A greater understanding of the many potential targets for treatment may soon be changing how pain specialists manage patients with systemic sclerosis (scleroderma). Until now, there have been few effective treatments to help with the constellation of pain syndromes associated with scleroderma. However, genomics are now offering new hope for helping patients with scleroderma in novel ways.
“I think we have learned a lot and have many potential targets for treatment, but I do think we still have a long way to go,” said Lorinda Chung, MD, who is an Associate Professor of Medicine at Stanford and heads up Stanford’s Scleroderma Center, Stanford, California.
Scleroderma is a chronic disease characterized by a thickening and hardening of the skin that is so severe, it steals away the use of patients’ fingers, hands and limbs. It is a multi-system autoimmune disease associated with disability and reduced quality of life. As it advances, the uncontrolled growth of fibrous tissue can damage patients’ hearts, lungs and other organs. “Most patients commonly present in the 30 to 60 year range, the prime of life, so it definitely can lead to depression and fatigue,” said Dr. Chung.
There are no effective treatments or cure for scleroderma. The current treatment goal is to help preserve or improve global health. The management is mainly symptomatic and there are no treatments available to switch the disease off. “Scleroderma is a multisystem disease and the key to management is an organ-based treatment approach. This often involves a combination therapy approach to treat inflammation, underlying vascular disease and fibrosis. Common treatment modalities include vasodilators for Raynaud’s phenomenon (RP) and pulmonary hypertension. Other treatments include immunosuppressive therapies for interstitial lung disease, inflammatory arthritis, or myositis and use of ACE-inhibitors for renal crisis,” said Nilofar Syed, MD, who is an Assistant Professor at the University of Texas (UT) Southwestern, Dallas, Texas.
The American College of Rheumatology reports that currently about 75000 to 100000 people in the U.S. have this disease, so it is considered rare.1 Studies show that most patients are women between the ages of 30 and 50, and twins and family members of those with scleroderma or other autoimmune connective tissue diseases may have a slightly higher risk of developing scleroderma.
“Pain management revolves around management of pain of digital ulceration and active inflammatory joint or muscle disease. The job of the rheumatologist is to get the disease under control with immunosuppressants, etc. The pain management team can treat ulcers with topical meds, lumbar or digital sympathectomy, and analgesics,” said Maggie Larché, MD, who is Chair Hamilton Scleroderma Group and an Associate Professor of Medicine, McMaster University, Montreal, Canada.
She said the current treatments for scleroderma can be divided in two different categories. For finger ulceration, RP and pain, clinicians commonly prescribe tadalafil (Cialis) or sildenafil (Viagra). In addition, antidepressants may be helpful says Dr Larché. For pulmonary hypertension, patients are treated with macitentan, and for pulmonary fibrosis, patients usually are prescribed pirfenidone and other antifibrotic medications, adds Dr Larché. For bacterial overgrowth, newer antibiotics and newer biologic agents are showing promise, such as tocilizumab.
“Cellcept is probably now considered first-line for lung fibrosis and possibly skin as well. There are many treatments available for pulmonary hypertension and ACE-inhibitors are used for renal crisis. Many targeted immune-modulatory and anti-fibrotic therapies are being evaluated in clinical trials,” Dr. Chung told Clinical Pain Advisor. “Patients suffer from pain related to skin tightness, joint swelling and contractures, and digital ulcers. They have slow gut motility, so narcotics might cause more constipation than with typical patients.”
Improving Quality of Life May Help Lower Morbidity
Dr. Chung said issues such as constipation need to be addressed proactively. Studies suggest that it is important to develop a team approach. It is recommended that clinicians utilize the Health Assessment Questionnaire and Disability Index (HAQ-DI), a self-administered tool to measure functional impairment. Clinicians should first determine what the patient values most, such as mobility and hand function, according to researchers in Portugal.2 Researchers at the Centro Hospitalar Vila Nova Gaia/Espinho (CHVNG/E), Gaia, Portugal report that a bigger issue for a given patient may be pain, fatigue, sleep, or depression. Body image can also be a factor in this patient population.2
Besides addressing issues of depression, anxiety and fatigue, clinicians should also consider addressing sleep disruption, pain, pruritus, body image dissatisfaction, and sexual dysfunction in patients with scleroderma, according to Canadian investigators.3 They believe it is paramount for clinicians to address the emotional and social consequences of living with this condition.3
A Lack of Awareness
Currently, there is a major barrier to timely diagnosis and treatment because of a lack of awareness about scleroderma. To deal with this issue, a group of nonprofits is working together in June during Scleroderma Awareness Month. North America’s leading scleroderma advocacy and research organizations (Scleroderma Foundation, Scleroderma Research Foundation and Scleroderma Society of Canada) have combined efforts to boost awareness and spark a greater interest in combating scleroderma. “I think there is still a long way to go. There is no good treatment for reversing the fibrotic disease process in scleroderma, but there are anti-fibrotic agents under investigation,” Dr. Syed told Clinical Pain Advisor.
Dr. Chung noted June 29 is World Scleroderma Day and she hopes this will bring a greater awareness to the disease and ultimately lead to lower rates of morbidity. “Barriers are related to the fact that it often takes time for a patient to be referred to a scleroderma center, causing delays in diagnosis,” said Dr. Chung. Delaying a proper diagnosis can affect not only quality of life but outcomes as well, she added.
2. Almeida C, Almeida I, Vasconcelos C. Quality of life in systemic sclerosis. Autoimmun Rev. 2015;14(12):1087-96.
3. Kwakkenbos L, Delisle VC, Fox RS, et al. Psychosocial Aspects of Scleroderma. Rheum Dis Clin North Am. 2015;41(3):519-28.