Systemic Sclerosis.pdf doctor maher tala

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1. SYSTEMIC SCLEROSIS
Prof. Dr. Maher A. AI-talah.
M.B.Ch.B. F.I.B.M.S

2. •SYSTEMIC SCLEROSIS
•previously called 'scleroderma‘ is a generalised
disorder of connective tissue affecting the skin,
internal organs and vasculature.
•The clinical hallmarkis the presence of Sclerodactyly
in combination with Raynaud's phenomenon or digital
ischaemia.
•The peak ageof onset is in the fourth and fifth
decades, and overall prevalence is 10-20 per 100 000
with a 4:1 female:maleratio.
•It occurs in individuals of all ages, from childhood to
the elderly, but it most frequently affects those
between the ages of 40 and 60 years.

3. •It is subdivided into diffuse cutaneous systemic sclerosis
(DCSS) and limited cutaneous systemic sclerosis (LCSS).
•Many patients with LCSS have features which are
phenotypically grouped into the 'CREST' syndrome
(Calcinosis, Raynaud's, oesophagealinvolvement,
Sclerodactyly, Telangiectasia).

4. •Aetiologyand pathogenesis
•The aetiologyis unknown,
•Environmental factors are important in isolated cases
that result from exposure to silica dust, vinyl chloride,
hypoxyresins and trichloroethylene.

5. •Clinical features and diagnosis
•Systemic sclerosis is predominantly a clinical diagnosis
based on the presence of sclerodactyly.
•Most patients are ANA-positive.
•30% of patients with diffuse disease and 60% with
limited disease have antibodies to topoisomerase 1
and centromererespectively.

8. •Cutaneous changes
•Raynaud's phenomenon is universal and may precede other
clinical features.
•The initial phase of skin disease is characterisedby non-pitting
oedemaof the fingers and flexor tendon sheaths.
•Subsequently, the skin becomes shiny and taut, and distal skin
creases disappear.

9. •
•The face and neck are usually involved next, with thinning
of the lips and radial furrowing.
•In some patients skin thickening stops at this stage.
•Skin involvement restricted to sites distal to the elbow or
knee (apart from the face) is classified as;
•'limited cutaneous disease' or CREST syndrome.

10. Typical facial appearance in the CREST syndrome

11. •Involvement proximal to the knee and elbow and on
the trunk is classified as 'diffuse cutaneous disease'.
•In the distal extremities, the combination of intimal
fibrosis and vessel wall inflammation may cause
critical tissue ischaemia, leading to skin ulceration
over pressure areas, localisedareas of infarction and
pulp atrophy at the fingertips.

12. •Musculoskeletal features
•Arthralgia, morning stiffness and flexor tenosynovitis
are common.
•Restricted hand function is due to skin rather than joint
disease and erosive arthropathyis uncommon.
•Muscle weakness and wasting are usually due to
myositis.

13. •Gastrointestinal features
•Gut involvement is common.
•Smooth muscle atrophy and fibrosis in the lower two-
thirds of the oesophaguslead to acid reflux with
erosive oesophagitis.
•Dysphagia and odynophagia (painful dysphagia) may
also occur.

14. •Gastroparesiswith early satiety and abdominal distention
is common.
•Gastric antral vascular ectasia (GAVE) in the antrum may
occur.
•These subepitheliallesions, reflecting the diffuse small-
vessel vasculopathyof SSc, are described as “watermelon
stomach” due to their endoscopic appearance.
•Patients with GAVE can have recurrent episodes of
gastrointestinal bleeding, resulting in chronic unexplained
anemia.

15. •Impaired intestinal motility may result in malabsorption and
chronic diarrhea secondary to bacterial overgrowth.
•Fat and protein malabsorption also can occur.
•Disturbed intestinal motor function can also cause intestinal
pseudoobstruction, with symptoms of nausea and abdominal
distension that are indistinguishable from those of delayed gastric
emptying.
•Colonic involvement may cause severe constipation, fecal
incontinence, gastrointestinal bleeding from telangiectasia, and
rectal prolapse.
•Although the liver is rarely affected, primary biliary cirrhosis may
coexist with SSc.

16. •Cardiac manefstations
•The endocardium, myocardium, and pericardium may be
affected separately or together.
•Manifestations include pericardial effusions, atrial and
ventricular tachycardias, conduction abnormalities, valvular
regurgitation, hypertrophy, and heart failure.
•Systemic and pulmonary hypertension and lung and renal
involvement may also impact on the heart.
•Pericardial effusions occur in over 15% of patients and, rarely,
may cause tamponade.

17. •pulmonary features
•There are two main types of significant pulmonary
involvement: ILD and PAH.
•Many patients with SScdevelop some degree of both
complications.
•Less frequent pulmonary manifestations of SScinclude
aspiration pneumonitis complicating gastroesophageal
reflux, pulmonary hemorrhage, obliterativebronchiolitis,
restrictive ventilatorydefect due to chest wall fibrosis and
spontaneous pneumothorax.

18. •The most frequent presenting respiratory symptoms—exertional
dyspnea, fatigue, and reduced exercise tolerance .
•Chronic dry cough may be present.
•Physical examination may reveal crackles at the lung bases.
Pulmonary function testing (PFT) is a sensitive method for
detecting early pulmonary involvement.
•The most common abnormalities are reductions in forced vital
capacity (FVC) or single breath diffusing capacity of the lung for
carbon monoxide (DLco).

19. •Approximately 15% of SScpatients have pulmonary arterial
hypertension(PAH).
•Patients with early PAH are generally asymptomatic.
•The initial symptom is typically exertional dyspnea and reduced
exercise capacity.
•With progression, angina, exertional near-syncope, and
symptoms and signs of right-sided heart failure appear.

20. •Renal features
•One of the main causes of death is hypertensive renal crisis,
characterisedby rapidly developing accelerated phase
hypertension and progressive renal insufficiency.
•Hypertensive renal crisis is much more likely to occur in dcSScl
than in lcSScl, and in patients with topoisomerase 1 and RNP
antibodies.

21. •Headache, blurred vision, and chest pain may accompany
elevation of blood pressure.
•Urinalysis typically shows mild proteinuria, granular casts, and
microscopic hematuria; thrombocytopenia and microangiopathic
hemolysis with fragmented red blood cells can be seen.
•Progressive oliguricrenal failure over several days generally
follows.
•Prompt aggressive intervention with short-acting ACE inhibitors
to achieve adequate blood pressure control before the onset of
renal failure results in improved prognosis.

22. •Investigations
•As SSclcan affect multiple organs, routine haematology, renal,
liver and bone function tests and urinalysis are essential.
•ANA is positive in about 95%.
•About 30% of patients with dcSSclhave antibodies to
topoisomerase 1 (Scl70).
•About 60% of patients have anticentromereantibodies and
this is a biomarker for lcSScland CREST syndrome.

23. •Chest X-ray, transthoracic echocardiography and lung function tests
are recommended to assess for interstitial lung disease and
pulmonary hypertension (low corrected transfer factor may
indicate early pulmonary hypertension).
•High-resolution lung CT is recommended if interstitial lung disease
is suspected.
•If pulmonary hypertension is suspected, right heart catheter
measurements should be arranged at a specialist cardiac centre.
•A barium swallow can assess oesophagealinvolvement.
•A hydrogen breath test can indicate small intestinal bacterial
overgrowth.

24. •Management Managementand prognosis
•Five-year survival is approximately 70%.
•For most patients, the focus of management is to ameliorate
symptoms and combat the effects of the disease on target
organs.
•In patients with severe dcSScl, encouraging results have been
obtained with autologous stem cell transplantation following
myeloablativetherapy with cyclophosphamide.

25. •Raynaud’s phenomenon and digital ulcers.
•Avoidance of cold exposure, If symptoms are persistent, calcium channel
blockers, losartan,fluoxetine, sildenafil can be effective.
•Courses of intravenous prostacyclin are used for severe disease and critical
ischemia.
•The endothelin-1 antagonist bosentanis licensed for treating ischaemicdigital
ulcers and digital tip tissue health can be maintained with regular use of
fucidin–hydrocortisone cream.

26. •Gastrointestinal complications.
•Oesophagealreflux should be treated with proton pump inhibitors
and anti-reflux agents.
•Rotating courses of antibiotics may be required for small intestinal
bacterial overgrowth , while metoclopramide or domperidonemay
help patients with symptoms of dysmotility/pseudo-obstruction.
•For advanced small bowel involvement with malabsorption,
supplementation of iron, calcium, and fat-soluble vitamins may be
required.
•Gastric antral vascular ectasias (i.e., watermelon stomach), which
are treated with laser photocoagulation as first-line therapy.

27. •Hypertension. Aggressive treatment with ACE inhibitors is needed,
even if renal impairment is present.
•Joint involvement. This may be treated with analgesics and/or
NSAIDs. If synovitis is present then therapy with MTX or other
cDMARDcan be of value.
•Progressive pulmonary hypertension. Early treatment with
bosentanis required. In severe or progressive disease, heart–lung
transplant may be considered.
•Interstitial lung disease. Cyclophosphamide is effective in slowing
progression of interstitial lung disease and similar results have
been observed with MMF. More recently the tyrosine kinase
inhibitor Nintedanib(150 mg twice daily) has shown efficacy in
slowing decline of lung function in dcSScl.

28. •Risk factors at presentation that associate with a poor prognosis
include;
•1-older age.
•2-diffuse skin disease.
•3-proteinuria.
•4-high ESR.
•5-a low gas transfer factor for carbon monoxide (TLCO).
•6-pulmonary hypertension.

29. POLYMYOSITIS AND DERMATOMYOSITIS
•disorders defined by the presence of muscle weakness
and inflammation.
•They can occur in isolation or in association with other
autoimmune diseases and both may be the presenting
features of a previously undiagnosed malignancy.

30. •The aetiologyis unknown.
•The most common clinical forms of (idiopathic
inflammatory myopathies) {IIM} are polymyositis,
dermatomyositisand inclusion body myositis.
•Usually only skeletal muscle is affected.
•Occasionally, the distribution is focal (e.g. orbital
myositis).

31. •Polymyositis
•The typical presentation is with symmetrical proximal muscle
weakness, usually affecting the lower extremities first.
•Patients report difficulty rising from a chair, climbing stairs and
lifting, sometimes in combination with muscle pain.
•The onset is usually between 40 and 60 years of age.

32. •Systemic featuresof …fever, weight loss and fatigue are
common.
•Respiratory or pharyngeal muscle involvement leading
to ventilatoryfailure/aspiration is ominous and requires
urgent treatment.
•Interstitial lung disease occurs in up to 30% of patients.

33. •Dermatomyositis
•The muscle manifestations are identical to polymyositis, but occur
in combination with characteristic cutaneous manifestations.
•Gottron'spapules are scaly erythematous/violaceousplaques or
papules occurring over the extensor surfaces of the proximal and
distal interphalangealjoints.
•The heliotrope rashis a violaceousdiscoloration of the eyelid in
combination with periorbitaloedema.

35. •Investigations
•Creatinekinase (CK)is usually raised and is a guide to
disease activity.
•However, a normal CK does not exclude the diagnosis,
particularly in juvenile myositis where only 70% of patients
have a raised CK at the time of diagnosis.

36. •Electromyography (EMG) may confirm the presence of
myopathy and exclude neuropathy.
•Muscle biopsy to look for the typical features of fibrenecrosis,
regeneration and inflammatory cell infiltrate.
•Occasionally, a biopsymay be normal, particularly if myositis is
patchy.
•MRIis a useful means of identifying areas of abnormal muscle
that are amenable to biopsy.

37. •Management
•Oral corticosteroids (e.g. prednisolone 40-60 mg daily) are the
mainstay of initial treatment.
•Patients with severe weakness or evidence of respiratory or
pharyngeal weakness may need methylprednisolone 1 g daily for
3 days.
•Although most patients have an initial response to steroids,
many will need additional immunosuppressive therapy,
especially if the disease relapses.

38. •Azathioprine and methotrexate are the initial agents of choice. If
these are ineffective or not tolerated, then ciclosporin,
cyclophosphamide, tacrolimusand intravenous immunoglobulin
are alternatives.
•If the patient fails to respond clinically to treatment, this may be
due to steroid-induced myopathyor the development of
inclusion body myositis.
•Further biopsy is indicated at this stage.
•If active necrosis and regeneration are present, then the disease
is still active, whereas the presence of type 2 fibreatrophy
suggests steroid myopathy.

39. •SJÖGREN'S SYNDROME
•This is an autoimmune disorder of unknown aetiology
characterisedby lymphocytic infiltration of salivary and
lachrymal glands, leading to glandular fibrosis and exocrine
failure.
•Age of onset is usually in the fourth and fifth decades with a
female:maleratio of 9:1.
•The disease may be primary or secondary in association with
other autoimmune disease such as RA, SLE, thyroiditis or
primary biliary cirrhosis.

40. •Clinical features
•The eye symptoms, termed keratoconjunctivitissicca, are due to a
lack of tears and lubrication.
•Conjunctivitis and blepharitis are frequent manifestations, and may
lead to filamentary keratitisdue to tenacious mucous filaments
binding to the cornea and conjunctiva.
•Oral involvement typically leads to the patient needing water to
swallow food, and there is a high incidence of dental caries.
•The disease is associated with a 40-fold increased lifetime risk of
lymphoma.

41. •FEATURES OF SJÖGREN'S SYNDROME
•Risk markers
••Age of onset 40-60
••F > M
••HLA-B8/DR3
•Common clinical features
••Keratoconjunctivitissicca
••Xerostomia
••Salivary gland enlargement
••Non-erosive arthritis
••Raynaud's phenomenon
••Fatigue

42. Less common features
•• Low-grade fever
•• Interstitial lung disease
•• Anaemia, leucopenia
•• hrombocytopenia
•• Cryoglobulinaemia
•• Vasculitis
•• Peripheral neuropathy
•• Lymphadenopathy
•• Lymphoreticularmalignancy
•• Glomerulonephritis
•• Renal tubular acidosis
•
•Autoantibodies frequently
detected
••Rheumatoid factor
••ANA
••SS-A (anti-Ro)
••SS-B (anti-La)
••Gastric parietal cell
••Thyroid
•Associated autoimmune disorders
••SLE
••Progressive systemic
sclerosis
••Primary biliary cirrhosis
••Chronic active hepatitis
••Myasthenia gravis

43. •Investigations
•Most patients will have an elevated ESR secondary to
hypergammaglobulinaemiaand one or more autoantibodies, of
which antinuclear antibody (ANA) and rheumatoid factor are the
most common.
•Siccacan be established by the Schirmertear test, which
measures flow of tears over 5 minutes using absorbent paper
strips placed in the lower lachrymal sac; a normal result is
greater than 6 mm of wetting.
•If the diagnosis is still in doubt, it can be confirmed by finding
focal lymphocytic infiltrate in the minor salivary glands on lip
biopsy.

44. •Management
•Artificial lubrication is the mainstay of symptomatic
treatment.
•Soft contact lenses can be useful for corneal protection in
patients with filamentary keratitis, and occlusion of the
lachrymal ducts is occasionally needed.
•Artificial saliva and oral gels can be tried for xerostomia,
but are often not effective.
•Stimulation of saliva flow by sugar-free chewing gum or
lozenges may be helpful.
•

45. •Adequate post-prandial oral hygiene and prompt treatment of
oral candidiasis are essential.
•Extraglandularand MSK manifestations may respond to
corticosteroidsand, if so, other immunosuppressive drugs such as
azathioprinecan be added for steroid-sparing effect.
•One of the most difficult symptoms to treat is fatigue; this is usually
due to non-restorative sleep (often because of xerostomia) and is
unresponsiveto steroids.

46. •The end