SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.
"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.
Dr. Virginia Steen
Keeping these patients moving requires that they be provided with adequate analgesia, she added.
A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).
Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.
Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.
"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."
Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.
"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.
Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.
Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.
Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.
"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.
Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.