1 / 41

Autoinflammatory diseases

Autoinflammatory diseases. Gilles Grateau Service de médecine interne Centre de référence des amyloses d’origine inflammatoire et de la fièvre méditerranéenne familiale Paris. Autoinflammatory diseases. No consensus definition. Autoinflammatory diseases. No consensus definition

tehya
Download Presentation

Autoinflammatory diseases

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Autoinflammatory diseases Gilles Grateau Service de médecine interne Centre de référence des amyloses d’origine inflammatoire et de la fièvre méditerranéenne familiale Paris

  2. Autoinflammatory diseases No consensus definition

  3. Autoinflammatory diseases No consensus definition Disease of the innate immune system and no autoimmune abnormality

  4. Autoinflammatory diseases No consensus definition Disease of the innate immune system and no autoimmune abnormality Hereditary recurrent fevers • A subgroup of Mendelian inherited disorders • Six diseases

  5. The core of hereditary recurrent fevers • Beginning in infancy • Intermittent symptoms • Biological signs of inflammatory response: neutrophils C reactive protein/SAA • Familial character • Amyloidosis

  6. Familial Mediterranean fever A prototypic auto-inflammatory disease

  7. Familial Mediterranean Fever(FMF)

  8. Age at Onset 0-20 years 82 % over 40 years 1%

  9. FMF attack Precipitating factors • physical activity • emotional stress • inter-current infections • cold exposure • menstruation Prodromes • pain at the attack site • constitutional symptom • unique manifestation Lidar M, 2006 Drenth JP, 2001

  10. Peritonitis • in 96% of the cases. • presenting feature in 80%. • resembles “surgical abdomen”. • about 30% undergo appendectomy. Zissin R et al

  11. Pleuritis • In 25-80% of the cases: (Armenians>Jews) • Severe pleuritic pain • May mimic pulmonary embolism • Sometimes with effusion Benchetrit E

  12. Pericarditis relatively rare <1% constrictive pericarditis in very few cases Benchetrit E

  13. Arthritis Acute monoarthritis • abrupt onset • short attack: 3-7 days • peak 24-48 hours • large effusion • complete resolution Chronic destructive arthritis • Commonly affects the hips and knees • Sacroiliitis-HLA B27 negative Benchetrit E

  14. Skin Involvement • In 7-40% of the cases • Erysipelas-like erythema • May be an only feature in children Benchetrit E

  15. TNF receptor associated periodic syndrome TRAPS

  16. TRAPS attack fever 100% myalgias 80% abdominal pain 88% pleuritic pain 40% arthralgias 52% headache 68% conjonctivitis 44% or orbital edema skin involvement 88% Toro, 2000 Drenth JP, 2001

  17. Inflammatory monocytic fasciitis of the thigh in a patient with TRAPS Hull et al, 2002

  18. TRAPS Mc Dermott E, 1997 Hull K, 2002

  19. Cold induced autoinflammatory syndrome 1 (CIAS1) associated periodic syndromeCAPS or Cryopyrinopathies Muckle-Wells syndrome Familial cold urticaria (FCU)/ Familial cold autoinflammatory syndrome (FCAS) Chronic infantile neurological cutaneous articular syndrome (CINCA)/Neonatal onset multisystem inflammatory disease (NOMID)

  20. Cryopyrinopathies Urticaria • Cold sensitivity in FCU • Nerve deafness in MW • Early onset in CINCA with severe CNS manifestations • Clinical continuum

  21. Cryopyrinopathies CINCA FCAS

  22. Cryopyrinopathies Joint involvement

  23. Mevalonate kinase deficiency associated periodic syndromeMKD or MAPS Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) Mevalonic aciduria (MA)

  24. HIDS-attack Clinical features fever 100% lymphadenopathy 94% skin lesions 82% diarrhea 82% arthralgia 80% chills 76% abdominal pain 72% arthritis 64% vomiting 56% splenomegaly 48% Drenth JP, 1994 Precipitatingfactors Immunization, viral infection Drenth JP, 2001

  25. HIDS Drenth JP

  26. A watershed in our knowledge of inflammatory diseases Cryopyrin/NLRP3 the protein involved in « cryopyrinopathies » Is involved in the IL-1 b processing

  27. NLRP/NALP family 14 members

  28. The concept of inflammasome Main features Martinon 2009 Multiproteic Complex Cytoplasmic localisation Activation of pro-inflammatory caspase : caspase-1

  29. 1 1 Secretion / activity IL-1 : a controlled process Control steps 1. Transcription / traduction of IL-1 pro-IL-1 ADN ARN immature

  30. 1 2 1 pro-IL-1 IL-1 Caspase-1 immature mature Secretion / activity IL-1 : a controlled process Control steps • Transcription / traduction of IL-1 • Cleavage of pro-IL1 to mature IL-1 through inflammasome ADN ARN

  31. 1 2 1 3 pro-IL-1 IL-1 Caspase-1 immature mature Secretion / activity IL-1 : a controlled process Control steps • Transcription / traduction of IL-1 • Cleavage of pro-IL1 to mature IL-1 through inflammasome • Active secretion of IL-1 out of the cell (Ca2+) ADN ARN

  32. 4 3 1 2 1 pro-IL-1 IL-1 Caspase-1 immature mature Secretion / activity IL-1 : a controlled process Control steps • Transcription / traduction of IL-1 • Cleavage of pro-IL1 to mature IL-1 through inflammasome • Active secretion of IL-1 out of the cell (Ca2+) • Competition with a naturalantagonist: IL-1Ra with a higher affinity for IL-1RI than IL-1 IL-1Ra IL-1 IL-1RI IL-1R-AcP signal transduction ADN ARN

  33. 5 4 1 2 1 3 pro-IL-1 IL-1 Caspase-1 immature mature Secretion / activity IL-1 : a controlled process Control steps • Transcription / traduction of IL-1 • Cleavage of pro-IL1 to mature IL-1 through inflammasome • Active secretion of IL-1 out of the cell (Ca2+) • Competition with a naturalantagonist: IL-1Ra with a higher affinity for IL-1RI • Preferential Fixation of IL-1 on the inactiveIL1-R-II at themembrane or soluble IL-1Ra IL-1 IL-1sRI IL-1sRII IL-1RI IL-1R-AcP IL-1RII no transduction signal transduction ADN ARN

  34. Serial measurements of plasma concentration of SAA protein in Two Patients with the Muckle –Wells Syndrome Treatment with the IL1-RA anakinra Hawkins PN, 2003

  35. DIRA Aksentijevich NEJM 2009

  36. Treatment of auto-inflammatory diseases • Cryopyrinopathies IL-1 inhibitors • TRAPS steroids TNF inhibitors IL-1 inhibitors • MKD TNF inhibitors IL-1 inhibitors • FMF colchicine TNF inhibitors IL-1 inhibitors • DIRA IL-1 inhibitors

  37. Classification of auto-inflammatory disorders Hereditary recurrent fever syndromes

  38. Classification of auto-inflammatory disorders Mendelian diseases of the innate immune system Blau Hereditary recurrent fever syndromes PAPA Majeed

  39. Classification of auto-inflammatory disorders Diseases of the innate immune system Mendelian diseases of the innate immune system Blau Hereditary recurrent fever syndromes PAPA JIA Majeed gout Adult onset Still’s disease

  40. Classification of auto-inflammatory disorders Diseases of the innate immune system Mendelian diseases of the innate immune system Blau Hereditary recurrent fever syndromes PAPA JIA Majeed gout Adult onset Still’s disease Atherosclerosis ?

  41. Thanks Hôpital Tenon Katia Stankovic Hôpital Trousseau Inserm U933 Serge Amselem Isabelle Jéru Marie Legendre Philippe Duquesnoy Hôpital Cochin Inserm U567 Marc Delpech Catherine Dodé Laurence Cuisset

More Related