• Systemic sclerosis (SSc); It is a connective tissue disease characterized by progressive fibrosis that may involve the skin and/or visceral organs.
• It is more common in women and is usually seen between the ages of 30-50.
• Three cardinal pathophysiological mechanisms responsible for SSc pathogenesis;
o Inflammation and autoimmunity (immune dysregulation)
o Diffuse microangiopathy
o Visceral and vascular fibrosis
• Systemic sclerosis is examined in two groups according to skin involvement;
o Limited SSc
Involves the skin of the distal extremity and face.
The specific antibody is the anticentromere.
It is associated with CREST syndrome and isolated pulmonary arterial hypertension.
o Diffuse SSc
It holds the skin of the whole body.
The specific antibody is anti-topoisomerase I (Scl-70).
It is associated with renal crisis and interstitial lung disease.
CREST syndrome
• Calcinosis cutis
• Esophageal dysmotility
• Sclerodactyly
• Telangiectasia
Skin findings
• Bilateral symmetrical skin thickening is the most prominent finding of SSc.
• Chronological order of skin involvement in SSk; edematous phase, indurative / fibrotic phase, atrophic phase
• Involvement; It starts from the fingers and progresses proximally bilaterally and symmetrically.
• Some other findings;
o Telangiectasias
o Cutaneous calcifications
o Mask face, microstomy
o Painful ulcers on the fingertips
o Abnormal vascular tangles on capillaroscopy
Gastrointestinal system findings
• It is the most common form of visceral involvement.
• All GIS can be kept. However, the distal esophagus is most commonly involved.
• The common pathological disorder that can be seen throughout the entire GIS is dysmotility.
• Esophageal involvement
o SSc is a disease that can cause both gastroesophageal reflux and dysphagia.
• Stomach involvement
o Delay in gastric emptying (gastroparesis), Gastric antral vascular ectasia (GAVE - watermelon stomach)
• Lower gastrointestinal system findings
o Decreased intestinal motility (pseudo-obstruction), bacterial overgrowth
o Intestinal gas can become trapped inside the intestinal wall (pneumatosis cystoides intestinalis)
Connective tissue disease and esophageal involvement (dysphagia)
Dermatomyositis and polymyositis---- Proximal esophagus
Scleroderma------------------------------- Distal esophagus
Lung findings
• It is the second most common form of visceral involvement in patients.
• It is the most important cause of mortality in SSc patients.
• While interstitial fibrosis is dominant in diffuse SSc, isolated pulmonary arterial hypertension is seen in the foreground in limited SSc.
- Interstitial fibrosis
• Exercise dyspnea, progressive shortness of breath and dry cough are common.
• On physical examination, velcro rales are heard at the lung bases.
• Risk factors;
o Male gender
o Diffuse skin involvement
o Presence of severe gastroesophageal reflux
o Presence of anti-topoisomerase I antibody
o Low DLCO diffusion capacity and FVC at first admission
- Isolated arterial artery I hypertension (PAH)
• Right heart failure findings are prominent.
• Risk factors;
o Limited SSC
o Onset of the disease at an older age
o Severe Raynaud's phenomenon
o Presence of excessive cutaneous telangiectasia
o Anti-centromere antibody positivity
o Ul-RNP, U3-RNP antibody positivity
Kidney involvement / Scleroderma renal crisis
• Obliterative vasculopathy in renal vessels and narrowing of the lumen play a role in the pathogenesis.
• Progressive decrease in renal blood flow; Activation of the renin-angiotensin-aldosterone system results in hypertensive crisis (malignant hypertension).
• Classic thrombotic microangiopathy pathology is observed in scleroderma renal crisis.
• Risk factors for renal crisis;
o Male gender
o Diffuse and progressive skin involvement (diffuse SSc)
o Tendon crepitations
o Presence of anti-RNA polymerase III antibodies
o Corticosteroid therapy
• Anticentromere antibody positivity and limited SSc are associated with a low risk of developing renal crisis.
• Clinical findings in the picture of renal crisis;
o Hypertensive crisis (10% of patients may be normotensive)
o Microangiopathic hemolytic anemia and thrombocytopenia
o Progressive oliguric acute kidney injury
o In urinalysis; mild proteinuria, granular casts, microscopic hematuria
Musculoskeletal findings
• Trap neuropathies such as carpal tunnel syndrome
• Decrease in joint movements and contraction deformities
• Tendon friction sound / tendon crepitation
• Resorption in the terminal phalanges (acro-osteolysis)
• Fingertip necrosis and autoamputations
SSc and Malignancy
• Some cancers trigger scleroderma (paraneoplastic scleroderma). The autoantibody associated with this condition is RNA polymerase III.
Treatment
• Immunosuppressive treatments are either not effective or have little effect in SSc. The only treatment approach that changes the natural course of the disease is hematopoietic stem cell transplantation.
• Corticosteroids increase the risk of renal crisis (if necessary, they should be used for a short time and at low doses).
• Cyclophosphamide, rituximab and mycophenolate mofetil are effective in early skin and lung involvement.
• Renal crisis treatment
o First choice ACE inhibitors / angiotensin receptor blockers.
• Treatment in pulmonary arterial hypertension
o Endothelin receptor blockers Ambrisentan, Sitaxentan, Bosentan,
macitentan
o Prostacyclin receptor agonists Ilioprost, Epoprostenol, Selexipag
o Phosphodiesterase 5 inhibitors Sildenafil, Tadalafil
o Soluble guanylate cyclase activator Riociguat
