Andrea Taddio

Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab.

To compare the efficacy and safety of adalimumab versus infliximab in an open‐label prospective, comparative, multicenter cohort study of childhood noninfectious chronic uveitis.

Looking for celiac disease : Diagnostic accuracy of two rapid commercial assays

BACKGROUND:Early diagnosis and treatment with gluten-free diet reduces mortality and the prevalence of associated disorders in celiac disease (CD). A simple “in the office” test of anti-transglutaminase antibodies might be of great help in first-line screening for CD.AIMS:We evaluated the sensitivity and specificity of two commercial kits based, respectively, on rapid detection of IgA-IgG anti-human-transglutaminase antibodies (anti-h-tTG) in serum and IgA anti-h-tTG antibody in one drop of whole blood. These assays were compared to a well-established enzyme-linked immunosorbent assay technique.METHODS:Serum samples were analyzed from 114 biopsy-confirmed celiacs, 120 healthy controls, 20 first-degree relatives of celiacs, and 75 diseased controls. The whole blood samples were analyzed from 51 biopsy-confirmed celiacs and 100 controls.RESULTS:The serum-based test was positive in all 114 celiacs (sensitivity 100%). Among the controls there were seven healthy blood donors, one first-degree relative, and three diseased controls who tested positive (specificity 94.9%). The blood drop-based assay testing IgA antibodies was positive in 46 of 51 (sensitivity 90.2%), and since three of the five patients testing negative had total IgA deficiency, the sensitivity value can be increased to 95.8%. All 100 controls tested negative (specificity 100%).CONCLUSIONS:The commercial kits described here produce high values of sensitivity and specificity, offering the general practitioner who suspects a possible case of CD the real possibility to look for anti-h-tTG antibodies in his own medical office during a standard visit at a satisfyingly low cost.

The resurgence of rheumatic fever in a developed country area: the role of echocardiography

OBJECTIVES The annual incidence of ARF ranges from 5 to 51/100, 000 population worldwide in the 5- to 15-year age group. In the past, there was a decline in the incidence of ARF; however, focal outbreaks have been reported. This study evaluated the incidence of ARF in 2007-08 in a region of a developed country compared with the previous decade. METHODS A retrospective review of all admission records for ARF in Trieste between January 2007 and December 2008 was undertaken. The diagnosis of ARF was established by the Jones criteria according to the 1992 revision. RESULTS Between January 2007 and December 2008: 13 cases of ARF were recorded, 11 females and 2 males. The estimated incidence was 23 and 27/100, 000 population new cases each year, respectively, in the 5- to 15-year age group. Migratory polyarthritis occurred in 6/13, chorea in 7/13 and clinical carditis in 5/13 cases. Five out of 13 patients had only echocardiographic abnormalities, with no clinical cardiac manifestations. Another two patients did not fulfil diagnostic criteria for ARF, presenting with only three minor criteria, but they revealed silent carditis at echocardiography evaluation. During the follow-up, in one case the carditis receded and in the other it significantly improved. CONCLUSIONS Our experience underlines that ARF has not yet disappeared in industrialized countries. We observed a high incidence of chorea, always associated with mild carditis. Echocardiographic assessment should be routinely performed in all patients with suspected ARF in order to identify those subclinical cases of valvulitis that would otherwise pass undiagnosed without receiving proper prophylaxis.

Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.

Medium-term survival without haematopoietic stem cell transplantation in a case of IPEX: insights into nutritional and immunosuppressive therapy

Immunodysregulation, polyendocrinopathy, enteropathy, Xlinked (IPEX; OMIM 304930) is a severe disorder of immune development characterised by a usually fatal course in early childhood [6]. It is due to mutations in the FOXP3 gene (locus Xp11.23-q13.3) [2, 4, 9], leading to failure in immune tolerance. Haematopoietic stem cell transplantation (HSCT) is the only definitive therapy and, even if its success is inconstant, it is considered to be the treatment of choice for the disease [6, 8, 10]. On the other hand, just two cases have been reported as surviving the first decade with a severe form of the disease without HSCT [5, 7]. A 1-month-old male was referred to our department for a severe eczema (Fig. 1), intractable mucous diarrhoea and failure to thrive. Extensive investigations ruled out a severe combined immunodeficiency (SCID). Symptoms were controlled with intravenous immunoglobulin, cyclosporin A, steroids and total parenteral nutrition (TPN) (Fig. 2). During his second year of life, he developed autoimmune diabetes, autoimmune haemolytic anaemia (AHA), inflammatory interstitial pneumonia, alopecia and thyroiditis. Due to the unsatisfactory response to prednisone, oral betamethasone was prescribed, with a dramatically greater efficacy at an equipotent dosage. A bone marrow transplantation was refused by the parents. Flares of dermatitis, AHA and pneumonia occurred after every cold and required increasing doses of steroids, antibiotics and oxygen administration. Cyclosporin A (10 mg/kg/day) did not allow a reduction of steroids and the child developed a Cushing-like aspect. An experimental treatment with fludarabine followed by the infusion of autologous lymphocytes treated in vitro with vincristine and prednisone was repeated twice, allowing a prolonged reduction of steroid dosage (0.5–0.25 mg/day of betamethasone) and fairly good clinical improvement with less frequent and less intense reactivation of symptoms. At Eur J Pediatr (2007) 166:1195–1197 DOI 10.1007/s00431-006-0395-6

Prognostic Impact of Atypical Presentation in Pediatric Systemic Lupus Erythematosus: Results from a Multicenter Study

OBJECTIVES The aim of the study is to assess the rate of atypical manifestations at onset in pediatric systemic lupus erythematosus (SLE) and to evaluate their effect on disease outcome. STUDY DESIGN This is a multicenter retrospective cohort study. A manifestation was considered atypical if it was not included in the American College Rheumatology classification criteria for SLE but was reported in literature as associated with SLE. Unfavorable outcome was considered presence of organ damage in the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index at the last available evaluation. RESULTS One hundred patients were enrolled in the study; 24% presented atypical clinical features at onset. Univariate analysis showed a significant association of worse outcome variables with the presence of atypical manifestations at onset (P = .004), as well as renal involvement (P = .027). A multivariate logistic regression analysis showed that atypical manifestations at onset (P = .018), renal involvement at onset or during follow up (P = .024), and central nervous system disease involvement during follow up (P = .021) were independent predictors of poor prognosis. CONCLUSIONS Our data support a relatively high rate of atypical onset in pediatric SLE. Presence of atypical manifestations at presentation and early kidney disease correlate with poor outcome. Similarly, during follow-up, kidney and central nervous system diseases are associated with worse outcome.

The universe of immune deficiencies in Crohn's disease: A new viewpoint for an old disease?

Abstract Crohns disease (CD) is generally considered a multifactorial disorder, since different genetic and environmental factors are thought to play a role in its pathogenesis. Recently, genome wide linkage studies allowed to identify the association of several loci with the increased risk of CD, although it is still unclear how they interact with environmental factors in causing the disease. The fact that many CD-risk-related genes are involved in the function of phagocytes seems in agreement with the well known role of these cells in CD histopathology. Functional defects in cytokine production or in clearance of bacteria in CD patients have recently been reported. Growing evidence that CD could arise from primary phagocyte immunodeficiency is also coming from the study of cases with early onset in infancy. We review such evidences starting from selected cases and discuss the clinical implications of these findings.

A comparison of three scales for measuring pain in children with cognitive impairment.

Pain is a neglected problem in children with cognitive impairments, and few studies compare the clinical use of specific pain scales. We compared the Non‐Communicating Childrens Pain Checklist Postoperative Version (NCCPC‐PV), the Echelle Douleur Enfant San Salvador (DESS) and the Childrens Hospital of Eastern Ontario Pain Scale (CHEOPS). The first two were developed for children with cognitive impairment, and the third is a more general pain scale.

Acute febrile cholestatic jaundice in children: keep in mind Kawasaki disease.

ABSTRACT Kawasaki disease (KD) is characterized by persistent fever in addition to 4 of 5 signs of mucocutaneous inflammation. Although gastrointestinal involvement does not belong to the classic diagnostic criteria, it has been often associated with KD onset. We reviewed patients who were admitted for febrile cholestatic jaundice between 2003 and 2010 in 2 tertiary pediatric care centers. KD was the second most frequent cause (21%) after viral infections. Considering the relative high frequency of this condition, a high index of suspicion of KD should be maintained in patients presenting with febrile cholestatic jaundice.

Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with Crohn's disease.

Mesenchymal stem cells (MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro. It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders. We present the case of a patient suffering from childhood-onset, multidrug resistant and steroid-dependent Crohns disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patients peripheral blood mononuclear cells. Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation. The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.