Boala mixta de tesut conjunctiv - 2012Descrisa 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.
EpidemiologieMai frecventa la femei 10/1 => 15/1
Vrsta de aparitie poate varia; media la 15-30 ani
Prevalenta = ?? 2,7-10 :100.000 (Japonia) Peste DM (1,5/1000.000) , sub LES (20/100.000)
Nu exista date despre o predispozitie etnica sau de rasa
EtiopatogenieFactori de mediu - siliciul - clorura de vinil- retrovirusuri animale cu similitudini structurale cu U1-RNPTerenul genetic- HLA DR2 si DR4Factori 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 RNPPrezenta Ac anti U1-RNP este definitorie pentru BMTCPrima constatare poate fi doar un titru crescut de Ac antinucleari (ANA) cu patern patat in titru crescutAu 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 - DebutDe regula insidios: astenie fizic, mialgii, artralgii, febra
Fenomen Raynaud (Maurice Raynaud1862=> W,B,R)SclerodactiliaArtriteMai rar: - nevralgie trigeminala - polimiozita - artrita acuta - gangrene digitale
Tablou clinicManifestari generale: Febra, astenia fizica Manifestari cutaneo-mucoase: edem al mainilor, rash, macule eritematoase la baza degetelorFenomenul Raynaud 70-90% -capilaroscopie
Sd Raynaud1. Ac antinucleari, Ac anti centr.,Ac anti Scl702.Capilaroscopie +++3.BRGE4.Puffy fingers5.Tendon friction rubs6. Varsta >30, sex M, necroze
Tablou clinicManifestari 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 clinicManifestari 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 clinicManifestari 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 perifericeSarcina (?) - ischemia vaselor placentare in prezenta Sd R sever; - Sd AFL
Tablou paraclinicTeste de inflamatie nespecifica: VSH, PCR ++ coreland cu gradul de activitate al boliiAnemia = normocroma, normocitara, sau (rar) hemolitica Leucopenia cu limfopenie ~ activitatea boliiTrombocitopenia raraAc anti U1 RNP la titru cresut => lipsa afectarii neuropsihiceabsenta afectarii renale severe artrite severe erozive in prezenta FR+risc pentru HTP
Tablou paraclinicGamaglobuline Ig G +++Hipocomplementemia ( 25% ) FR ( 50%) => artrite eroziveAnticorpi anticardiolipina si anticoagulantul lupic mai putin asociati manifestarilor de tip trombotic si mai mult HTPAc antiendoteliali => HTP
Tablou clinic
Criterii de diagnostic (Alarcon-Segovia)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 clinica1/3 semne generale si artrite usoare => analgezice si AINSFenomen Raynaud=> masuri generale, nifedipin ret., pentoxifilin, Artritele neerozive si afectarile cutanate => hidroxiclorochinaArtrite severe, pleurezii => CS doze mici Miozita, vasculitele=> CS doze mariBRGE => IPP, dar si prednison 25mg /zi
Alveolita fibrozanta => ciclofosfamida + CS
HTP => -anticoagulante, -diuretice, -oxigenoterapie, PG in perfuzie continua (epoprostenol);antagonist al receptorului de endotelina (Bosentan);inhibitori de fosfodiesteraza (sildenafil);
Transplantul pulmonar.
Evolutie, complicatii, prognosticStrict dependenta de tipul afectarii organiceComplicatii ale terapiei => necroza aseptica, osteoporoza, ATS accelerata Artrite deformante - numar mic de pacienti BRGE => esofag Barret cu risc de carcinom esofagianMortalitatea (mai redusa decat in LES) =>1. HTP progresiva2. Miocardita3. HTA renovasculara4. Hemoragie intracerebrala5. Infectii
BibliografieSharp, GC, Irvin, WS, Tan, EM, et al. Mixed connective tissue disease: an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen. Am J Med 1972; 52:148.Sharp GC, Irwin WS, May CM et al. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective tissue disease, systemic lupus erythematosus and other rheumatic diseases. N Engl J Med 1976; 29: 1149-1154.Nakae, K, Furusawa, F, Kasukawa, R, et al. A nationwide epidemiological survey on diffuse collagen diseases: Estimation of prevalence rate in Japan. In: Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Kasukawa, R, Sharp, G (Eds), Excerpta Medica, Amsterdam, 1987. p.9.Feldman F. Mixed connective tissue disease. Radiol Clin North Am 1988;26:1235-1246Robert W Hoffman, Eric L Greidinger, Mixed Connective-Tissue Disease May 2, 2005 eMedicine.com, Inc.Kahn MK, Borgeois P, Aeschlimann A, De Truchis P. Mixed connective tissue disease after exposure to vinyl chloride. J Rheumatol 1989; 16: 533-535.Bennett, RM. Anti-U1 RNP antibodies in mixed connective tissue disease. In: Up To Date, Rose,BD (Ed), Up To Date, Wellesley, MA, DEC, 2004.Hoffman, RW, Greidinger, EL, Mixed Connective-Tissue Disease eMedicine.com, Inc. May 2, 2005.Bennett, RM. Definition and diagnosis of mixed connective tissue disease. In: Up To Date, Rose,BD (Ed), Up To Date, Wellesley, MA, DEC, 2004.Black CM, Maddison PJ, Welsh KI et al. HLA and immunoglobulin allotypes in mixed connective tissue disease. Arthritis Rheum 1988; 31: 131-135. Query CC, Keene JD. A human autoimmune protein associated with U1 RNA contains a region of homology that is cross reactive with retroviral p30 gag antigen. Cell 1987; 51: 211-220.Bennett, RM. Clinical manifestations of mixed connective tissue disease. In: Up To Date, Rose,BD (Ed), Up To Date, Wellesley, MA, DEC, 2004.Venables,PJW. Mixed connective tissue disease. In Rheumatology, Third Edition. Hochberg, MC, Silman, JA, Smolen,JS, Weinblatt, ME,Weisman, MH (Eds), Rheumatology Online. 2005 Elsevier: 1574-1577Piirainen 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.
