1. Inflammatory myopathies
N. Movaffagh MD Rheumatologist

2. The inflammatory myopathies represent the largest group of acquired and potentially treatable causes of skeletal muscle weakness

3. They are classified into three major groups:
Polymyositis (PM)
Dermatomyositis (DM)
Inclusion body myositis (IBM)

4. CLINICAL FEATURES
prevalence of the inflammatory myopathies is estimated at 1 in
PM as a stand-alone entity is a rare disease
DM affects both children and adults and women more often than men
IBM is three times more frequent in men than in women, more common in whites than blacks, and is most likely to affect persons age >50 years

5. These disorders present as:
progressive and symmetric muscle weakness
except for IBM

6. Weakness of proximal muscles, such as difficulty in:
getting up from a chair
climbing steps
stepping onto a curb
lifting objects
combing hair

7. Weakness of distal muscles such as difficulty in:
buttoning a shirt, sewing, knitting, writing, are affected only late in the course of PM and DM, but fairly early in IBM

8. Ocular and Facial muscles are unaffected in PM and DM
Mild facial muscle weakness is common in IBM
Falling is common in IBM because of early involvement of the quadriceps muscle, with buckling of the knees

9. In all forms of IM :
Involvement of pharyngeal and neck-flexor muscles
are causing dysphagia or head drop
Respiratory muscles
(advanced and rarely in acute cases)
Severe weakness, if untreated, is almost always associated with muscle wasting

10. Sensation is normal
Tendon reflexes are preserved
(but may be absent in severely weakened or atrophied
muscles, especially in IBM)
Myalgia and muscle tenderness
usually early in the disease, and particularly in DM associated with connective tissue disorders

11. Weakness in PM and DM progresses subacutely period (weeks or months)
Weakness in IBM progresses very slowly (years)

13. HIV and HTLV-1
Drugs include:
penicillamine (dermatomyositis and polymyositis)
zidovudine (polymyositis)
statins (necrotizing, toxic, autoimmune myositis)
Protozoa (cestodes , nematodes) Tropical and bacterial myositis (pyomyositis)

14. Dermatomyositis
characteristic rash accompanying, or more often preceding, muscle weakness
heliotrope rash:
blue-purple discoloration on the upper eyelids with edema
Gottron’s sign:
erythema of the knuckles with a raised violaceous scaly
eruption
flat red rash on the face and upper trunk .

16. Erythematous rash on knees, elbows, malleoli
V sign
Erythematous rash on neck and anterior chest
shawl sign
The erythematous rash on back and shoulders
may worsen after sun exposure

18. shawl sign

19. In some patients, the rash is pruritic, especially on the scalp, chest and back
Dilated capillary loops at the base of the fingernails are also characteristic
The cuticles may be irregular, thickened, and distorted

21. lateral and palmar areas of the fingers may become rough and cracked, with irregular, “dirty” horizontal lines, resembling mechanic’s hands.

22. Mechanic’s hand

23. The weakness can be mild, moderate, severe enough
to lead to quadriparesis

24. DM sine myositis
The muscle strength appears normal but in muscle biopsy significant perivascular and perimysial inflammation is often seen

25. Polymyositis A subacute inflammatory myopathy
There are not any of the following:
rash, involvement of the extraocular and facial muscles
family history of a neuromuscular disease
history of exposure to myotoxic drugs or toxins
endocrinopathy
neurogenic disease
muscular dystrophy
biochemical muscle disorder

26. As an isolated entity, PM is a rare disorder
more commonly, PM occurs in association with :
Systemic autoimmune
Connective tissue disease
Known viral or bacterial infection

27. Inclusion Body Myositis
Most common of the IM in patients ≥50 years
Weakness and atrophy of the distal muscles
especially foot extensors & deep finger flexors
(may be a clue to early diagnosis)

28. Inclusion Body Myositis
weakness and atrophy can be : Asymmetric and involve:
quadriceps, iliopsoas triceps, biceps, finger flexors

29. Inclusion Body Myositis
Dysphagia is common
episodes of choking
Normal Sensory examination
mildly diminished vibratory sensation at the ankles
pattern of distal weakness
which superficially resembles motor neuron or peripheral nerve disease
Disease progression is slow
familial inflammatory IBM

30. Hereditary-IBM(h-IBM)
Non inflammatory myopathies
recessive, and less frequently dominant
A subset of h-IBM that spares the quadriceps
muscles in Iranian Jews and many ethnic groups

31. ASSOCIATED CLINICAL FINDINGS
Extramuscular Manifestations
Association with Malignancies
Overlap Syndromes

32. Extramuscular Manifestations
1. Systemic symptoms
2. Joint contractures
3. Dysphagia and gastrointestinal symptoms
4. Cardiac disturbances
5. Pulmonary dysfunction
6. Subcutaneous calcifications
7. Arthralgias, synovitis

33. Systemic symptoms, such as fever, malaise, weight loss, and Raynaud’s phenomenon
2. Joint contractures, mostly in DM and especially in children
Dysphagia and gastrointestinal symptoms, especially in DM and IBM

34. 4. Cardiac disturbances:
Atrioventricular conduction defects, Tachyarrhythmias Dilated cardiomyopathy low ejection fraction Congestive heart failure

35. Pulmonary dysfunction, due to:
weakness of thoracic muscles
ILD
drug-induced pneumonitis (e.g methotrexate)

36. Arthralgias, synovitis, or deforming arthropathy with subluxation in the interphalangeal joints, which can occur in some patients with DM and PM who have Jo-1 antibodies

37. Association with Malignancies
the incidence of malignant conditions appears
to be specifically increased only in patients with DM
The most common tumors associated with DM:
ovarian cancer
breast cancer
Melanoma
colon cancer
non-Hodgkin’s lymphoma

38. A complete annual physical examination with pelvic ,breast(mammogram, if indicated) rectal examinations (with colonoscopy according to age and family history)
urinalysis; complete blood count; blood chemistry tests; and a chest film

39. In Asians, nasopharyngeal cancer is common
Careful examination of ENT is indicated
If malignancy is clinically suspected, screening with a whole-body positron emission tomography (PET) scan should be considered

40. Overlap Syndromes
DM with manifestations of systemic sclerosis or mixed connective tissue disease
Such as sclerotic thickening of the dermis, contractures, esophageal hypomotility, microangiopathy and calcium deposits

41. overlap syndrome of DM and systemic sclerosis may have a specific ANA, anti-PM/Scl

42. PATHOGENESIS various autoantibodies (MHC) genes
T cell–mediated myocytotoxicity
complement-mediated microangiopathy

43. Autoantibodies and Immunogenetics
antinuclear antibodies
antibodies to cytoplasmic antigens ,against ribonucleoproteins(antisynthetases& anti-signal-recognition particles)
antisynthetases directed against the histidyl-transfer RNA synthetase( anti-Jo-1)

44. Immunopathologic Mechanisms in DM
In DM, humoral immune mechanisms
are implicated, resulting in a microangiopathy and
muscle ischemia
Bcells ,CD4 T cells, plasmacytoid dendritic cells,and macrophages in Endomysiom
Relative absence of lymphocytic invasion of nonnecrotic muscle fibers

45. DM Activation of the complement C5b-9
membranolytic attack complex(critical early event)
release of proinflammatory cytokines and chemokines
induces expression of vascular cell adhesion molecule
facilitates migration of activated lymphoid cells to the perimysial and endomysial spaces

46. Immunopathogenesis of DM

47. DM Reduced numbers of endomysial capillaries, ischemia,
The remaining capillaries often have dilated lumens in response to the ischemia
perifascicular atrophy reflects the endofascicular
hypoperfusion

48. PM, IBM In PM and IBM, a mechanism of T cell–mediated cytotoxicity
CD8 T cells, along with macrophages, initially surround and eventually invade and destroy healthy, non necrotic muscle fibers that express class I MHC
The CD8/MHC-I complex is characteristic of PM and IBM

49. muscle damage in PM and IBM

50. IBM
possibility B cells and the humoral immune system might also play a role in IBM

51. Expression of cytokines and upregulation of MHC class I by the muscle fibers activation of nuclear factor κB (NF-κB), leading to further cytokine activation

52. Association with Viral Infections and the Role of Retroviruses
Coxsackie viruses, influenza, paramyxoviruses,
mumps ,CMV,EBV, have been indirectly associated with myositis
The best evidence of a viral connection in PM
and IBM is with the retroviruses

53. Some individuals infected with HIV or with HTLV-1 develop PM or IBM
Histologic findings are identical to retroviral-negative PM or IBM

54. AZT-induced myopathy, which generally improves when the drug is discontinued
It is a mitochondrial disorder characterized histologically by “ragged-red” fibers

55. GLOBAL ISSUES PM more often in Asia and southern Europe
IBM North America, northern Europe, Australia
Pyomyositis and parasitic myositis tropics

56. DIFFERENTIAL DIAGNOSIS
Subacute or Chronic Progressive Muscle Weakness
Acute Muscle Weakness
Myo fasciitis (The most common form is eosinophilic
Myofasciitis)
Hyper acute Necrotizing Fasciitis/Myositis (Flesh-Eating Disease)
Drug-Induced Myopathies
Necrotizing Autoimmune Myositis

57. Necrotizing Autoimmune Myositis
acute or subacute onset of symmetric muscle weakness
CK is typically extremely high
interstitial lung disease and cardiomyopathy may be present
may develop after a viral infection
in association with cancer
in patients taking statins
muscle biopsy demonstrates necrotic fibers infiltrated by macrophages but only rare, if any, T cell infiltrates.
muscle

58. Necrotizing Autoimmune Myositis
Some patients have antibodies against signal recognition particle (SRP)
The muscle biopsy demonstrates necrotic fibers infiltrated by macrophages but only rare, if any, T cell
Muscle MHC-I expression is only slightly
capillaries may be swollen with hyalinization
Most patients respond to immunotherapy, but some are resistant.

59. DIAGNOSIS
The clinically suspected diagnosis of PM, DM, IBM is confirmed by :
serum muscle enzymes
EMG findings
muscle biopsy

60. muscle enzymes The most sensitive enzyme is CK
it can be normal in active IBM or DM (especially when associated with a connective tissue disease)
CK is always elevated in patients with active PM
SGOT, SGPT, LDH, aldolase may be elevated

61. EMG myopathic potentials characterized by:
Short duration & low-amplitude polyphasic units on voluntary activation
Increased spontaneous activity with fibrillations
complex repetitive discharges
positive sharp waves

62. Mixed potentials (polyphasic units of short and long duration) indicating:
chronic process and muscle fiber regeneration are often present in IBM

63. These EMG findings are not diagnostic of an IM
They are useful to identify :
1.presence of active or chronic myopathy
2.exclude neurogenic disorders

64. Muscle biopsy
the most sensitive and specific test for establishing the diagnosis of IM
Histologic hallmark: Inflammation

65. PM In PM the inflammation is primary
T cell infiltrates primarily within the muscle fascicles (endomysially) surround individual,healthy muscle fibers and result in phagocytosis and necrosis

66. Muscle biopsy in PM

67. The CD8/MHC-I lesion is characteristic and useful to confirm or establish the diagnosis

68. DM Endomysial inflammation is predominantly perivascular
or in the interfascicular septae
around muscle fascicles
obliteration of capillaries
This results in perifascicular atrophydi

69. perifascicular atrophy is diagnostic ofDM
even in the absence of inflammation

70. Muscle biopsy in DM

71. IBM Primary inflammation with CD8/MHC-I complex
vacuolated fibers with β-amyloid deposits
cytochrome oxygenase–negative fibers
Eosinophilic cytoplasmic inclusions

72. Muscle biopsy in IBM

75. TREATMENT The goal of therapy is to improve muscle strength
ameliorate the extramuscular manifestations (rash, dysphagia, dyspnea, fever)
When strength improves, the serum CK falls
discontinue these drugs if, after an adequate trial, there is no objective improvement in muscle strength
or not CK levels are reduced

76. Glucocorticoids
A feeling of increased energy or a reduction of the CK level without a concomitant increase in muscle strength is not a reliable sign of improvement
in general, DM responds better than PM
steroid myopathy
In uncertain cases, the prednisone dosage can be steadily increased or decreased as desired
the cause of the weakness is usually evident in 2–8 weeks

77. Azathioprine Methotrexate Mycophenolate mofetil rituximab
Cyclosporine has inconsistent and mild benefit
Tacrolimus (Fk506)
IVIg improved strength and rash ,underlying immunopathology
The benefit is(≤8 weeks), and repeated infusions every 6–8 weeks
cyclophosphamide