CREST syndrome is a subtype of systemic sclerosis (also known as scleroderma) that primarily affects the skin and vascular system, but can also involve multiple organ systems. It is considered a collagen vascular disease and is widely believed to be an autoimmune disorder where the body’s immune system mistakenly attacks its own tissues. The prognosis for CREST is generally favorable, especially when diagnosed early and managed appropriately. 

CREST is characterized by the presence of five hallmark features, which provide the basis for its acronym: Calcinosis, Raynaud’s phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasia.

Etiology and Pathogenesis

CREST syndrome is a chronic, progressive autoimmune disease characterized by the abnormal accumulation of collagen and other matrix components, leading to fibrosis and vascular abnormalities in various organs. The exact pathophysiology remains unclear, but it is believed to involve immune-mediated damage to the small blood vessels and connective tissue. Environmental triggers, such as UV radiation, and genetic predisposition may play roles in the disease’s onset. In addition to these features, the condition often manifests as an overlap syndrome, where multiple collagen vascular diseases present concurrently, necessitating careful evaluation and management.

Key Features of CREST Syndrome

• Calcinosis: refers to the deposition of calcium salts in the subcutaneous tissue, commonly found on the fingers, arms, knees, and other extremities. These deposits can cause severe pain, skin ulcerations, and infection if the calcium protrudes. Treatment for infected calcinosis typically involves oral or intravenous antibiotics, and in severe cases, surgical intervention may be necessary to remove the calcium deposits and prevent complications.
• Raynaud’s Phenomenon: is a vascular disturbance characterized by spasms of small blood vessels, leading to color changes in the fingers and toes in response to cold or emotional stress. This is often the most debilitating symptom of CREST syndrome. Treatment options for Raynaud’s phenomenon aim to alleviate symptoms and prevent complications, such as ulcerations or infections. Pharmacologic treatments include calcium channel blockers (e.g., nifedipine), alpha-adrenergic blockers (e.g., prazosin), and vasodilators like nitroglycerin ointment, which has shown promising results in managing symptoms. Additionally, biofeedback therapy, paraffin baths, and the use of occlusive dressings can provide symptom relief.
• Esophageal Dysfunction: typically results from fibrosis and scarring of the lower esophagus, leading to difficulty swallowing and frequent gastroesophageal reflux disease (GERD). Patients often experience symptoms such as heartburn and difficulty swallowing solids. Treatment strategies for esophageal dysfunction include esophageal dilation in severe cases and pharmacologic management with proton pump inhibitors (PPIs) like omeprazole and H2 blockers (e.g., ranitidine), which reduce acid production and help protect the esophagus. Lifestyle modifications, such as eating smaller meals and elevating the head of the bed, are also recommended.
• Sclerodactyly: characterized by the thickening and tightening of the skin, typically involving the fingers and toes. This condition impairs joint mobility, and in severe cases, contractures may occur, making the fingers stiff and difficult to move. Management of sclerodactyly involves physical therapy or occupational therapy to maintain joint function. In some cases, topical treatments such as tretinoin and vitamin D supplementation may help improve skin elasticity, although these therapies are not universally effective.
• Telangiectasia: refers to the appearance of dilated capillaries near the skin’s surface, often manifesting as red spots on the face, hands, lips, and tongue. These capillaries are often visible in the affected areas and can be distressing for patients due to their cosmetic appearance. While there is no proven treatment to eliminate telangiectasia completely, patients may use cosmetic camouflage products, such as Dermablend or Covermark, to reduce visibility. In more severe cases, laser therapy can be considered as a cosmetic intervention.

Treatment Options

The management of CREST syndrome involves a multidisciplinary approach, including pharmacologic therapies, lifestyle modifications, and, when necessary, surgical interventions:

• Pharmacologic Treatments

• • Immunosuppressive agents, such as methotrexate, mycophenolate mofetil, and cyclophosphamide, are occasionally used to slow disease progression, especially in systemic involvement.
  • Calcium channel blockers (e.g., nifedipine) and vasodilators help to manage Raynaud’s phenomenon, a hallmark of CREST.
  • Proton pump inhibitors (PPIs) and H2 blockers are used to manage esophageal reflux symptoms and reduce esophageal dysfunction.
  • In the case of calcinosis, intravenous immunoglobulin (IVIg) or bisphosphonates may be considered for patients with refractory cases .
• Physical and Occupational Therapy: Therapy is crucial for maintaining joint mobility and improving quality of life in patients with sclerodactyly. Regular sessions can help reduce contractures and improve hand function.
• Surgical Interventions: In some cases, surgical excision may be necessary for calcinosis deposits, particularly if they cause severe pain, ulceration, or infection. Esophageal dilation can also be performed in patients with significant swallowing difficulties or esophageal strictures.

Conclusion

CREST syndrome is a subset of systemic sclerosis, characterized by a constellation of symptoms that involve the skin, vascular system, and internal organs. Early diagnosis and treatment are essential for managing the disease and improving patient outcomes. While no cure exists, the use of immunosuppressive therapies, vasodilators, and lifestyle modifications can help alleviate symptoms and improve quality of life. Ongoing research into the pathophysiology and treatment of CREST syndrome holds promise for more effective interventions in the future.

References

1. Bühl, A., Bohl, H., & Hoppe, T. (2022). Advances in the treatment of calcinosis in systemic sclerosis: A review of current options and emerging therapies. Rheumatology International, 42(5), 797-805. https://doi.org/10.1007/s00296-022-04992-9
2. Clements, P. J., Lachenbruch, P. A., & Hurwitz, R. W. (2000). Calcinosis in systemic sclerosis: Analysis of its prevalence, prognostic significance, and association with other clinical manifestations. Journal of Rheumatology, 27(11), 2771-2779.
3. Furst, D. E., Clements, P. J., & Khanna, D. (2009). Immunosuppressive treatment of systemic sclerosis. Current Rheumatology Reports, 11(2), 141-146. https://doi.org/10.1007/s11926-009-0044-4
4. Hachulla, E., Launay, D., & Diot, E. (2015). Sclerodactyly and systemic sclerosis: Pathogenesis and treatment options. Clinical Reviews in Allergy & Immunology, 48(1), 52-60. https://doi.org/10.1007/s12016-014-8472-5
5. Khanna, D., & Furst, D. E. (2013). Systemic sclerosis: Update on clinical and laboratory findings. Best Practice & Research Clinical Rheumatology, 27(3), 443-453. https://doi.org/10.1016/j.berh.2013.06.005
6. Kuo, C. F., See, L. C., & Yang, T. W. (2022). The pathogenesis and clinical management of overlap syndromes in autoimmune diseases: A review. Autoimmunity Reviews, 21(4), 102831. https://doi.org/10.1016/j.autrev.2021.102831
7. LeRoy, E. C., & Medsger, T. A. (2001). Scleroderma (systemic sclerosis): Classification, subsets and pathogenesis. Journal of Rheumatology, 28(2), 165-168.
8. Michaud, G., Dahan, S., & Bensussan, A. (2021). Dermatological manifestations of systemic sclerosis: Diagnosis and management. European Journal of Dermatology, 31(2), 199-211. https://doi.org/10.1684/ejd.2020.3891
9. O’Callaghan, J. M., Tyndall, A. J., & Kahan, A. (2019). Raynaud’s phenomenon and systemic sclerosis: Pathogenesis, diagnosis and management. Nature Reviews Rheumatology, 15(3), 139-148. https://doi.org/10.1038/s41584-019-0140-7