Cutaneous and Articular Manifestations
In the early stages, the skin becomes edematous, doughy in consistency, and glossy. Microscopically, perivascular infiltrates of CD4+ T-lymphocytes and plasma cells are found in the dermis, and the connective tissue becomes disorganized. The walls of capillaries and arterioles thicken, and their lumina narrow.
Subsequently, coarse sclerosis of the dermis, vascular hyalinosis, and atrophy of the epidermis with appendages (sweat and sebaceous glands, hair follicles) develop. Skin calcinosis is specific, especially periarticularly on the fingers. In the final stage, a mask-like facies, sclerodactyly, and severe trophic disorders (ulcers, alopecia) develop, sometimes leading to autoamputation of the fingers.
Joint involvement presents as polyarthritis of the small joints of the hands. Lymphoplasmacytic infiltration and synoviocyte hyperplasia occur in the synovial membrane. Unlike rheumatoid arthritis, tissue destruction is not characteristic — the process ends with synovial sclerosis and vascular obliteration.
Renal Involvement
Renal involvement occurs in 75% of patients and is one of the primary life-threatening complications. It is based on scleroderma microangiopathy, primarily affecting interlobular arteries.
Morphological features:
- Concentric intimal hyperplasia.
- Mucoid swelling.
- Fibrinoid necrosis of vessel walls with luminal thrombosis.
These changes lead to renal infarctions. The "true scleroderma kidney" syndrome develops — a severe condition combining infarctions and acute renal failure. Additionally, 30% of patients develop arterial hypertension due to renal artery involvement. Chronic glomerulonephritis is rare in this context.
Pulmonary and Cardiac Changes
The lungs are affected in more than 50% of cases. The early phase features alveolitis with tissue infiltration by macrophages, lymphocytes, and band neutrophils. In the late phase, basal diffuse interstitial pulmonary fibrosis develops, which is inevitably accompanied by pulmonary hypertension. Pleural fibrosis is frequently observed, and fibrinous pleuritis is less common.
In 30% of patients, a "scleroderma heart" develops. Pathomorphologically, this manifests as productive vasculitis, and micro- and macrofocal cardiosclerosis. Sclerosis of the parietal and valvular endocardium, as well as tendinous cords, leads to specific scleroderma heart disease.
Gastrointestinal Tract and Liver
Gastrointestinal pathology is observed in 90% of patients. The most severe changes occur in the esophagus:
- Sclerosis of the muscular layer (predominantly in the lower third).
- Motility disorders and reflux esophagitis.
- Formation of strictures and peptic ulcers.
- Epithelial metaplasia (Barrett's esophagus).
Other parts of the GI tract also develop motility disorders, sclerosis, and mucosal atrophy, clinically manifesting as malabsorption syndrome. Diverticula and diverticulitis may develop in the large intestine.
In CREST syndrome, the liver is involved, potentially leading to primary biliary cholangitis (PBC).
Outcomes
Progression of systemic sclerosis leads to severe organ and systemic failure. The primary causes of mortality are uremia (due to renal failure), as well as cardiovascular and cardiopulmonary failure.