![SSc SUBSETS
• Diffuse cutaneous SSc[dcSSc]
• Limited cutaneous SSc[leSSc]
• SS sine scleroderma in which pt have only
internal organs involvement
• Environmental induced scleroderma
• Overlap syndrome in which features of SSc
coexist with elements of other rheumatic
disorders](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-10-320.jpg)
![CERTAIN NOTES
• Pt with Lc SSc have very high mortality rate
• High mortality rate with pt with isolated
pulmonary hypertension
• Pt with LcSSc who develop significant lung
fibrosis or acute renal failure have a poor
prognosis as those with DcSSc
• Pt with antibodies to topoisomerase-I[Scl-70]
are associated with an increased risk of
pulmonary fibrosis in both the DcSSc and Lc-
SSc](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-18-320.jpg)
![• Anticentromere antibodies[ACA] are almost
always indicative of LcSSc and are seen in the
classical CREST
• Autoimmune Raynaud phenomenon are
characterized by abnormal nailfold
capillaroscopic findings and the presence of
positive antinuclear Ab, anticentromere Ab,
antitopoisomerase-I.](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-19-320.jpg)
![2- Vascular Disease
• Raynaud phenomena, defined as sequential
color changes in digits precipitated by cold,
stress or even change in temperatures.
• Raynaud phenomena is due to arterial
vasoconstriction in the digits. The color
changes pallor [‘white’], acrocyanosis [‘blue’],
& reperfusion hyperemia [‘red’] are
characteristic.](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-21-320.jpg)
![• Any part of the gastrointestinal tract from
mouth to anus may be affected.
• Dysphagia ad choking, heart burn, cough
after swallowing, bloating, alternating
constipation & diarrhea, pseudo-obstruction
& bacteria small bowel overgrowth with
malabsorption, & fecal incontinence.
• Chronic gastroesophageal reflux & recurrent
episodes of aspiration may contribute to the
development of interstitial lung disease.
• Vascular ectasia in the stomach [‘watermelon
stomach’] is frequent, & may cause chronic
gastrointestinal bleeding & anemia.](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-24-320.jpg)
![Pulmonary disease
• It is seen in more than 70% of PTS is interstitial lung
disease [also called fibrosing alveolitis or pulmonary
fibrosis] & pulmonary vascular disease, leading to
pulmonary arterial hypertension.
• Interstitial lung disease occurs in more than three-
quarters of PTS with SSc.
• Fibrosis is commonly preceded by alveolitis.
• The most common symptoms are breathlessness on
exertion [which may progress to dyspnea at rest], &
nonproductive cough.
• Chest pain is infrequent & hemoptysis is rare.
• On examination, auscultation over the lungs reveals
fine rales most prominent at the lung bases.](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-25-320.jpg)
![• Scleroderma renal crisis is more frequent in
PTS with DcSSc than those with LcSSc.
• This form of renal involvement is characterized
by: acute onset of renal failure urine analysis
reveals only mild proteinuria with few cells or
casts
• abrupt onset of moderate to marked or
malignant HTN [although some PTS remain
normotensive ]
• Other features of scleroderma renal crisis may
be due to the effects of severe HTN or
vasculopathy & include: microangiopathic
hemolytic anemia, pulmonary edema,
headache, blurred vision, & hypertensive
encephalopathy, often complicated by
generalized seizures.](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-28-320.jpg)
![JOINT INVLVEMENT
• True inflammatory arthritis is uncommon in
SSc. Joint pain, immobility & contractures
develop as the result of fibrosis around tendons
& other particular structures. Contractures of
the fingers from this process are most common,
but large joint contractures involving the wrists,
elbows & ankles may also occur.
• The most common sites of involvement are the
extensor & flexor tendons of the fingers & wrist,
tendons over the elbow [triceps], knees
[patellar], & ankle [anterior & posterior tibial,
peroneal & Achilles].](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-31-320.jpg)
![The American College of Rheumatology/European League
Against Rheumatism criteria for the classification of SS
Weight/sco
re^
Sub-item(s)
Item
9
Skin thickening of the fingers of
both hands extending proximal to
the metacarpophalangeal joints
(sufficient criterion)
2
4
Puffy fingers, Sclerodactyly of the fingers (distal to the
metacarpophalangeal joints but proximal to the proximal
interphalangeal joints)
Skin thickening of the fingers (only
count the high scores)
2
3
Digital tip ulcer
Fingertip pitting scars
Fingertip lesions (only count the
higher score)
2
Telangiectasia
2
Abnormal nailfold capillaries
2
2
Pulmonary arterial hypertension
Interstitial lung disease
Pulmonary arterial hypertension
and/or interstitial lung disease
(maximum score is 2)
3
Raynaud's phenomenon
3
Anticentromere
Anti-topoisomerase I
Anti-RNA polymerase III
SSc-related autoantibodies
(anticentromere, anti-
topoisomerase I [anti-Scl-70], anti-
RNA polymerase III) (maximum](https://image.slidesharecdn.com/systemicsclerosis-240527111425-756ad3c0/85/systemic-sclerosis-and-scleroderma-powerpoint-37-320.jpg)
systemic sclerosis and scleroderma powerpoint
- 1. Systemic sclerosis MOHAMED KHALED LECTURER OF INTERNAL MEDICINE
- 2. Systemic sclerosis • C.T disorder characterized by degenerative and inflammatory changes with subsequent intense fibrosis; affecting skin, synovium, blood vessels, skeletal muscles, GIT, heart, lung, kidney.
- 3. Etiopathogenesis Unknown triggering Fibroblasts Mononuclear cells platelet endothelial cell Overproduction of collagen Fibrosis Obliteration of nutritional vessels Ischemia
- 4. Environmental triggering factors • Silica • Organic solvents: ▫ Benzene ▫ Amino acide: hydroxy tryptophan • Drugs: ▫ Cardiodopa ▫ Vitamin K ▫ Bleomycin ▫ Penicillamin ▫ Appetite suppressors • Cosmotics: ▫ Silicon implants • Pesticides/insecticides • Hydrocarbon: ▫ Ethyline
- 5. Pathogenesis Genetic factors HLAB8, DR3, DR52, DQB2 Environmental factors Stimulation of macrophages, T & B lymphocytes, mast cells, & fibroblasts Cytokine secretion, enzyme inhibitors Production of profibrotic cytokines: TGF-β, PGF, IL- 4, IL-6, CT growth factor Increase collagen I, III, V, VII, fibrinectin, & proteoglycans VEGF & anti endothelial Abs Scarring and vascular disfunction Expression of adhesive molecules Apoptosis with free radical release
- 7. CLASSIFICATION OF SCLERODERMA DISORDERS • The simplest division of the SS related disorders is into localized and systematic • Disorders other than SS cause skin thickening are DM ,hypothyroidism, eosinophilic fasciitis ,amyloidosis, exposure to certain drugs, toxins, & environmental exposure.
- 9. Linear scleroderma • Most commonly occurring in childhood • On one side of body • Face or scalp lesion is accompanied by marked abnormalities of underlying mesenchymal derived tissue, including skull.
- 10. SSc SUBSETS • Diffuse cutaneous SSc[dcSSc] • Limited cutaneous SSc[leSSc] • SS sine scleroderma in which pt have only internal organs involvement • Environmental induced scleroderma • Overlap syndrome in which features of SSc coexist with elements of other rheumatic disorders
- 11. Limited cutaneous SSc • Skin sclerosis restricted to the hands and to a lesser extent the face and neck • Have prominent vascular manifestations • Suffer from CREST syndrome • Presence of severe vascular abnormalities on nailfold capillary microscopy
- 12. DIFFUSE CUTANEOUS SSc • Have extensive skin sclerosis • Have greater risk for the development of significant renal, lung and cardiac disease • Extension of skin sclerosis proximal to wrists • Over proximal limbs and trunk but commonly sparing the upper back
- 14. SSc SINE SCLERODERMA • Rare form of the illness • Vascular features and visceral fibrosis of systemic disease • Without skin sclerosis • Prognosis like LcSSc
- 16. OVERLAP SYNDROMES • Features of SSc in combination with manifestaion of other rheumatic diseases such as SLE ,dermatomyositis or rheumatoid arthritis
- 17. Diagnosis of early disease: preterm scleroderma • Use of capillary nailfold microscopy and serologic testing for autoantibodies • Early diagnosis of SSc in absence of sclerodermal skin change by abnormal wide field capillary microscopy plus • Autoantibodies (anticentromere- antitopoisomerase, anti-Scl70)
- 18. CERTAIN NOTES • Pt with Lc SSc have very high mortality rate • High mortality rate with pt with isolated pulmonary hypertension • Pt with LcSSc who develop significant lung fibrosis or acute renal failure have a poor prognosis as those with DcSSc • Pt with antibodies to topoisomerase-I[Scl-70] are associated with an increased risk of pulmonary fibrosis in both the DcSSc and Lc- SSc
- 19. • Anticentromere antibodies[ACA] are almost always indicative of LcSSc and are seen in the classical CREST • Autoimmune Raynaud phenomenon are characterized by abnormal nailfold capillaroscopic findings and the presence of positive antinuclear Ab, anticentromere Ab, antitopoisomerase-I.
- 20. 1- skin Involvement • Skin involvement is characterized by variable thickening & hardening of the skin. The fingers, hand & face are generally the earliest areas of the body involved. Edematous swelling & erythema of the skin may precede skin induration • Other prominent skin manifestation include: • Pruritis in the early stages • Edema in the early stages sclerodactyly • Digital ulcers pitting at the fingertips • Telangiectasia • Calcinosis cutis
- 21. 2- Vascular Disease • Raynaud phenomena, defined as sequential color changes in digits precipitated by cold, stress or even change in temperatures. • Raynaud phenomena is due to arterial vasoconstriction in the digits. The color changes pallor [‘white’], acrocyanosis [‘blue’], & reperfusion hyperemia [‘red’] are characteristic.
- 22. • Vascular injury & subsequent chronic damage underlies other serious complications of SSC, including pulmonary artery hypertension, scleroderma renal crisis & gastric antra vascular ectasia. • It also contributes to the pathogenesis of cardiac & gastrointestinal complications.
- 23. ORGAN INVOLVMENT • Lungs, kidneys, gastrointestinal tract, & heart are commonly affected • Gastrointestinal involvement nearly 90% of patients have some degree. Nearly half of these patients may be asymptomatic. • Esophageal hypomotility & incompetence of lower esophageal sphincter was the earliest visceral manifestation of SS.
- 24. • Any part of the gastrointestinal tract from mouth to anus may be affected. • Dysphagia ad choking, heart burn, cough after swallowing, bloating, alternating constipation & diarrhea, pseudo-obstruction & bacteria small bowel overgrowth with malabsorption, & fecal incontinence. • Chronic gastroesophageal reflux & recurrent episodes of aspiration may contribute to the development of interstitial lung disease. • Vascular ectasia in the stomach [‘watermelon stomach’] is frequent, & may cause chronic gastrointestinal bleeding & anemia.
- 25. Pulmonary disease • It is seen in more than 70% of PTS is interstitial lung disease [also called fibrosing alveolitis or pulmonary fibrosis] & pulmonary vascular disease, leading to pulmonary arterial hypertension. • Interstitial lung disease occurs in more than three- quarters of PTS with SSc. • Fibrosis is commonly preceded by alveolitis. • The most common symptoms are breathlessness on exertion [which may progress to dyspnea at rest], & nonproductive cough. • Chest pain is infrequent & hemoptysis is rare. • On examination, auscultation over the lungs reveals fine rales most prominent at the lung bases.
- 26. • Pulmonary arterial HTN is generally a late complication of SSc, is typically progressive &, if serve, can lead to cor pulmonale & right-sided heart failure. • Thrombosis of the pulmonary vessels is a common complication of late-stage pulmonary arterial HTN, & is a frequent cause of death. • The incidence rate of malignant lung neoplasms is approximately 5 fold higher than for an age & gender matched subset of the general population.
- 27. Renal disease • 60 to 80% of PTS with dcSSc have pathologic evidence of kidney damage. • Impaired renal reserve may be present in the absence of clinical renal disease. • Some degree of proteinuria, a mild elevation in the plasma creatinine concentration, &/or HTN are observed in as many as 50% of PTS.
- 28. • Scleroderma renal crisis is more frequent in PTS with DcSSc than those with LcSSc. • This form of renal involvement is characterized by: acute onset of renal failure urine analysis reveals only mild proteinuria with few cells or casts • abrupt onset of moderate to marked or malignant HTN [although some PTS remain normotensive ] • Other features of scleroderma renal crisis may be due to the effects of severe HTN or vasculopathy & include: microangiopathic hemolytic anemia, pulmonary edema, headache, blurred vision, & hypertensive encephalopathy, often complicated by generalized seizures.
- 29. Cardiac disease • PTS with symptomatic cardiac involvement due to SSc have a poor prognosis. • Cardiac complications secondary to systemic or pulmonary HTN are most common in SSc, but primary cardiac involvement also occurs. • Primary cardiac involvement include pericarditis, pericardial effusion, myocardial fibrosis, heart failure, myocarditis associated with myositis, conduction disturbances, & arrhythmias
- 30. Arrhythmias • Conduction system disease & arrhythmias are common to result from fibrosis of the myocardium & conduction system. • Many deaths among SSc PTS are sudden, some of witch may result from a ventricular arrhythmia.
- 31. JOINT INVLVEMENT • True inflammatory arthritis is uncommon in SSc. Joint pain, immobility & contractures develop as the result of fibrosis around tendons & other particular structures. Contractures of the fingers from this process are most common, but large joint contractures involving the wrists, elbows & ankles may also occur. • The most common sites of involvement are the extensor & flexor tendons of the fingers & wrist, tendons over the elbow [triceps], knees [patellar], & ankle [anterior & posterior tibial, peroneal & Achilles].
- 32. Investigations A. Lab • High ESR (rare or mild) • CBC: anemia (low iron, autoimmune, traumatic, microangiopathic) • Serology: ▫ Anticentromere (limited type) ▫ anti-scl 70 (diffuse type) ▫ Antinucleolar (diffuse type) ▫ Anti PM-Scl (overlap) ▫ Hypocomplementaemia, andti dsDNS rare (overlap) ▫ +ve Rf (overlap)
- 33. B. Radiology 1. Joints • Disuse atrophy, osteopenia • Rheumatoid like erosive arthritis • Picture of arthritis mutilance 2. GIT (barium or other contrast) • Stricture, low motility lower third esophagus, GERD, hiatal hernia • Dilatation & hypomotility of small intestine • Diverticulosis of large intestine
- 34. 3. Lung: basal fibrosis, cor-pulmonale 4. Heart: restrictive cardiomyopathy, pericarditis. 5. Renal: stenosis of renal artery & interlobular arteries C. Synovial fluid • High WBCs (less than 10,000), high plasma cells, high lymphocytes, fibrin deposits, low mucin, low viscosity
- 35. D. Others • Pulmonary function (restrictive) • Renal function (impaired) • Tests for malabsorption • Wide field nailfold capillary microscope: loss of capillaries, dilatation tortuosity of others.
- 36. • Glucocorticoids – long term , high dose are potentially toxic & have been implicated in precipitating renal crisis. any use of it may increase risk of this complication. Glucocorticoids should therefore be restricted to patients with myositis , active fibrosing alveolitis, symptomatic serositis, early edematous phase of skin disease & refractory arthritis & tenosynovitis.
- 37. The American College of Rheumatology/European League Against Rheumatism criteria for the classification of SS Weight/sco re^ Sub-item(s) Item 9 Skin thickening of the fingers of both hands extending proximal to the metacarpophalangeal joints (sufficient criterion) 2 4 Puffy fingers, Sclerodactyly of the fingers (distal to the metacarpophalangeal joints but proximal to the proximal interphalangeal joints) Skin thickening of the fingers (only count the high scores) 2 3 Digital tip ulcer Fingertip pitting scars Fingertip lesions (only count the higher score) 2 Telangiectasia 2 Abnormal nailfold capillaries 2 2 Pulmonary arterial hypertension Interstitial lung disease Pulmonary arterial hypertension and/or interstitial lung disease (maximum score is 2) 3 Raynaud's phenomenon 3 Anticentromere Anti-topoisomerase I Anti-RNA polymerase III SSc-related autoantibodies (anticentromere, anti- topoisomerase I [anti-Scl-70], anti- RNA polymerase III) (maximum
- 38. Definition of items/sub-items in the American College of Rheumatology/European League Against Rheumatism criteria for the classification of SSc Definition Item Skin thickening or hardening not due to scaring after injury, trauma, etc. Skin thickening Swollen digits-a diffuse, usually nonpitting increase in soft tissue mass of the digits extending beyond the normal confines of the joint capsule. Normal digits are tapered distally with the tissue following the contours of the digital bone and joint structures. Swelling of the digits obliterates these conours. Not due to other causes such as inflammatory dactylitis. Puffy fingers Ulcers or scars distal to or at the proximal interphalangeal joint not thought to be trauma. Digital pitting scars are depressed areas at digital tips as a result of ischemia, rather than trauma or exogenous causes. Fingertip ulcers or pitting scars Telangiectasiae are visable macular dilated superficial blood vessels, which collapse upon pressure and fill slowly when pressure is released. Telangiectasiae in a scleroderma-like pattern are round and well demarcated and found on hands, lips, inside of the mouth, and/or are large mat-like Telangiectasiae. Distinguishable from rapidly filling spider angiomas with central arteriole and from dilated superficial vessels. Telangiectasi a
- 39. Enlarged capillaries and/or capillary loss with or without pericapillary hemorrhages at the nailfold. May also be seen on the cuticle. Abnormal nailfold capillary pattern consistent with systemic sclerosis Pulmonary arterial hypertension diagnosed by right-sided heart catheterization according to standard definitions. Pulmonary arterial hypertension Pulmonary fibrosis seen on high-resolution computed tomography or chest radiography, most pronounced in the basilar portions of the lungs, or occurrence of "Vecro" crackles on auscultation, not due to another cause such as congestive heart failure Interstitial lung disease Self-reported or reported by a physician, with at least a 2-phase color change in finger(s) and often toe(s) consisting of pallor, cyanosis, and/or reactive hyperemia in response to cold exposure or emotion; usually one phase is pallor. Raynaud's phenomenon Anticentromere antibody or centromere pattern seen on antinuclear antibody testing, anti-topoisomerase I antibody (also known as anti-Scl-70 antibody), or anti-RNA polymerase III antibody. Positive according to local laboratory standards. SSC-related autoantibodies
- 40. Treatment of scleroderma manifestations Treatment Manifestation calcium channel blockers Angiotensin type II receptor blocker (losartan) Prostacyclin analogues (intravenous iloprost) Phosphodiesterase inhibitors Digital sympathectomy Raynaud's phenomenon Endothelin receptor antagonists (bosentan) Digital ulcers Immunosuppressives (methotrexate, cyclosporine, tacrolimus, IVIG) Skin fibrosis NSAIDs Steroids DMARDs (methotrexate) Arthritis Immunosuppressives (steroids, methotrexate and azathioprine) Myositis
- 41. ACE: Angiotensin-converting enzyme; ALG: Antilymphocyte globulin; ATG: Antithymocyte globulin; DMARD: Disease-modifying antirheumatic drug; IVIG: Intravenous immunoglobulin; MMF: Mycophenolate mofetil. Proton pump inhibitors Prokinetic agents Gastrointestinal involvement ACE inhibitors Antihypertensives Dialysis Renal transplant Scleroderma renal crisis Calcium channel blockers Prostacyclin/analogues Endothelin receptor blockers Phosphodiesterase inhibitors Combinations therapy Imatinib Lung transplant Pulmonary hypertension Immunosuppressives (steroids, cyclophosphamide) Imatinib Lung transplant Interstitial lung disease Immunosuppressives (ATG, ALG and MMF) Autologous stem cell transplant Advanced stage multisystem disease