Systemic Sclerosis: More Than Skin Deep

Updates from the ACR Convergence 2023 Review Course, part 6

SAN DIEGO—The pre-conference Review Course at ACR Convergence 2023, held Saturday, Nov. 11, and moderated by Noelle Rolle, MBBS, assistant professor in the Division of Rheumatology, associate program director of the Rheumatology Fellowship at the Medical College of Georgia, Augusta University, and Julia Schwartzmann-Morris, MD, associate professor, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, N.Y., tackled numerous important topics in rheumatology. Here, we report on the presentation by Francesco Boin, MD, professor of medicine, director, Division of Rheumatology, Cedars-Sinai, Los Angeles.

Dr. Boin

Dr. Boin provided an overview of how and when to screen for organ involvement in patients with systemic sclerosis (SSc). Dr. Boin noted that the evaluation of the patient with SSc always begins with the skin and with classifying the patient as having limited or diffuse cutaneous disease. Regardless of the degree of skin involvement, it’s important to realize that any patient with SSc can have multi-organ manifestations. Indeed, the risk of organ complications is higher early in the disease course than later.¹

Autoantibodies in SSc

An understanding autoantibodies in SSc can help clinicians predict manifestations and prognosis in patients:²

Anti-centromere antibodies:

• Are associated with limited cutaneous disease;

• Are more often seen in patients who are white;

• Confer a higher risk of vascular disease, such as pulmonary hypertension, compared with patients with scleroderma without this autoantibody;

• Are associated with thyroid disease and primary biliary cholangitis; and

• Are protective against interstitial lunge disease (ILD).

Anti-Scl-70 antibodies (also known as topoisomerase) are more often seen in patients who are Black and can be associated with an increased risk of ILD, advanced contractions and myocarditis.

Anti-RNA polymerase III antibodies can increase the risk of rapid skin progression, renal involvement—specifically scleroderma renal crisis—gastric antral vascular ectasias (GAVE) and cancer.

Anti-U1RNP antibodies are more common in patients who are Black, increase the risk of ILD and are often seen with overlap of connective tissue disease manifestations.

Antibodies to Anti-PM/Scl antibodies can be seen in young patients and can be associated with myositis and calcinosis, but these patients do not have an elevated risk of malignancy.

Finally, anti-U3RNP antibodies can be associated with the risk of pulmonary hypertension, severe gastrointestinal disease, ILD and pericarditis.

SSc with ILD

ILD is more commonly seen in patients with diffuse than limited cutaneous SSc. Most decline in lung function occurs in the first two to four years of disease onset. Early on, ILD may be silent, and when shortness of breath is present, it is important to rule out other causes, such as anemia, deconditioning, muscle weakness or aspiration due to chronic cough from gastroesophageal reflux disease.

Pulmonary function testing (PFT) is a part of screening for ILD in patients with SSc, but there is a high false negative rate. A PFT conducted to evaluate for ILD may also show evidence of myopathy (e.g., with decreased forced vital capacity with normal diffusing capacity of the lungs for carbon monoxide [DLCO]) or pulmonary hypertension (e.g., decreased DLCO out of proportion to other parameters). PFTs can be helpful in following restrictive lung disease, and changes over time in PFT parameters can provide insight into disease activity.

On the subject of lung imaging, high-resolution computed tomography (CT) of the chest can help characterize ILD patterns, such as nonspecific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP). If there are atypical findings on imaging, it is important to look for infections or malignancy. Fibrosis on CT imaging implies a poorer prognosis for patients.

Dr. Boin posed the question: Should all patients with SSc be screened with high-resolution CT of the chest? Although one survey-based study has indicated that a majority of rheumatologists would do so, it is not clear if this should be the standard of care.³

In the future, techniques for screening for ILD in SSc patients may include routine use of bronchoscopy and bronchoalveolar lavage, genetic testing (e.g., with single nucleotide polymorphisms and measuring telomere length) and exhaled breath analysis.

Pulmonary Hypertension

Pulmonary hypertension may be asymptomatic early in the SSc disease course. Risk factors for pulmonary hypertension include later age of onset, limited skin involvement, severe Raynaud’s and the presence of telangiectasias. Right heart catheterization is the gold standard for confirming pulmonary hypertension, and the key question is how best to identify which patients should undergo this testing.

The DETECT algorithm (https://www.suspectpahctd.com/DETECT) is a freely available tool with high sensitivity for detecting pulmonary hypertension (96%). However, this comes at the cost of low specificity, meaning a fair number of patients without pulmonary hypertension will be referred for right heart catheterization.

Dr. Boin described the balance of risks and benefits well: Although we want to avoid costly, unnecessary, and invasive tests, we also don’t want to miss pulmonary hypertension because it is associated with an increased risk of death. Detecting pulmonary hypertension earlier rather than later is ideal because effective therapies exist and can prevent severe complications.

Scleroderma Renal Crisis

Scleroderma renal crisis is a medical emergency for patients, explained Dr. Boin. Risk factors for this condition include early diffuse cutaneous disease, the presence of anti-RNA polymerase III antibodies and use of ≥15 mg of prednisone per day or lower doses of corticosteroids for longer periods of time.

Scleroderma renal crisis can precede the diagnosis of SSc or be the presenting manifestation of the disease. Rapid clinical assessment of these patients is critical, looking for elevated blood pressure, acute kidney injury, signs of malignant hypertension and signs of thrombotic microangiopathies (i.e., hemolytic anemia, low platelets; also see https://www.the-rheumatologist.org/article/thrombotic-microangiopathies-rheumatology).

Confounding the picture is the fact that patients with renal crisis can present without renal failure or without hypertension. Dr. Boin stressed that performing a renal biopsy is key when renal crisis is suspected. This is important to confirm the diagnosis, rule out other entities and assess the extent of damage and potential for reversibility, all of which can inform prognosis.

Myocardial Disease

The final area of organ involvement that Dr. Boin discussed was myocardial involvement. This complication drives early mortality in SSc, with small vessel ischemia and myocardial inflammation. These patients may even experience sudden death, and thus an automated implantable defibrillator (AICD) can be lifesaving.

Patients at highest risk for the development of myocardial disease in SSc are those who are older, male, Black, and have a history of myositis and arthritis.

Jason Liebowitz, MD, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

References

1. Jaeger VK, Wirz EG, Allanore Y, et al; EUSTAR co-authors. Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: A longitudinal EUSTAR study. PLoS One. 2016 Oct 5;11(10):e0163894.
2. Shah AA, Wigley FM. My approach to the treatment of scleroderma. Mayo Clin Proc. 2013 Apr;88(4):377–393.
3. Bernstein EJ, Khanna D, Lederer DJ. Screening high-resolution computed tomography of the chest to detect interstitial lung disease in systemic sclerosis: A global survey of rheumatologists. Arthritis Rheumatol. 2018 Jun;70(6):971–972.