Małgorzata Biernacka-Zielińska

Distribution and clinical significance of blood dendritic cells in children with juvenile idiopathic arthritis

Background: A role for dendritic cells (DC) in the development of adult rheumatoid arthritis has been suggested. To date, this problem has been poorly explored in juvenile idiopathic arthritis (JIA). Objective: To analyse distribution and maturation status of blood DC (BDC) in JIA. Methods: Absolute BDC counts were assessed by the “single platform” method in peripheral blood (PB) of 47 untreated children with JIA and 32 healthy controls. Moreover, BDC were investigated in JIA synovial fluid (SF). When the panel of monoclonal antibodies against BDC antigens (BDCA) was used, three BDC subpopulations were determined: myeloid type 1 (mDC1; BDCA-1+/HLA-DR+/CD19−), myeloid type 2 (mDC2; BDCA-3+/HLA-DR+/CD14−) and plasmacytoid (pDC; BDCA-2+/HLA-DR+/CD123+). Results: A considerable deficiency of all subtypes of BDC was found in the PB of children with JIA. BDC counts in JIA SF were significantly higher than in PB both from children with JIA (p<0.001) and healthy children (p<0.001). SF BDC, especially mDC1 and mDC2 subtypes, had significantly higher expression of maturation markers (CD40, CD80, CD86 or CD83 antigens) than those from PB. A smaller number of PB BDC at diagnosis correlated significantly with poor response to treatment. Conclusions: A deficiency of BDC in PB is accompanied by enrichment of SF with those cells. Probably, circulating BDC migrate to joints where they undergo maturation and help to mediate and maintain the local immune response. Interestingly, the level of PD BDC deficiency seems to influence the outcome in children with JIA.

Apoptosis of peripheral blood lymphocytes in patients with juvenile idiopathic arthritis

Background: Recent data suggested that abnormalities in mechanisms regulating apoptosis may have a role in the development of the rheumatoid process. Objective: To evaluate different aspects of apoptosis in children with juvenile idiopathic arthritis (JIA). Methods: The frequency of TUNEL positive peripheral blood (PB) lymphocytes (apoptotic index (AI)), as well as serum CD95 (APO1/Fas) antigen expression and serum levels of sFas and interleukin 15 (IL15), were examined in 44 cases of JIA. Results were correlated with type of onset, activity of JIA, and acute phase indicators. Results: The AI of lymphocytes was significantly higher in patients with JIA than in controls (p=0.020). The mean AI of lymphocytes was increased in JIA with systemic type of onset and high activity (p=0.001). Moreover, IL15 levels in systemic disease were higher than in controls (p=0.012). An increased AI correlated with raised IL15 (p=0.046), erythrocyte sedimentation rate (p=0.005) and C reactive protein (CRP; p=0.017). Additionally, correlation was found between IL15 and CRP levels (p=0.039). CD95 and sFas levels were unchanged compared with controls. Conclusion: PB lymphocytes of children with JIA have an increased tendency to undergo apoptosis. The degree of apoptosis depends on the type of onset and activity of JIA and correlates with serum levels of IL15. Further studies are needed to explain whether this is an epiphenomenon of the disease activity or is related to the pathogenesis of JIA.

Recurrent arterial and venous thrombosis in a 16-year-old boy in the course of primary antiphospholipid syndrome despite treatment with low-molecular-weight heparin: a case report

IntroductionAntiphospholipid syndrome is a multisystem autoimmune disease characterized by arterial and/or venous thrombosis and persistent presence of antiphospholipid antibodies. It can be a primary disease or secondary when associated with other autoimmune diseases.Case presentationWe present a case of a 16-year-old Caucasian boy with a massive arterial and venous thrombosis in his lower limbs as well as in his central nervous system with clinical symptoms such as headaches and chorea. He did not present any clinical or laboratory signs of a systemic inflammatory connective tissue disease, including systemic lupus erythematosus. Based on the clinical picture and results of the diagnostic tests (positive antibodies against β2-glycoprotein and a high titre of anticardiolipin antibodies) we finally diagnosed primary antiphospholipid syndrome. During a 9-month follow up after the acute phase of the disease, he was treated with low-molecular-weight heparin. Neurological symptoms were relieved. Features of recanalization in the vessels of his lower limbs were observed. After a subsequent 6 months, because of the failure of preventive treatment – an incident of thrombosis of the vessels of his testis – treatment was modified and heparin was replaced with warfarin.ConclusionAlthough the preventive treatment with warfarin in our patient has continued for 1 year of follow up without new symptoms, further observation is needed.

Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

Objectives Connective tissue diseases (CTD) are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA). Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patients clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS), it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods Data from 24 patients with CTD treated with tumor necrosis factor-α-blockers (etanercept, adalimumab, golimumab) and an interleukin-6 receptor blocker (tocilizumab) were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1%) during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS daily doses.

Comparison of uveitis in the course of juvenile idiopathic arthritis with isolated uveitis in children – own experiences

Objectives Uveitis and juvenile idiopathic arthritis (JIA) relatively often coexist. Inflammatory changes in the anterior segment of the eye are the most common extra-articular symptom in children with JIA, and JIA is, in turn, the main systemic cause of anterior uveitis in children. The aim of our study was to compare the course of anterior uveitis accompanying JIA and isolated uveitis. Material and methods We analyzed 25 children with JIA and uveitis (group I) and 28 children with isolated uveitis (group II). The study population was retrospectively selected from the patients treated in our center in the years 1998–2016 through a search of the hospital database. All data were presented as descriptive statistics. Results In group I there was a higher percentage of girls than in group II (64% vs. 50%) and uveitis occurred at a significantly younger age (8.7 years vs. 11.6). Patients from group I more often presented with immunological abnormalities (positive antinuclear antibodies or HLA-B27 antigen). The majority of children from group I developed uveitis prior to (44%) or simultaneously with (20%) arthritis. In patients who first presented with uveitis, arthritis appeared on average after 28 months (median 12 months). In children in whom arthritis developed first, uveitis appeared on average after 51 months (median 36 months). In some patients the time interval between the involvement of these two organs was as long as 9–10 years. Four children from group I and three from group II were qualified for biological treatment. Conclusions The results of our analysis indicate the need for constant cooperation between the pediatric rheumatologist and the ophthalmologist. Although the risk of uveitis in JIA decreases with the disease duration, in some cases this complication can develop after many years. Children with present antinuclear antibodies, at younger age and of female gender should be subject to particularly close observation.

The paediatric rheumatologist and orphan disease – a story without happy ending

Orphan diseases are not a common challenge in the everyday practice of the rheumatologist. Despite their extremely rare occurrence one of the patients under our care developed one of them – neuronal ceroid lipofuscinosis, the most frequent neurodegenerative disease observed in the paediatric population. We report a case of 2-year-old girl diagnosed with oligoarticular form of juvenile idiopathic arthritis treated in our Department with steroids and methotrexate and staying in the stage of disease remission. During routine checkups at Outpatient Clinic we observed progressive deterioration of girls neurological condition resulting in ataxia, gait disturbances with no rheumatological cause behind and speech impairment. The appearance of the symptoms was accompanied by frequent episodes of epileptic seizures, with little clinical improvement on combined antiepileptic treatment. Magnetic resonance imaging that we performed showed a picture highly suggestive of neuronal ceroid lipofuscinosis – atrophy of the patients cerebrum and cerebellum. Genetic testing conducted resulted in the diagnosis of late infantile neuronal ceroid lipofuscinosis (LINCL).

Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl.

Mixed connective tissue disease (MCTD) is a systemic inflammatory disease affecting connective tissue with the underlying autoimmunological mechanism. The core of MCTD is an appearance of symptoms of several other inflammatory diseases of connective tissue – systemic lupus erythematosus, systemic scleroderma, poly- or dermatomyositis, rheumatoid arthritis at the same time, accompanied by a high level of anti-ribonucleoprotein antibodies (anti-U1RNP). The disease was described more than 40 years ago by Sharp et al. During recent years, many efforts to better understand clinical and serological features of MCTD have been made. Diagnosis of MCTD can be difficult. Obligatory international diagnostic criteria are required to be fulfilled. Several versions of such criteria have been proposed, but the most widely used one was described by Kasukawa. There is no consensus about treatment – a choice of drugs depends on symptoms. We present a case of a 10-year-old girl with sclerodactyly and trophic damages of fingers accompanied by symptoms of Raynauds phenomenon. After an almost 2-year course of the disease, a diagnosis of MCTD has been established.

Choroba Kawasakiego u 11 dzieci – charakterystyka przebiegu klinicznego i reakcji na leczenie oraz wyniki długofalowej obserwacji pacjentów

Streszczenie Wstep Choroba Kawasakiego nalezy do ukladowych zapalen naczyn, wystepujących najcześciej u niemowląt i malych dzieci, czego powaznym powiklaniem mogą byc zmiany w naczyniach wiencowych. Dzieki postepowi diagnostyki coraz cześciej bywa rozpoznawana rowniez u dzieci polskich, u ktorych obserwuje sie przedluzającą sie gorączke i typowe objawy kliniczne. Cel Analiza przebiegu klinicznego, wynikow leczenia oraz dlugofalowej obserwacji pacjentow z rozpoznaniem choroby Kawasakiego. Pacjenci i metody Badaniem objeto 11 dzieci hospitalizowanych w Klinice Kardiologii i Reumatologii Dzieciecej UM w Łodzi w latach 2005–2010. W przeprowadzonej analizie uwzgledniono dane demograficzne, wstepne rozpoznanie, charakterystyke objawow klinicznych i badan laboratoryjnych, reakcje na leczenie oraz dlugofalową obserwacje pacjentow. Wyniki Wszystkie dzieci spelnialy kryteria konieczne do ustalenia rozpoznania. Jedynie u 1 dziecka nie obserwowano zajecia naczyn wiencowych. 8 dzieci dobrze zareagowalo na standardowe leczenie immunoglobulinami, u 3 konieczna byla modyfikacja w postaci dodatkowego wlewu z immunoglobulin lub podania pulsu z metylprednizolonu. W dlugofalowej obserwacji stwierdzano systematyczną regresje zmian w naczyniach. Wnioski Autorzy podkreślają znaczenie wczesnego ustalenia rozpoznania i wdrozenia prawidlowego leczenia oraz koniecznośc dlugoterminowej obserwacji dzieci po przebytej chorobie Kawasakiego.

Kompleksowa ocena zaburzeń funkcji rozkurczowej lewej komory u dzieci z młodzieńczym idiopatycznym zapaleniem stawów

Do najczestszych zapalnych ukladowych chorob tkanki lącznej u dzieci nalezy mlodziencze idiopatyczne zapalenie stawow (MIZS). U dzieci z MIZS do objecia procesem chorobowym serca dochodzi u 30–80% przypadkow, natomiast objawy kliniczne wystepują u 3–9% chorych. Celem pracy byla ocena zaburzen funkcji rozkurczowej lewej komory u pacjentow z MIZS. Metody Badaniem objeto 50 dzieci z rozpoznanym wcześniej MIZS. Grupe kontrolną stanowilo 20 zdrowych dzieci. U kazdego pacjenta wykonano badanie echokardiograficzne z oceną funkcji skurczowej i rozkurczowej serca (MPI, E/A, VpMV, AEF). Wyniki Statystycznie istotną roznice stwierdzono pomiedzy wartościami wskaźnika E/A (1,456 ± 0,353 i 1,864 ± 0,385). Wartości fali A w grupach wyniosly średnio 0,6 ± 0,131 m/s i 0,48 ± 0,078 m/s. Wartośc MPI w grupie badanej wyniosla średnio 0,476 ± 0,13. W grupie kontrolnej średnia wartośc MPI wyniosla 0,411 ± 0,075. Średnia wartośc AEF wyniosla 12,09 ± 6,04 kdyn i 6,17 ± 1,9 kdyn. Wartośc VpMV wyniosla średnio 0,7 ± 0,14 m/s i 0,81 ± 0,13 m/s. Wartości te statystycznie istotnie roznily sie miedzy sobą. Nie odnotowano statystycznie istotnej korelacji pomiedzy czasem trwania choroby a ktorymkolwiek ze wskaźnikow opisujących zaburzenia relaksacji lewej komory. Wnioski 1. U pacjentow z MIZS stwierdzono zaburzenia funkcji rozkurczowej lewej komory. 2. W ocenie zaburzen funkcji rozkurczowej lewej komory u pacjentow z MIZS wskazane jest zastosowanie kilku parametrow. Na szczegolną uwage, ze wzgledu na niezaleznośc od innych czynnikow, zaslugują MPI oraz VpMV. 3. Sila wyrzutu przedsionka (AEF) jest wartościowym parametrem oceniającym funkcje rozkurczową lewej komory.