Inflammatory Myositis Presented by- Dr. Mohammad Rehan DNB Medicine SDMH Jaipur Moderator- Dr. Madhulika Sharma HOD (General Medicine)

1. InflammatoryMyositis
Dr. MohammadRehan

2. Contents
• Introduction
• History
• Classification
• Clinical Features
• Associated Conditions
• Pathogenesis
• Autoantibodies
• Antisynthetase syndrome
• Diagnosis
• Treatment
• Prognosis

3. Introduction
• Inflammatory Myopathies are sporadic disorders representing the
largest group of acquired and potentially treatable causes of skeletal
muscle weakness.
• Annual incidence ~ 1 in 100,000
• Women > Men , Polymyositis (PM) and Dermatomyositis (DM)
• Men > Women , Inclusion Body Myositis (IBM)

4. Age at onset for Inflammatory myopathies is different.
• PM > 18 years.
• DM affects both Juvenile population and Adulthood.
• IBM affects persons aged >50 years.

5. History
• In 1888 the first American biopsy documented polymyositis in ruling
out Trichinella.
• Heliotrope rash was first described in 1875 in France.
• In 1930 Gottron’s reported skin lesions .
• In 1967 the pathology of IBM was described.

6. Classification
• There is no internationally accepted classification system for
Inflammatory myopathies.
• For discussion purpose IM’s can be classified as :-
Polymyositis.
Dermatomyositis and Juvenile Dermatomyositis.
Inclusion Body Myositis.
Autoimmune Necrotising Myopathies.
Myositis associated with Collagen Vascular disorder.
Myositis associated with malignancy and Juvenile Dermatomyositis.

7. ClinicalFeatures
Polymyositis
• A rare, subacute inflammatory myopathy affecting adults and rarely
children.
• Progressive, symmetric proximal muscle weakness with sparing of
ocular and facial muscles.
• Pharyngeal and Neck Flexors, also involved causing dysphagia and
Head drop.

8. • Associated with Myalgia and Muscle tenderness in some cases
• In Advanced and Acute cases Respiratory muscles may be affected.
• Severe weakness if untreated leads to muscle wasting.
• Sensations and DTR’s remain intact.

9. ClinicalFeatures
Dermatomyositis
Subacute inflammatory myopathy with muscle weakness similar to
polymyositis with distinctive rash more often preceding the muscle
weakness.

10. DM:DermatologicManifestations
Heliotrope rash
• Periorbital violaceous erythema
with or without edema of eyelids
and periorbital tissue.
• Highly characteristic of DM

11. DM:DermatologicManifestations
Gottron’s Papules
• Violaceous flat
topped papules and
plaques over dorsal
aspect of
interphalangeal and
MCP joints
• Pathognomonic of DM,
seen in > 80%
patients with DM

12. DM:DermatologicManifestations
V- sign
• Macular violaceous
erythema over V-shaped
region of the neck and
upper chest.
• Sometimes rash is
pruritic.

13. DM:DermatologicManifestations
Shawl Sign
• Macular violaceous
erythema over
Nape,back and
shoulders.
• May show
photosensitivity

14. DM:DermatologicManifestations
Mechanic’s Hand
• Also considered
characteristic.
• hyperkeratosis,
scaling, and horizontal
fissuring of the palms
and fingers bilaterally.
• Can be a manifestation
of the Antisynthetase
syndrome.

15. DM:DermatologicManifestations
Nailfold Talengectasia
• Occur in 30 to 60 %
early in disease

16. AmyopathicandHypo-myopathic
Dermatomyositis
• Amyopathic DM : present with typical dermatological manifestations
of DM, with normal muscle strength, enzyme levels and EMG findings.
• Hypo-myopathic DM : Dermatological manifestations of DM with no
muscle weakness with mild elevation in Enzymes and Abnormal EMG &
Biopsy.

17. JuvenileDermatomyositis
Presents with clinical features similar to dermatomyositis with
following differences
 Age of onset ~ 7 years
 Less incidences of Malignancy and ILD.
 Increased risk for Vasculopathy, Lipodystrophy and calcinosis.
Associations: SOJIA ; Macrophage activation syndrome
 Less mortality.

18. InclusionBodyMyositis
• Symmetric or asymmetric weakness.
• Insidious onset.
• After 50 years, Male to female ratio of 3:1.
• Proximal and/or distal muscle involvement.
• Classically forearm flexors, finger flexors and Quadriceps.
• Facial and Pharyngeal muscles are more commonly involved than PM/DM.

19. Immune-MediatedNecrotizingMyopathy
• Subacute progressive proximal muscle weakness without a rash.
• Female to Male ratio 2:1.
• Generally develops more rapidly than with PM, and is markedly
severe.
• Associated myalgia and dysphagia can be seen.
• Associated with Paraneoplastic syndrome and Statin use.

20. ParaneoplasticNM
• Rare, rapid progression, association with Adenocarcinoma.
• Age > 40 years.
• Presentation in Fall or Winter.
• Antibodies against signal recognition particles (SRP) seen.
• Coexisting cardiomyopathy and ILD maybe present.
• Muscle Biopsy : Necrotic fibres infiltrated by macrophages and rare
T- cells

21. StatinInducedAutoimmuneNM(SANAM)
• Associated with statin use.
• Age ~ 46 to 89 years.
• Progress beyond 3 to 6 months after drug discontinuation.
• Require immunosuppresive therapy

22. AssociatedConditions
Systemic symptoms
e.g. fever, malaise ,wt. loss, arthralgia, Raynaud’s phenomenon
Joint contractures
mostly in DM and in children
Dysphagia
Cardiac
e.g. AV conduction defects, tachyarrythmias, DCMP, CHF

23. Interstitial lung diseases:
• Seen in 10-25% patients with PM/DM.
• Associated with Jo-1 antibodies.
 Malignancies:
• Risk increased in patients with DM only.
• Most common are ovarian, breast, colon cancer, melanoma and
non-Hodgkin lymphoma.
SC Calcifications
Arthralgias etc

24. AssociatedConditions
• Deforming arthritis of anti Jo-1
antibody patient.

25. Characteristics Polymyositis Dermatomyositis Inclusion Body
Myositis
Age at onset >18 yrs Adulthood and Childhood >50 yrs
Familial associations No No Yes, in some cases
Extramuscular
manifestations
Yes Yes Yes
Connective Tissue
Diseases
Yes Scleroderma and Mixed
CTD (Overlap Syndromes)
Yes in upto 20% of cases
Systemic AI Diseases Frequent Infrequent Infrequent
Malignancy No Yes in upto 15% of cases No
Drugs Yes Yes, rarely No
Parasites and Bacterias Yes No No
Viruses Yes Unproven Yes
FeaturesAssociatedwithInflammatory
Myopathies

26. Pathogenesis
• Both immune and non immune mechanism are
involved in pathogenesis.
• Immune mechanism involve T-cell, B-cells,Dendritic cells,
macrophages, cytokines and Antibodies.
• Non immune mechanisms involve endoplasmic reticulum stress ,
hypoxia and Autophagy.

27. ImmuneMechanism
• Immune Activators trigger
disease in myositis susceptibility
gene carriers.
• Environmental factors
may contribute

28. ImmuneMechanism
• Innate and Adaptive
responses are activated
in Lymph nodes

29. ImmuneMechanism
• Activated immune cells
enter general circulation,
and encounter with specific
antigen and penetrate
endothelia into local muscle

30. ImmuneMechanism
• In PM and IBM CD8+ Tcells
expressing perforin 1 and
Granzyme invade muscle fibres
expressing MHC 1 molecule
leading to muscle inflammation
and necrosis ( In IBM).

31. ImmuneMechanism
• In DM; CD4+ T cells ,
B-cells , Dendritic cells
and Macrophages
invade perivascular and
perimysial muscle
tissue.

32. MyositisSpecificAutoantibodies

33. Antisynthetasesyndrome
• Aminoacyl-tRNA synthetase is a cytoplasmic enzyme
involved in aminoacylation.
• The most common ARS is histidyl-RNAsynthetase,
also called Jo-1 (75%)

34. Antisynthetasesyndrome
• Myositis : Polymyositis or dermatomyositis
• Non-destructive polyarthritis of finger joints, wrists,
elbows or knees
• Fever in 80% of patients
• Mechanic’s hands : Thick cracked skin over the tips
and sides of the fingers
• Interstitial lung disease in over 70% of patients
• Raynaud’s phenomenon in 60% of patients

35. OtherMyositisSpecificAutoantibodies

36. Anti-PM-Sclantibodies
• Directed against a nucleolar macromolecular complex.
• Primarily polymyositis or dermatomyositis /scleroderma overlap.
• Strongly associated with HLA-DR3.
• Seen in 5-25% of patients with myositis

37. NonImmuneMechanism
HMGB1 : High mobility group protein B1

38. Diagnosis
• In 1975, Bohan and Peter used the following criteria for the diagnosis
and classification of PM and DM.
The Bohan and Peter Classification criteria
1. Symmetric proximal muscle weakness
2. Elevation of skeletal muscle enzyme levels.
3. Abnormal EMG results - Polyphasic, short, small motor unit potentials; fibrillation; positive
sharp waves; insertional irritability; and bizarre, high-frequency, repetitive discharges.
4. Muscle biopsy abnormalities -Degeneration/regeneration, perifascicular atrophy, necrosis,
phagocytosis, fiber size variation, and mononuclear inflammatory infiltrate
5. Typical skin rash of DM

39. DrawbacksofBohanandPetercriteria
• Case series and data developed from a single institution and based on
clinical observations.
• Only skin features were used to differentiate DM from PM.
• IBM was not recognized as a separate entity.

40. NewDiagnosticCriteria
• New diagnostic criteria considers :
1. Muscle Weakness.
2. Creatine Kinase
3. Electromyographic Findings.
4. Muscle biopsy.
5. Rash / Calcinosis.

41. MuscleWeakness
• In PM and DM there is progressive, symmetric proximal
muscle weakness with sparing of ocular and facial muscles.
• In IBM : Symmetric or asymmetric weakness, involving
the proximal and/or distal muscles classically forearm
flexors, finger flexors and quadriceps.

42. MuscleEnzymes
• In PM, Creatine Kinase is always elevated upto 5 – 50 times the ULN.
• In DM, CK is elevated upto 50 times the ULN, in 90% of patients.
While in others CK levels may be normal.
• In IBM, CK levels are elevated upto 10 times of UNL or
may be Normal.
• Necrotising Myopathy, CK is increased 10 times or more

43. EMGinMyopathies
• In acute myopathies EMG must be conducted about
3 weeks from the onset of symptoms to ensure good sensitivity.
• EMG of the muscle is done in two situations : at rest and at
voluntary activity.
• The Resting values also called spontaneous activity (not seen in
normal muscles) are of three types.
1.Fibrillations and Positive waves
2.High frequency discharges
3.Myotonic Discharges

44. EMGinMyopathies
• Fibrillations and Positive waves
These are small positive rhythmic electric potential typical of
denervation.

45. EMGinMyopathies
• High frequency discharges (Pseudomyotonic or Complex repetitive
discharges)
Rhythmic electric
potential with abrupt
beginning and end
typical of long standing
denervation.

46. EMGinMyopathies
Myotonic Discharges
• Electrophysiological representations of difficulty of relaxation
following voluntary muscle contraction.

47. EMGinMyopathies
• During Voluntary activity motor unit potentials (MUP) ie. are
recorded and MUP phase are studied
• ≥5, phases are called polyphasic.
• Acute myopathy: MUP are small in amplitude, short
duration and polyphasic.
• Chronic myopathy: MUP are large and of longer duration.

48. EMGinMyopathies
• EMG in IM show
• Increased insertional and spontaneous activity.
• Small-amplitude low-frequency fibrillation potentials
and positive sharp waves.
• Occasionally pseudomyotonic and complex repetitive
discharges indicating chronicity.
• Electrical myotonia : SANAM.
• Helpful in assessing relapse during treatment with
corticosteroids.

49. MusclebiopsyinPolymyositis
Endomysial inflammatory infiltrate (CD8+ MHC1 complexes) surrounding and
invading non-necrotic muscle fibers, with no vacuolization.

50. MusclebiopsyinDermatomyositis
Perifascicular and Perivascular infiltrates with perifascicular atrophy.

51. Inclusionbodymyositis
Basophilic rimmed vacuoles Vacuole filled with granules
Vacuolated muscle fibres infiltrated with CD8/MHC-1complexes. Beta-amyloid deposits and
cytochrome oxidase negative fibres may be seen.

52. NecrotizingMyopathy
Scattered necrotic myofibres with myophagocytosis in the paucity of T-lymphocytic
infiltration.

53. Polymyositis Dermatomyositis Inclusion Body
Myositis
Criterion Definite Probable
Myopathic Muscle
Weakness
Yes Yes Yes Yes, slow onset, early
involvement of distal
muscles, frequent falls
EMG Findings Myopathic Myopathic Myopathic Myopathic with mixed
potentials
Muscle Enzymes Elevated(upto
50 fold)
Elevated(upto
50 fold)
Elevated(upto 50 fold)
or Normal
Elevated(upto 10 fold)
or Normal
Muscle Biopsy Findings Primary
inflammation
with the
CD8/MHC-I
complex and no
vacuoles
Ubiquitous
MHC-I
expression
but
minimal
inflammati
on and no
vacuoles
Perifascicular,
perimysial, or
perivascular
infiltrates,
perifascicular
atrophy
Primary inflammation
with CD8/MHC-I
complex; vacuolated
fibres with -amyloid
deposits; cytochrome
oxygenase–negative
fibers; signs of chronic
myopathy

54. OtherInvestigations
• MRI-T1-weighted, T2-weighted, and sequences
using fat suppression techniques and short “tau” inversion recovery
(aka STIR), provides useful information to:
– diagnose myositis
– monitor treatment response,
– and identify a muscle site for biopsy.
• Muscle biopsy guided by MRI contains significantly more
inflammatory cells than the biopsy taken from MRI non-affected sites.

55. STIR imaging show
fibrosis or diffuse or
patchy signal symmetric
increase in the proximal
muscles and
intramuscular fascia
indicative of muscle
oedema due to
inflammation.

56. Other Investigations
Malignancy work up (for DM and PM)
• Chest , Abdomen and Pelvic CT scans
• Mammogram, Breast and Pelvic examination in women
• Colonoscopy in patients – Age >50 years or in those with
GI symptoms.

57. Other Investigations
In patients with IM:
• Chest X-ray, PFT and HRCT – especially in Jo1 positive
patients to rule out ILD.
• ECG- for myocardial involvement
• Echocardiogram- in patients with symptoms and signs of
heart failure.
• Video fluoroscopy- to objectively assess swallowing in
patients with dysphagia.

58. Treatment
Goals
• To eliminate inflammation.
• To restore muscle performance.
• To prevent chronic muscle disease.
• To prevent other organ system damage
• To regain quality of life

59. InitialTreatmentApproach

60. InitialTreatment
Approach Prednisone, 0.5-1 mg/kg/day.
for 2-4 wk
Concurrent with:

61. InitialTreatment
Approach Prednisone, 0.5-1 mg/kg/day.
for 2-4 wk
Concurrent with:
MTX, 15 mg/wk, to
Target dose of 25
mg/wk
Azathioprine, 2
mg/kgIBW
Twice daily
Mycophenolate mofetil,
500
mg
Twice daily. Increase by
500
mg/wk
until 1000 mg twice daily

62. InitialTreatment
Approach Prednisone, 0.5-1 mg/kg/day.
for 2-4 wk
Concurrent with:
MTX, 15 mg/wk, to
Target dose of 25
mg/wk
Azathioprine, 2
mg/kgIBW
Twice daily
Mycophenolate mofetil,
500
mg
Twice daily. Increase by
500
mg/wk
until 1000 mg twice daily
Taper prednisone every
2 wk
until completed:
60mg/d
40mg/d
30mg/d
25mg/d
20mg/d
17.5mg/d
15mg/d
12.5mg/d
10mg/d
7.5mg/d
5mg/d
2.5mg/d

63. Treatment
Initiate treatment with high dose corticosteroids and steroid sparing
agents.
• Prednisolone – Dose 0.5 to 1 mg/kg/day for 2- 4 weeks and then
taper off.
• Duration : 3 to 6 months.
• If no objective benefits after 3 months of high dose therapy switch
over to next immunosuppresive drug.
• Long term use of steroids may lead to steroid myopathy.

64. Treatment
• Azathioprine : Dose 2 mg/kg/day for 3 months.
• Before starting Azathioprine patient’s thiopurinemethyl- transferase
levels should be checked, otherwise it may lead to myelosuppression.
• Side Effects : Nausea, Loose stools, fever, and Liver toxicity

65. Treatment
• Methotrexate : Initial dose of 15 mg orally once weekly to a target
dose of 25 mg once weekly within 3 to 6 months.
• Folic acid supplementation to be given along.
• Side Effects : BM suppression, Liver toxicity, Pneumonitis.
• Should be used cautiously in patients with ILD

66. Treatment
• Mycophenolate Mofetil (MMF) : initial dose of 500mg BD to a dose of
1000mg BD over 4 weeks.
• Side Effects : Nausea, Loose stools, Leukopenia, elevation in liver
enzymes and Teratogenicity.
• Concurrent treatment : In Patients with ILD or on Prednisolone or
Immunosuppressive agents TMP-SMX prophylaxis is given for
Pneumocystis.

67. TreatmentMonitoring
• Within 2 to 4 weeks of starting MTX or azathioprine, a complete
blood cell count, liver enzyme function tests, and creatinine
measurement should be obtained once a month for 3 consecutive
months.
• Once a stable dosage is achieved, laboratory follow-up every 2 to 3
months thereafter is appropriate.
• DEXA scan is obtained at Baseline and Every year while patients
receive steroids.

68. SevereandRefractoryIM
• Myopathy refractory to conventional therapy or with severe organ-
threatening manifestations like ILD, severe dysphagia, notable weight
loss, severe rash, or weakness.

69. TreatmentofrefractoryIMorsevereorgan-
threateningIM
Methylprednisolone, 500-1000 mg/d IV (10-30 mg/kg/ day in JDM), for 1-3 days
IVIG, 1 g/kg (divided doses over 1-2 days) Repeated once monthly for 1-6 months
CPM, 0.6-1.0 g/m2 IV every 4 Wk or 1-2 mg/kg/day orally, for 3-12 months
Rituximab, 1000 mg repeated on day 15, Or 375 mg/m2 once weekly for 4 wk
CSA, 3.0-3.5 mg/kg/day

70. Treatment:IBM
• Treat patients of IBM with immunosuppression using the same
algorithms as used for DM and PM
• Goal is to suppress muscle inflammation, although the disease
typically is resistant to standardimmunotherapy.

71. Treatment:JDM
• Begin Prednisone at 2mg/kg to a max of 60mg/day.
• Subcutaneous MTX, at 15 mg/m2 once weekly is added at the onset.

72. SpecialConsiderations
Therapy for Skin disease.
• Avoid UV rays.
• Judicious use of Sunscreen with SPF of > 50.
• Topical steroids and Tacrolimus.
• Hydroxychloroquine at 200mg BD.
• For refractory cases MMF can be used.

73. SpecialConsiderations
Therapy for Calcinosis. Not satisfactory
• Drugs used are
• Diltiazem
• Colchicine
• Bisphosponates
• Intralesional Steroids.
• Abatacept
• Sodium Thiosulphate

74. Prognosis
• Older studies (before the availability of steroids) revealed a 50%
mortality from complications.
• Current estimates of mortality, excluding patients with malignancy, is
less than 10% at 5 years after initial diagnosis.
• DM has a favorable prognosis among all, IBM has least favorable
prognosis.

75. Poorprognosticfactors
• Older age
• Malignancy
• Delayed steroid treatment
• Dysphagia with aspiration
• ILD

76. TakeHomeMessage
• Inflammatory myopathies should be considered in all patients with
proximal muscle weakness.
• Diagnosis is made by Clinical findings, raised CPK, typical EMG and
muscle biopsynfindings.
• Treatment is by immunosuppression.
• Prognosis is generally good for DM and worst for IBM.

77. THANK YOU