Skin prick test results to artesunate in children sensitized to Artemisia vulgaris L.

Artemisia vulgaris L and Artemisia annua L (Chinese: qinghao) are similar plants of the Asterbaceae family. Artesunate, a semi-synthetic derivate of artemisin which is the active principle extract of the plant qinghao, has antimalarial properties. Some cases of severe allergic reactions to artesunate have been described. The purpose of this study was to evaluate the association between positive skin tests to Artemisia vulgaris L allergen and a preparation of injectable artesunate. A total of 531 children were skin prick tested with inhalants (including Artemisia vulgaris L), foods, and artesunate. Among the 59 patients positive to Artemisia vulgaris L only one child was also positive to artesunate. No child was positive to artesunate in those negative to Artemisia vulgaris L. We conclude that Artemisia vulgaris L sensitization is not associated with sensitization to artesunate; consequently, skin test to artesunate should not be carried out before using the drug considering the rare allergic reactions.

Azithromycin is more allergenic than clarithromycin in children with suspected hypersensitivity reaction to macrolides.

BACKGROUND: Macrolides are considered safe antibiotics with reduced allergenic activity. However, studies on the safety of macrolides are scarce, particularly in children. OBJECTIVE: The aim of this study was to assess the frequency of hypersensitivity reactions to clarithromycin and azithromycin in a group of children referred to our allergy unit for suspected macrolide allergy. METHODS: We retrospectively reviewed the charts of 90 children aged 1-17 years with symptoms suggestive of hypersensitivity reaction to clarithromycin or azithromycin between December 31, 2008 and December 31, 2013. The allergy workup included skin tests (ie, skin prick tests and/or intradermal tests), determination of serum specific IgE (sIgE) to clarithromycin and azithromycin, and, if necessary to reach a diagnosis, oral provocation tests. RESULTS: Seventy-seven children completed the allergy workup. A reaction to clarithromycin was recorded in 58 children (75.3%): 21 (36.2%) had a history of immediate reactions, and 37 (63.8%) had a history of nonimmediate reactions. A reaction to azithromycin was recorded in 19 children (24.6%): 6 (31.5%) had a history of immediate reaction, and 13 (68.42%) had a history of nonimmediate reaction. Positive results in skin tests and oral provocation tests with the suspect drug confirmed the diagnosis in 15.5% of reactions to clarithromycin (9 of 58) and in 47.3% of reactions to azithromycin (9 of 19) (P = .004). CONCLUSION: A complete allergy workup enabled us to confirm a diagnosis of clarithromycin and azithromycin allergy in 15.5% and 47.3% of cases, respectively. Azithromycin was more allergenic than clarithromycin in children.

Azithromycin anaphylaxis in children.

Allergic reactions associated to the use of macrolides are uncommon; in particular only two cases of anaphylaxis with erithromycin and clarithromycin have been reported to date. The aim of this study was to investigate macrolide-induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive children were referred to the Allergy Unit of A. Meyer Children's Hospital because of a past history of reactions to macrolides. Allergy work-ups were carried out according to the European Network for Drug Allergy protocol. Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients completed the allergologic work-up and among them we investigated three cases of anaphylaxis due to azithromycin which included one child with anaphylaxis to both clarithromycin and azithromycin. In two of the children with anaphylaxis, the diagnosis was only confirmed with the skin prick test, the third was positive to the Intradermal Test. The azithromycin allergy shows a surprisingly high sensitivity to the in-vivo tests. Moreover, this study shows that cross-reactivity may occur between different macrolidic molecules; it has even been suggested that macrolide allergies are unlikely to be class allergies.

Upper airways disease: role of corticosteroids.

Nasal topical steroids (INCSs) are well established effective therapy in allergic rhinitis both in children and adults. There is clear benefit in using INCSs over antihistamines in allergic rhinitis while short courses of oral corticosteroids (CSs) may be indicated in severe cases. The addition of INCSs to oral antibiotics has been proven to be more effective than antibiotics alone for achieving symptomatic improvement in patients with acute rhino sinusitis. INCSs as monotherapy are also effective in the treatment of allergic rhinosinusitis (ARS). Several randomized controlled trials have evaluated the role of INCSs in chronic RS with the majority demonstrating a beneficial effect. In adults, the clinical efficacy of oral corticosteroids in the management of chronic RS with nasal polyposis is well established. There are no randomized controlled trials evaluating the efficacy of systemic CSs in chronic RS without nasal polyposis.

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.

Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.

Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.

Fatty acid chain-shortening activity in the pulmonary type II cell.

Type II cells obtained from fetal rabbit lung tissue in culture were incubated with [14C]palmitic and [14C]stearic acids labeled at either the carboxyl or the terminal methyl groups. Significant chain shortening of [18-14C]stearic acid to radiolabeled palmitic acid was observed, with little chain shortening of palmitic acid to myristic acid. Incorporation of 14C into palmitic acid by beta-oxidation followed by de novo fatty acid biosynthesis was not detectable under the same experimental conditions. The palmitic acid supplied by chain shortening was preferentially incorporated into phosphatidylcholine instead of other lipids. Fatty acid chain-shortening activity in the type II cell appears to be capable of increasing the amount and relative proportion of palmitic acid available for phosphatidylcholine biosynthesis.

VIP restores natural killer cell activity depressed by hepatitis B surface antigen.

Vasoactive intestinal peptide (VIP) has recently been shown to bind to human lymphocytes and modulate immune functions. The ability of VIP in restoring natural killer (NK) cell activity depressed by hepatitis B surface antigen (HBsAg) has been investigated in the present research. Human lymphocytes were incubated with HBsAg and, after washing, a 4-hr cytotoxicity assay was performed. VIP was coincubated with lymphocytes during the preincubation with HBsAg or, alternatively, throughout the cytotoxicity assay. The study revealed that VIP, either preincubated or coincubated in the 4-hr assay, strongly restores NK cell activity depressed by viral antigen. This is noteworthy considering that a number of lymphocyte modulators such as interferons fail in restoring viral-dependent NK cell activity depression. In contrast with previous reports, even when coincubated in the 4-hr assay, VIP is a strong activator of NK cell activity. Further studies will be required to understand which mechanisms are involved in the interrelation between VIP and NK cells during viral infections.

Inhibition of natural killer cell cytotoxicity and interferon gamma production by the envelope protein of HIV and prevention by vasoactive intestinal peptide.

Natural killer (NK) cell dysfunction is common in human immunodeficiency virus (HIV)-infected subjects, although its mechanisms are poorly understood. A direct effect of HIV envelope glycoprotein gp120 may be involved. We investigated the in vitro effects of gp120 on the major NK cell effector functions, natural cytotoxicity and cytokine production. In addition, the ability of the vasoactive intestinal peptide (VIP) to modulate these effects was investigated. Our results indicated that gp120 inhibits NK natural cytotoxicity and showed, for the first time, that the inhibition affects also the production of the proinflammatory cytokine interferon-gamma (IFN-gamma). Interestingly, the inhibitory effect on NK cell functions was obtained with gp120 at concentrations within the range measured in the serum of HIV-infected subjects. Furthermore, we showed that the inhibitory activity of gp120 can be prevented by coincubation with VIP, even if VIP has no stimulatory activity by itself. Taken together these data suggest that (1) an inhibitory effect of gp120 may account for the NK cell dysfunction in HIV-infected subjects; (2) the gp120-mediated decrease in IFN-gamma production by NK cells may contribute to the cytokine imbalance observed in HIV infection; and (3) VIP counteracts the inhibitory effect of gp120 on NK cell functions.

T lymphocytes in children with recurrent respiratory infections: effect of the use of thymostimulin on the alterations of T-cell subsets.

OKT3-, OKT4- and OKT8-positive cells were estimated in 303 children with recurrent respiratory infections. The patients (selected by a score method) had experienced 13 or more infections a year. Modifications in T-cell subsets were observed in 154 patients (50.8%). Decreased OKT3- and OKT4-positive cells were present in 80 children (26.4%), while 74 patients (24.4%) showed normal values of OKT3-positive cells but decreased OKT4- and increased OKT8-positive cells. An attempt at treatment with thymostimulin was undertaken in a group of randomly chosen children with modifications in T-cell subsets. The use of thymostimulin induced the treated children more readily than the untreated ones to show improvement in both the score for respiratory infections and the distribution of T-cell subsets.

[Hepatitis B virus: new markers and their immunology]. / Il virus dell'epatite B: i nuovi markers e la loro immunologia.

Hepatitis B virus (HBV) is one of the most important causes of chronic liver disease. HBV is a DNA virus with an external glycoprotein surface and an internal nucleocapsid which contains the viral genome. HBV infection is revealed by the appearance of specific markers. Some of these markers are well known and their presence in serum is important to understand the behaviour of the disease. Among them HBsAg, HBeAg, anti-HBs and anti-HBe are found in serum, so as anti-Core; the HBcAg may be found in hepatic tissue and marks infectivity and virus replication. In the few last years some new antigens and antibodies have been studied and their importance in diagnosis and follow-up of hepatitis has been recognized. HBxAg, Pre-S and DNA-Polymerase (Pol) seem to be specific and early signals of viral replication. More studies showed the trans-activating properties of HBxAg; actually the X protein seems to be involved in replicative cycle of HBV. Many Authors also demonstrated a relationship between the presence of X in serum and/or liver and the progression of disease to cirrhosis and hepatocellular carcinoma. The Pol antigen and its antibody seem to be very common markers of HBV infection in serum of patients with hepatitis. Moreover their presence is the only signal of viral infection in some patients which have no other marker of HBV. More studies are of course needed to exactly establish the significance of these new markers and their importance for diagnosis and prognosis of HBV infection.

[IgG subclasses against bovine alpha-lactalbumin and beta-lactoglobulin in infants fed with a seroprotein hydrolysate]. / Sottoclassi IgG anti-alfa-lattoalbumina e anti-beta-lattoglobulina bovina in lattanti alimentati con un idrolisato di sieroproteine.

Prevention of food allergy in infancy has been the aim of important researches in the last years but many studies have produced conflicting conclusions. The use of hydrolysate formulas seems to be an helpful tool in prevention of cow milk protein allergy but confusion often remains about capability of small hydrolysate molecules to be "allergens" or "antigens". In order to clarify this point IgE, IgG and IgM as well as IgG subclasses against alfa-lactoalbumin (ALA) and beta-lactoglobulin (BLG) have been evaluated in 41 infants at risk for allergy and in 30 controls at the fourth month. The same evaluation has been done on their mothers. The 41 "at risk" children were fed with breast milk or with an hypoallergenic formula (Nidina HA, Nestlè) or both. The control children received an adapted formula. No difference between the two groups of children was found regarding IgM or IgG against ALA while antibodies against BLG were more frequently found in controls than in "at risk" children. Only one child in the group fed with Nidina HA developed specific IgE against whole milk. Therefore hydrolysate formula seems to be as antigenic (not allergenic) as adapted formula in respect of ALA while BLG contained in adapted formula seems to be a stronger immunogen. The pattern of specific IgG subclasses against ALA and BLG is different between the two groups of children because of the absence in "at risk" group of specific IgG2 and IgG3. As for the mothers, the presence in their sera of IgG against ALA or BLG seems to induce in infants a reduced response to the same antigen.

[Subclasses of IgG: biological aspects and functional behavior in response to vaccination]. / Le sottoclassi delle IgG: aspetti biologici e comportamento funzionale in risposta alle vaccinazioni.

The IgG subclasses are known to have different structure and functions. The IgG1 and IgG3 bind to monocyte and neutrophils and activate the complement more easily then IgG2 and IgG4. The levels of IgG subclasses found in newborns are mainly determined by the transplacental passage since the synthesis, in the first time of life, is very low. The levels found in adults are reached only during the adolescence. The immune response to a protein antigen is mainly in the IgG1 subclass, on the contrary the response to polysaccharide antigens is mainly IgG2. For that reason children, who produce very few IgG2 till they are 2 years old, cannot be vaccinated with carbohydrate vaccines unless a protein conjugate vaccine is used. In addition, the route of subministration, the dose of antigen, the age of vaccinated people and genetic factors can modify the subclass pattern obtained in response to vaccinations. For these reasons, probably, the immune response studied after a vaccination or in individuals who recovered from a natural disease is not always the same. Since the role of the different subclasses is not yet completely clarified, the interpretation of the importance of a selective "choice" of a subclass instead of another after vaccination is still difficult.

[A case of Behçet's disease in a child: clinical, genetic, and immunologic characteristics]. / Un caso di malattia di Behçet in età pediatrica: rilievi clinici, genetici ed immunologici.

Behçet's disease, which is rarely observed in infancy, is a systemic inflammatory disease of unknown etiology, whose clinical feature consist in the triad of mouth ulcers, genital ulcers and iritis. A 14 years old girl has been studied in whom classical findings of Behøcet's disease were associated with neurological symptoms miming a neuro-Behøcet's syndrome, but which were caused by previous abuse in corticosteroid therapy. Interestingly some features (arthritis, gastrointestinal manifestations), which can be connected with Behøcet's disease, resulted to be present since the very first years of life. Partial features of the disease (arthritis or mouth ulcers) were present in three members of the patient's family on the father's side. Extensive immunological studies have been carried out. T and B lymphocyte number and function were normal. T-cell subsets (defined by monoclonal antibodies) and natural killer activity (both never examined in patients with Behøcet's disease) resulted to be within normal range. Secretory Component, which has been claimed to be absent in these patients, was normally present in saliva. A defect in neutrophil chemotaxis has been found which promptly improved by levamisole therapy. Authors discuss clinical, genetic and immunological findings of the patient, on the basis of a review of literature.

[Active and passive immunoprevention of hepatitis B in newborn infants with HBsAg-positive mothers]. / L'immunoprofilassi attiva e passiva dell'epatite da virus B nel neonato da madre HBsAg-positiva.

Infants born to HBsAg-positive mothers are at high risk of contracting perinatal hepatitis B infection. The prevention is based on active as well as passive immunoprophylaxis. We have used hepatitis vaccine in 18 newborns of as many HBsAg-positive mothers. Some haematologic and immunologic parameters are here reported. No alterations were observed as to liver function. Immunoglobulin values were normal for age. Auto-antibodies and rheumatoid factor were constantly absent. Immunecomplexes were present in the serum of some infants. The study of T cell subsets and of natural killer cells activity did not reveal any important changes, whereas minor modifications were present in polymorphonuclear leucocyte function. In all infants submitted to vaccination serum conversion was observed a with different antibody levels.

[Reduced natural killer function in children with recurrent respiratory tract infections]. / Ridotta funzionalità natural killer in bambini con infezioni respiratorie ricorrenti.

Respiratory infections are the major cause of disease in childhood in the industrialized areas of the world. This essentially depends on two factors: immunological immaturity and immunological naivety. In most cases a virus has been considered the causative agent in respiratory infection. A defect in immune responses has been described in children with recurrent respiratory infections and in particular a decrease in CD4/CD8 T lymphocyte ratio or in IL-2 and IFN-gamma production. Our results show that Natural Killer (NK) cell activity is defective in children with recurrent respiratory infections. That is particularly noteworthy since NK cells play an important role in host defense against viral infections. At present it is difficult to understand whether the NK defect is a primary defect or it is secondary to viral infections. Further studies will help to clarify whether NK decreased activity depends on a cell damage directly caused by virus or it depends on the decreased levels of cytokines.

[Changed levels of substance P and somatostatin in HIV-positive children]. / Alterati livelli di sostanza P e somatostatina nei bambini HIV positivi.

Substance P (sP) and Somatostatin (SOM), so as other neuropeptides can modulate neurologic and immunologic functions. sP has been described to enhance both in vitro and in vivo immunoglobulin synthesis. On the contrary, SOM has an inhibitory effect on the same activity. The modulating effect is more evident on IgA isotype. Hypergammaglobulinemia and in particular high levels of IgA is a common finding in pediatric AIDS and an imbalance among regulatory effects of neuropeptides might be suggested. In order to evaluate the plasma levels of sP in pediatric AIDS we studied 15 children with HIV infection (status P2), 10 seronegative children born to HIV positive mothers and 10 healthy children of the same age. All the HIV positive children had high plasma levels of IgG and IgA. The plasma level of sP was extremely higher in HIV positive children while no significant difference was found between seronegative children born to HIV positive mothers and healthy children. SOM was decreased in HIV positive children when compared to control groups but a significant difference was not reached. It might be supposed that HIV infection, through a dysregulation among neuropeptides interferes on immune functions and in particular on IgA synthesis. On the other hand it might be suggested that the imbalance between sP and SOM depends on the viral infection of immune cells since it has been demonstrated that SOM and other neuropeptide are synthesized by lymphoid tissue. Further studied relevance of neuropeptide disorders in pediatric AIDS.

[Specific IgA against multiple antigens as expression of immunologic deregulation in HIV-positive children]. / IgA specifiche contro antigeni multipli come espressione della disregolazione immunologica nel bambino HIV-positivo.

B-cell dysfunction in HIV-infected children is reflected by hypergammaglobulinemia and high levels of serum IgA. Little is known about antibody specificity since only a small portion of serum IgA appears to be directed against HIV proteins. In the present study the specificity of IgA antibodies against food, inhalant, bacterial and fungi antigens were evaluated in a population of HIV infected children. ELISA method was used for antibody testing. Our results show that in 84.6% of patients IgA against at least one food antigen are present. IgA against inhalant allergens were present in most of HIV-infected children but in none of controls. As for anti-tetanus toxoid antigens and anti-fungi antigens, though present in higher percentage in patients, specific IgA were found also in healthy children. If a gastrointestinal dysfunction might be supposed as the cause of presence of anti-food antigen IgA, it is difficult to consider this factor as the cause of presence of specific IgA directed against different antigens. It is possible to postulate that an immunologic dysregulation based on an imbalance between Th1 and Th2 cells or on higher levels of IL-5 and/or IL-6 may lead to a misfunction of B cell and consequently to hypergammaglobulinemia with high IgA levels.

[Pseudoallergies]. / Le pseudoallergie.

Pseudo-allergic-reactions (PAR) are clinical manifestations including urticaria, angioedema, conjunctivitis, rhinitis, asthma, and anaphylaxis. The prevalence of PAR ranges from 0.1% to 75% according to various studies. The pathogenetic mechanism of these diseases is not immunologically mediated. Food, additives, and drugs are the main responsibilities for PAR. The diagnosis of PAR is characterized by the absence of specific IgE for the suspected products. The absence of immunological mechanisms is confirmed by in vitro and in vivo tests. The treatment of PAR is similar to that of allergic diseases (antihistamine drugs, steroids, B2 agonists, epinephrine).