Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping anti-inflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. METHODS: Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. RESULTS: 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. CONCLUSIONS: Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.

Antiretroviral use in Italian children with perinatal HIV infection over a 14-year period.

BACKGROUND: Information on the use of new antiretroviral drugs in children in the real setting of clinical fields is largely unknown. METHODS: Data from 2554 combined antiretroviral therapy (cART) regimens administered to 911 children enrolled in the Italian Register for HIV infection in children, between 1996 and 2009, were analysed. Factors potentially associated with undetectable viral load and immunological response to cART were explored by Cox regression analysis. RESULTS: Proportion of protease inhibitor (PI)-based regimens significantly decreased from 88.0% to 51.2% and 54.9%, while proportion on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens increased from 4.5% to 38.8% and 40.2% in 1996-1999, 2000-2004 and 2005-2009, respectively (p < 0.0001). Significant change in the use of each antiretroviral drug occurred over the time periods (p < 0.0001). Factors independently associated with virological and immunological success were as follows: later calendar periods, younger age at regimen (only for virological success) and higher CD4(+) T-lymphocyte percentage at baseline. Use of unboosted PI was associated with lower adjusted hazard ratio (aHR) of virological or immunological success with respect to NNRTI- and boosted PI-based regimens, with no difference among these two latter types. CONCLUSION: Use of new generation antiretroviral drugs in Italian HIV-infected children is increasing. No different viro-immunological outcomes between NNRTI- and boosted PI-based cART were observed.

Does improvement management of atopic dermatitis influence the appearance of respiratory allergic diseases? A follow-up study.

BACKGROUND: Atopic dermatitis (AD) is often the prelude to allergic diseases. The aim of this study was 1) to evaluate if an integrated management regime could bring about a change in the evolution of the disease in comparison to the results of a previous study; 2) to determine whether the refinement of allergic investigations allowed to identify more promptly the risk factors of evolution into respiratory allergic diseases. METHODS: The study included 176 children affected by AD and previously evaluated between 1993 and 2002 at the age of 9-16 months, who underwent a telephonic interview by means of a semi-structured, pre-formed questionnaire after a mean follow-up time of 8 years. According to the SCORAD, at first evaluation children had mild AD in 23% of cases, moderate in 62%, severe in 15%. RESULTS: AD disappeared in 92 cases (52%), asthma appeared in 30 (17%) and rhinoconjunctivitis in 48 (27%). The factors significantly related to the appearance of asthma were: sensitization to food allergens with sIgE > 2 KU/L (cow's milk and hen's egg; P < 0.05); to inhalant allergens with sIgE > 0.35 KU/L (P < 0.05). Logistic regression analysis showed that inhalant sensitization was positively related to the occurrence of asthma (OR = 4.219). While AD showed similar rates of disappearance to those of our previous study, the incidence of asthma was reduced, at the same follow-up time, from 29% to 15% (P = 0.002), and the incidence of rhinoconjunctivitis from 35% to 24% (P = 0.02). CONCLUSION: Comparing the results with those of the previous study, integrated management of AD does not seem to influence its natural course. Nevertheless, the decrease in the percentage of children evolving towards respiratory allergic disease stresses the importance of early diagnosis and improvement management carried out by specialist centers. The presence of allergic sensitization at one year of age might predict the development of respiratory allergy.

The spectrum of plant and animal sterols in different oil-derived intravenous emulsions.

Intravenous lipid constituents have different effects on various biological processes. Some of these effects are protective, while others are potentially adverse. Phytosterols, in particular, seem to be implicated with parenteral nutrition-associated cholestasis. The aim of this study is to determine the amount of plant and animal sterols present in lipid formulations derived from different oil sources. To this end, animal (cholesterol) and plant (beta-sitosterol, campesterol, and stigmasterol) sterols in seven different commercially available intravenous lipid emulsions (ILEs) were quantified by capillary gas chromatography after performing a lipid extraction procedure. The two major constituents of the lipid emulsions were cholesterol (range 14-57% of total lipids) and beta-sitosterol (range 24-55%), followed by campesterol (range 8-18%) and stigmasterol (range 5-16%). The fish oil-derived formulation was an exception, as it contained only cholesterol. The mean values of the different sterols were statistically different across ILEs (P = 0.0000). A large percentage of pairwise comparisons were also statistically significant (P = 0.000), most notably for cholesterol and stigmasterol (14 out of 21 for both), followed by campesterol (12 out 21) and beta-sitosterol (11 out 21). In conclusion, most ILEs combined significant amounts of phytosterols and cholesterol. However, their phytosterols:cholesterol ratios were reversed compared to the normal human diet.

Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy.

BACKGROUND: Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking. METHODS: We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided. RESULTS: Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001). CONCLUSION: Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.

Use of the Italian version of the Pediatric Asthma Quality of Life Questionnaire in the daily practice: results of a prospective study.

BACKGROUND: Asthma is a serious global health problem and its prevalence is increasing, especially among children. It represents a significant social and economic burden, and it can severely affect the health-related quality of life (HRQL) of patients. Among the numerous questionnaires aiming at evaluating asthma HRQL in children, the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) has proved to have good measurement properties.The present study was aimed at investigating the possible role of the Italian, self-administered version of the PAQLQ in the routine clinical evaluation of children affected by bronchial asthma. METHODS: 52 Italian children and adolescents (40 males and 12 females), aged 6 to 17 years, affected by allergic asthma, were enrolled. Each patient was evaluated twice, and at each visit asthma control and severity were assessed, spirometry was performed and the patients completed the self-administered version of the PAQLQ. RESULTS: The questionnaire was well-accepted and understood by the children. Children showed an overall good quality of life, with mild impairment in the activity and emotional function domains. The PAQLQ showed an overall good correlation with the clinical and functional indexes that are normally evaluated in follow-up visits of asthmatic patients. The PAQLQ appeared to be strongly related to asthma control, both at the first (p < 0.01) and second (p < 0.001) time of the study. The PAQLQ was also seen to decrease with increasing asthma severity. The results suggest a better compliance of the children towards completion of the questionnaire at t1. Finally, the PAQLQ does not appear to discriminate HRQL in patients with good lung function. CONCLUSION: The Italian version of the PAQLQ is a quick-to-administer aid to clinical activity and can add valuable information to symptom reports, objective measurements and clinical assessment of asthma control and severity in daily clinical practice. Re-administration at each follow-up visit allows HRQL to be monitored over time.

Three years of Italian experience of an educational program for parents of young children affected by atopic dermatitis: improving knowledge produces lower anxiety levels in parents of children with atopic dermatitis.

The chronic course of atopic dermatitis is a problem for children and their families: it can be extremely disabling, and may cause psychologic problems for both child and family. As atopic dermatitis affects 10% of the pediatric population, pediatricians and dermatologists spend much time on the treatment of this disease, which requires a multidisciplinary approach. To improve the quality of life of children and families affected by atopic dermatitis we have offered an educational program to the parents of young children affected by the disease. The program consists of six meetings at weekly intervals involving a pediatric allergist, a dermatologist, and a psychologist. Our experience has been positive. This type of program may help to improve the quality of life of families with children affected by atopic dermatitis. Lower levels of anxiety were observed among parents at the end of the program. We believe that educational programs of this type, in association with conventional treatment, can be useful in the long term management of the disease. They may be considered to improve the quality of life of the family and children and to create more interaction and compliance between physicians, parents, and children.

Systemic therapy of atopic dermatitis in children.

Atopic dermatitis (AD) is a common disease in childhood that is a serious burden on patients and their families. Most AD is mild and can be managed with the use of emollients and standard therapy consisting of topical corticosteroids or topical calcineurin inhibitors. However, in a subgroup of patients with moderate to severe AD, the disease is recalcitrant to topical therapy and systemic treatments become necessary. Short courses of systemic corticosteroids are often used in clinical practice, but their use is controversial. International guidelines suggest that in the case of acute flare-ups, patients might benefit from a short course of systemic corticosteroids, but long-term use and use in children should be avoided. Ciclosporin is an immunosuppressant agent that acts directly on cells of the immune system, with an inhibitory effect on T cells. When AD cannot be controlled by standard topical therapies, ciclosporin significantly decreases symptom scores, disease extent, pruritus and sleep deprivation, and improves quality of life. The most frequent adverse effects associated with the use of ciclosporin are hypertension and renal dysfunction, but they are usually reversible after drug discontinuation. Ciclosporin has been found to be safely used, effective and well tolerated in children with severe AD. However, studies to assess the long-term effectiveness and safety of ciclosporin in AD are lacking. In patients for whom ciclosporin is not suitable, or when there is a lack of response, alternative drugs should be considered, such as azathioprine or interferon-gamma. Intravenous immunoglobulins and the monoclonal antibody infliximab only have a place in the systemic therapy of AD when other drugs have failed. Mycophenolate mofetil has recently been introduced in the treatment of recalcitrant AD. Efalizumab and omalizumab are monoclonal antibodies with a possible future role in the treatment of AD, but further studies are needed.

Atopic dermatitis: quality of life of young Italian children and their families and correlation with severity score.

The aim of this study was to determine the ways in which atopic dermatitis (AD) affects the lives of young Italian children and their families, in terms of quality of life, and correlate it with AD severity and the perception of severity as estimated by the family. The parents of 45 children aged 3-84 months affected by AD were asked to complete two validated questionnaires after clinical examination. The first questionnaire was about the child's quality of life (Infants' Dermatitis Quality of Life Index); the second regarded the family's quality of life (Dermatitis Family Impact questionnaire). In a further question parents were asked to estimate the severity of the disease of the child. Children's quality of life appeared slightly-moderately altered (mean score 10.2) compared with the value of a control group (3.3), and itching, sleep problems and the influence of the disease on the child's mood were the cause of greatest discomfort for the child. Family quality of life appeared moderately altered (mean score 11) compared with the value of the control group (7.4). The greatest problem was the disturbed sleep of the family members. Other important problems were the economic cost for the management of the disease and the tiredness and irritability caused by the disease in parents. Analysis of the responses confirms the incorrect estimation of the severity of the disease perceived by the family. In our opinion, the two questionnaires may be useful in clinical practice to understand better the difficulties suffered by a family with a child affected by AD. They also provide data that may help to improve the clinical approach for the child and the family, and to assess the degree of under-/overestimation of the disease by the family.

Evaluation of the antibacterial activity of a special silk textile in the treatment of atopic dermatitis.

BACKGROUND: Increased skin Staphylococcus aureus colonization is frequently found in atopic patients. The reduction of local overinfection decreases skin inflammation and improves the flares. OBJECTIVE: To evaluate the effectiveness of the antimicrobial activity of a silk fabric (MICROAIR DermaSilk) coated with alkoxysilane quaternary ammonium with durable antimicrobial properties (AEGIS AEM 5572/5) in children affected by atopic dermatitis (AD). METHODS: Sixteen children, 12 affected by AD with symmetric eczematous lesions on the antecubital areas and 4 without any cutaneous disease, used, for 7 days, tubular arm covers made of this special silk fabric but only one of each pair was coated with AEGIS AEM 5572/5. Microbiological examinations were done with standard cultural swabs and by means of quantification of bacterial agents using agar plates at baseline, after 1 h and after 7 days. RESULTS: After 7 days a significant improvement in the mean value of the 'local SCORAD' index was observed in both the covered areas compared to the values obtained at baseline. The reduction in the mean number of colony forming units per square centimetre was similar in both areas. CONCLUSIONS: Although this special silk fabric seems to be able to improve skin lesions in AD, we were unable to demonstrate that such silk fabrics coated with AEGIS AEM 5572/5 have an antibacterial activity in vivo, as shown in vitro.

Long-term follow-up of atopic dermatitis: retrospective analysis of related risk factors and association with concomitant allergic diseases.

BACKGROUND: The association of atopic dermatitis (AD) with other allergic diseases has been extensively studied; however, there is a lack of reports focusing on long-term studies of the clinical and allergometric evaluations observed during the course of AD in respect to its evolution and association with allergic responses in affected patients. OBJECTIVE: The aim of this study was to evaluate, with defined criteria of clinical diagnosis, severity assessment, and objective allergometric test at the time of inclusion, the natural course of AD, the factors influencing its healing or persistence, and the appearance of other allergic diseases with particular focus on asthma and the presence of specific immunoglobulin E at first observation. METHODS: This study included only children, aged between 6 and 36 months, whose first clinical examination was made between 1981 and 1989. A total of 252 children satisfied these criteria. A semistructured interview was performed by the physician using a preformed questionnaire, which was completed for 205 children (104 boys and 101 girls). RESULTS: AD had completely disappeared in 124 cases (60.5%). Other allergic manifestations that appeared included asthma in 70 cases (34.1%) and rhinoconjunctivitis (RC) in 118 cases (57.6%). Generally the average age of patients recovering from AD was higher in severe AD (6.0 +/- 3.5 years) than in its moderate or mild forms (5.8 +/- 4.5 and 5.5 +/- 3.9 years, respectively). This phenomenon was particularly evident in children with hen's egg sensitization, who show a longer persistence of the condition (Student t = 2.462 and P < .02). The initial severity score of AD was found to be associated with a high frequency of asthma appearance (Pearson chi2 = 14.225 and P < .001). Hen's egg sensitization was significantly related to the appearance of asthma (Fisher's exact test P < .007) and RC (Fisher's exact test P < .05). A retrospective analysis of related risks factors and their association with concomitant allergic diseases in our case studies shows that the egg sensitization, severity of AD, and onset of RC were positively related to the occurrence of asthma. In addition, our analysis shows that, although the appearance of RC was proportional to the incidence of atopy and asthma, it was inversely related to the persistence of AD (corrected odds ratio confidence intervals <1). LIMITATIONS: The study includes children referred to the hospital. However, it is the practice of local national health pediatricians to send all patients with suspected AD, whatever the severity grade, to hospital specialists to perform allergometric assessment. CONCLUSION: The use of defined criteria of clinical diagnosis for the determination of the condition's severity, along with the performance of objective allergometric tests at the time of inclusion, shows that the course of AD is significantly related to egg sensitivity. In addition, the average healing time is higher in egg-sensitive patients affected by the most severe form of AD than in mild or moderate cases.

Atopic dermatitis in Italian children: evaluation of its economic impact.

INTRODUCTION: The aim of our study was to evaluate the economic impact of atopic dermatitis (AD) on the family of young children affected by the disease in Italy. METHODS: Thirty-three families of young children affected by AD were asked to fill in a questionnaire about financial costs associated with providing health care during the past year for their child affected by AD. For each child AD severity was evaluated by using the SCORAD index. RESULTS: By analyzing the questionnaire, an annual average cost of 1254euro (about U.S. $1540) for each family was determined. Main expenses concern the use of moisturizing therapies, particular detergent, and private specialist consultations. Annual family average cost was lower for children with mild AD compared with those with moderate to severe AD. DISCUSSION: AD has a deep impact on the family budget, with an increasing cost in proportion to the increasing severity of the disease. These data support previous reports suggesting that the management of AD in children is complex and costly, altering the quality of life of children and their families.

Frequency and clinical role of Staphylococcus aureus overinfection in atopic dermatitis in children.

The goal of this study was to evaluate the frequency and role of Staphylococcus aureus infection in patients with atopic dermatitis (AD). In 81 children, ages 2 months to 9 years, affected with moderate to severe AD, 308 samples from the cutaneous lesions were obtained and analyzed. S. aureus was isolated in 52 children (64.2%). Five of these were also colonized by Streptococcus pyogenes and one by Candida albicans. In 61 patients, total IgE serum level and specific IgE were tested to evaluate their allergic status: in 43 children a diagnosis of extrinsic AD was made, while 18 were affected by intrinsic AD. A higher presence of the bacterium was observed in allergic (71%) versus nonallergic children (49%). Our data demonstrate the importance of S. aureus in the clinical manifestation of AD and, in particular, its role in worsening the eczematous lesions of the face, neck, and perineum in children less than 1 year of age.

Gianotti-Crosti syndrome and allergic background.

The aim of the study was to verify whether there is a relationship between Gianotti-Crosti syndrome and an allergic background in children. Twenty-nine children affected by Gianotti-Crosti syndrome were first screened for a large panel of microbiological examinations, including serological and cultural tests for viruses and bacteria. A causative agent was identified in only 10 cases (34.4%). In five cases a diagnosis of Epstein-Barr virus infection was made on the basis of significant titres of anti-Epstein-Barr virus antibodies (IgM) associated with constitutional symptoms (fever, pharyngitis-tonsillitis). Our data concur with several clinical studies demonstrating that Epstein-Barr virus is now the most common viral agent associated with Gianotti-Crosti syndrome. For allergic evaluation, a group of 59 age- and sex-matched children investigated for recurrent infections were used as controls. The presence of atopic dermatitis (24.1%) in those with Gianotti-Crosti syndrome was significantly higher (p < 0.005) than in the control group (6.8%). In addition, a more common family history for atopy was 51.7% vs. 31% (p < 0.027) and the percentage of patients with total IgE greater than +2 SD for age higher than in controls (27.6% vs. 13.7%), as was the percentage of specific IgE present (31% vs. 17.2%). These results indicate that atopy is significantly associated with Gianotti-Crosti syndrome.

Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study.

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.