Invasive meningococcal disease in three siblings with hereditary deficiency of the 8(th) component of complement: evidence for the importance of an early diagnosis.

BACKGROUND: Deficiency of the eighth component of complement (C8) is a very rare primary immunodeficiency, associated with invasive, recurrent infections mainly caused by Neisseria species. We report functional and immunochemical C8 deficiency diagnosed in three Albanian siblings who presented with severe meningococcal infections at the age of 15 years, 4 years and 17 months, respectively. The youngest suffered serious complications (necrosis of fingers and toes requiring amputation). METHODS: Functional activity of the classical, alternative and mannose-binding lectin complement pathways was measured in serum from the 3 siblings and their parents (37-year-old woman and 42-year-old man). Forty healthy subjects (20 males and 20 females aged 4-38 years) served as normal controls. Serum complement factors were measured by haemolytic assays and immunoblotting. Sequence DNA analysis of the C8B gene was performed. RESULTS: Analyses of the three complement pathways revealed no haemolytic activity and also absence of C8beta in serum samples from all three siblings. The genetic analysis showed that the three siblings were homozygous for the p.Arg428* mutation in the C8B gene on chromosome 1p32 (MIM 120960). The parents were heterozygous for the mutation and presented normal complement activities. A 2-year follow-up revealed no further infective episodes in the siblings after antibiotic prophylaxis and meningococcal vaccination. CONCLUSIONS: Complement deficiencies are rare and their occurrence is often underestimated. In presence of invasive meningococcal infection, we highlight the importance of complement screening in patients and their relatives in order to discover any genetic defects which would render necessary prophylaxis to prevent recurrent infections and severe complications.

Disease associated malnutrition correlates with length of hospital stay in children.

BACKGROUND & AIMS: Previous studies reported a wide range of estimated malnutrition prevalence (6-30%) in paediatric inpatients based on various anthropometric criteria. We performed anthropometry in hospitalised children and assessed the relationship between malnutrition and length of hospital stay (LOS) and complication rates. METHODS: In a prospective multi-centre European study, 2567 patients aged 1 month to 18 years were assessed in 14 centres in 12 countries by standardised anthropometry within the first 24 h after admission. Body mass index (BMI) and height/length <-2 standard deviation scores (SDS, WHO reference) were related to LOS (primary outcome), frequency of gastrointestinal (diarrhoea and vomiting) and infectious complications (antibiotic use), weight change during stay (secondary outcomes) and quality of life. RESULTS: A BMI <-2 SDS was present in 7.0% of the patients at hospital admission (range 4.0-9.3% across countries) with a higher prevalence in infants (10.8%) and toddlers aged 1-2 years (8.3%). A BMI <-2 to ≥-3 SDS (moderate malnutrition) and a BMI <-3 SDS (severe malnutrition) was associated with a 1.3 (CI95: 1.01, 1.55) and 1.6 (CI95: 1.27, 2.10) days longer LOS, respectively (p = 0.04 and p < 0.001). Reduced BMI <-2 SDS was also associated to lower quality of life, and more frequent occurrence of diarrhoea (22% vs 12%, p < 0.001) and vomiting (26% vs 14%, p < 0.001). CONCLUSION: Disease associated malnutrition in hospitalised children in Europe is common and is associated with significantly prolonged LOS and increased complications, with possible major cost implications, and reduced quality of life. This study was registered at clinicaltrials.gov as NCT01132742.

Hyper-IgE syndrome: dental implications.

Hyper-IgE syndrome (HIES) is a rare multisystem disorder with both immunologic and nonimmunological features. It is characterized by extremely elevated IgE serum levels, eczema, and recurrent skin and pulmonary infections. Dental anomalies are often included, such as retention of deciduous teeth together with ectopic eruption or noneruption of permanent teeth. Severe susceptibility to caries and mycotic infections, insufficient transversal diameter of the palate, mucosal plaques, and fissures typically located on the tongue and on the palate are often present. The aim of this study was to review the literature and to report a 6-year observation of 6 patients with HIES (aged 8-39 years) with focus on their oral problems and the treatment provided. The importance of the role of the dentist both in early diagnosis of this syndrome and in monitoring oral conditions was stressed. The dentist can prevent infective complications and intercept the development of malocclusion with a reduction of the need for complex treatment.

Atopy in preschool Italian children with recurrent respiratory infections.

OBJECTIVES: Recurrent respiratory infections (RRI) are a common problem mainly in pre-school age, due to the presence of unfavourable environmental conditions, including early socialization, as well as the immaturity and inexperience of the immune system. The relation between atopy and RRI has been evaluated in several studies, but the results were not conclusive. This study sought to determine the impact of atopy, the immunological and clinical profile in 297 Italian children with RRI, younger than 6 years. METHODS: All children were assessed for blood leukocyte count, serum immunoglobulin level, IgG subclasses, lymphocytic subpopulations, total and specific IgE levels for common food and inhalant allergens. RESULTS: A total of 218 children (73.4%) provided a positive family history of atopic disorders. Atopy was found in 150 out of 297 children (50.5%). Early onset (<1 year) of RRI symptoms occurred more frequently in atopic children that in non atopic ones (58.9% vs 44%, p=0.02). A higher percentage of the male children (61.6%) got sick, as compared with the percentage of female children (38.4%), and the male children were more frequently atopic (67.3% vs 55.8%, p=0.03). Thirty-nine out of 297 children (13.2%) were diagnosed as having immunological disorders (IgA deficiency, IgG2 deficiency and transient hypogammaglobulinemia). CONCLUSIONS: Our results provide evidence that, in our population, atopy is a frequent condition and it's likely to be a favouring factor for RRI, while the presence of an underlying immunological disease is relatively uncommon and immune defects are mostly mild.

Outcome of tonsillectomy in selected patients with PFAPA syndrome.

OBJECTIVE: To assess the practicability of integrated medical and surgical management and the effectiveness of tonsillectomy in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, and cervical lymphadenopathy). DESIGN: A prospective study. SETTING: Secondary pediatric and otolaryngological university center. PATIENTS: Of 30 patients evaluated for periodic fever, 18 children with PFAPA syndrome were included in the study. INTERVENTIONS: Patients underwent long-term pediatric and otolaryngological assessments, and their parents were asked to keep monthly diaries with reports of any subsequent episodes, symptom, and related sign. Patients received traditional medical therapies, and 9 patients underwent tonsillectomy for the lack of lasting recovery. MAIN OUTCOME MEASURES: The association between postoperative outcomes and age at tonsillectomy and the differences in the patients' condition before and after tonsillectomy were statistically tested. In addition, the removed tonsillar tissue was analyzed molecularly to evaluate concomitant infections. RESULTS: All of the surgical patients reported a symptomatic improvement, with complete clinical recovery in 5 cases (56%) and significant reduction in number (P = .005) and duration (P = .03) of recurrences in the remaining 4 (44%). Results of molecular analysis of tonsillar specimens were negative for bacteria in all but 1 patient. CONCLUSION: Otolaryngologists should be trained to recognize PFAPA syndrome, for which management consists of a regular and prolonged second-level pediatric and otolaryngological follow-up, with surgery only after the failure of traditional medical therapy.