Systemic sclerosis is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. It is more common in females and there are three subtypes: limited cutaneous, diffuse cutaneous, and morphea. Complications can include pulmonary hypertension, interstitial lung disease, gastrointestinal issues, and renal crisis. Treatment involves managing symptoms, slowing disease progression, and treating complications aggressively. Scleroderma renal crisis, in particular, requires strict blood pressure control using ACE inhibitors.

1. Systemic sclerosis
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2. Definition; It is a chronic autoimmune disease condition of unknown
etiology characterized by increased
• fibroblast activity and fibrosis in a number of different organ
systems in the form of hardened,
• sclerotic skin and other connective tissues.
• It is 4 times more common in females.
There are three patterns of disease:
• 1) Limited cutaneous systemic sclerosis:
• Raynaud's may be first sign
• Scleroderma affects face and distal limbs predominately
• Associated with anti-centromere antibodies
• CREST syndrome is an older term for the limited cutaneous form.
• CREST syndrome is a subtype of limited cutaneous systemic
sclerosis: Calcinosis, Raynaud's
• phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia

3. Complications of CREST syndrome:
Malabsorption can develop in these patients secondary
to bacterial overgrowth of the sclerosed
• small intestine (dysmotility secondary to infiltration of
the intestinal wall with fibrous tissue).
• Also, unfortunately pulmonary hypertension is one of
the more common late complications seen
• in such patients.
• It is often difficult to distinguish between interstitial
lung disease and pulmonary hypertension as the
• cause of breathlessness in systemic sclerosis

4. • NB: Lung involvement is a frequent complication of systemic
sclerosis, and can be split into 2 main
• syndromes:
• 1- pulmonary vascular disorder evolving over time into relatively
isolated pulmonary
• hypertension
• 2- interstitial lung disease.
• 2) Diffuse cutaneous systemic sclerosis
• Scleroderma affects trunk and proximal limbs predominately
• Associated with scl-70 antibodies
• Hypertension, lung fibrosis and renal involvement seen
• Poor prognosis
• Whilst diffuse systemic sclerosis is associated with more severe and
rapid internal organ
• involvement it is also seen in the limited form.

5. • 3) Morphea (Localized Scleroderma) (without internal
organ involvement)
• tightening and fibrosis of skin
• May be manifest as plaques (morphoea) or linear.
• This is a well-defined oval to round plaque. (Like a painless
lesion to his left subcostal region,
• dry, indurated and slightly coarse to palpation).
• The pathogenesis is poorly defined.
• An autoimmune component is suggested by enhanced T
helper 2 (Th2) dependent interleukin 4
• (IL-4) activity, which in turn up regulates transforming
growth factor beta (TGF -beta). TGF-beta
• stimulates fibroblast production of collagen and other
extracellular matrix proteins.

6. Presentation:
• Typical patient is a young female (35-65); Male: female ratio of about 1:4; Prevalence about 10-20
per 100000
• in the population
• Onset: Initial symptoms are typically non-specific and include Raynaud’s phenomenon, fatigue, and
• musculoskeletal complaints.
• The first specific clue is skin thickening that begins as swelling or puffiness of the fingers and hands.
• The patient feels a progressive tightening of the skin and decreased flexibility.
• In diffuse SSC various degrees of hypo or hyper pigmentation may occur giving the skin a tanned or
• “salt and pepper” appearance.
• Limited SSc (L-SSc): Usually have RP for 1-10 years prior to onset; skin involvement is distal to the
• elbows and knees but may involve the face.
• Diffuse SSc (d-SSc): Short interval between onset of RP and skin involvement which includes the
trunk
• & extremities

7. Progression:
• As SSc progresses the skin becomes progressively tighter and
thicker. This stage may persist for one to
• three years, after which the skin tends to soften and either thins
(becomes atrophic and thinned, with
• tethering to underlying structures) or returns toward normal
texture. After this initial improvement
• the disease may be progressive.
• Constitutional Features: Fatigue may be prominent, weight loss due
to activity of the disease and GI
• involvement with anorexia.
• Functional Status: Reduced functional status with difficulties with
ADLs; Difficulty at work; Loss of
• libido - Erectile dysfunction in men is common; Depression in up to
50%

8. Review of systems:
• Vascular: Raynaud’s Phenomenon (RP): Present in 95% of patients with SSc vs 4%
of general
• population; In SSC, RP is associated with tissue fibrosis of the fingers, loss of the
digital pads, digital
• ulceration, and on occasion digital ischemia with amputation
• Musculoskeletal: Arthralgias and myalgias are one of the earliest symptoms; A
rheumatoid-like
• erosive polyarthritis is occasionally seen (<20%); Inflammation and fibrosis of the
tendon sheaths also
• lead to pain and restriction of movement with accompanying tendon friction rubs;
Muscle weakness
• and atrophy is a dominant problem in late SSc secondary to fibrosis, disuse,
contractures of fibrotic
• skin, along with malnutrition
• Mucocutaneous: Xerostomia and xerophthalmia
• Neurologic: Trigeminal neuralgia; Other entrapment neuropathies such as carpal
tunnel
• Cardiac: Pericardial effusions; Myocardial fibrosis with diastolic dysfunction;
Premature coronary
• artery disease

9. • Respiratory: Leading cause of mortality in SSc;
• (a) Interstitial Fibrosis: Occurs with diffuse disease (30-60%), anti-topoisomerase-1
antibodies (Scl-70),
• and FVC<75 early in the course of disease;
• (b) Pulmonary hypertension without fibrosis occurs in 20-25% of limited SSc
patients and less often in
• diffuse disease: Risk factors include long standing RP and limited SSc; Poor survival
- 90% were dead at
• 5 years; Pulmonary arterial pressures (PAP) >45 with right sided heart changes
correlate with
• catheterization in 90% of cases. Right heart catheterization should be done in all
cases to confirm the
• diagnosis.
• Gastrointestinal: Small oral aperture; Dental disease and oral sicca features;
Esophageal dysmotility
• with resulting GERD; Gastric ectasia (watermelon stomach); Pseudo obstruction
secondary to small

10. .
• Respiratory: Leading cause of mortality in SSc;
• (a) Interstitial Fibrosis: Occurs with diffuse disease (30-60%), anti-
topoisomerase-1 antibodies (Scl-70),
• and FVC<75 early in the course of disease;
• (b) Pulmonary hypertension without fibrosis occurs in 20-25% of limited
SSc patients and less often in
• diffuse disease: Risk factors include long standing RP and limited SSc; Poor
survival - 90% were dead at
• 5 years; Pulmonary arterial pressures (PAP) >45 with right sided heart
changes correlate with
• catheterization in 90% of cases. Right heart catheterization should be
done in all cases to confirm the
• diagnosis.
• Gastrointestinal: Small oral aperture; Dental disease and oral sicca
features; Esophageal dysmotility
• with resulting GERD; Gastric ectasia (watermelon stomach); Pseudo
obstruction secondary to small
• Renal : one of the main causes of death is hypertensive renal crisis ,
characterized by rapidly developing accelerated phase hypertension and
renal failure , much more likely to occur in DCSSCL

11. INVESTIGATIONS:
CBC: Thrombocytopenia and microangiopathic hemolysis (schistocytes) with
renal crisis.
• Urinalysis: Proteinuria with renal crisis
• Creatinine: May be elevated with renal crisis
• Elevated AST/ALT/ALP: Think PBC associated with L-SSc
• ANA: In majority of cases
• Anti-Topoisomerase-1 (Scl-70): Diffuse SSc associated with interstitial
pulmonary fibrosis
• Anti-centromere antibodies: Limited SSc
• Anti-Polymerase-III: Diffuse SSc associated with cardiac or renal disease
• Radiology: Soft-tissue calcification; Usually a non-erosive arthritis with
deformities secondary to
contraction of the overlying skin; Reported cases of erosive arthritis
Screening (yearly): Chest radiographs; ECG & echocardiogram; Pulmonary
function test

12. M.

13. management:
• Disease Modifying Interventions: Methotrexate -
Possible favorable outcome in skin; D-Penicillamine,
chlorambucil, and interferon-alpha have not been
fruitful
• Treatment of Skin Disease: Topical moisturizers; Treat
ulcers with anti-septic, antibiotic ointments,
and analgesics; Calcinosis - Can try colchicine
• Raynaud’s Phenomenon: Avoid cold and keep warm
(socks, hat, scarf, gloves); Stop smoking; Avoid
estrogen containing compounds; Calcium channel
blockers; Topical nitroglycerin paste; IV iloprost

14. .
• Gastrointestinal: Reduce caffeine and alcohol, stop
smoking, elevate head of the bed, avoid foods
which precipitate GERD, eat frequent small meals; Oral
antacids, H2 blockers, and proton pump
inhibitors; Metoclopromide, erythromycin, or
domperidone for dysmotility; Broad spectrum
antibiotics; Supplemental vitamins
• Cardiopulmonary: cyclophosphamide is effective in
slowing progression of interstitial lung disease and
similar result observed with MMF. More recently the
tyrosine kinase inhibitor nintedanib ( 150mg twice
daily has shown efficacy in slowing decline of lung
function in DCSSCL

15. Scleroderma Renal Crisis management:
• Control blood pressure: Discontinue any medications which may
worsen blood pressure; ACEInhibitors - Have improved survival
from 10% in 1 year to 90% in 5 years. Captopril is most commonly
used aiming to reduce blood pressure slowly. Dose 25 mg PO BID-
TID increasing to max 150 mg TID; Angiotensin receptor blockers -
Less effective than ACE (? Lack of bradykinin effect; Calcium channel
blockers; Dialysis and renal care; Consult nephrology; Continue ACE
during dialysis as persistent hyperreninemia may occur; Supportive
• Treatment: Consult cardiology if CHF is an issue; Oxygen; Careful
use of diuretics; Nitrates; Statins; Neurology involvement if
associated encephalopathy or seizures; Correct electrolyte
abnormalities
• Musculoskeletal: Physiotherapy - Early and aggressive to prevent
joint contractures; Acetaminophen; NSAIDs and COXIBs;
Methotrexate and corticosteroids for inflammatory myopathies

16. Poor Prognosis:
• Older age
• Diffuse skin disease
• Proteinurea
• High ESR
• Low gas transfer factor for carbon monoxide
• Pulmonary hypertension