Emerging targets for the treatment of scleroderma

Scleroderma is an often-fatal autoimmune connective tissue disease. Recommendations for treating digital ulcers and pulmonary hypertension in scleroderma have recently been established by the European League Against Rheumatism. Conversely, although many valuable insights have been generated into the molecular mechanism underlying the persistent fibrotic phenotype in scleroderma, no safe, clinically proven effective treatment has been found for this aspect of the disease.

Recent evidence suggests that, based on genome-wide molecular profiling, scleroderma can be loosely divided into 'fibroproliferative' and 'inflammatory' cohorts. The latter cohort contains patients with localized and 'limited' disease, as well as a small subset of those with 'diffuse' disease. Drugs targeting either B cells or ILs might be useful to treat patients who possess an 'inflammatory' gene expression signature.

In the future, a 'personalized medicine' approach might be used to treat patients with scleroderma: individuals with an 'inflammatory' gene expression signature may be successfully treated with drugs specifically targeting the immune system. Indeed, drugs currently approved for other rheumatic disease might also be used to treat scleroderma patients bearing an 'inflammatory' gene expression profile.