Recognizing the Emergent and Submerged Iceberg of the Celiac Disease: ITAMA Project-Global Strategy Protocol.

Coeliac disease (CD) is frequently underdiagnosed with a consequent heavy burden in terms of morbidity and health care costs. Diagnosis of CD is based on the evaluation of symptoms and anti-transglutaminase antibodies IgA (TGA-IgA) levels, with values above a tenfold increase being the basis of the biopsy-free diagnostic approach suggested by present guidelines. This study showcased the largest screening project for CD carried out to date in school children (n=20,000) aimed at assessing the diagnostic accuracy of minimally invasive finger prick point-of-care tests (POCT) which, combined with conventional celiac serology and the aid of an artificial intelligence-based system, may eliminate the need for intestinal biopsy. Moreover, this study delves deeper into the "coeliac iceberg" in an attempt to identify people with disorders who may benefit from a gluten-free diet, even in the absence of gastrointestinal symptoms, abnormal serology and histology. This was achieved by looking for TGA-IgA mucosal deposits in duodenal biopsy. This large European multidisciplinary health project paves the way to an improved quality of life for patients by reducing the costs for diagnosis due to delayed findings of CD and to offer business opportunities in terms of diagnostic tools and support.

Streptococcus equi subsp. equi meningitis, septicemia and subdural empyema in a child.

Streptococcus equi subsp. equi is a group C ß-hemolytic streptococcus, and is an invasive pathogen with a very restricted host, causing the equine infection known as 'strangles'. It is a poor colonizer in horses, preferentially causing invasion and infection, compared with its ancestor Streptococcus equi subsp. zooepidemicus, which is considered an opportunistic commensal of the equine upper respiratory tract. In humans, S. equi subsp. equi causes invasive infections in immunocompromised hosts, often following close contact with horses. Such infections are associated with a high mortality, as well as a poor neurological outcome in survivors. Beta-lactam antimicrobials form the mainstay of treatment, while neurosurgical intervention is occasionally required. We present the case of a 13-year old boy with systemic lupus erythematosus being treated with hydroxychloroquine, who presented with S. equi subsp. equi meningitis and sepsis after contact with a sick pony. Although he recovered fully following eight weeks of intravenous ceftriaxone and oral rifampin, the clinical course was complicated by subdural empyema requiring neurosurgical evacuation.

Manifestations of paediatric Leishmania infantum infections in Malta.

Leishmania infantum is endemic in the Maltese archipelago, a group of islands in the Mediterranean which are visited frequently by tourists from Northern European countries. The burden of leishmaniasis is highest in children who may present with cutaneous or visceral manifestations. We describe systematically the manifestations, diagnosis and management of leishmaniasis in children <14 years of age, who had a histopathological diagnosis of leishmaniasis in Malta, from 2004 to 2008. Eleven children were diagnosed with leishmaniasis; 8 children (15-44 months of age) had visceral disease and three (aged 9-13 years) suffered cutaneous infections. Prolonged high grade fever, pallor, hepatosplenomegaly, and pancytopenia were common presenting features of visceralisation. Diagnosis was based on the visualisation of amastigotes from bone marrow aspirates. Pentavalent antimonials were associated with treatment failure in two children, whilst liposomal amphotericin B was curative in all. Children with cutaneous leishmaniasis had dry crusted ulcero-nodular lesions on exposed areas which responded to intra-lesional instillation of sodium stibogluconate or to cryotherapy. Leishmaniasis should be included in the differential diagnosis of fever and hepatosplenomegaly or chronic cutaneous lesions in children who travel to Malta.

Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency.

CONTEXT: Mutations within the gene encoding the pituitary-specific transcription factor POU1F1 are associated with combined pituitary hormone deficiency (CPHD). Most of the affected individuals manifest GH, prolactin, and TSH deficiency. OBJECTIVE: We have now screened 129 individuals with CPHD and isolated GH deficiency for mutations within POU1F1. RESULTS: Causative mutations were identified in 10 of 129 individuals (7.8%). Of these, five patients harbored the dominant negative R271W mutation, which is a well-recognized mutational hot spot. We have also identified a second frequently occurring mutation, E230K, which appears to be common in Maltese patients. Additionally, we describe two novel mutations within POU1F1, an insertion of a single base pair (ins778A) and a missense mutation (R172Q). Functional studies have revealed that POU1F1 (E230K) is associated with a reduction in transactivation, although DNA-binding affinity is similar to the wild-type protein. On the other hand, POU1F1 (R172Q) is associated with a reduction in DNA binding and transactivation, whereas POU1F1 (ins778A) is associated with loss of DNA binding and a reduction in transactivation. CONCLUSIONS: Our data suggest that the phenotype associated with POU1F1 mutations may be more variable, with the occasional preservation of TSH secretion. Additionally, our data revealed POU1F1 mutations in three patients who were diagnosed as having ACTH deficiency but who, on further evaluation, were found to have normal cortisol secretion. Hence, elucidation of the genotype led to further evaluation of the phenotype, with the cessation of cortisol replacement that had been commenced unnecessarily. These data reflect the importance of mutational analysis in patients with CPHD.

Assessment of use of spacer devices for inhaled drug delivery to asthmatic children.

In the treatment of bronchial asthma, inhaled therapy with both bronchodilators and corticosteroids represents the basis for acute and long-term management. Drug therapy in asthma is predominantly by pressurized metered dose inhalers. The impact of treatment on the disease morbidity and mortality depends to a large extent on appropriate delivery of drug to the lungs by means of a spacer device. We performed an audit on spacer use in 200 children and showed that 99% owned a spacer, 2% owned but did not use their spacer, 11% were using a spacer which was not ideal for their age, 17% had a poor technique, and 24% were not following the recommendations given on previous visits to wash the spacer only with a soapy solution. Although physicians frequently associate poor control of asthma with inadequate doses of drugs, many factors must be considered before increasing the dose of inhaled medications to children. We should all ensure that the drugs we prescribe are delivered in the best possible manner, thus improving control of asthma, reducing side effects and offering a more cost-effective therapy.

Increasing age at diagnosis of celiac disease in Malta.

OBJECTIVE: Recent studies have shown that celiac disease is being diagnosed at a progressively later age. This paper analyses trends in age at diagnosis in a closed island population. METHODS: Patient case notes of all known patients with celiac disease were retrieved and demographic information, mode of presentation including symptomatology and diagnostic criteria were obtained. Over the period 1985 to 2000, information was available on 42 patients with celiac disease. All were aged 14 years. RESULT: The mean age at diagnosis showed an increasing age, with a constant disease incidence. A highly significant positive correlation was found for age at diagnosis with time (rho=0.4, p=0.009). CONCLUSION: It is thought that breast feeding, with later introduction of gluten containing products in the diet, leads to a later presentation of celiac disease. In Malta, over the period under study, the breast feeding rate rose from 20% to 60%. Our findings support the hypothesis that breast feeding offers a degree of protection against the early development of celiac disease, without actually reducing the incidence of the disease.

The prevalence of coeliac disease in Down's syndrome in Malta.

The prevalence of coeliac disease is increased in individuals with Down's syndrome. The objective of this study was to assess the frequency of coeliac disease in Down's syndrome in Malta. One hundred children and adults with Down's were screened for coeliac disease. A history was taken from all of them and they were examined and measured for weight and height. A full blood count, antigliadin (IgG and IgA) and anti-endomysial antibodies were estimated. Equivocal cases were also screened for antireticulin antibodies. Jejunal biopsy was recommended in all serologically positive cases. The frequency of coeliac disease in Down's syndrome was 8%, much greater than that in the general population. Screening for coeliac disease in all cases of Down's syndrome is therefore recommended.

Type 2 cryoglobulinemia treated with plasmapheresis associated with IgA nephropathy.

Cryoglobulinemia is caused by antibodies which precipitate in blood on exposure to cold, and redissolve on warming. The authors present a child with essential, Type 2 cryoglobulinaemia, successfully treated with plasmapheresis, who developed glomerulonephritis due to IgA nephropathy. Conservative treatment resulted in spontaneous improvement with no deterioration in renal function.