Il morbillo è una malattia infettiva virale, altamente contagiosa e diffusiva caratterizzata da esantema maculopapuloso confluente, mucositi (manifestazioni catarrali a carico delle prime vie aeree) e compromissione delle condizioni generali.
Eziologia
Il virus del morbillo appartiene al genere Morbillivirus e alla famiglia Paramyxoviridae. A forma sferica e struttura icosaedrica, un diametro compreso tra 100 e 250 nm. Il virione è rivestito da un doppio strato lipidico dal quale protrudono due proteine glicosilate: emoagglutinina e la proteina di fusione; la prima è responsabile dell’adesione alle cellule suscettibili, la seconda provoca la fusione con la membrana cellulare della cellula ospite.
Epidemiologia
L’unica sorgente di infezione è l’ammalato che elimina abbondantemente il virus con le secrezioni nasofaringee e con i colpi di tosse durante tutta la fase prodromica e i primi giorni della fase esantematica della malattia; non si riconoscono portatori sani o convalescenti del virus. La trasmissione respiratoria avviene principalmente attraverso droplets a breve distanza e meno frequentemente con particelle di aerosol che rimangono sospesi in aria più a lungo. È una malattia a elevata contagiosità ma nonostante da oltre 50 anni sia disponibile un vaccino rimane un importante causa di morbilità e una delle principali cause di mortalità infantile dovuta alla scarsa copertura vaccinale.
Patogenesi
Una volta che il virus è penetrato nell’organismo le emoagglutinine virali si legano ai recettori cellulari e interagiscono con le proteine di fusione che mediano la fusione dell’ envelope con la membrana della cellula ospite. Una iniziale fase replicativa della durata di 3 giorni avviene nelle mucose delle prime vie aeree e nei linfonodi regionali. Successivamente il virus veicolato da linfociti e monociti, passa in circolo e raggiungere le cellule del sistema reticolo- endoteliale di tutti gli organi dove ha luogo una seconda importante fase replicativa, seguita da una massiva viremia. La replicazione virale determina la formazione di cellule giganti multinucleate e si accompagna iperplasia linfoide. In undicesima giornata cominciano a presentarsi segni prodromici e in quattordicesima giornata appare l’esantema, che sembra sia dovuto a una reazione di ipersensibilità ritardata nei confronti dei complessi immuni virus-anticorpo presenti a livello dei piccoli vasi del derma. L’ emoagglutinina induce una forte risposta immunitaria e l’immunità permanente indotta dall’infezione naturale in gran parte è conseguenze degli anticorpi neutralizzanti diretti verso
l’ emoagglutinina.
Manifestazioni cliniche
Dopo un periodo di incubazione di 9-12 giorni inizia la malattia nella quale si susseguono tre fasi.
Fase prodromica o delle mucositi o catarrale della durata di 4-5 giorni e caratterizzata da: a. febbre continuo-remittente; b. mucositi; c. enantema (chiazze di Koplik). Le mucose congiuntivali, nasali e faringee sono contemporaneamente coinvolte (triplice catarro). Il paziente lamenta fotofobia, lacrimazione, secrezione nasale sierosa e tosse secca. La mucosa orofaringea è arrossata e tumefatta e a livello del palato molle e spesso si evidenziano piccole petecchie. Tra la seconda e la terza giornata del periodo prodromico compaiono, sulla faccia interna delle guance in corrispondenza dei premolari, elementi puntiformi biancastri circondati da alone eritematoso e noti come “chiazze o segni di Koplik”, che scompaio nel volgere di di 24-48 ore.
Fase esantemica della durata di 4-5 giorni. L’esantema costituito da maculopapule di pochi millimetri inizia alcollo, alle regioni retroauricolari e alla nuca e si estende in senso craniocaudale, interessando nelle prime 24 ore il volto, il tronco e gli arti superiori e successivamente il dorso e l’addome e nel volgere di 2-3 giorni anche gli arti inferiori. Gli elementi, inizialmente isolati, tendono dopo 12-24 ore a confluire il larghe chiazze a carta geografica da assumere un colore più vivace.
Fase di risoluzione: l’esantema una volta raggiunto l’acme, tende a sbiadire e scompare del tutto nel volgere di 5-6 giorni; sulla cute rimane una lieve pigmentazione brunastra accompagnata da desquamazione furfuracea. Contemporaneamente la febbre che cede per lisi. La tosse può durare a lungo.
Sono state descritte forme cliniche gravi, attenuate e atipiche. Le principali forme cliniche con andamento grave sono il morbillo emorragico e quello ipertossico. La forma emorragica si manifesta con petecchie, soffusioni emorragiche cutanee, ematuria, epistassi e melena. Frequentemente si associano ipertermia e stato di agitazione psicomotoria. La forma ipertossica colpisci pazienti defedati, malnutriti con deficit immunitari e si presenta con ipertermia, esantema molto intenso, diarrea, disidratazione e sintomi neurologici. Le forme attenuate sono dovute alla parziale immunizzazione dell’ospite. Si presentano in lattanti con età inferiore a 6 mesi in cui è presente un residuo degli anticorpi trasmessi per via diaplacentare o in soggetti a cui sono state somministrate dosi inadeguate di immunoglobuline a scopo profilattico. Clinicamente la febbre è assente o modica, le mucositi sono spesso assenti e compaiono contemporaneamente a un fugace esantema costituito da uno scarso numero di maculopapule non confluenti.
Alterazioni di laboratorio
L‘esame emocromocitometrico evidenzia leucocitosi nei primi giorni di malattia e leucopenia con linfocitosi relativa durante la fase esantematica.
Complicanze
Le complicanze del morbillo hanno una frequenza globale del 10-15% e in alcuni casi sono particolarmente gravi. Le più frequenti sono quelli a carico dell’apparato respiratorio e possono dipendere dalla localizzazione diretta del virus o da infezioni batteriche sovrapposte; comprendono otite, laringite, broncopolmonite batterica e polmonite interstiziale (1-2 casi su 100). Più rare ma con prognosi riservata, sono le complicanze neurologiche come l‘encefalite acuta e subacuta (1 caso su 1000) e la panencefalite sclerosante subacuta (10 casi per milione). Altre complicanze sono quelle cardiache, oculari, la porpora piastrinopenica e la linfoadenopatia mesenterica. Il polmone è frequentemente coinvolto in quadri radiologici di interstiziopatia con ingrandimento delle ombre ilari. In pazienti con deficit immunitari può però manifestarsi in un grave quadro di bronchiolite o di polmonite interstiziale.
L’ encefalite acuta insorge in genere da 2 a 7 giorni dopo la comparsa dell’esantema. È una forma di tipo demielinizzante. Inizia con febbre elevata, cefalea, tremori, irritabilità e spesso segni di flogosi meningea; confusione mentale, obnubilamento del sensorio, atassia, paresi e paralisi a carico degli arti, ipertonie ecc.. ecc.. La prognosi è riservata, l’exitus si verifica nel 10-12% dei casi e in circa il 40% di soggetti che sopravvive, residuano gravi sequele neurologiche.
La panencefalite sclerosante subacuta (PESS) ha un insorgenza tardiva (in genere a distanza di 5-8 anni dal pregresso morbillo), con maggiore frequenza in pazienti che hanno contratto la malattia nel primo biennio di vita. È provocata da un’infezione persistente del virus a livello del sistema nervoso centrale con una lenta e continua liberazione di particelle virali che determinano lesioni degenerative sia dei neuroni sia degli oligodendrociti. La malattia inizia con disturbo del comportamento, (cambiamento di umore, ansia ecc..) e della memoria; dopo alcuni mesi cominciano a rendersi evidenti segni ipercinetici quali tremori, mioclonie e convulsioni, ai quali, in seguito si aggiungono fenomeni spastici e obnubilamento del sensorio. Il deterioramento intellettuale e la compromissione del sensorio progressivamente e lentamente si aggravano fino al subentrare di uno stato comatoso seguito dal exitus, in un periodo variabile tra 1 a 3 anni anche se talvolta la durata della malattia è più protratta.
Diagnosi
E’ di solito agevole nel periodo esantematico mentre può risultare difficile nella fase prodromica. Me nei casi dubbi si può ricorreree alla ricerca degli anticorpi specifici di classe IgM che compaiono entro 1-2 giorni dall’esordio dell’esantema.
Prevenzione
Il morbillo è soggetto a notifica obbligatoria. La prevenzione si basa sull’ immunizzazione attiva (vaccinazione) e su quella passiva (somministrazione di immunoglobuline). Il vaccino è costituito da virus vivo attenuato, disponibile in formulazione monovalente associato ad antirosolia e antiparotite. In Italia la vaccinazione viene praticata dai 13-15 mesi con una seconda somministrazione fra i 5-6 e i 14 anni. In circa il 10% dei vaccinati 7- 8 giorni dopo la vaccinazione può insorgere febbre (38 -39°) che generalmente regredisce in 24-48 ore. Nelle 5-8% dei casi la febbre è accompagnata da un eruzione maculopapulosa di breve durata. La vaccinazione è controindicata nelle donne in gravidanza, nei soggetti con allergia alle proteine dell’uovo e in quelli con deficit dell’immunità cellulomediata; i pazienti HIV-sieropositivi con numero di linfociti T CD4+ più non inferiore al 15% devono comunque essere vaccinati.
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