From the Guidelines
Skin thickening in CREST syndrome is primarily managed with immunosuppressive medications, with mycophenolate mofetil (MMF) being the most common first-line treatment, as it has shown positive benefits for interstitial lung disease (ILD) and skin manifestations 1. The mechanism of skin thickening in CREST syndrome involves excessive collagen production by activated fibroblasts, triggered by immune dysregulation and vascular damage. Some key points to consider in the management of skin thickening in CREST syndrome include:
- The use of MMF as a first-line treatment, with methotrexate as an alternative or second-line option 1
- The potential use of cyclophosphamide, rituximab, or tocilizumab in more severe cases or in patients who do not respond to initial treatment 1
- The importance of regular monitoring of skin thickness using modified Rodnan skin scores to assess treatment effectiveness 1
- The need for a multifaceted approach to management, including physical therapy, moisturizers, and vasodilators to improve circulation and prevent contractures 1
In terms of specific treatment options, MMF is often prescribed at a dose of 1-2 g daily, while methotrexate is typically started at a dose of 15 mg weekly, with the potential for dose escalation to 25 mg weekly 1. Cyclophosphamide may be used at a dose of 1-2 mg/kg/day orally, although the optimal dose and duration of treatment are not well established 1. Overall, the management of skin thickening in CREST syndrome requires a comprehensive and individualized approach, taking into account the severity of disease, patient comorbidities, and response to treatment.
From the Research
Mechanism of Skin Thickening in Crest Syndrome
- The mechanism of skin thickening in Crest syndrome, a subtype of systemic sclerosis, is characterized by excessive deposition of extracellular matrix components, leading to fibrosis [(2,3,4)].
- Transforming growth factor-beta (TGF-β) plays a crucial role in the regulation of inflammation, proliferation, differentiation, and wound healing, and its increased expression is often correlated with disease severity [(2,4)].
- TGF-β stimulates the activation and proliferation of fibroblasts, resulting in the deposition of extracellular matrix components, such as collagen, which leads to skin thickening [(2,4)].
Management of Skin Thickening in Crest Syndrome
- The management of skin thickening in Crest syndrome involves targeting the underlying fibrotic process, and several therapeutic strategies have been developed to inhibit TGF-β signaling [(2,5,6)].
- These strategies include the use of antisense oligonucleotides, neutralizing monoclonal antibodies, soluble TGF-β receptors, and small molecule inhibitors 2.
- Immunomodulatory therapies, such as methotrexate and mycophenolate mofetil, have also been used to treat skin involvement in systemic sclerosis [(5,6)].
- Treatment algorithms for systemic sclerosis, including Crest syndrome, have been developed, and experts agree on the use of certain therapies, such as methotrexate and mycophenolate mofetil, for skin involvement 6.