FIFTH STAGE
INTERNAL MEDICINE
DR.FADHIL – LECTURE 8
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Anti-Phospholipid Antibody Syndrome
Patients who have thrombosis(arterial or venous) and/or recurrent miscarriages and
who also have persistently positive blood tests for antiphospholipid antibodies(APAs)
have the antiphospholipid syndrome(APS).
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APS - no associated rheumatic disease (50%)= primary APS
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APS - associated rheumatic disease present in 10% of SLE patients=secondary
APS
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aPL - antiphospholipid antibodies (no symptoms)
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CAPS - catastrophic APS ~ 238 worldwide reported cases
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APAs can be detected by several tests:
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*anticardiolipin test, which detects antibodies (IgG or IgM) that bind to
negatively charged phospholipid, cardiolipin.
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*the lupus anticoagulant test which detect changes in the ability of the blood
to clot in a test tube. This test act as a procoagulant factor inside the body.
False positive tests for syphilis that found in patients with SLE are actually
caused by APAs
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*the anti-B2-glycoproten1 test, which detects antibodies that bind B2-
glycoproten1, a molecule that interacts closely with phospholipids.
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A persistently positive test( i:e. positive on at least two occasions, 6 weeks or
more a part) in one or more of these assays is needed to diagnose APS.
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However, some people who test positive for APAs will never get APS, i:e. not all
APAs are harmful.
According to these facts, APS can be defined as a disorder that characterized by
any or all of the fallowing three manifestations in the setting of positive
antiphospholipid antibody tests:
1- recurrent arterial & or venous thrombosis
2- thrombocytopenia
3- recurrent spontaneous abortions
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ETIOLOGY:
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APAs are directly pathogenic, but the exact mechanism of action is unknown.
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The presence of other co-factors for the development of APS may explain why
subset of people can develop this disease than others . The most important co-
factor is B2-glycoprotien.
B
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-GLYCOPROTEIN I
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structure : 5 "sushi" domains
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synthesis : liver
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function : "in vitro" anticoagulant
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congenital deficiency : asymptomatic
CLINICAL FEATURES:
DEFENITIVE FEATURES
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- arterial thrombosis - venous thrombosis -thrombocytopenia
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-recurrent abortions
POSSIBLE FEATURES
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- hemolytic anemia
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- livedo reticularis
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- Leg ulcers
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- chorea
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- transverse myelitis
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- vasculitis
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- cardiac valvular malformations
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ANTIPHOSPHOLIPID SYNDROME. LIVEDO RETICULARIS:
CATASTROPHIC APS
Describes patients who present with multiple thromboses, positive APAs, & often life
threatening illness. Treatment requires cyclophosphamide& plasmapharesis
DIAGNOSIS:
• is made by clinical features & lab. evidence of APAs . the diagnosis should not
be made unless at least one of the major criteria of APS is present.
• APAs are of two types: anticardiolipin & Lupus anticoagulant. Any patient with
APS should be screened for SLE or other autoimmune diseases.
• Lupus anticoagulant results in prolonged partial thrmboplastin time, but PTT is
not a screening test for lupus anticoagulant.
TREATMENT:
• NO cure from APS & NO single treatment is estimated & the treatment is directed
into each manifestation.
• In patients with APS who have had one or more thrombosis, the recommended
treatment to prevent further thrombosis is long term anticoagulation with
warfarin.
• Pregnant ladies with APS are given oral aspirin and subcutaneous heparin earlier
in gestation to reduce the chance of abortion but pre-eclampsia and poor fetal
growth remain common. Thrombocytopenia often does not need treatment, but it
usually respond to steroids, IV Ig, danasol, splenectomy& immunosuppressive
agents
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SJOGREN'S SYNDROME
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IS a chronic immune mediated inflammatory disorder of exocrine glands&
other systemic features . The most common manifestations include
inflammation & destruction of lacrimal & salivary glands leading to dry
eyes(keratoconjunctivitis sicca or xerophalmia)& dry mouth(xerostomia).
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It associated with various autoantibodies& systemic features like interstitial
lung diseases, vasculitis & lymphoma. Patients considered to have secondary
Sjogren,s if they have another autoimmune disease such as SLE, RA,
Scleroderma, primary biliary cirrhosis & to have primary Sjogren's if they have
no underlying immune disease .
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It is a disease of both males &females, although females are common patients.
All races, ages ðnicities are affected.
DIAGNOSIS
DIAGNOSTIC CRITERIA
1- subjective & objective evidence of keratoconjunctivitis sicca & xerostomia
2- presence of at least one of the fallowing 4 autoantibodies:
• antinuclear antibodies, Rheumatoid factor, anti- Ro(SS-A)& anti-La(SS-B)
antibodies
3- exclusion of any disease that may mimic Sjogren's syndrome
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SCHIRMER TEST:
Normal
：
≥10mm/5min
BIOPSY
from involved salivary glands may demonstrate the characteristic findings
of focal lymphocytic infiltration of CD-4 T-cells which imply that cell mediated
immunity is essential in the pathogenesis of Sjogren's syndrome.
MANAGEMENT:
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Generally speaking the management of systemic manifestations is the same as
other autoimmune diseases & include steroids, antimalarials , &
immunosuppressive agents. For xerostomia ; artificial saliva& avoidance of
anticholinergic drugs. For xerophalmia we use artificial tears & eye glasses.
POLYMYOSITIS & DERMATOMYOSITIS
INFLAMMATORY MYOPATHIES
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Rare heterogeneous group of acquired diseases characterized by inflammatory
infiltrate of skeletal muscles. They are Potentially treatable.
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Bimodal age distribution in PM/DM
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Between 10-15 years in children
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Between 45-60 in adults
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Inclusion body
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More common after the age of 50
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Female predominance
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The etiology is unknown with variable genetic association. The commonest
forms are poliomyelitis, dermatomyositis& inclusion body myositis.
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Usually only skeletal muscles are affected. Sometimes, the myositis is focal(
orbital myositis).
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There is an increased incidence of malignancy in patients with
dermatomyositis(3 fold) , polymyositis(30% increase). Malignancy may be
apparent at the time of diagnosis or appears later.
THE CLASSIFICATION OF BOHAN ET AL(1977) IS AS FALLOWS:
Group1: Primary idiopathic polymyositis.
Group 2:primary idiopathic dermatomyositis.
Group 3:dermatomyositis(or polymyositis) associated with neoplasia.
Group 4: childhood dermatomyositis (or polymyositis) associated with vasculitis.
Group 5: polymyositis(or dermatomyositis) with associated collagen vascular
disease.
POLYMYOSITIS
symmetrical proximal muscle weakness usually of the lower extremities first. The
patient have difficulty in rising from a chair, climbing stair or lifting. Sometimes
associated with muscle pain. The onset is between 40-60 years& is gradual, but can
be insidious or explosive.
Fever, weight loss& fatigue are common. Respiratory & pharyngeal muscle
involvement with respiratory failure& aspiration can occur & considered an
emergency. Interstitial lung disease occurs in 30% & strongly associated with Jo-1
antibodies.
DERMATOMYOSITIS
the muscle manifestations are similar to those of polymyositis but occur in
combination with characteristic cutaneous manifestations:
Gottron's papules are violaceous plaques or papules, scaly, erythematosus on the
extensor surface of proximal & distal interphalangeal joints.
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DERMATOLOGIC MANIFESTATIONS
Heliotrope rash is a violaceous discoloration of eye lid with
periorbital edema. similar rashes occur on the upper back,
chest& shoulders('shawl' distribution). Fever ,weight
loss& arthralgia also occur.
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INVESTIGATIONS
• the diagnosis of IIM is suspected by typical history& physical examination.
Muscle enzymes such as creatine phosphokinase(CPK) & aldolase are markedly
elevated. The diagnosis is confirmed by muscle biopsy.
• Ideally open biopsy is optimal, but fine needle muscle biopsy may be adequate.
• Involved not atrophic muscle should be used. Commonly quadriceps or deltoid
muscle is used.
TREATMENT
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corticosteroids are the gold standard in the treatment of inflammatory
myopathies. 60 mg / day prednisolone is begun until CPK has returned to
normal or muscle strength is greatly improved . Occasionally, extremely high
dose IV corticosteroids are used for severely ill patients.
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Gradual tapering of drug is attempted according to clinical response . One
fourth to one third of patients require additional immunosuppressive drugs
such as methotrexate or azathioprine because of steroid resistance, intolerable
side effects or inability to taper steroids .
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Cyclophosphamide & cyclosporine also used but they have toxic side effects.
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Recently IV gamma globulin has proven effective in dermatomyositis . It works
by blocking deposition of complement fragments in muscle capillaries , thereby
prevents further injury. However, its long term efficacy is unknown & it is
highly expensive.
Thank you,,,