1. 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)

3. 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

4. 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

5. Scleroderma: Onset 80% females
Age: 50% are < 40 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

6. 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.
Small to medium-sized blood vessels, which show bland fibrotic change.
Small thrombi may form on the altered intimal surfaces.
Microvascular disease
Cold
Normal
Cold
PSS

7. 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.

16. 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.

20. 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

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

23. Arthralgia/Arthritis
Comparison CREST v. PSS
 Feature
Limited+ CREST
Diffuse+ PSS
 Calcinosis ++ +
 Arthralgia/Arthritis
 ++
 ++++
 Pulmonary fibrosis  +
 Pulmonary HTN  0
 Tend friction rubs
+++
 Renal crisis
 Centromere Ab*
 +++
+/0
 Anti-Scl 70 Ab
* Ab: antibody
+ Relative percentages: %; %; %; %; %

24. Treatment of Scleroderma
Localized: none
Raynauds: warmth, skin protection, vasodilator therapy
CREST: none
PSS: none proven
Penicillamine: controversy
Cytoxan: for lung disease?
Steroids have no value

25. Polymyositis Dermatomyositis
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

26. Proposed Criteria for Myositis
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

27. Polymyositis Classification Bohan & Peter
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

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

31. MYOPATHIIES Toxic/Drugs Infectious Inflammatory Myopathies Congenital
Etoh, Cocaine, Steroids, Plaquenil, Penicilamine, Colchicine, AZT, Lovastatin, Clofibrate, Tryptophan, Taxol, Emetine
Infectious
Coxackie A9, HBV, HIV, Stept., Staph, Clostridial, Toxoplasma, Trichinella
Inflammatory Myopathies
Congenital
Neuropathic/Motor Neuron Disorders
Endocrine/Metabolic

32. NONMYOPATHIC CONSIDERATIONS
Fibromyalgia/Fibrositis/Myofascial Pain Disorder
Polymyalgia Rheumatica
Caucasians, > 55 yrs, M=F
ESR > 100, normal strength, no synovitis RA
SLE
Adult Still's Disease

33. 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

34. DERMATOMYOSITIS 5 Skin Features
Heliotrope Rash: over eyelids
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

41. Calcinosis

43. 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

44. 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

45. INFLAMMATORY MYOSITIS Biopsy Findings
Inflammatory cells
Edema and/or fibrosis
Atrophy/ necrosis/ degeneration
Centralization of nuclei
Variation in muscle fiber size
Rarely, calcification

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

49. Autoantibodies in PM/DMAb
Freq (%)
Clinical Syndrome
ANA 50
Myositis
U1-RNP 15
SLE + myositis Ku
<5
PSS + myositis
Mi2 30
Dermatomyositis
PM1
PSS – PM overlap
Jo-1 25
Arthritis+ ILD+ arthritis
SS-B (La)
SLE,Sjogrens, ILD, PM
PL-12,7
ILD + PM

52. INFLAMMATORY MYOSITIS
NORMAL/NOT INVOLVED:
Face Uncommon
Renal
RES: LN, spleen, liver (enzymes from muscle)
NOT UNCOMMON
RA-like arthritis
Fever/chills/night sweats
Myalgias

53. 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

54. PM/DM Complications PULMONARY Aspiration pneumonitis
Infectious pneumonitis
Drug induced pneumonitis
Intercostal, diagphragm involvement
Fibrosing alveolitis
RARE:
Pulmonary vasculitis
Pulmonary neoplasia
CARDIAC
Elev. CPK-MB
Mitral Valve prolapse
AV conduction disturbances
Cardiomyopathy
Myocarditis

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

56. INFLAMMATORY MYOSITIS Treatment
Early Dx, physical therapy, respiratory Rx
Corticosteroids : mg/day
80% respond within 12 weeks
Steroid resistant
Methotrexate
Azathioprine
IVIG, Cyclosporin, Chlorambucil: unproven
No response to apheresis

57. 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. 7 yrs.
Relapses & functional disability are common
Death: due to malignancy, sepsis, pulm. or cardiac failure, and complications of therapy

58. 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

59. 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?

60. Inflammatory Myositis
Polymyositis (PM) and dermatomyositis (DM) are types of idiopathic inflammatory myopathy (IIM). IIM are characterized clinically by proximal muscle weakness
Etiology: There is now known etiology.
Demographics: PM is more common than DM in adults. Peak incidence occurs between 40 and 60 yrs. F:M 2:1
Muscles: Proximal muscle weakness, dysphagia, aspiration. respiratory failure or death.
Skin: Gottron's papules, heliotrope rash, "V" neck rash, periungual erythema, "Mechanic's hands", calcinosis
Dx: Muscle enzymes (CPK, aldolase), EMG, Biopsy
Rx: Steroids, MTX, Azathioprine, IVIG