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Cacoub p hcv meh 2014
1. Extrahepatic Manifestations of
Hepatitis C Virus Infection
Pr Patrice CACOUB
Service de Médecine Interne, et CNRS UMR 7087
Université Pierre et Marie Curie
Centre National de Référence Maladies Auto-immunes
Hôpital La Pitié-Salpêtrière, Paris, FRANCE
6. Les cryoglobulines sont des Immunoglobulines
qui précipitent à une température < 37°C et se
dissolvent lors du réchauffement
Ferri C et al. Orphanet J Rare Dis 2008
Brouet J et al. Am J Med 1974
15. Features of Mixed Cr yoglobulinemia
Age at disease onset
Female/Male ratio
Purpura
Weakness
Arthralgias
Arthritis (non-erosive)
Raynaud's phenomenon
Sicca syndrome
Peripheral neuropathy
Renal involvement
B-cell non-Hodgkin's lymphoma
Hepatocellular carcinoma
n=250
54 ± 13 (29-72)
3
98%
98%
91%
8%
32%
51%
81%
31%
11%
3%
Ferri C, Mascia MT, Saadoun D, Cacoub P. 2009
16
16. Mixed Cryoglobulin and Distal Polyneuropathy
Peripheral Nerve Biopsy
- important peri-vascular infiltrate of lymphocyte
- around small vessels i.e. venules, capillaries
- no PMN, no destruction of the vascular wall
17. Cellular Infiltrate in HCV-Vasculitis
Who’s the culprit ?
HCV Core Protein in Skin Vascular
Structures
18
18. Detection of Genomic Viral RNA in
Ner ve
and Muscle of Patients with HCV
Neuropathy
Inflammatory vascular lesions in 26/30 (87%) patients
Positive-strand genomic HCV RNA detected in 10/30
patients (muscle 9, nerve 3)
Negative-strand replicative HCV RNA never
detected
--> HCV neuropathy probably results from virus-triggered
immune-mediated mechanisms rather than direct nerve
infection and in situ replication
Authier JF et al, Neurology, 2003
19
19. A Role for B Cell
Immunity
in HCV-Vasculitis
Rationale for
Rituximab treatment
in cryoglobulinemic
vasculitis
Roccatello, D. et al. Nephrol. Dial. Transplant. 2004
Rocatello D, Nephrol Dial Transplant, 2004
20
22. Biais de répertoire des Lympho B CD21-/low CD27+ IgM+
avec expression préférentielle de la chaîne lourde
d’Ig VH1-69
Accumulation de mutations somatiques témoignant
de la maturation d’affinité
Terrier B. et al. J Immunol 2011
23. Etude de l’apoptose et de la prolifération
Apoptose (expression annexine V)
Prolifération (incorporation 3H)
Les LymphoB CD21-/low CD27+ IgM+
sont des cellules anergiques
Notes de l'éditeur
Diagnosis of neuropathic pain requires identifying the nerve structures that are involved. Pattern recognition is a common means of identifying the location of the deficit. Once the pattern of involvement is recognized, the next step is to identify the etiology.
Mononeuropathies are usually posttraumatic or caused by entrapment neuropathies.1 Occasionally systemic disease (eg, diabetes or vasculitis) can produce a mononeuropathy.2
Mononeuropathy multiplex means that a patient has multiple mononeuropathies, usually asymmetric and involving multiple parts of the body. Causes include vasculitis, sarcoidosis, and inflammatory polyneuropathies.2
Involvement of most of an extremity in the neuropathic process suggests involvement of the plexus, or a plexopathy.2,3 Common causes include trauma, cancer, radiation, and some systemic illnesses.3
Peripheral polyneuropathy, resulting in a “stocking-and-glove” pattern, is perhaps the pattern most easily recognized.4 It is always the result of a systemic process, such as a toxic exposure, diabetes, or alcohol.1
1.Boulton AJM, Malik RA. Diabetic neuropathy. Med Clin North Am. 1998;82:909-929.
2.Portenoy RK. Neuropathic Pain. In: Portenoy RK, Kanner RM, eds. Pain Management: Theory and Practice. Philadelphia, Pa: FA Davis Company; 1996:108-113.
3.Katz N. Neuropathic pain in cancer and AIDS. Clin J Pain. 2000;16:S41-S48.
4.Galer BS, Dworkin RH. A Clinical Guide to Neuropathic Pain. Minneapolis, Minn: McGraw-Hill Companies Inc; 2000:100.