Infections With SSc Often Lead to Hospitalization, 10-Year Analysis Finds

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by Steve Bryson, PhD |

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Infection was the leading cause of acute hospitalization and mortality in people with systemic sclerosis (SSc), a 10-year hospital study in Portugal found.

Although most infection-related hospital admissions occurred in those with underlying lung disease, the scientists noted that a decrease in the total number of hospitalizations during the last five years of follow-up might reflect advances in disease management.

The study, “Acute hospitalization in a cohort of patients with systemic sclerosis: a 10-year retrospective cohort study,” was published in the journal Rheumatology International.

The accumulation of scar tissue in the skin and internal organs, including the lungs, heart, kidney, and digestive tract, are hallmarks of systemic scleroderma, also called systemic sclerosis. SSc is associated with significantly high rates of disease complications and mortality.

Most studies investigating SSc outcomes have focused on patients outside a hospital setting. Few reports have examined acute hospitalization patterns of SSc, apart from those in intensive care or with specific SSc complications.

Most of these studies were also published more than 10 years ago, and may not reflect the impact of recent advances in treatment and disease management, the scientists noted.

A team of researchers at the Fernando Fonseca Hospital in Amadora, Portugal, analyzed all acute hospital admissions of SSc patients between 2010 and 2020.

“Our aim was to analyze the causes and predictors of acute hospitalizations and inpatient mortality, in a cohort [group] of SSc patients,” the team wrote.

Acute admissions were defined as hospitalizations due to unexpected health problems needing urgent care. The researchers collected clinical data from hospital medical files and the National Healthcare Registry Platform.

Of the 95 SSc patients included in the study, 53 (56%) needed acute hospitalization in a total of 164 admissions. Most hospital admissions (73.2%) were in the medical department, while 6.8% were admitted to the intensive care unit (ICU).

The most frequent reason for acute hospitalization was infectious diseases, occurring in 27% of patients, of which 70% were due to pneumonia. Heart disease accounted for 16.5% (heart failure in 55.6%), peripheral vascular disease for 12.8% — all these cases due to ulcers on fingers and toes (digital ulcers) and Raynaud’s phenomenon — and 9.8% were because of pulmonary hypertension, an SSc complication characterized by high blood pressure in the arteries of the lungs.

Interstitial lung disease (ILD) — a group of lung conditions characterized by progressive scarring of lung tissue — was responsible for 9.1% of acute hospitalizations (without infection), and was a recurrent cause of admissions.

Between 2010 and 2015, the total number of hospitalizations rose, primarily due to infections and heart complications. From 2016 to 2020, total admissions decreased with ILD as the primary cause, which “can be the result of a more effective treatment approach following the results of clinical trials,” as well as “due to an earlier recognition of lung involvement in these patients,” the researchers wrote.

Compared to non-hospitalized SSc patients, those admitted to the hospital had the more diffuse cutaneous disease, more frequently tested positive for disease-related antibodies, had more digital ulcers, and experienced pulmonary hypertension and heart problems.

Patients with digital ulcers were at a more than a six-fold higher risk of acute hospitalization, and a more than a sevenfold higher risk of impairment of the left heart ventricle, which “reinforces the need of further research in [digital ulcers] and cardiac disease approach as those are still one of the main causes of hospitalization in SSc,” the scientists added.

In contrast, females and Caucasian patients had lower odds of hospitalization.

Patients treated with the immune system suppressant methotrexate also had a lower risk of hospital admission, which “might reflect more a bias related to our treatment protocol, as [methotrexate] is used only for patients with arthritis or cutaneous involvement, excluding those with internal organ involvement such as cardiac disease or ILD,” the investigators wrote.

All 14 deaths occurred in patients who were hospitalized at any point, and happened during the hospital stay. The causes of death were pneumonia (36%), followed by heart failure (21%), tumor-related diseases (21%), pulmonary hypertension (14%), and ILD (7%). Five deaths occurred in the ICU.

Individual factors predicting mortality were older age, diffuse cutaneous disease, the presence of disease-related antibodies, calcium deposits, right ventricle impairment, ILD, and pulmonary hypertension. More hospital admissions and at least one due to infection were also associated with a higher risk of death.

In comparison, the use of immunosuppressants was not linked with mortality, while being female and having a shorter disease duration associated with lower risk.

A statistical analysis adjusting for individual factors found right ventricle impairment was associated with more than a fivefold increased risk of death, while female sex and shorter disease duration remained linked to a lower risk of mortality.

Finally, the team focused on infections because they were among the most frequent causes of acute admission and mortality, which increased over the 10 years. Of these, there were 31 admissions due to pneumonia, of which 74% had SSc-associated ILD.

Overall, 44 admissions were related to infectious diseases; among this group, 31 (70.5%) patients were taking immunosuppressants when hospitalized. Five required ICU admission, all due to pneumonia.

All participants admitted due to infectious diseases were up-to-date with vaccinations. In those hospitalized with pneumonia, 26 had the flu vaccine, and 13 had the pneumococcal polysaccharide vaccine.

Patient characteristics significantly associated with infection were the diffuse cutaneous subtype, having disease-related antibodies, calcium deposits, right ventricle impairment, ILD, and treatment with the immunosuppressant CellCept (mycophenolate mofetil). After adjusting for individual factors, none of these characteristics remained significant, except for those with more than one acute hospital admission.

“In conclusion, in our cohort, infection was the principal cause of acute hospitalization and of inpatient mortality, mainly due to pneumoniae,” the team wrote. “Although a high percentage of those patients had ILD, this disease feature, in our [group], has been decreasing over the last years as a direct cause of hospital admission and of mortality, probably reflecting the advances in its management.”

Researchers said the relatively low number of patients and of admissions may have limited their study’s statistical analysis.