Randolf Brehler

Latex-fruit syndrome: frequency of cross-reacting IgE antibodies.

An association between allergies to latex proteins and to various foods has been reported and confirmed by RAST and immunoblotting inhibition. However, no significant data had been collected on the frequency of specific IgE antibodies to fruits in these patients and the frequency of a history of fruit intolerance. Serum samples of 136 patients with well‐documented, clinically relevant, immediate‐type hypersensitivity against latex proteins were analyzed for IgE antibodies against a panel of different fruits. Patient history of food intolerance was documented by a standardized questionnaire. Fruit‐specific IgE antibodies were detected in 69.1% of serum samples. Cross‐reacting IgE antibodies recognizing latex and fruit allergens (papaya, avocado, banana, chestnut, passion fruit, fig, melon, mango, kiwi, pineapple, peach, and tomato) were demonstrated by RAST‐inhibition tests. Of our patients, 42.6% reported allergic symptoms after ingestion of these fruits and a total of 112 intolerance reactions were recorded. However, fruit‐specific IgE antibodies were detected only in serum samples from 32.1% of the patients who perceived symptoms due to these fruits. Thus, serologic tests seem to be of low significance for prediction of food allergy in latex‐allergic patients.

Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi‐centre, randomized, dose–response study

Background:  The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi‐centre, randomized dose–response trial, double‐blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed.

Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study

Background:  Data supporting a carry‐over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double‐blind, placebo‐controlled study evaluated the efficacy, carry‐over effect and safety of grass pollen SLIT using co‐seasonal treatment.

Hev b 8, the Hevea brasiliensis latex profilin, is a cross-reactive allergen of latex, Plant foods and pollen

Background: Plant profilins are important pan-allergens. They are responsible for a significant percentage of pollen-related allergies. Limited information is available about their involvement in the latex-fruit syndrome and the cross-reactivities between latex and pollen. We aimed to clone and express the Hevea brasiliensis latex profilin to investigate its allergological significance and serological cross-reactivities to profilins from plant foods and pollens. Methods: A DNA complementary to messenger RNA (cDNA) coding for the Hevea latex profilin, Hev b 8, was amplified by polymerase chain reaction from latex RNA. Recombinant (r)Hev b 8 was produced in Escherichia coli and used to screen sera from 50 latex- allergic health care workers (HCWs) with well-documented histories of food and pollen allergy and 34 latex-allergic spina bifida (SB) patients. The cross-reactivity of natural Hev b 8 and rHev b 8 with other plant profilins was determined by ELISA inhibition assays. A three-dimensional homology model of Hev b 8 was constructed based on known profilin structures. Results: The cDNA of Hev b 8 encoded a protein of 131 amino acids with a predicted molecular mass of 14 kD. Twelve of the 50 HCWs and 2 of the 34 SB patients were sensitized to Hev b 8. All Hev b 8-sensitized patients showed allergic symptoms to pollen or plant foods. Cross-reactivities between profilins of latex, pollen and plant food were illustrated by their ability to inhibit IgE binding to rHev b 8. Homology modeling of Hev b 8 yielded a structure highly similar to Bet v 2, the birch pollen profilin, with the most distinct differences located at the N-terminus. Conclusions: We conclude that primary sensitization to latex profilin in the majority of cases takes place via pollen or food profilins. Additionally, pollinosis and food-allergic patients with profilin-specific IgE can be at risk of developing latex allergy.

Guideline for the diagnosis of drug hypersensitivity reactions

Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1–6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks–6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an „allergy passport“ in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.

Cross-reactivity between Ficus benjamina (weeping fig) and natural rubber latex

The importance of hypersensitivity to Ficiis allergens is reported, Cross‐sensitization between fig (Ficus carica), weeping fig (F. benjamina [Fb]), and natural rubber latex (NRL) was confirmed by RAST inhibition. We performed skin prick tests with fresh Fb tree sap and NRL extracts in 346 consecutive patients and in 151 patients with immediate‐type hypersensitivity to NRL, Total serum IgE and IgE antibodies to NRL and Ficus spp. were analyzed in sera. By the RAST‐inhibition method, we studied cross‐reactivity among latex, fig. and weeping fig, Sensitization to Fb was diagnosed in 23 of the 346 consecutive patients, and the simultaneous presence of latex‐specific IgE was highly significant. Of 151 NRL‐allergic patients, 35 were also sensitized to Fb. Cross‐reacting IgE antibodies recognizing latex and Ficus allergens were demonstrated by RAST inhibition. The present study reinforces the importance of Fb as an indoor allergen. Cross‐reacting IgE antibodies to NRL and Ficus spp, allergens frequently found in the sera of atopic patients. Development of commercially available standardized extracts for skin tests is urgently necessary.

Specific Immunotherapy—Indications and Mode of Action

BACKGROUND It is estimated that up to 24% of the population in Germany suffers from allergic rhinoconjunctivitis and 5% from allergic asthma. Allergic rhinoconjunctivitis is closely related to other atopic diseases. METHODS This review is based on pertinent publications retrieved by a selective search of the Medline database, guidelines from Germany and abroad, and Cochrane meta-analyses. RESULTS Specific immunotherapy (SIT) is the only diseases-modifying treatment option for allergies. Meta-analysis reveals standardized mean differences in allergic rhinitis symptom scores of -0.73 for subcutaneous immunotherapy (SCIT) and -0.49 for sublingual immunotherapy (SLIT); the corresponding mean differences in medication scores are -0.57 and -0.32, respectively. The treatment should be carried out for at least three years. It is indicated when the symptoms are severe and allergen avoidance is not a realistic option. The efficacy of treatment depends on the allergen dose; thus, every allergen preparation should be evaluated individually, independent of route of administration. SCIT can cause systemic adverse effects, including anaphylaxis. SLIT is safer but often causes allergic symptoms of the oral mucosa at the beginning of treatment. CONCLUSION Even though the efficacy of SIT is well documented, it is still underused. SIT should be offered as standard treatment to patients suffering from allergic rhinitis.

Neutrophilic hidradenitis induced by chemotherapy involves eccrine and apocrine glands

Neutrophilic eccrine hidradenitis is a self-limited inflammatory dermatosis primarily induced by chemotherapeutic agents. We report the case of a 43-year-old patient treated with cytarabine, daunorubicin, and thioguanine for acute myelogenous leukemia who developed painful, red nodules in both axillae on the third day of chemotherapy. The lesions healed spontaneously without sequelae and reappeared once when chemotherapy was readministered. Histologic examination and immunohistochemical staining for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and S100 revealed necrosis of eccrine and apocrine glands. As a secondary event, neutrophils, histiocytes, and lymphocytes of T and B cell types were infiltrating the glandular coils. Electron microscopic examination confirmed the presence of severe cellular degeneration of the secretory epithelia and coiled sweat ducts. Ultrastructural features and absence of labeling with a nick-end labeling technique were consistent with a non-apoptotic mode of cell death. Our findings strongly suggest a cytotoxic effect of chemotherapeutic agents as accumulated in the secretory epithelia of sweat glands. Distal ducts and myoepithelial cells remained intact and may account for rapid regeneration of the glandular structures after discontinuation of chemotherapy. In view of the involvement of both eccrine and apocrine glands, we suggest the term neutrophilic hidradenitis, which is part of the spectrum of drug-associated sweat gland reactions.

IgE-mediated hypersensitivity to latex in childhood

A total of 267 children scheduled to receive anesthesia during a surgical, neurosurgical, or orthopedic intervention were investigated. IgE antibodies against latex were detected in serum samples of 6.4% (17/267 children) of the patients. The most important difference between sensitized and nonsensitized children was the number of surgical interventions in the past. The median of surgical interventions was 1.0 in the nonsensitized group of children and 3.0 in the sensitized group. Only 0.9% of the children with up to two surgical interventions and 34.1% with three or more procedures were sensitized to latex. Only one of the sensitized children developed intraoperative anaphylaxis during intervention after our investigation. We conclude that children with a history of three or more surgical interventions have a high risk of sensitization to latex proteins. Nevertheless, the predictive value of IgE antibodies against latex for development of anaphylaxis during anesthesia seems to be low.

Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated with a reduction of FcεRI-positive cells in the skin

Background. Treatment with omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of omalizumab in CSU has not been elucidated in detail. Objectives. To determine the effects of omalizumab on levels of high affinity IgE receptor-positive (FcεRI+) and IgE-positive (IgE+) dermal cells and blood basophils. Treatment efficacy and safety were also assessed. Study design. In a double-blind study, CSU patients aged 18‑75 years were randomized to receive 300 mg omalizumab (n=20) or placebo (n=10) subcutaneously every 4 weeks for 12 weeks. Changes in disease activity were assessed by use of the weekly Urticaria Activity Score (UAS7). Circulating IgE levels, basophil numbers and levels of expression of FcεRI+ and IgE+ cells in the skin and in blood basophils were determined. Results. Patients receiving omalizumab showed a significantly greater decrease in UAS7 compared with patients receiving placebo. At Week 12 the mean difference in UAS7 between treatment groups was -14.82 (p=0.0027), consistent with previous studies. Total IgE levels in serum were increased after omalizumab treatment and remained elevated up to Week 12. Free IgE levels decreased after omalizumab treatment. Mean levels of FcεRI+ skin cells in patients treated with omalizumab 300 mg were decreased at Week 12 compared with baseline in the dermis of both non-lesional and lesional skin, reaching levels comparable with those seen in healthy volunteers (HVs). There were no statistically significant changes in mean FcɛRI+ cell levels in the placebo group. Similar results were seen for changes in IgE+ cells, although the changes were not statistically significant. The level of peripheral blood basophils increased immediately after treatment start and returned to Baseline values after the follow-up period. The levels of FcεRI and IgE expression on peripheral blood basophils were rapidly reduced by omalizumab treatment up to Week 12. Conclusions. Treatment with omalizumab resulted in rapid clinical benefits in patients with CSU. Treatment with omalizumab was associated with reduction in FcɛRI+ and IgE+ basophils and intradermal cells.