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Stevens-Johnsonov sindrom (SJS) in toksična epidermalna nekroliza (TEN) sta redki življenje ogrožajoči bolezni, ki se kažeta z nastajanjem mehurjev ter odstopanjem povrhnjice kože in sluznic. Najpogosteje sta posledica imunsko sprožene reakcije na zdravilo, redkeje zaradi drugih vzrokov. Poleg prekinitve zdravljenja z zdravilom, ki je lahko sprožilo SJS/TEN, ali uvedbe zdravljenja bakterijske okužbe, če je ta kot vzročni dejavnik dokazana, uvedemo lokalno zdravljenje sprememb na očeh, koži in sluznicah, v težjih primerih pa še sistemsko zdravljenje z glukokortikosteroidi (GKS) in/ali intravenskimi imunoglobulini (IVIG). Za optimalni izid bolezni je bistveno sodelovanje med specialisti različnih strok. Prispevek predstavi skupino bolnikov, obravnavanih na Kliničnem oddelku za otroško alergologijo, revmatologijo in klinično imunologijo Pediatrične klinike UKC v Ljubljani in pregled literature. V letih 2011–2019 smo zdravili šest otrok s SJS/TEN. Pri štirih otrocih je bil sprožilni dejavnik zdravilo, pri enem okužba z Mycoplasmo pneumonie, pri enem bolniku pa etiologije nismo mogli opredeliti. Z GKS in IVIG so bili zdravljeni štirje otroci, en otrok z okužbo z M. pneumonie je bil zdravljen z azitromicinom in IVIG, en otrok pa je prejel le zdravila lokalno. Izid bolezni je bil pri vseh otrocih dober, in sicer tudi brez poznih posledic bolezni.

The pathogenesis, clinical course, and response to treatment in systemic juvenile idiopathic arthritis (SJIA) differ from other types of juvenile idiopathic arthritis and are similar to other interleukin-1 (IL-1)-mediated diseases. The main cytokine involved in the pathogenesis of SJIA is IL-1β, which can be neutralized by targeted anti-IL-1 therapy. In SJIA, no antibodies have been found and there is growing evidence that it is mainly an autoinflammatory and not an autoimmune disease. Before the era of biologic therapy, treatment of SJIA was primarily based on long-term treatment with high doses of glucocorticosteroids (GCS). The side effects of GCS could have a significant impact on the outcome of the disease and could cause long-term damage. Treatment with anti-IL-1 agents early in the disease course has revolutionized the management principles of SJIA. However, not all SJIA patients respond equally well to anti-IL-1 therapy, and it has been shown that age at the onset of disease, duration of the disease, number of affected joints, neutrophil count, and ferritin level can predict the response to anti-IL-1 therapy. In particular, an elevated ferritin level should prompt testing for macrophage activation syndrome (MAS), the most severe complication of SJIA. Anti-IL-1 therapy has been shown to be effective also in patients with MAS. Although anti-IL-1 agents are currently not recommended as first-line treatment, there is growing evidence that anti-IL-1 agents introduced at the beginning of SJIA could enable lower doses and a shorter duration of GCS therapy, change the long-term disease outcome, and even influence molecular disease patterns. There are currently three anti-IL-1 agents available: anakinra, canakinumab, and rilonacept. In this review, we present the current knowledge on the pathogenesis of SJIA, the rational for anti-IL-1 treatment, and future perspectives on the treatment of SJIA.

Background The symptoms of pediatric Sjogren’s syndrome (SS) are different than in adults. There are currently no validated pediatric diagnostic criteria or treatment guidelines for SS. In most cases adult criteria are used, but they apply poorly to children. Objectives To present pediatric patients with primary SS who were treated at University Children’s Hospital (UCH) Ljubljana in the past 10 years. Methods Eight children with primary SS were identified. Demographic data, clinical and laboratory findings and therapy were analysed by retrospective review of medical records at UCH Ljubljana. Results Six girls and 2 boys were evaluated. The mean age at disease onset was 12.3 years (range 6.5 – 17) and mean age at diagnosis was 13.8 years (range 7.5 – 17.5). The mean follow-up duration was 2.8 years (range 0.5 – 8.5). Four patients presented with recurrent bilateral parotitis, two with rash, one with arthralgia and fatigue and one with acute central nervous system vasculitis. The latter patient presented with rheumatic fever at the same time. During disease course arthritis and/or arthralgia was present in 5/8, parotitis in 4/8, oral symptoms in 4/8, rash in 4/8, fatigue in 3/8 and ocular symptoms in 2/8 patients. One patient developed calcinations on fingers. All patients had high titer of antinuclear antibodies, 7/8 were positive for anti-Ro and 5/8 for anti-La antibodies. Three patients were tested for rheumatoid factor and all were positive. 6/8 patients had elevated ESR and hypergammaglobulinemia. 4/8 patients had elevated serum amylase. Biopsy of salivary glands was performed in 5 patients and foci of lymphocytic infiltration were shown in all of them. Further two patients had salivary gland changes on MRI and/or US. On ophthalmologic evaluation 3 patients had positive Schirmer test and one had unstable tear film. One patient had CNS vasculitis and two decreased diffusing capacity of the lungs. Other patients showed no signs of internal organ involvement. 4/8 patients were treated with NSAIDs, 7/8 patients with hydroxychloroquine, 2/8 also received corticosteroids and one patient MMF. At this point the patient with CNS vasculitis has stable changes on head MRI without clinical symptoms. Other patients have no signs of internal organ damage. Calcinations that appeared on fingers in one patient are not progressing. Conclusion Most common symptoms in our cohort were arthritis and/or arthralgia, parotitis, oral symptoms and rash. Half of the children presented with recurrent parotitis. One child developed calcinations on fingers, which have not yet been described in patients with SS. Pediatric SS differs from adult SS and specific pediatric diagnostic criteria would improve management of these patients. References [1] Yokogawa N, Lieberman SM, Sherry DD, Vivino FB. Features of childhood Sjogren’s syndrome in comparison to adult Sjogren’s syndrome: considerations in establishing child-specific diagnostic criteria. Clin Exp Rheumatol2017; 34(2): 343–351. Disclosure of Interests None declared

Antibody deficiency is common finding in patients with Jacobsen syndrome (JS). In addition, there have been few reports of T-cell defects in this condition, possibly because most of the reported patients have not been specifically evaluated for T-cell function. In this article, we present a child with an 11q deletion and combined immunodeficiency and we perform a literature overview on immunodeficiency in JS. Our patient presented with recurrent bacterial and prolonged viral infections involving the respiratory system, as well as other classic features of the syndrome. In addition to low IgM, IgG4, and B-cells, also low recent thymic emigrants, helper and naïve T-cells were found. We propose that patients with Jacobsen syndrome need thorough immunological evaluations as T-cell dysfunction might be more prevalent than previously reported. Patients with infections consistent with T-cell defects should be classified as having combined immunodeficiency. © 2016 Wiley Periodicals, Inc.

An abnormal regulation of immune responses leads to autoimmune and inflammatory manifestations in patients with primary immunodeficiencies (PIDs). The objective of our study was to evaluate the frequency of non-infectious and non-malignant manifestations in a large cohort of patients included in the Slovenian national PID registry and to assess the time of manifestation onset with respect to the time of PID diagnosis. Medical records of registered patients were reviewed. Data on autoimmunity, lymphoproliferation, autoinflammation, allergies, PID diagnosis, and underlying genetic defects were collected and analyzed. The time of each manifestation onset was determined and compared with the time of PID diagnosis. As of May 2015, 247 patients with 50 different PIDs were registered in the Slovenian national PID registry (147 males, 100 females; mean age 20 years). Mean disease duration was 14 years; 78 % of patients were younger than 18 years; and 22 % of patients were adults. Diagnosis of PID was genetically confirmed in 51 % of patients. Non-infectious and non-malignant manifestations were present in 69/235 (29 %) patients, including autoimmune manifestations in 52/235 (22 %), lymphoproliferative/granulomatous in 28/235 (12 %), autoinflammatory in 12/247 (5 %), and allergic manifestations in 10/235 (4 %) of all registered patients. Autoimmune manifestations were present in all patients whose PIDs were classified as diseases of immune dysregulation, 47 % of patients with chronic granulomatous disease, and 38 % of patients with predominantly antibody immune deficiencies. A high prevalence of non-infectious and non-malignant manifestations among patients in the Slovenian national PID registry suggests common genetic factors of autoimmunity, inflammation, and immunodeficiency. Patients with PID should be routinely screened for autoimmune and inflammatory manifestations at the time of PID diagnosis and during the long-term follow up.

To assess vaccination status in a cohort of children with rheumatic diseases followed at the University Children's Hospital Ljubljana and to evaluate the most common reasons for vaccination dropout.Patients with rheumatic diseases who were evaluated at the rheumatology outpatient clinic between January 2015 and January 2017 received a questionnaire about their vaccination status and reasons for potential vaccination dropout. Vaccination coverage for individual vaccines was determined at 5, 10, 18 years and at the time of their last clinic visit.Data were received from 187 out of 424 enrolled patients (44.1%). Majority of included patients had juvenile idiopathic arthritis (n=165), followed by childhood-onset systemic lupus erythematosus (n=6), juvenile dermatomyositis (n=5), mixed connective tissue disease (n=3), chronic recurrent multifocal osteomyelitis, juvenile systemic sclerosis, Takayasu's arteritis (n=2 each), granulomatous polyangiitis and fibromyalgia (n=1 each). Vaccination coverage was complete in 91.9%, 70.3%, 66.7% and 64.7% of patients at 5, 10, 18 years and at their last clinic visit, respectively. Most commonly omitted vaccines were hepatitis B and second dose of measles, mumps and rubella vaccine. Most common additional vaccine was against rotavirus. Most common reason for vaccination dropout was suggestion of the treating rheumatologist.Thirty-five percent of our patients remain incompletely vaccinated and thus susceptible to vaccine-preventable diseases. Physicians play a crucial role in the decision to vaccinate.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. The outcome in patients with JIA has markedly improved with the advent of biologic drugs. Although early aggressive therapy with biologics seems to be very effective, this approach leads to overtreatment in patients who would respond to classic disease-modifying anti-rheumatic drugs. Therefore, methotrexate remains first-line long-term therapy for most children with polyarticular JIA. Tumor necrosis factor-α inhibitors have shown tremendous benefit in children with refractory non-systemic JIA. Similar effects have been observed with interleukin-1 and interleukin-6 blockade in patients with systemic JIA. Correct choice and timely use of available medications to achieve early and sustained remission with as few side effects as possible remain challenges for the treating physician. In this review, a practical, clinically oriented guide to the management of JIA is provided, focusing on pharmacological treatment with non-steroidal anti-inflammatory drugs, intra-articular and systemic corticosteroids, disease-modifying anti-rheumatic drugs, and biologic agents. In addition, issues regarding treatment failure, early aggressive treatment, and drug tapering are discussed, with alternative treatment options being suggested.

Objectives Low bone mineral density (BMD) is common in children and adolescents with celiac disease. Strict gluten-free diet (GFD) improves bone mineralization, even in 1 year. The effect of occasional gluten intake is not known. The aims of this study were to compare BMD and prevalence of low BMD in children and adolescents on strict and not strict GFD. Methods We measured BMD in 55 children and adolescents (strict GFD) with negative endomysium antibodies (EMA) in the last 2 years and in 19 (not strict GFD) with positive EMA at the time of the study. Lumbar, left hip and total body BMD were measured by dual-energy X-ray absorptiometry. Four-day weighted dietary protocols were obtained by means of a self-completed questionnaire of total food and beverage intake. Energy and calcium intake were calculated using nutrition data software. EMA, tissue transglutaminase antibodies, serum calcium, phosphate, 25-hydroxy vitamin D, intact parathormone, albumin, urea and creatinine levels were determined in all patients. Results BMD in patients on strict GFD was significantly higher than in patients on not strict GFD (lumbar p = 0.01; total body p = 0.005). There were significantly more patients with total body BMD below − 1.0 in not strictly compliant group (71% compared to 38%; p = 0.03). Calcium intake and vitamin D levels were below recommendations in both groups. Conclusion Children and adolescents on not strict GFD are at increased risk for low BMD. We therefore recommend that BMD should be evaluated in patients with positive EMA. In addition, patients on strict GFD are at risk for low BMD because of low calcium intake or vitamin D deficiency. Therefore, strict GFD with recommended calcium intake and vitamin D supplementation during winter and spring should be encouraged in all children and adolescents with celiac disease.

Data from Slovene national primary immunodeficiency (PID) registry are presented. Besides clinical and genetic data of patients with PID, quality indicators in patient care are included. Data are systematically collected in Department of Allergology, Rheumatology and Clinical Immunology in collaboration with physicians of different specialities. Increasing number and spectrum of PID are recognised in Slovenia. After establishment of Slovene multidisciplinary group in PID care in 2007 thorough immunological and genetic diagnostics, subcutaneous immunoglobulin replacement and treatment of PID with haematopoietic stem cell transplantation were introduced in routine clinical practice in Slovenia. Increased medium age of PID patients reflects improved survival and better recognition of PID in adults. According to the data in comparable registries percentages of patients with predominantly antibody deficiencies and complement deficiencies are low and high, respectively.

Takayasu arteritis (TA) is a rare chronic granulomatous vasculitis of large vessels. Initial symptoms and signs are usually non-specific, therefore a high index of suspicion is needed to make a timely and correct diagnosis.

Background Primary immunodeficiency (PID) can present as rheumatic disease due to improper immune regulation. Objectives Study objective was to evaluate prevalence of rheumatic diseases in Slovene patients with PID. Methods Medical records of patients entered in Slovene PID registry were reviewed. Data on rheumatic disease and PID were collected and analysed. Results 240 patients with 49 different PIDs are registered in Slovene PID registry. At least one rheumatic disease is diagnosed in 12 (5%) patients in Slovene PID registry. Five different rheumatic diseases were diagnosed: juvenile idiopathic arthritis (6 patients), rheumatoid arthritis (2 patients), skin vasculitis (2 patients), systemic lupus erythematosus (1 patient) and Kawasaki disease (1 patient). Rheumatic disease was the presenting manifestation of PID in 8 patients. Four patients developed rheumatic disease after PID has been diagnosed. Rheumatic disease was present in 5 out of 19 patients with IgA deficiency, 3 patients with yet undefined PID, 2 out of 12 patients with CVID, 1 out of 3 patients with autoimmune lymphoproliferative syndrome and 1 out of 13 patients with DiGeorge syndrome. Conclusions Patients with PID do suffer from different rheumatic diseases. Therefore patients with rheumatic disease should be evaluated for possible underlying PID. Rheumatic diseases are most common in Slovene patients with predominantly antibody deficiencies which form the largest group of inherited disorders of immune system. Patients with PID should be screened for signs of autoimmunity when diagnosis of PID is made and during follow up. Disclosure of Interest None declared

Little is known about the reasons for prescribing adrenalin auto-injectors in Slovenian children. Our objective was to evaluate prescription of adrenaline auto-injectors in children in our department in year 2013 and also to evaluate management of anaphylaxis of those children.