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Prezentare de caz

Autori- gr 33: Moroianu Madalina Popa Cristina Predescu Laura Coordonator: sef de lucrari dr. Violeta Bojinca

Pacienta M.C, 64 ani, mediul rural, pensionara


Internata 12.06.2012 pentru: Tumefactie + dureri + impotenta functionala genunchi bilateral > art. maini

APP
1. Gastrita cronica

2.
3.

HTAE max TAs= 180 mmHG -blocant, Preductal, IECA


Anemie hipocroma microcitara dg 2008

4.

DZ II postmedicamentos (sec corticoterapiei) dg dec 2010 regim alimentar + Metformin cp seara, dupa masa
IMA subendocardic NSTEMI dg aug 2011 Gastrita acuta postmedicamentoasa (AIS) dg iun 2012 Boala Parkinson dg iun 2012 Mirapexin 0.25 mg

5. 6. 7.

AHD

Mama afectare CV (?) Tatal boala osoasa (?) Sora cancer mamar

2005
ian- Dg: PR FR+ std II
Trat: SSZ 3 cp/zi + Prednison fara raspuns

mar: reinternare in puseu inflamator de boala:


Tratament: 1. SSZ 3 cp/ zi
2. MTX 15 mg/ sapt

FR: 161 UI/ml VSH= 70 mm/h PCR = 108 mg/l

3. Celestone 1 fi la 2 zile X 10 fi, apoi Medrol 4 mg la 2 zile

mai: sdr inflamator nespecific remis


Tratament:

VSH= 18 mm/h PCR = 4.74 mg/l

MTX 15 mg/ sapt


Arava 20 mg/ zi Medrol 4mg la 2 zile

2008 Reevaluare:
Feb clinic: durere + tumefactie + functio lessa la: genu + RCC + MCF bilateral + T - paraclinic: FR= 48 UI/ml
VSH= 62 mm/h

Apr VSH= 38 mm/h Nov VSH= 50 mm/h


TRATAMENT 2008 2009 :

MTX 20 mg/ sapt SSZ 4 cp/ zi

2009 2010: SSZ 4 cp/ zi

2010
Iunie: clinic:
tumefactie importanta si impotenta functionala genunchi artrocenteza + trat intraarticular cu Diprophos

paraclinic: VSH= 41 mm/h PCR= 50.76 mg/l trat: Imuran 2 cp / zi (100 mg/zi) Medrol 4 mg la 2 zile x 1 luna Ketoprofen 100 mg 1-2/zi, la nevoie

Sep Dec:

MTX 20 mg/ sapt Medrol 8 mg/ zi

Dec: artrocenteza + trat intraart. ( Diprophos 1 ml + Xilina 2% 5 ml)


VSH: 92 mm/h PCR: 24 mg/l Trat: MTX 5 mg x 3 fi/ sapt
ARAVA 20 mg/ zi MEDROL 12 mg/zi x 10zile 8 mg/zi x 10 4 mg/zi

Continuat pana in 2012

2012
Apr: clinic: agravare importanta paraclinic: VSH= 56 mm/h PCR= 73 mg/l tratament: Imuran 50 mg x2/zi Medrol 4 mg (1/2 la 2 zile)

La internarea actuala (12-27.06.2012)..


Exam obiectiv: stare generala alterata Osteo-art.:

Tumefactie genunchi bilat Soc rotulian + bilateral Limitare mobilitate genunchi Ortostatiune dificila

Tumefactie MCF IFP I, II Tremor maini in repaus

Laborator
Hb Ht VEM CHEM Tc Leu 8.61 g/dl 25.50% 69 fl 33.8 g/dl 519*10^3/ul 8.3*10^3/mmc

Neu
sideremie glicemie Na

85.60%
10 ug/dl 197 mg/dl 131 mEq/l (N 50-170)

GGT
FR

133 UI/ml
362 UI/ml

(N 9-36)

PCR

193.6 mg/l

Rx

Demineralizare difuza, accentuata juxtaarticular Carpita stanga Elemente artrozice IFD bilateral

Gonartroza bilateral

ECHO

Stadializare PR

CLINICO-FUNCTIONALA Cls I: activitate fizica normala Cls II: durere mobilitatii artic Cls III: capacitate de auto ingrijire Cls IV: imobilizare la pat scaun cu rotile incapacitate de autoingrijire

Anatomica STD. I: PRECOCE Rx: Normal +/- tumefactie de parti moi +/- osteoporoza STD. II: MODERAT osteoporoza limitare miscare art. eroziuni absenta deformarilor art atrofie mm +/- noduli reumatoizi +/- tenosinovite ST. III: SEVER Distructie os si cartilaj deformare articulara cu subluxatii Deviere ulnara Atrofie musculara marcata ST. IV: TERMINAL Fibroza articulara Anchiloza

DAS4v 28 CRP
Internare: 8.6 High disease activity

Externare: 7.4 High disease activity

VA N G E S T E L AM, HAAGSMA CJ, VA N R I E L P L C M: Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998; 41: 184550.

Tratament Pe durata internarii: CARE ESTE TRAT?

Igieno-dietetic

La externare

Medicamentos: PR: Leflunomid 20 mg/zi Medrol 16 mg cp x2/zi -CV: Aspacardin 2cp/zi Concor (Bisoprolol) 5mg 1cp/zi Zenra (Ramipril) 5 mg 1cp/zi Trombex 7.5 mg 1 cp/zi -Anemie: Ferro gradumet 2cp/zi -DZ II: Siofor 1g/zi -b. Parkinson: Mirapexin (pramipexol) 0.25 mg 2cp/zi Rivotril (clonazepam) 2 mg 1 cp/zi -osteoporoza: Alfa D3 2cp/zi -protectie gastrica: Nolpaza (pantoprazol) 20 mg 1 cp/zi

EVOLUTIA PR SUB TRATAMENT 2005-2012


02 12.201 02 12 2008 11 2008 06 2010 0 2011 2012 12 2012 12 06 2012 15 06 2012 27 06 2012

DATA

03 2005

05 2005

PCR mg L

108

91 85

52

24

9 31

73

193 69

50

2008 2009 MTX SSZ SSZ MTX MTX ARAVA 2009 2010 IMURAN TRAT MEDROL MEDROL SSZ MEDROL
250 200 150 100 50 0 03 2005 05 2005 02 2008 11 2008 06 2010

MTX ARAVA MEDROL

IMURAN
MEDROL

ARAVA

MEDROL

MEDROL

PCR mg L

01.12.2010

02 2011

12 2012

12 2012

12 06 2012

15 06 2012

27 06 2012

CRITERII DE INITIERE TERAPIE BIOLOGICA 1. Diagnostic cert de PR 2. PR sever, activ (DAS > 5,1) + >=5 art + sinovit activ + 2/3 criterii: redoare matinal >60 in ciuda tratamentului VSH > 28 mm/h PCR > 20 mg/l sau de 3 ori val. N 3. PR nonresponsiva (persistenta criteriilor de activitate >3 luni de trat. Continuu, cu doza maxima admisa/tolerata) dup utilizarea a cel puin 2 soluii terapeutice remisive standard x minim 3 luni fiecare
4. Evaluarea riscului pentru TBC anamneza, examen clinic, radiografie pulmonar, IDR la PPD i teste de tip IGRA - Quantiferon TB Gold. Pentru pacienii cu IDR >5mm sau testai pozitiv la Quantiferon se indic consult pneumologic n vederea chimioprofilaxiei cu hidrazid sau rifampicin. Terapia biologic se poate iniia dup minim o lun de tratament profilactic. innd cont de riscul reactivrii infeciilor cu virusuri hepatitice se impune la iniierea terapiei cu un agent biologic screening pentru Ag HBs i Ac VHC.

www.ms.ro/documente/1322%20Anexa%201_8730_6666.doc Ghid de tratament al Poliartritei Reumatoide

Algoritm de tratament al poliartritei reumatoide

Terapia de prima linie

Methotrexat 7,5-20mg/spt

Leflunomid 20mg/zi

Sulfasalazina 2 g/zi

Hydroxychloroqui na 400mg/zi

Ciclosporina 3-5 mg/kgc/zi Azathioprina 100mg/zi

Terapia de linia a-IIa -P.R. activ( DAS28>5,1), VSH>28mm/h, CRP>20mg/l, redoare matinal >1h -Utilizarea a cel puin 2 soluii terapeutice remisive standard, cu durata de minim 12 sptmni fiecare, cu boala activ n continuare

Terapia anti TNF : Infliximab, Etanercept, Adalimumab, Golimumab, Certoliyumab pegol (se permite ncercarea altui blocant TNF la non responderii la primul anti TNF )

Non responderi la unul sau mai muli blocanti TNF : Rituximab Abatacept,Tocilizumab

www.ms.ro/documente/1322%20Anexa%201_8730_6666.doc Ghid de tratament al Poliartritei Reumatoide

Complicatii
Ale bolii: ? Ale tratamentului:
Gastrita acuta DZ II Osteoporoza Toxicitate hepatica Anemie

Ce complicatii ar putea dezvolta in viitor

Particularitatile cazului.. Terapii remisive multiple logica? Riscul CV in PR

IMA SI PR
Aug 2011 precordialgii caracter constrictiv, >30, iradiere submandibular + umar stang coronarografie: stenoza 25-50% ADA

!PR este factor de risc independent pentru ateroscleroz!

Ateroscleroza precoce i accelerat reprezinta o manifestare extraarticular a PR

BOALA CV I PR
FR traditionali: HTAE dislipidemie (Cho 230 mg/dl, lipemie 695 mg/dl) DZ II obezitate gr. I istoric familial

FR adiionali dependeni de boal PCR, Fi trombocitoza MMP

FR adiionali dependeni de tratament: DMARDs: MTX GC AINS

Krause D, Schleusser B, Herborn G et al Response to methotrexate treatment is associated with reduced mortality in patients with severe rheumatoid arthritis, Arthritis Rheum 2000; 43:14-21

MEDIATORI INFLAMATORI COMUNI


MEDIATOR Lipoproteine FUNCIE BIOLOGIC
Reglatori ai inflamaiei (H), Efect proatrogen (A)

PR
LDL: HDL:

ATS
LDL: HDL:

PcR
TNF RANKL

Activitate proinflamatoare (H, A)


Efecte proinflamatoare (H, A) Creterea instabilitii plcii (H), Creterea calcificrilor vasculare (A) Efecte antiinflamatoare (H,A) Reglator al funciei/supravieuirii imune (H) Creterea recrutrii leucocitare (A) Inducere de citokine de tip Th1 (H) Promovarea inflamaiei tisulare (A) Chemoatractant pentru monocite Instabilitatea plcii i leziune tisular (H, A) Creterea funciei leucocitare (H) Creterea inflamaiei vasculare (A) Creterea recrutrii celulare (H, A)

Adiponectina
CD40L IL18, IL20 MCP-1

Insulina
VCAM-1, ICAM-1

Montecuco F, March F, Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosi, Rheumatology 2009, 48 (1): 11-12

FACTORI CELULARI COMUNI


Mf activate sinteza citokine (TNF,IL-1, IL-6) proinflamatorii sinteza MMP cu efect distructiv (eroziuni, destabilizarea plcii de aterom)

Celule T CD4+ CD28- infiltreaz sinoviala reumatoid i placa aterosclerotic rol in dezvoltarea precoce a aterosclerozei n PR (disfuncie endotelial, grosime I-M) -proliferarea monoclonal cu rol distructiv i de instabilitate a plcii
Gerli R, Schillaci TG, Giordano A et al CD4+CD28- T lymphocytes contribute to early atherosclerotic damage in rheumatoid arthritis patients, Circulation 2004; 109: 2744-48 Liuzzo G, Goronzy JJ, Yang H et al Monoclonal T cell proliferation and plaque instability in acute coronary syndromes, Circulation 2000;101: 2883-2888

Riscul de evenimente CV in PR

.. similar cu al pacientului non- PR cu 5-10 ani mai vrstnic .. comparabil cu DZ tip II .. crescut chiar la debutul PR (faza preclinic) .. Influentat major de durata bolii Pacienii cu PR care dezvolt IM au mai muli factori de risc tradiionali dar NU activitate a bolii mai mare (DAS 28)

Nivele joase dar persistente ale inflamaiei sunt suficiente pentru accelerarea aterosclerozei i excesul de risc CV n PR

! Identificarea riscului CV la pacienii cu PR asimptomatici n vederea preveniei primare este obligatorie!


Peters MJ et al Does rheumatoid arthritis equal diabetes mellitus as an independent factor fpr CV disease: a prospective study, Arthritis Rheum 2009, 61 (11):1571-9 Solomon DH, Goodson NJ, Katz J et al patterns of cardiovascular risk in rheumatoid arthritis Ann Rheum Dis, 2006; 65: 1608-12

Maradit Kremers H et al High Ten-Year Risk of Cardio-Vascular Disease in Newly Diagnosed Rheumatoid Arthritis Patients, Arthitis & Rheum, Vol. 58, Nr. 8:2268-74

RISCUL LA 10 ANI DE BOALA CV FATAL LA PACIENI LA RISC CV CRESCUT

5-9% HDL 46 Cho 186 TAs 180

Peters

MJL, Symmons DPM, McCarey D et al.EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other form of inflammatory arthritis Ann Rheum Dis 2010;69:325-331

June 11, 2012 (Berlin, Germany) In patients with rheumatoid arthritis (RA), tumor necrosis factor (TNF) inhibitors are associated with a significantly lower risk for cardiovascular events than non-TNF agents, according to research presented here at the European League Against Rheumatism Congress 2012.

Prognostic
Al bolii- nefavorabil: raspuns negativ la multiplele terapii remisive FR + sdr inflamator nespecif intens pozitive Nr mare art tumefiate Status functional alterat (HAC) Prezenta manifestarilor extraarticulare (ATS.. ?) General: risc CV crescut <- f. r. multiplicarea indicelui SCOR cu 1.5 daca exista 2/3: evolutie boala > 10 ani prezena FR i a anticorpilor anti-CCP manifestri extraarticulare

concluzii