Transcript File

Musculoskeletal disorders
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Systemic Connective Tissue Disorders
Inflammatory Joint diseases
Osteoarthritis
Fibromyalgia
Diseases of bone
SYSTEMIC CONNECTIVE TISSUE
DISORDERS
SYSTEMIC CONNECTIVE TISSUE
DISORDERS
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SLE
Scleroderma
Mixed CTD
Sjoren’s syndrome
Polymyositis and dermatomyositis
Systemic vasculitis
SYSTEMIC LUPUS ERYTHEMATOSUS
(SLE)
• SLE is a chronic autoimmune multisystem connective
tissue disease.
• In autoimmune diseases, the immune system attacks
the body’s cells and tissue, resulting in inflammation
and tissue damage.
• SLE most often affects the heart, joints, skin, lungs,
blood vessels, liver, kidney, and nervous system.
• The course of the disease is unpredictable, with
periods of illness (called flares) alternating with
remissions.
• Peak age: 2nd-3rd decade
• Female : male ratio =9:1
Etiology:
• Exact cause of SLE is unknown.
• The predisposing factors are:
1. Genetic predisposition
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Genes are located in the HLA region on chromosome 6
Mutations may occur randomly (de novo) or it may be
inherited
When triggered by environmental factors
2. Environmental factors like :
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UV rays(sunlight)
Drugs: Hydralazine , procainamide , Isoniazid , methyldopa and
chlorpromazipine, Penicillamine, sulfasalazine, lithium and
lovastin
Extreme stress
Viral infection
Pregnancy and puerperium
Pathogenesis:
• This is Multifactorial disorder in which there is
profound disturbance of immune regulation
• Defect of suppressor T lymphocytes is associated
with uncontrolled production of auto antibodies
and immune complexes
Inflammatory process in SLE may occur by the
two mechanisms:
1. Auto antibodies react with cell nuclei therefore
antigen-antibody reaction results in
inflammation.
2. Deposition of immune complexes in the tissues
causing vasculitis.
Clinical features:
• May involve one organ system at the onset
• Multisystem involvement
• Severity varies from mild and intermittent to
persistent and fluminant
• Exacerbations with intermittent remissions
• True remission with no symptoms and
requiring no therapy occur up to 20% cases
1. Systemic features:
• Fatigue, fever, anorexia and weight loss
2. Musculoskeletal manifestations:
• Arthralgia and non deforming Arthritis,
Myalgia
• Small joints of hands ,wrist and knee are
involved in symmetrical fashion
• Joint deformities are unusual and erosions
are rare
3. Skin lesion:
• Erythema on the cheeks of the face and across
the bridge of the nose Malar rash/Butterfly rash
is the characteristic of SLE. It is present in 50% of
cases and is photosensitive.
• Photosensitivity
• Loss of scalp hair
• Discoid lupus erythematous: Occurs in
20%,presents as circular erythematous lesions
with scaliness and telengectasia, scarring
causing disfiguring. Found in scalp, ears, face
and sunexposed areas of arms, back and chest
Butterfly rash
Malar rash
• Vasculitic skin lesions are purpura,
subcutaneous nodules, nail folds infarcts,
ulcer, urticaria and gangrene of digits
• Painful ulcers occurring in mouth and in nose
• Raynaud’s phenomenon: May be sever
enough to result in digital gangrene
Raynaud’s phenomenon:
Photosensitivity:
Discoid rash
4. Kidneys:
• Renal involvement ranges from insignificant
proteinuria to nephrotic syndrome and renal
failure
• Urinalysis may show hematuria and
proteinuria>0.5g/day, Renal biopsy show
types of glomerulonephritis responding to
steroids or not
• HTN may occur due to either nephrotic
syndrome or renal failure
5. CNS manifestations:
• Mild cognitive dysfunction, headache,
depression, psychosis, Focal infarcts, seizures,
aseptic meningitis
• Abnormal EEG and CSF shows elevated protein
6. Vascular changes:
• Thrombosis to vessel of any size
7. Pregnancy:
• Spontaneous abortion/stillbirth
8. Hematologic changes:
• Hemolytic anemia: Coomb’s positive
• Leucopenia
• Lymphopenia
• Thrombocytopenia
9. Cardiovascular manifestations:
• Pericarditis, Pericardial effusion, pericardial
tamponade, Myocarditis
• Valvular insufficiency
• SLE induced endocarditis called “Libman-sacks
syndrome”
10. Respiratory changes:
• Pleurisy, Pleural effusion, Lupus pneumonia
11.Gastrointestinal manifestations:
• Anorexia, nausea, diarrhea and vague
discomfort are common
• Vasculitis of intestine manifest as acute
crampy abdominal pain, vomiting and
diarrhea, Intestinal perforation can occur
12.Eye changes:
• Episcleritis
• Retinal vasculitis is serious manifestation,
blindness can develop over a few days.
DIAGNOSTIC CRITERIA FOR SLE
REVISED AMERICAN RHEUMATISM ASSOCIATION
1. Malar rash:
• Fixed erythema, flat or raised over the Malar
eminence
2. Discoid rash:
• Erythematous raised patches with adherent keratotic
scaling and follicular plugging, atrophic scarring may
occur
3. Photosensitivity:
• Skin rash due to unusual reaction to light
4. Oral ulcer:
• Oral and nasopharyngeal ulceration
5. Arthritis:
• Non erosive arthritis involving 2 or >2 peripheral
joints
• characterized by tenderness, swelling and effusion
6. Serositis:
• Pleuritis or Pericarditis
7. Renal disorder:
• Proteinuria>0.5g/day or
• cellular cast(RBC/WBC/Granular)
8. Neurological disorder:
• Seizures/psychosis in the absence of offending
drug/metabolic derangement
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Hematologic disorder:
Hemolytic anemia or
leucopenia<4000/mm or
Lymphopenia<1500/mm or
Thrombocytopenia <100,000/mm in the
absence of offending drugs
10.Immunologic disorder:
• Anti-DNA antibodies in abnormal titer or
• Anti-Sm antibodies or
• Positive phospholipid antibodies
11. Antinuclear antibodies:
• An abnormal titer of ANA by
immunofluorescence in absence of drugs
Diagnosis:
• Presence of 4 criteria at anytime during
course of disease.
• Specificity:98%
• Sensitivity:97%
LUPUS VARIANTS
1.CHRONIC DISCOID LUPUS ERYTHEMATOSUS(DLE):
• Benign variant of SLE in which skin involvement is often the only
feature although systemic abnormalities may occur with time.
• The rash appears on face as well defined erythematous plaque that
progress to scarring and pigmentation.
2. DRUG INDUCED SLE:
• Characterized by Arthralgia and mild systemic features, rashes and
Pericarditis, but often without involvement of kidneys and CNS.
• Often disappears after withdrawal of responsible drug.
• Hydralazine and procainamide are the common cause, others are
Isoniazid, methyldopa, Chlorpromazine, Alpha interferon and
Penicillamine
• All patients have ANA but Anti-dsDNA and hypocomplementaemia
are rare.
3. SLE AND PREGNANCY:
• SLE patients in remission are not likely to have
exacerbations during pregnancy, however women with
active SLE, especially those with renal disease, have
increased frequency of exacerbations of their disease.
• Pre-eclampsia is a frequent complication of pregnancy
• Fertility rates are normal but spontaneous abortion
occur in 10-30% of women .
• Disease flares in a small proportion, especially during
the first weeks of postpartum
Prognosis:
• Disease pursues a relapsing and remitting
course.
• 10 year survival rates are >85%
• In some patients there is severe impairment of
vital organs such as lungs,heart,brain or
kidneys
• Infection specially with opportunistic
organisms have become the number one
cause of death followed by active SLE, mainly
due to renal and CNS disease.
Poor prognostic factors:
• Hypertension
• High serum creatinine
• Anemia
• Hypoalbuminemia
• Hypocomplementaemia at the time of diagnosis
• Thrombocytopenia
• Severe CNS involvement
• Presence of antibodies against Phospholipids
 20% patients achieve remissions-transient
 Likelihood of remission increase with each decade after
diagnosis
 Increase morbidity
 Death due to: Renal failure and Thrombo-embolism
Investigations:
1. Blood:
• Normochromic Normocytic Anemia
• Leucopenia
• Thrombocytopenia
• Lymphopenia
2. ESR and C-reactive protein
• ESR is raised and co-relates with disease activity
• C-reactive protein is normal
3. Immunological findings:
• Antinuclear antibodies (ANA) =95%
• Anti-Double stranded DNA (Anti-dsDNA)=60%
• Anti-Sm antibodies=30%
• Anti Phospholipid antibodies
• RA factor
• LE cells
• Anti histone antibodies=>95%
• Serum complement level=Low
4.VDRL
5.Urinalysis
6. Serum creatinine
Treatment:
• There is no cure of SLE therefore
management plan is:
1. To control exacerbation
2. To suppress symptoms to an acceptable level
3. Treatment option depends upon severity of
disease.
1. NSAIDS:
• Mild disease with Arthralgia, arthritis, fever and mild
Serositis
2. Glucocorticoids:
• Systemic Glucocorticoids are reserved for patients with life
threating manifestations of SLE such as CNS or Renal
involvement, myocarditis, Pericarditis or significant
thrombocytopenia
• In active SLE with fever and pleurisy start Prednisolone 1-2
mg/kg orally in 2-3 divided doses
• After the controlling of disease only one morning dose is
given
• Thereafter the daily dose should be tapered .
• With remission of disease withdraw steroids after few weeks
or kept to maintenance level of around 10-15mg daily or
alternate day regimen
• In life threating, severely disabling patients
including those with proliferative
glomerulonephritis can be started with 3-5
days of 1g IV “Pulses” of Methylprednisolone
followed by maintenance dose of daily or
alternate day Prednisolone.
Steroid pulse therapy:
• Prednisolone 40-60mg/day
• Methylprednisolone 0.5-1 g/day
Cyclophosphamide pulse therapy:
• 500-750mg/m2 monthly and
• Monthly for every 6 months
• 3 monthly for 6 months then
• Every 6 months once for 2 years
ADR: Hemorrhagic cystitis, Bone marrow
suppression, Hepatotoxicity
3. Chloroquine:
• Useful in management of troublesome skin lesions or
Arthralgia that cannot be controlled with NSAIDS
• Dose of Hydroxychloroquine is 400mg daily
4. Immunosuppressive drugs:
• Drugs such as Azathioprine, Cyclophosphamide and
Chlorambucil are used in:
1. Patients with severe focal or diffuse proliferative
Glomerulonephritis not responding adequately to
corticosteroids.
2. Patients in whom maintenance dose of steroid is so high as
to cause severe side effects
3. Steroid resistant patients.
5. Immunomodulators:
• Mycophenolate mofetil
• Tacrolimus
Monitoring:
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Complete blood count:TLC,DLC,Hb,Platelet
Urine:Proteinuria,cast
ANA level
Anti-dS-DNA
SCLERODERMA
• This is a generalized connective tissue
disorder characterized by fibrosis and
degenerative changes in the skin , Blood
vessels and Visceral organs.
Etiology and incidence:
• Unknown , May be immunologically mediated
• Environmental risk factors : Silica dust, Vinyl
chloride, Resins
• F:M ratio=4:1
• Peak age of onset:30-50 years
Types of Scleroderma:
• Scleroderma is classified according to degree and
extent of skin thickening
1.Systemic scleroderma:
• Diffuse Cutaneous scleroderma
• Limited Cutaneous scleroderma
2.Localized scleroderma:
• Morphea
• Linear scleroderma
3.In combination of other connective tissue
disease:
• Overlap syndrome
• Mixed connective tissue disease.
1.Systemic Scleroderma:
Diffuse cutaneous scleroderma:
• It is characterized by the rapid development of symmetric skin
thickening or tightening of proximal and distal
extremity,face,and trunk.
• These patients are at greater risk for developing kidney and
other visceral involvement early in the course of disease.
Limited cutaneous scleroderma:
• It is characterized by symmetric skin thickening limited to the
distal extremities and face.
• It is also called as CREST syndrome. [Calcinosis, Raynaud's phenomenon,
Esophageal dysmotility, Sclerodactyly, and Telengectasia]
• Prognosis is better than diffuse variety because of much lower
frequency of internal organ involvement.
2.Localized scleroderma:
• It is limited to skin, subcutaneous tissue and
muscle without systemic involvement.
1.Morphea:
• Occurs as a single or multiple plaques of skin
indurations and skin discoloration which
evolve in sclerotic lesions
2.Linear scleroderma:
• It appears as a linear streaks or bands most
commonly on extremities and less frequently
on forehead, trunk or fronto-parietal scalp.
Clinical
features:
1.Raynaud’s phenomenon:
• Severe Raynaud’s phenomenon is usually the presenting complaint .
• It presents with three color changing, initially pallor, then blue due
to peripheral cyanosis and then red due to reactive hyperemia
along with tingling sensation.
2. Cutaneous changes:
a. Hand:
• Non pitting edema and indurations with restriction of movement
• Later skin becomes shiny with atrophy and ulcerations of the finger
tips
b. Face:
• In advanced cases the face may become taut and difficulty in
opening the mouth.
• Thinning and furrowing of the lips
3. Musculoskeletal:
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Arthralgia
Mild non-erosive inflammatory arthritis
Morning stiffness
Muscle weakness and wasting due to tissue atrophy and low
grade Myositis
• Restricted hand movement.
4. GI:
• Reflux oesophagitis
• Esophageal dysmotility
• Dysphasia and heart burn
• Small bowel can be involved, producing Malabsorption from
bacterial overgrowth due to dilatation and atony.
5. Respiratory:
• Pulmonary hypertension
• Lower lobe fibrosis leads to cyst formation and
honeycombing in advance disease.
6.Cardiovascular:
• Diffuse myocardial fibrosis with development
of arrhythmias
• Pericarditis , cardiomyopathy , heart block and
aortic valve lesion may occur.
7. Renal:
• Renal failure and malignant hypertension
Investigations:
1. Autoantibodies:
• Antinuclear antibody(ANA)
• Anticentromere antibody(ACA) is most commonly seen in
limited scleroderma
• Antibodies to Topoisomerase 1(Scl 70) called Anti-Scl 70 –
--30% with diffuse scleroderma, and
--60% with limited scleroderma
2. Radiography:
• X-ray chest
• X-ray hands
• Barium swallow
3. Blood: Normocytic Normochromic anemia
4. Urea and electrolytes
5. Urinalysis
Management:
General management:
• Regular monitoring to detect complications
with measurement of BP,Blood
counts,Urinaylysis and renal and pulmonary
function test
• Regular exercise to maintain flexibility of
extremities
• Avoidance of cold exposure,frequent use of
detergent and soap as they can cause dryness
of skin.
• Massaging of skin may be helpful
Specific management:
 Patients with Myositis and Alveolitis and arthritis:
• Corticosteroids : 40-60mg/day
• Immunomodulators like: Mycophenolate mofetil
and Tacrolimus
 Penicillamine: Reduce skin thickening and prevent
development of significant organ involvement.
Start with 250mg/day and increases at 1-3 month
interval up to 1.5g/d
 For Raynaud’s phenomenon: Nifidipine and
Prostacycline infusion
 ACE inhibitors are drug of choice in patients with
Renal crisis and Accelerated Hypertension.
POLYMYOSITIS AND
DERMATOMYOSITIS
Polymyositis:
• Disorder of the muscle in which the
pathological features are necrosis of muscle
fibers together with evidence of regeneration
and inflammation.
• It presents with proximal muscle weakness
and wasting
• When Polymyositis is accompanied by skin
rash, it is called dermatomyositis.
DERMATOMYOSITIS
• Autoimmune disease
1. Cutaneous:
• Gottron’s papule
• Heliotrope rash
• Abnormal nail fold capillaries
2. Musculoskeletal:
• Arthralgia
• Myositis: Proximal muscle weakness, pain
3. Systemic
• Fever, loss of weight
 Investigations:
• Creatinine kinase
• EMG
• Muscle biopsy
Gottron's papules, seen in dermatomyositis (an inflammatory disease
of the muscles and skin). Violet colored inflammation (violaceous
color) over the knuckles
This photograph demonstrates the sign "heliotrope eyelids" in
which the eyelids develop a brown (violaceous - rather than
red) color
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Management:
1. Steroid:
• Prednisolone
2.Immunosuppresive therapy:
• Azathioprine
• Methotrexate
3. Intravenous immunoglobulins
SJOGREN’S SYNDROME
SJOGREN’S SYNDROME
• Autoimmune disorder of unknown etiology
• Occurs as a result of chronic dysfunction of
exocrine glands and is characterized by:
 Dryness of mouth,eyes, and other areas
covered by mucus membranes
• Onset:40-50 years
• F:M=9:1
Clinical features:
 Salivary gland and lacrimal glands are mainly affected
1. Salavary gland enlargement
• Decrease salivary secretion—Dryness of mouth i.e Xerostomia
leading to difficulty in speaking and swallowing, and to severe
dental caries.There may be loss of taste and smell
2.Ocular:
• Decrease tear production
• Keratoconjunctivitis sicca– Results from inadequate tear
production caused by lymphocyte and plasma cell infitration
of lacrimal glands
3.Pancreatitis,Pleuritis,neuropsychiatric dysfunction and
vasculitis may be present.
4.Renal tubular acidosis and chronic interestitial nephritis may
also occur.
Investigations:
1. Autoantibodies:
• ANA
• Rheumatoid Factor
• Anti-Ro, Anti-La
2. Schirmer’s test
• To determine/demonstrate decrease tear
production
3. Raised ESR
4. Salivary gland biopsy
Management:
1.General
• Artificial tear drop
• Oral gel for shooting effect
2.Steroid :
• Prednisolone
3. Immunosuppressive:
• Azathioprine
• Methotrexate.
MIXED CONNECTIVE TISSUE
DISORDER
Mixed connective tissue
disease(MCTD)
 The condition is characterized by overlapping clinical features
suggesting :
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SLE
Scleroderma
Rheumatoid arthritis
Myositis
 These conditions should be associated with very high titers of
circulating autoantibodies to nuclear RNP,(Anti-nRNP)
 With time in many patients, the manifestations evolve to one
of the predominant disease such as scleroderma or SLE
Clinical features:
• Age:3rd-4th decade, F:M=4:1
• Raynaud’s phenomenon, Puffy hands, Arthralgia and myalgia
are common presenting features
• High grade fever, Polymyositis, Arthritis
• Sclerodermal changes are usually limited to distal extremities
• Some present with Butterfly rash and other features of SLE
• Deformities of hands similar to RA may present without
erosions
• Esophageal dysmotility is present causing dysphagia:70%
• Lung involvement: Pleurisy, Diffuse interstitial Pulmonary
fibrosis and Pulmonary Hypertension
• ESR and Muscle enzymes are moderately raised
Investigation:
• Anemia, Coomb’s test positive>60%
• Leucopenia, Thrombocytopenia
• Hypergammaglobinemia
• RA factor positive in >50%
Management:
• Depends upon predominant cause.