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Rheumatology - Systemic Sclerosis - Fast Facts | NEJM Resident 360

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease characterized by vasculopathy and fibrosis of the skin and internal organs. SSc has a poor prognosis, and mortality risk is estimated anywhere between two- to fivefold higher than the general population. Most SSc-related deaths are due to complications of pulmonary fibrosis; pulmonary arterial hypertension; cardiac, renal, or gastrointestinal disease; and infections. There is no cure for any manifestation of SSc.

The American College of Rheumatology (ACR) has defined the following subsets of systemic sclerosis:

• limited cutaneous****SSc (lcSSc) includes CREST syndrome (calcifications, Raynaud phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia)

• diffuse cutaneous****SSc (dcSSc)

• SSc without skin involvement (or “systemic sclerosis sine scleroderma” [ssSSc])

Manifestations

A range of systems can be affected by systemic sclerosis and are outlined in the following table:

System	Symptoms & Signs
Skin	Scleroderma

• lcSSc: typically restricted to hands, face, and neck
• dcSSc: involves chest, abdomen, forearms, upper arms, and shoulders
  Sclerodactyly
  Telangiectasias | | Musculoskeletal | Fibrosis around tendons and nerves, manifesting as:
• arthralgia
• tendinopathy
• myalgia
• neuropathy | | Vascular | Raynaud phenomenon (occurs in almost all patients with SSc)
  Abnormalities in nail-fold capillaries (seen with a dermatoscope or other similar device)
  Digital ulcers | | Gastrointestinal | Esophageal dysmotility
  Wide-mouthed diverticula
  Telangiectasias
  Primary biliary cirrhosis | | Renal | Mild-to-moderate proteinuria
  Increased creatinine
  Hypertension
  Scleroderma renal crisis | | Pulmonary | Interstitial lung disease
  Pulmonary arterial hypertension
  Pleuritis
  Endobronchial telangiectasias | | Cardiac | Cardiac fibrosis
  Coronary artery disease
  Pericarditis |

Although not diagnostic for SSc, Raynaud phenomenon develops in almost all patients with SSc:

Findings in Patients with Raynaud’s Phenomenon

Panel A shows the pallor phase and Panel B the cyanotic phase.
(Source: Raynaud’s Phenomenon. N Engl J Med 2016.)

Diagnosis

There is no single test to confirm diagnosis of SSc. Rather, diagnosis depends on a combination of clinical, laboratory, and, in some cases, pathologic manifestations. In 2013, the ACR revised classification criteria for SSc. These guidelines are more sensitive for identifying early SSc and are useful for evaluating patients with possible SSc. Using this classification system, a score of 9 classifies a patient as having definite SSC.

ACR Classification Criteria for SSc

(Source: 2013 Classification Criteria for Systemic Sclerosis: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Reproduced with permission.)

Many antibodies are associated with the various manifestations of SSc. For a summary of the phenotypic characteristics and their autoantibody associations, see table 1, “ Phenotypic Characteristics and Their Autoantibody Associations in Scleroderma,” from Mayo Clinic Proceedings, “My Approach to the Treatment of Scleroderma.” 

Treatment

Treatment varies depending on the patient’s clinical manifestations. Therapies are either immunomodulatory, target vascular function, or target specific symptoms (i.e., proton pump inhibitors for reflux).

For an outline of important management considerations, see table 2, “Management Principles,” from Mayo Clinic Proceedings, “My Approach to the Treatment of Scleroderma.”

Current Available Treatments for SSc

Indication	Therapy	Mechanism of Action
Skin changes	Glucocorticoids (used cautiously due to potential link with renal crisis)	Anti-inflammatory
Immunosuppression
Methotrexate
Mycophenolate mofetil	Immunosuppression
Musculoskeletal changes	Glucocorticoids	Anti-inflammatory
Immunosuppression
Methotrexate
Leflunomide	Immunosuppression
Surgery for nerve entrapment	Reduction in pressure on nerve
Raynaud phenomenon	Avoidance of exposure to the cold	Prevents vasoconstriction
Topical nitrates	Promotes vasodilation
Calcium-channel blockers, especially dihydropyridine-type	Vasodilation
Iloprost	Synthetic analogue of prostacyclin (PGI2)
Digital ulceration	Aspirin	Antiplatelet agent
Sildenafil/tadalafil	Phosphodiesterase type 5 inhibitor (PDE5) inhibitor
Bosentan	Endothelial receptor antagonist
Gastrointestinal dysmotility	Metoclopramide
Erythromycin	Promotility agents
Reflux	Pantoprazole
Omeprazole	Proton pump inhibitor
Renal crisis	Ramipril
Perindopril	Angiotensin-converting–enzyme (ACE) inhibitor
Interstitial lung disease	Glucocorticoids	Anti-inflammatory
Immunosuppression
Cyclophosphamide
Mycophenolate mofetil	Immunosuppression
Pulmonary arterial hypertension	Supplemental oxygen	Improved cardiac and systemic oxygenation
Ambrisentan
Bosentan
Macitentan	Endothelial receptor antagonist
Riociguat	Stimulates soluble guanylate cyclase
Epoprostenol
Treprostinil	Synthetic prostacyclin analogue
Rapidly progressive SSc with risk of organ failure	Autologous hemopoietic stem-cell transplantation
Lung transplantation	Immunomodulatory
Resets immune system

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