1. MIOPATÍAS INFLAMATORIAS.
Aproximación diagnóstica
Josep M. Grau
Medicina Interna
Hospital Clínic de Barcelona
BOGOTÁ
Marzo 2012

2. MIOPATÍAS INFLAMATORIAS.
Clasificación
POLIMIOSITIS (no cáncer)
DERMATOMIOSITIS (20% cáncer en adultos)
MIOSITIS CON CUERPOS DE INCLUSIÓN
MIOSITIS ASOCIADAS
- PM: ESP, LES, AR, Sjögren, PAN…
- DM: ESP, LES, AR
- MCI: ESP, LES, PTI, Sjögren…..
MIOPATIA NECROTIZANTE INMUNOMEDIADA
(estatinas)
CAM (Cancer associated myositis)

3. BIOPSIES MÚSCUL, NERVI I ARTERIA TEMPORAL
IRA: 70%
MDI: 75%
Altres Serveis i Hospitals: 25%
300
250
200
150
100
50
0
95
96
97
98
99
00
01
02
03
04
05
06
07
08
09
10
11
19
19
19
19
19
20
20
20
20
20
20
20
20
20
20
20
20
total múscul nervi arteria arteria +

4. MIOSITIS. DISTRIBUCIÓN SEGÚN TIPO
90
80
70
60
50 DM
40 PM
30 MCI
20
10
0
1977-1997 1998-2005 2005-2010

5. MIOPATIAS INFLAMATORIAS. DIAGNÓSTICO
DM: Diagnóstico positivo
Lesión cutánea: típica o no
Histopat: Atrofia perifascicular
C5b9 (MAC) precoz
Células B, necrosis subletal
ICAM-1 (sobreexpr.), VCAM
PM: Diagnóstico de exclusión
(distrofias FEH, cinturas, MCI, tóxicas…)
MCI: Formas de presentación variadas
En ocasiones más de una bx

6. DERMATOMIOSITIS. FORMAS DE
PRESENTACIÓN
• Lesiones cutáneas (Gottron, eritemas, poiquilodermia,
hiperplasia cuticular, edema palpebral, manos mecánicas,
paniculitis, edema…..). FORMAS “A-HIPOMIOPÁTICAS”
• Debilidad muscular (simétrica, proximal, aguda-subaguda)
(formas sine dermatitis)
• Elevación de enzimas musculares (CPK, LDH,
GOT/GPT)

17. Dermatomiositis

21. Autoanticuerpos en MII
• Jo-1 : Afectación pulmonar
• Mi-2 : Dermatomiositis clásica
• P-155: Miositis asociada a neoplasia
– Elevado valor predictivo negativo
• Anti SRP: Miositis grave (pulmón, corazón...)

22. POLIMIOSITIS. FORMAS DE
PRESENTACIÓN
• Debilidad muscular (simétrica, proximal, subaguda)
• (no afectación facial, atrofia tardía, no datos de neuropatia…)
• Elevación de enzimas musculares (CPK, LDH,
GOT/GPT)

23. POLIMIOSITIS

24. Polimiositis. (Ag de clase I)

25. UNICORNS, DRAGONS, POLYMYOSITIS,
AND OTHER MYTHOLOGICAL BEASTS
A.A. Amato and R. Griggs
Neurology 2003;61:288-290

26. POLYMYOSIYTIS: NOT A UNICORN OR
MYTHOLOGICAL BEASTS……..BUT MAY BE A DUCK?
JT Kissel
Neurology 2008;70:414-5
Correlation of muscle biopsy, clinical course, and outcome in
PM and sporadic IBM.
N. Chahin and A. Engel
Neurology 2008;70:418-24

27. DISTROFIAS MUSCULARES DE
CINTURAS (Limb girdle)
• LGMD 2C
• LG MD 2D Sarcoglicanos
• LGMD 2E
• LGMD 2F
• LGMD 2A : Calpaína 3
• LGMD2 B: Disferlina
• LGMD 2G: Teletonina
• LGMD 2H:

28. DEFICIENCIA DE DISFERLINA
(gen cromosoma 2p13)
• Fenotipo clínico:
– Miopatía de Miyoshi
– LGMD 2B
– Miopatía distal compartimento anterior

29. DEFICIENCIA DE DISFERLINA
(gen cromosoma 2p13)
Cuadro clínico:
Inicio 2ª-3ª década
EEII proximal y distal
Lenta progresión
CK muy elevadas
Histopatología:
70%: Inflamación y necrosis
<CD8, >CD68 que PM
HLA clase I: negativo

31. DISTROFIA MUSCULAR F-E-H

35. Sporadic Inclusion Body Myositis
Josep M. Grau and Albert Selva-O’Callaghan
DIAGNOSTIC CRITERIA IN AUTOIMMUNE DISEASES.
Y. Shoenfeld et al. (eds)
2008 Humana Press, Totowa, NJ
Abstract: Sporadic inclusion body myositis (sIBM) is the most common
acquired muscle disease in elderly individuals, particularly men.
Its prevalence varies among ethnic groups, but it is estimated at 35
per one million people over 50 years.
Genetic as well as environmental factors and autoimmune processes
might both have a role in its pathogenesis. Unlike other inflammatory myopathies,
sIBM causes very slowly progressive muscular weakness and atrophy. It has a
distinctive pattern of muscle involvement and different forms of clinical
presentation. In some cases a primary autoimmune disease coexists.
Diagnosis is suspected on clinical grounds and is established by a typical
muscle pathology.
The rule for sIBM is its refractoriness to conventional forms of immunotherapy.

36. Miositis con cuerpos de inclusión

37. MIOSITIS AMB COSSOS D’INCLUSIÓ.
HISTÒRIA
1967 S. Chou. Science. Myxovirus-like structures……
1970 S.Carpenter. Neurology. Virus-like filaments….
1971 EJ Yunis. Lab Invest. Inclusion body myositis…
1978 S. Carpenter. Neurology. IBM, a distinct variety…..
1982 M. Danon. Neurology. A corticosteroid-resistant…..
1987 L. Calabrese. Arthr & Rheum. IBM as treatment-resistant…
1989 H. Nishino, A Engel. Ann Neurol. IBM. The mumps hypothesis…..
1989 P. Lotz A. Engel. Brain. IBM. 40 patients…..
1989 JM. Grau. Med Clin. MCI. Una variedad….
1992 G. Suarez. Neurology. The dropped head syndrome….
1993 V. Askanas. Neurology. Congo-red positive amyloid….
1993 M. Schröder. Moll Cell Biochem. Mitochondrial deletions in 3 cases…
1994 JM. Grau. Rev Clin Esp. Tres casos de MCI……
2002 MC. Dalakas. Lancet. PM, DM, IBM….
2006 MC. Dalakas Nat Clin Pract Neurol. sIBM…
2008 A. Engel. Neurology, PM/IBM…..
2012 J Milisenda, JM Grau Sem. Fund. Esp. Reum MCI (esporádica)

39. MCI (Patogenia)
• INFLAMACIÓN
– Citocinas, quimiocinas, Clase I CHM, cel. B....
• DEGENERACIÓN
– Proteína Beta-amiloide, priónica, ubiquitina.....
• MITOCONDRIAL
– Deficiencia parcial de COX
– FGF-21 (marcador biológico?)

48. Proposed diagnostic criteria for sIBM (2008)
Clinical features:
duration of illness >6 months
age at onset > 30 years
slowly progressive muscle weakness and atrophy: selective pattern with early involvement of quadriceps
femoris and finger flexors (frequently not symmetric)
Dysphagia
Laboratory features:
serum CK levels might be high but can be normal
EMG: myopathic or mixed patterns, with both short and long duration motor unit potentials and spontaneous
activity

49. Muscle biopsy:
- Myofiber necrosis and regeneration
- Endomysial mononuclear cell infiltrate (in variable degree)
- Mononuclear cell-invasion of non-necrotic fibers (mainly CD8)
- MHC class I expression in otherwise morphologically healthy muscle fibres
- Vacuolated muscle fibers (rimmed vacuoles)
- Ubiquitin- positive inclusions and amyloid deposits in muscle fibres
- Nuclear and/or cytoplasmic filamentous inclusions of 16-20 nm on electron
microscopy
- COX-negative fibers

50. Diagnostic categories:
Definite sporadic inclusion body myositis:
· Characteristic clinical features with biopsy confirmation: inflammatory
myopathy with autoaggressive T cells, rimmed vacuoles, COX-negative fibers,
amyloid deposits or filamentous inclusions and upregulation of MHC class I
expression. With these pathological findings the presence of other laboratory
features are not mandatory.
· Atypical pattern of weakness and atrophy but with diagnostic biopsy
features.

51. Probable sporadic inclusion body myositis:
· Characteristic clinical and laboratory findings but
incomplete biopsy criteria (eg. features of necrotising inflammatory
myopathy with T cell invasion but absence of rimmed vacuoles,
amyloid deposits, filamentous inclusions and COX-negative fibers.
Possible sporadic inclusion body myositis:
· Atypical pattern of weakness and incomplete biopsy
criteria

52. Differential diagnoses
(prominent data for each condition)
Motor neuron disease: Hyperreflexia, cramps, fasciculations
typical EMG.
Polymyositis: Subacute (weeks to months)
Proximal and symmetrical muscle weakness
High CK levels.
Vacuolar myopathies: Lack of inflammation, negative MHC HLA-class I
(myofibrillar myopathies, hIBM)

53. I.B.M. PRESENTING SYMPTOMS
36/144 MII cases
(1997-2007)
20 19
18
16
14
12
10 9
8
6 5
4
2
2 1
0
Proximal Distal Mixed Axial Resp.
weakness weakness weakness weakness Failure

54. I.B.M. PRESENTING SYMPTOMS
36/144 MII cases
(1997-2007)
20
18 3
16
14
12
10
8 16 2
6
4 7 2
2 1 3
0 1 1
Proximal Distal Mixed Axial Resp.
weakness weakness weakness weakness Failure
Without dysphagia With dysphagia

55. Camptocormia ?

57. Algorithm for diagnosis of occult cancer in inflammatory myopathies (Selva et al., 2010).
MYOSITIS
DM PM sIBM
PET/CT PET/CT
p155 (+) p155 (-) once at No screening once at
diagnosis diagnosis
PET/CT PET/CT
yearly for 3-5 once at
years diagnosis

58. MIOSITIS. (CONCLUSIONES )
1. Las lesiones cutáneas son de gran ayuda en el diagnóstico de DM.
2. Hay características A-P distintivas entre las formas de miositis.
3. Hay formas de miositis (PM/DM/MCI) asociadas a otras entidades.
4. El diagnóstico de PM es de exclusión.
5. La MCI es frecuente y puede presentarse de forma muy variada.
6. La práctica de PET-TAC (únicamente) es adecuada para descartar
neoplasia asociada.