In the last decades, the spectrum of primary immunodeficiency diseases (PIDs) has greatly widened, including disorders that can variably impair different immune functions. Although several case series have been published for each disorders, no data is available on how these changes have reflected in the clinical practice of pediatric departments. Aim of the study: Based on the analysis of registry data, we evaluated the distribution of diagnoses among different PID categories, the clinical features and diagnostic investigations at disease onset in two pediatric departments, namely in Slovenia and in Italy. Results: 136 patients have been diagnosed at the two centers, with a widespread distribution into different disease categories. Considering the 109 patients who were still alive at the last follow-up, prevalence of pediatric-onset-PID in our area was roughly estimated to be around 31 per million inhabitants. Diagnosis was genetically confirmed in 79 cases (58.1%), with 29 different genes found mutated. The most common presenting symptoms were: recurrent infections (52.2%), inflammatory manifestations (36.7%), specific syndromic features (30.8%), unusual infections (1.6%) and failure to thrive/growth retardation (22.8%). Treatments at follow-up include antimicrobials (20), hematopoietic stem cell transplantation (17), immunoglobulin replacement therapy (16), and immunosuppressants (9). Conclusions: A huge number of different PIDs are encountered in pediatric departments, often presenting with complex clinical pictures. Our results suggest that the identification of PID may be improved by a multidisciplinary approach, attaching importance not only to infections but also to other symptoms arising from a defective immune function.

Background Familial Mediterranean Fever (FMF) is an autosomalrecessive disorder characterized by recurrent attacks of fever and serositis. It is common in eastern Mediterranean population. There are only few FMF patients in Slovenia and Macedonia and the mutation carrier rate is not known. So far, over 80 disease associated mutations have been identified in MEFV gene; the most common are M694V, V726A, M680I, E148Q and M694I.The distribution pattern of MEFV mutation along the Mediterranean Sea is not uniform; eastern populations have the highest number of carriers (20-39%), whereas the number of carriers in western Mediterranean populations is considerably lower.

Background QI are retrospectively measurable elements of practice performance for which there is evidence or consensus that can be used to assess the quality of care provided. Aim To develop a set of consensus-derived QI for pSLE to serve as international benchmarks for the quality of patient care. Methods Based on the medical literature a Delphi survey was created and distributed to the physician membership of PRES, PANLAR, CARRA and the ACR via e-mail. Consensus was considered 80% or higher. Results There was consensus (97%) among the 297 respondents that simply applying QI developed by the ACR and EULAR for adults with SLE (adult QI) was insufficient and that distinct QI for pSLE were needed. Respondents concurred that 5 of the 20 ACR and 6 of the 24 EULAR adult QI are also suitable for pSLE. An additional 14 ACR and 13 EULAR adult QI might be useful for pSLE after modifications. There was no consensus whether to consider “Pregnancy” (45%) and “Reproductive Health” (65%) as domains in the set of pSLE QI. Conclusion There is great demand among pediatric rheumatologists to develop QI for pSLE. Initial agreement has been reached about the types and domains of QI for pSLE, but additional discussion and consensus formation under consideration of the medical evidence is needed to finalize a set of QI for pSLE that can be used to define standard of care treatment for children and adolescents with pSLE.

A 7-year-old boy with hyperimmunoglobulin M syndrome presented with intermittent bloody diarrhea since the age of 6 months. On physical examination he had hepatosplenomegaly, generalized lympadenopathy, and hyperpigmented papular/vesicular rash around the umbilicus. The growth parameters were normal. The skin biopsy wasconsistent withmastocytoma. Endoscopic evaluationrevealednodular smallintestinal mucosa. Themostprominent nodularity wasseen intheduodenum (Fig. 1), and less so in the terminal ileum. The histology revealed acute and chronic inflammation without architectural changes, and a high number of mastocytes, confirming systemic mastocytosis (Fig. 2). Treatment with monthly intravenous gamma globulin, antihistamines, ketotifen, and proton pump inhibitor resulted in almost complete resolution of gastrointestinal symptoms. Mastocytosisischaracterizedbyexcessiveproliferationofmastocytesinseveralorgans,mostfrequentlyskin,bones,lymphnodes,liver,spleen,andthegastrointestinaltract(1).Systemicmastocytosisisrareinchildren(2).Therapyisbasedonsymptomatictreatmentandavoidingtriggersofmastcellmediatorrelease.Long-termprognosisforpediatric-onsetdiseaseisbetterincontrasttoadult-onsetmastocytosis(3).HyperimmunoglobulinMalsocanbeassociatedwithchronicdiarrhea.Both Cryptosporidium and Giardia rarelycausenodularityofthesmallintestine(4);however,noetiologicmicroorganismwasidentifiedonstooltesting.Therefore,giventhe histologic picture a showing high number of mastocytes, we presume that the symptoms and the nodular mucosal changes were caused by systemic mastocytosis.

Objective: Anti-β2glycoprotein I antibodies (a-β2GPI) are a laboratory criterion for the antiphospholipid syndrome (APS) and were demonstrated to be involved in the pathogenesis of APS. However, they can also be detected in asymptomatic subjects. It has been suggested that a-β2GPI against Domain1 (D1) associate with thrombosis, while those recognizing Domain4/5 (D4/5) have been identified in non-thrombotic conditions. We evaluate the specificity of a- β2GPI in different clinical situations. Methods: We studied 39 one-year-old healthy children born to mothers with systemic autoimmune diseases (SAD) (15 (38.4%) were born to mothers who were a-β2GPI positive), 33 children with atopic dermatitis (AD) and 55 patients with APS (50 adults and 5 paediatrics). All subjects were IgG a-β2GPI positive. IgG a-β2GPI were performed by homemade ELISA, while IgG a-β2GPI D1 and D4/5 were tested on research ELISAs containing recombinant β2GPI domains antigens. Results: One-year-old children and AD children displayed preferential reactivity for D4/5; patients with APS recognized preferentially D1. We also found a good correlation between a-β2GPI and D4/5 in one-year-old (r=0.853) and AD children (r=0.879) and between a-β2GPI and D1 in the APS group (r=0.575). No thrombotic events were recorded in both groups of children. Conclusions: A-β2GPI found in non-thrombotic conditions (healthy children born to mothers with SAD and AD children) mostly recognize D4/5, in contrast to the prevalent specificity for D1 in the APS group. The different specificity could at least partially explain the “innocent” profile of a-β2GPI in children.

OBJECTIVE Anti-β2 GPI are a formal laboratory criterion for the antiphospholipid syndrome (APS). They were demonstrated to be a risk factor for thrombosis and fetal losses but can also be detected in patients with systemic autoimmune disease (SAD), in healthy adults individuals and pre-school children. It has been suggested that different subpopulations of anti-β2GPI may carry different pathogenetic potential: autoantibodies against Domain1 seem to be associated with thrombosis; autoantibodies against Domain4/5 have been identified in patients with non-thrombotic conditions. METHODS We studied 48 patients with SAD (32 systemic lupus erythematosus, 16 undifferentiated connettive tissue disease), 64 patients with APS, 57 one-year-old healthy children born to mother with SAD, 33 children with atopic dermatitis. All subjects were IgG anti-β2 GPI positive. The specificity of anti-β2 GPI was investigated using ELISA research products containing recombinant β2 GPI D1 and D4/5 antigens. Cut-off values are calculated as 95th percentile on 100 NHD. IgG anti-β2 GPI were tested at a validated home-made ELISA routinely performed in our laboratory. No thrombotic events were recordered in patients with SAD and in both groups of children. RESULTS Patients with SAD and APS showed prevalent reactivity for D1 while children in both groups preferentially recognize D4/5. CONCLUSIONS IgG anti-β2 GPI against D1 seem to cluster in patients with systemic autoimmune conditions. Their pathogenic potential in determine APS manifestations may be mitigated by adequate prophylaxis.

ObjectiveTo analyze the prevalence of diagnosed and suspected autoinflammatory diseases in Eastern and Central European (ECE) countries, with a particular interest on the diagnostic facilities in these countries.MethodsTwo different strategies were used to collect data on patients with periodic fever syndromes from ECE countries- the Eurofever survey and collection of data with the structured questionnaire.ResultsData from 35 centers in 14 ECE countries were collected. All together there were 11 patients reported with genetically confirmed familial Mediterranean fever (FMF), 14 with mevalonate-kinase deficiency (MKD), 11 with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and 4 with chronic infantile neurological cutaneous and articular syndrome (CINCA). Significantly higher numbers were reported for suspected cases which were not genetically tested. All together there were 49 suspected FMF patients reported, 24 MKD, 16 TRAPS, 7 CINCA and 2 suspected Muckle-Wells syndrome (MWS) patients.ConclusionsThe number of genetically confirmed patients with periodic fever syndromes in ECE countries is very low. In order to identify more patients in the future, it is important to organize educational programs for increasing the knowledge on these diseases and to establish a network for genetic testing of periodic fever syndromes in ECE countries.