Systemic Sclerosis (SSc)


Systemic sclerosis (SSc) is a rare autoimmune and connective tissue disorder that causes widespread fibrosis and vascular abnormalities, impacting the skin, joints, and/or internal organs.

People affected by SSc have variable clinical presentations. The treatment regimen depends on the presenting symptoms, complications due to affected organs, and disease subtype.1

Commonly presenting signs and symptoms of SSc include Raynaud phenomenon, digital ulceration, calcinosis secondary to the subcutaneous deposition of calcium hydroxyapatite, and secondary infections. Commonly affected organs include the skin, kidneys, lungs, heart, skeletal muscles, and gastrointestinal system.2

Systemic sclerosis disease subtypes include limited cutaneous SSc, diffuse cutaneous SSc, and SSc without skin involvement.2,3 

Medications

There are no cures or disease-modifying medications that can prevent the progression of SSc. The early diagnosis of SSc and accurate identification of affected organs improve treatment efficacy and outcomes. Current interventions target symptom relief, prevention of end-organ damage, and management of disease-related complications.1,2 

Read more about SSc guidelines

Immunosuppressive Agents

Systemic sclerosis is an autoimmune condition in which the immune system attacks normal healthy tissues. Although the exact mechanism for how autoimmunity contributes to SSc is poorly understood, immunosuppressive agents may be helpful in reducing symptoms.2 

Some immunomodulatory medications commonly used to treat SSc include1,2:

  • Methotrexate for skin disease, inflammatory arthritis, and myositis
  • CellCept® (mycophenolate mofetil) for both skin and lung disease
  • Cytoxan® (low-dose intravenous cyclophosphamide) for both skin and lung disease
  • Imuran® (azathioprine) for skin disease, lung disease, and myositis
  • Plaquenil® (hydroxychloroquine) for skin disease
  • Actemra® (subcutaneous tocilizumab) for lung disease

Read more about SSc signs and symptoms

Antifibrotic Agents

Due to antifibrotic features, the tyrosine kinase inhibitors, Gleevec® (imatinib) and Ofev® (nintedanib), may be helpful treatments in slowing the accumulation of fibrosis in SSc.4 In particular, Ofev has demonstrated efficacy in slowing the rate of pulmonary function decline in individuals with SSc and interstitial lung disease.1

Read more about SSc prognosis

Anti-Inflammatory Agents

Corticosteroids are generally avoided in the treatment of SSc as they may precipitate renal crisis; however, with careful renal monitoring, steroids (maintaining as low a dose as possible) may help to manage overt myositis or mixed connective tissue disease if absolutely necessary.1,3,4 

Calcium Channel Blockers

Nifedipine (sold as Adalat® and Procardia®, among others) may improve the symptoms of Raynaud phenomenon, but it may also exacerbate gastroesophageal reflux in some patients.1 Calcium channel blockers are also used in patients with cardiac complications, as studies have shown their effectiveness in reducing the risk of systolic heart failure in patients with SSc.3

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Specific Treatments for Raynaud Phenomenon

Calcium channel blockers and angiotensin II receptor antagonists are the first-line treatments for Raynaud phenomenon to promote relaxation of the blood vessels. Second- or third-line drug treatments may include selective serotonin reuptake inhibitors, statins, alpha-blockers, phosphodiesterase type 5 inhibitors such as Adcirca® (tadalafil) or Revatio® (sildenafil), and intravenous prostanoid therapy. In severe, refractory cases of Raynaud phenomenon, clinicians may consider digital (palmar) sympathectomy with or without injections of Botox® (botulinum toxin).3

Specific Treatments for Digital Ulceration

Oral vasodilators, analgesics, and any required intervention for infections are the recommended treatments for digital ulceration. Intravenous prostanoid therapy, Tracleer® (bosentan), and phosphodiesterase type 5 inhibitors may help manage digital ulcers in SSc. Similar to Raynaud phenomenon, in severe, refractory cases of digital ulceration, clinicians may consider digital (palmar) sympathectomy with or without Botox injections.3

Procedures

Several procedural interventions may assist with the management of SSc symptoms and progression, including stem cell transplantation (SCT), esophageal dilation, and hemodialysis.

Stem Cell Transplantation

Stem cell transplantation offers the potential for symptom improvement and optimized quality of life in patients with SSc; however, the procedure carries a higher risk of transplant-related mortality and possibilities for SSc relapse, secondary autoimmune diseases, and gonadal failure. As such, SCT should be a treatment option only for carefully selected patients with early, rapidly progressing diffuse SSc who have a poor clinical prognosis prior to advanced-stage organ involvement.5

Read more about SSc life expectancy

Esophageal Dilation

Systemic sclerosis often causes esophageal dysfunction, including gastroesophageal reflux (GERD) and motor dysfunction affecting peristalsis.6 GERD is associated with the formation of strictures in approximately 30% of patients with SSc.6,7 

Esophageal dilation is a procedure using an inflatable balloon that physically stretches a narrowed part of the esophagus to widen the passage for food. Esophageal dilation is a potential treatment option for patients with SSc who have strictures due to GERD.6,7 

Read more about SSc complications

Hemodialysis

While the use of angiotensin-converting enzyme (ACE) inhibitors may successfully treat SSc patients with renal dysfunction who are experiencing renal crisis, they may require hemodialysis to support kidney function and remove waste from the blood.8,9 

Approximately 50% of individuals with SSc who experience disease-related renal crisis may recover sufficient kidney function after 3 to 18 months of continued dialysis to the point of discontinuation. Other patients may require long-term dialysis or renal transplantation.9

Physical Therapy

Physical therapy exercises may help maintain strength; however, they will not be able to stop the gradual progression of skin tightening around the joints and the formation of contractures.1

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Surgical Interventions

Surgical treatments to decrease GERD, which promotes stricture formation in patients with SSc, may include Nissen fundoplication and Roux-en-Y gastric bypass surgeries.6,7 

Kidney transplantation may be a treatment option for patients with SSc with end-stage renal failure; however, these patients demonstrate poorer overall survival and graft survival than individuals with other primary kidney disorders.10

Lung transplantation may be a treatment option for patients with SSc who have severe interstitial lung disease, pulmonary arterial hypertension (PAH), or rapidly progressing SSc.11,12 A systematic review of lung transplantation in patients with SSc revealed that short-term and intermediate-term survival up to 3 years post-transplantation remained similar to the survival of patients with PAH and interstitial lung disease without SSc.11

Read more about SSc surgical management

References

  1. Nevares AM. Systemic sclerosis (scleroderma). Merck Manual Professional Version. Updated October 2022. Accessed April 26, 2023.
  2. Adigun R, Goyal A, Hariz A. Systemic sclerosis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. Updated May 8, 2022. Accessed April 26, 2023. 
  3. Denton CP, Hughes M, Gak N, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford). 2016;55(10):1906-1910. doi:10.1093/rheumatology/kew224
  4. Schwartz RA. Systemic sclerosis treatment & management: medical care. Medscape. Updated April 16, 2021. Accessed April 26, 2023.
  5. Walker UA, Saketkoo LA, Distler O. Haematopoietic stem cell transplantation in systemic sclerosis. RMD Open. 2018;4(1):e000533. doi:10.1136/rmdopen-2017-000533
  6. Denaxas K, Ladas SD, Karamanolis GP. Evaluation and management of esophageal manifestations in systemic sclerosis. Ann Gastroenterol. 2018;31(2):165-170. doi:10.20524/aog.2018.0228
  7. Voulgaris TA, Karamanolis GP. Esophageal manifestation in patients with scleroderma. World J Clin Cases. 2021;9(20):5408-5419. doi:10.12998/wjcc.v9.i20.5408
  8. Carr ZJ, Klick J, McDowell BJ, Charchaflieh JG, Karamchandani K. An update on systemic sclerosis and its perioperative management. Curr Anesthesiol Rep. 2020;10(4):512-521. doi:10.1007/s40140-020-00411-8
  9. Vaidya PN, Basyal B, Finnigan NA. Scleroderma and renal crisis. In: StatPearls. StatPearls Publishing; 2023. Accessed April 25, 2023.
  10. Bertrand D, Dehay J, Ott J, et al. Kidney transplantation in patients with systemic sclerosis: a nationwide multicentre study. Transpl Int. 2017;30(3):256-265. doi:10.1111/tri.12923
  11. Khan IY, Singer LG, de Perrot M, et al. Survival after lung transplantation in systemic sclerosis. A systematic review. Respiratory Medicine. 2013;107(12):2081-2087. doi:10.1016/j.rmed.2013.09.015
  12. Cottin V, Brown KK. Interstitial lung disease associated with systemic sclerosis (SSc-ILD). Respiratory Research. 2019;20(1):13. doi:10.1186/s12931-019-0980-7

Reviewed by Harshi Dhingra, MD, on 4/30/2023.

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