Autoinflammatiós kórképek = Autoinflammatory diseases

Absztrakt: Az autoinflammatiós szindrómák a veleszületett immunrendszert érintő, visszatérő szisztémás gyulladásos tünetekkel, súlyos szövődményekkel jellemezhető kórképek. A kórképek patomechanizmusában az inflammasoma kóros működése, fokozott interleukin-1-produkció áll. A ritka kórképek felismerése a visszatérő jellegű klinikai tünetek felismerésén és az egyéb kórképek kizárásán alapul. A láz mellett rash, serositis (pleuritis, peritonitis), arthritis, meningitis és uveitis jelentkezhet. A hosszan fennálló gyulladás szekunder amyloidosis kialakulásához vezethet. A betegségek hátterében álló molekuláris és patofiziológiai okok fejlődő ismerete új terápiák bevezetését tette lehetővé. A betegség korai felismerése és hatásos kezelése révén az irreverzibilis szervkárosodás megelőzhető. A közlemény a leggyakoribb autoinflammatiós kórképek klinikai, genetikai jellemzőit és a terápiás lehetőségeket kívánja bemutatni. Orv Hetil. 2018; 159(23): 898–907. | Abstract: Autoinflammatory diseases are disorders of the innate immune system characterized by recurrent systematic inflammation and serious complications. Dysregulation of inflammasome and overproduction of interleukin-1 play a major role in the pathogenesis of autoinflammatory diseases. The diagnosis of these rare conditions rely on recognising the pattern of presentation and differential diagnosis. Manifestations may include fever, rash, serositis (pleuritis and peritonitis), arthritis, meningitis and uveitis. Secondary amyloidosis may complicate longstanding disease. Advances in our understanding of the molecular and pathophysiological basis of the autoinflammatory diseases have resulted in new treatment strategies. Early diagnosis and effective therapy are critical to prevent irreversible organ damage. The purpose of this review is to describe the major clinical, genetic, and therapeutic features of the most common autoinflammatory syndromes. Orv Hetil. 2018; 159(23): 898–907

A gyermekkori uveitis klinikai jellemzői és terápiája = Clinical features and therapy of uveitis in childhood

Absztrakt: Bevezetés: Az uveitis a szem középső burkát alkotó képletek gyulladásával járó betegség, melynek incidenciája alacsony. Hátterében a leggyakrabban autoimmun megbetegedések és infekciók állnak. Az autoimmun kórképek közül a juvenilis idiopathiás arthritishez asszociáltan előforduló uveitis a leggyakoribb. A betegek jelentős része a lokális szemészeti kezelésre kevésbé mutat javulást, így szükség lehet immunmoduláló terápia bevezetésére. Célkitűzés és módszer: Retrospektív vizsgálatunkban összesen 33 gyermek adatait elemeztük, akiket az elmúlt 5 év során a Pécsi Gyermekgyógyászati és Szemészeti Klinikán uveitisszel diagnosztizáltak és kezeltek. Eredmények: A betegek átlagéletkora 9,3 (0,3–17,8) év volt. A nemi megoszlásban lényeges különbséget nem észleltünk, de juvenilis idiopathiás arthritishez társult uveitis esetén női túlsúlyt találtunk. Az esetek 60%-ában (20/33) sikerült a betegség háttérében etiológiai faktort azonosítani. 12 betegnél juvenilis idiopathiás arthritishez, két esetben Behcet-kórhoz, egy gyermeknél gyulladásos bélbetegséghez társultan alakult ki uveitis. 5 betegnél az uveitis hátterében infekció igazolódott. A kórkép az autoimmun betegségek többségében anterior, ezzel szemben infekciók esetén posterior lokalizációjú volt. A betegek többsége a lokális szerek mellett szisztémás terápiában is részesült. 3 gyermek szisztémás szteroidot kapott, 18 esetben betegséglefolyást módosító reumaellenes szer, per os metotrexátkezelés került bevezetésre. 13 betegnél a súlyos betegségaktivitásra való tekintettel biológiai terápiát (adalimumabinjekció) indítottunk. A gyógyszer bevezetését követően átlagosan 1,45 (0,75–2,5) hónapon belül remisszió alakult ki. Következtetés: A gyermekkori uveitis kiemelt jelentőséggel bír. A korai diagnózis, a megfelelő terápia, a rendszeres kontrollvizsgálatok a társszakmák szoros együttműködését igénylik. Orv Hetil. 2019; 160(34): 1335–1339. | Abstract: Introduction: Uveitis is characterized by inflammation of the middle layer of the eye. Its overall incidence is low. Autoimmune diseases and infections are the most common underlying diseases. Out of the autoimmune diseases, juvenile idiopathic arthritis is associated most frequently with uveitis. The topical ophthalmological treatment may fail in a significant proportion of the patients and immunomodulatory therapy may be required. Aim and method: In a retrospective study, data of 33 children diagnosed and treated with uveitis at the Department of Pediatrics and Ophthalmology, University of Pécs during the last 5 years were collected and analyzed. Results: The mean age of the patients was 9.3 (0.3–17.8) years. Boys and girls were equally affected with an exception of patients with juvenile idiopathic arthritis where female predominance was found. An underlying disease could be identified in 60% of the cases (20/33). Uveitis was associated in 12 patients with juvenile idiopathic arthritis, in 2 patients with Behcet’s disease and in a single case with inflammatory bowel disease. Infections have been proven in 5 patients. The autoimmune diseases caused an eye inflammation typically in anterior localization, in contrast to the infections that resulted in posterior uveitis. The majority of the patients required systemic treatment. 3 of them received systemic corticosteroid and 18 patients methotrexate as disease-modifying antirheumatic drug. 13 children with severe disease activity required biological therapy (adalimumab injection). Remission could be achieved in 1.45 (0.75–2.5) months. Conclusion: Pediatric uveitis is of great importance. Early diagnosis, adequate therapy and follow-up require multidisciplinary cooperation. Orv Hetil. 2019; 160(34): 1335–1339

Severe acrocyanosis precipitated by cold agglutinin secondary to infection with Mycoplasma pneumoniae in a pediatric patient

This is the first report describing a severe form of cold agglutinin- induced acrocyanosis with cutaneous necrosis after Mycoplasma infection in a 9-year-old patient without any other severe symptoms and laboratory alterations. We also present the results of two non-invasive methods used to determine the viability of tissues, degree of tissue perfusion impairment, and the responsiveness of the microvasculature. Laser Doppler flowmetry and laser speckle contrast imaging, both suitable to measure tissue blood perfusion non-invasively, have been used in the diagnosis and follow-up of various peripheral vascular diseases. In our patient, we demonstrated remarkably reduced microcirculation before the treatment and a significant perfusion increase in the acral regions after pentoxifylline therapy. The investigational techniques were useful tools to assess and quantify the severity of peripheral perfusion disturbances and to monitor the efficacy of the treatment in our patient

Pregnancy outcomes of women whom spouse fathered children after tyrosine kinase inhibitor therapy for chronic myeloid leukemia : A systematic review

The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the therapy of chronic myeloid leukemia (CML). Although the efficacy of TKIs is beyond dispute, conception-related safety issues are still waiting to be explored, particularly in males. This systematic review aimed to summarize all available evidence on pregnancy outcomes of female spouses of male CML patients who fathered children after TKI treatment for CML.We performed a systematic search in seven electronic databases for studies that reported on male CML patients who did or did not discontinue TKI treatment before conceiving, and the pregnancy outcomes of their female spouse are available. The search centered on the TKI era (from 2001 onward) without any other language or study design restrictions.Out of a total of 38 potentially eligible papers, 27 non-overlapping study cohorts were analyzed. All were descriptive studies (case or case series studies). Altogether, 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. A total of ten offspring with a malformation (2.5%) were reported: six with imatinib (of 313 live births, 1.9%), two with nilotinib (of 26 live births, 7.7%), one with dasatinib (of 43 live births, 2.3%), and none with bosutinib (of 12 live births). Data on CML status were scarcely reported. Only nine pregnancies (from nine males) and no malformation were reported in males who discontinued TKI treatment before conception.Malformations affected, on average 2.5% of live births from fathers who did not discontinue TKI treatment before conception, which is comparable with the rate of malformations in the general population. Large-scale studies with representative samples are awaited to confirm our results

A gyermekkori koronavírus-fertőzést követő sokszervi gyulladás diagnosztikája és kezelése

A SARS-CoV-2-fertőzés ritka gyermekkori szövődménye a sokszervi gyulladás, angol terminológiával paediatric inflammatory multisystem syndrome (PIMS). Két vagy több szerv érintettségével járó, súlyos tünetekkel induló betegségről van szó, amelynek tünetei átfedést mutatnak a Kawasaki-betegséggel, a toxikus sokk szindrómával és a makrofágaktivációs szindrómával. A PIMS-betegek intenzív terápiás osztályon vagy intenzív terápiás háttérrel rendelkező intézményben kezelendők, ahol biztosítottak a kardiológiai ellátás feltételei is. A szükséges immunterápia a klinikai prezentációtól függ. A jelen közleményben a szerzők a releváns nemzetközi irodalom áttekintését követően ajánlást tesznek a PIMS diagnosztikai és terápiás algoritmusára. Orv Hetil. 2021; 162(17): 652-667. Summary. Pediatric inflammatory multisystem syndrome (PIMS) is a rare complication of SARS-CoV-2 infection in children. PIMS is a severe condition, involving two or more organ systems. The symptoms overlap with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. PIMS patients should be treated in an intensive care unit or in an institution with an intensive care background, where cardiological care is also provided. The required specific immunotherapy depends on the clinical presentation. In this paper, after reviewing the relevant international literature, the authors make a recommendation for the diagnostic and therapeutic algorithm for PIMS. Orv Hetil. 2021; 162(17): 652-667

The effects of TNF-alpha inhibitor therapy on the incidence of infection in JIA children

Juvenile Idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The diagnosis is based on the underlying symptoms of arthritis with an exclusion of other diseases Biologic agents are increasingly used on the side of disease-modifying anti-rheumatic drugs (DMARD) in JIA treatment.The aim of this meta-analysis was to investigate the observed infections in JIA children during tumor necrosis factor (TNF)-alpha inhibitor therapy. A systematic search of three databases (Medline via PubMed, Embase, Cochrane Library) was carried out up to May 2018. Published trials that evaluated the infectious adverse events in patients receiving TNF-alpha inhibitor vs. a control group were included in the analysis. Full-text data extraction was carried out independently by the investigators from ten relevant publications. 1434 patients received TNF-alpha inhibitor therapy; the control group consisted of 696 subjects. The analysis presented the risk of infection in the active treatment group (OR = 1.13; 95% CI: 0.76-1.69; p = 0.543). The majority of infections were upper respiratory tract infections (URTIs). Furthermore, the subgroup analysis demonstrated a higher infection rate in the observed localization.Anti-TNF therapy slightly but not significantly increases the incidence of infection in JIA children compared to other therapies (GRADE: moderate evidence). The most common infections reported were mild URTIs. Further studies with larger patients number with a strong evidence level are crucially needed to finalize the answer whether anti-TNF therapy elevates and if yes on what extent the incidence of infection in JIA children.Prospero: CRD42017067873

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

Manifestations and Investigation of Functional Vascular Diseases in Children

Raynaud’s phenomenon, acrocyanosis and erythromelalgia are functional vascular diseases that differ with respect to clinical signs, prevalence, pathogenesis, therapy and prognosis. The most common form is Raynaud phenomenon. Raynaud phenomenon is a transient vasospasm of peripheral arteries and arterioles that classically results in triphasic discoloration of the affected region. The symmetrical triphasic colour pattern is not typical in children. The fingers are the most commonly affected region. It may be associated with sensation of numbness and insensitivity (80%), pain (50%) and prolonged wound healing. The phenomenon is typically triggered by cold exposure or stress. In the primary form the age at onset is the adolescent period, the secondary form can manifest later. It is 3-4 times more common in women. It is classified into primary and secondary RP. Primary Raynaud is more common in which patients are seronegative for immunserological test and have normal nailfold capillaroscopy. Secondary RP refers to the presence of the disorder in association with a related illness, mostly connective tissue disorders. Although, the prognosis of Raynaud phenomenon is good, 5-20 % of patients might develop connective tissue disease. The pathophysiology of Raynaud phenomenon is not completely understood. The mechanism behind the vasospasm might include both central and peripheral neuronal mechanisms, endothelial damage, abnormal immune reactivity and intravascular causes. In primary Raynaud phenomenon only a functional abnormality can be detected, in secondary Raynaud phenomenon structural changes are involved. The diagnosis is based on medical history, physical examination, laboratory tests and nailfold capillaroscopy