Systemic Sclerosis — DCE Clinical Case

Long Case — Scleroderma renal crisis in early diffuse cutaneous disease

Patient scenario

Mr Robert Nguyen is a 47-year-old carpenter who presents to the emergency department with a two-week history of headache, blurred vision and malaise. [1]

History of presenting complaint: [1]

• Three months ago: onset of rapidly progressive skin thickening, beginning in the fingers and hands, spreading to the forearms, arms, anterior chest wall and face over weeks. He noticed tightening of the skin, reduced hand mobility, and difficulty making a fist.
• Two months ago: arthralgia in the wrists and fingers, for which a locum GP started oral prednisolone 40 mg daily for a presumptive diagnosis of inflammatory arthritis.
• One month ago: onset of Raynaud phenomenon (white then blue then red colour changes in the fingers on cold exposure) and new-onset heartburn and reflux.
• Two weeks ago: progressive headache, blurred vision, and malaise. His GP checked his blood pressure at 168/104 (no prior history of hypertension). Blood tests showed creatinine 190 micromol per litre (previously 78 micromol per litre 6 months ago).
• One week ago: creatinine has risen to 290 micromol per litre. [1]

Past medical history: Hypertension diagnosed 2 months ago (attributed to the prednisolone). No previous autoimmune disease. No asthma or atopy. [1]

Medications: Prednisolone 40 mg daily (started 4 weeks ago by locum GP). Amlodipine 5 mg daily (started 2 weeks ago). Pantoprazole 40 mg daily. No over-the-counter or herbal medications. [1]

Family history: Father with type 2 diabetes. No family history of autoimmune or renal disease. [1]

Social history: Married with two children aged 10 and 14. Works as a carpenter (significant exposure to organic solvents and silica dust historically). Non-smoker, minimal alcohol. No illicit drug use. No recent overseas travel. [1]

Examination findings: [1]

• Afebrile, heart rate 96, blood pressure 182/110 (measured in both arms), respiratory rate 18, oxygen saturation 97 per cent on room air.
• Skin: Thickened, tight and shiny skin extending from the fingers to the proximal arms, anterior chest wall and face — diffuse cutaneous systemic sclerosis. The skin score (modified Rodnan skin score) is approximately 28 out of 51. There is perioral tightening with reduced oral aperture. Tendon friction rubs are palpable over the extensor surfaces of the forearms and knees.
• Hands: Sclerodactyly, digital pitting scars on multiple fingertips, two active digital ulcers on the right index fingertip, and active Raynaud changes (distal pallor with cyanosis). Nailfold capillaroscopy (at the bedside) shows dilated and giant capillary loops with areas of dropout.
• Cardiovascular: Normal heart sounds, no murmurs, no signs of heart failure. Blood pressure elevated at 182/110.
• Respiratory: Fine bibasal inspiratory crackles.
• Abdomen: Soft, non-tender. No organomegaly.
• Neurological: Alert and oriented. Fundoscopy shows cotton-wool spots and flame haemorrhages consistent with hypertensive retinopathy. No focal neurological deficits. [1]

Investigations: [1]

Candidate's opening statement (model answer — SASPOP format)

"Mr Robert Nguyen is a 47-year-old carpenter presenting with a two-week history of headache, blurred vision and malaise on a background of a three-month history of rapidly progressive diffuse cutaneous systemic sclerosis and a four-week history of high-dose prednisolone therapy (40 mg daily, started by a locum GP for inflammatory arthralgia). [1]

His creatinine has risen from 78 to 290 micromol per litre over two weeks, his blood pressure is 182/110 with new-onset hypertension, he has microangiopathic haemolytic anaemia (schistocytes, platelets 82, elevated LDH, low haptoglobin), and his ADAMTS13 is normal. He is anti-RNA polymerase III positive. This constellation — early diffuse cutaneous SSc, anti-RNA polymerase III, recent high-dose prednisolone above the 15 mg threshold, malignant-pattern hypertension with AKI, and microangiopathic haemolytic anaemia with a normal ADAMTS13 — is diagnostic of scleroderma renal crisis [3].

My problem list is: (1) scleroderma renal crisis — a medical emergency requiring immediate ACE inhibitor initiation; (2) malignant hypertension with hypertensive retinopathy; (3) microangiopathic haemolytic anaemia and thrombocytopenia; (4) rapidly progressive diffuse cutaneous systemic sclerosis with anti-RNA polymerase III positivity, requiring immunosuppression for the active skin disease and the prednisolone must be tapered and stopped; (5) early NSIP-pattern ILD requiring surveillance; (6) active digital ulcers and Raynaud requiring vasodilator therapy; (7) the anti-RNA polymerase III cancer association requiring age-appropriate screening; and (8) the psychosocial impact on a working father. [1]

My immediate management is: captopril 6.25 to 12.5 mg orally, up-titrated every 6 to 12 hours against the blood pressure, continued even as the creatinine rises; immediate tapering and cessation of the prednisolone; nephrology involvement; transfusion and haematology support for the anaemia and thrombocytopenia; and admission to a monitored bed with serial blood pressure, renal function, and haematology monitoring." [1]

Integrated management plan

1. Scleroderma renal crisis — the ACE-inhibitor emergency: [1]

• Start captopril 6.25 to 12.5 mg orally immediately, up-titrating every 6 to 12 hours against the blood pressure to a target of below 140/90 (lower if tolerated), guided by symptoms. The three non-negotiable rules:
  • Start the ACE inhibitor even if the blood pressure is normal at presentation (about 10 per cent of patients are normotensive).
  • Continue and up-titrate the ACE inhibitor even as the creatinine rises — the transient rise reflects the necessary blood-pressure reduction and the recovery of surviving nephrons. Stopping the ACE inhibitor is the single most common avoidable error.
  • Continue the ACE inhibitor even if the patient becomes dialysis-dependent — ACE-inhibitor continuation through dialysis maximises the chance of renal recovery. ACE inhibitors transformed 1-year survival from under 20 per cent to about 76 per cent (Steen, Ann Intern Med 1990) [4].
• Stop and taper the prednisolone — the trigger for this renal crisis. High-dose prednisolone (at or above 15 mg daily) is a recognised and modifiable trigger for SRC [3].
• Avoid all other nephrotoxins (NSAIDs, contrast, aminoglycosides).
• 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 for SRC.

2. Renal replacement therapy and the recovery paradigm: [1]

• Up to half of patients with scleroderma renal crisis need dialysis acutely. I would commence renal replacement therapy (haemodialysis or continuous renal replacement) for uraemia, fluid overload or hyperkalaemia.
• A substantial proportion (around a third to a half) recover enough renal function to discontinue dialysis over weeks to months — so I would continue the ACE inhibitor through dialysis and monitor for renal recovery. This is the key prognostic message for the patient: needing dialysis does not mean being dialysis-dependent forever.
• Predictors of poor renal recovery: older age, delayed ACE-inhibitor initiation, sustained severe hypertension, and prolonged dialysis. [1]

3. Microangiopathic haemolytic anaemia: [1]

• The MAHA (schistocytes, low platelets, elevated LDH, low haptoglobin) is a consequence of the proliferative intimal arteriolopathy in the renal vasculature — the same vascular lesion causing the renal crisis. It typically resolves as the blood pressure is controlled and the renal crisis is treated.
• ADAMTS13 is normal, which excludes thrombotic thrombocytopenic purpura — the critical differential. Plasma exchange is NOT indicated for scleroderma renal crisis (unlike TTP).
• Transfuse packed red cells for symptomatic anaemia. Platelet transfusion only if there is active bleeding or the platelet count is critically low (typically below 20). Monitor platelet count, haemolysis markers (LDH, haptoglobin, schistocytes) daily during the acute phase. [1]

4. The active skin disease and prednisolone cessation: [1]

• The prednisolone must be tapered and stopped (it triggered the renal crisis) but not abruptly discontinued (to avoid adrenal suppression after 4 weeks of 40 mg daily). I would taper over 2 to 4 weeks.
• For the active inflammatory skin disease (oedematous skin, tendon friction rubs), I would use mycophenolate mofetil 2 to 3 g daily as the first-line immunosuppressant — it avoids the prednisolone trap and also treats any concurrent ILD.
• Avoid prednisolone above 15 mg daily in all patients with diffuse systemic sclerosis. This is a critical counselling point for the patient, his GP and any future clinician. [1]

5. ILD surveillance and management: [1]

• His HRCT shows early basal NSIP-pattern ILD. Baseline PFTs are needed. I would start mycophenolate mofetil (which covers both the skin disease and the early ILD).
• Monitor FVC and DLCO at baseline, then every 3 to 6 months. An FVC decline of 10 per cent or more, or an FVC below 70 per cent predicted, signals significant disease requiring escalation. Nintedanib can be added to slow FVC decline (SENSCIS trial) [6].
• Annual echocardiography for PAH screening (right ventricular systolic pressure, TR velocity) for life.

6. Digital ulcers and Raynaud phenomenon: [1]

• Optimise oral vasodilator therapy: amlodipine 5 to 20 mg daily (already started) plus a PDE5 inhibitor (sildenafil 20 mg three times daily).
• IV iloprost for the active digital ulcers (admit for a 3 to 5 day course).
• Bosentan 62.5 mg twice daily (titrating to 125 mg twice daily) for prevention of new digital ulcers (RAPIDS-2) [7], with monthly LFT monitoring.
• Wound care for the existing ulcers.
• Smoking cessation (non-negotiable), cold-avoidance strategies, and avoidance of beta-blockers.

7. Anti-RNA polymerase III and cancer screening: [1]

• The Shah studies demonstrated a close temporal relationship between cancer and SSc onset in patients with anti-RNA polymerase III antibodies — cancer is often diagnosed within 12 to 36 months of SSc onset [10]. This suggests a paraneoplastic trigger in some patients.
• I would arrange age-appropriate cancer screening: a thorough history and examination for red-flag symptoms, plus standard screening (colonoscopy if age-appropriate, PSA discussion, skin examination). A low threshold for targeted investigation if any concerning symptoms emerge.

8. Psychosocial support: [1]

• Frame scleroderma renal crisis as a serious but treatable emergency in which the ACE inhibitor is the life-saving therapy.
• Address the fact that the prednisolone was a contributing trigger — delivered sensitively, without blame, but ensuring the patient and GP understand the principle.
• Offer psychology referral, patient support through Scleroderma Australia, and a named clinical contact.
• Address the impact on his work (carpenter with hand involvement) and arrange occupational therapy assessment. [1]

Communication and shared decision-making

I would sit with Mr Nguyen and his wife in a private room. My key messages: [1]

• "You have a condition called systemic sclerosis, or scleroderma. The skin thickening you have been experiencing is part of this disease. The high blood pressure and kidney problem that brought you to hospital is a recognised complication called scleroderma renal crisis — it is an emergency, but it has a specific treatment that saves kidneys and lives."
• "The medication that is most important right now is called captopril — an ACE inhibitor. I will start it immediately and increase it gradually to bring your blood pressure down. Your kidney function may get a little worse before it gets better — this is expected and is not a reason to stop the medication. The ACE inhibitor is the single most important thing we can do for your kidneys."
• "The prednisolone you were given for your joint pain was a contributing factor to this crisis. We will taper and stop it safely and use a different medication for your scleroderma. You should avoid prednisolone at high doses in future — I will make sure your GP knows."
• "Some people with this condition need dialysis temporarily. If that happens, it does not mean you will be on dialysis forever — a substantial proportion of people recover enough kidney function to come off dialysis. We will keep the ACE inhibitor going even if you need dialysis."
• "You also have a separate antibody called anti-RNA polymerase III. This antibody is associated with a slightly higher risk of certain cancers, so we will make sure you are up to date with all your cancer screening." [1]

I would document the shared decision, provide written information, and arrange a named contact. [1]

Probing questions and model answers

Examiner: Why is the ADAMTS13 result critical, and what would you do differently if it were low? [1]

"The ADAMTS13 result is the key discriminator between scleroderma renal crisis with microangiopathic haemolytic anaemia and thrombotic thrombocytopenic purpura (TTP). Both present with MAHA (schistocytes, thrombocytopenia, elevated LDH, low haptoglobin), but the pathophysiology and treatment are entirely different. [1]

Scleroderma renal crisis causes MAHA through the proliferative intimal arteriolopathy (onion-skinning) in the renal microvasculature — the same vascular lesion that causes the hypertension and AKI. The MAHA is a secondary consequence of microvascular fragmentation of red cells and platelet consumption. ADAMTS13 is normal (because the problem is not a deficiency of the von Willebrand factor-cleaving protease). [1]

TTP is caused by an autoimmune antibody against ADAMTS13 (or a hereditary deficiency), producing ultra-large von Willebrand factor multimers that cause platelet aggregation across the microvasculature. ADAMTS13 activity is severely reduced (typically below 10 per cent). TTP requires urgent plasma exchange (to remove the antibody and replace the enzyme), plus corticosteroids and rituximab — without plasma exchange, TTP is rapidly fatal. [1]

If his ADAMTS13 were low (below 10 per cent), I would immediately involve haematology and start plasma exchange, alongside the ACE inhibitor for the scleroderma (because both conditions can coexist). The normal ADAMTS13 in this patient confirms scleroderma renal crisis as the sole diagnosis and means plasma exchange is NOT indicated." [1]

Examiner: Why does prednisolone trigger scleroderma renal crisis? [1]

"The mechanism by which high-dose prednisolone (at or above 15 mg daily) triggers scleroderma renal crisis is not fully understood, but the association is robustly established from the Steen and Medsger data [3]. The prevailing hypothesis is that corticosteroids upregulate the renin-angiotensin-aldosterone system and alter the balance of prostacyclin and thromboxane in the renal microvasculature, precipitating the proliferative intimal arteriolopathy that defines the renal crisis lesion. High-dose prednisolone also causes endothelial dysfunction and may activate the same vascular injury pathway that underlies all scleroderma vasculopathy, concentrated in the kidney.

The clinical lesson is absolute: avoid prednisolone at or above 15 mg daily in patients with systemic sclerosis, particularly in early diffuse disease and particularly in anti-RNA polymerase III-positive patients. For inflammatory features (arthralgia, myositis, early inflammatory skin disease), use mycophenolate mofetil or methotrexate as first-line immunosuppression. If corticosteroids are unavoidable (for example, for myositis), use the lowest possible dose for the shortest possible time. This patient was given 40 mg daily for an inflammatory arthralgia by a locum GP who did not recognise the scleroderma — a tragic but instructive example of why every clinician needs to know this principle." [1]

Examiner: What is the long-term outlook for his kidneys? [1]

"The prognosis is guarded but hopeful. With prompt and sustained ACE inhibition, 1-year survival is about 76 per cent [4]. 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 — this is the renal recovery paradigm that justifies continuing the ACE inhibitor through dialysis. Predictors of poor renal recovery include older age, delayed ACE-inhibitor initiation, sustained severe hypertension, and the need for prolonged dialysis. Some patients require permanent dialysis or proceed to renal transplantation.

For this patient, the favourable factors are his age (47), the immediate recognition and ACE-inhibitor initiation, and the fact that the trigger (prednisolone) has been identified and will be stopped. The unfavourable factors are the severity of presentation (creatinine 290, blood pressure 182/110, MAHA with platelets 82) and the anti-RNA polymerase III positivity (which identifies a high-risk group). I would monitor his renal function daily during the acute phase, then weekly as he stabilises, and would expect the creatinine to rise further before it begins to fall — this is the expected trajectory and is not a reason to stop the ACE inhibitor." [1]

Short Case — Hand examination: sclerodactyly, digital ulcers and Raynaud

Examination instruction

"Examine this patient's hands. She is a 58-year-old woman with longstanding Raynaud phenomenon." [1]

Systematic examination routine

Step 1 — Inspect at the end of the bed:

• General appearance — the patient may be wrapped up warmly (cold sensitivity). Look for facial changes (microstomia, perioral rhagades, pinched nose, telangiectasia). [1]

Step 2 — Examine the hands:

• Skin — thickened, tight, shiny skin (sclerodactyly). Determine the extent: is it confined to the fingers (distal to MCPs — limited cutaneous SSc) or does it extend proximal to the MCPs onto the hands, forearms, arms or trunk (diffuse cutaneous SSc)? This is the critical limited-versus-diffuse call.
• Digits — tapering of the fingertips (digital pitting scars), loss of fingertip pulp, digital ulcers (especially on the fingertips, over the extensor surfaces of the PIP joints, or over bony prominences). Calcinosis cutis (firm white subcutaneous deposits). Distal cyanosis or pallor from active Raynaud.
• Nailfold capillaroscopy — using a dermoscope or ophthalmoscope with immersion gel, examine the nailfold capillaries. The SSc pattern shows dilated and giant capillary loops, tortuosity, microhaemorrhages, and areas of dropout (avascular areas).
• Telangiectasia — mat telangiectasia on the palms, fingers and face (dilated capillary mats that blanch with pressure).
• Joints — check for contractures from skin tightness (reduced finger flexion). Look for tendon friction rubs (palpable creaking over extensor tendons — a feature of active early diffuse disease). There is no inflammatory synovitis unless there is an overlap syndrome.
• Function — grip strength, ability to make a fist, pinch grip. Functional limitation from skin tightness and contractures. [1]

Step 3 — Complete the systemic examination:

• Face — microstomia (reduced oral aperture), perioral radial furrows (rhagades), mat telangiectasia, pinched nose, reduced facial mobility.
• Chest — basal crackles for ILD; loud P2 or TR murmur for PAH.
• Abdomen — no specific findings, but consider gut involvement (bloating, distension from bacterial overgrowth).
• Other skin — look for telangiectasia, calcinosis and skin thickening elsewhere on the body. [1]

Presentation template

"This patient has sclerodactyly with thickened, tight, shiny skin confined to the fingers distal to the metacarpophalangeal joints — consistent with limited cutaneous systemic sclerosis. There are digital pitting scars, two active digital ulcers on the right index fingertip, calcinosis cutis over the fingertips, and distal cyanosis consistent with active Raynaud phenomenon. Nailfold capillaroscopy shows dilated and giant capillary loops with areas of dropout — the active SSc pattern. There are mat telangiectasia on the palms and face, with perioral tightening and reduced oral aperture. [1]

These findings are consistent with limited cutaneous systemic sclerosis — the CREST phenotype (Calcinosis, Raynaud, oEsophageal dysmotility, Sclerodactyly, Telangiectasia). I would confirm with a full autoantibody panel (anti-centromere, anti-Scl-70, anti-RNA polymerase III) and arrange an organ-screening bundle: PFTs (FVC and DLCO) and HRCT for ILD, echocardiography for PAH screening, renal function and blood pressure monitoring, and upper GI endoscopy for reflux and GAVE. The patient requires lifelong structured surveillance in a scleroderma clinic."* [1]

Discussion questions

Examiner: "How do you distinguish limited from diffuse cutaneous disease on examination?" [1]

"The distinction is made on skin distribution, not on the presence of CREST features. Limited cutaneous SSc has skin thickening confined to distal to the elbows, distal to the knees, and the face — the fingers, hands (distal to MCPs), and face. Diffuse cutaneous SSc has skin thickening proximal to the elbows, proximal to the knees, or on the trunk. The modified Rodnan skin score quantifies the extent of skin thickening across 17 body areas on a 0 to 3 scale. [1]

This distinction matters because it predicts the organ-risk profile: limited disease carries a later risk of PAH, calcinosis, telangiectasia and GAVE, with a lower risk of renal crisis and severe early ILD. Diffuse disease carries an earlier risk of renal crisis (especially in the first 4 years), severe ILD, and more aggressive skin disease. The antibody confirms the subtype: anti-centromere in limited disease, anti-Scl-70 or anti-RNA polymerase III in diffuse disease."* [1]

Examiner: "What is the significance of the nailfold capillaroscopy pattern?" [1]

"Nailfold capillaroscopy is the window into the fundamental microvascular pathology of SSc. The SSc pattern — dilated and giant capillary loops, microhaemorrhages, and dropout (avascular areas) — reflects the endothelial injury, capillary structural disruption and eventual capillary loss that is the vascular 'first hit' of the disease. Three patterns are recognised: early (few giant capillaries, no dropout), active (giant capillaries, dropout, haemorrhage), and late (few capillaries, extensive dropout). [1]

Nailfold capillaroscopy is valuable because it can detect SSc before skin thickening develops — the changes are part of the very early diagnosis of SSc (VEDOSS) criteria, alongside Raynaud phenomenon and SSc-specific autoantibodies. The pattern and progression correlate with disease severity and with the risk of PAH and digital ulcers. Every SSc patient should have nailfold capillaroscopy at baseline and periodically to track microvascular progression."* [1]

Examiner: "How would you counsel this patient about her prognosis?" [1]

"I would frame the prognosis honestly but with measured optimism. Systemic sclerosis is a chronic multisystem disease for which there is no cure, but survival has improved markedly over the past three decades — five-year survival is now around 80 to 85 per cent overall — driven by ACE inhibitors for renal crisis, modern PAH therapy, ILD screening and immunosuppression. The prognosis depends on subtype, antibody and organ involvement. [1]

For limited cutaneous SSc with anti-centromere (the typical limited-disease profile), the skin prognosis is better, but the late risk of PAH defines the trajectory — annual PAH screening with echo and DLCO is non-negotiable. For diffuse disease, the first four years carry the highest risk of renal crisis and ILD progression, after which the skin often softens and the risk profile stabilises.* [1]

I would emphasise the importance of structured surveillance (annual PFTs and echo for life), the non-negotiable ACE-inhibitor rule for renal crisis, smoking cessation, cold avoidance, and a multidisciplinary clinic. I would address body-image distress from the visible skin change, the psychosocial impact, and offer patient support through Scleroderma Australia. And I would frame the conversation around living well with a chronic disease, not just surviving it — quality of life, function, work, and relationships all matter."* [1]