Scleroderma and Myositis J. Cush by sammyc2007

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									Scleroderma
Three major disease subsets: Based on extent of skin dz
 

Diffuse disease - skin abnormalities extending to the proximal extremities (AKA - PSS) Limited disease AKA "CREST" syndrome


Calcinosis, Raynauds, Esophageal dysmotility Sclerodactyly, Telangiectasias



Localized Scleroderma
Morphea: manifests as focal patches  Linear scleroderma: band-like (linear) areas of thickening. (Coup de Sabre)


Other causes of Tight Skin
 

Pseudosclerodactyly
 IDDM,

Hypothyroidism

Drugs: Tryptophan, bleomycin, pentazocine, vinyl chloride, solvents  Eosinophilic fasciitis  Overlap Conditions  Scleroderma-like conditions
Eosinophil myalgia syndrome (tryptophan) Porphyria cutanea tarda

ACR Systemic Sclerosis Preliminary Classification Criteria*


Major Criterion
 Proximal

Scleroderma



Minor Criteria
 Sclerodactyly  Digital

pitting or scars or loss of finger pad  Bibasilar pulmonary fibrosis
* One major and two minor required for diagnosis

Scleroderma: Onset
   
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80% females Age: 50% are < 40 yrs @ onset (20-50)


Incidence 20/million/year

Raynauds Swollen or puffy digits Loss of skin folds, no hair growth Digital pulp sores/scars Arthralgias >> Arthritis

Scleroderma A disorder of Collagen, Vessels
 



Etiology: unknown? Autoimmune disorder suggested by the presence of characteristic autoantibodies such as ANA, anticentromere and anti-SCL-70 antibodies. Pathology:
 




Early dermal changes lymphocytic infiltrates primarily of T cells Major abnormality is collagen accumulation with fibrosis. Small to medium-sized blood vessels, which show bland fibrotic change. Small thrombi may form on the altered intimal surfaces.
Cold Cold



Microvascular disease

Normal PSS

PSS - Clinical


Skin:
Skin thickening is most noticeable in the hands, looking swollen, puffy, waxy.  Thickening extends to proximal extremity, truncal and facial skin thickening is seen.  Raynaud's phenomenon is present.  Digital pits or scarring of the distal digital pulp




Musculoskeletal: Arthralgias and joint stiffness are common.
Palpable tendon friction rubs associated with an increased incidence of organ involvement.  Muscle weakness or frank myositis can be seen.


PSS - Clinical
Gastrointestinal: Esophageal dysmotility, dysphagia, malabsorptive or blind loop syndrome, constipation.  Renal: Kidney involvement is an ominous finding and important cause of death in diffuse scleroderma. A hypertensive crisis (AKA renal crisis) may herald the onset of rapidly progressive renal failure.


Pulmonary Manifestations of PSS
  

Dyspnea Pulmonary HTN only in CREST Interstitial fibrosis (fibrosing alveolitis)
High resolution CT vs Galium Scan  Major cause of death




RARE:
Pulmonary embolism  Pulmonary vasculitis


Cardiac Findings in PSS
Myocardial fibrosis  Dilated cardiomyopathy  Cor pulmonale  Arrhythmias  Pericarditis  Myocarditis  Congestive heart failure


Comparison CREST v. PSS
Feature
Calcinosis

Limited+ CREST
++

Diffuse+ PSS
+

Arthralgia/Arthritis
Pulmonary fibrosis

++
+

++++
++

Pulmonary HTN
Tend friction rubs

+
0

0
+++

Renal crisis Centromere Ab* Anti-Scl 70 Ab

0 +++ +

+ +/0 ++

* Ab: antibody + Relative percentages: +++++ 81-100%; ++++ 61-80%; +++ 41-60%; ++ 21-40%; + 1-20%

Treatment of Scleroderma
Localized: none  Raynauds: warmth, skin protection, vasodilator therapy  CREST: none  PSS: none proven


controversy  Cytoxan: for lung disease?  Steroids have no value

 Penicillamine:

Polymyositis Dermatomyositis
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   

F:M = 2:1 Acute onset Weakness (+ myalgia): Proximal > Distal Skeletal muscle: dysphagia, dysphonia Sx: Rash, Raynauds, dyspnea 65% elevated CPK, aldolase 50% ANA (+) 90% +EMG; 85% + muscle biopsy

Proposed Criteria for Myositis
1. 2.
3. 4. 5. 

Symmetric proximal muscle weakness Elevated Muscle Enzymes (CPK, aldolase, AST, ALT, LDH) Myopathic EMG abnormalities Typical changes on muscle biopsy Typical rash of dermatomyositis
PM Dx is Definite w/ 4/5 criteria and Probable w/3/5 criteria DM Dx Definite w/ rash and 3/4 criteria and Probable w/ rash and 2/4 criteria



Polymyositis Classification
Bohan & Peter 1. 2. 3. 4. 5.

Primary idiopathic dermatomyositis Primary idiopathic polymyositis Adult PM/DM associated with neoplasia Childhood Dermatomyositis (or PM)
 often associated with vasculitis

Myositis associated with collagen vascular disease

MYOPATHY: HISTORICAL CONSIDERATIONS
 

 
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Age/Sex/Race Acute vs. Insidious Onset Distribution: Proximal vs. Distal Pain? Drugs/Pre-existing Conditions Neuropathy Systemic Features

MYOPATHIIES
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Toxic/Drugs


Etoh, Cocaine, Steroids, Plaquenil, Penicilamine, Colchicine, AZT, Lovastatin, Clofibrate, Tryptophan, Taxol, Emetine
Coxackie A9, HBV, HIV, Stept., Staph, Clostridial, Toxoplasma, Trichinella



Infectious


   

Inflammatory Myopathies Congenital Neuropathic/Motor Neuron Disorders Endocrine/Metabolic

INFLAMMATORY MYOSITIS Immunopathogenesis
      

Infiltrates - T cells (HLA-DR+) & monocytes Muscle fibers express class I & II MHC Ags T cells are cytotoxic to muscle fibers t-RNA antibodies: role? FOUND IN <50% OF PTS Infectious etiology? Viral implicated HLA-B8/DR3 in childhood DM DR3 and DRW52 with t-RNA synthetase Ab

DERMATOMYOSITIS 5 Skin Features
1.

Heliotrope Rash: over eyelids
 Seldom seen in adults

2.

3.

4. 5.

Gottrons Papules: MCPs, PIPs, MTPs, knees, elbows V-Neck Rash: violaceous/erythema anterior chest w/ telangiectasias Periungual erythema, digital ulcerations Calcinosis

Calcinosis

DIAGNOSTIC TESTING


 

Physical Examiniation: Motor Strength (Gowers sign), Neurologic Exam Acute phase reactants unreliable Muscle Enzymes

  

CPK: elevated >65%; >10% MB fraction is possible Muscle specific- Aldolase, Troponin, Carb. anhydraseIII AST > LDH > ALT Beware of incr. creatinine (ATN) and myoglobinuria



Electromyogram: increased insertional activity, amplitude, polyphasics, associated neuropathic changes, incremental/decremental MU changes

DIAGNOSTIC TESTING


Muscle Biopsy (an URGENT not elective procedure)
Call the neuropathologist! 85% Sensitive.  Biopsy involved muscle (MRI guided)  Avoid EMG/injection sites or sites of trauma




 

Magnetic Resonance Imaging - detects incr. water signal, fibrous tissue, infiltration, calcification Investigational: Tc-99m Scans, PET Scans Serologic Tests: ANA (+) 60%, Abs against t-RNA synthetases

INFLAMMATORY MYOSITIS Biopsy Findings
  


 

Inflammatory cells Edema and/or fibrosis Atrophy/ necrosis/ degeneration Centralization of nuclei Variation in muscle fiber size Rarely, calcification

Anti-synthetase syndrome: ILD, fever, arthritis, Raynauds, Mechanics hands

MALIGNANCY & MYOSITIS
    



Controversial Reports range from 10-25% If real, men over age 50 yrs at greatest risk Common tumors: Breast, lung, ovary, stomach, uterus, colon 60% the myositis appears 1st, 30% neoplasm 1st, and 10% contemporaneously Avoid invasive, expensive searches for occult neoplasia

PM/DM Complications


 


 

PULMONARY Aspiration pneumonitis Infectious pneumonitis Drug induced pneumonitis Intercostal, diagphragm involvement Fibrosing alveolitis RARE:
 

    

CARDIAC Elev. CPK-MB Mitral Valve prolapse AV conduction disturbances Cardiomyopathy Myocarditis

Pulmonary vasculitis Pulmonary neoplasia

PM/DM Diagnosis
Symmetric progressive proximal weakness  Elevated muscle enzymes (CPK, LFTs)  Muscle biopsy evidence of myositis  EMG: inflammatory myositis  Characteristic dermatologic findings


INFLAMMATORY MYOSITIS Treatment
 

Early Dx, physical therapy, respiratory Rx Corticosteroids : 60-80 mg/day


80% respond within 12 weeks



Steroid resistant
Methotrexate  Azathioprine


 

IVIG, Cyclosporin, Chlorambucil: unproven No response to apheresis

PROGNOSIS

   

  

Poor in pts. with delayed Dx, low CPK, early lung or cardiac findings, malignancy Neoplasia in 10% of adults PT for muscle atrophy, contractures, disability Kids:50% remission, 35% chr active disease Adult < 20 yrs. do better than >55 yrs. Adults: Mortality rates betw. 28-47% @ 7 yrs. Relapses & functional disability are common Death: due to malignancy, sepsis, pulm. or cardiac failure, and complications of therapy

RHABDOMYOLYSIS






Injury to the sarcolemma of skeletal muscle with systemic release of muscle macromolecules such as CPK, aldolase, actin, myoglobin, etc Maybe LIFE-THREATENING: from hyperkalemia, met. acidosis, ATN from myoglobinuria Common causes: EtOH, Cocaine, K+ deficiency, infection, PM/DM, infection (clostridial, staph, strept), exertion/exercise, cytokines

INCLUSION BODY MYOSITIS
     



Bimodal age distribution, maybe hereditary Slow onset, progressive weakness Painless, distal and proximal weakness Normal or mildly elevated CPK Poor response to corticosteroids Dx: light microscopy may be normal or show CD8+ lymphs. Tubulofilamentous inclusion bodies on electron microscopy Role for amyloid?


								
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