Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

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

Immunoglobulin G4-hez kapcsolt betegség első gyermekkori esete Magyarországon

Az immunglobulin G4-hez kapcsolt betegség fibrosissal, gyulladással kísért több szervet érintő tisztázatlan etiológiájú betegség, mindössze 25 gyermekkori eset ismert a szakirodalomban. Egy 12 éves fiúgyermeknél leukopenia, krónikus sinusitis, Mikulitz-betegség, cholangitis, eosinophil gastritis tünetei mellett az emelkedett IgG4 alosztály szint vetette fel a betegség gyanúját, PET-CT vizsgálattal váltak egyértelművé a szervi érintettségek, a diagnózist a szövettan alapján állítottuk fel. Glükokortikoid adása mellett tünetmentessé vált a beteg, de a kiújulás miatt tartós immunszuppresszió vált szükségessé. Terápiás plazmacsere az irodalomban eddig nem leírt alkalmazása gyors kezdeti javulást hozott a beteg állapotában. A kórkép gyermekkori előfordulásának ismerete fontos, így megelőzhetőek a későbbi szervkárosodások

Infekciók kockázatának csökkentése veleszületett és szerzett komplementdefektusokban : Irodalmi áttekintés és javaslat hazai gyakorlatra = Reducing the risk of infections in hereditary and acquired complement deficiencies : Review of the literature and proposal for best practice in Hungary

A veleszületett komplementdefektusok világszerte ritkán fordulnak elő, a primer immunhiányok 1–10%-át teszik ki. A szerzett komplementdefektusok gyakoribbak, és a komplementgátló kezelések egyre elterjedtebb alkalmazásával a szerzett komplementhiányos betegek incidenciája nő. A terápia okozta komplementdeficientia a genetikailag meghatározott formákhoz hasonlóan döntően tokos baktériumok által okozott, visszatérően jelentkező, életveszélyes fertőzésekre hajlamosít (sepsis, meningitis). A leggyakoribb kórokozók a Neisseria meningitidis, a Streptococcus pneumoniae és a Haemophilus influenzae. Hazánkban C5- és C3-komplement-gátló gyógyszerek érhetők el a klinikai gyakorlatban, melyek elsődlegesen paroxysmalis nocturnalis haemoglobinuria, myasthenia gravis, neuromyelitis optica és atípusos haemolyticus uraemiás szindrómás betegek kezelésére indikáltak. A fenti kezelésben részesülő betegek körében kiemelt jelentőségű és a kezelésnek elengedhetetlen feltétele a súlyos, potenciálisan életet veszélyeztető, gyors progressziójú bakteriális fertőzések megelőzése. Ennek ellenére az infekciós kockázatot csökkentő hazai ajánlás nem létezik, a megelőzési stratégia nem standardizált, gyakran hiányos, ami az érintett betegeket súlyosan veszélyezteti. Közleményünk célja a nemzetközi gyakorlat és klinikai útmutatók áttekintésével a komplementhiányos betegeknél alkalmazható szakmai javaslat megfogalmazása a bakteriális fertőzések prevenciójára vonatkozóan, mely egy későbbi hazai irányelv alapjául szolgálhat. Orv Hetil. 2023; 164(25): 971–980. | Hereditary complement deficiencies are relatively rare worldwide, they account for about 1–10% of primary immunodeficiencies. Acquired complement deficiencies are more prevalent and with the more frequent use of complement inhibitor therapy, the incidence of patients with iatrogenic complement deficiency is increasing. Alike in the inherited forms, patients have a high risk of severe and life-threatening infections caused by encapsulated bacteria (sepsis, meningitis). The most frequent pathogens are Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. C5 and C3 complement inhibitor therapies are available in Hungary, which are mostly indicated in the treatment of paroxysmal nocturnal hemoglobinuria, myasthenia gravis, neuromyelitis optica and atypical haemolytic uremic syndrome. It is of utmost importance to prevent severe, potentially life-threatening bacterial infections in this group of patients. Nevertheless, there is no Hungarian guidance to decrease the risk of infections, preventive measures are incomplete and not standardized posing potential risk of infections for these patients, so far. In this review, we aim to summarize the international clinical practices and guidance on the infection prevention in complement deficient patients. This recommendation might be a source of an evidence-based Hungarian guideline regarding vaccination and antibiotic prophylaxis in this specifically vulnerable group of patients

Sikeres autológ haemopoeticus őssejt-transzplantáció gyermekkori, súlyos, terápiarezisztens Crohn-betegségben. Az első hazai beteg esetének ismertetése | Successful autologous haemopoietic stem cell transplantation in severe, therapy-resistant childhood-onset Crohn’s disease. Report on the first case in Hungary

A Crohn-betegség pontos oka ismeretlen, így terápiája sem megoldott. Kezelésében az infliximab jelentős áttörést jelentett, a mindennapi gyakorlatban azonban vannak olyan betegek, akik a kombinált immunszuppresszív, illetve biológiai terápia ellenére sem kerülnek remisszióba. Ezekben az esetekben új esélyt jelenthet az őssejt-transzplantáció. A szerzők egy 15 éves fiúgyermek történetét mutatják be, akinél 2008 februárjában súlyos Crohn-betegséget (aktivitási index [PCDAI]: 82,5 – maximumérték: 100) kórisméztek. Konzervatív kezelésének 3 éve alatt a kombinált terápia (immunszuppresszió, antibiotikum, infliximab) ellenére sem került tartós remisszióba. Az ígéretes külföldi esetközlések nyomán autológ őssejt-transzplantációt végeztek, amely a Crohn-betegség remisszióját eredményezte. Egy évvel az őssejt-transzplantáció után az alapbetegség relapsusa jelentkezett, amely a korábbiakhoz képest lényegesen enyhébb, konzervatív terápiával uralható formában zajlott. A szerzők tudomása szerint hazánkban még nem végeztek őssejt-transzplantációt terápiarezisztens Crohn-betegség kezeléseként, amely – noha végleges gyógyulást nem jelentett – terápiás alternatíva lehet súlyos, refrakter esetekben. Orv. Hetil., 2014, 155(20), 789–792. | The biological therapy of Crohn’s disease, such as infliximab is a powerful approach in the therapy of inflammatory bowel diseases. However, in some patients with aggressive disease course, even a combined immunosuppressive therapy will not result in permanent remission. Hematopoietic stem cell transplantation has emerged as a new potential therapeutic tool for inflammatory bowel diseases. The authors report the case of a 15-year-old boy with severe Crohn’s disease resistant to combined immunosuppressive therapy. After a 3-years course of unsuccessful conventional therapy including infliximab, autologous hematopoietic stem cell transplantation was performed which resulted in a complete remission. One year after transplantation the patient has relapsed, but he could be treated effectively with conventional therapy regiments. To the best of knowledge of the authors, this is the first report in Hungary presenting hematopoietic stem cell therapy in patient with severe Crohn’s disease. Orv. Hetil., 2014, 155(20), 789–792

Peripheral Bone Relapse of Paediatric TCF3-HLF Positive Acute Lymphoblastic Leukaemia during Haematopoietic Stem Cell Transplantation: A Case Report

The present case report features a highly uncommon form of a paediatric TCF3-HLF positive acute lymphoblastic leukaemia (ALL) relapse, an extramedullary, peripheral bone manifestation. Following complete remission, during the conditioning for haematopoietic stem cell transplantation (HSCT), our sixteen-year-old male patient complained of fever, pain and swelling of the right forearm. Radiography suggested acute osteomyelitis in the right ulna with subsequent surgical confirmation. Intraoperatively obtained debris culture grew Staphylococcus aureus and Acinetobacter pittii. Measures taken to control the infection were deemed to be successful. However, after the completion of the otherwise uneventful HSCT, a very early medullary relapse was diagnosed. Revising the original surgical samples from the ulna, bone relapse of ALL was immunohistochemically confirmed. Reviewing the previous cases found in the literature, it is advised to consider uncommon forms of ALL relapse when encountering ambiguous cases of osteomyelitis or arthritis during haematological remission