Boala mixta de tesut conjunctiv

• Descrisa de Sharp in 1972

• Asociere de caracteristici comune cu LES, SD, PM, PR

• Prezenta in titru crescut a Ac anti-RNP - astazi definiti ca

Ac anti U1-RNP
 Boala mixta de tesut conjunctiv

Sindromul Overlap ( Overlap Syndromes ) caracterizeaza pacienti

care intrunesc criterii pentru mai multe boli de tesut conjunctiv
( ex: LES+PR, Scl+PM, CREST+CBP ).

Boala nediferentiata de tesut conjunctiv - se refera la pacienti

care nu intrunesc suficiente argumente diagnostice pentru nici
una din bolile de tesut conjunctiv .

Boala mixta de tesut conjunctiv este o entitate clinica distincta

definita pe baza argumentelor genetice, serologice si clinice.
 Epidemiologie

Mai frecventa la femei 10/1 => 15/1

Vrsta de aparitie poate varia; media la 35-40 ani

Prevalenta 2,7-10 :100.000

Nu exista o predispozitie etnica sau de rasa

 Etiopatogenie

Factori de mediu
- siliciul
- clorura de vinil
- retrovirusuri animale cu similitudini structurale cu U1-RNP
Terenul genetic
- HLA DR2 si DR4
Factori hormonali

Mecanismul leziunilor este imun cu implicarea directa a Ac anti U1

RNP => ipoteza: individ genetic predispus (HLA DR4,DR2) dezvolta
un raspuns imun impotriva unui antigen microbial (ex: glicoproteina
CMV) ce reactioneaza incrucisat cu peptidul U1 70 KD
 Boala mixta de tesut conjunctiv-
Rolul Ac ani U1 RNP

Prezenta Ac anti U1-RNP este definitorie pentru BMTC

Prima constatare poate fi doar un titru crescut de Ac antinucleari
(ANA) cu patern patat in titru crescut
Au pattern patat Ac anti Sm , Ac anti U1-RNP, anti Ro, anti La
Uneori la debut pot fi prezenti in titru scazut Ac anti Ro, anti Sm,
anti ADNdc
Spectrul clinic al bolii depinde de persistenta la titru inalt a Ac anti
U1-RNP
U1-RNP = ARN bogat in uridina complexat specific cu trei
polipeptide A’ , C’ si 70 kD
 Tablou clinic - Debut

De regula insidios: astenie fizică, mialgii, artralgii, febra

Fenomen Raynaud
Sclerodactilia
Artrite
Mai rar: - nevralgie trigeminala
- polimiozita
- artrita acuta
- gangrene digitale
 Tablou clinic

Manifestari generale: Febra, astenia fizica

Manifestari cutaneo-mucoase: edem al mainilor, rash, macule
eritematoase la baza degetelor
Fenomenul Raynaud 70-90%
-capilaroscopie
 Tablou clinic

Manifestari articulare: - artrite nespecifice MCF si IFP

- neerozive, nemutilante
- tenosinovite ale flexorilor

Manifestari musculare - Mialgia – de regula - fara slabiciune

musculara, enzime, modificari EMG
- Miozita de tipul afectarii din PM

Manifestari digestive - 1/3 inferioara a esofagului => BRGE

- vasculita mezenterica,pseudodiverticuli
 Tablou clinic

Manifestari pulmonare (80%)

- fibroza pulmonara interstitiala -sindrom restrictiv cu scaderea

TLCO
- hipertensiunea pulmonara – principala cauza de mortalitate
- afectare pleurala – revarsate pleurale mici
- pneumonie de aspiratie
- tromboembolii
- infectii
 Tablou clinic

Manifestari cardiovasculare - pericardita, cu risc de tamponada

- miocardita
Manifestari renale - GN membranoasa
- amiloidoza si insuficienta renala
- HTA maligna
- Ac anti U1-RNP in titru mare au probabil efect protector

Afectarea nervoasa – lipsa complicatiilor neuropsihice severe

- nevralgia trigeminala
- cefalee, migrene
- infarcte cerebrale
- neuropatii periferice
Sarcina ? – ischemia vaselor placentare in prezenta Sd R sever;
- Sd AFL
 Tablou paraclinic

Teste de inflamatie nespecifica: VSH, PCR ++ coreland cu gradul

de activitate al bolii
Anemia => normocroma, normocitara, sau (rar) hemolitica
Leucopenia cu limfopenie ~ gradul de activitate al bolii
Trombocitopenia – rara
Ac anti U1 RNP la titru cresut =>
lipsa afectarii neuropsihice
absenta afectarii renale severe
artrite severe erozive in prezenta FR+
risc pentru HTP
 Tablou paraclinic

Gamaglobuline – Ig G +++
Hipocomplementemia ( 25% )
FR ( 50%) => artrite erozive
Anticorpi anticardiolipina si anticoagulantul lupic mai putin asociati
manifestarilor de tip trombotic si mai mult HTP
Ac antiendoteliali => HTP
 Criterii de diagnostic

1.Criteriul serologic: Ac anti U1-RNP la un titru de peste 1:1600

( test de hemaglutinare )

2.Criterii clinice:
- edem al mainilor
- sinovite
- miozita
- fenomen Raynaud
- acroscleroza

Diagnostic pozitiv = Criteriul serologic + 3 criterii clinice

 Tratament

• Terapii similare cu cele din LES, Scl, PM, in functie de forma

clinica
• 1/3 semne generale si artrite usoare => analgezice si AINS
• Fenomen Raynaud=> masuri generale, nifedipin ret., pentoxifilin,
• Artritele neerozive si afectarile cutanate => hidroxiclorochina
• Artrite severe, pleurezii => CS doze mici
• Miozita, vasculitele=> CS – doze mari
• BRGE => IPP, dar si prednison 25mg /zi
• Alveolita fibrozanta => ciclofosfamida + CS
• HTP => anticoagulante, diuretice, oxigenoterapie, prostaciclina in
perfuzie continua (epoprostenol); antagonist al receptorului de
endotelina (Bosentan); inhibitori de fosfodiesteraza(sildenafil);
transplantul pulmonar
 Evolutie, complicatii, prognostic

Strict dependenta de tipul afectarii organice

Complicatii ale terapiei => necroza aseptica, osteoporoza, ATS
accelerata
Artrite deformante - numar mic de pacienti
BRGE => esofag Barret cu risc de carcinom esofagian
Mortalitatea (mai redusa decat in LES) =>
1. HTP progresiva
2. Miocardita
3. HTA renovasculara
4. Hemoragie intracerebrala
5. Infectii
 Bibliografie
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associated with a specific antibody to an extractable nuclear antigen. Am J Med 1972; 52:148.
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tissue disease, systemic lupus erythematosus and other rheumatic diseases. N Engl J Med 1976; 29: 1149-1154.
3. Nakae, K, Furusawa, F, Kasukawa, R, et al. A nationwide epidemiological survey on diffuse collagen diseases: Estimation
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Wellesley, MA, DEC, 2004.
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Wellesley, MA, DEC, 2004.
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Weinblatt, ME,Weisman, MH (Eds), Rheumatology Online. 2005 Elsevier: 1574-1577
13. Piirainen HI; Kurki PT. Clinical and serological follow-up of patients with polyarthritis, Raynaud's phenomenon, and
circulating RNP antibodies. Scand J Rheumatol 1990;19(1):51-6.