SYSTEMIC SCLEROSIS

 SSc is a multisystem disease characterized by widespread vascular dysfunction and variable

fibrosis of the skin and internal organs
 30-40 years of age
 Females > males

RISK FACTORS

 Infection : CMV, Parvo- B19, EBV

 Occupational exposure : silica, epoxy resins, PVC
 Toxic oil syndrome : rapseed oil
 Radiotherapy
 Drugs : bleomycin, pentazocine, cocaine

PATHOGENESIS

Complex and dynamic interplay among these three cardinal processes in genetically susceptible
individuals initiates and sustains the fibrotic process and tissue damage.
 Diffuse microangiopathy
 Inflammation and autoimmunity
 Visceral and vascular fibrosis in multiple organs

CLASSIFICATION

 Diffuse cutaneous SSc (dcSSc)

 Limited cutaneous SSc (lcSSc)
 SSc sine scleroderma : only internal organ involvement
 Environmentally-induced scleroderma
 Overlap syndromes : features of SSc coexist with elements of other rheumatic disorders

CLINICAL FEATURES

General features
- Fatigue
- Stiff joints
- Loss of strength
- Pain
- Sleep difficulties
- Skin discoloration

Vascular disease
 Raynaud’s phenomenon
- Most common
- Precedes skin changes by > 10 years
- DOC : CCB, ilpoprost
Skin involvement
- Early non specific : edema over face and extremities
- Late specific : shortening of fingers, claw hand defect, mask like face, microstomia
- DOC : d- penicillamine (antifibrotic)

 Limited SSc
- Restricted to face and distal to elbow
- Assoc. with : CREST syndrome (calcinosis, raynaud’s, esophageal dysmotility, sclerodactyly,
telengectasia)
- Screening antibody : ANA(Sn95%)
- Specific antibody : anti centromere antibody

 Diffuse SSc
- Proximal to elbow, trunk is involved
- Assoc. with : 1) lung -NSIP, Rx- steroids
2) PAH, Rx- iloprost
3) Renal crisis, Rx- ACE inhibitors
4) mononeuritis multiplex, Rx- steroids
- Screening antibody : ANA(Sn 95%)
- Specific antibody : anti topoisomerase-1

GI involvement
- Microstomia, xerostomia, reflux, strictures, baretts esophagus , gastroparesis, GAVE,
diarrhea, constipation, malabsorption, sphincter incompetence

Cardiac involvement
- Frequent in dcSSc>lcSSc
- Pericarditis, effusion, tamponade, heart block, arrhythmias

Musculoskeletal involvement
- Arthralgia/ arthropathy, Rx : NSAIDS
- Inflammatory myopathy, Rx : low dose glucocorticoids+/-immunosuppressive agents

Genitourinary involvement
- Erectile dysfunction, Rx : PDE4 inhibitors

Cancer
- Increased risk of lung cancer and esophageal adenocarcinoma
- SSc can also represent a paraneoplastic syndrome triggered by the anti tumour immune
response

DIAGNOSIS

1. Physical examination : look for the above signs and symptoms

2. Lab diagnosis :
- CBC and DC : reveal anemia due to malabsorption, iron deficiency or GI blood loss
- S. creatinine level : indicate renal dysfunction
 - Creatine kinase : elevated in patients with myopathy or myositis
- Urinalysis
- Serologic tests (auto antibodies) support the diagnosis if positive
- To rule out D/D : Rheumatoid factor, anti CCP, Lupus-assoc. antibodies (eg, anti-
double-stranded DNA and/or anti-Smith)

3. Evaluate internal organ involvement :

- HRCT (more Sn) is preferred to a CXR : pulmonary involvement
- PFT : presence or absence of a restrictive ventilatory defect or a decrease in the single
breath DLCO
- Doppler echocardiography : initial assessment for PAH
- Nuclear imaging, c MRI : abnormal myocardial perfusion/function
- N terminal pro BNP : primary cardiac involvement

MANAGEMENT

1. Organ based symptomatic therapy

2. Systemic immunosuppressive therapy due to increased risk of complications and organ failure in
patients with :
● diffuse skin involvement that is severe or progressive
● interstitial lung disease
● myocarditis
● severe inflammatory myopathy and/or arthritis
They reduce progression or severity of SSc complications.
Drugs used : cyclophosphamide, methotrexate, tocilizumab, MMF

3. These patients may be candidates for investigational therapies such as hematopoietic stem cell
transplantation.

4. Screening at routine intervals for the development of major organ complications, particularly
cardiac disease, ILD , PAH , and renal involvement.

PROGNOSIS

Risk factors associated with increased mortality :

- presence of extensive skin involvement

- cardiac and/or pulmonary involvement
- renal disease
- presence of anti-topoisomerase I antibodies and/or anti-Th/To antibodies
- male
- younger age at disease onset
- dcSSc>lcSSc