Boala mixta de tesut conjunctiv - 2018

• Descrisa de Sharp in 1972

• Asociere de caracteristici comune cu LES, SD, PM

• 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

Varsta de aparitie poate varia; media la 15-30 ani

Prevalenta = ??
2,7-10 :100.000 (Japonia)
3.8 per 100,000 Norvegia 2011

Peste DM (1,5/1000.000) , sub LES (20/100.000)

Nu exista date despre 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

=>Hiperactiv cel B => Ac anti U1 RNP
 ipoteza: individ genetic predispus (HLA DRB1*04) dezvolta un raspuns
imun impotriva unui antigen – microbian?? => (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 patern 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 cu trei polipeptide A’, C’ si 70 kD
DAYS OF OUR LIFE!!
 Tablou clinic - Debut

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

Fenomen Raynaud (W,B,R)

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
 Sd Raynaud
1. Ac antinucleari, Ac anti centr.,Ac anti Scl70
2.Capilaroscopie +++
3.BRGE
4.Puffy fingers
5.Tendon friction rubs
6. Varsta >30, sex M, necroze
 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 ~ activitatea 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 in special:
Ac IgG anticardiolipin
Ac antiendoteliali => HTP
Tablou clinic
 Criterii de diagnostic

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

sau >1/1280
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 cu compl Cardiace
2. Miocardita
3. HTA renovasculara
4. Hemoragie intracerebrala
5. Infectii
 Bibliografie
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