Ekaterini Syrigou

Skin-prick test findings in atopic asthmatic children: A follow-up study from childhood to puberty

In a prospective cohort study we investigated the course of allergic sensitization from childhood to puberty in a group of children with atopic asthma. An attempt was made to correlate the findings with the persistence of asthma. A total of 150 children with atopic asthma established at 7 years of age were evaluated when 8–10 years of age. A battery of skin‐prick tests (SPTs) to common environmental allergens, a detailed clinical history for asthma severity classification, and spirometric analyses, were performed. In 127 of these children a re‐evaluation was performed at puberty. A variety of statistical methods were used to analyze the results regarding changes in skin test reactivity to individual aeroallergens and atopic index (degree of atopy), as well as to determine any correlation between these changes and the persistence of asthma in puberty. A wide spectrum of modification in skin reactivity to common environmental allergens was observed, including the complete loss of sensitization to some allergens or the development of a new one to others. Specifically, 34% of asthmatic children sensitive to Dermatophagoides pteronyssinus and 52.7% sensitive to cat lost their sensitivity in puberty, while only 7.5% and 11.1%, respectively, became sensitized (p = 0.03 and p = 0.001, respectively). In contrast, regarding pollen sensitivity, 30.2% and 24% of asthmatic children became sensitive in puberty to olive pollen and grasses mix, respectively, and only 11.7% and 12.5%, respectively, lost their sensitivity to these allergens (p = 0.04). No correlation was shown between the skin test reactivity changes to individual allergens and the persistence of asthma, but a significant correlation was found between atopic index to indoor allergens in childhood and the persistence of asthma at puberty (p = 0.04). Interestingly, multi‐sensitivity to allergens (≥ 4 allergens) in childhood was also found to correlate with the persistence of asthma at puberty [p = 0.05, odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.2–7.2]. Our findings indicate that significant modification of skin reactivity to common environmental allergens in atopic children with asthma in puberty can occur. However, no association between these changes and the persistence of asthma could be demonstrated, although children with indoor allergic sensitization and multi‐reactivity were found to have a higher probability of maintaining their asthma in puberty.

Hypersensitivity Reactions to Docetaxel: Retrospective Evaluation and Development of a Desensitization Protocol

Background: Docetaxel (DT) is an extensively used taxane, frequently associated with hypersensitivity reactions. The aim of this study was to record the epidemiological and clinical features of hypersensitivity to DT in non-small cell lung cancer patients in order to obtain useful information concerning the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. Methods: We retrospectively reviewed records of 620 non-small cell lung cancer patients treated with DT-containing regimens in the adjuvant, first-, second- or next-line setting. Data from 102 patients who had exhibited hypersensitivity reactions were analyzed according to the Common Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for the desensitization protocol. We applied the standard protocol for parenteral desensitization to β-lactam antibiotics, and DT treatment was carried out with a series of 10-fold dilutions in sufficient volume to administer the total dose. Results: One hundred and two patients (16.5%) were recorded as having hypersensitivity to DT. Reactions were observed after approximately 2.5 ± 1.0 cycles. Only 14 patients (14/620, 2%) developed grade 3–4 hypersensitivity. Reactions were more likely in patients during second- or third-line chemotherapy, but no other correlation (age, gender, atopic status) was observed. Five patients completed a parenteral desensitization protocol and continued their treatment uneventfully. Conclusions: Hypersensitivity reactions to DT respond quickly to discontinuation along with appropriate supportive care. Premedication and increased infusion time may allow readministration. The desensitization protocol that we developed provides a reliable alternative to permanent discontinuation of DT.

Allergy-test-driven elimination diet is useful in children with eosinophilic esophagitis, regardless of the severity of symptoms

A combination of PPIs and corticosteroids is the pharmacotherapy mostly used to treat eosinophilic esophagitis (EoE), while dietetic manipulations consist also an efficient option. The aim of this study was to compare the efficacy of allergy‐test‐driven elimination diet in children with mild symptoms of EoE to a group of children with moderate/severe symptoms.

Correlation of Lymphocyte Proliferating Cell Nuclear Antigen Expression with Dietary Cow’s Milk Antigen Load in Infants with Allergy to Cow’s Milk

Background: Controversial results have been reported on the participation and diagnostic value of lymphocyte reactivity in cow’s milk (CM) allergy. In this study, we used a specific nuclear marker to evaluate lymphocyte proliferation in IgE–mediated CM allergy in infants, and examine its relation with diets containing different CM antigen loads. Methods: Infants with IgE–mediated CM allergy, as assessed by open provocation and RAST, were grouped according to their exclusive diet, either CM formulae, breast feeding, or hydrolysed whey formulae. A group of non–atopic infants receiving CM was also examined. Lymphocyte proliferation to β–lactoglobulin was evaluated by quantitation of the proliferating cell nuclear antigen (PCNA) expression in peripheral blood mononuclear cells, by flow cytometry. Immunophenotypic surface markers were also examined. Results: A marked difference of PCNA expression between CM–fed allergic infants and healthy controls was observed (p<0.001). In this setting, PCNA expression ≥10% was highly specific and sensitive as a marker of CM allergy in CM–fed infants. Moreover, a significant correlation (p<0.001) between antigen load and PCNA was established in CM–allergic infants under different diets, higher values obtained with increasing antigen loads. In addition, within the group fed hydrolyzed formulae, low–molecular–weight products resulted in marginally lower PCNA expression than higher–molecular–weight formulae. No differences in immunophenotype were found, with the exception of a higher CD23 expression in the breast–fed group. Conclusions: PCNA could be a useful marker in the assessment of lymphocyte proliferation to CM antigens. Low CM antigen diets are related with reduced lymphocyte reactivity, which may partly explain the clinical benefit observed with such diets.

Interferon-gamma pretreatment of peripheral blood mononuclear cells partially restores defective cytokine production in children with atopic dermatitis.

Interferon‐gamma (IFN‐γ) is considered an important determinant of the balance between T‐helper type 1 and 2 cytokines and has been used experimentally for the treatment of atopic dermatitis. However, contrasting results have been reported relative to the Th‐UTh‐2 cytokine profile in atopic patients. In this study, we examined cytokine production by polyclonally activated peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis, and assessed the influence of in vitro IFN‐γ pretreatment on these cells. A fraction of PBMC isolated from children with severe atopic dermatitis, as well as from age‐matched controls, was initially exposed to IFN‐γ. After washing, both treated and untreated cells were then put into culture either alone or with the addition of phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) plus ionomycin. IL‐4, IL‐5, IL‐10 and IFN‐γ production were measured in the supernatants using commercially available ELISAs. PBMC from atopic patients produced more IL‐4 (P = 0.04) and IL‐10 (P = 0.03) and less IFN‐γ (P = 0.01) than controls, when stimulated with PHA. Interestingly, in PMA + ionomycin stimulated cultures, the atopic cytokine profile was different with more IL‐5 (P = 0.0068) and less IFN‐γ production (P = 0.00046) than the control group. When cells were pretreated with IFN‐γ, there were no significant differences between patients and controls. PBMC from children with atopic dermatitis show alterations in cytokine production, compatible in general terms with the Th‐l/ Th‐2 model. Exposure of PBMC to IFN‐γ before activation results in a reduction of these differences, so that cytokine production becomes similar in the atopic and normal groups.

Filaggrin and Periostin Expression Is Altered in Eosinophilic Esophagitis and Normalized With Treatment

Objectives: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls. Methods: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex- and age-matched healthy children were enrolled. Patients with EoE were treated with skin testing–driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE-related clinicopathological parameters. Results: Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P < 0.001). A statistically significant decrease of the proportion of cases with negative FLG and positive POSTN staining was observed from the first (pretreatment) to the second (post-treatment) biopsy in the subgroup of patients with EoE (P < 0.001 in both correlations). Conclusions: FLG and POSTN expression may be downregulated and upregulated, respectively, in the esophageal mucosa of patients with active EoE, and these changes may be restored with treatment in a significant percentage of cases.

Acute Generalized Exanthematous Pustulosis Induced by Amoxicillin/Clavulanic Acid Report of a Case Presenting With Generalized Lymphadenopathy

Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin reaction, most commonly triggered by antibiotics. Although its diagnosis is based primarily on the presence of specific clinical and histopathologic features, additional in vivo (patch testing) or in vitro testing may be required, especially in atypical cases, to more accurately determine the causative agent. The authors report a histologically confirmed case of acute generalized exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as documented by subsequent patch testing, and presented with generalized painful lymphadenopathy, mimicking an acute infectious process. This is a very rare and diagnostically challenging clinical presentation of acute generalized exanthematous pustulosis, which has been reported, to the best of our knowledge, only once previously.

Anaphylaxis during rapid oral desensitization to rifampicin

Rifampicin (also known as rifampin) is one of the most potent first-line antituberculosis drugs and an indispensable treatment option for isoniazid-resistant, rifampicin-sensitive tuberculosis (TB). Hypersensitivity reactions to rifampicin, mainly including fever, flu-like syndrome, rash, thrombocytopenia, acute renal failure, urticaria, and anaphylaxis, are considered rare but may occur among susceptible individuals and lead to premature discontinuation of the drug. Drug desensitization is a well-established procedure that may temporarily modify a patient’s immunologic response to the sensitizing agent, thus allowing for continuation of treatment. Desensitization to rifampicin has been previously described in rare case reports, almost invariably with successful results. We herein report a case of anaphylaxis during rapid oral desensitization to rifampicin in a male patient with active TB and a history of anaphylactic reactions to this agent. To the best of our knowledge, this is the first report in the English literature of a severe immediate-type reaction during desensitization to rifampicin. A 72-year-old man presented to the outpatient pulmonary clinic of “Sotiria” General Hospital, Athens, Greece, with fever, nonproductive cough, and weakness, lasting for 2 weeks. His medical history was significant for adult-onset diabetes mellitus and rheumatoid arthritis, treated with metformin and low-dose prednisone and intravenous infliximab, respectively. The patient was diagnosed with miliary TB and was started on anti-TB treatment with isoniazid (300 mg/day), rifampicin (600 mg/day), pyrazinamide (1500 mg/day), and ethambutol (1200 mg/day). Within 2 weeks after initiation of the above regimen, and 30 minutes after administration of the last dose of rifampicin, the patient developed fever and widespread urticaria; all drugs were subsequently discontinued and gradually reintroduced—after resolution of the cutaneous reaction—to identify the culprit drug. Urticaria, palmoplantar, and oropharyngeal pruritus were noted within 5 minutes after reintroduction of rifampicin and the drug was stopped; rifampicin was thereafter replaced with rifabutin. Ten days after initiation of rifabutin, the patient developed a maculopapular rash that affected the trunk and lower extremities. A skin biopsy was compatible with drug-induced eruption and rifabutin was discontinued. Approximately 3 years after his initial diagnosis of TB, the patient developed recurrent TB and was again started on a multidrug anti-TB regimen comprising isoniazid, rifabutin, pyrazinamide, and ethambutol. Twelve days after initiation of treatment a maculopapular rash appeared on the patient’s upper and lower extremities; rifabutin was again discontinued, followed by gradual resolution of the eruption, and the patient was referred to the Allergy Department of our hospital for further evaluation and management. At the time of the patient’s presentation to our department, skin prick test (SPT) and intradermal (ID) skin testing to rifampicin were performed, based on previous recommendations defining the highest nonirritant intradermal skin concentration of rifampicin (0.002 mg/mL). Histamine and saline were also used as positive and negative controls, respectively. SPT at a concentration of 2 mg/mL was negative, whereas a positive reaction (with a wheal of 15 17 mm and a flare of 42 44 mm) was shown on ID skin testing at a concentration of 0.002 mg/ mL. After obtaining the patient’s informed consent, oral desensitization to rifampicin was carried out in the intensive care unit. Premedication with antihistamines or steroids was not used (prednisone was discontinued for 3 days before the procedure) because these drugs may mask initial symptoms of anaphylaxis during desensitization, as previously emphasized, and the patient was not taking b-blockers or angiotensin-converting enzyme inhibitors. Increasing dosages of rifampicin were administered every 30 minutes, at a starting dose of 0.0002 mg followed by gradual dose escalation (Table I), as described in previously published desensitization protocols. Twenty minutes after administration of the 50 mg rifampicin dose, the patient started complaining of pruritus of the palms, soles, and groin followed by facial and trunk erythema, cough, generalized urticaria, hypotenstion, and sinus tachycardia followed by sinus bradycardia (without other ECG abnormalities). The desensitization procedure was discontinued, and the patient was treated with IV fluids, oxygen and nebulized salbutamol, intramuscular adrenaline, and intravenous methylprednisolone, dimetindene and ranitidine, with gradual recovery. Serum tryptase obtained at 1 hour after the onset of symptoms was 25 mg/L. Repeat serum tryptase, measured 1 week later, was found to be within normal limits (4 mg/L). Given the patient’s anaphylactic reaction during rapid desensitization, anti-IgE treatment and desensitization to rifampicin using slow dose increment over several days were recommended but the patient refused. Hypersensitivity reactions to anti-TB agents are relatively uncommon, encountered in approximately 4%-5% of the treated population, but may as well lead to withdrawal of the culprit drug and switching to an alternative agent. Rifampicin, in particular, is generally considered a well-tolerated drug with a low percentage of adverse events, especially when administered in usual therapeutic doses and outside the context of HIV infection. Delayed reactions, including a variety of cutaneous manifestations, are the commonest adverse reactions induced by rifampicin, whereas severe immediate reactions, such as anaphylaxis, are exceedingly rare.

Soy allergy complicating disease management in a child with coeliac disease

Keywords: food allergy; food intolerances; gluten-free diet; refractory coeliac disease

Treatment response to omalizumab in patients with refractory chronic spontaneous urticaria

Previous clinical trials have demonstrated the efficacy and safety of the anti‐IgE monoclonal antibody omalizumab in chronic spontaneous urticaria (CSU) not responding to antihistamine treatment. The primary aim of our study was to describe the response patterns of patients with refractory CSU treated with omalizumab in a real‐world clinical setting.