Systemic sclerosis. Part I: epidemiology, diagnosis and therapy

Learning objectives.

By reading this article you should be able to:

• •Recall the epidemiology of systemic sclerosis relevant to anaesthesia.
• •Describe the features of systemic sclerosis and which features affect postoperative outcomes.
• •Explain the pathophysiology and the impact of modern treatments on clinical outcomes.
• •Discuss the importance of multidisciplinary management and the benefit of specialist input during perioperative period.

Key points.

• •Systemic sclerosis is a rare, multisystem, immune-mediated, inflammatory disease characterised by fibrosis and vasculopathy.
• •Associated pulmonary arterial hypertension is an independent predictor for 30-day postoperative pneumonia, congestive heart failure and all-cause mortality.
• •Of all major adverse cardiac events, only myocardial infarction is independently associated with systemic sclerosis.
• •Postoperative pneumonia accounts for more than one-third of 30-day mortality.
• •Involvement of a rheumatology specialist is recommended to estimate the extent of disease severity, optimise therapy and contribute to managing postoperative complications.

Systemic sclerosis (SSc) is a rare autoimmune, inflammatory and progressive multisystem connective tissue disease (CTD), characterised by small vessel vasculopathy and abnormal collagen deposition, leading to fibrosis of the skin and internal organs.

This, the first of a two-part review, focuses on its epidemiology, pathophysiology, diagnosis and medical therapies. In a forthcoming article, we will address the perioperative management of patients with SSc.

The hallmark of SSc is scleroderma (Greek, meaning ‘hard skin’) and sclerodactyly (finger involvement). The condition is perhaps best conceptualised as a disease spectrum. Two main phenotypes are recognised in clinical practice, defined by the extent of cutaneous involvement: limited cutaneous systemic sclerosis (lcSSc; skin involvement limited to distal to knees or elbows) and diffuse cutaneous systemic sclerosis (dcSSc; skin involvement extending proximal to the knees and elbows) (Table 1). It is important to highlight that ‘limited’ does not mean limited to skin, as lcSSc may involve many internal organs. A third phenotype (SSc sine scleroderma, without scleroderma) is described in a minority of patients.¹ In addition, a subgroup of patients (up to 20%) may have overlap features with other CTDs such as systemic lupus erythematosus or polymyositis (SSc overlap).¹

Table 1.

Clinical subtypes of systemic sclerosis. PAH, pulmonary arterial hypertension; GI, gastrointestinal; CTD, connective tissue disease.

	Prevalence	Features
Limited cutaneous systemic sclerosis (lcSSc) Previously known as knows as CREST syndrome: Calcinosis, Raynaud's phenomenon, (O)Esophageal dysmotility, Sclerodactyly, Telangiectasia	Up to 70–80%	Onset Often there is a long interval between onset of Raynaud's and skin changes. Cutaneous features Early ‘puffy hands’ followed by skin thickening and tightening on the limbs, distal to the elbows and knees but may include neck and face. The limited skin pattern should not underestimate internal organ involvement (see text). The limited skin involvement may be locally severe (i.e. susceptible to digital ischaemia and autoamputation, soft tissue calcification, telangiectasia). Predominant antibodies Anti-centromere autoantibody. Other features Higher risk of PAH and severe GI disease. Late-stage complications are common.
Diffuse cutaneous systemic sclerosis (dcSSc)	Up to 20–30%	Onset Usually there is a short interval (<1 yr) between onset of Raynaud's and skin changes. Cutaneous features Skin sclerosis extends proximal to elbows and knees with or without trunk. Skin involvement may recede as disease progresses. Predominant antibodies Mainly anti-Scl-70/anti-topoisomerase 1 and anti-U3-RNP autoantibodies. Other features It is not synonym with organ internal organ involvement but rather associated. Higher risk of certain internal organ involvement: cardiac disease, interstitial lung disease, renal crisis.
Overlap syndromes	Up to 20%	Presents features of SSc (e.g. skin changes, vasculopathy) plus manifestations of other CTD (e.g. myositis, Sjogren's syndrome or undifferentiated/mixed CTD). Autoantibodies not specific for SSc (e.g. anti RNP) or specific for overlap syndrome (polymyositis/SSc overlap)
SSc sine scleroderma	Rare (<5%)	Characterised by Raynaud's phenomenon, typical SSc serology, organ-based vascular involvement but no skin thickening.

Although terms such as scleroderma or CREST (calcinosis, Raynaud syndrome, [o]esophageal dysmotility, sclerodactyly and telangiectasia) syndrome have been used in the past, in this review, the term systemic sclerosis will be used, in keeping with the nomenclature recommended by the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR).²

Because of its multisystem involvement, these patients can find themselves under the care of anaesthetist in a variety of environments: for disease-specific elective surgery (e.g. debulking of soft tissue calcinosis, peripheral or proximal sympathectomy, lung transplantation); for elective surgery or emergency care unrelated to the disease process (e.g. emergency surgery, out of operating theatre resuscitation, obstetric delivery). Systemic sclerosis has implications for all aspects of anaesthesia. Features such as pulmonary arterial hypertension (PAH), cardiac dysfunction, renal failure and severe interstitial lung disease (ILD) carry significant morbidity and present particular challenges for the anaesthetist. Subclinical organ involvement can cause unanticipated difficulties.

Epidemiology

The overall global incidence is 1:10,000.³ In Europe the prevalence ranges from seven to 33 per 100,000 individuals, being almost four times higher in women.⁴ It most commonly presents in the third to fifth decade, and has the highest mortality among rheumatic diseases, with 10-yr survival of only 66%.^5,6 Risk factors for SSc include female sex, a history of silicone breast implants, Native American or African American race, previous chemotherapy (bleomycin, taxanes, gemcitabine) radiotherapy, exposure to gadolinium (in patients with renal failure), silica dust, vinyl chloride or organic solvents.^7,8

Scleroderma renal crisis (SRC) was the main cause of mortality in the past, but this has been attenuated with the use of angiotensin-converting enzyme inhibitors (ACEi). The main causes of death in patients with SSc are now pulmonary fibrosis/ILD (19%), myocardial disease (14%) and PAH (14%).⁹ In the past 10 yrs, improved understanding, screening for subclinical involvement (e.g. for PAH and ILD) and targeted management of associated organ impairment have resulted in improved outcomes, including increased survival duration and quality of life.

Cardiac involvement and interstitial lung fibrosis emerge in approximately 50% patients within the first 5 yrs.¹⁰ Overall, SSc is associated with a three-fold increased risk of myocardial ischaemia, and symptomatic cardiac involvement is associated with 75% mortality at 5 yrs.^11,12 Occult cardiac disease has been suspected in patients with intraoperative cardiac conduction defects leading to low output state and sinus arrest, despite unremarkable preoperative cardiac investigations.^13,14 The prevalence of mild PAH can be as high as 64%, and progression may be rapid, over a median observation time of 12 months.¹⁵ The presence of PAH carries a three-times higher risk of mortality than SSc alone.¹⁶ In addition, up to 31% of patients with SSc may have sleep disordered breathing.¹⁷

Overall, patients with SSc seem to require more high-risk surgeries than patients without SSc (36% vs 21%, p<0.001).¹⁸ When compared with the general population, patients with SSc undergo twice the number of thoracic, breast and vascular surgeries, but fewer urological and gynaecological/obstetric procedures.¹⁸ Although transplant surgery is required in <2% of cases, this is six times higher than that in patients without SSc (1.9% vs 0.3%, p<0.001).¹⁸ Isolated heart transplantation is performed rarely in those with SSc because of multisystem (particularly lung) involvement, with only a few cases described.¹²

Perioperative outcomes

There are few specific data on perioperative outcomes. Risk factors reported for adverse outcomes include: advanced age, male sex, rapidly progressing disease, extensive involvement of internal organs, extensive skin involvement, the presence of PAH and ILD, documented cardiac disease, renal dysfunction, and treatment with immunosuppressant drugs and steroids. Although some of these features may theoretically influence perioperative outcomes, the literature is not consistent.

Although there is a quoted general non-operative risk for myocardial infarction (MI) and stroke of three and two times higher, respectively, in patients with SSc, the perioperative data are inconclusive.^11,18 In one study of 4385 patients undergoing non-cardiac surgery, univariate analysis found that there was a higher risk of major adverse cardiac events (MACE) (odds ratio [OR]=2.45, p<0.001) including MI (OR=3.33; p<0.001), ischaemic stroke (OR=2.02; p<0.001), cardiac arrest (OR=2.11; p<0.001) and in-hospital all-cause death (OR=3.07; p<0.001). However, on multivariate analysis, only MI was independently associated with SSc (model 1 OR=1.85, P=0.048; model 2 OR=1.94, P=0.031) with no associations with ischaemic stroke, cardiac arrest or all-cause death. The typical patient with SSc in this study was an older female (mean age, 63 yrs) of Caucasian background with significantly (p<0.001) more cardiac and systemic comorbidities (hypertension 43%, dyslipidaemia 30%, coronary artery disease 17%, pulmonary hypertension 17%, tachyarrhythmias 16%, chronic kidney disease 16%, ILD 14%, congestive heart failure 11%, cerebrovascular disease 10%, and cardiac conduction disorders 2%) than patients without SSc. Patients with SSc required significantly more (p<0.001) orthopaedic (44%), gastrointestinal (GI) (22%), vascular (11%), breast (5.5%), thoracic (3.5%), and non-cardiac transplant surgeries (1.9%).

Patients with SSc who required lung transplantation had a multivariate-adjusted 48% relative increased risk of death at 1 yr compared with those without SSc who received lung transplantation for ILD, but similar to those who had a diagnosis of non-SSc-associated PAH.¹⁹

There are few data on ICU outcomes after surgery, most information being provided by small non-operative studies or pooled data of patients with systemic rheumatic disease (SDR), which includes SSc. Exacerbation of SDR (43%) and isolated infections (34%) seem to be the main current causes for ICU admission in patients with SDR.²⁰ For those with SSc, respiratory failure (66%) and acute renal failure (15%) are the main organ dysfunctions requiring critical care support.²¹ Interestingly, 72% of the patients had pulmonary fibrosis on baseline imaging.²¹ Associated PAH and ILD were also common (32% and 72% respectively).²¹ The dcSSc phenotype seem to be more prevalent among those requiring critical care.^21,22 A high proportion of patients with SDR require renal replacement support (39%).²⁰ Those with SSc requiring ICU admission had a 30-day mortality of 31%, increasing at 6 months and 1 yr.²¹ Respiratory complications, infection, or both are the main causes of ICU mortality. Invasive mechanical ventilation in ICU was associated with an in-hospital mortality of 85%.²¹

Chronic pain is common in patients with SSc. A study of 42 patients revealed a high incidence of pain (93%).²³ Almost half (45%) experienced pain daily. Joints and hand pain, Raynaud's phenomenon pain and back pain are common sites.^23,24 Although neuropathic pain was present in 26% of patients, this was a feature of more severe disease, though pain intensity does not seem to correlate with disease severity.^23,24 Low back pain was present even in early disease stages and was associated with anxiety and depression.²⁴

Pathophysiology

The pathophysiology of SSc is complex and as yet incompletely understood (Fig 1). Systemic sclerosis is most likely initiated by unknown triggers in an individual with a susceptible genetic background. Initiation sets off a complex pathological interplay between the key triad of endothelial cells, circulating immune cells (and their inflammatory mediators) and fibroblasts. Overall, this leads to several interacting processes: immune system dysfunction leading to production of autoantibodies and cell-mediated autoimmunity, fibroproliferative vasculopathy in small vessels, and fibroblast dysfunction causing excessive collagen and matrix components accumulation.²⁵

Fig 1.

Schematic representation of SSc pathophysiology. SSc, systemic sclerosis; ET1, endothelin 1; TGF β, transforming growth factor beta; PDGF, platelet derived growth factor.

Although traditionally SSc was regarded as a prototypical fibrotic disease, recent data suggest dysregulated tissue healing, rather than primary fibrosis as core concept.⁷ Microvascular endothelial cell injury and apoptosis activate an immune response (T and B lymphocytes, monocytes and macrophages) leading to an inappropriate and sustained overproduction of cytokines (e.g. endothelin 1 [ET-1], transforming growth factor beta [TGF-β], and platelet derived growth factor [PDGF]). These amplify and promote inflammation and the transformation of fibroblasts into activated myofibroblasts. Myofibroblasts secrete extracellular matrix proteins and collagen resulting in fibrosis, and profibrotic cytokines (TGF-β) which further enhance the profibrotic milieu. Persistent immune activation leads to diffuse microvascular injury and tissue fibrosis which becomes systemic and progressive. Amplification and persistence of this activated profibrotic state is mediated via (i) tissue hypoxia, which promotes further endothelial cell dysfunction and amplification of the pathological processes; (ii) mechanical tissue stress arising in affected tissues which further promotes fibroblast activation; and (iii) dysregulated production of cytokine mediators (TGF-β, ET-1 and PDGF). The continuous ischaemia–reperfusion small-vessel injury leads to pathological changes involving the skin (e.g. Raynaud's phenomenon, digital ulceration and gangrene), stomach (e.g. gastric antrum vascular ectasia [GAVE] – which may be responsible for silent blood loss), kidneys (e.g. renal crisis) and pulmonary vasculature (e.g. PAH).²⁶ Raynaud's phenomenon is likely to be triggered by endothelial cell injury and perpetuated by ensuing small vessel vasculopathy and arterial vasospasm.²⁶ Interestingly, a so-called ‘myocardial Raynaud's phenomenon’ with small vessel disease and coronary vasospasm has been described to explain the MIs occurring in patients with no evidence of epicardial atherosclerotic changes.²⁷

The rate of progression, generation of autoantibodies and organ involvement vary widely between individual patients, resulting in a heterogenous clinical picture. Improved understanding of disease pathogenesis has allowed identification of molecular targets for therapeutic intervention, with promising results in clinical trials. Interleukin 6 (IL-6) overexpression, produced mainly by activated macrophages, was reported to be associated with skin progression, and worse long-term survival.²⁸

Diagnosis and treatment

Patients may present with constitutional symptoms or a constellation of symptoms and signs suggestive of the diagnosis. Pathognomonic signs include scleroderma, sclerodactyly (Fig 2), calcinosis (Fig 3) and widespread telangiectasia. These changes eventually lead to terminal tuft resorption (Fig 4). The subjective sensation of ‘puffy’ hands (in early disease) prevents pressing palms and fingers tightly together (Fig 5). The early ‘puffy hands’ phase is usually followed by progressive distal to proximal sclerodactyly. Some may present with clinically manifest organ specific dysfunction or failure (e.g. lung fibrosis, PAH or renal failure).⁷ Raynaud's phenomenon is a consistent finding and can precede other features by years. Characteristics of ‘pathological Raynaud's’ (Fig 6) include new adult onset, unusual triggers (spicy food, emotion, anxiety), asymmetrical finger or hand involvement, severe or prolonged episodes and the presence of digital scars, pits or dystrophic changes on finger pulps.

Fig 2.

Sclerodactyly, Raynaud's phenomenon and digital necrosis.

Fig 3.

Cutaneous calcinosis.

Fig 4.

Terminal tuft resorption.

Fig 5.

(A) Early illness ‘puffy’ hands. (B) Inability to join palms together.

Fig 6.

Asymmetric Raynaud's.

The diagnosis is challenging, and any suspicion – particularly for cases presenting out of hours – should involve a rheumatologist. The autoantibody profile in SSc is broadly predictive of the clinical phenotype or associated complications. Most patients have antinuclear (ANA) autoantibodies, and specific SSc autoantibodies are found on extractable nuclear antigen (ENA) autoantibody screening. The presence of overlapping syndromes, the negative autoantibodies screen and the variable disease presentations adds to the complexity of diagnosis.

No specific, molecular targeted treatment is yet available as disease modifying therapy for SSc, although several promising agents are being investigated.²⁹ Tocilizumab, a monoclonal antibody against IL-6 receptor, has showed promising results in SSc ILD in phase 3 trials.^30,31 Historically, treatment has been oriented towards specific organ dysfunction (e.g. ACEi for renal crisis, proton pump inhibitors [PPI] for gastro-oesophageal reflux, etc.; Table 2). Recent additions to this include nintedanib and tocilizumab for ILD and evidence-based management strategies for PAH.¹⁵ Traditionally there was no role for immunosuppression in SSc. This paradigm is changing as understanding of disease pathogenesis evolves. Immunosuppressants (e.g. mycophenolate mofetil or rituximab) are now used in the early phases of dcSSc, with evidence for improved pulmonary function tests and reduction of the ILD extent.³² As evidence and opinions change regarding steroids, those with evidence of inflammation and at highest risk of poor outcomes (e.g. rapidly progressive skin involvement dcSSc) may be taking medium-term moderate-dose regimens and require additional ‘stress’ doses perioperatively.³³

Table 2.

Supportive treatment and perioperative significance. SIADH, syndrome of inappropriate antidiuretic hormone secretion; ACEi, angiotensin-converting enzyme inhibitors; TGF β, transforming growth factor beta; PDGF, platelet derived growth factor; TNF α, tumour necrosis factor alpha; cGMP, cyclic guanosine monophosphate; cAMP, cyclic adenosine monophosphate.

Drug and mechanism of action	Adverse effects
Skin and musculoskeletal
Skin thickening/restriction of joints
Methotrexate Mechanism Immunomodulator; inhibits dihydropholic acid reductase leading to impaired DNA synthesis and immune cells replication impairment.	Hepatic fibrosis (rare), bone marrow suppression (rare), acute pneumonitis (rare).
Mycophenolate mofetil Mechanism Immunomodulator; antimetabolite with antifibrotic role via lymphocytes (T and B) activation suppression and antibody production impairment.	Myelosuppression, pancytopenia, hepatotoxicity, increased risk infection.
Cyclophosphamide Mechanism Immunomodulator; cytotoxic effect on both resting and active lymphocytes (particularly T-helper and B cells).	Drug-induced cardiomyopathy, immunosuppression, haemorrhagic cystitis, pneumonitis, SIADH.
Steroids (e.g. prednisolone) Mechanism Immunomodulator; supresses lymphocytes, fibroblasts and antibody production.	Hypertension, diabetes, electrolyte imbalances, peptic ulcer disease, skin frailty, adrenal suppression.
Rituximab Mechanism Immunomodulator; induces killing of the CD20+ cells (lymphocytes B depletion).	Progressive multi-focal leucoencephalopathy, increased risk of infection including serious infections.
Finger ulcers
Phosphodiesterase 5 inhibitor (PDEI) (e.g. sildenafil) Mechanism Vasodilator; increases intracellular cGMP leading to vasodilatation.	Ischaemic optic neuropathy, ventricular function reduction, cerebral venous thrombosis. Risk of severe hypotension with gram-negative sepsis. Unpredictable effects when nitrates are co-administered.
Endothelin-1 receptor antagonists (ERAs) (e.g. bosentan) Mechanism Vasodilator and (?) antifibrotic role via competitive inhibition of endothelin-1 receptors; endothelin also plays a role in cell proliferation, fibrosis and inflammation.	May increase blood loss (vasoconstriction inhibition), negative lusitropic effect.
Reynaud's phenomenon
Calcium channel blockers	Reduces cardiac morbidity in non-cardiac surgery.
Fluoxetine Mechanism Vasodilator; selective serotonin uptake inhibitor; serotonin causes direct vasodilation through 5HT7 and 5HT2B receptors.	Bradycardia, coronary vasospasm, SIADH, platelet inhibition, prolonged bleeding times, cytochrome P450 inhibition
Angiotensin receptor blockers Mechanism Vasodilator; displacement of angiotensin II via competitive antagonism of the angiotensin II receptors.	Hyperkalaemia (dysrhythmias), renal impairment
Prostacyclin receptors analogues (e.g. epoprostenol) Mechanism Vasodilator and platelet aggregation/adhesion inhibitor; increases intracellular cAMP via action on the prostacyclin IP receptor.	May increase blood loss through vasodilation.
Interstitial lung disease
Mycophenolate mofetil	See above.
Cyclophosphamide	See above.
Azathioprine Mechanism Immunomodulator; purine synthesis inhibition leading to DNA/RNA synthesise inhibition affecting B and T cells.	Reduces the effect of atracurium, vecuronium and pancuronium.
Nintedanib Mechanism Antifibrotic and anti-inflammatory; reduces fibroblasts activity via inhibition of profibrotic mediators (PDGF, fibroblast growth factor, TGF-β and vascular endothelia growth factor).	Vomiting, gastrointestinal perforation, weight loss, arterial thromboembolism, myocardial infarction, bleeding, hypothyroidism, increased liver enzymes.
Pirfenidone Mechanism Antifibrotic and anti-inflammatory; reduces fibroblasts proliferation, collagen production and reduces the production of mediators such as TGF-β, TNF-α and IL-1β.	Gastroesophageal reflux disease, vomiting, photosensitivity, increase hepatic enzyme concentrations (high risk if a CYP1A2 inhibitor is being used concomitantly).
Rituximab	See above.
Tocilizumab Mechanism Immunomodulator; monoclonal antibody that inhibits competitively the IL-6 receptor leading to failure of inflammatory recruitment of B and T cells.	Mouth ulcers, gastrointestinal perforation, hypertension, increased risk of infections, malignancy, liver dysfunction.
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus) Mechanism Immunomodulator; inhibits calcineurin enzyme leading to decreased T cell activation and signalling.	Used post lung transplant in some SSc patients. Associated with renal vasoconstriction and SRC.
Cardiac disease
Systolic dysfunction: ACEi	Hyperkalaemia (dysrhythmias), renal impairment.
Diastolic dysfunction: diuretics	Hypovolemia, electrolyte losses, dysrhythmias.
Cardiac resynchronisation therapy/pacemakers	May require preoperative reprogramming to avoid interference from diathermy.
Pulmonary arterial hypertension
ERAs, PDE5i, Prostacyclin analogues	See above.
Prostacyclin receptor agonists (e.g. selexipag) Mechanism Vasodilator and platelet aggregation/adhesion inhibitor; prostacyclin IP receptor agonism leading to vasodilatation, decreased cell proliferation and platelet aggregation inhibition.	Myalgia, anaemia, nasopharyngitis.
Anticoagulation	Ensure timely discontinuation or reversal.
Oesophageal disease
Proton pomp inhibitors	Hypomagnesaemia, hypocalcaemia.
H2 blockers	Confusion, pancreatitis, hepatitis, seizures.
Antiacids	Hypermagnesemia, milk-alkali syndrome, hypophosphataemia.
Gastric disease
Prokinetics	Risk of aspiration in patients who missed prokinetics or are not on them.
Scleroderma renal crisis
ACEi	See above.

Although spanning various classes, different mechanisms of action and treating various SSc complications, the drugs used in SSc belong largely to five main pathways:

• (i)Immunomodulation (e.g. steroids, rituximab, mycophenolate mofetil, tocilizumab, etc.)
• (ii)ILD antifibrotics (e.g. nintedanib, pirfenidone)
• (iii)Vasodilators (calcium channel blockers, phosphodiesterase 5 inhibitors [PDEI], prostacyclin analogues, etc.)
• (iv)General cardiac disease (e.g. ACEI, diuretics, antihypertensives, etc.)
• (v)General GI disease (e.g. antacids, PPIs, prokinetics, etc.)

Of major importance for the anaesthetist are the vasodilators used for the management of PAH (e.g. endothelin-1 receptor antagonists, PDEIs, prostacyclin analogues) and their perioperative management (see Part 2). In addition to PAH, these vasodilators may be used on specialist advice for the perioperative management of Raynaud's phenomenon or finger ulceration.

Role of the rheumatologist

The SSc perioperative literature to guide evidence-based care is scarce. Reflecting this, there are no guidelines to guide management of anaesthesia or perioperative care. Most evidence is observational and derived from case reports or series, and expert opinion. With exception of some perioperative cardiovascular outcomes, the care of these patients relies on extrapolating data from the rheumatology literature.¹⁸ Although there are multiple specialty guidelines for the management of the disease and its complications (e.g. SRC, antiphospholipid syndrome [APS]), only one European guideline to date includes advice on anaesthesia.³⁴ It also includes a concise summary of some of the associated emergencies relevant to the anaesthetist such as SRC, PAH and right heart decompensation.

In the absence of robust data and guidelines, the rheumatologist has an essential role in the perioperative period (Table 3). Their input bridges the current gap between specialty guidelines and perioperative care. In our experience, most perioperative requests for specialist input are for (i) immunosuppression queries (including steroids and infection), (ii) use of beta blockers and (iii) development of new complications (e.g. is this postoperative creatinine increase a precursor of SRC or not?).

Table 3.

The rheumatologist's role in the perioperative period. SRC, scleroderma renal crisis; VTE, venous thromboembolism; ACEi, angiotensin-converting enzyme inhibitors.

•Provides support for the out-of-hours cases • Facilitate diagnosis ○ Assesses autoantibody associations, clarifies the presence of overlap features •Offers a better insight regarding diseases progression •Delineates disease extent and severity •Advises on the risk of subclinical organ involvement • May suggest/support specific perioperative investigations ○ (e.g. cardiac MRI, right heart catheterisation) • Advise on optimal perioperative therapies management ○ Risk of discontinuing medication (e.g. ACEi) ○ Risk of commencing medication (e.g. beta blockers) ○ Steroids management ○ Potential drug interactions •Advise on complications prevention •Should be consulted in the postoperative period should complications ensue (e.g. SRC, VTE, digital gangrene, etc.)

Conclusions

Systemic sclerosis is a rare progressive autoimmune CTD. Its multisystem involvement and the need for more high-risk surgical procedures present a major clinical challenge for the anaesthetist. Pulmonary hypertension is present in more than half of patients and is a major perioperative risk factor. In addition, postoperative MI is strongly associated with systemic sclerosis. Specific issues for the anaesthetist, such as difficult direct laryngoscopy and intraoperative aspiration, add to the risks of perioperative morbidity. Although there is no specific treatment, the overall outcome and survival have improved in recent decades as a result of better understanding of the disease and progress in providing specific organs support. This increases the likelihood of encountering older patients with significant comorbidities requiring anaesthesia and critical care. Unfortunately, the lack of guidelines to drive evidence-based perioperative care adds to the complexity of management. Hence, the involvement of the rheumatology specialist is paramount for successful perioperative outcomes.

Declaration of interests

The authors declare that they have no conflicts of interest.

Biographies

Catalin Iulian Efrimescu FCAI is a post-CST fellow in anaesthesiology at Mater Misericordiae University Hospital.

Suzanne Donnelly MD MRCPI is a consultant rheumatologist at Mater Misericordiae Hospital. She provides clinical expertise for the patients with systemic sclerosis at the Irish national centres for pulmonary hypertension and heart/lung transplant. Associate Professor Donnelly is also associate dean (education) and programme director at the School of Medicine, University College Dublin.

Donal Buggy DSc MD MSc FRCPI FFSEM FRCA FESA-IC FCAI is a consultant anaesthesiologist at Mater Misericordiae Hospital and professor of anaesthesiology and perioperative medicine at University College Dublin. He is an active clinician, scientist and mentor and has published extensively on diverse topics across the specialty.

Matrix codes: 1A02, 1C01, 1H02, 2A03, 2A07, 3A01, 3I00

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