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Histamine intolerance (HIT) is characterized by an imbalance between histamine intake and the capacity for histamine degradation. The main enzyme for metabolizing ingested histamine is diamine oxidase (DAO). Determining DAO activity in serum may be useful in diagnosing HIT.Over a period of 3.5 years we recruited 316 subjects with clinically suspected HIT and 55 healthy controls. Serum DAO activity was measured with a quantitative enzyme immunoassay. Twenty patients with highly reduced DAO activity went on a histamine-free diet for 6-12 months. Afterwards, their DAO activity was determined again.We found that DAO activity was significantly lower in patients than in healthy control subjects (P 0.0001). Furthermore, 54 patients had highly reduced serum DAO activity ( 40 HDU/ml). Their main symptoms involved the skin, gastrointestinal tract, respiratory system, and eyes. In all the 20 patients with highly reduced DAO activity, the main clinical symptoms typical of histamine intolerance disappeared after they adopted a histamine-free diet. Furthermore, the serum DAO activity values measured increased significantly (P 0.0001).Our results suggest that determining DAO activity in serum is a useful tool in diagnosing HIT. Furthermore, our results showed the benefit of a histamine-free diet because after the diet the majority of symptoms disappeared and the serum DAO activity significantly increased.

BACKGROUND: Although immunotherapy is effective in allergic rhinitis, conjunctivitis, asthma and stinging insect hypersensitivity, it carries a risk of anaphylactic reactions. METHODS: In a 4-year retrospective survey, we investigated 1257 adult patients who had received venom or inhaled-allergen subcutaneous immunotherapy. The dose-increase phase was performed as the 2-day rush protocol for venom immunotherapy and the 6-week protocol for inhaled-allergen immunotherapy. RESULTS: A total of 904 patients received venom immunotherapy and 353 patients inhaled-allergen immunotherapy. The prevalence of systemic reactions was 13.6%. The frequency of systemic reactions was higher during the maintenance phase than in the dose-increase phase (9.6% vs. 5.9%) and was highest in both phases of treatment with honeybee venom (P < 0.001). The majority of systemic reactions were mild. Five (0.4%) patients had reaction with a fall of blood pressure and were treated with adrenaline. There was no fatal outcome. The systemic side-effects during the dose-increase phase of venom immunotherapy occurred at a median dose of 46 μg (range 2–100 μg). Large local reactions occurred in 13.9% of patients without any significant difference between the allergens. CONCLUSIONS: We have shown that systemic reactions are not rare even during maintenance phase in patients with a well tolerated dose-increase phase of treatment. The most prominent risk factor for systemic reactions was immunotherapy with honeybee extract.

BACKGROUND: Among patients with allergy to insect stings, double positivity in tests for IgE antibodies specific to honey bee and wasp venoms is a frequent diagnostic problem. True double sensitization and possible cross-reactivity of venom hyaluronidases and with carbohydrate determinants must be considered in such patients. We studied the frequency of sensitization to carbohydrate determinants and the role of these in double positivity in tests for specific IgE antibodies. MATERIALS AND METHODS: A group of 66 patients (41 men, 25 women; 16–66 years) with double positivity for wasp and bee venoms were tested in the FEIA inhibition test in order to distinguish true double sensitization from cross-reactivity. Patients were tested for the presence of IgE antibodies specific to oilseed rape (OSR) pollen and MUXF3 allergens, both of which are rich in cross-reacting carbohydrate epitopes. RESULTS: Inhibition tests revealed true double sensitization in 37 patients (56.1%) and cross-reactivity in 29. Among those showing cross-reactivity, five were sensitized to honey bee venom and 24 to wasp venom. The median value of IgE specific for OSR pollen in patients sensitized to honey bee venom was 4.350 IU/ml, in patients sensitized to wasp venom 0.61 IU/ml, and in patients with double sensitization 0.25 IU/ml (P = 0.028, Kruskal–Wallis test). Findings for IgE specific for MUXF3 were similar. Discordance between OSR pollen positivity and MUXF3 positivity was found in 11.1% of the patients. CONCLUSION: The values of IgE specific for OSR pollen and MUXF3 in patients with primary sensitization to either honey bee venom or wasp venom were significantly higher than in patients with double sensitization. These results confirm that IgE antibodies against carbohydrates epitopes are a frequent cause of double positivity in tests for anti-venom IgE antibodies.

Background: Systemic side-effects of venom immunotherapy (VIT) represent a considerable problem in the treatment of patients allergic to Hymenoptera venom. We examined the hypothesis whether basophil responsiveness might be connected with the adverse reactions to VIT. Methods: Basophil surface expression of activation marker CD63 induced by different concentrations of honeybee and wasp venom (0.1 and 1 μg/ml) was measured by flow cytometry in 34 patients with history of systemic anaphylactic reactions to Hymenoptera sting just before rush honeybee or wasp VIT. Results: Eleven of 34 patients had systemic anaphylactic reaction (Mueller grades I–III) and one patient a large local reaction to VIT. In those 12 patients, median percentage of activated basophils after stimulation with VIT-specific venom in concentration of 0.1 μg/ml was 99% (range: 17–195) of value reached with stimulation with 1 μg/ml. Side-effects occurred in all patients with 0.1/1 ratios over 92% (eight of 12). In contrast, in 22 patients with no side-effects, the median 0.1/1 ratio was 25% (range: 2–92). These concentration-dependent activation ratios were significantly different between the groups with and without side reactions (P

Background: Invasive pulmonary aspergillosis usually occurs in immunocompromised patients. Mild abnormality of host defence is usually present in the chronic necrotising form of the disease. Acute aspergillus pneumonia usually affects patients who are seriously immunocompromised. Objectives: The purpose of the study was to highlight the possibility of occurrence of invasive pulmonary aspergillosis also in patients with mild abnormality of host defence. Methods: In a retrospective study 6 patients were analysed. The inclusion criterion was evidence of Aspergillus sp. invasion in lung tissue. Lung tissue was obtained by biopsy or post mortem examination. Results: There were 4 patients with acute aspergillus pneumonia. Two of them were severely immunocompromised – one with dermatomyositis, who was treated with high doses of corticosteroids and methotrexate, and the other with undiscovered miliary tuberculosis, who was treated for myelodysplastic syndrome instead with low doses of corticosteroids. The other 2 had mild immunosuppression: one was suffering from sarcoidosis and was treated with low doses of corticosteroids, the other had dilated cardiomyopathy, renal insufficiency and diabetes mellitus. The two patients with chronic necrotising pulmonary aspergillosis had mild abnormality of host defence: one had reactivation of tuberculosis and diabetes mellitus, the other had inactive tuberculosis and aspergilloma. Conclusions: Invasive pulmonary aspergillosis must be considered also in patients with mild immunosuppression and pulmonary infiltrates which do not respond to conventional treatment with antibiotic chemotherapy. The key to the diagnosis of invasive pulmonary aspergillosis is the histopathological demonstration of fungal invasion in lung tissue.

Background Although local anesthetics (LA) are generally well tolerated, patients frequently report allergy-like adverse reactions to these agents. We studied the causes of adverse reactions during local anesthesia and the role of tolerance evaluation by means of allergy testing and incremental challenge with LA in patients at risk for adverse reactions during local anesthesia.

BACKGROUND: Diagnosis of allergy to Hymenoptera venom is usually confirmed with skin testing and measurement of specific serum IgE antibody, tests which are sometimes inconclusive. In these cases, additional in vitro tests are necessary. The aim of this study was to show the applicability of the basophil activation test in detecting sensitization to Hymenoptera venom and to compare the test sensitivity and clinical positive-predictive value with skin prick tests and measurement of allergen-specific serum IgE. METHODS: This prospective study was conducted between June 2004 and December 2007 and included a large group of 204 patients. All patients had a history of at least one systemic allergic reaction of Muller grades II–IV after a Hymenoptera sting. We compared results of the basophil activation test, specific serum IgE and skin prick tests with patients' clinical history and data on culprit insects. RESULTS: The overall clinical sensitivities of the basophil activation test, specific serum IgE and skin prick tests were 90%, 76% and 64%, respectively; the clinical positive-predictive values of the three tests were 79%, 73% and 78% for bee venom, 86%, 59% and 43% for wasp venom; and 84%, 77% and 22% for both venoms. CONCLUSIONS: Our results revealed a higher clinical sensitivity and comparable or better clinical positive-predictive value of basophil activation tests than skin prick tests and allergen-specific serum IgE in the detection of allergy to Hymenoptera venom.

Upala pluća je na četvrtome mjestu uzroka smrti u starijoj životnoj dobi, odnosno u starijih od 65 godina. Među rizične čimbenike u toj životnoj dobi ubrajaju se popratne kronične bolesti, oslabljen mukocilijarni klirens, slabljenje opće i specifi čne obrane, učestala kolonizacija nazofarinksa, slabija psihofi zička kondicija te loše socijalne i higijenske prilike. Klinička slika upale pluća u toj dobi nije uvijek karakteristična. Hipoksemija uzrokovana upalom pluća vrlo brzo mijenja psihofi zičku sliku bolesnika, čineći ga smetenim ili dezorijentiranim. Među novostima u liječenju upale pluća osoba starije životne dobi na prvom je mjestu ocjena težine bolesti, odnosno rizičnih čimbenika za nepovoljan ishod. Uz ocjenu težine bolesti po američkom sustavu PORT (Pneumonia Outcome Research Team), u Europi se upotrebljava i britanska ocjena težine upale pluća po sistemu CURB (Confusion, Urea, Respiratory rate, Blood pressure), koja za osobe starije od 65 godina ima varijantu CURB-65. Ona je jednostavnija, a u nas se može nazvati SFS-65 i SUFS--65 (Smetenost, Urea, Frekvencija disanja, Sistolički tlak, Starost). Jednostavnost primjene navedenih postupaka znatno pomaže pri donošenju odluke o liječenju bolesnika kod kuće ili u bolnici, odnosno primjeni lijekova, poglavito antibiotika. U radu je prikazan praktičan algoritam za ambulantno liječenje i liječenje u bolnici. Pravilan izbor antibiotika vrlo je važan, a ako popratne bolesti dopuštaju peroralnu primjenu, bolesnika treba liječiti kod kuće. U starijoj životnoj dobi antibiotici prvog izbora su najčešće amoksicilin s klavulanskom kiselinom ili respiratorni kinolon, jer su vrlo rijetki laki oblici upale pluća bez popratnih kroničnih bolesti. Mogu se upotrijebiti i cefalosporinski antibiotici iz druge ili treće generacije. U posebnim epidemiološkim okolnostima i u bolesnika s težom kliničkom slikom preporučljivo je dodavati i makrolidni antibiotik. Isto tako, ako se liječenje teške pneumokokne upale pluća provodi penicilinom, korisno je dodati makrolidni antibiotik. Ako početno liječenje nije dalo zadovoljavajuće rezultate odnosno ako su uzročnici pneumonije rijetki i neočekivani, treba se osloniti na dostupne mikrobiološke nalaze., Pneumonia ranks fourth among causes of death in the elderly, i.e. in patients over 65 years of age. Risk factors in this age group include accompanying chronic diseases, compromised mucociliary clearance, reduced general and specifi c defence mechanisms, frequent nasopharyngeal colonization, weakened physical and mental state, as well as poor social and hygienic conditions. Clinical picture of pneumonia is not always typical. Hypoxia caused by pneumonia rapidly alters a patient’s mental and physical status. A new approach introduced in the treatment of pneumonia in the elderly includes the assessment of disease severity, i.e. the assessment of risk factors. In addition to the U.S. score system PORT (Pneumonia Outcome Research Team), the British score system CURB (Confusion, Urea, Respiratory rate, Blood Pressure), as well as the CURB-65 version for people over 65 years of age, is also available. A simple use of these score systems signifi cantly helps in making a decision on hospital or outpatient treatment and choice of medicines, especially antibiotics. This article provides guidelines for outpatient and hospital treatment. The proper choice of antibiotics is very important. If accompanying conditions allow oral use, patients should be treated at home. Amoxicillin with clavulanic acid or respiratory quinolones most often represent the antibiotics of choice in the treatment of elderly patients since less severe forms of pneumonia without accompanying chronic diseases have been reported very rarely. Second or third generation cephalosporin antibiotics can be also used. The addition of a macrolide antibiotic is recommended in special epidemiological circumstances and for patients with a more severe clinical picture, as well as in the treatment of pneumococcal pneumonia with penicillin. If the initial therapy does not yield satisfactory results or if causative agents are rare and unexpected, one should rely on the available microbiological tests.

Background Histamine intolerance (HIT) is characterized by an imbalance between histamine intake and the capacity for histamine degradation. The main enzyme for metabolizing ingested histamine is diamine oxidase (DAO). Determining DAO activity in serum may be useful in diagnosing HIT.