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Scleroderma and Myositis K. Dao

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Scleroderma and Myositis  K. Dao Powered By Docstoc
					     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
      Digitalpitting 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   Normal
                                Cold   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    10 yr
                              Sclerodactyly 79-84     47-75
                              Truncal         48-50   22-26




J Rheumatol 1988;15:276-83.
                  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                   Limited CREST                   Diffuse PSS
               Calcinosis                      ++                              +
          Arthralgia/Arthritis                 ++                           ++++
          Pulmonary fibrosis                   ++                            +++
           Pulmonary HTN                       ++                              +
          Tend friction rubs                    0                            +++
              Renal crisis                      0                              +
           Centromere Ab                      +++                            +/0
            Anti-Scl 70 Ab                      +                             ++
              Raynaud’s                     +++++                          +++++
            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
   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.   Symmetric proximal muscle weakness
2.   Elevated Muscle Enzymes (CPK, aldolase,
     AST, ALT, LDH)
3.   Myopathic EMG abnormalities
4.   Typical changes on muscle biopsy
5.   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.   Primary idiopathic dermatomyositis
2.   Primary idiopathic polymyositis
3.   Adult PM/DM associated with
     neoplasia
4.   Childhood Dermatomyositis (or PM)
       often associated with vasculitis and
        calcinosis
5.   Myositis associated with collagen
     vascular disease
       MYOPATHY: HISTORICAL
         CONSIDERATIONS
   Age/Sex/Race
   Acute vs. Insidious Onset
   Distribution: Proximal vs. Distal
   Pain?
   Drugs/Pre-existing Conditions
   Neuropathy
   Systemic Features
               DDX MYOPATHIIES
   Toxic/Drugs
       Etoh, Cocaine, Steroids, Plaquenil, Penicillamine,
        Colchicine, AZT, Statins, Clofibrate, Tryptophan,
        Taxol, Emetine
   Infectious
       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
    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

   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.   Gottrons Sign/Papules
     (pathognomonic): MCPs, PIPs, MTPs,
     knees, elbows
3.   V-Neck Rash: violaceous/erythema
     anterior chest w/ telangiectasias
4.   Periungual erythema, digital ulcerations
5.   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
       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
    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
                              Polymyositis: CD8+Tcells,
                              endomysial infiltration




Dermatomyositis: Humoral
response B cells, CD4+ T
cells;
perifascicular/perivascular
infiltration
     Autoantibodies in PM/DM
Ab          Freq (%)   Clinical Syndrome
ANA            50      Myositis
U1-RNP         15      SLE + myositis
Ku             <5      PSS + myositis
Mi2            30      Dermatomyositis
PM1            15      PSS – PM overlap
Jo-1           25      Arthritis+ ILD+ Raynaud
SS-B (La)      <5      SLE,Sjogrens, ILD, PM
PL-12,7        <5      ILD + PM
Anti-synthetase syndrome: ILD, fever, arthritis, Raynauds,
       Mechanics hands– association with Jo-1
      MALIGNANCY & MYOSITIS
   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 age-
    appropriate 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                     CARDIAC
 Aspiration pneumonitis
                               Elev. CPK-MB
 Infectious pneumonitis
                               Mitral Valve prolapse
 Drug induced
  pneumonitis                  AV conduction
 Intercostal, diaphragm        disturbances
  involvement                  Cardiomyopathy
 Fibrosing alveolitis
                               Myocarditis
 RARE:
      Pulmonary vasculitis
      Pulmonary neoplasia
     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
    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
    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

				
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