Systemic Sclerosis — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mrs Margaret Sullivan is a 54-year-old woman with a 14-year history of limited cutaneous systemic sclerosis (anti-centromere positive), presenting with six months of progressive exertional dyspnoea, fatigue, two episodes of pre-syncope, and new ankle swelling. Her DLCO is 38 per cent predicted (with FVC 85 per cent predicted), her transthoracic echo estimates a pulmonary artery systolic pressure of 62 mmHg with right ventricular dilatation, and her right heart catheterisation confirms pulmonary arterial hypertension (mean PAP 48 mmHg, wedge 11 mmHg, PVR 6 Wood units). She also has longstanding Raynaud phenomenon with recurrent digital ulcers, severe gastro-oesophageal reflux, and calcinosis over the fingertips. Her blood pressure is 122/78 and creatinine 76. [1]

Her main problems are:*

1. Severe pulmonary arterial hypertension (WHO Group 1) secondary to limited cutaneous SSc — her dominant prognostic problem and the immediate management priority, confirmed by right heart catheterisation with right ventricular dilatation and a pericardial effusion.
2. Intestinal lung disease — mild on HRCT (minor basal reticulation only), with the disproportionately low DLCO pointing to the vasculopathy as the dominant lung problem rather than significant fibrosis.
3. Refractory Raynaud phenomenon with recurrent digital ulcers requiring optimised vasodilator therapy and wound care.
4. Gastrointestinal disease — severe reflux, possible gastric antral vascular ectasia (iron-deficient anaemia), and possible small intestinal bacterial overgrowth.
5. The scleroderma renal crisis contingency — she is at lower risk (limited disease, anti-centromere), but I must counsel her and her GP to start an ACE inhibitor immediately if she develops new hypertension or AKI.
6. The psychosocial impact of a progressive multisystem disease on a working woman. [1]

My management plan is: urgent referral to the specialist pulmonary hypertension centre for initial combination PAH therapy (endothelin receptor antagonist plus PDE5 inhibitor, with a low threshold for adding a prostacyclin pathway agent); mycophenolate mofetil for the ILD if it progresses; optimised vasodilator therapy for Raynaud with IV iloprost for active digital ulcers and bosentan for prevention of new ulcers; high-dose PPI, IV iron, and investigation of the iron deficiency with upper GI endoscopy; structured organ-based surveillance with annual PFTs and echo; and the ACE-inhibitor contingency plan for renal crisis." [1]

Examiner probing questions and model answers

Q1: "How do you classify her disease, and why does the classification matter?" [1]

"Her disease is classified as limited cutaneous systemic sclerosis using the 2013 ACR/EULAR criteria [1]. She has skin thickening distal to the elbows and knees (sclerodactyly), a longstanding history of Raynaud phenomenon preceding skin disease by years, abnormal nailfold capillaroscopy, and the SSc-specific antibody anti-centromere. Each of these items scores points under the 2013 criteria, and her total far exceeds the classification threshold of 9.

The classification matters because the limited-versus-diffuse distinction drives the surveillance strategy and the prognostic conversation. Limited cutaneous SSc carries a different risk profile from diffuse disease: Raynaud precedes other features by many years; skin involvement is confined to the extremities and face; the risk of pulmonary arterial hypertension, calcinosis, telangiectasia and gastric antral vascular ectasia is higher; and the risk of scleroderma renal crisis and severe early ILD is lower. The anti-centromere antibody confirms the limited subtype and is mutually exclusive with anti-Scl-70 (topoisomerase I) and anti-RNA polymerase III in most patients. If two antibodies come back positive, suspect a lab error or an overlap syndrome.* [1]

This patient's anti-centromere-positive limited disease trajectory is typical: decades of Raynaud, then the late emergence of PAH as the defining complication. This is exactly why annual PAH screening — echo with TR velocity and PFTs with DLCO — is non-negotiable for life in all SSc patients, and particularly in limited disease."* [1]

Q2: "Walk me through your approach to her pulmonary arterial hypertension." [1]

"Her PAH is confirmed by right heart catheterisation — mean PAP 48 mmHg, wedge 11 mmHg, PVR 6 Wood units — which is the gold standard and the prerequisite for PAH-specific therapy. The echo estimated a pulmonary artery systolic pressure of 62 mmHg with right ventricular dilatation and a small pericardial effusion, placing her in a high-risk category. [1]

My approach follows current ESC/ERS guidance and the EULAR systemic sclerosis framework [2], in collaboration with the specialist pulmonary hypertension centre. The modern paradigm is initial combination therapy for most patients at diagnosis, rather than the older sequential approach. I would commence:*

First, an endothelin receptor antagonist — macitentan 10 mg daily (or bosentan 125 mg twice daily, with the additional benefit of preventing new digital ulcers, relevant given her recurrent ulcers [7], with monthly LFT monitoring).

Second, a phosphodiesterase type 5 inhibitor — sildenafil 20 mg three times daily or tadalafil 40 mg daily. [1]

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. Intravenous epoprostenol is reserved for functional class IV or rapidly deteriorating patients. [1]

I would avoid beta-blockers (they worsen Raynaud and are relatively contraindicated in PAH), avoid pregnancy (PAH carries a high maternal mortality), provide supplemental oxygen if hypoxaemic, and use gentle diuresis for right heart failure (recognising that over-diuresis can precipitate cardiorenal decline in a preload-dependent right ventricle). Serial reassessment at 3 to 6 months with a six-minute walk test, NT-proBNP and echo, with right heart catheterisation if there is clinical deterioration, drives escalation." [1]

Q3: "How do you manage her ILD alongside the PAH?" [1]

"Her HRCT shows only minor basal reticulation, and her FVC is 85 per cent predicted — the ILD is mild at present. The disproportionately low DLCO (38 per cent predicted) with preserved FVC is the classic pattern indicating a predominant vasculopathy (PAH) rather than significant fibrotic lung disease. This is a key diagnostic point: in SSc, a low DLCO with preserved FVC points to PAH, while a low FVC points to ILD. [1]

For the mild ILD, my approach is surveillance — annual PFTs (FVC, DLCO) and HRCT, watching for progression. An FVC decline of 10 per cent or more, or an FVC below 70 per cent predicted, would signal significant disease requiring treatment. If the ILD progresses, first-line therapy is mycophenolate mofetil 2 to 3 g daily for at least 2 years — the Scleroderma Lung Study II (SLS II) established equivalence to oral cyclophosphamide with a substantially better safety profile, making mycophenolate the standard [5]. Nintedanib (an antifibrotic that inhibits tyrosine kinases including the TGF-beta pathway) can be added to slow FVC decline in SSc-ILD, based on the SENSCIS trial [6]. The combination of mycophenolate plus nintedanib is increasingly used for progressive disease.*

The ILD and PAH need to be managed in a coordinated, multidisciplinary setting (rheumatology, respiratory, cardiology, pulmonary hypertension centre), because the therapies can interact — for example, bosentan for PAH reduces nintedanib exposure through CYP3A4 induction."* [1]

Q4: "What is her renal crisis risk and what is your contingency plan?" [1]

"Her renal crisis risk is low but not zero. Scleroderma renal crisis occurs almost exclusively in early diffuse cutaneous disease (within the first 4 years), and is strongly associated with anti-RNA polymerase III positivity and prednisolone at or above 15 mg per day [3]. She has limited cutaneous disease, anti-centromere antibody, and longstanding disease (14 years) — placing her in the lower-risk group. However, I must not be complacent.

My contingency plan has three components. First, I educate her and her GP about the symptoms — new or worsening headache, blurred vision, chest pain, or any new symptom suggesting malignant hypertension — and the instruction to check blood pressure immediately and present to hospital if there is a significant rise. Second, I monitor her blood pressure and renal function at every clinic visit, and she is given a home blood pressure cuff. Third, the non-negotiable rule: if she develops new-onset or accelerating hypertension with AKI, start an ACE inhibitor immediately — captopril 6.25 to 25 mg, up-titrated every 6 to 12 hours against the blood pressure, even if normotensive, and continue even as the creatinine rises [4]. ACE inhibitors transformed 1-year survival in SRC from under 20 per cent to about 76 per cent. I also ensure she avoids high-dose prednisolone (above 15 mg daily), which is a recognised trigger, and NSAIDs (which can precipitate AKI in SSc)."*

Q5: "What is the role of autologous stem cell transplant, and is it relevant for her?" [1]

"Autologous haematopoietic stem cell transplant (HSCT) is considered for carefully selected patients with severe early diffuse cutaneous disease — typically under 60, within 2 years of onset, with significant skin and/or lung involvement and no irreversible organ failure. The evidence base is the ASTIS trial (van Laar, JAMA 2014) [8] and the SCOT trial (Sullivan, NEJM 2018) [9]. ASTIS showed long-term event-free and overall survival favoured transplant, at the cost of higher treatment-related mortality in the first year. SCOT showed that myeloablative HSCT was superior to cyclophosphamide for event-free and overall survival at 72 months, with a treatment-related mortality of about 3 per cent.

HSCT is not relevant for this patient. She has limited cutaneous disease of 14 years' duration — her dominant problems are PAH and GI disease, not the active inflammatory skin and lung disease that HSCT targets. HSCT is a treatment for severe early diffuse disease with active inflammation, not for late-stage organ complications. The decision is always a high-stakes shared one, performed only in specialist centres after exhaustive counselling."* [1]

Q6: "What is the significance of the anti-RNA polymerase III antibody and the cancer association?" [1]

"Anti-RNA polymerase III is the third major SSc-specific antibody, alongside anti-centromere and anti-Scl-70, and the one candidates most often forget. It identifies a group with rapid diffuse skin disease, a high renal-crisis risk, and a close temporal cancer association. The Shah studies showed that in patients with anti-RNA polymerase III positivity, cancer is often diagnosed within 12 to 36 months of SSc onset, suggesting a paraneoplastic trigger in which the tumour drives the autoimmunity [10]. A new diagnosis of anti-RNA polymerase III-positive systemic sclerosis warrants age-appropriate cancer screening plus a low threshold for targeted investigation.

This patient is anti-centromere positive, not anti-RNA polymerase III positive, so the cancer association is less relevant to her specifically. However, the antibody framework is a high-yield exam topic: anti-centromere (limited disease, PAH, late onset), anti-Scl-70 (diffuse disease, ILD), anti-RNA polymerase III (diffuse disease, renal crisis, cancer). The three antibodies are mutually exclusive in most patients."* [1]

Short Case Discussion

Examination of the hands in systemic sclerosis

Examiner instruction: "Examine this patient's hands. She is a 58-year-old woman with a long history of Raynaud phenomenon." [1]

Candidate's model answer: [1]

"I would like to examine this patient's hands systematically — skin, digits, nailfolds, joints, function — then the face, the chest, and the abdomen, to identify the systemic manifestations. [1]

Inspection: I am looking at the dorsal and palmar surfaces of both hands. The skin is thickened, tight and shiny, confined to the fingers distal to the metacarpophalangeal joints — this is sclerodactyly, consistent with limited cutaneous systemic sclerosis. There is tethering of the skin to underlying structures with loss of normal skin folds and a reduced ability to pinch the skin. The fingertips show tapering (digital pitting scars) with loss of the normal pulp contour. There are painful-looking digital ulcers on the right index and left middle fingertips, with surrounding erythema. There is calcinosis cutis — firm subcutaneous deposits over the fingertips. There is distal cyanosis consistent with active Raynaud phenomenon. I can see telangiectasia on the palms and fingers — dilated capillary mats that blanch with pressure. [1]

Nailfold capillaroscopy: Using the ophthalmoscope (or a dermoscope with immersion gel) at 10 to 20x magnification on the nailfold, I can see dilated and giant capillary loops with areas of dropout (avascular areas) — the active (late) SSc pattern. This is one of the earliest signs of SSc and can precede skin disease by years. Normal nailfold capillaries are evenly spaced, hairpin-shaped loops; the SSc pattern shows dilatation, tortuosity, giant capillaries and dropout. [1]

Palpation and function: The skin feels thickened and tethered. There is reduced finger flexion due to skin tightness. Hand function is limited — making a fist is incomplete. There is no synovitis to suggest an inflammatory arthritis overlap. [1]

Face: I examine the face — there are perioral radial furrows (rhagades) with reduced oral aperture (microstomia) from perioral skin tightening. There are mat telangiectasia on the face and lips. The nose may appear pinched. [1]

Chest and abdomen: I listen for basal crackles (SSc-ILD) and a loud pulmonary component of the second heart sound or a tricuspid regurgitation murmur (PAH). I examine the abdomen for signs of gut involvement. [1]

Synthesis: The findings of sclerodactyly confined to the digits, digital pitting scars, calcinosis, active Raynaud with digital ulcers, nailfold capillaroscopy changes, perioral tightening, telangiectasia, and mat telangiectasia are consistent with limited cutaneous systemic sclerosis — the CREST phenotype (Calcinosis, Raynaud phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia). [1]

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 and PAH screening, echocardiography for PAH and right heart function, 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]

Examiner: "What is the mechanism of the nailfold capillary changes, and why do they matter?" [1]

"The nailfold capillary changes reflect the fundamental microvascular pathology of systemic sclerosis — repeated endothelial injury to small arteries and capillaries, producing capillary dilatation, structural disruption and eventual dropout (avascular areas). This is the vascular 'first hit' of the three-hit hypothesis (microvascular injury, immune activation, fibroblast dysregulation). Nailfold capillaroscopy is valuable because it provides a window into the disease process at the earliest stage — the changes can precede skin thickening by years, and are part of the very early diagnosis of SSc (VEDOSS) criteria. Three patterns are recognised: early (few giant capillaries, no dropout), active (giant capillaries, dropout, haemorrhage), and late (few capillaries, extensive dropout, ramified vessels). The pattern and progression correlate with disease severity and with the risk of PAH and digital ulcers." [1]

Examiner: "How would you manage her active digital ulcers?" [1]

"Digital ulcers are a major source of morbidity in SSc and require a structured approach. For the active ulcers, I would arrange: first, IV iloprost (a prostacyclin analogue) administered over 3 to 5 days in hospital for active, painful or non-healing ulcers — this provides vasodilation and anti-platelet effects and is the most effective agent for healing. Second, optimise oral vasodilator therapy — she should be on the highest tolerated dose of a calcium channel blocker (amlodipine 5 to 20 mg or nifedipine MR 30 to 60 mg) and a PDE5 inhibitor (sildenafil 20 mg three times daily or tadalafil daily). Third, local wound care — dressings, debridement as needed, antibiotics for secondary infection, analgesia, and hand therapy. Fourth, address contributing factors — smoking cessation is non-negotiable, cold-avoidance strategies, and avoidance of beta-blockers and sympathomimetic decongestants. [1]

For prevention of new ulcers, I would add bosentan 62.5 mg twice daily (titrating to 125 mg twice daily), based on the RAPIDS-2 trial which showed bosentan reduced the cumulative number of new digital ulcers by about 30 per cent [7]. Bosentan does not heal existing ulcers but prevents new ones. Monthly LFT monitoring is required.*

For a threatened critical digit (fixed discolouration, severe pain, absent perfusion), this is a medical emergency — admit for urgent IV iloprost, consider digital sympathectomy or botulinum toxin injection, and involve vascular surgery and the hand therapy team. The goal is to save the digit and prevent amputation."* [1]

Examiner: "What are the exam traps in systemic sclerosis?" [1]

"The traps are several. First, confusing limited and diffuse subtypes on skin distribution — the call is made on whether skin thickening extends proximal to the elbows, not on the presence of CREST features. Second, assuming anti-centromere and anti-Scl-70 can coexist — they are mutually exclusive; if both positive, suspect lab error or overlap. Third, forgetting anti-RNA polymerase III — it is the third major antibody, the one with renal crisis risk and cancer association. Fourth, stopping the ACE inhibitor in scleroderma renal crisis when the creatinine rises — this is the single most common avoidable error; continue and increase the ACE inhibitor even as the creatinine rises and even through dialysis. Fifth, giving high-dose prednisolone (above 15 mg daily) for the inflammatory features of SSc — this triggers renal crisis. Sixth, missing PAH because the patient 'only has dyspnoea' — screen every SSc patient annually with echo and DLCO. Seventh, confusing the DLCO pattern — a low DLCO with preserved FVC points to PAH, not ILD." [1]