The immunity of upper airways.

A specialized immune system, called the nasopharynx-associated lymphoid tissue (NALT), is located on the mucosal surface of upper airways and is composed of both innate and specific immunity elements, closely related to each other and to the systemic defence, and spread over the nasopharynx, the nose and the middle ear. The NALT has a major role as regards to the infectious diseases of this area, which are the most common in children. It is also an interesting field of experimentation for new vaccine strategies in the future.

Urticaria and urticaria related skin condition/disease in children.

Urticaria is a rash, that typically involves skin and mucosa, and is characterized by lesions known as hives or wheals. In some cases there is an involvement of deep dermis and subcutaneous tissue that causes a skin/mucosa manifestation called angioedema. Urticaria and angioedema are very often associated: urticaria-angioedema syndrome. The acute episodic form is the most prevalent in the pediatric population, and it is often a recurrent phenomenon (recurrent urticaria). Acute episodic urticaria it is usually triggered by viruses, allergic reactions to foods and drugs, contact with chemicals and irritants, or physical stimuli. In many instances it is not possible to identify a specific cause (idiopathic urticaria). Chronic urticaria is a condition that can be very disambling when severe. In children is caused by physical factors in 5-10% of cases. Other trigger factors are infections, foods, additives, aeroallergens and drugs. The causative factor for chronic urticaria is identified in about 20% of cases. About one-third of children with chronic urticaria have circulating functional autoantibodies against the high affinity IgE receptor or against IgE. (chronic urticaria with autoantibodies or "autoimmune" urticaria). It is not known why such antibodies are produced, or if the presence of these antibodies alter the course of the disease or influence the response to treatment. Urticaria and angioedema can be symptoms of systemic diseases (collagenopathies, endocrinopathies, tumors, hemolytic diseases, celiachia) or can be congenital (cold induced familiar urticaria, hereditary angioedema). The diagnosis is based on patient personal history and it is very important to spend time documenting this in detail. Different urticaria clinical features must guide the diagnostic work-up and there is no need to use the same blood tests for all cases of urticaria. The urticaria treatment includes identification of the triggering agent and its removal, reduction of aspecific factors that may contribute to the urticaria or can increase the itch, and use of anti-H1 antihistamines (and/or steroids for short periods if antihistamines are not effective). In some instances an anti-H2 antihistamine can be added to the anti-H1 antihistamines, even if the benefits of such practice are not clear. The antileucotriens can be beneficial in a small subgroup of patients with chronic urticaria. In case of chronic urticaria resistant to all the aforementioned treatments, cyclosporine and tacrolimus have been used with good success. When urticaria is associated to anaphylaxis, i.m epinephrine needs to be used, together with antihistamines and steroids (in addition to fluids and bronchodilatators if required).

Allergen specific nasal challenge to latex in children with latex allergy: clinical and immunological evaluation.

There are no data concerning the significance of allergen specific nasal challenge to latex (ASNCL) in the pediatric population and the effect of mometasone furoate nasal spray (MFNS), topic corticosteroid exerting a potent anti-inflammatory activity in children with latex allergic rhinitis. The aims of this study are: to investigate the clinical and immune pathological effects of ASNCL in children with latex allergy; to study the effects of MFNS pre-medication on the clinical and immune pathological effects of ASNCL in children with latex allergy. Thirteen children: 6 male and 7 female, mean (SD) age 9.6 (2.9) years, with latex allergy and seven children: 3 male and 4 female, mean (SD) age 9.9 (3.8) years, without latex allergy underwent ASNCL. Nasal symptoms were recorded, nasal lavage fluid was collected to measure tryptase, eosinophil cationic protein (ECP), interleukin-5, interferon-gamma levels, and spirometric test was performed for each patient without or with premedication with MFNS. ASNCL induced a clinical allergic response and increased tryptase levels only in children with latex allergy. No serious adverse events occurred after ASNCL. MFNS premedication reduced both tryptase and ECP levels only in children with latex allergy. ASNCL is a simple, reliable and useful tool to make or confirm the diagnosis of nasal symptoms due to latex; it allows us to study both clinical symptoms and local immunological changes. MFNS premedication before an ASNCL may prevent some immunological responses induced by ASNCL without clinical allergic modifications.

Eyelash length in children with vernal keratoconjunctivitis: effect of treatment with cyclosporine eye drops.

The upper eyelashes in vernal keratoconjunctivitis (VKC) patients have been reported to be longer than in healthy age- and gender-matched subjects. Eyelash length positively correlated to the severity of the disease and negatively to the employment of cyclosporine eye drops, suggesting that specific humoral factors could be involved in both ocular inflammation and elongation of the eyelashes. The aim of the present study is to evaluate a possible relationship between eyelash length and the duration of topical cyclosporine treatment. The length of the upper eyelashes of 34 VKC patients never treated with topical cyclosporine (Cyc-NT) was matched with that of 58 VKC patients treated with cyclosporine (Cyc-T). The latter group was divided into three subgroups, depending on the duration of therapy: 1-6 months (group 1; 21 subjects) , 7-12 months (group 2; 19 subjects), greater than 12 months (group 3; 19 subjects). Cyc-NT patients eyelashes were significantly longer than those of VKC patients treated for 1-6 months (group 1). No significant difference was found between Cyc-NT and Cyc-T patients in group 2 and group 3. The differences between Cyc-T patients and group 1 and 2, group 2 and 3, and group 1 and 3 were not statistically significant. The eyelash shortening observed seems directly related to the rapid improvement of ocular symptoms induced by the treatment. A receptor down-regulation by mediators of ocular inflammation may explain this data, although different cytokines, hormones or other humoral mediators could be expressed on the ocular surface at different stages of the disease, mainly in periods of rapid change of the clinical course.

Diagnostic value of three different latex extracts.

The diagnosis of latex allergy is made on clinical history, but a confirmatory skin prick test (SPT) or a serological assay based on a commercial latex extract is always recommendable. Different raw materials can be used in the preparation of commercial latex extracts. Such extracts can consequently show both different qualitative profiles and a different diagnostic potential. Therefore, the selection of a proper latex extract is essential for in vitro and in vivo diagnosis of latex allergy. In the present study three different latex extracts, prepared from different raw materials (ammoniated -AL-, serum -SL-, or rubber particles -RPE- latex), are compared by in vitro techniques using sera from twenty patients with latex allergy. SDS-PAGE technique was used to compare the antigenic profile of the three latex extracts. Subsequently, their allergenic profiles were evaluated by immunoblotting technique using the individual sera from the twenty latex allergic patients. The diagnostic potential of the three latex extracts was also evaluated using direct Radio-Allergo-Sorbent Test (RAST) as well as skin prick tests (SPTs). In order to establish the more appropriate latex extract in a perspective of in vivo diagnosis of latex sensitization, the same latex extracts were subsequently compared by an in vivo SPT involving ten of the above subjects. The SDS-PAGE profiles of the three latex extracts examined were quite different. SL extract showed numerous bands comprised between 10-100 kDa. RPE extract was characterized by two intense bands at 14 and 20 kDa while AL extract showed the poorer antigenic composition. Analogously, immunoblotting analysis evidenced a different profile in relation to both different patients and extracts. For only two out of the twenty sera, direct RAST results showed a same positive class in relation to the different latex extracts used. SPT with SL extract showed, in respect to the other extracts (AL, RPE), a significantly higher wheal. This study showed that SL extract is able to express the best in vitro and in vivo diagnostic potential. Thus, its use should be preferred for the diagnosis of patients affected by latex allergy.

SEN virus co-infection among HCV-RNA-positive mothers, risk of transmission to the offspring and outcome of child infection during a 1-year follow-up.

SEN is a newly discovered blood-transmissible virus. Among its variants, SENV-D and -H are most often associated with non-A, -E hepatitis. Very little is known about the risk of vertical transmission of the virus. By using polymerase chain reaction with specific primers for SENV-D and -H, we investigated the prevalence of SENV-H and -D infection, the transmission rate of SENV infection and clinical features of SENV-infected children in 89 hepatitis C virus (HCV)-positive human immunodeficiency virus type 1-negative mothers. SENV infection was found in 36 (40%) mothers, and SENV-D was more frequent than SENV-H infection (34/36, 94%vs 5/36, 14%, P < 0.01). No difference in SENV infection rates was found between injection drug user (IDU) mothers (17/51, 33%) and mothers with no risk for bloodborne infection (19/38, 50%, P = ns). SENV-H infection was found only in IDU mothers and mothers with HCV genotype1b. Both SENV-D and -H can be transmitted to the offspring with an overall rate of 47%. Vertical transmission of HCV does not facilitate SENV infection of the offspring. Among 17 SENV-infected children, none was co-infected with HCV. Maternal HCV genotype or viral load does not interfere with mother-to-infant transmission of SENV. Persistence of SENV infection was demonstrated in 100% of infected children after 1-year follow-up, but none had clinical evidence of liver disease.

Systemic treatment of rhinosinusitis in children.

Systemic acute rhinosinusitis therapy consists mostly of antibiotic treatment because pathogens play a major role. Amoxicillin is the drug of choice for treatment of acute rhinosinusitis, with second- and third- generation cephalosporins, azythromycin, clarithromycin, and telithromycin as possible options, especially in the case of allergy to amoxicillin. If the clinical course suggests that an anaerobic pathogen is more likely, clindamycin or metronidazole can be considered in combination with a broad-spectrum drug. In antimicrobial treatment of chronic sinusitis there is no consensus on treatment length, organism coverage, or which antibiotics are most effective because the bacteriology is variable with polymicrobial anaerobic and aerobic organisms present. Adjuvant therapies need to be proven by additional studies. Chronic rhinosinusitis is heterogeneous and treatment should vary according to the causative factor involved. Short courses of systemic steroids have been found very useful to decrease mucosal swelling and inflammation in chronic rhinosinusitis. However, no randomized controlled studies have been performed to validate their efficacy in children. A variety of other agents are used in the treatment of chronic rhinosinusitis including antihistamines, decongestants, and leukotriene modifiers. To date, there is no good evidence from randomized controlled studies to support the use of any of these agents in the treatment of this disease in either children or adults.

High intracytoplasmatic levels of Il-4 and Il-5 in a patient with Gleichs syndrome: case report.

Gleichs syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleichs syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8- and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleichs syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleichs syndrome.

Biphasic anaphylactic reaction to Ketorolac tromethamine.

Ketorolac tromethamine is a recent injectable non-steroidal anti-inflammatory drug (NSAID) with analgesic properties approved for short-term pain management. In spite of its increasing use both in adults and children, relatively few allergic-like reactions have been reported. Reactions are often severe, and a death occurred following an intramuscular injection of ketorolac.

Cross-reactivity between IgE-binding proteins from Anisakis simplex and Dermatophagoides pteronyssinus.

An association was found between Anisakis simplex (As) and Dermatophagoides pteronyssinus (Dp) sensitization. One recent study shows a cross-reactivity between As and Dp and tropomyosin (tr)is suspected as being one of the proteins responsible of this cross-reaction. The aim of our study was: 1) to confirm the cross-reactivity between Dp and As; 2) to determine the importance of tr in this cross reaction. SDS-PAGE analysis of Dp and As (metabolic and somatic) extracts was carried out. Then an IgE immunoblotting test using serum from a patient who had specific IgE only to Dp and As and immunoblotting inhibition experiments using Dp extract and tr as inhibitors were performed. We found that patients serum reacted: 1) against larval As antigens with a molecular weight (mw) of 25 kilodalton (kD) and a mw > than 100 kD, 2) against various metabolic As antigens with a mw > than 100 kD, a mw ranging approximately from 35 to 50 kD, and a mw around 20 kD, and 3) against Dp proteins with mw between 35 and 55 kD. Preincubation of patient's serum with Dp extract caused the disappearance of reactivity against antigens with a mw > than 100 kD in both larval and metabolic As extracts and against proteins with mw ranging approximately from 35 to 50 kD in the metabolic As extract. Preincubation of patients serum with As extract caused the disappearance of reactivity against antigens with mw between 35 and 55 kD in the Dp extract. Pre-incubation of patients serum with tr did not induce any change in the immunoblotting profile. The results show that 1) cross-reactive components between Dp and As are some proteins with a mw ranging approximately from 35 to 50 kD and with a mw > than 100 kD, and 2) tr is not involved in cross-reactivity between As and Dp.

Scoring atopic dermatitis in infants and young children: distinctive features of the SCORAD index.

BACKGROUND: Atopic dermatitis (AD) affects infants, children, and adults with a wide degree of severity; several scoring systems have been used in trials and clinical practice. Infants and young children have a typical distribution of the lesions, but a correlation among skin surface involvement, intensity and subjective symptoms has not been reported in age groups. AIMS OF THE STUDY: To evaluate the clinical features of AD in infants and young children, by using the SCORAD index. A simplified scoring method for clinical practice is also discussed. METHODS: The SCORAD index was assessed in 63 infants and young children with AD [mean age (+/-SD) 17.5 +/- 11.15 months]; the single parameters of the index were evaluated, and compared with each other. Serum eosinophil cationic protein (s-ECP) and urinary eosinophil protein X (u-EPX) levels were determined and correlated with the SCORAD index. RESULTS: The presence of erythema, edema/papulation, and oozing/crust was significantly high in these patients. A strong positive correlation resulted among the three SCORAD index parameters (extent-intensity: P <0.001; extent-subjective symptoms: P <0.001; intensity-subjective symptoms: P <0.001). S-ECP and u-EPX levels positively correlated to almost every single parameter of the SCORAD index as well as to its total. CONCLUSIONS: Distinctive intensity items were found in infants and young children with AD. A strong correlation resulted among the extent, intensity, and subjective symptoms; each of the three parameters was positively correlated with the total SCORAD. Immunologic parameters positively correlated to each of the SCORAD index items, which remains the gold standard for assessing disease severity in clinical trials.

Atopy and serum eosinophil cationic protein in 110 white children with vernal keratoconjunctivitis: differences between tarsal and limbal forms.

BACKGROUND: A predominance of Th2 response has been suggested in vernal keratoconjunctivitis (VKC), and a high prevalence of IgE-sensitized (IgE-S) patients has been reported (positive skin prick test or serum-specific-IgE). Palpebral and bulbar VKC are considered to be expressions of the same disease and only occasional racial and histopathological differences are described between the two forms. Tear levels of eosinophil cationic proteins have been correlated with the severity of ocular symptoms; however, there is no published study that demonstrates the presence of serum markers of disease activity. OBJECTIVE: This study was performed to evaluate the prevalence of IgE-sensitization in palpebral, bulbar and mixed VKC and to determine possible useful markers of disease activity in peripheral circulation. METHODS: A total of 110 white VKC patients (mean age 8.3 years, range 3.2-18 years) were evaluated for ocular score in the active phase of the disease. Skin prick tests and serum-specific IgE for common allergens, serum-total IgE, peripheral blood eosinophil counts (PBECs) and serum eosinophil cationic protein (s-ECP) were determined. Fifteen age-matched non-IgE-S control children underwent the same determinations. RESULTS: s-ECP, PBECs and s-total IgE were significantly higher in IgE-S than in non-IgE-S VKC patients and in non-IgE-S VKC patients than in controls. A lower prevalence of IgE-S patients was found in bulbar vs. tarsal (P = 0. 050) or mixed forms (P = 0.002). The score of giant papillae was strongly correlated with s-ECP levels (P < 0.001) and with PBECs (P = 0.001). CONCLUSIONS: Our data suggest that an overall eosinophilic response is present in VKC independently of IgE-sensitization; bulbar forms, unlike tarsal and mixed forms, were associated with a low prevalence of IgE-sensitization. Serum ECP was a useful marker of disease activity in tarsal and mixed forms.

Assessment of residual immunoreactivity in red or white wines clarified with pea or lupin extracts.

Vegetable proteins could be a suitable alternative to animal proteins in the clarification of wine, but their residues could represent a risk for subjects with food allergy or intolerance. The aim of this study was to investigate the presence of specific immunoreactivity in red and white wines treated, as must or wine, with vegetable proteins in the clarification process. The proteins considered were prepared from lupins and peas, which are not included among the allergens listed in annex Illbis of Directive 2003/89/EC. The presence of residual immunoreactivity to specific rabbit anti-lupin and anti-pea polyclonal antibodies in treated wines was assessed by electrophoresis (SDS-PAGE) and immunoblotting. Residual protein was not detectable in red wines clarified with lupin, pea or a mixture of pea and lupin proteins or in white wines clarified with pea proteins. A small number of musts treated with lupin or pea proteins and white wines treated with lupin proteins yielded equivocal results, probably because of the presence of interfering material (e.g., sugar-rich proteins from grape and yeast). The use of bentonite as a secondary clarifying agent is therefore recommended since its combination with vegetable proteins is particularly effective in removing overall protein immunoreactivity.

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure.

To analyse the effect of highly active antiretroviral therapy (HAART) on T-lymphocyte functions we selected seven HIV-1 perinatally infected children (CDC immunological category 1 or 2) who had neither a fall in their plasma HIV-1 RNA levels nor a significant rise in CD4+ lymphocyte counts while receiving HAART. Clinical signs and symptoms were monitored monthly. Plasma viral load, CD4+, CD8+, CD19+ lymphocyte counts and in vitro T-lymphocyte proliferative responses to mitogens (anti-CD3, phytohaemoagglutinin, concanavalin A and pokeweed mitogen) and recall antigens (Candida albicans and tetanus toxoid) were tested at baseline and after 1, 3, 6 and 12 months of HAART. Twenty-two healthy age-matched children were studied as controls. A gain in body weight, no worsening of the disease and no recurrence of opportunistic infections were observed. At baseline, the majority of the children had low responses to mitogens, and all of them had a defective in vitro antigen-specific T-lymphocyte response (<2 standard deviations below the mean result for controls). During HAART, a significant increase in the response to mitogens and antigens was observed in all the patients. The T-lymphocyte response was restored more consistently against antigens to which the immune system is constantly exposed (Candida albicans, baseline versus 12 months: P < 0.001) compared with a low-exposure antigen (tetanus toxoid, baseline versus 12 months: P < 0.01). HAART restores in vitro T-lymphocyte responses even in the absence of a significant viral load decrease and despite any significant increase in CD4+ lymphocyte counts. It implies that a direct mechanism might be involved in the overall immune recovery under HAART.