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Ministerul Sntii
al Republicii Moldova
ARTRITA JUVENIL
IDIOPATIC,
FORMA SISTEMIC
PCN-7
Chiinu 2008
MINISTERUL
SNTII
AL REPUBLICII MOLDOVA
ARTRITA JUVENIL
IDIOPATIC,
FORMA SISTEMIC
Protocol clinic naional
Chiinu 2008
Elena Maximenco
Constantin Babiuc
Ala Nemerenco
Grigore Bivol
Victor Ghicavi
Valentin Gudumac
Ivan Zatusevski
Iurie Osoianu
Maria Bolocan
Mihai Rotaru
EDIIA I
Tiprit T-PAR SRL, 2008.
Tiraj: 2000 ex.
Aceast publicaie a fost posibil datorit susinerii generoase a poporului american prin intermediul Programului
Preliminar de ar al Fondului Provocrile Mileniului pentru Buna Guvernare (Programul pentru Buna Guvernare),
implementat de Millenium/IP3 Partners. Programul pentru Buna Guvernare este finanat de Corporaia Millennium
Challenge Corporation (MCC) i administrat de Agenia Statelor Unite ale Americii pentru Dezvoltare Internaional
(USAID) sub auspiciile Programului Preliminar de ar.
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
CUPRINS
ABREVIERILE FOLOSITE N DOCUMENT.............................................................................................................................. 4
PREFA........................................................................................................................................................................................... 4
A. PARTEA INTRODUCTIV........................................................................................................................................................ 5
A.1. Diagnosticul............................................................................................................................................................................ 5
A.2. Codul bolii (CIM 10).............................................................................................................................................................. 5
A.3. Utilizatorii............................................................................................................................................................................... 5
A.4. Scopurile protocolului............................................................................................................................................................. 5
A.5. Data elaborrii protocolului.................................................................................................................................................... 5
A.6. Data urmtoarei revizuiri........................................................................................................................................................ 5
A.7. Lista i informaiile de contact ale autorilor i ale persoanelor care au participat la elaborarea protocolului........................ 6
A.8. Definiiile folosite n document............................................................................................................................................... 7
A.9. Informaia epidemiologic...................................................................................................................................................... 7
B. PARTEA GENERAL................................................................................................................................................................. 8
B.1. Nivel de asisten medical primar........................................................................................................................................ 8
B.2. Nivel de asisten medical specializat de ambulator (reumatolog)...................................................................................... 9
B.3. Nivel de asisten medical spitaliceasc.............................................................................................................................. 10
C.1. ALGORITMII DE CONDUIT............................................................................................................................................. 12
C. 1.1. Algoritmul de tratament al AJI forma sistemic . ............................................................................................................. 12
C.2. DESCRIEREA METODELOR, TEHNICILOR I A PROCEDURILOR........................................................................ 13
C.2.1. Clasificarea AJI................................................................................................................................................................... 13
C.2.2. Factorii de risc.................................................................................................................................................................... 13
C.2.3. Conduita pacientului cu AJI, forma sistemic.................................................................................................................... 13
C.2.3.1. Anamneza................................................................................................................................................................... 14
C.2.3.2. Examenul fizic............................................................................................................................................................. 14
C.2.3.3. Investigaiile paraclinice............................................................................................................................................ 14
C.2.3.4. Diagnosticul diferenial.............................................................................................................................................. 15
C.2.3.5. Criteriile de spitalizare............................................................................................................................................... 16
C.2.3.6. Tratamentul................................................................................................................................................................ 16
C.2.3.7. Evoluia ..................................................................................................................................................................... 19
C.2.3.8. Supravegherea pacienilor cu AJI, forma sistemic................................................................................................... 19
C.2.4. Complicaiile AJI (subiectul protocoalelor separate)......................................................................................................... 20
D. RESURSELE UMANE I MATERIALE NECESARE PENTRU RESPECTAREA PREVEDERILOR
PROTOCOLULUI........................................................................................................................................................................... 21
D.1. Instituiile de asisten medical primar.............................................................................................................................. 21
D.2. Instituiile/seciile de asisten medical specializat de ambulator..................................................................................... 21
D.3. Instituiile de asisten medical spitaliceasc: secia Reumatologie pentru copii a ICOSMC........................................ 22
E. INDICATORII DE MONITORIZARE A IMPLEMENTRII PROTOCOLULUI............................................................ 23
ANEXE............................................................................................................................................................................................. 25
Anexa 1. Chestionar de evaluare a statusului funcional......................................................................................................... 25
Anexa 2. Aprecierea capacitii funcionale dup Steinbrocker.............................................................................................. 26
Anexa 3. Indicele de activitate a bolii sau scorul DAS............................................................................................................ 26
Anexa 4. Formular de consultaie la medicul de familie (AJI, forma sistemic)..................................................................... 27
Anexa 5. Scara vizual analoag a durerii................................................................................................................................ 28
Anexa 6. Criterii de ameliorare ACR30................................................................................................................................... 28
Anexa 7. Evaluarea pacientului cu AJI, forma sistemic......................................................................................................... 29
Anexa 8. Formular al pacientului........................................................................................................................................... 30
Anexa 9. Informaie pentru prini........................................................................................................................................... 32
BIBILOGRAFIE.............................................................................................................................................................................. 33
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
PREFA
Acest protocol a fost elaborat de grupul de lucru al Ministerului Sntii al Republicii
Moldova (MS RM), constituit din specialitii catedrei Pediatrie nr.1 a Universitii de Stat de
Medicin i Farmacie Nicolae Testemianu, n colaborare cu Programul Preliminar de ar
al Fondului Provocrile Mileniului pentru Buna Guvernare, finanat de Guvernul SUA prin
Corporaia Millenium Challenge Corporation i administrat de Agenia Statelor Unite ale Americii
pentru Dezvoltare Internaional.
Protocolul naional este elaborat n conformitate cu ghidurile internaionale actuale
privind AJI forma sistemic i va servi drept baz pentru elaborarea protocoalelor instituionale.
La recomandarea MS, pentru monitorizarea protocoalelor instituionale pot fi folosite formulare
suplimentare, care nu sunt incluse n protocolul clinic naional.
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
A. PARTEA INTRODUCTIV
A.1. Diagnosticul: Artrita juvenil idiopatic, forma sistemic
Exemple de diagnostice clinice:
1. Artrita juvenil idiopatic, forma sistemic (febr, erupie cutanat eritematoas, limfadenopatie, hepatosplenomegalie, cardit), gradul 2 de activitate, clasa funcional II teinbrocker, stadiul
radiologic II teinbrocker, evoluie monociclic.
2. Artrita juvenil idiopatic, forma sistemic, perioada inducerii remisiunii medicamentos controlate. n anamnez febr, artrit, anemie, splenomegalie, cardit.
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Pai
(modaliti i condiii de realizare)
III
Motive
(repere)
II
Descriere
(msuri)
I
1. Diagnosticul
1.1. Recunoaterea semnelor
precoce de AJI, forma
sistemic
B. PARTEA GENERAL
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
10
Descriere
(msuri)
I
1. Diagnosticul
1.1. Confirmarea AJI forma
sistemic
4. Recuperarea
3.1. Supravegherea
permanent pn la vrsta de
18 ani
I
3. Supravegherea
III
Obligatoriu:
Pai
(modaliti i condiii de realizare)
III
Motive
(repere)
II
II
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Descriere
(msuri)
I
1. Spitalizarea
3. Supravegherea
3.1. Supravegherea
permanent pn la vrsta de
18 ani
I
1.2. Deciziile n tactica de
tratament: staionar versus
ambulatoriu
2. Tratamentul
2.1. Tratamentul
medicamentos i de
reabilitare, n condiii de
ambulatoriu al copilului n
remisiune medicamentos
indus sau n remisiune fr
suport medicamentos
III
Evaluarea criteriilor de spitalizare (casetele 9, 10).
Motive
(repere)
II
Pai
(modaliti i condiii de realizare)
III
Obligatoriu:
II
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
11
12
4. Externarea, nivelul
primar, tratament continuu
i supraveghere
3.2 Tratamentul
nemedicamentos
3. Tratamentul
3.1. Tratamentul
medicamentos
I
2. Diagnosticul
2.1 Confirmarea AJI
III
II
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Protocol clinic naional Artrita juvenil idiopatic forma sistemic, Chiinu 2008
C.1. C.1.1.
ALGORITMII
AlgoritmulDE
de CONDUIT
tratament al AJI, forma sistemic [12]
C.1.1. Algoritmul de tratament al AJI, forma sistemic [12]
DA
Form grav?
Prezint pericol
pentru via?
NU
DA
NU
AINS
Glucocorticosteroizi
zilnic plus AINS
Puls-terapia cu
glucocorticosteroizi i.v. +
ciclosporine i.v. sau
Metotrexat, zilnic
glucocorticosteroizi,
citostatice, i.v. IgG i/sau
Inhibitori IL 1 i TNF
alfa
NU
mbuntirea
considerabil a strii
pacientului n prima lun
i normalizarea testelor
de laborator?
Remisiune n
decurs de
1 lun?
DA
Micorarea treptat a
dozei de
glucocorticosteroizi
DA
Acutizare?
Continu tratamentul
pn la remisiune
complet
NU
DA
Metotrexat,
inhibitor IL 1 sau
inhibitor TNF
alfa
NU
De continuat
AINS
Not:
AINS antiinflamatoare
nestoroidiene
`
TNF-alfa factor de necroz tumoral alfa
IL 1 interleukina 1
13
11
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
14
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
C.2.3.1. Anamneza
Caseta 5. Recomandri n colectarea anamnesticului
Evidenierea factorilor de risc (infeciile intercurente frecvente, traumatismul articular
frecvent, hiperinsolaia, reaciile adverse postvaccinale i medicamentoase).
Determinarea susceptibilitii genetice.
Debutul recent al bolii (acut sau insidios).
Simptomele AJI, forma sistemic, (durat a febrei >14 zile, dureri i/sau tumefieri articulare,
erupii eritematoase, maculopapuloase la picul febril, limfadenopatie, hepatosplenomegalie,
dispnee, palpitaii, dureri n cutia toracic, astenie, fatigabilitate).
Tratament anterior (glucocorticosteroizi, antiinflamatoare nesteroidiene, tratament de remisiune).
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Examinarea serologic pentru excluderea infeciilor virale sau bacteriene (infecia cu virus
Ebtein-Barr, citomegalovirus, infecie herpetic).
Sumarul urinei.
Examinarea radiologic articular, a cutiei toracice.
Ultrasonografia articular sau tomografia computerizat (la necesitate) sau rezonana
magnetic nuclear articular (la necesitate).
Ecocardiografia.
Electrocardiografia.
Spirografia.
Puncia articular sau pleural (la necesitate) cu examinarea bacteriologic a acestor fluide.
Hemocultura.
Puncia sternal (la necesitate).
Ultrasonografia organelor interne.
Scintigrafia scheletal (la necesitate).
Not: AJI, forma sistemic nu poate fi diagnosticat sau confirmat prin metode paraclinice. Rezultatele
de laborator sunt utile pentru excluderea altor diagnostice critice (infeciile sau malignitile).
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
C.2.3.6. Tratamentul
Caseta 11. Principiile tratamentul AJI, forma sistemic
Regim crutor (cu evitarea eforturilor fizice excesive n prezena semnelor de insuficien
poliorganic).
Dieta cu restricii n lichide i hiposodat (n prezena semnelor de IC), cu aport
sporit de Microelemente (n prezena semnelor de osteoporoz i tratament cronic cu
glucocorticosteroizi).
Tratamentul medicamentos:
AINS;
glucocorticosteroizi;
tratament de remisiune.
Tratament intervenional (plasmaferez) la necesitate.
Tratament chirurgical (ortopedic) la necesitate.
Tratament de reabilitare.
17
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
18
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
19
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
C.2.3.7. Evoluia
Caseta 16. Variantele evolutive ale AJI, forma sistemic
Monociclic (tratarea maladiei n cteva luni fr sechele articulare.
Policiclic (varianta cu dezvoltarea poliartritei distructive care nu rspunde la terapia
convenional i induce un handicap sever i mortalitate precoce).
Persistent.
20
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
21
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
D.1. Instituiile de
asisten medical
primar
tonometru;
fonendoscop;
electrocardiograf;
oftalmoscop;
taliometru;
panglica-centimetru;
cntar;
laborator clinic standard pentru determinare de: creatinin
seric, hemoglobin, ALT, AST, bilirubin total i fraciile ei,
fosfataz alcalin, VSH, proteina C reactiv i realizarea de
sumar al urinei.
Medicamente:
AINS.
Glucocorticosteroizi.
Metotrexat.
Personal:
D.2. Instituiile/
seciile de asisten
medical specializat
de ambulator
22
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Medicamente:
AINS.
Glucocorticosteroizi.
Metotrexat.
Personal:
medic-reumatolog certificat;
medic-funcionalist certificat;
asistente medicale;
acces la consultaiile calificate: neurolog, nefrolog,
endocrinolog, oftalmolog, hematolog, pulmonolog, ortoped,
kinetoterapeut, fizioterapeut, psiholog;
laborani cu studii medii;
medici de laborator.
Aparataj, utilaj:
D.3. Instituiile de
asisten medical
spitaliceasc: secia
Reumatologie pentru
copii a ICOSMC
tonometru;
fonendoscop;
electrocardiograf;
oftalmoscop;
taliometru;
panglica-centimetru;
cntar;
ecocardiograf;
cabinet de diagnostic funcional;
cabinet radiologic;
tomograf computerizat;
rezonana magnetic nuclear;
laborator radioizotopic;
densitometru prin raze X;
ultrasonograf articular;
laborator clinic standard pentru determinare de: creatinin
seric, hemoglobin, ALT, AST, bilirubin total i fraciile ei,
fosfataz alcalin, VSH, proteina C reactiv i realizarea de
sumar al urinei;
laborator imunologic;
laborator virusologic;
laborator bacteriologic;
secie de reabilitare;
secie ortopedie.
Medicamente:
AINS.
Glucocorticosteroizi.
Metotrexat.
23
24
4. Sporirea numrului de
pacieni cu AJI, forma
sistemic, supravegheai
conform recomandrilor
din protocolul clinic naional Artita juvenil idiopatic, forma sistemic
3.
4.
2. Sporirea calitii n
examinrile clinice i paraclinice ale pacienilor
cu AJI, forma sistemic
2.
Indicatorul
1. Sporirea numrului de
pacieni, crora li s-a stabilit n primele 3 luni de la
debutul bolii diagnosticul
de AJI, forma sistemic
Scopul
1.
Nr.
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
5. Sporirea numrului
de pacieni cu AJI, forma sistemic, crora li se
vor monitoriza posibilele
efectele adverse la tratamentul continuu cu preparate de remisiune
6. Sporirea numrului de
pacieni cu AJI, forma
sistemic, cu inducerea
remisiunii complete
7. Sporirea numrului de
pacieni cu AJI, forma
sistemic, cu meninerea
funciei articulare i a activitii zilnice
6.
7.
Scopul
5.
Nr.
Indicatorul
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
25
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
ANEXE
Cu ajutor din
partea altei
persoane
Nu pot efectua
Cu dificultate
Activitate
Fr
dificultate
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
3
26
7=2,33
8=2,67
9=3,0
10=3,33
11=3,67
12=4,0
13=4,33
14=4,67
15=5,0
16=5,33
17=5,67
18=6,0;
19=6,33
20=6,67
21=7,0
22= 7,33
23=7,67
24=8,0
25=8,33
26=8,67
27=9,0
28=9,33
29=9,67
30=10,0
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Satisfctor
Moderat
Moderat
Moderat
Moderat
Absent
Absent
Absent
Absent
27
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Data
Data
nlimea/greutatea
Frecventarea instituiei de nvmnt
colar: da/nu
Evaluarea global a bolii de ctre medic
(dup SVA)
Evaluarea global a bolii de ctre pacient
(dup SVA)
Numrul de articulaii dureroase (28)
Numrul de articulaii tumefiate (28)
Aprecierea durerii (dup SVA)
Durata redorii matinale (minute)
Tratamentul la zi:
1.
2.
3.
4.
Efectele adverse
1.
2.
3.
Monitorizarea de laborator
(VSH, proteina C reactiv)
Programul ocupaional
Examinarea oftalmologic
Alte probleme
Pacientul (a) ___________________________________feti/bieel.
Anul naterii __________
28
Data
Data
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Realizate
______
______
______
______
______
______
29
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Stnga pacientului
0=absent
1=prezent
Articulaie
Umr
Cot
Radiocarpian
MCF I
MCF II
MCF III
MCF IV
MCF V
MTF I
MTF II
MTF III
MTF IV
MTF V
Genunchi
Durere
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Inflamare
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
Articulaie
Umr
Cot
Radiocarpian
MCF I
MCF II
MCF III
MCF IV
MCF V
MTF I
MTF II
MTF III
MTF IV
MTF V
Genunchi
Durere
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Inflamare
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
30
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Da
Nu
V rugm s precizai preparatele care sunt noi, modificate sau pe care nu le mai utilizai de la
ultima vizit la medic
Denumirea
preparatului
Preparatul
nou, modificat,
suspendat
(n caz de
modificare
a dozajului,
indicai doza
curent)
31
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
Punctajul
Condiia
Insomnii
Probleme de stomac
Erupie a pielii
Insomnii
Tuse
Durere n piept
Ulcer oral
Ulceraii tegumentare
Dureri de cap
Senzaie de uscciune n ochi
Pierdere n greutate
32
Punctajul
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
33
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
BIBILOGRAFIA
1. Assessing, managing and monitoring biologic therapies for inflammatory arthritis. Guidance
for rheumatology practitioners, 2002. Available from: http://www.rcn.org.uk/__data/assets/pdf_
file/0004/78565/001984.pdf
2. Batthism M., Scheider R., Ramanan A.V. et. al. What does active disease mean? Patient and
parent perceptions of disease activity in the systemic arthritis form of juvenile idiopathic arthritis
(SO-JIA). Rheumatology. 2005;44:796-799.
3. Boers M., Verhoeven A.C., Marcusse H.M., Van Der Laar Mart Afg. et. al. Randomized
comparison of combined step-down prednisolone, methotrexate and sulphasalazine alone in early
rheumatoid arthritis. The Lancet. 1997;350 (9074):309-318.
4. Breedveld F.C., Weisman M.H., Kavanaugh A.F. et. al. The premier study: A multicenter,
randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexat
versus methotrexat alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis
who had not had previous methotrexat treatment. Arthritis & Rheumatism. 2006, January;54
(1):26-37.
5. Cassidy J.T., Petty R.E. Juvenile rheumatoid arthritis. In: Cassidy J.T., Petty R.E. editors. Textbook
of Pediatric Rheumatology. 4th ed. Philadelphia: W. B. Saunders Company; 2001, p.218.
6. Duffy C. Measurement of health status, functional status, and quality of life in children with
juvenile idiopathic arthritis: clinical science for the pediatrician. Pediatr Clin North Am. 2005;52
(2):359-372.
7. Foedvari I., Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with
juvenile idiopathic arthritis. J. Rheumatol. 2005;32:362.
8. Guidance on the use of etanercept and infliximab for the treatment of rheumatoid arthritis.
Technology appraisal guidance. 2005, March;36:22.
9. GUIPCAR Group. Clinical practice guideline for the management of rheumatoid arthritis.
Madrid: Spanish Society of Rheumatology. 2001, p.12.
10. Gutieriez-Suarez R., Pistorio A., Cespedes C.A. et. al. Health-related quality of life of
patients with juvenile idiopathic arthritis coming from 3 different geographic areas. The PRINTO
multinational quality of life cohort study. Rheumatology. 2007;46(2):314-320.
11. Hofer M.F., Mouz R., Prieur A.M. Juvenile idiopathic arthritides evaluated prospectively in a
single center according to the Durban criteria. J. Rheumatol.; 2001:28:1083.
12. Hofter M., Saurenmann Ozen S. et. al. Pediatric rheumatology European society clinical
guidelines: systemic arthritis. Pediatric Rheumatology Online Journal. 2004;9(24):1-10.
13. Horneff G., Schmeling H., Biedermann T. et. al. The German etanercept registry for treatment
of juvenile idiopathic arthritis. Ann. Rheum. Dis., 2004;63:1638.
14. Kirkham B.W., Lassere M.N., Edmonds J.P. et. al. Synovial membrane cytokine expression is
predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the
DAMAGE study cohort). Arthritis & Rheumatism. 2006, April;54(4):1122-1131.
15. Kounami S., Yoshyiyama M., Nakayama K. et. al. Macrophage activation syndrome in children
with systemic-onset juvenile chronic arthritis. Acta Haematol., 2005;113(2):124-129.
16. Hull R.G. Management Guidelines for arthritis in children.. Rheumatology. 2001;40:13081312.
34
Protocol clinic naional Artrita juvenil idiopatic, forma sistemic, Chiinu 2008
17. Oen K., Fast M., Postl B. Epidemiology of juvenile rheumatoid arthritis in Manitoba, Canada,
1975-95 cycles in incidence. J. Rheumatol., 1995;22:745.
18. Pteretson L.S., Mason T., Nelson A.M. et. al. Juvenile rheumatoid arthritis in Rochester,
Minnesota 1960-1993. Is the epidemiology changing? Arthritis Rheum., 1993;39:1385.
19. Petty R.E., Southwood T.R., Baum J. et. al. Revision of the proposed classification criteria for
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