Atopic dermatitis (AD) therapeutic approach calls for a long‐term treatment. Treatment options for AD have recently undergone a revolutionary change by the introduction of the first biologic drug. ...Availability in daily practice of the last version of international AD guidelines, taking peculiarities of the country into account, can contribute to good clinical practice in Italy. To adapt European Dermatology Forum (EDF) guidelines for AD to the Italian medical–legal context, the EDF guidelines were assessed independently by two independent Italian renowned experts in the field and further integrated with articles published and systematically reviewed before May 2019. The first draft was collegially corrected and updated by the members of the SIDEMAST, ADOI, and SIDAPA. Recommendation levels (A; B; C; D) were graded based on the evidence levels (1–4). The adapted guidelines presented here focus on topical and systemic therapies in AD patients, both children and adults. As opposed to previous Italian guidelines, they include indications about biologics. New relevant evidence available from very recent literature and peculiarities of the Italian medical and legal context have been integrated in the revision process. If compared to general guidelines for AD not adapted to a specific national and cultural context, a revision for specific Italian needs is now available: It comprises the option of implementing the new biologic treatments and is likely to provide an important contribution to the improvement of clinical practice in Italy. Cooperation between patients, dermatologists, allergologists, and pediatricians remains mandatory in AD management. The authors of the present revision recommend an update of the Italian guidelines to be performed at least every second year.
Ulcerozni kolitis kronična je upalna bolest za koju su karakteristične ulceracije sluznice debeloga crijeva i klinički tijek obilježen razdobljima remisije i relapsa bolesti. Klinički se ulcerozni ...kolitis najčešće očituje učestalim sluzavo-krvavim proljevima. Azatioprin je tiopurin koji imunosupresiju postiže putem svojih aktivnih metabolita. Oni potiču apoptozu T-limfocita, te, inkorporirajući se u replicirajući lanac DNA i blokirajući de novo sintezu purina, smanjuju njihovu proliferaciju. Mjerenjem aktivnosti tiopurin Smetiltransferaze i praćenjem metabolita tiopurina, uspješno se postiže optimizacija terapije. Time se poboljšava klinička djelotvornost liječenja, te sprječava neuspjeh liječenja uzrokovan štetnim nuspojavama azatioprina. Unatoč pretpostavkama da će u budućnosti, zbog razvoja učinkovitijih i sigurnijih lijekova, uloga tiopurina u liječenju bolesnika s ulceroznim kolitisom biti ograničenija, azatioprin i dalje ostaje neizostavan lijek u liječenju bolesnika s ulceroznim kolitisom.
Ulcerative colitis is a chronic inflammatory disease characterized by ulcerative lesions of the colon mucosa and clinical course characterized by periods of remissions and relapses. The most common clinical symptom of ulcerative colitis is frequent bloody diarrhea usually accompanied by mucus. Azathioprine is a thiopurine which achieves immunosuppression through its active metabolites. They induce apoptosis of T-lymphocytes and, by incorporating into the replicating DNA chain and blocking de novo purine synthesis, reduce its proliferation. The measurement of thiopurine S-methyltransferase together with thiopurine metabolites monitoring successfully lead to therapy optimization. Thus, improving clinical effectiveness of the therapy and preventing management failure from adverse effects. Despite assumptions that in future, due to the intensive development of more effective and safer medicaments, the role of thiopurines in the treatment of patients with ulcerative colitis will be more restricted, azathioprine still remains an unavoidable medicament in the treatment of patients with ulcerative colitis.
Liječenje upalnih bolesti crijeva je kompleksno i zahtijeva individualan pristup svakom pojedinom bolesniku. Aminosalicilati su dugo vremena bili lijek prvog izbora u liječenju tih bolesnika. Uloga ...aminosalicilata u liječenju Crohnove bolesti je danas prilično minorizirana, lijek su prvoga izbora za liječenje blagih do srednje teških oblika ulceroznog kolitisa. Kortikosteroidi su terapija izbora u liječenju Crohnove bolesti, te u postizanju remisije srednje do teško aktivnog ulceroznog kolitisa. Azatioprin i 6-merkaptopurin imaju primarnu ulogu u liječenju bolesti ovisne ili refraktorne na kortikosteroide, te u održavanju postignute remisije. Sve se više predlaže rano uvođenje tih lijekova u terapiju s ciljem povećanja postotka bolesnika koji ostaju u remisiji. Metotreksat se koristi za liječenje aktivne i relapsirajuće Crohnove bolesti te je alternativa kod bolesnika koji ne podnose ili ne reagiraju na terapiju azatioprinom ili 6-merkaptopurinom. Ciklosporin se koristi u liječenju steroid-refraktornog teškog oblika ulceroznog kolitisa, te kod nekih bolesnika može odgoditi potrebu za kolektomijom. Antibiotici nemaju dokazani učinak na tijek upalnih bolesti crijeva, a primarna im je uloga u rješavanju septičkih komplikacija bolesti. Klasični lijekovi i danas su standard terapije upalnih bolesti crijeva, a kombinacija navedenih klasičnih lijekova često ima bolji učinak za tijek bolesti od izoliranih preparata i predmet je daljnjih istraživanja.
La leucopenia relacionada con tiopurina está asociada con polimorfismos en la tiopurina metiltransferasa (TPMT, por sus siglas en inglés) y con el gen NUDT15. Sin embargo, estos polimorfismos ...explican solo una fracción de la leucopenia relacionada con tiopurina. Nuestro objetivo fue estudiar el papel de un polimorfismo de pirofosfatasa inosina trifosfato (ITPA, por sus siglas en inglés) en pacientes con enfermedad inflamatoria intestinal (EII) y la leucopenia relacionada con tiopurina que no fue explicada por los polimorfismos de TPMT o NUDT15.
Reclutamos a pacientes consecutivos con EII tratados con tiopurinas (azatioprina o 6-mercaptopurina) entre enero del 2019 y marzo del 2020, en un centro de tercer nivel en el norte de la India. La presencia de polimorfismo en ITPA (C.94C>A) fue evaluada en todos los pacientes, junto con su asociación a la leucopenia relacionada con tiopurina.
De los 33 pacientes (de un total de 119 pacientes) que desarrollaron leucopenia, 8 presentaron polimorfismo en TPMT (n=1) o NUDT15 (n=7). De los 111 pacientes restantes, la edad promedio fue de 36.36± 13.54 años y 57 (51.3%) fueron varones. Veinticinco (21.01%) presentaron leucopenia no explicada. El polimorfismo en ITPA fue detectado en 4 (16%) pacientes del grupo de leucopenia no explicada y en 24 (27.9%) pacientes del grupo sin leucopenia (p=0.228). La razón de momios para predecir la leucopenia con polimorfismo en ITPA fue de 0.4921 (IC 95%: 0.1520-1.5830; p=0.234).
El polimorfismo en ITPA (C.94C>A) fue frecuentemente detectado en la población de estudio, pero no fue predictivo para leucopenia en pacientes con EII en terapia con tiopurina.
Thiopurine-related leukopenia is associated with polymorphisms in the thiopurine methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X type motif 15 (NUDT15) genes. However, those polymorphisms explain only a fraction of thiopurine-related leukopenia. Our aim was to study the role of an inosine triphosphate pyrophosphatase (ITPA) polymorphism in patients with inflammatory bowel disease (IBD) and thiopurine-related leukopenia that was unexplained by the TPMT and NUDT15 polymorphisms.
We enrolled consecutive IBD patients on thiopurines (azathioprine or 6-mercaptopurine) from January 2019-March 2020, at a tertiary care center in North India. The presence of the ITPA (C.94C>A) polymorphism was evaluated in all patients, along with its association with thiopurine-related leukopenia.
Of the 33 patients (from a total of 119 patients) that developed leukopenia, 8 had the TPMT (n=1) or NUDT15 (n=7) polymorphism. Of the remaining 111 patients, their mean age was 36.36±13.54 years and 57 (51.3%) were males. Twenty-five (21.01%) had unexplained leukopenia. The ITPA polymorphism was detected in 4 (16%) patients in the unexplained leukopenia group and 24 (27.9%) patients in the non-leukopenia group (P=.228). The odds ratio for predicting leukopenia with the ITPA polymorphism was 0.4921 (95% CI: 0.1520-1.5830; P=.234).
The ITPA (C.94C>A) polymorphism was frequently detected in the study population but was not predictive for leukopenia in patients with IBD on thiopurine therapy.
El éxito obtenido en los últimos años con los trasplantes cardíacos es en buena parte debido al desarrollo de técnicas adecuadas de inmunosupresión, que permiten e! tratamiento del rechazo y su ...prevención. El descubrimiento de la ciclosporina en 1972, marcó una nueva era en este sentido y modificó el pronóstico de los pacientes sometidos a trasplante, haciendo de! trasplante cardíaco la elección terapéutica en pacientes con falla cardíaca severa refractaria al tratamiento médico. A continuación hacemos una revisión de los agentes inmunosupresores actuales, de algunos que se encuentran en fase experimental y de los protocolos para su manejo.
la determinación de la enzima tiopurina metiltransferasa (TPMT) nos permite pautar la dosis inicial individualizada de azatioprina (AZA). Las determinaciones de los metabolitos tiopurínicos de la ...AZA, la 6-tioguanina (6-TGN) y la 6-metilmercaptopurina (6-MMP) se han descrito como nuevos marcadores de la actividad del fármaco.
describir el fenotipo de TPMT en nuestra población y relacionar los valores de los metabolitos tiopurínicos con la actividad terapéutica y los efectos adversos.
se recogieron retrospectivamente los valores de TPMT de 107 pacientes y de 6-TGN y 6-MMP de 18 pacientes en tratamiento con AZA (8 con enfermedad de Crohn, 5 con colitis ulcerosa y 5 con hepatitis autoinmune).
la media de determinación de TPMT fue 20,19
U/ml. Ninguno presentó actividad de TPMT menor que 5
U/ml. De los 18 pacientes, 13 mostraron concentraciones subterapéuticas de 6-TGN (<235
pmol/8×10
8 hematíes). El 45% de los pacientes mantuvieron remisión clínica. La media de concentración de 6-TGN en los pacientes en remisión fue 259
pmol/8×10
8 hematíes frente a 209
pmol/8×10
8 hematíes en los no respondedores (p=0,37). Hay una relación inversa (r=−0,28) entre los valores de TPMT y los de 6-TGN. En 6/18 pacientes encontramos toxicidad: 5 con leucocitopenia y uno con hiperamilasemia.
la determinación de TPMT y la monitorización de los metabolitos tiopurínicos nos permite optimizar tratamiento con AZA, aunque son necesarios nuevos estudios que permitan el correcto conocimiento de los intervalos de efectividad terapéutica y toxicidad.
Individualised doses of azathioprine (AZA) may be prescribed by monitoring the levels of the enzyme thiopurine methyltransferase (TPMT). The measurements of thiopurine metabolites of AZA, 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP), have also been reported as new markers of AZA activity.
To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects.
Data on TPMT were retrospectively collected from 107 patients, and 6-TGN and 6-MMP levels in 18 patients currently on treatment with AZA (Crohn's disease 5, ulcerative colitis 5, autoimmune hepatitis 5).
Mean value of TPMT was 20.19
U/ml. None of the patients had a TPMT activity<5
U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235
pmol/8×10
8 red blood cells). Clinical remission was maintained in 45% of patients. Mean levels of 6-TGN in patients with clinical remission were 259
pmol/8×10
8 red blood cells versus 209
pmol/8×10
8 red blood cells in non-responders (p=0.37). There was an inverse relationship (r=−0.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1.
Determination of TPMT and monitoring of thiopurine metabolites allows AZA treatment to be optimised, although further studies are necessary to establish therapeutic effectiveness and toxicity ranges.
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