MIOPATÍAS INFLAMATORIAS.

Aproximación diagnóstica

Josep M. Grau

Medicina Interna

Hospital Clínic de Barcelona

BOGOTÁ

Marzo 2012

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)

BIOPSIES MÚSCUL, NERVI I ARTERIA TEMPORAL

IRA: 70% MDI: 75%

Altres Serveis i Hospitals: 25%

0

50

100

150

200

250

300

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

total múscul nervi arteria arteria +

MIOSITIS. DISTRIBUCIÓN SEGÚN TIPO

0

10

20

30

40

50

60

70

80

90

1977-1997 1998-2005 2005-2010

DM

PM

MCI

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

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)

Dermatomiositis

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...)

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)

POLIMIOSITIS

Polimiositis. (Ag de clase I)

UNICORNS, DRAGONS, POLYMYOSITIS,

AND OTHER MYTHOLOGICAL BEASTS

A.A. Amato and R. Griggs

Neurology 2003;61:288-290

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

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:

DEFICIENCIA DE DISFERLINA

(gen cromosoma 2p13)

• Fenotipo clínico:

– Miopatía de Miyoshi

– LGMD 2B

– Miopatía distal compartimento anterior

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

DISTROFIA MUSCULAR F-E-H

Sporadic Inclusion Body Myositis Josep M. Grau and Albert Selva-O’Callaghan

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.

DIAGNOSTIC CRITERIA IN AUTOIMMUNE DISEASES. Y. Shoenfeld et al. (eds) 2008 Humana Press, Totowa, NJ

Miositis con cuerpos de inclusión

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)

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?)

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

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

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.

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

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)

Differential diagnoses (prominent data for each condition)

I.B.MI.B.M. PRESENTING SYMPTOMS. PRESENTING SYMPTOMS36/144 MII cases36/144 MII cases

(1997(1997--2007)2007)

19

2

9

5

1

0

2

4

6

8

10

12

14

16

18

20

Proximal

weakness

Distal

weakness

Mixed

weakness

Axial

weakness

Resp.

Failure

I.B.MI.B.M. PRESENTING SYMPTOMS. PRESENTING SYMPTOMS36/144 MII cases36/144 MII cases

(1997(1997--2007)2007)

16

3

11

7

2

3

2

10

2

4

6

8

10

12

14

16

18

20

Proximal

weakness

Distal

weakness

Mixed

weakness

Axial

weakness

Resp.

Failure

Without dysphagia With dysphagia

Camptocormia ?

MYOSITIS

DM PM sIBM

No screening

PET/CT

once at

diagnosis

PET/CT

once at

diagnosis

p155 (+) p155 (-)

PET/CT

yearly for 3-5

years

PET/CT

once at

diagnosis

Algorithm for diagnosis of occult cancer in inflammatory myopathies (Selva et al., 2010).

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.