Ülitundlikkusreaktsioonid kemoteraapiale ja desensibiliseeriv ravi

Järjest suurenev kasvajavastase ravi kasutamine viimaste kümnendite jooksul on suurendanud ka erinevate kõrvaltoimete esinemist. Ülitundlikkusreaktsioonid kemoteraapilistele ravimitele, sh monokloonsetele antikehadele, põhjustavad sageli patsiendi esmavaliku ravi lõpetamise ning sellest omakorda elukvaliteedi halvenemise ja elulemuse kahanemise, sest kasutatavad alternatiivsed ravimid võivad sageli olla vähem efektiivsed, toksilisemad ja/ või kallimad. Tekkivate reaktsioonide mehhanismid ei ole sageli teada, kuid eeldatavasti on kaasatud erinevad ülitundlikkusmehhanismid. Nii IgE vahendatud kui mitte-IgE poolt vahendatud kasvajavastaste ravimite ülitundlikkusreaktsioonide korral on üheks võimaluseks kasutada kiiret desensibiliseerimist, mis võimaldab patsientidel vajalik ravikuur ohutult läbida ja parandab seeläbi nii patsiendi ravivõimalusi kui ka prognoosi. Eesti Arst 2017; 96(5):275–27

Tsöliaakia – kliiniline kameeleon

Tsöliaakia on mitmeteguriline pärilik krooniline haigus, mille korral nisu-, rukki-, odra- ja võimalik, et ka kaeravalkude poolt vallandatavad ning tsöliaakia autoantigeeni – koe transglutaminaasi – vastu tekkivad autoimmuunreaktsioonid põhjustavad peensoole limaskesta kahjustuse. Seda autoimmuunset haigust esineb kuni 2%-l rahvastikust. Haigusele iseloomulikuks histoloogiliseks leiuks on peensoole limaskesta hattude atroofia ja krüptide hüperplaasia, millest tulenevalt on tsöliaakia klassikaliseks sümptomiks malabsorptsiooni sündroom. Eesti Arst 2007; 86 (2): 121–13

Eosinofiilne gastroenteriit seedetrakti vaevuste ühe põhjusena

Eosinofiilne gastroenteriit on harva esinev, täpselt teadmata põhjuse ja tekkemehhanismiga, ägenemiste ning remissioonidega kulgev krooniline haigus. Sellele haigusele on iseloomulik seedetrakti erinevate vaevuste ja sümptomite esinemine, eosinofiilsed infiltratsioonid seedetrakti ühes või enamas piirkonnas ning ühes või enamas seinakihis, eosinofiilia muu põhjuse ning seedetraktiväliste eosinofiilsete infiltratsioonide puudumine. Kliiniline leid sõltub eosinofiilse infiltratsiooni paiknemise piirkonnast ja seedetrakti seinakihi kahjustuse sügavusest. Haigus võib esineda kogu seedetrakti ulatuses, kuid kõige sagedamini on kahjustunud magu ja peensool

Onkoloogiliste patsientide immuniseerimine

Maailma Terviseorganisatsiooni andmetel on onkoloogiliste haiguste põhjustatud surmad kõikidest surmapõhjustest teisel kohal. Sageli võib selle patsiendirühma vahetuks surmapõhjuseks olla vaktsiiniga välditav infektsioon, mistõttu on väga oluline pöörata tähelepanu onkoloogiliste haigete immuniseerimisele. Nii haigusest endast kui ka selle ravist tingituna võib tekkiv immuunvastus vaktsiinidele olla ebapiisav.Artikli eesmärk on selgitada kasvajavastast ravi saava patsiendi immuniseerimise üldisi põhimõtteid. Eestis ei ole seni sellele patsiendirühmale välja toodud selgeid soovitusi, mistõttu on artiklis tuginetud erinevate riikide immuniseerimisjuhistele ja -soovitustele. Kuigi immuniseerimiste ajastamine võib onkoloogiliste haiguste korral olla keeruline, on adekvaatne immuniseerimine väga vajalik, et vähendada infektsioonidest tingitud haigestumust ja suremust. Seetõttu on väga oluline, et onkoloogiliste patsientide raviga tegelevad arstid mõistaksid immuniseerimise vajadust. Et tagada patsientidele võimalikult hea kaitse infektsioonide vastu, on väga oluline kõigi patsiendiga kokku puutuvate meditsiinitöötajate ja pereliikmete adekvaatne immuniseerimine.Eesti Arst 2017; 96(5):267–27

Lapseea tsöliaakia Eestis, esinemine atoopilise dermatiidiga lastel ja koosesinemise immunoloogiline iseloomustus

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Uuringu eesmärgiks oli hinnata lapseea tsöliaakia haigestumust Eestis, levimust atoopilise dermatiidiga lastel ning iseloomustada nende koosesinemise kliinilisi ja immunoloogilisi eripärasid. Nii tsöliaakia kui ka atoopiline dermatiit on ühed sagedasemad lapseea kroonilised haigused, mille tekkes on oluline roll nii geneetilisel eelsoodumusel, immuunsüsteemi häiretel kui ka keskkonna-faktoritel. Tsöliaakia korral põhjustavad teraviljades esinevate valkude poolt vallandatavad autoimmuunreaktsioonid peensoole limaskesta kahjustuse. Pikka aega peeti tsöliaakiat väga harva esinevaks väikelapseea haiguseks, kuid viimastel aastatel on Euroopas tsöliaakiat leitud kuni 3%-l rahvastikust. Tsöliaakia levimuse hindamiseks Eestis teostati sõeluuringud 1160-l juhuslikult valitud Eesti koolilapsel ning leiti, et tsöliaakiat esineb Eestis oluliselt sagedamini kui varasemalt arvatud (vähemalt 0.34%). Analüüsides kõiki aastatel 1976-2010 diagnoositud tsöliaakiajuhte Eesti lastel selgus, et antud perioodil on haigestumus tõusnud enam kui 30 korda. Kui uuringu algaastail diagnoositi tsöliaakia vaid alla kaheaastastel tüüpiliste kaebustega lastel, siis perioodil 2006-2010 diagnoositi enamus juhte atüüpiliste kaebustega või hoopis kaebusteta üle viie aastastel lastel. Tsöliaakia võib esineda koos ligi 100 erineva haigusega, sagedamini erinevate immuunsüsteemi haigustega, sealhulgas allergiahaigustega. Võrreldes 351 atoopilise dermatiidiga last eelnevalt uuritud koolilastega, esineb tsöliaakiat atoopilise dermatiidiga lastel üle nelja korra sagedamini (1.4%). Seejuures pooltel diagnoositud lastest ei esinenud vaatamata väljendunud soolekahjustusele tsöliaakiale viitavaid kaebusi. Seetõttu tuleks peensoole limaskesta kahjustusest tulenevate tüsistuste vältimiseks kaaluda atoopilise dermatiidi lisamist tsöliaakia riskigruppide hulka. Lisaks leidsime atoopilise dermatiidiga lastel tuumavastaseid autoantikehi veidi kõrgemas tiitris ja nooremas eas kui kontrollgrupis, ei olnud erinevused statistiliselt olulised. Kuna aga autoantikehad ilmuvad sageli aastaid enne autoimmuunhaiguse väljakujunemist, tuleks raskekululise atoopilise dermatiidiga patsiente uurida nende antikehade suhtes ning antikeha-positiivseid isikuid jälgida regulaarselt võimaliku autoimmuunhaiguse väljakujunemise suhtes.The aim of our study was to find the incidence of childhood coeliac disease in Estonia, the prevalence in atopic dermatitis and to characterise their immunological peculiarities. Coeliac disease and atopic dermatitis are among the most common chronic diseases of childhood. Genetic predisposition, dysregulated immune responses and environmental factors play role in the pathogenesis of both diseases. In coeliac disease the ingestion of wheat gluten and related prolamines leads to inflammation and autoimmune damage of the small intestinal mucosa. For a long time coeliac disease was considered a very rare disease in small children, but in recent decades it has been shown to occur in up to 3% in Western populations. In order to assess the prevalence of childhood coeliac disease, 1160 randomly selected Estonian schoolchildren were studied and the prevalence of 0.34% was found. Analysing data from all coeliac disease cases diagnosed in 1976-2010 in Tallinn Children’s Hospital and Children’s Clinic of Tartu University Hospital, we found more than 30-fold increase in coeliac disease incidence over the years. In 1976-1980 coeliac disease was diagnosed only in under-two-year-old children with classical clinical picture (diarrhoea with failure to thrive and/or weight loss, stomach pain), however, in 2006-2010 it was mostly diagnosed with atypical or silent clinical presentation in over-five-year-old patients. Celiac disease has been described together with nearly 100 different diseases, especially with different diseases of the immune system, including allergic diseases. Comparing prevalence of coeliac disease in 351 children with atopic dermatitis and in 1160 school children, it occurs four times more frequently in atopic dermatitis (1.4%). However, half of the children were asymptomatic for coeliac disease, despite the overt damage at the intestinal mucosa. Therefore, in order to prevent serious long-term complications, children with atopic dermatitis should be considered as a risk-group for coeliac disease, especially in the presence of gastrointestinal symptoms. Although, antinuclear autoantibodies were found in atopic dermatitis patients at an earlier age and higher titer when compared to control group, the difference was not statistically significant. Since, the auto-antibodies are detectable often many years before the development of autoimmune disease, atopic dermatitis patients with early onset and severe dermatitis should be screened for antinuclear antibodies, and antibody positive subjects should be regularly followed-up for the possible development of autoimmune disease

Hüper-IgE-sündroom – primaarse immuunpuudulikkuse haruldane vorm

Hüperimmunoglobuliin-E-sündroom (HIES) on primaarse immuunpuudulikkuse haruldane vorm, millele on iseloomulik klassikaline sümptomitriaad: nahalööve, korduv raske pneumoonia ning seerumi üld-IgE-sisalduse suurenemine. Nelja-aastasel tüdrukul, kes põdes raskeid hingamisteede infektsioone, kandidoosi ja kelle vereseerumi üld-IgE-sisaldus oli suurenenud, diagnoositi HIES, kuigi tal tüüpilist löövet ei olnud. Tegemist on Eestis esimest korda geneetiliselt kinnitatud hüperimmunoglobuliin- E-sündroomiga.Eesti Arst 2014; 93(9):521–52

Seclusion Management in an Acute In-Patient Unit

Trends in modern day mental health facilities have been towards the least restrictive environment with emphasis on patients’ rights, but these rights have to be balanced against the safety of both the patients themselves and anyone else in the immediate environment. One way of restricting a person’s movement is through the use of seclusion, a means of isolating a person in a locked room with minimal stimulus and from where that person cannot freely exit. This study was developed to explore the use of seclusion in an acute in-patient unit for people with mental illnesses. Investigation into this issue was considered important due to an identified large increase in seclusion use over the previous two years. The study used a qualitative research methodology with a descriptive and interpretive approach. Data collection included a retrospective file audit of patients who had been secluded over the past seven years, and one-to-one staff interviews. I also included some personal reflections of seclusion events. The principle reason for using seclusion was violence and aggression in the context of mental illness. It was also used for people who were at risk of, or who had previously absconded from the unit. A recovery approach and the use of the strengths model was fundamental to nurses’ way of working with patients in the unit. Nurses believed that the strengths process should be adapted to the person’s level of acuity and to their ability to engage in this approach in a real and tangible way. Seclusion continues to be a clinical management option in the unit that is the subject of this study. It is used when a person is so unwell that they cannot be managed in any other identified way. However, in many circumstances there are other options that could be explored so that the utmost consideration is given to the dignity, privacy and safety of that person

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries

DataSheet_2_Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.docx

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.</p