1.2.2 Systemic scleroderma (SSc)

 4A42.1

Progressive Systemic Sclerosis.

Incidence varies between 0.1-4.3/100000; F:M = 4:1. 

Chronic progressive multi-systemic disease involving skin, vessels and internal organs (lung, heart, gastrointestinal tract, kidney).

Multi-factorial: immunogenetic predisposition (HLA association), disturbed vascular regulation, humoral & cellular immune phenomena, altered collagen synthesis. Some chemical triggers identified (polyvinyl chloride, organic solvents, epoxy resins, silica).

Cutaneous:

• Hands: sclerodactyly, painful fingertip ulcers, fingers initially puffy, later atrophic with distal thinning
• Face: microstomia, perioral radial folds (purse string mouth), telangiectases
• Entire skin: increasing thickness 
• Vessels: Raynaud's syndrome, often presenting feature

Internal organs:

• Gastrointestinal tract: sclerosis of frenulum of tongue, disturbed swallowing, constipation, diarrhea
• Lungs: pulmonary fibrosis, pulmonal artery hypertension (PAH)
• Kidneys: proteinuria, hematuria, renal crisis due to nephrosclerosis
• Heart: myocardial fibrosis, right heart failure secondary to PAH
• Liver: primary biliary cirrhosis (possible)
• Joints: pain, swelling, arthralgias, arthritis, dermatogenic contractures
• Bones: osteolysis, osteomyelitis possible due to digital ulcerations
• Muscles: muscle weakness from myositis.

See Classification.

1. Limited SSc (43%): Raynaud's phenomenon precedes skin changes by years. Limited cutaneous sclerosis distal to knees and elbows, involvement of the face. Esophageal disease, telangiectases, increased risk of developing PAH. Anti-centromere antibodies usually positive.
2. Diffuse SSc (32%): Raynaud's phenomenon usually appears shortly before (
3. Overlap syndrome (10%): Patients simultaneously show typical signs of SSC and other rheumatologic diseases.
4. Others (undifferentiated forms, sclerosis sine scleroderma).

Immune serology: antinuclear antibodies (ANAs)/extractable nuclear antibodies (ENAs), anti-centromere antibodies (acral type), anti-Scl70 antibodies (diffuse type). Nail fold capillary microscopy (giant capillaries). Depending on clinical pattern, organ-specific studies. CAVE: Clinically silent pulmonary or renal involvement.

Early lesions: dense superficial and deep perivascular and periadnexal lymphocytic infiltrate.

Late lesions: increased collagen (sclerosis) with loss of adnexal structures (alopecia, decreased sweating).

Chronic and progressive.

Contractures, trophic ulcers, esophageal stenosis, Barrett eosophagus, pulmonary fibrosis (pulmonary hypertension), renal failure (renal hypertension, renal crisis), cardiac failure, cardiac rhythm disorders, right heart overload.

Clinical features, histology, immune serology.

• Provocation testing for Raynaud's phenomenon: immerse hands in ice water for 10-20 minutes
• Capillary microscopy: early stage: ectasia of capillaries; active stage: mega-capillaries, hemorrhages; late stage: rarefaction and tufting of capillaries

In case of respiratory problems:

• Pulmonary function test, high-resolution CT (if pulmonary fibrosis is suspected)
• EKG, echocardiogram, 6-minute walking test to assess right heart overload

In case of gastrointestinal problems:

• Scintigraphy or dynamometry of esophagus, gastroscopy, (dysphagia, refluxesophagitis), colonoscopy.

In case of renal involvement:

• Blood pressure monitoring, renal function tests, 24 hour urine, ultrasound, kidney biopsy in selected cases

In case of musculoskeletal problems:

• Muscles: CK, myositis-specific antibodies, EMG, MRI, muscle biopsy
• Joints: x-ray, sonography, rheumatoid factor, anti-CCP antibodies

(Pseudosclerodermas)

Eosinophilic fasciitis, chronic graft-vs-host-disease, genodermatoses (Werner syndrome), porphyria cutanea tarda, amyloidoses, mucinoses, gadolinium-induced sclerosis.

Chemically induced scleroderma (polyvinyl chloride, silica, organic solvents, epoxy resins), drug-induced sclerosis (bleomycin, pentazocine, L-tryptophan). 

No causal therapy available. Interdisciplinary treatment and guidance.