Transcript Chest Pain, SOB, Tachycardia

Scleroderma
Three major disease subsets: Based on extent of skin dz
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Diffuse disease - skin abnormalities extending
to the proximal extremities (AKA - PSS)
Limited disease AKA "CREST" syndrome
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Calcinosis, Raynauds, Esophageal dysmotility
Sclerodactyly, Telangiectasias
Localized Scleroderma
Morphea: manifests as focal patches
 Linear scleroderma: band-like (linear) areas of
thickening. (Coup de Sabre)
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Other causes of Tight Skin
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Pseudosclerodactyly
 IDDM,
Hypothyroidism
Drugs: Tryptophan, bleomycin,
pentazocine, vinyl chloride, solvents
 Eosinophilic fasciitis
 Overlap Conditions
 Scleroderma-like conditions
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Eosinophil myalgia syndrome (tryptophan)
Porphyria cutanea tarda
ACR Systemic Sclerosis
Preliminary Classification Criteria*
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Major Criterion
 Proximal
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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)
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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
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Etiology: unknown?
Autoimmune disorder suggested by the presence of
characteristic autoantibodies such as ANA, anticentromere and anti-SCL-70 antibodies.
Pathology:
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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.
Microvascular disease
Cold
Cold
Normal
PSS
PSS - Clinical
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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
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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.
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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.
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Pulmonary Manifestations of PSS
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Dyspnea
Pulmonary HTN only in CREST
Interstitial fibrosis (fibrosing alveolitis)
High resolution CT vs Galium Scan
 Major cause of death
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RARE:
Pulmonary embolism
 Pulmonary vasculitis
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Cardiac Findings in PSS
Myocardial fibrosis
 Dilated cardiomyopathy
 Cor pulmonale
 Arrhythmias
 Pericarditis
 Myocarditis
 Congestive heart failure
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Comparison CREST v. PSS
Feature
Limited+ CREST
Diffuse+ PSS
Calcinosis
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+
Arthralgia/Arthritis
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++++
Pulmonary fibrosis
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++
Pulmonary HTN
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0
Tend friction rubs
0
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Renal crisis
0
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Centromere Ab*
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+/0
Anti-Scl 70 Ab
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++
* 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
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 Penicillamine:
controversy
 Cytoxan: for lung disease?
 Steroids have no value
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
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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
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Primary idiopathic dermatomyositis
Primary idiopathic polymyositis
Adult PM/DM associated with
neoplasia
Childhood Dermatomyositis (or PM)
 often associated with vasculitis
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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
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Infectious
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Etoh, Cocaine, Steroids, Plaquenil, Penicilamine,
Colchicine, AZT, Lovastatin, Clofibrate, Tryptophan,
Taxol, Emetine
Coxackie A9, HBV, HIV, Stept., Staph, Clostridial,
Toxoplasma, Trichinella
Inflammatory Myopathies
Congenital
Neuropathic/Motor Neuron Disorders
Endocrine/Metabolic
INFLAMMATORY MYOSITIS
Immunopathogenesis
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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
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Seldom seen in adults
Gottrons Papules: MCPs, PIPs, MTPs,
knees, elbows
V-Neck Rash: violaceous/erythema
anterior chest w/ telangiectasias
Periungual erythema, digital ulcerations
Calcinosis
Calcinosis
DIAGNOSTIC TESTING
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Physical Examiniation: Motor Strength
(Gowers sign), Neurologic Exam
Acute phase reactants unreliable
Muscle Enzymes
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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
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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
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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
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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
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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
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PULMONARY
Aspiration pneumonitis
Infectious pneumonitis
Drug induced
pneumonitis
Intercostal, diagphragm
involvement
Fibrosing alveolitis
RARE:
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Pulmonary vasculitis
Pulmonary neoplasia
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CARDIAC
Elev. CPK-MB
Mitral Valve prolapse
AV conduction
disturbances
Cardiomyopathy
Myocarditis
PM/DM Diagnosis
Symmetric progressive proximal
weakness
 Elevated muscle enzymes (CPK, LFTs)
 Muscle biopsy evidence of myositis
 EMG: inflammatory myositis
 Characteristic dermatologic findings
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INFLAMMATORY MYOSITIS
Treatment
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Early Dx, physical therapy, respiratory Rx
Corticosteroids : 60-80 mg/day
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80% respond within 12 weeks
Steroid resistant
Methotrexate
 Azathioprine
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IVIG, Cyclosporin, Chlorambucil: unproven
No response to apheresis
PROGNOSIS
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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
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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
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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?