Systemic Sclerosis Overview

Systemic Sclerosis (SSc)

• Autoimmune disorder of connective tissue
• Fibrosis affects skin, internal organs, and vasculature
• Characterized by Raynaud's phenomenon, digital ischemia, sclerodactyly, and involvement of cardiac, lung, gut, and renal systems
• Peak onset in the fourth and fifth decades
• Prevalence: 10-20 per 100,000, with a 4:1 female-to-male ratio

Types of Systemic Sclerosis

• Diffuse cutaneous systemic sclerosis (dcSScl): 30% of cases. Skin involvement extends beyond sites distal to the elbow and knee (including the face).
• Limited cutaneous systemic sclerosis (lcSScl): 70% of cases. Skin involvement is restricted to sites distal to the elbow or knee (except the face).

Prognosis in dcSScl

• Poor prognosis associated with older age, diffuse skin disease, proteinuria, high ESR, low carbon monoxide gas transfer factor (TLCO), and pulmonary hypertension.

Pathophysiology

• Cause not fully understood; genetic component and associations with HLA alleles
• Isolated cases triggered by exposure to silica dust, vinyl chloride, epoxy resins, or trichloroethylene
• Immunological dysfunction (T lymphocytes infiltrate the skin, abnormal fibroblast activation, leading to increased type I collagen production)
• Arterial and arteriolar narrowing due to intimal proliferation and vessel wall inflammation, endothelial injury, vasoconstrictors release, platelet activation, resulting in further ischemia which exacerbates the fibrotic process.

Clinical Features

• Skin: Initial non-pitting edema of fingers and flexor tendon sheaths, followed by shiny, taut skin, disappearance of distal skin creases, capillary loss, and thinning of the face and neck (sometimes with radial furrowing)
• Raynaud's Phenomenon: Universal feature, often precedes other symptoms. Involvement of small blood vessels in extremities, leading to critical tissue ischemia, distal skin infarction, and necrosis.
• Musculoskeletal: Arthralgia, flexor tenosynovitis are common. Restricted hand function, due to skin involvement rather than joint disease; erosive arthropathy is uncommon.
• Cardiovascular: Cardiac involvement, accelerated hypertension, scleroderma renal crisis
• Gastrointestinal: Smooth muscle atrophy and fibrosis in lower two-thirds of esophagus leading to reflux with erosive esophagitis; dysphagia, odynophagia, recurrent occult upper gastrointestinal bleeding (watermelon stomach), small intestine involvement leading to malabsorption due to bacterial overgrowth, and intermittent bloating, pain or constipation.
• Pulmonary: Pulmonary hypertension, interstitial lung disease. Exertional dyspnea and signs of right heart failure are common
• Renal: Hypertensive renal crisis, one of the main causes of death.
• Telangiectases
• Other: Skin thickening, Calcinosis (occurs mainly over pressure points)

Skin Manifestations (images)

• Images show different skin presentations (e.g., discoloration, thickening)

Investigations

• Routine haematology, renal, liver, and bone function tests alongside urinalysis
• Antinuclear antibodies (ANA) are positive in about 70% of cases; Antibodies to topoisomerase 1 (Scl70) in about 30% of dcSScl patients and anticentromere antibodies in about 60% of lcSScl patients
• Chest X-ray, echocardiography, Pulmonary Function Tests (PFTs), high-resolution lung CT (if interstitial lung disease suspected)
• Right heart catheter measurements, barium swallow (for esophageal involvement), hydrogen breath test (for bacterial overgrowth)

Management

• No treatment reverses fibrosis; focus is on slowing disease progression
• Raynaud's Phenomena & Digital Ulcers: Avoidance of cold exposure, thermal insulation, calcium channel blockers, losartan, fluoxetine, sildenafil
• Gastrointestinal Complications: Proton pump inhibitors, anti-reflux agents, courses of antibiotics for bacterial overgrowth, metoclopramide or domperidone for dysmotility/pseudo-obstruction
• Hypertension: Aggressive ACE inhibitor treatment, even if renal impairment is present
• Joint Involvement: Analgesics, NSAIDs, low-dose methotrexate
• Pulmonary Hypertension: Bosentan, transplant may be considered in severe or progressive cases.
• Interstitial Lung Disease: Glucocorticoids, cyclophosphamide (pulse intravenous)