CONNECTIVE TISSUE DISORDERS

Shamsuddeen Alhassan
MBChB
 Introduction to CTDs
• The connective tissue diseases are a group of
chronic inflammatory disorders that involve
multiple body systems and exhibit wide
spectrum of clinical manifestations.
• Their aetiology is multifactorial, involving genetic
and environmental factors (exposure to sunlight,
viral infections, drugs (hydralazine, isoniazid).
• Although these diseases have different clinical
and pathological features but they share enough
characteristics to be considered overlapping
conditions.
 Systemic diseases of connective tissue
• Systemic lupus erythematosus (SLE)
• Rheumatoid arthritis
• Systemic sclerosis
• Sjögren’s syndrome
• Dermatomyositis, Myositis
 SYSTEMIC SCLEROSIS
• Systemic sclerosis is a generalized disorder of
connective tissue affecting skin, internal
organs and vasculature.
• It is characterized by sclerodactyly in
combination with Raynaud’s or digital
ischemia
• Peak age of onset is 40-50yrs
• Female preponderance is 3:1
Cont…
• It is subdivided into diffuse cutaneous
systemic sclerosis (DCSS; 30% of cases) and
limited cutaneous systemic sclerosis (LCSS;
70% of the cases.
• Many patients with LCSS have features which
are phenotypically grouped into CREST
syndrome (Calcinosis, Raynaud’s, Esophageal
involvement, Sclerodactyly and
Talengiectasia).
PATHOPHYSIOLOGY
• The cause of systemic sclerosis is poorly
understood, but there is an evidence for a
genetic component and association with
alleles at the HLA locus.
• DCCS is significantly more common in black
compared to white women
• Exposure to silica dust, vinyl chloride,
hypoxyresins and tricholoethylene can trigger
a systemic sclerosis-like disease.
Cont..
• There is clear evidence of immunological
dysfunction; T lymphocytes infiltrates 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 ischemia which is thought
to exacerbate the fibrotic process
CLINICAL FEATURES
• SKIN
-Non pitting edema of finger’s and flexor tendon sheaths.
-skin becomes shiny and taut, distal skin creases disappear
-erythema and tortuous dilation of capillary loops in the
nail-fold bed.
-face and the neck with thinning of the lips and radial
furrowing.
-involvement of 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’.
 RAYNAUD’S PHENOMENON
• This is a universal feature and can precede
other features by many years,
• Involvement of small blood vessels in the
extremities may cause critical tissue ischemia
leading to skin ulceration over pressure areas
• Localised areas of infarction and pulp atrophy
at the fingertips
MUSCULOSKELETAL
• Arthralgia
• Morning stiffness
• Flexor tenosynovitis
• Restricted hand function is due to skin rather
than joint disease.
• Muscle weakness and wasting can occur due
to myositis.
GASTROINTESTINAL
• Smooth muscle atrophy and fibrosis in the lower two-
thirds of the oesophagus lead to reflux with erosive
oesophagitis.
• Dysphagia and odynophagia may also occur.
• Involvement of stomach causes early satiety and outlet
obstruction
• Small intestine involvement may lead to malabsorption
due to bacterial overgrowth and intermittent bloating,
pain or constipation.
• Dilatation of large or small bowel due to autonomic
neuropathy may cause pseudo-obstruction with
nausea , vomiting, abdominal discomfort and
distention, often worse with food.
 PULMONARY INVOLVEMENT
• Pulmonary hypertension
• Progressive dyspnea
• Right heart failure and angina
• Fibrosing alveolitis mainy affects patients with
DCSS.
RENAL
• Malignant hypertension
• Renal failure
 INVESTIGATIONS
• Scleroderma is a clinical diagnosis but various
lab abnormalities are characteristic.
• ESR is usually elevated
• Raised level of IgG
• ANA is positive in about 70% of patients
 MANAGEMENT
• The focus of management is to ameliorate the
effects of the disease on target organs
• No treatments are available that halt or
reverse the fibrotic changes which underlie
the disease, but Corticosteroids and cytotoxic
drugs like methotrexate, cyclophosphamide,
and azathioprine are the mainstay of
treatment
• Raynaud’s syndrome and digital ulcers should
be treated by avoidance of cold exposures.
Supplement with calcium antagonists or
angiotensin II receptor blocker. Infusion of
epoprostenol may benefit severe digital
ischemia.
• Infection in ulcerated lesions should be
treated with antibiotics.
• Oesophageal reflux should be treated with
PPIs, and anti-reflux agents.
• Metoclopromide in patients with pseudo-
obstruction.
• Hypertension should be aggressively treated
with ACEIs
• Analgesics for joint involvement
• Lung transplant may be considered
MIXED CONNECTIVE TISSUE DISEASE
• This is an overlap condition in which there are
clinical features of SLE, systemic sclerosis and
myositis.
• It commonly present with synovitis and edema
of the hands in combination with Raynaud’s
phenomenon and muscle pain/weakness.
• Most patients have anti ribonucleoprotein
(RNP) antibodies but these can occur in SLE
without overlap features.
• Management focuses on treating individual
components of the syndrome.
SJÖGREN’S SYNDROME
• This is an autoimmune disorder of unknown
cause characterized by lymphocytic infiltration
of salivary gland and lachrymal glands leading
to glandular fibrosis and exocrine failure
• Typical age onset is between 40-50yrs
• Female preponderance 9:1
• The disease may be primary or secondary to
other autoimmune diseases.
 CLINICAL FEATURES
• Eye symptoms, keratoconjuctivitis sicca are
due to lack of lubricating tears.
• Conjunctivitis and blepharitis are frequent,
and may lead to filamentary keratitis due to
tenacious mucous filaments binding to the
cornea and conjunctiva.
• Oral involvement manifests as a dry mouth
and typically the patient needs water to
swallow food.
 INVESTIGATIONS
• The diagnosis can be established by Schirmer’s
tear test.
• ESR
• RF
• ANA
• Lip biopsy
 MANAGEMENT
• Treatment is symptomatic
• Lachrymal substitute such as hypromellose
should be used in during the day combination
with more viscous lubricating ointment at night.
• Soft contact lenses can be useful for corneal
protection in patients with filamentary keratitis.
• Artificial saliva and oral gels can be tried for
xerostomia but are not often effective
• Stimulation of saliva flow by sugar-free chewing
gum may be helpful.
Cont…
• Adequate post-prandial oral hygiene and
prompt treatment of oral candidiasis are
essential.
• Vaginal dryness is treated with lubricants such
as K-Y jelly.
POLYMYOSITIS AND DERMATOMYOSITIS
• Polymyositis is characterized by an
inflammatory process affecting the skeletal
muscle. Dermatomyositis describes the same
disease but with skin involvement.
• They are rare with incidence of 2-10 cases per
million/year.
• Polymyositis can occur in isolation with other
autoimmune diseases such as SLE, systemic
sclerosis and Sjögren’s syndrome
• The cause is unknown although there is
evidence for a genetic contribution.
 CLINICAL FEATURES
• Typical presentation of polymyositis is symmetrical
proximal muscle weakness usually affecting the
lower limb more than the upper limbs.
• Myositis is usually gradual over few weeks.
• Myositis is widespread but focal disease can also
occur like orbital myositis
• Affected patients report difficulty rising from a chair,
climbing stairs and lifting, sometime in combination
with muscle pain.
• Systemic features of fever, weight loss and fatigue
are common.
• Dermatomyositis presents similarly but in
combination with characteristic skin lesions.
These include Gotton’s papules, which are scaly
erythematous or violaceous psoriasiform plaques
occurring over the extensor surfaces of proximal
and distal IPJs and a violaceous (helioptre) rash on
the eyelid in combination with perorbital edema.
• Similar rashes occur on the upper back, chest and
shoulders (‘shawl’ distribution).
• Nailfold erythema.
 INVESTIGATIONS
• Muscle biopsy is a pivotal investigation and
shows a typical features of fibre necrosis,
regeneration and inflammatory cell infiltrate.
• Electromyography can confirm the presence
of myopathy and exudative neuropathy.
• MRI will identify areas of abnormal muscle for
biopsy.
• Serum levels of CK are usually raised.
 MANAGEMENT
• Oral corticosteroids (e.g prednisolone 40-
60mg daily) are the mainstay of initial
treatment but high dose of IV
methylprednisolone 1g/day for 3 days may be
required in patients with respiratory of
pharyngeal weakness.
• Some patients may need additional
immunosuppressive therapy, azathioprine and
methotrexate are drug of choice.