Annett Walker’s research while affiliated with Ludwig-Maximilians-Universität in Munich and other places

Sensitization to common ragweed (Ambrosia artemisiifolia) is associated with a variety of risk factors, which are incompletely defined. Our aim was to evaluate the association of a variety of clinical, geographical and demographical variables with ragweed sensitization and also to determine its frequency in southern Bavaria. In this cross-sectional multicentre study, we enrolled 977 patients with a documented or suspected atopic disease or food allergy. Data were collected on aeroallergen sensitization, age, sex, type and history of allergic disease, place of residence and potential local ragweed exposure. For this last variable, county ragweed cover was taken as a surrogate variable. Relative rates were calculated with multiple additive logistic regression models. Randomly selected patients with ragweed sensitization had a conjunctival provocation test. According to skin prick tests, 190 patients (19.5%) were sensitized to ragweed. The frequency of this finding increased significantly with a rising number of additional sensitizations. Other less important predictors for a ragweed sensitization were male gender, mugwort sensitization, food allergy and a maximum of complaints in September or October. County of residence, extent of local ragweed cover or type of residential area were without relevance. Of 48 sensitized patients, 26 (54.2%) had a positive conjunctival provocation test. Patients with multiple sensitizations may be more readily sensitized to a new aeroallergen. Local geographic or environmental conditions are presumably of minor importance for becoming sensitized to ragweed. The frequency of ragweed allergy among sensitized patients might be high.

Allergic reactions caused by stings of honey bees (Apis mellifera) or social wasps (particularly Vespula vulgaris, V. germanica) nearly always present as large local reactions (in up to 25 % of the population) or as systemic reactions with symptoms of immediate type allergy (anaphylaxis; in up to 3.5 % of the population). Systemic sting reactions are induced by IgE antibodies interacting with venom components. Other clinical presentations of allergic reactions („unusual sting reactions“) and toxic reactions after numerous stings are very rare. Particularly severe anaphylactic reactions may be fatal or result in disability. Acute reactions are managed by symptomatic treatment. Patients with allergic reactions profit from long-term treatment comprising education to avoid further stings, and from training to be prepared for self-management including the use of emergency medication in case of further stings. Adrenaline for self-administration is part of the emergency kit in those patients presenting with systemic immediate type reactions. Specific immunotherapy (SIT) is the main treatment option to prevent subsequent systemic reactions. Diagnostics in patients with systemic immediate type reactions are based on history, skin tests, and assessment of specific IgE antibodies to whole venom. Sometimes, these tests may not yield a venom sensitization which corresponds with the patient’s history. In such cases, it is recommended to determine concentrations of specific serum IgE antibodies to relevant single venom allergens (currently Api m 1 and Ves v 5 are available) and to perform cellular tests, if appropriate. The results of diagnostic procedures, however, are sensitive to a variety of interferences. Therefore, “false-negative” or “false-positive” reactions may occur in any system. Patients with an elevated serum concentration of baseline tryptase (95th percentile 11.4 µg/l) and/or with mastocytosis frequently suffer from very severe anaphylactic sting reactions. To recognize these risks, baseline serum tryptase concentration should be determined and the skin should be inspected for the presence of cutaneous mastocytosis. SIT with bee or wasp venom is mandatory for patients who have experienced sting reactions with respiratory or cardiovascular symptoms. For patients with mild systemic sting reactions limited to the skin and with individual risk factors, SIT is also urgently recommended. Beyond that, SIT is advisable to all adult patients with systemic immediate type sting reactions independently of the severity grade. Only for children with systemic immediate type reactions confined to the skin data are available showing that SIT is not mandatory. There are numerous protocols for dose increase during the initial phase of venom SIT: The maintenance dose may be reached within one day (ultrarush), after three to five days (rush) or within weeks or months (conventional SIT). The frequency of adverse effects is related to the speed of dose increase. The standard maintenance dose is 100 µg. Bee venom SIT is less effective than wasp venom SIT. Therefore, high-risk patients suffering from bee venom-allergy may receive an increased maintenance dose of 200 µg right from the start; this strategy may be also indicated in selected high-risk patients with wasp venom allergy. Systemic anaphylactic reactions and subjective complaints are the most important adverse effects of venom SIT, occurring particularly during the incremental phase. Mostly, these reactions are mild. Rarely, there are repeated anaphylactic reactions which substantially hamper treatment or even necessitate its termination. In such cases, co-treatment and/or pre-treatment with the anti-IgE antibody omalizumab appears to be the best option currently available to achieve tolerance of SIT; it has to be considered, however, that using omalizumab for this indication would be an off-label use. Also, these patients are treated with an increased maintenance dose (≥ 200 µg). There are no laboratory tests to determine the efficacy of SIT. A sting challenge test using a living insect should be performed about six to 18 months after the maintenance dose has been reached to identify treatment failure. If necessary, this interval may be shortened in high-risk patients. Sting challenge tests need to be performed with utmost caution providing emergency room conditions. If a patient continues to develop a systemic reaction despite SIT, administration of an increased maintenance dose nearly always provides protection (usually 200 µg are sufficient). In most patients, SIT can be stopped after three to five years, if SIT and a re-sting were tolerated without systemic reactions. If there is no tolerance or if a patient presents with individual risks, a decision has to be made as to whether SIT should be continued or not. This decision largely depends on the patient’s individual risk profile, and usually prolonged treatment is necessary. Life-long SIT is indicated for some patients, e. g. for those with mastocytosis or in case of a prior sting reaction requiring cardiopulmonary resuscitation.

Despite their frequent use, systemic corticosteroids have rarely elicited immediate-type reactions. We report two male patients, aged 26 and 70 years, respectively, with severe immediate-type hypersensitivity secondary to the administration of corticosteroids esterified with succinate. Skin tests, basophil activation tests and challenge tests were performed for diagnostic evaluation. In both patients, immediate-type skin test reactions were found to methylprednisolone sodium hemisuccinate (MSH) and prednisolone sodium hemisuccinate (PSH). In contrast, nonsuccinylated corticosteroids (including methylprednisolone and prednisolone in one patient) yielded no test reactions. Basophils from one patient exhibited a stimulated expression of the activation marker CD63 upon in vitro incubation with PSH or hydrocortisone sodium succinate, but not with hydrocortisone. Skin tests and basophil activation tests were negative in controls. One patient was challenged with the incriminated drugs. He developed flush, conjunctivitis, tachycardia and dyspnea 2 min after injection of MSH, and dyspnea shortly after intravenous administration of PSH. Oral and intravenous challenge tests with nonsuccinylated corticosteroids were tolerated well by both patients. These case reports should alert clinicians to rare, but severe immediate-type reactions to corticosteroids, related to the succinate moiety in our patients. In case of allergic reactions to corticosteroids, it is mandatory to identify the causative agent and find safe alternatives.