In the JournalsPerspective

Patients with systemic sclerosis, SLE overlap younger at diagnosis, lack skin symptoms

Sindhu R. Johnson

Patients with systemic sclerosis that overlaps with systemic lupus erythematous are generally younger at the time of diagnosis, more frequently demonstrate pulmonary arterial hypertension and less often have cutaneous sclerosis symptoms, according to recent findings in the Journal of Rheumatology.

“Patients with features of both systemic sclerosis — also called scleroderma, or SSc — and systemic lupus erythematous are seen in our clinics and hospitals, but very little is known about how these patients compare with patients who have systemic sclerosis without features of systemic lupus erythematous,” Sindhu R. Johnson, MD, PhD, of Toronto Western Hospital, told Healio Rheumatology. “The aim of this study was to investigate the epidemiology of SSc-SLE overlap patients, specifically prevalence, disease manifestations and survival.”

To analyze the prevalence of SSc-SLE overlap, the differences in SSc symptoms and characteristics, and survival compared with SSc without SLE, Johnson and colleagues conducted a cohort study of 1,252 patients aged 16 years and older at the Toronto Scleroderma Program, a health network made up of Toronto Western Hospital, Mount Sinai Hospital and Toronto General Hospital. Among the participants, 1,166 had SSc and 86 demonstrated SSc-SLE overlap.

The researchers followed up with participants every 6 to 12 months, with the primary outcome identified as the time from diagnosis to all-cause mortality. Johnson and colleagues used Kaplan-Meier and Cox proportional hazard models to analyze survival. Participants alive as of Jan. 1, 2017 were censored, the researchers wrote.

According to the researchers, 6.8% of participants demonstrated SSc-SLE overlap. In addition, patients with SSc-SLE overlap were younger at diagnosis (P < .001), were more frequently East Asian or South Asian, and more frequently demonstrated pulmonary arterial hypertension (P < .001). However, such patients were also less likely to have calcinosis (P = .007), telangiectasia (P < .001) or diffuse subtype (P < .001).

“There was no difference in the occurrence of renal crisis, interstitial lung disease and digital ulcers,” Johnson said. “Having both SSc and SLE does not confer worsening mortality as both groups had comparable survival. The takeaway here is that the occurrence of both SSc and SLE is not infrequent. Despite the lack of diffuse skin involvement, SSc-SLE overlap patients should be monitored for renal crisis, interstitial lung disease and digital ulcers. Having SLE with SSc does not worsen survival.” – by Jason Laday

Disclosure: Johnson reports support from the Oscar and Eleanor Markovitz Fund for Scleroderma Research of the Arthritis Research Foundation, and a Canadian Institutes of Health Research Clinician Scientist award. Please see the study for all other authors’ relevant financial disclosures.

Sindhu R. Johnson

Patients with systemic sclerosis that overlaps with systemic lupus erythematous are generally younger at the time of diagnosis, more frequently demonstrate pulmonary arterial hypertension and less often have cutaneous sclerosis symptoms, according to recent findings in the Journal of Rheumatology.

“Patients with features of both systemic sclerosis — also called scleroderma, or SSc — and systemic lupus erythematous are seen in our clinics and hospitals, but very little is known about how these patients compare with patients who have systemic sclerosis without features of systemic lupus erythematous,” Sindhu R. Johnson, MD, PhD, of Toronto Western Hospital, told Healio Rheumatology. “The aim of this study was to investigate the epidemiology of SSc-SLE overlap patients, specifically prevalence, disease manifestations and survival.”

To analyze the prevalence of SSc-SLE overlap, the differences in SSc symptoms and characteristics, and survival compared with SSc without SLE, Johnson and colleagues conducted a cohort study of 1,252 patients aged 16 years and older at the Toronto Scleroderma Program, a health network made up of Toronto Western Hospital, Mount Sinai Hospital and Toronto General Hospital. Among the participants, 1,166 had SSc and 86 demonstrated SSc-SLE overlap.

The researchers followed up with participants every 6 to 12 months, with the primary outcome identified as the time from diagnosis to all-cause mortality. Johnson and colleagues used Kaplan-Meier and Cox proportional hazard models to analyze survival. Participants alive as of Jan. 1, 2017 were censored, the researchers wrote.

According to the researchers, 6.8% of participants demonstrated SSc-SLE overlap. In addition, patients with SSc-SLE overlap were younger at diagnosis (P < .001), were more frequently East Asian or South Asian, and more frequently demonstrated pulmonary arterial hypertension (P < .001). However, such patients were also less likely to have calcinosis (P = .007), telangiectasia (P < .001) or diffuse subtype (P < .001).

“There was no difference in the occurrence of renal crisis, interstitial lung disease and digital ulcers,” Johnson said. “Having both SSc and SLE does not confer worsening mortality as both groups had comparable survival. The takeaway here is that the occurrence of both SSc and SLE is not infrequent. Despite the lack of diffuse skin involvement, SSc-SLE overlap patients should be monitored for renal crisis, interstitial lung disease and digital ulcers. Having SLE with SSc does not worsen survival.” – by Jason Laday

Disclosure: Johnson reports support from the Oscar and Eleanor Markovitz Fund for Scleroderma Research of the Arthritis Research Foundation, and a Canadian Institutes of Health Research Clinician Scientist award. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Michael H. Weisman

    Michael H. Weisman

    The accomplished and very rigorous epidemiology group from Toronto has published a paper taking advantage of their careful data collection from an enormous cohort of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) patients, all very well characterized and placed into buckets where patients fulfill classification criteria for both SSc and SLE.

    The authors identified 1252 patients who fulfill classification for SSc where 6.8% of them also fulfill criteria for SLE; they found that this overlap group were younger, more frequently had pulmonary arterial hypertension, and less frequently possessed certain presumed-to-be distinguishing cutaneous findings of SSc. However, their survival was no different and the occurrence of interstitial lung disease, scleroderma renal crisis, and digital ulcers were the same between both groups.

    What did we learn from this exercise? Are the words mixed, undifferentiated, or over-lap connective tissue diseases all the same? Probably not. In the early years of mixed connective tissue disease studies and publications, we learned that this form of “mild” SLE was not really mild at all and many patients later did evolve into SSc with significant PAH, ILD, or even SSc renal crisis. The auto-antibodies did not help us make any distinction. When ‘undifferentiated’ connective tissue disease became a vogue title, if you waited long enough patients did not remain undifferentiated at all and most evolved into either SLE or SSc.

    In this very large cohort, as well characterized clinically as possible by very bright clinicians and epidemiologists, we find a similar situation: Most of these patients (SSc-SLE overlap vs. SSc) have more in common than they do as separate entities. This makes us concerned that, clinically, we need to be vigilant as to the risk of serious internal organ involvement over time regardless of the initial presentation. Until we have a gold standard for classifying phenotypes, this issue remains with us.

    • Michael H. Weisman, MD
    • Director, Division of rheumatology
      Cedars-Sinai Medical Center

    Disclosures: Weisman reports no relevant financial disclosures.