SSc. For childbirth, obstetric analgesia is recommended. In the case of respiratory impairment, opioid drugs should be used sparingly. Locoregional anesthesia allows for prolonged postoperative analgesia.

Whenever general anesthesia is required, endotracheal intubation is recommended to avoid the risk of reflux and aspiration. Assisted ventilation can be tricky, and the ventilatory mode should be adapted to the decrease of pulmonary compliance in cases of pulmonary fibrosis.

## General precautions

The use of vasopressor amines may aggravate Raynaud's phenomenon and the risk of digital necrosis. Their use must be limited as much as possible. In cases of deep digital ischemia, treatment with Iloprost IV should be offered as soon as possible depending on the hemodynamic status of the patient.

NSAIDs should be avoided because of the risk of gastrointestinal complications, the risk of peptic ulcer of the esophagus, the risk of gastrointestinal hemorrhage due to the presence of telangiectasias in some cases, and the risk of renal damage in certain patients, particularly those with a diffuse cutaneous form that has been evolving for less than 3–5 years.

The surgical procedure must be accompanied by gastrointestinal protection through the use of intravenous proton pump inhibitors (PPIs). In patients with gastro-paresis, an intravenous injection of erythromycin at the time of induction of anesthesia allows the stomach to be emptied and limits the risk of inhalation.

### Cardiorespiratory monitoring

Skin thickening and/or joint contractures can make it very difficult to establish a venous line.

Oxygen saturation should not be measured on the finger or ear as Raynaud's phenomenon is frequent in the operating room and in acute situations, but on the forehead using a suitable sensor.

For lengthy procedures, it is recommended to avoid invasive blood pressure measurement, especially radial pressure measurement. The risk of this procedure is radial thrombosis and digital necrosis, or even acute ischemia of the hand if there is ulnar thrombosis (10–15% of patients).

General anesthesia is very delicate if there is pulmonary arterial hypertension due to the consequences of hemodynamic variations. Surgery in these situations must be discussed at length, and if it is to be performed in emergency situations, the advice of the reference center or a pulmonary arterial hypertension competence center is essential. In this situation, local or locoregional anesthesia will be preferred. For orthopedic procedures, cemented prostheses should be avoided because of the

embolic risk at the time of nailing, which can increase pulmonary arterial hypertension.

### Risks of complications

Patients with SSc are at greater risk for intubation failure and difficulty, GERD, and aspiration.

Patients with pulmonary fibrosis are at risk of hypoxia, desaturation, and reduced lung compliance, especially if there is thoracic skin involvement. There is therefore an increased risk of sudden desaturation in these situations, particularly when maneuvering in the upper airways.

Scleroderma patients may be hypersensitive to opiates and therefore at a higher risk of postoperative respiratory failure when forced vital capacity is < 1 L.

In case of cardiac damage with diastolic and/or systolic dysfunction, there is a risk of hypotension, which is sometimes severe, at the time of induction of anesthesia due to the induced vasodilatation. There may also be a risk of pulmonary edema with rapid filling if there is an unknown systolic and/or diastolic dysfunction.

Stress, pain, dehydration, hypothermia, and vasoconstrictive therapies increase the risk of vasospastic crisis and thus of distal ischemia and digital necrosis.

In the case of colic or small bowel disease, gastroparesis can be induced by the procedure, thus creating a risk of obstipation. In some cases, microbial pullulation can lead to abdominal bloating and diarrhea. Some patients may develop a pseudo bowel obstruction. Others may develop true occlusions if there is obstipation. In these situations, if there is the slightest doubt, an abdominal CT scan should be performed to look for obstipation or chronic intestinal pseudo-obstruction.

The concomitant use of low doses of corticosteroids and/or immunosuppressants increases the risk of postoperative infection.

### Postoperative care

Postoperative care depends on the type of surgery and the severity of the disease. Postoperative ventilation is sometimes necessary because of the risk of postoperative respiratory failure in some patients. Temporary supervision in the ICU may be required. The same is true in patients with a specific heart disease or pulmonary arterial hypertension.

Continuous EKG monitoring is recommended in the postoperative period with volume and tension monitoring.

Postoperative analgesia is locoregional at best. NSAIDs should be avoided, and opioids should be used with caution.

Kidney function and blood pressure should be carefully monitored throughout the surgical procedure and in the days following it. There is indeed a risk of scleroderma renal crisis, especially in patients with a diffuse cutaneous form that has been evolving for less than 3–5 years.
Early warning signs are the occurrence of high blood pressure (≥ 140/90 mmHg confirmed at least twice) and/ or a rapidly progressive renal failure that may become oligoanuric. Biologically, microangiopathic hemolytic anemia with schizocytes should be investigated for the occurrence of microangiopathic hemolytic anemia with schizocytes and for decreased haptoglobinemia with elevated LDH.

### Obstetrical particularities

In the vast majority of cases, women with scleroderma can give birth through the vaginal route. Epidural analgesia is possible and recommended in women with SSc. An episiotomy may be necessary for first-time deliveries, as in women without SSc. In certain situations of very pronounced sclerosis that may hinder the passage of the newborn through the birth canal, caesarean section may be indicated under local anesthesia.

The occurrence of a scleroderma renal crisis during pregnancy may appear as preeclampsia, but in the case of a renal crisis, the plasma renin level is very high, and renal failure is progressive and rapidly develops into microangiopathic hemolytic anemia. Emergency treatment is the use of ACE inhibitors, regardless of the creatinine level and of the stage of the pregnancy, due to the therapeutic emergency.

### Conclusion

Anesthesia and the perioperative period are situations with a high risk of morbidity and mortality in patients with SSc. A well-conducted preoperative check-up involving close collaboration with reference and competent centers enables optimal precautions to be taken during this period. The medical and technical specificities encountered in the perioperative situation can for the most part be extended to intensive care management for acute medical situations.

## Appendix 7: Emergency guidelines

This appendix has been extracted and modified from ORPHANET's 2017 emergency guidelines on SSc. www.orpha.net/data/patho/Emg/Int/fr/Sclerodermie_FR_fr_EMG_ORPHA801.pdfxii **Emergency guidelines for paramedics**

### Mechanisms

Associated autoimmune disease: Raynaud's phenomenon, cutaneous sclerosis and severe gastroesophageal reflux, a variable visceral involvement.

### Special risks in emergencies

Malignant arterial hypertension, cardiac decompensation (on PAH or scleroderma cardiomyopathy), respiratory distress (on fibrosis or severe PAH), upper gastrointestinal hemorrhages

### Frequently prescribed long-term treatments

* Raynaud's phenomenon: calcium channel blockers

* Ulcer or digital necrosis: iloprost (antiplatelet agents)

* Heart disease or PAH: conversion enzyme inhibitor, diuretics, digitalis, low-salt diet

* Pseudo-occlusive syndrome: octreotide, erythromycin

* Pulmonary fibrosis, muscle damage: immunosuppressants

* Pulmonary fibrosis: respiratory physiotherapy

* PAH: sildenafil, tadalafil, bosentan, ambrisentan, intravenous epoprostenol, subcutaneous treprostinil, iloprost aerosol

* Painkillers

### Traps:

* Decompression of PAH during physical exertion, altitude, excess salt, or taking antiinflammatory drugs

* Risk of focal myocardial ischemia, rhythm disturbance or healthy coronary conduction on myocardial fibrosis

### Specifics of pre-hospital medical care

* Difficult venous approach (skin is sometimes brittle, fibrotic veins)

* Patient is usually allergic

* Electrocardiogram indicated in initial assessment

* Urine test strip: existence and severity of a renal crisis

* On-board biology: kalemia, hemoglobin, troponin, gasometry to assess the impact of the SSc and referral to an intensive care setting

* Contraindication of nitrates or similar derivatives if treated with phosphodiesterase V inhibitors (sildenafil, tadalafil, etc.)

* Increased risk of bleeding for patients on iloprost

* Anti-aggregants need be adjusted according to etiology and ischemic risk

* Precautions for GA and the choice of the mode and parameters of invasive or noninvasive ventilation, depending on the systemic damage, in particular pulmonary or cardiac.

* Vasopressive amines capable of increasing peripheral vasoconstriction, especially digital vasoconstriction

* Risk of difficult intubation: limitation of the mouth opening, severe GERD

### Guidelines for hospital emergencies

#### A. Emergency recommendations
<caption>**Table 9** Criteria for the classification of the hypertensive form of scleroderma renal crisis</caption>

a. HBP ≥ 140/90 mmHg (or increase of systolic BP ≥ 30 mmHg or diastolic BP ≥ 20 mmHg) obtained on two different measurements with a minimum separation of 5 min, without other explanation than the SSc

b. Acute renal injury, without other explanation than the SSc AKI according to the KDIGO classification: more than 50% increase of serous creatinine from the reference value within the preceding 7 days or an absolute increase of 26.5 µmol/l (≥ 0.3 mg/dl) in 48 h

c. Thrombotic microangiopathy
New or aggravated anemia without other explanation
Schizocytes
Thrombopenia ≤ 100,000/mm³ confirmed on a smear
Signs of hemolysis: elevated LDH, low haptoglobin, increased reticulocytes
Negative antiglobulin test
Target organ dysfunction
Hypertensive retinopathy
Hypertensive encephalopathy
Pulmonary edema
Acute pericarditis

Anomalies suggestive of renal biopsy (fibrinous thrombi, fibrinoid necrosis, glomerular collapse, onion bulb proliferation in pre-glomerular arterioles and arch arteries)

HBP high blood pressure, BP blood pressure, SSc systemic sclerosis, AKI acute kidney injury, LDH lactate dehydrogenase

## B. Emergency situation 1: Malignant hypertension on scleroderma renal crisis

Scleroderma renal crisis is a complication that occurs more particularly in patients with recent (<3–5 years of evolution) and rapidly progressive diffuse cutaneous scleroderma.

It is associated with de novo hypertension and increased creatinine levels.

The presence of anti-RNA polymerase III ABs constitutes an over-risk of kidney failure.

It is a malignant HTA with retinal hemorrhaging and exudates.

Diagnosis is therefore generally easy (Table 9) with a sudden onset of severe hypertension accompanied by headache, visual disturbances, sometimes convulsions, heart failure, pericardial effusion, microangiopathic hemolytic anemia with schizocytes and thrombopenia with rapidly progressive oliguric renal failure.

<table><caption>**Table 10** Definition of normotensive scleroderma renal crisis</caption><thead><tr><th colspan="2">Normotensive scleroderma renal crisis</th></tr></thead><tbody><tr><td colspan="2">Creatinine levels over 50% above baseline or creatinine ≥ 120% of the upper normal range in the lab</td></tr><tr><td colspan="2"><strong>And one of the following five criteria:</strong></td></tr><tr><td colspan="2">At least one of the following 5 criteria:</td></tr><tr><td colspan="2">Proteinuria ≥ 2+ by strip</td></tr><tr><td colspan="2">Hematuria ≥ 2+ by strip or ≥ 10 RBC by field</td></tr><tr><td colspan="2">Thrombopenia &lt; 100,000/mm³</td></tr><tr><td colspan="2">Hemolysis defined by an anemia not linked to another cause with:</td></tr><tr><td colspan="2">(1) Schizocytes or other RBC fragments found on the blood smear</td></tr><tr><td colspan="2">(2) Increase in the reticulocyte level</td></tr><tr><td colspan="2">Renal biopsy showing a typical appearance of scleroderma renal crisis (fibrinous thrombi, fibrinoid necrosis, glomerular collapse, onion bulb proliferation in pre-glomerular arterioles and arch arteries)</td></tr></tbody></table>

Microscopic hematuria, proteinuria with an extremely high plasma renin level is also sometimes found. This table may be incomplete.

Any de novo arterial hypertension and acute renal failure in a scleroderma patient should raise concerns of a scleroderma renal crisis.

In the case of malignant arterial hypertension on renal attack, the initial severity is neurological (convulsions) and cardiopulmonary by the risk of acute pulmonary edema (APE).

Approximately 10% of scleroderma renal crisis are normotensive (Table 10), which is difficult to diagnose.

**Emergency diagnostic measures**

**Formalized criteria for assessment of scleroderma renal crisis**

**Assessing the severity:**

**Malignant hypertension with neurological complications**

**Threatening hyperkalemia on acute renal failure**

**Hydro-sodium inflation requiring emergency extrarenal purification**

**Severe respiratory distress requiring positive pressure, noninvasive or invasive ventilation**

**Emergency exams:**

**Urine test strip**

**Electrocardiogram with at least 12 leads**

**Blood count with schizocyte and platelet, creatinine, and kalemia counts**

**Immediate therapeutic measures (Fig. 5)**
<figure><img src="image_9.png" /><figcaption>Fig. 5 Management of scleroderma renal crisis</figcaption></figure>

### Symptomatic measures:

Treatment of hyperkalemia, extrarenal purification if necessary.

### Specific treatments:

Refer to reference specialists or entrust to regional or national centers of reference for rare diseases (or centers of competence).

## Emergency situation 2: Right cardiac decompensation on pulmonary arterial hypertension (PAH)

Dyspnea is the main symptom. It often sets in gradually and insidiously.

PAH can sometimes appear suddenly, for example during exertion (possible syncope of effort), during a high-altitude stay or when taking antiinflammatory drugs. It may be class IV dyspnea with signs of right heart decompensation.

In the case of right heart decompensation on PAH, the clinical picture is obvious: lower limb edema, hepato-jugular reflux in a patient with known PAH. The risk is heart failure and syncope. If it is not inaugural, the evolution of such a clinical picture may be heightened with a shock on heart failure or consciousness disorders.

### Emergency diagnostic measures

### Clinical elements of diagnosis:

Clinical signs of right heart decompensation in a patient with known and treated PAH

Right heart decompensation can sometimes be indicative of PAH

### Assessing the severity:

Signs of respiratory distress, hypoxia, syncope, functional angina

BNP or NT-proBNP tests

### Emergency exams:

**If the diagnosis of PAH is not known**, the diagnosis is suspected on echocardiography, which finds dilatation of the right cavities and elevated pulmonary BP (PBP) with no sign of pulmonary embolism (post-embolic PH).

**Warning**

In this context, the **angioscan** is used to evaluate thromboembolic disease (TED).

It is imperative to use a **hypo-osmolar contrast agent with slow diffusion** because of the risk of defusing the cardiac pump in case of very high PBP.

Integrated into an exhaustive check-up, not adapted to the context of the emergency department, right cardiac catheterization is necessary to confirm the diagnosis and
direct the patient to the care channel best suited to his or
her acuity subgroup.

If PAH is known, an echocardiography will assess
immediate signs of severity. There is no indication to per-
form an emergency right heart catheterization.

Immediate therapeutic measures

Symptomatic measures:

Limit the patient's efforts and any event likely to
increase cardiac output (tolerance to the increase in
afterload, but output limited by the preload, which
cannot absorb the variations in venous return) or,
conversely, related to hypovolemia, which may
increase or cause coronary hypoperfusion.

Oxygen therapy, diuretics depending on the clinic.

Make sure that, if PAH is known and treated, that
there have been no untimely treatment interrup-
tions.

An ultrasound of the vena cava will make it possible
to evaluate the indication of diuretics at high doses
(sometimes doses of up to 1.5 or 2 g/24 h of furo-
semide—40 mg of bumetanide are necessary).

Preventive treatment with low molecular weight heparin to prevent TED, but the benefit of hypocoagulation is discussed in PAH associated with scleroderma and, on the other hand, there is a risk of gastrointestinal hemorrhage on telangiectasias.

After management in the emergency department,
treatment will require discussion of specific anti-
PAH therapy adjustment: refer the patient to a spe-
cialized center such as a PAH reference or compe-
tence center.

Specific treatments:

Vasoactive amines if heart failure and low volume
filling.

Transfer to a reference or competence center for dis-
cussion of treatment by endothelin receptor antago-
nists, phosphodiesterase V inhibitors or prostacyc-
lin (or in combination).

Discussion of a bipulmonary transplant in extreme
emergency.

Emergency situation 3: Acute decompensation of pul-
monary fibrosis

The emergency is oxygenation by high-flow oxygen therapy or noninvasive or invasive mechanical ventilation.

Since PAH may be underlying in an unsuspecting and
therefore untreated patient, there is a great deal of cau-
tion and therefore similarities in the emergency ventila-
tory approach with the emergency situation 2.

Emergency diagnostic measures

Clinical elements of diagnosis:

Worsening dyspnea if pulmonary fibrosis known,
cyanosis.

Assessing the severity:

Altered consciousness, pause in breathing.

In case of abrupt respiratory aggravation in a sclero-
derma patient with known pulmonary fibrosis, look for:

- A bronchial or pulmonary superinfection

- A pulmonary embolism

- Left or global cardiac decompensation

- Onset or exacerbation of severe PH on fibrosis

If no embolism, no superinfection, and no evidence
of PH, consider an acute exacerbation of pulmonary
fibrosis.

Emergency exams:

As part of the recommendations for the evaluation
of the etiologies mentioned in the previous paragraph,
blood gas evaluation and chest CT imaging (more or less
injected) are usual.

Immediate therapeutic measures

Symptomatic measures:

Oxygenation via a device adapted to the oxygen
flow, possibly by noninvasive mechanical ventilation
or even intubation and invasive ventilation.

Respiratory physiotherapy in case of bronchial con-
gestion.

Antibiotic therapy in case of suspected infection.

Specific treatments:

Specific treatments should be discussed with spe-
cialists in a reference center or a competence center
for rare diseases.

No specific emergency treatment, symptomatic sta-
bilization, and assessment of the depth of SSc signs.

If acute exacerbation of pulmonary fibrosis with ARDS: consider high-dose corticosteroid therapy after discussion with a SSc reference or competence center.

Emergency situation 4: gastrointestinal bleeding

It can occur on esophageal ulcers or on gastric, duode-
nal or even small intestine or colon telangiectasias.

Emergency diagnostic measures

Clinical elements of diagnosis:

Anemia on digestive bleeding.

Assessing the severity:

Hemodynamic status
Severity criterion: “watermelon” stomach evaluated by gastric fibroscopy

Emergency exams:

CBC-platelets, hematocrit, pretransfusion workup

Emergency endoscopy: confirms the diagnosis and allows treatment

Symptomatic (laser if telangiectasias)

## Immediate therapeutic measures

**Symptomatic measures:**

- Blood transfusion if necessary

- Admission to the ICU

- Intravenous iron

**Specific treatments:**

- Hemostatic laser treatment

- Antral surgical resection (if severe bleeding in the “watermelon” stomach)

**Emergency situation 5: Decompensation of scleroderma cardiomyopathy**

Pericardial, myocardial or, more rarely, endocardial damage.

Most often secondary to PAH or PH secondary to pulmonary fibrosis causing progressive dilation of the right cavities, sometimes resulting in right heart failure.

Sometimes primitive, specific to SSc, often not very symptomatic.

Usually, there is no damage to the coronary trunks, but the coronary reserve is defective with a functional inability of the microcirculation to adapt to the increased cardiac work, causing myocardial ischemia with a risk of conduction or rhythm disturbance.

**Emergency diagnostic measures**

Clinical elements of diagnosis:

**The clinical expression is variable:**

- Absence of symptoms or chest pain, healthy coronary arteries, rhythm or conduction disturbances

- When myocardial fibrosis affects the left cavities: frequent alteration of ventricular diastolic function with systolic function maintained for a long time

- Brain natriuretic peptide test: BNP/NT-proBNP

- Assessing the severity:

- Type IV dyspnea of the functional classification of heart disease according to the New York Heart Association (NYHA)

- Cyanosis

- Right or left heart failure

- Look for a ventricular rhythm disorder and a conduction disorder (risk of sudden death)

- Emergency exams:

- EKG

- Echocardiogram

- BNP/NT-proBNP test

- Troponin

Coronary angiography according to the clinical presentation, biological and electrical data (most often normal, the cardiac involvement of scleroderma is often microcirculatory).

## Immediate therapeutic measures

- Monitoring:

Continuous EKG: elevated risk of heart rhythm disorders. Continuous electrocardiographic monitoring in the cardiac intensive care unit or intensive care unit.

- Symptomatic measures:

Usual measures: low-salt diet, ACE inhibitors II, diuretics

Calcium channel blockers of the dihydropyridine family can improve myocardial perfusion

- Specific treatments:

Refer the patient to specialists in reference or competence centers for an assessment of all potential SMA impairments.

**Emergency situation 6: digestive motility disorder**

The clinical expression depends on the primary level of impairment:

- Esophagus (75-90% of patients): pyrosis, dysphagia, peptic esophagitis

- Stomach (50% of patients): early feeling of fullness, nausea, vomiting, bloating

- Small intestine (40-70% of patients): diarrhea, constipation, digestive distension, malabsorption syndrome, microbial swelling, pseudo-obstructive syndrome

- Colon (20-50% of patients): colonic distension, constipation, pseudobstructive syndrome

## 1. Emergency diagnostic measures

- Clinical elements of diagnosis:

Sub-occlusive or occlusive state.

- Assessing the severity:
Complications: fecal impaction, perforations, volvulus, cholestasis, digestive infarction.

* Emergency exams:

The plain abdominal X-ray can be used to look for signs of occlusion, sternal stasis, but the abdominal CT scan is much more efficient.

## 2. Immediate therapeutic measures

* Monitoring:

Monitoring of intestinal transit, beware of false diarrhea on chronic constipation, make sure there is no obstructive fecal impaction.

* Symptomatic measures:

**Warning:** Remove an obstruction on fecal impaction.

* If pseudo-obstructive syndrome or obstipation with digestive distension: octreotide (recommended initial dose of 50 µg × 2/day, to be increased if clinical response is inadequate, but not to exceed 100 µg × 2/day) may be effective.

* If colic attack: hospitalization (sometimes prolonged), manual evacuation if obstructive fecal impaction occurs, use of laxatives and enemas in combination with a high-fiber diet.

* Serious complications can occur such as stercoral perforation, volvulus, cholestasis and even digestive infarction.

* Prokinetic drugs are not very effective.

### Specific treatments:

Refer the patient to specialists in reference or competence centers with expertise on rare autoimmune diseases for assessment of all visceral disorders.

## B. Drug precautions (possible interactions, contraindications, precautions for use, etc.)

Never abruptly stop PAH treatments (sildenafil, tadalafil, bosentan, ambrisentan, selexipag, intravenous epoprostenol, subcutaneous treprostinil, aerosolized iloprost): risk of cardiac decompensation.

In patients treated with a phosphodiesterase V inhibitor (sildenafil, tadalafil) for PAH: major risk of vasoplegic shock if the patient is treated with nitrates or analogues.

## C. Technical precautions and prevention of complications

* Systemic damage, particularly to the lungs or heart, can limit the indications for general anesthesia (GA) and requires great vigilance in the choice of the mode and parameters of invasive or noninvasive ventilation.

* GA indications must be discussed and put into perspective with any anticipated directives.

* For the performance of certain procedures indicating a GA, give preference to alternative techniques (locoregional anesthesia, anesthesia with a concentration objective).

* Venous vascular edges: peripheral perfusion is often difficult, with frequent use of central venous lines.

* Arterial vascular edges: significant risk of digital ischemia or thenar eminence when inserting radial catheters: perform an Allen's test and discuss a first femoral approach despite a higher risk of infection.

* Vasopressor amines are associated with a high risk of digitalis vasoconstriction and digital necrosis.

* Potentially difficult endotracheal intubation (microstomia, cervical stiffness). Anticipate a difficult intubation procedure with experienced operators: smaller probe diameter, Eichmann type clamp, video laryngoscopy, fibroscopy.

* Special monitoring of the patient in the immediate aftermath of an extubation (high risk of aspiration due to gastroesophageal reflux).

* In resuscitation, in an unintubated patient, especially when resuming oral feeding:

* Prevent gastroesophageal reflux, as there is a major risk of inhalation pneumopathy.

* If the patient is suffering from severe reflux, maintain a 45° semi-seated Trendelenburg position.

* Nutritional support by preferential enteral route. The insertion of the gastric tube may be made difficult by esophageal motility disorders and must sometimes be inserted during a gastric fibroscopy.

* Passive physiotherapy in sedated patients, then active as soon as possible to prevent joint retraction and amyotrophy.

## D. Organ and tissue donation

In the current state of knowledge, the donation of certain organs and tissues may be possible pending a case-by-case analysis.

### 1. Risk of disease transmission

In the absence of evidence in the literature, since the exact cause of the disease is related to an autoimmune reaction for which the triggering factors are not known, it is not possible to make a statement on this risk.

Corticosteroids and long-term immunosuppressants (cyclophosphamide, methotrexate, mycophenolate
mofetil, azathioprine, etc.) cause a decrease in the donor's immune response to certain transmissible infectious diseases (acute or not), with a risk of delayed or weak serological reactions that are difficult to diagnose. The use of viral genomic screening is the solution.

## 2. Organ donation: depending on the type

* Limited cutaneous SSc: no contraindication for liver (in the absence of associated primary biliary cirrhosis) and pancreas donation. For other organs, a careful assessment is required.

* Diffuse cutaneous SSc: the validation for organ donation needs to be more cautious; liver and pancreatic sampling may be considered. Above all, do not underestimate the possibility of kidney damage, as kidney sampling is then impossible.

Some studies show that, even when asymptomatic, 69% of hearts and 50% of kidneys (pre-implantation biopsy is often recommended) are affected by the disease. The transplant decision is therefore based on the team's estimate of the risk incurred by the recipient in relation to the expected benefits of the transplant (benefits & risks).

## 3. Tissue donation:

The European guide contraindicates SSc for bone and skin sampling. It also seems reasonable to contraindicate donations of vascular tissue and heart valves. The inherent risks in long-term treatment followed by the donor must be known and taken into account.

Corneal collection is possible except when there is an association with severe Sjögren's syndrome with corneal damage. It then seems reasonable to contraindicate the collection unless prior ophthalmological advice is given.

ABM's Regulatory and Field Support Services (SRA): numbers for the four regulatory territories (24/7)

<table><thead><tr><th>SRA Northeast</th><th>+ 33</th><th>9</th><th>69</th><th>32</th><th>50</th><th>20</th></tr></thead><tbody><tr><td>SRA Southeast/Indian Ocean</td><td>+ 33</td><td>9</td><td>69</td><td>32</td><td>50</td><td>20</td></tr><tr><td>SRA Great West</td><td>+ 33</td><td>9</td><td>69</td><td>32</td><td>50</td><td>20</td></tr><tr><td>SRA Ile de France/Center/West Indies/French Guiana</td><td>+ 33</td><td>9</td><td>69</td><td>32</td><td>50</td><td>20</td></tr></tbody></table>

# Appendix 8: List of useful links for healthcare professionals and patients

Information for healthcare professionals:

* FAI²R—Health Network for Rare Autoimmune and Autoinflammatory Diseases, www.fai2r.org

* GFRS—Francophone Scleroderma Research Group, www.sclerodermie.net

* EUSTAR—EULAR scleroderma trials, www.eustar.org

* Orphanet, www.orpha.net/

* SNFMI—French National Society of Internal Medicine, www.snfmi.org

* SFR—French Rheumatology Society, http://sfr.larhu matologie.fr

* SFD—French Dermatology Society, http://www.sfder mato.org

* SFMC—French Microcirculation Society

* SFMV—French Society of Vascular Medicine, http:// www.portailvasculaire.fr/espace-sfmv/accueil

* SFGM-TC—Francophone Society of Bone Marrow Transplantation and Cellular Therapy, http://www. sfgm-tc.com

* SOFREMIP—Francophone Society for Rheumatology and Pediatric Inflammatory Diseases, www.sofre mip.sfpediatrie.com

* Reference Center for Rare Pulmonary Diseases, www. maladies-pulmonaires-rares.fr

Information for patients:

* ASF—French Scleroderma Patient Association, www. association-sclerodermie.fr

* Rare Disease Alliance, www.alliance-maladies-rares. org

* EURORDIS—Federation of Associations of Patients and Individuals Active in the Domain of Rare Diseases, www.eurordis.org

* FAI²R—Health Network for Rare Autoimmune and Autoinflammatory Diseases, www.fai2r.org

* FMO—Orphan Disease Federation, www.maladies- orphelines.fr

* Rare Disease Info Services—www.maladiesraresinfo. org

## Abbreviations

ANA: Antinuclear antibodies; Ab: Antibody; ACR: American College of Rheumatology; GA: General anesthesia; NSAID: Nonsteroidal antiinflammatory drug; ALD: Affection de longue durée [long-term illness], also refers to part of the French national healthcare system; MA: Marketing authorization; ANCA: Anti-neutrophil cytoplasmic antibody; ARB: Angiotensin II receptor blockers; ARS: Agence régionale de santé [regional health agency]; ALT: Alanine transaminase; AST: Aspartate transaminase; BAFF: B-cell activating factor; BNP: B-type natriuretic peptide; CCP: Cyclic citrullinated peptide; CPK: Creatine phosphokinase; TLC: Total lung capacity; CRP: C-reactive protein; HSC: Hematopoietic stem cells; FVC: Forced vital capacity; DLCO: Carbon monoxide diffusing capacity; cDLCO: Corrected carbon monoxide diffusing capacity; DMARD: Disease-modifying antirheumatic drug; ECG: Electrocardiogram; PFT: Pulmonary function tests; ELISA: Enzyme-linked immunosorbent assay; TPE: Therapeutic patient education; EULAR: European League Against Rheumatism; EUSTAR: European Scleroderma Trials and Research Group; SA: Spontaneous abortion; LVEF: Left ventricular ejection fraction; FGF: Fibroblast growth factor; FT4: Free thyroxine; γGT: Gamma-glutamyltransferase; HAS: High Health Authority [of France]; HBP: High blood pressure; PAH: Pulmonary arterial hypertension; PH: Pulmonary hypertension; ACEI: Angiotensin-converting enzyme inhibitor; IL: Interleukin;
BMI: Body mass index; PPI: Proton pump inhibitor; MRI: Magnetic resonance imaging; BAL: Bronchoalveolar lavage; LDH: Lactate dehydrogenase; MCP: Metacarpophalangeal; MMF: Mycophenolate mofetil; mRSS: Modified Rodnan skin score; MTX: Methotrexate; CBC: Complete blood count; NT-proBNP: N-terminal pro b-type natriuretic peptide B-type natriuretic peptide; NYHA: New York Heart Association; WHO: World Health Organization; PAP: Pulmonary arterial pressure; ILD: Interstitial lung disease; NDCP: National diagnostic and care protocol; IUGR: Intrauterine growth restriction; MCM: Multidisciplinary coordination meeting; GERD: Gastroesophageal reflux disease; PVR: Pulmonary vascular resistance; WOA: Week of amenorrhea; SSc: Systemic scleroderma; SLS: Scleroderma Lung Study; aPTT: Activated partial thromboplastin time; PT: Prothrombin time; TSH: Thyroid-stimulating hormone; VEGF: Vascular endothelial growth factor; LV: Left ventricle; HIV: Human immunodeficiency virus; TRV: Tricuspid regurgitation velocity.

**Acknowledgements**

We would like to thank the rare autoimmune and auto-inflammatory diseases network (FAI'R) for its technical assistance and publishing support (Charlotte Lejeune and Hélène Maillard).

* Collaborators: Marc Bayen, General Medicine, Guesnain, France; Emmanuel Bergot, Pneumology, CHU Caen, France; Sabine Berthier, Internal Medicine, CHU Dijon, France; Julia Bosco, Dentistry, AP-HP La Pitié-Salpêtrière, Paris, France; Yoram Bouhnik, Hepato-Gastroenterology, AP-HP Hôpital Beaujon, France; Benjamin Chaigne, Internal Medicine, AP-HP Cochin, Paris, France; Vincent Cottin, Pneumology, CHU Lyon, France; Bruno Crestani, Pneumology, AP-HP Bichat, Paris, France; Christophe Deligny, Internal Medicine, CHU Fort-de-France, France; Vianney Descroix, Dentistry, AP-HP La Pitié-Salpêtrière, Paris, France; Dominique Farge, Internal Medicine, AP-HP Saint-Louis, Paris, France; Dominique Godard, French Scleroderma Patient Association, Estavar, France; Brigitte Granel, Internal Medicine, AP-HM, Marseille, France; Philippe Guilpain, Internal Medicine, CHU Montpellier, France; Bernard Imbert, Vascular Medicine, CHU Grenoble, France; Alain Le Quellec, Internal Medicine, CHU Montpellier, France; Christophe Lega, Internal and Vascular Medicine, CHU Lyon, France; Catherine LOK, Dermatology, CHU Amiens, France; Hélène Maillard, Internal Medicine, CHU Lille, France; Thierry Martin, Internal Medicine, CHU Strasbourg, France; Grégory Pugnet, Internal Medicine, CHU Toulouse, France; Viviane Queyrel, Internal Medicine, CHU Nice, France; Loïc Raffray, Internal Medicine, CHU Saint Denis de la Réunion, France; Frédéric Rilliard, Dentistry, AP-HP La Pitié-Salpêtrière, Paris; Ms. Mélanie Romier, Therapeutic Education Nurse, CHU Lyon, France; Ms. Laurence Schuller, French Scleroderma Patient Association, Talmont Saint Hilaire, France; Amélie Servettaz, Internal Medicine, CHU Reims, France.

**Authors' contributions**

All authors read and approved the final manuscript.

**Funding**

Publication costs were funded by The French Rare Diseases Healthcare Network: rare auto-immune and autoinflammatory diseases (FAI2R).

**Declarations**

**Ethics approval and consent to participate**

Not applicable.

**Consent for publication**

Not applicable.

**Competing interests**

EH reports consulting fees/meeting fees from Actelion, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme; speaking fees from Actelion, GSK, Roche-Chugai; and research funding from Octapharma, CSL Behring, GSK, Roche-Chugai and Actelion. CA reports no conflicts of interest. YA reports consulting fees/meeting fees from Actelion, Sanofi; Boehringer, Inventiva, Roche, Bayer, Sandoz, Medac, BMS; and research funding from Pfizer, BMS, Sandoz, Roche, Inventiva and Sanofi. JA reports no conflicts of interest. BBM reports no conflicts of interest. ABELOT reports no conflicts of interest. ABEREZNE reports no conflicts of interest. ASB reports no conflicts of interest. GW reports no conflicts of interest. JC reports no conflicts of interest. PDG reports consulting fees/meeting fees from Actelion, Bayer, MSD; speaking fees from Actelion,

BAYER. ED reports consulting fees/meeting fees from Actelion. FD reports no conflicts of interest. PJ reports no conflicts of interest. FJ reports no conflicts of interest. DL reports no conflicts of interest. VL reports consulting fees/meeting fees from GSK and Astra-Zeneca. JSL reports no conflicts of interest. GL reports no conflicts of interest. CM reports no conflicts of interest. BM reports no conflicts of interest. CN reports no conflicts of interest. NO reports no conflicts of interest. FP reports no conflicts of interest. MAR reports no conflicts of interest. JR reports no conflicts of interest. AR reports no conflicts of interest. OS reports no conflicts of interest. VS reports no conflicts of interest. MET reports consulting fees/meeting fees from UCB, Lilly, Abbvie, MSD, Pfizer, Medac, Roche, Novartis, and BMS. LM reports no conflicts of interest.

**Author details**

¹Service de Médecine Interne et Immunologie Clinique, Centre de Référence Des Maladies Autoimmunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000 Lille, France. ²Internal Medicine, Nantes University Hospital, University of Nantes, Nantes, France. ³Rheumatology Department, Hôpital Cochin, AP-HP, Université de Paris, Paris, France. ⁴Department of Pediatric Immunology and Rheumatology; Hospital Necker, APHP, Paris, France. ⁵Pediatric Nephrology, Rheumatology, Dermatology, HFME, Hospices Civils de Lyon, Bron, France. ⁶Department of Internal Medicine, CHR Annecy-Genevois, Annecy, France. ⁷Anaesthesia Intensive Care Unit, Jeanne de Flandre Women Hospital, Academic Hospital, ULR 7365 - GRITA - Groupe de Recherche Sur Les Formes Injectables Et Les Technologies Associées, University Lille, Lille, France. ⁸Vascular Medicine Department, Bordeaux University Hospital Centre, Saint André Hospital, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) Peripheral Artery DISEASE Network (PALADIN), Bordeaux, France. ⁹Cardiology Department, Lung-Heart Institute, CHU de Lille, 59000 Lille, France. ¹⁰Service de Médecine Interne, CHU Tours, Tours, France. ¹¹Emergency Department, Cochin Hospital, Paris University, Paris, France. ¹²Internal Medicine and Clinical Immunology Unit, CHU Rennes, Rennes, France. ¹³Department of Gastroenterology, IBD and Nutrition Support, Beaujon Hospital, INSERM UMRS-1149, Assistance Publique-Hôpitaux de Paris, University of Paris, Clichy, France. ¹⁴Service de Médecine Interne, Centre de Référence Maladies Autoimmunes Systémiques Rares D'Ile de France, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), APHP-CUP, Hôpital Cochin, Université de Paris, 75014 Paris, France. ¹⁵Centre d'Immunologie et Maladies Infectieuses (CIMI-Paris), Department of Odontology, Paris Diderot/Paris 07, Sorbonne Paris Cité, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. ¹⁶Cardiology Department, Hôpital Avicenne, AP-HP, Université de Paris, Paris, France. ¹⁷Department of Nephrology and Kidney Transplantation, Nouvel Hôpital Civil, University Hospitals of Strasbourg, Strasbourg, France. ¹⁸Physical Medicine and Rehabilitation Department, Hôpital Cochin, AP-HP, Université de Paris, Paris, France. ¹⁹Oral and Dental Medicine, Hôpital Pitié-Salpêtrière, APHP, Université de Paris, Paris, France. ²⁰Medical Intensive Care Unit, Hôpital Cochin, AP-HP. Centre & Université de Paris, Paris, France. ²¹Department of Dermatology, Timone Hospital, University Hospital of Marseille, Marseille, France. ²²AP-HP Cochin Hospital, Université Paris Descartes Sorbonne Paris Cité, INSERM U1153, Paris, France. ²³Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Laboratoire d'Excellence en Recherche Sur le Médicament et Innovation Thérapeutique, Université Paris-Sud, Le Kremlin-Bicêtre, France. ²⁴Rheumatology Department, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.

Accepted: 26 April 2021

Published: 26 July 2021

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