

Prompt: Outline your integrated assessment, the investigations you would order, your management plan addressing each problem, and the shared decision-making framework. Justify each decision with reference to evidence. [1]

Model Answer

Problem list (4 marks): [1]

1. Severe pulmonary arterial hypertension (WHO Group 1) secondary to limited cutaneous systemic sclerosis — mean pulmonary artery pressure 48 mmHg, wedge 11 mmHg, pulmonary vascular resistance 6 Wood units on right heart catheterisation, with right ventricular dilatation and a pericardial effusion on echo. This is her dominant prognostic problem and the immediate management priority.
2. Limited cutaneous systemic sclerosis (anti-centromere positive) — the underlying multisystem disease, with Raynaud phenomenon, recurrent digital ulcers, calcinosis, severe gastro-oesophageal reflux, and an established NSIP-equivalent minor interstitial abnormality on HRCT.
3. Recurrent digital vasculopathy — active digital ulcers with critical ischaemia risk, despite ongoing therapy.
4. Iron-deficiency anaemia — haemoglobin 102 g/L with iron-deficient indices, likely from occult gastrointestinal blood loss (gastric antral vascular ectasia or reflux oesophagitis) and contributing to her dyspnoea.
5. Functional and psychosocial impact — exertional limitation, pre-syncope, the visible and painful skin disease, and the implications for work and family life. [1]

Step 1 — Immediate assessment and stabilisation (4 marks): [1]

Her dyspnoea, fatigue and pre-syncope, together with the right-heart-catheterisation confirmation of pulmonary arterial hypertension, place her in a high-risk category that requires urgent specialist intervention. I would admit her for symptom control if she is in overt right heart failure, or arrange urgent referral to the specialist pulmonary hypertension centre if she is stable. I would assess her haemodynamic status (jugular venous pressure, hepatic congestion, ascites, peripheral oedema), oxygen saturation (with ambulatory monitoring — exertional desaturation is common), arrange an ECG and NT-proBNP as baselines, and a six-minute walk test to stratify risk and establish a baseline. I would avoid systemic glucocorticoids (the renal-crisis risk applies even in limited disease, though less than in diffuse disease), avoid pregnancy (PAH carries a high maternal mortality), and avoid beta-blockers (they worsen Raynaud). I would start supplemental oxygen if she is hypoxaemic, and gentle diuresis with furosemide for the right heart failure, recognising that over-diuresis can precipitate cardiorenal decline in a preload-dependent right ventricle. [1]

Step 2 — Confirm the diagnostic workup and exclude mimics (2 marks): [1]

The diagnosis of pulmonary arterial hypertension is confirmed by right heart catheterisation. I would complete the workup to characterise severity and exclude contributing factors: a ventilation-perfusion scan to exclude chronic thromboembolic pulmonary disease (the echo and catheter alone do not exclude it); pulmonary function tests already done confirm the disproportionately low DLCO (38 per cent predicted) with preserved FVC (85 per cent predicted), the classic isolated vasculopathy pattern that distinguishes PAH from significant ILD; an autoimmune screen to confirm the anti-centromere positivity and exclude an overlap syndrome; an HIV test and a liver ultrasound (portopulmonary hypertension); and iron studies (already low), B12 and folate, thyroid function, and a sleep study to exclude contributory obstructive sleep apnoea. I would arrange upper gastrointestinal endoscopy to investigate the iron deficiency (gastric antral vascular ectasia is common in limited SSc and is treated endoscopically with argon plasma coagulation). [1]

Step 3 — Definitive PAH-specific therapy (5 marks): [1]

Following current ESC/ERS guidance and the EULAR systemic sclerosis framework, the modern approach to PAH is initial combination therapy for most patients at diagnosis [2]. I would, in collaboration with the pulmonary hypertension centre, commence:

• An endothelin receptor antagonist — macitentan 10 mg daily (or bosentan 125 mg twice daily, with monthly liver-function monitoring and the additional benefit of preventing new digital ulcers, relevant here given her recurrent ulcers [7]), AND
• A phosphodiesterase type 5 inhibitor — tadalafil 40 mg daily (or sildenafil 20 mg three times daily, which she is already taking at a lower Raynaud dose, uptitrated).

For a patient at this severity (pre-syncope, right ventricular dilatation, pericardial effusion, functional class III), I would have a low threshold for adding a prostacyclin pathway agent early — oral selexipag, or inhaled or subcutaneous treprostinil — and intravenous epoprostenol is reserved for the most severe (functional class IV) or rapidly deteriorating patients. I would arrange serial reassessment at three to six months with a six-minute walk test, NT-proBNP and echo, with right heart catheterisation if there is clinical deterioration, and would escalate therapy on the basis of predefined treatment goals. [1]

Step 4 — Manage the systemic sclerosis vasculopathy (3 marks): [1]

For her refractory Raynaud and recurrent digital ulcers, I would optimise the vasodilator strategy: she is already on amlodipine and sildenafil. I would add intravenous iloprost (a prostacyclin analogue) over three to five days for the active digital ulcers and consider a maintenance strategy. I would add bosentan for prevention of new digital ulcers, recognising that it does not heal existing ulcers but reduces the cumulative number of new ulcers by about 30 per cent (RAPIDS-2) [7], with the monthly liver-function monitoring already required for her PAH therapy. I would arrange wound care (dressings, debridement as needed, antibiotics for infection, analgesia), and review by hand therapy. I would reinforce smoking cessation (non-negotiable), cold-avoidance strategies, and the absolute avoidance of beta-blockers and sympathomimetic decongestants. For a threatened critical digit I would admit for urgent IV iloprost and consider digital sympathectomy.

Step 5 — Manage the gastrointestinal disease and anaemia (2 marks): [1]

I would arrange upper gastrointestinal endoscopy to investigate the iron deficiency, looking for gastric antral vascular ectasia (treat with argon plasma coagulation), reflux oesophagitis, stricture and Barrett oesophagus. I would continue a high-dose proton pump inhibitor (pantoprazole 40 mg twice daily), add a prokinetic if there is delayed gastric emptying, and arrange a hydrogen or glucose breath test for small intestinal bacterial overgrowth given her bloating, with cyclic rotating antibiotics if positive. I would correct the iron deficiency with intravenous iron (oral iron is poorly tolerated in SSc gut dysmotility), and assess her nutritional status with a dietitian. [1]

Step 6 — Communication, shared decision-making and prognosis (3 marks): [1]

I would sit with her and her partner in a quiet room, with the rheumatologist and the pulmonary hypertension clinical nurse specialist. I would frame the diagnosis honestly: pulmonary arterial hypertension is the most feared complication of her form of scleroderma, and untreated it carries a poor prognosis, but modern combination therapy has transformed survival (three-year survival now above 70 per cent in treated cohorts). I would explain the immediate priorities — starting PAH combination therapy, treating the right heart failure, healing the digital ulcers, and investigating the anaemia — and the longer-term surveillance plan (regular review in the combined scleroderma-pulmonary hypertension clinic, with serial six-minute walk tests, NT-proBNP, echocardiography and intermittent right heart catheterisation). I would explicitly address pregnancy as contraindicated and arrange reliable contraception. I would address her fears about respiratory failure and the visible skin disease, document the shared decision, and arrange a named contact and written information. I would also, sensitively, raise advance care planning — not because we expect the worst, but because PAH is a life-limiting diagnosis and honest planning is part of good care. I would offer psychological support and a patient support group through Scleroderma Australia. [1]

SAQ 2 — Scleroderma renal crisis: the ACE-inhibitor emergency (10 marks, 20 minutes)

Prompt: A 47-year-old man presents with a three-month history of rapidly progressive skin thickening over the forearms, arms and chest, and a two-week history of headache and blurred vision. He was started on oral prednisolone 40 mg daily four weeks ago by another clinician for an inflammatory arthralgia. Blood pressure is 182/110 (no prior hypertension). Serum creatinine has risen from 78 to 290 micromol per litre over the same two weeks. Full blood count shows haemoglobin 96 g/L with schistocytes on the blood film, platelets 82, LDH elevated and haptoglobin low. Anti-RNA polymerase III antibody is positive. Outline the diagnosis, your immediate management, and the monitoring and prognostic framework, with evidence. [1]

Model Answer

Step 1 — Establish the diagnosis (2 marks): [1]

This is scleroderma renal crisis until proven otherwise. The diagnostic constellation is: early diffuse cutaneous systemic sclerosis (skin thickening proximal to the elbows and on the trunk of three months onset), anti-RNA polymerase III antibody positivity (a high-risk antibody for renal crisis), new-onset severe hypertension, rapidly progressive acute kidney injury, and microangiopathic haemolytic anaemia (schistocytes, low platelets, elevated LDH, low haptoglobin). The recent initiation of prednisolone 40 mg daily — well above the 15 mg per day threshold — is a recognised and modifiable trigger for scleroderma renal crisis (Steen and Medsger, Arthritis Rheum 1998) [3]. The principal differential is thrombotic thrombocytopenic purpura, but ADAMTS13 would be normal in scleroderma renal crisis, and the clinical context (early diffuse SSc, anti-RNA polymerase III, recent high-dose steroid) makes renal crisis overwhelmingly more likely. I would not delay treatment to obtain a renal biopsy; the biopsy, if performed, would show the characteristic proliferative intimal arteriolopathy (onion-skinning) and fibrinoid necrosis, but it is not required to begin therapy.

Step 2 — Immediate management: the ACE-inhibitor first principle (4 marks): [1]

The non-negotiable immediate intervention is an angiotensin-converting enzyme inhibitor. I would commence captopril 6.25 to 12.5 mg orally, up-titrating every 6 to 12 hours against the blood pressure to a target of below 140/90 (or lower if tolerated), guided by his symptoms (avoid precipitating hypotension, which worsens renal perfusion). The key rules are three. First, the ACE inhibitor is started even if the blood pressure is normal at presentation (about 10 per cent of patients are normotensive). Second, the ACE inhibitor is continued and up-titrated even as the creatinine rises — the transient rise reflects the necessary blood-pressure reduction and the recovery of surviving nephrons, and stopping the ACE inhibitor is the single most common avoidable error. Third, the ACE inhibitor is continued even if the patient becomes dialysis-dependent, because ACE-inhibitor continuation through dialysis maximises the chance of renal recovery. ACE inhibitors transformed one-year survival in scleroderma renal crisis from under 20 per cent to about 76 per cent (Steen, Ann Intern Med 1990) [4]. I would immediately stop and taper the prednisolone (the trigger), avoid all other nephrotoxins, and involve the nephrology team early. I would commence renal replacement therapy (haemodialysis or continuous renal replacement) for uraemia, fluid overload or hyperkalaemia, with the expectation that a substantial proportion of patients who need dialysis recover renal function over weeks to months and can come off dialysis. An angiotensin receptor blocker is a second-line substitute if an ACE inhibitor is not tolerated, but it is not equivalent. Endothelin receptor antagonists, prostacyclin and calcium channel blockers have no proven role as primary therapy.

Step 3 — Monitoring, prognosis and follow-up (2 marks): [1]

I would monitor blood pressure, renal function, platelet count, haemolysis markers (LDH, haptoglobin, schistocytes) and fluid status daily during the acute phase, then weekly as he stabilises. The prognosis is guarded but hopeful: with prompt and sustained ACE inhibition, 1-year survival is about 76 per cent; up to half of patients need dialysis acutely, but a substantial proportion (around a third to a half) recover enough renal function to discontinue dialysis over weeks to months [4]. Predictors of poor renal recovery include older age, delayed ACE-inhibitor initiation, sustained severe hypertension, and the need for prolonged dialysis. I would counsel the patient and his family honestly about the trajectory, the likelihood of needing dialysis at least temporarily, and the possibility of long-term dialysis dependence in a minority.

Step 4 — Communication and the wider management plan (2 marks): [1]

I would explain to the patient and his family that this is a recognised emergency complication of his scleroderma, that the high-dose steroid was a contributing trigger, and that the ACE inhibitor is the specific, life-saving therapy — to be continued regardless of the creatinine. I would address the immediate plan (ACE inhibitor, dialysis if needed, monitoring), the medium-term plan (renal recovery assessment, weaning from dialysis if possible, immunosuppression for the active skin disease with a non-steroidal agent such as mycophenolate or methotrexate), and the long-term surveillance plan (close monitoring of blood pressure and renal function, surveillance for ILD and PAH as for all diffuse disease, and age-appropriate cancer screening given the anti-RNA polymerase III positivity and its temporal cancer association [10]). I would document the shared decision, give written information, and arrange a named contact. I would also raise advance care planning, given the gravity of the acute presentation. The principle: scleroderma renal crisis is the paradigm example of a scleroderma emergency in which a single class of drug, correctly used and sustained, transforms outcome.