uveiti associate a malattie reumatiche
TRANSCRIPT
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Uveiti associate a malattie reumatiche
Adriana BonoraClinica Oculistica
Az. Ospedaliera Universitaria Integrata
Verona
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Quali sono le malattie reumatiche che interessano l’occhio
· Artrite reumatoide · Sindrome di SjÖgren · Malattia di Behçet · Artrite idiopatica giovanile · Artriti reattive · Spondilite anchilosante · Lupus eritematoso sistemico
· Sclerodermia · Polidermatomiosite · Granulomatosi di
Wegener · Arterite a cellule giganti · Poliarterite nodosa · Granulomatosi allergica · Arterite di Takayasu
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Perché viene colpito l’occhio
• L'occhio, come altri organi, può essere colpito da processi autoimmuni ed autoinfiammatori per alterazione dei meccanismi immunitari (innati e adattativi)
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Quali sono le manifestazioni più comuni in corso di malattia reumatica
Ogni malattia si può manifestare tipicamente con un interessamento oculare diverso.
• Occhio secco (Sindrome di SjÖgren, Artrite reumatoide, Lupus eritematoso sistemico, Sclerodermia)
• Uveite anteriore acuta, cronica, recidivante (Spondilite anchilosante, Artrite idiopatica giovanile, M. di Beçhet)
• Uveite posteriore (M. di Beçhet) • Episclerite (Artrite reumatoide, Poliarterite nodosa, Lupus
eritematoso sistemico, M. di Beçhet) • Sclerite (Artrite reumatoide, Arterite di Wegener)
***********• Cheratiti periferiche ulcerative (Artrite reumatoide, Arterite di
Wegener, Poliarterite nodosa) • Vasculiti retiniche (Lupus eritematoso sistemico) • Otticopatie anteriori e posteriori (Arterite a cellule giganti)
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La comparsa di una patologia oculare può essere:
· il primo segno di una manifestazione reumatica sistemica
· il segno di una riattivazione della patologia
· può indicare la gravità della malattia reumatica
· può essere bersaglio degli effetti collaterali dei farmaci usati per la malattia reumatica
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Quale è il ruolo dell’oculista
· Gestire le manifestazioni oculari
· Indirizzare alla diagnosi
· Collaborare con il reumatologo
· Controllare gli effetti collaterali dei farmaci
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Uveiti
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Uveiti
• anamnesi oculare
• anamnesi generale
• esame obiettivo oculare- localizzazione anatomica
- caratteristiche tipiche- tipo di infiammazione
• esami selettivi
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CLASSIFICAZIONE DELLE UVEITI DEL SUN* WORKING GROUP
Sito primario infiammazione Manifestazioni
Uveiti anteriori
Camera anterioreIridocicliteCiclite anteriore
Uveiti intermedie
VitreoPars planiteCiclite posterioreIalite
Uveiti posteriori
Retina o coroide
Coroidite (focale, multifocale o diffusa)CorioretiniteRetinocoroiditeRetiniteNeuroretinite
PanuveitiCamera anteriore, vitreo, retina, coroide
*SUN = Standardization of uveitis nomenclature
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Esame obiettivo
Segni caratteristici possono orientarci
nella diagnosi in pochi minuti
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Uveiti anteriori granulomatose
• Idiopatica• Sarcoidosi • Tubercolosi• Sifilide• Sclerosi multipla • Malattia di Lyme
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Uveiti anteriori non granulomatose
• Idiopatica • HLA-B27 correlata • Ciclite eterocromica di Fuchs • Artrite idiopatica giovanile • Malattia di Behçet
• Uveite associata a sclerite• TINU (nefrite tubulo-interstiziale associata ad uveite)
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Artrite idiopatica giovanile
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Artrite idiopatica giovanile
• la più comune causa di uveite nei bambini
• uveite presente nel 20-30% dei casi di AIG
• 3: 1
• iridociclite asintomatica
• sinechie
• cheratopatia a bandelletta
• cataratta
• glaucoma
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Artrite idiopatica giovanile
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AIG
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Artrite idiopatica giovanile
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Intervallo uveite-AIG
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Severità
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Gestione AIG
• controllo oculistico periodico
• tropicamide
• steroidi topici (cell in CA)
• controllo TOO (successo chirurgia filtrante < 50%)
• chirurgia della cataratta (!!!)
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Uveite HLA B27 correlata
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Sindromi HLA B27 correlate
• uveite anteriore acuta
• spondilite anchilosante
• artrite reattiva a infezioni genitourinarie o gastointestinali (sr. di Reiter)
• malattie infiammatorie croniche dell’intestino(RCU e m. di Crohn)
• artrite psoriasica
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Uveite HLA B27+
• uveite anteriore acuta monolaterale
• non granulomatosa
• triade: iperemia pericheratica
dolore
fotofobia
• fini precipitati endoteliali
• intensa risposta cellulare
• fibrina in CA
• I° attacco < 40 aa
• recidivante
• spesso associata con spondiloartropatie sieronegative
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Uveite HLA B27+
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Sacroileite
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Progressione della spondilite anchilosante
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Trattamento
• STEROIDI: topici, perioculari, orali, intravitreali• MIDRIATICI • TERAPIA IMMUNOSOPPRESSIVA:
• casi refrattari• effetti avversi degli steroidi• corticodipendenza• rischio di danni visivi permanenti
– azatioprina, methotrexate, ciclosporina, ciclofosfamide, clorambucile– agenti biologici antiTNF:
• etanercept (Enbrel)• infliximab (Remicade)• adalimumab (Humira)
– interferon alpha • IFNα-2a
– sulfasalazina (artriti reattive)
• CONSULENZA REUMATOLOGICA
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Br J Ophthalmol. 2010 Oct 22.
Distress, depression and coping in HLA-B27-associated anterior uveitis with focus on gender differences.
Maca SM, Schiesser AW, Sobala A, Gruber K, Pakesch G, Prause C, Barisani-Asenbauer T.
Medical University Vienna, Vienna, Austria.
Patients with B27-AU patients exhibited significant psychopathology concerning depression and disease coping. Distress and life events were subjectively suspected to be a trigger. By imparting knowledge to the patients on probable development of depressive moods and the role of stress/life events as trigger for relapses, as well as offering behaviour therapy to optimise coping, may help patients to cope better with B27-AU.
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Malattia di Behçet
Hulûsi Behçet (1889–1948)
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• età 30 anni
• bacino Mediterraneo - Oriente
• cause multifattoriali – genetiche (HLA B51)
– infettive (Streptococcus sanguis, HSV)
– immunologiche
• decorso cronico recidivante
• diagnosi clinica:Criteria for diagnosis of Behçet's disease. International Study Group for Behçet's Disease.Lancet. 1990 May 5;335(8697):1078-80
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CRITERI MAGGIORI
• afte orali (99.3%)
• uveite 80% bilaterale, 20% monolaterale
– anteriore (60%)
– posteriore (75%)
– panuveite (90%)
• lesioni cutanee: pseudofollicolite,
eritema nodoso, lesioni papulopustolose, noduli acneiformi
• afte genitali (60%)
• pathergy test positivo
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CRITERI MINORI
• artrite
• ulcere ileocecali
• epididimite
• lesioni vascolari
• sintomi neurologici
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Laboratorio
• HLA B51
• anemia e leucocitosi
• aumento VES e Proteina C reattiva
• aumento alfa2globuline, IgA
• immunocomplessi circolanti
• assenza FR e ANA
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Joint Bone Spine. 2010 Jul;77(4):330-4. Epub 2010 May 8.
A study on thrombophilic factors in Italian Behcet's patients.Caramaschi P, Poli G, Bonora A, Volpe A, Tinazzi I, Pieropan S, Bambara LM, Biasi D.
BACKGROUND: Behcet's disease (BD) may complicate with arterial and venous thrombosis. The purpose of this work is to evaluate in an Italian group of BD patients with thrombotic events a large panel of inherited and acquired thrombophilic factors.
METHODS: Thirty BD patients, of which nine with previously arterial or venous thrombosis and 21 without,
underwent the following investigations: plasma antithrombin activity, protein C activity, free protein S level, sensitivity to APC, total plasma homocysteine concentration, serum folate level, determination of anti-phospholipid antibodies, serum Lp(a) levels, tests for gene polymorphisms of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase genes. Tests for the gene polymorphisms were also
performed in a group of healthy control subjects.
RESULTS: All the six patients with arterial or deep venous thrombosis showed thrombophilic conditions such as protein C or protein S deficiency (one case each), hyperhomocysteinemia (two cases), positivity of anti-phospholipid antibodies associated with APC resistance or hyperhomocysteinemia (one case each). Among three subjects with superficial thrombophlebitis only one showed a mild hyperhomocysteinemia. No differences were found between BD patients and control subjects concerning polymorphisms of the genes considered. Among BD patients the Factor V H1299R mutation showed a weak association with venous thrombosis (P=0.048).
CONCLUSION: In BD patients different concomitant significant thrombophilic risk factors may contribute to the development of thrombotic events. Patients affected by vasculo-Behcet should be evaluated for the presence of coexisting major thrombophilic conditions.
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Manifestazioni oculari
• sono precoci
• il coinvolgimento oculare è il più grave e il più temuto → cecità
• interessa il 60-80% dei pz con M. di Behçet
• uveite posteriore con vasculite occlusivavenosa e arteriosa (più raramente u. anteriore, sclerite, neurite ottica)
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Ipopion
• Ophthalmology. 2010 Feb;117(2):366-72.
• Hypopyon in patients with uveitis.
• Zaidi AA, Ying GS, Daniel E, Gangaputra S, Rosenbaum JT, Suhler EB, Thorne JE,
Foster CS, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Kempen JH; Systemic
Immunosuppressive Therapy for Eye Diseases Cohort Study.
• 4911 pazienti
• CONCLUSIONS: Hypopyon is an uncommon occurrence in patients
with uveitis. Risk factors included Behçet's disease, HLA-B27
positivity, and spondyloarthropathy. Intermediate uveitis cases (+/-
anterior uveitis) had a lower risk of hypopyon. On average, post-
hypopyon eyes were no more likely than other eyes with uveitis to
develop structural ocular complications or lose visual acuity.
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Conseguenze
• manicotti vascolari
• cicatrici corioretiniche
• atrofia retinica
• atrofia ottica
• neovascolarizzazione retinica
• glaucoma neovascolare
→CECITA’
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EULAR RECOMMENDATIONS FOR THEMANAGEMENT OF BEHÇET’S DISEASEAnn Rheum Dis, 2008
1. Any patient with BD and inflammatory eye disease affecting the posterior segment should be on a treatment regime, which includes azathioprine and systemic corticosteroids
2. If the patient has severe eye disease defined as >2 lines of drop in visual acuity on a 10/10 scale and/or retinal disease (retinal vasculitis or macular involvement), it is recommended that either cyclosporine A or infliximab be used in combination with azathioprine and corticosteroids; alternatively interferon-alpha with or without corticosteroids could be used instead
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Terapia
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SOMMINISTRAZIONE TOPICA CS
desametazone 2%
• uveiti anteriori
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SOMMINISTRAZIONE PERIOCULARE CSbetametasone disodio fosfato
metilprednisolone acetato
• u. anteriori non controllate dalla terapia topica
• u. intermedie
• u. posteriori acute
• u. diffuse
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SOMMINISTRAZIONE SISTEMICA CSprednisone
metilprednisolone
• u. anteriori, intermedie, posteriori non sufficientemente controllate dalla terapia topica e/o perioculare
• u. bilaterali posteriori e diffuse
• u. associate a malattie sistemiche
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SOMMINISTRAZIONE ENDOBULBARE CStriamcinolone
• uveiti gravi in cui non è praticabile la terapia corticosteroidea per via sistemica
• edema maculare
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dexamethasone intravitreal implant 0.7 mg
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Ocul Immunol Inflamm. 2010 Oct 31.
Clinical Review: Update on Treatment of Inflammatory Macular Edema.
Ossewaarde-van Norel A, Rothova A.
Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
The aim of this review is to summarize the recent developments in the treatment of inflammatory macular edema (ME). Inflammatory ME represents a major cause of visual loss in uveitis and its adequate management is crucial for the maintenance of useful vision in patients with uveitis. Recent studies favor early treatment of inflammatory ME, even in patients with full visual acuity. After recapitulating the standard treatment modalities for inflammatory ME the authors address novel corticosteroid implants. They review the literature on the efficacy of anti-VEGFagents for inflammatory ME and point out their beneficial, but transient effects. Further, they present recent data on the value of systemic biologics in uveitic ME and evaluate the effectiveness of vitrectomy. Finally, they propose an algorithm for the treatment of inflammatory ME and point out that the individual risk-benefit ratio, especially with systemic immunosuppressive therapy, should always be considered.
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IMMUNOSOPPRESSORI
INDICAZIONI
ASSOLUTE:
• M. di Behçet
• uveite simpatica steroido-resistente
INDICAZIONI
RELATIVE:
• uveiti bilaterali, non infettive,corticoresistenti, con prognosi visiva infausta
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ANTIMETABOLITI e AGENTI ALCHILANTI
Utilizzati in associazione con steroidi e/o
ciclosporina per ridurne i singoli dosaggi.
• EFFETTI COLLATERALI:
leucopenia, trombocitopenia, epato-nefrotossicità, effetti carcinogenetici,effetti teratogeni, azoospermia irreversibile.
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ANTIMETABOLITI
• AZATIOPRINA
1-2.5 mg/kg/die x os
• METHOTREXATE
7.5-15 mg/sett x os o IM
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AGENTI ALCHILANTI
• CLORAMBUCILE(Leukeran 2 mg)
6-12/mg/die
• CICLOFOSFAMIDE(Endoxan 50 mg)
2 mg/kg/die
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CICLOSPORINA A
• 5 mg/kg/die in due somministrazioni
• riduzione graduale fino a 2 mg/kg/die
• durata terapia?
• effetto rebound
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CICLOSPORINA A
EFFETTI COLLATERALI:
• ipertensione arteriosa• anemia• iperuricemia• aumento VES• aumento transaminasi• nefrotossicità
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Farmaci Biologici neltrattamento delle Uveiti
• agenti biologici antiTNF:• etanercept (Enbrel)
• infliximab (Remicade)
• adalimumab (Humira)
• interferon alpha • IFNα-2a
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Agenti biologici antiTNF:
• uveite associata alle SpA
• uveite associata alla artrite idiopatica giovanile
• uveite posteriore
– m. di Behçet
– panuveite
– vasculite
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Interferon alpha
• M. di Behçet
• VKH