Study of ‘Pre-Ulcer’ Stage May Inform Treatment of Digital Ulcers in Scleroderma

Study of ‘Pre-Ulcer’ Stage May Inform Treatment of Digital Ulcers in Scleroderma
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A pre-clinical stage preceding the development of digital ulcers could provide a window of opportunity for treatment before serious tissue damage occurs in people with scleroderma, according to a new study.

The study was summarized in a letter to the editor titled, “Patient experiences of digital ulcer development and evolution in systemic sclerosis,” published in the journal Rheumatology.

Digital ulcers — small sores in fingers and toes — are seen frequently in patients with scleroderma and frequently do not respond well to treatment. These small sores, which are prone to infection, are generally considered to result from tissue ischemia, which refers to insufficient oxygen supply reaching tissue.

Little is known about the stage preceding overt tissue damage related to digital ulcers. Prior work, from the same international team behind the current research, identified five major themes that characterize the patient experience of digital ulcers in scleroderma: disabling pain and hypersensitivity; broad-ranging emotional impact; impaired physical and social activity; factors worsening occurrence, duration and impact; and easing, managing and adapting.

Now, the researchers set out to explore patients’ perceptions and beliefs about digital ulcer development to inform clinical practice and design of clinical trials.

They recruited 29 patients with scleroderma (average age 59.9) to participate in four focus groups across the United Kingdom. Average disease duration was 12.8 years.

Participants had a variable history of digital ulcers, having experienced one to five or more sores. Most (20) had limited cutaneous scleroderma. Also, the majority of patients were receiving treatment with vasodilators (blood vessel wideners), including calcium channel blockers and phosphodiesterase type-5 inhibitors.

During the course of the focus groups, three major topics emerged.

The first was underlying cause of digital ulcers. Most participants believed there were both “external” and “internal” reasons behind the development of the ulcer rather than being a random occurrence.

“External” factors included experiencing trauma, cuts or skin splitting, being exposed to water or chemicals, infection, and cold or variation in temperature.

In turn, “internal” causes included “poor” blood circulation, calcinosis (formation of calcium deposits in soft tissue), and residual effects of previous ulcers, which would make specific areas of the fingers more vulnerable to new ulcers.

The second theme was symptoms before the development of digital ulcers. Most participants reported they knew when an ulcer was about to develop.

While the most common symptom was pain below the skin, some participants also reported physical skin signs, such as a white patch.

The third theme was patient experiences during digital ulcer development and healing, which were variable between individuals.

Some patients reported feeling the surface of the ulcer moist, while others said it was dry. Pain related to the small sore also varied greatly between participants.

“Our data provide novel patient-perceived insights into the pathogenesis and natural history of SSc-DU [digital ulcers in scleroderma]. The emergence of SSc-DUs is not considered a random event and many patients have explanations for, and sometimes can anticipate development of new ulcers,” the investigators wrote.

They added that these findings can help develop strategies to prevent digital ulcers, such as avoiding severe cold, hand hygiene, and avoiding mechanical injury.

“To our knowledge, we are the first to describe a ‘pre-ulcer’ stage that could provide a ‘window of opportunity’ to intervene before the onset of overt tissue damage and ulceration,” the researchers wrote.

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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