Download Chest Pain, SOB, Tachycardia

Scleroderma
and
Inflammatory Myositis
Kathryn Dao, MD
Arthritis Center
February 16, 2006
Scleroderma
“Skleros-” = hard
“-derma” = skin
 Incidence 1-2/100,000 in USA
 Peak age of onset 30-50 y.o.
 Female:male 7-12: 1
 Disease manifestation is a result of host
factors + environment (concordance is
similar in monozygotic and dizygotic
twins)

Scleroderma
Three major disease subsets: based on extent of skin dz

Localized Scleroderma
Morphea: manifests as focal patches
 Linear scleroderma: band-like (linear) areas of
thickening. (Coup de Sabre)


Limited disease AKA "CREST" syndrome



Calcinosis, Raynauds, Esophageal dysmotility
Sclerodactyly, Telangiectasias
Diffuse disease - skin abnormalities extending
to the proximal extremities (AKA - PSS)
(Scleroderma sine scleroderma)
DDX of Tight Skin





Pseudosclerodactyly
 IDDM, Hypothyroidism
Drugs: Tryptophan,
bleomycin, pentazocine,
vinyl chloride, solvents
Eosinophilic fasciitis
Overlap syndromes
Scleredema
DDX of Tight Skin


Scleromyxedema
(popular mucinosis)
Scleroderma-like
conditions
Eosinophil myalgia
syndrome (tryptophan)
 Porphyria cutanea
tarda
 Toxic oil syndrome
 Nephrogenic fibrosing
dermopathy

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





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, anti-centromere and anti-SCL-70
antibodies.
Pathology:
 Early dermal changes lymphocytic infiltrates
primarily of T cells
 Major abnormality is collagen accumulation
with fibrosis.
Scleroderma
A disorder of Collagen, Vessels



Small to medium-sized
blood vessels, which
show bland fibrotic
change
Vasculopathy, NOT
vasculitis!
Small thrombi may
form on the altered
intimal surfaces.
Microvascular disease
Cold
Cold
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.

Skin Scores
Extent of skin involvment
predictive of survival:
% Survival at
5 yr
Sclerodactyly 79-84
Truncal
J Rheumatol 1988;15:276-83.
10 yr
47-75
48-50 22-26
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.
Scleroderma Renal Crisis

Risk Factors
 diffuse skin involvement
 rapid progression of skin thickening
 disease course < 4 years
 anti-RNA-polymerase III-antibodies
 newly manifested anemia
 newly manifested cardiac involvement
pericardial effusion
heart insufficiency
preceded high-dose corticoid therapy
 pregnancy

Am J Med 1984;76:779-786.
Scleroderma Renal Crisis



Microangiopathic hemolytic anemia
+Microscopic hematuria
Fatal before the introduction of ACE-I, CCB
 Survival without ACE-I 16% @ 1 year, with
ACE-I 45% at 5 years
Continue use of ACE-I even if dialysis
appears imminent
Ann Int Med 1990;113:352-357.
Pulmonary Manifestations of PSS





Dyspnea
Pulmonary HTN primarily in CREST
Ground glass (alveolitis)
Interstitial fibrosis (bibasilar)
High resolution CT vs Gallium Scan


Major cause of death
RARE:
Pulmonary embolism
 Pulmonary vasculitis

PFT’s in Systemic Sclerosis
Decreased DLCO is the Earliest Marker
 Increased A-a Gradient with Exercise
 Restrictive Pattern



VC,  FEV1/FVC
Pulmonary Vascular Disease

DLCO with Normal Volumes
Cardiac Findings in PSS
Myocardial fibrosis
 Dilated cardiomyopathy
 Cor pulmonale
 Arrhythmias
 Pericarditis
 Myocarditis
 Congestive heart failure
 Myocardial infarction (Raynaud’s)

Comparison CREST v. PSS
Feature
Calcinosis
Arthralgia/Arthritis
Pulmonary fibrosis
Pulmonary HTN
Tend friction rubs
Renal crisis
Centromere Ab
Anti-Scl 70 Ab
Raynaud’s
Limited CREST
++
++
++
++
0
0
+++
+
+++++
Diffuse PSS
+
++++
+++
+
+++
+
+/0
++
+++++
Telangiectasia
+++++
++++
Esophageal dysmotility
+++++
+++++
5 yr Survival
+++++
++++
+ Relative percentages: +++++ 81-100%; ++++ 61-80%; +++ 41-60%; ++ 21-40%; + 1-20%
Treatment of Scleroderma
Localized: none
 Raynauds: warmth, skin protection,
vasodilator therapy
 CREST: same as Raynauds
 PSS: none proven

 No
Value: Steroids, Penicillamine, MTX
 Cytoxan: for lung disease?
 Experimental: stem cell transplant, TNF-I
– Epoprostenol (Flolan): Prostacyclin
– Bosentan (Tracleer): Endothelin receptor antagonist
 Finger
ulcers: difficult; vasodilators, Abx
Inflammatory Myositis:
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 with 4/5 criteria and
Probable with 3/5 criteria
DM Dx Definite with rash and 3/4 criteria and
Probable w/ rash and 2/4 criteria
Polymyositis Classification
Bohan & Peter
1.
2.
3.
4.
Primary idiopathic dermatomyositis
Primary idiopathic polymyositis
Adult PM/DM associated with
neoplasia
Childhood Dermatomyositis (or PM)
 often associated with vasculitis and
calcinosis
5.
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
DDX MYOPATHIIES

Toxic/Drugs

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Infectious

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Etoh, Cocaine, Steroids, Plaquenil, Penicillamine,
Colchicine, AZT, Statins, Clofibrate, Tryptophan,
Taxol, Emetine
Coxsackie, HBV, HIV, Stept, Staph, Clostridium,
Toxoplasma, Trichinella
Inflammatory Myopathies
Congenital/metabolic myopathies
Neuropathic/Motor Neuron Disorders-MG, MD
Endocrine/Metabolic-hypothyroidism
Inclusion body myositis
NONMYOPATHIC
CONSIDERATIONS
 Fibromyalgia/Fibrositis/Myofascial

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Pain disorder
Polymyalgia Rheumatica
 Caucasians, > 55 yrs, M=F
 ESR > 100, normal strength, no
synovitis
CTD (SLE, RA, SSc)
Vasculitis
Adult Still's Disease
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

2.
3.
4.
5.
Seldom seen in adults
Gottrons Sign/Papules
(pathognomonic): MCPs, PIPs, MTPs,
knees, elbows
V-Neck Rash: violaceous/erythema
anterior chest w/ telangiectasias
Periungual erythema, digital ulcerations
Calcinosis
Why is it called a
heliotropic rash?
Calcinosis
DIAGNOSTIC TESTING



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
EMG: increased insertional activity,
amplitude, polyphasics, 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



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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
Polymyositis: CD8+Tcells,
endomysial infiltration
Dermatomyositis: Humoral
response B cells, CD4+ T
cells;
perifascicular/perivascular
infiltration
Autoantibodies in PM/DM
Ab
ANA
U1-RNP
Ku
Mi2
PM1
Jo-1
SS-B (La)
PL-12,7
Freq (%)
50
15
<5
30
15
25
<5
<5
Clinical Syndrome
Myositis
SLE + myositis
PSS + myositis
Dermatomyositis
PSS – PM overlap
Arthritis+ ILD+ Raynaud
SLE,Sjogrens, ILD, PM
ILD + PM
Anti-synthetase syndrome: ILD, fever, arthritis, Raynauds,
Mechanics hands– association with Jo-1
MALIGNANCY & MYOSITIS


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Higher association with DM, less common
with polymyositis
Common tumors: Breast, lung, ovary,
stomach, uterus, colon, NHL
60% the myositis appears 1st, 30%
neoplasm 1st, and 10% contemporaneously
Studies found 20-32% with DM developed
CA
Lancet 2001
Ann Int Med 2001.
Dermatomyositis and Malignancy

All adults with DM should have ageappropriate screening annually during
first several years after presentation:
 CXR
 Colonoscopy
or sigmoidoscopy
 PSA/prostate exam in men
 Mammogram, CA-125, pelvic exam,
transvaginal ultrasonography in women
PM/DM Complications
PULMONARY
 Aspiration pneumonitis
 Infectious pneumonitis
 Drug induced
pneumonitis
 Intercostal, diaphragm
involvement
 Fibrosing alveolitis
 RARE:


Pulmonary vasculitis
Pulmonary neoplasia
CARDIAC
 Elev. CPK-MB
 Mitral Valve prolapse
 AV conduction
disturbances
 Cardiomyopathy
 Myocarditis
Recap: 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



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

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Poor in pts. with delayed Dx, low CPK, early
lung or cardiac findings, malignancy
PT for muscle atrophy, contractures, disability
Kids:50% remission, 35% chronic active
disease
Adult < 20 yrs. do better than >55 yrs.
Adults: Mortality rates between 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), medications,
exertion/exercise, cytokines
INCLUSION BODY MYOSITIS


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Bimodal age distribution, maybe
hereditary
Males > females
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 and vacuoles with
amyloid. Tubulofilamentous inclusion
bodies on electron microscopy