Many Systemic Sclerosis Patients with Raynaud’s Syndrome Soon Develop Other Conditions

Patients with systemic sclerosis and Raynaud’s syndrome have a high risk of developing other organ complications within two years after the onset of Raynaud’s, according to a study published in the journal PLoS One. The authors reported that these complications mainly occur in the skin, gastrointestinal tract, lungs, heart, kidneys and prostate.

The study, “Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study,” was conducted by Veronika Jaeger and her colleagues from the University Hospital Basel in Switzerland.

SSc is characterized by fibrosis in the skin and other organs, along with dysfunctional blood vessels. In most patients, SSc starts with the onset of Raynaud’s, a disease in which cold temperatures or emotional stress cause the narrowing of blood vessels in the hands and feet for a period of time, decreasing blood flow in these areas and leading to cell death. Raynaud’s patients often have abnormally cold fingers and toes.

“Numerous cross-sectional studies have already assessed the prevalence of internal organ manifestations and calculated risk factors in patients with established SSc,” the authors wrote in their report.

“These studies have demonstrated that the presence of specific autoantibodies in the patient’s serum, the patient’s sex, and age at SSc onset as well as the extent of skin involvement are associated with the prevalence and severity of internal organ involvement. However, only a few studies have prospectively assessed the evolution of SSc-related organ manifestations after the onset of [Raynaud’s],” they wrote.

To map the incidence of organ manifestations during the early course of disease, researchers analyzed data from a subset of SSc patients from the EUSTAR study. This subset included patients who had a baseline visit within the first year after Raynaud’s onset to ensure they were enrolled early in their disease course. The team then evaluated the development of organ manifestations after Raynaud’s onset, according to the following symptoms:

• Skin involvement – defined as a modified Rodnan skin score (mRSS) above or equal to two points in at least one body area;
• Gastrointestinal (GI) symptoms – defined as the presence of either dysphagia, reflux, early satiety, vomiting, diarrhea, bloating or constipation;
• Increased systolic pulmonary artery pressure (PAPsys) – suspected pulmonary hypertension when higher than 40 mmHg;
• Pulmonary restrictive defect – determined as a forced vital capacity (FVC) below 80%;
• Digital ulcers (DU);
• Cardiac involvement – presence of diastolic dysfunction, conduction blocks, left ventricular ejection fraction (LVEF) below 50% or a pericardial effusion;
• Renal crisis and erectile dysfunction – score of less than 22 points in the International Index of Erectile Function (IIEF-5) questionnaire.

Of the initial 9,891 SSc patients followed during the EUSTAR study, 695 patients with a median age of 52.7 years had a baseline visit within one year after Raynaud’s onset, and developed skin sclerosis (75%); GI symptoms (71%); impaired diffusing capacity for monoxide below 80% (65%); DU (34%); cardiac involvement (32%); FVC below 80% (31%); increased PAPsys (14%); and renal crisis (3%).

Regarding cardiac manifestations, the higher rates were associated with diastolic dysfunction, conduction blocks and pericardial effusion.

The team also observed that these manifestations were correlated with patients’ characteristics. For instance, development of FVC impairment was associated with diffuse skin involvement, whereas increased PAPsys and cardiac manifestations were associated with higher patient age. Also, male gender and older age were risk factors associated with renal crisis.

“In SSc patients presenting early after [Raynaud’s] onset, approximately half of all incident organ manifestations occur within two years and have a simultaneous rather than a sequential onset,” the authors wrote.

“These findings have implications for the design of new diagnostic and therapeutic strategies aimed to widen the still very narrow window of opportunity. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.”

“Another important point is that approximately 75% of the patients develop organ involvement during the first five years of the disease. This is good news for the patients who reach that point without any organ involvement,” the team wrote.