Connective tissue Diseases

Dr Shaila Kabir
 Connective tissue diseases
• Connective tissue disease refers to a group of
disorders due to dysregulation of immune responses.
• Autoantibody production often directed at
components of the cell nucleus leading to widespread
tissue damage.
• May present with overlapping clinical features
involving the Joints, bone, cartilage, muscles, and
skin.
• They can also involve other organs and organ systems,
including the eyes, heart, lungs, kidneys,
gastrointestinal tract, and blood vessels.
• There are more than 200 disorders that affect the
connective tissue.
Autoimmune Disorders of Connective Tissue

• Systemic lupus erythematosus

• Systemic sclerosis
• Mixed connective tissue disease
• Sjögren’s syndrome
• Polymyositis and dermatomyositis
 Systemic Lupus Erythematosus
• SLE is the most common connective tissue
disease.
• Around 90% of affected individuals are
women
• The peak age at onset is between 20 and 30
years
• Diagnosis by Systemic Lupus International
Collaboration Clinics (SLICC) criteria
 SLICC* Classification Criteria for SLE
• Requirements: 4 criteria (at least 1 clinical &
1 laboratory criteria) or biopsy-proven lupus
nephritis with positive ANA or Anti-DNA

11 clinical criteria

6 immunological criteria

Systemic Lupus International Collaboration Clinics (SLICC)*

 Clinical criteria for Systemic Lupus
Erythematosus
1. Acute cutaneous Lupus: 6. Serositis
Malar rash, photosensitive 7. Renal involvement
rash. 8. Neurologic
2. Chronic cutaneous Lupus: 9. Haemolytic anaemia
Discoid rash.
10. Leukopenia
3. Oral ulcers or nasal ulcers
11. Thrombocytopenia
4. Non- scarring alopecia
5. Arthritis: Synovitis
involving 2 or more joints
Immunological criteria for Systemic Lupus
Erythematosus
1. ANA
2. Anti DNA
3. Anti Sm
4. Antiphospholipid Ab
5. Low complement (C3, C4, CH50)
6. Direct Coombs’ test (do not count in the
presence of haemolytic anaemia)
Management of Systemic Lupus Erythematosus

Patient Education
• About the nature of the illness, to control
symptoms and to prevent organ damage.
• Patients should be advised to avoid sun and
UV light exposure, and to employ sun blocks.
• Cardiovascular risk factors, such as
hypertension and hyperlipidaemia, should be
controlled
• Patient should be advised to stop smoking.
 Management of SLE
Mild disease restricted to skin and joints

• Analgesics and/or NSAIDs

• Hydroxychloroquine (200-400 mg daily)
• Short courses of oral steroids may be
required for rash, synovitis, pleurisy and
pericarditis
 Life-threatening disease
• Pulse methylprednisolone (500 mg-1 g i.v)
coupled
• with cyclophosphamide (2 mg/kg i.v.),
• repeated at 2-3 weekly intervals on 6-8
occasions, depending on the clinical response.
• Mesna (2-mercaptoethane sulfonate Na)is
given with bolus cyclophosphamide to reduce
the risk of haemorrhagic cystitis.
• Mycophenolate mofetil (MMF) with high-
dose steroids for renal involvement in SLE
 Systemic sclerosis, or scleroderma
• It refers to a chronic, progressive disorder of
connective tissue affecting the skin, internal
organs and vasculature.
• The peak age of onset is in the 4th & 5th
decades
• Overall prevalence is 10–20 per 100 000
• 4 : 1 female preponderance.
• It is characterised by hardening and tightening
of the skin, sclerodactyly in combination with
Raynaud’s and digital ischaemia.
 Scleroderma Types
Diffuse cutaneous systemic sclerosis (DCSS)
• DCSS: 30% of cases
• The prognosis is poor, with a 5-year survival of
approximately 70%.
• Features indicating a poor prognosis include older
age, diffuse skin disease, proteinuria, high ESR, a low
TLCO (gas transfer factor for carbon monoxide) and
pulmonary hypertension.
Limited cutaneous systemic sclerosis (LCSS)
• LCSS: 70% of cases
• Many patients with LCSS have features that are
phenotypically grouped into the ‘CREST’ syndrome:
(Calcinosis, Raynaud’s, oEsophageal involvement,
Sclerodactyly and Telangiectasia).
 Pathophysiology of systemic sclerosis
• The disorder occurs due to an accumulation or
overproduction of collagen in the tissues of the body
due to immunological dysfunction.
• Systemic sclerosis can be triggered by exposure to silica
dust, vinyl chloride, hypoxyresins and trichloroethylene.
• T lymphocytes, especially Th17 subtype, infiltrate the
skin and there is abnormal fibroblast activation, leading
to increased production of extracellular matrix in the
dermis, primarily type I collagen.
• This results in symmetrical thickening, tightening and
induration of the skin (sclerodactyly).
• Arterial and arteriolar narrowing occurs due to intimal
proliferation and vessel wall inflammation. Endothelial
injury causes release of vasoconstrictors and platelet
activation, resulting in further ischaemia, which is
thought to exacerbate the fibrotic process.
 Clinical Feature of systemic sclerosis
Skin
• Initially, there is non-pitting oedema of fingers and
flexor tendon sheaths.
• Subsequently, the skin becomes shiny and taut, and
distal skin creases disappear.
• This is accompanied by erythema and tortuous
dilatation of capillary loops in the nail-fold bed.
• Thinning of the lips and radial furrowing.
• Skin involvement restricted to sites distal to the elbow
or knee (apart from the face) is classified as ‘limited
disease’ or CREST syndrome
• Involvement proximal to the knee and elbow and on
the trunk is classified as ‘diffuse disease’.
 Clinical Feature of systemic sclerosis
Raynaud’s phenomenon
• Involvement of small blood vessels in the
extremities may cause critical tissue
ischaemia, leading to skin ulceration over
pressure areas, localised areas of infarction
and pulp atrophy at the fingertips.
Musculoskeletal features
• Arthralgia, morning stiffness and flexor
tenosynovitis are common.
• Restricted hand function is due to skin
tightening
• Muscle weakness and wasting can occur due
to myositis.
 Clinical Feature of systemic sclerosis
Gastrointestinal involvement Pulmonary involvement
• Smooth muscle atrophy and fibrosis • Pulmonary hypertension (LCSS) may
in the lower two-thirds of the presents with rapidly progressive
oesophagus lead to reflux with
erosive oesophagitis. dyspnoea , right heart failure and
• Dysphagia and odynophagia may angina,.
occur. • Fibrosing alveolitis mainly affects
• Early satiety and occasionally outlet patients with DCSS.
obstruction.
Renal involvement
• Recurrent occult upper
gastrointestinal bleeding in • One of the main causes of death is
‘watermelon’ stomach (antral hypertensive renal crisis.
vascular ectasia),
• Rapidly developing malignant
• Small intestine involvement may
lead to malabsorption & hypertension & renal failure.
intermittent bloating, pain or • It is common in DCSS.
constipation.
• Dilatation of large or small bowel
due to autonomic neuropathy may
cause pseudo-obstruction.
 Investigations for systemic sclerosis

• ESR : usually elevated

• IgG: raised levels
• CRP: tend to be normal unless there is severe
organ involvement or coexisting infection.
• ANA: positive in about 70% patients
• Antibodies to topoisomerase 1 (Scl-70): Positive in
about 30% of patients with DCSS
• Anticentromere antibodies: Positive in about 60%
of patients with CREST syndrome have
 Management of Scleroderma
Raynaud’s syndrome:
• Avoidance of cold exposure and use of mittens .
• Calcium antagonists, Intermittent infusions of prostacyclin may benefit severe
digital ischaemia.
• The endothelin 1 antagonist bosentan for healing of digital ulcers.
Oesophageal reflux:
• Proton pump inhibitors and anti-reflux agents.
• Antibiotics if bacterial overgrowth syndromes
• Metoclopramide or domperidone may help in pseudo-obstruction.
Hypertension:
• ACE inhibitors, even if renal impairment is present.
Joint involvement:
• Analgesics and/or NSAID.
• If synovitis is present, methotrexate can also be of value.
Pulmonary hypertension:
• Bosentan.
• Phosphodiesterase inhibitors (Sildenafil) can be used
• In late stage, heart–lung transplantation.
• Corticosteroids and cytotoxic drugs if the patients have myositis or fibrosing
alveolitis.