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.

High arteriovenous fistula (AV fistula) blood flow may impair distal limb perfusion and cause irreversible ischemic damage. Since tissue temperature reflects blood perfusion, we tried to assess distal blood flow using an infrared camera. We examined all 12 patients with an AV fistula in our dialysis unit. Seven were pediatric patients aged 11.0–18.9 years (mean 14.9 years) and five were adults aged 26.9–62.1 years (mean 38.6 years). Infrared thermal imaging (thermography) of their hands was performed after the completion of their regular dialysis sessions. In each patient, the spot temperature of each fingertip on both hands was assessed separately, with three measurements being performed for each measuring point. The mean spot temperature of all fingertips was calculated for each hand and the results compared. A statistically significant difference (P < 0.05) indicated distal perfusion insufficiency. Perfusion of the hands was also assessed by inspecting the visualized temperature distribution on the thermal image. Finally, we compared the results to the clinical findings in relevant patients. In 8/12 patients (66.7%), the mean spot temperature of the fingertips was statistically significantly lower on the fistula side (P < 0.05). Only 4/12 patients (33.3%) had clinical symptoms, and all were detected by thermography. Abnormal findings were more frequent in elderly patients. Although we realize that the diagnosis of steal syndrome is primarily clinical, thermography might be a safe, noninvasive, cheap tool for the timely detection of children at risk of developing symptoms of hand ischemia.

Over the past decade, the treatment of a variety of immune-mediated diseases has improved greatly due to the introduction of biologics for therapies in cases that are nonresponsive to traditional treatments. However, a side effect not encountered in traditional treatments is the immunogenicity of the biologics themselves. Our aim was to investigate the anti-infliximab-antibody response in pediatric patients receiving infliximab for juvenile idiopathic arthritis and other pediatric rheumatic diseases, with a focus on an analysis of the binding sites of these antibodies. We show that anti-infliximab antibodies developed in 43% of patients receiving infliximab therapy. Neutralization studies showed that in all these patients, the antibodies were directed toward the variable domains of infliximab, as they inhibited binding of infliximab to TNF. A more precise determination of the antibody epitopes using synthetic peptides was not achieved, indicating that all the antibody binding sites were composed of discontinuous segments of infliximab.

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.

SUMMARY Objective: Anti-b 2 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-b 2 GPI may carry different pathogenetic potential: autoantibodies against Domain1 seem to be associated with thrombosis; autoantibodies against Domain4/5 have been identifi ed 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-b 2 GPI positive. The specifiof anti-b 2 GPI was investigated using ELISA research products containing recombinant b 2 GPI D1 and D4/5 antigens. Cut-off values are calculated as 95th percentile on 100 NHD. IgG anti-b 2 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-b 2 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.

Background Anti-β2-glycoprotein-I (anti-β2GPI) were demonstrated to be pathogenic in the antiphospholipid syndrome (APS). However, they can be detected in patients with no features of APS, especially those affected by systemic autoimmune diseases (SAD), and so in healthy children. It has been suggested that anti-β2GPI against domain 1 (D1) associate with thrombosis, while those recognising domain 4/5 (D4/5) are present in non-thrombotic conditions. Objective To evaluate the fine specificity of anti-β2GPI in adults and infants. Methods Three groups were examined—group A: 57 1-year-old healthy children born to mothers with SAD; group B: 33 children with atopic dermatitis; group C: 64 patients with APS. Subjects were selected based on positive anti-β2GPI IgG results. Serum samples were tested for anti-β2GPI IgG D1 and D4/5 using research ELISAs containing recombinant β2GPI domain antigens. Results Children (A and B) displayed preferential IgG reactivity for D4/5, whereas patients with APS were mainly positive for D1. No thrombotic events were recorded in groups A and B. Conclusions The specificity for D4/5 suggests that anti-β2GPI IgG production in children born to mothers with SAD is a process neither linked to systemic autoimmunity nor related to the maternal autoantibody status. This unusual fine specificity might, at least partially, account for the ‘innocent’ profile of such antibodies.

The registry is an European, multicentre, prospective and longitudinal study which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). In this article we report preliminary results obtained from 138 mothers and 141 babies (three twin pregnancies). At birth, 16.3% of neonates were less than 37 weeks of gestation and 17% were low birth weight; in addition, 11.3% of neonates were small for gestational age. No cases of neonatal thrombosis were observed. During follow-up period five children showed behavioral abnormalities. A long term clinical follow-up will be necessary to evaluate the neuropsychological development of these children.