Bradykinin mediated gastrointestinal edema as a cause of abdominal attacks in patients with hereditary angioedema due to C1-inhibitor deficiency.

Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is a rare hereditary disease characterized by recurrent subcutaneous or submucosal angioedema due to uncontrolled bradykinin production caused by C1-INH dysfunction. Submucosal gastrointestinal swellings provoking abdominal attacks are common and mimic acute abdomen, thus constituting a diagnostic challenge. We aimed to investigate the difficulties in diagnosing abdominal attacks in patients with C1-INH-HAE and to assess the diagnostic value of medical history, the course of the attack, abdominal imaging, and treatment efficacy. The retrospective analysis of diagnostic problems and treatment complications of abdominal attacks in 274 patients with C1-INH-HAE were performed. The value of history, laboratory findings, prodromal symptoms and course of attacks and imaging were assessed. Abdominal attacks were confirmed in 274 of the 322 patients (85%; 190 women and 84 men; age, 4-70 years). In 49% of cases, the abdominal attack was the first and the only symptom for years. The simultaneous presence of marginal erythema (45% of cases), subcutaneous edema (30%), and pharyngo-laryngeal edema (10%) facilitated the diagnosis of an abdominal attack due to C1-INH-HAE. Abdominal attacks manifested with recurrent acute abdominal symptoms lasting 2 to 5 days. The disease course was characterized by the phase of progressive prodromal symptoms followed by peak symptoms and spontaneous symptom resolution. Abdominal imaging often revealed abundant ascites and limited bowel edema. In 60 cases (22%), the diagnostic difficulties resulted in exploratory laparotomy, which was inconclusive in 48 patients (80%). The attacks usually subsided within 2 hours from the administration of recommended drugs (plasma-derived C1-INH, recombinant C1-INH or icatibant). We conclude that recurrent abdominal attacks lasting a few days and resolving spontaneously were common symptoms of C1-INH-HAE. Abdominal imaging revealed transitional fluid or bowel edema. The effectiveness of recommended drugs as plasma-derived C1-INH, recombinant C1-INH or icatibant confirmed the diagnosis.

Recombinant human C1 inhibitor for the prophylaxis of hereditary angioedema attacks: a pilot study.

BACKGROUND: Hereditary angioedema (HAE) is a disease characterized by recurrent tissue swelling affecting various body locations. Recent literature shows that patients with frequent attacks may benefit from long-term prophylaxis. This study evaluated the safety and prophylactic effect of weekly administrations of recombinant C1INH (rhC1INH). METHODS: Patients with a history of HAE attacks occurring ≥every 2 weeks received a once weekly administration of 50 U/kg rhC1INH. Hereditary angioedema attack history was collected at screening. Breakthrough attacks during the study were recorded at each visit. Following a 2-week run-in period, HAE patients received 8 weekly rhC1INH administrations and were followed-up for an additional 6 weeks. Efficacy was evaluated by comparing the HAE attack incidence during the treatment period to the historical attacks over the previous 2 years. Safety evaluation was based on clinical laboratory and adverse events (AEs) reports. RESULTS: The 25 participants reported a mean of 0.9 attacks/week over the past 2 years. The mean breakthrough attack rate during the treatment period was 0.4 attacks/week (95% CI 0.28-0.56). A total of 30 treatment-emergent-AEs were reported in 13 patients, all mild to moderate. One patient died from a laryngeal attack 25 days after last study drug administration. The only possible drug related AEs reported were dry mouth, dizziness and anxiety in one patient and hypotension in another. There were no allergic AEs and no neutralizing antibodies observed. CONCLUSIONS: Weekly administrations of 50 U/kg rhC1INH appeared to reduce the frequency of HAE attacks and were generally safe and well tolerated.

A half of schoolchildren with 'ISAAC eczema' are ill with allergic contact dermatitis.

BACKGROUND: Similarity in clinical symptoms between atopic eczema (AE) and allergic contact dermatitis (ACD) may lead to misdiagnoses in both clinical practice and epidemiological studies. As patch testing for contact allergy does not seem popular among paediatric allergists, the resulting bias leads mainly to under diagnosing of ACD and over diagnosing of AE in children and adolescents. OBJECTIVES: To assess the frequency of AE and ACD among children and adolescents who answered affirmatively the eczema module of ISAAC questionnaire. METHODS: Of 9320 schoolchildren involved in an allergy screening programme, 143 consecutive participants were recruited for the present study. The inclusion criterion was affirmative answers to questions from the eczema module of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The children were examined by two allergists: a paediatrician and a dermatologist, and the children underwent patch testing. RESULTS: We diagnosed AE in 46 (55.4%) children and 18 (30.0%) adolescents, whereas 32 (38.6%) children and 31 (51.7%) adolescents were diagnosed with ACD, with a considerable overlap of both diseases. Nine of 46 (19.6%) children and 13 of 25 (52.0%) adolescents with affirmative answers to the question about flexural eczema were diagnosed with ACD, while lacking features sufficient for the diagnosis of AE according to Hanifin and Rajka. Based on the indices from the whole population tested (9320 pupils), a rough estimate of the general ACD prevalence was 5.8% for adolescents, and 8.5% for children, which is close to the figure of 7.2% observed previously in Danish schoolchildren. CONCLUSIONS: Our data demonstrate that 'ISAAC eczema' is an epidemiological entity that embraces comparable portions of cases of atopic eczema and allergic contact dermatitis, and possibly also other less frequent pruritic dermatoses. Each case of chronic recurrent dermatitis in children requires differential diagnosis aimed at allergic contact dermatitis and inflammatory dermatoses other than atopic eczema, even when predominantly localized in flexural areas.

Environmental pollutants and allergy diseases.

A rapid increase in the prevalence of allergic diseases of our times as well as a significant increase in the IgE production in our population cannot be explained only by the genetic influence. Allergy is a growing, special problem of the industrial regions and well developed countries. The environmental factors and style of life seem to be the most important reasons of this phenomenon. The environment in which we live is full of natural and manmade substances capable of causing reactions in susceptible individuals. Xenobiotic--unnatural substances which appeared in polluted environment and act on our immunity may induce the suppression of it and in this way provoke the infection or neoplastic diseases. They may also induce the hyper-reactivity reaction and then become the reason of allergic or autoagression diseases. We distinquish two types of environmental pollution. Type I--with a high level of SO2 which induce infections and the chronic inflammation as a consequence of their irritants and a toxic action and type II pollutants (NOx, O3, VOC--volatile organic chemicals) which promote allergic diseases. The allergy in polluted areas additionally is accompanied very often by pseudo-allergy and toxic reactions. In order to stop the present increasing trend of allergic diseases we must increase our attempts to control allergens and irritants. There is no doubt today that the development of allergic diseases is related to the genetic predisposition and environmental factors.

Allergic nasal polyps under scanning electron microscope.

The study material consisted of 18 patients (10 men, 8 women, aged 26-66 years), suffering from recurrent nasal polyps and bronchial asthma. Nine patients manifested intolerance to aspirin and non-steroid anti-inflammatory drugs (NSAIDs). The polyps removed during one of polypectomies were analysed with the help of scanning electron microscope (SEM) in order to evaluate the morphology of their surface. All the specimens displayed the increase in areas of cilium-free epithelium, covered with short microvilli and squamous epithelial cells. The arrangement of these changes was irregular and they were more pronounced in patients with intolerance to aspirin and NSAIDs. Apart from this, there were no other differences which would allow to differentiate in SEM investigation between polyps derived from patients with and without tolerance to NSAIDs.

[Drug allergy among patients suffering from nasal polyps]. / Alergia na leki wsród chorych z polipami nosowymi.

The study was performed in order to evaluate quantity and morphology of nasal polyps in patients with diagnosed drug allergy to aspirin, antibiotics, polocain, procain and other drugs. The study included 60 patients (27 females, 33 males aged between 18-69 years). Nasal polyp morphology was examined under electron microscope and light microscope. Morphological evaluation of epithelial and subepithelial structures was done under light microscope, taking not of inflammatory infiltration type, basal membrane, as well as degree of intestinal edema. Evaluation of epithelial cell type, their relative proportion, as well as area percentage covered by cilium, microvilli and squamous epithelium was done under electron microscope. Polyps in patients with idiosyncrasy to polish aspirin and sodium metamizole (12 patients) featured increased eosinophilic infiltration, thickened basal membrane, with elevated eosinophil percentage differential count. The epithelial percentage area was covered by squamous cells without villi. Polyps associated with idiosyncrasy to polish aspirin differed morphology compared to polyps originality from patients allergic to other medications. On the other hand polyps from patients allergic to other drugs, such as: penicillin, procainamide were morphologically (electron light microscope, light microscope) similar to those polyps caused by inflammatory factors.

[Occupational allergic diseases in the steel industry. Population studies]. / Alergiczne choroby zawodowe w hutnictwie. Badania populacyjne.

The aim of this study was to evaluate the occurrence of occupational allergic diseases of the respiratory system and skin. The study was carried out in a population of 17,600 employees of Huta im. T. Sendzimira (T. Sendzimir Steelworks) in 1992-96. During this period 543 employees were referred to the Occupational Diseases Department with a suspection of occupational allergy. Connection between the kind of occupation and disease was confirmed in 215 cases. 104 (48%) suffered from upper respiratory tract diseases or bronchial asthma and 111 patients (52%) suffered from allergic skin disease as contact dermatitis of the hand or generalized dermatitis. The analysis showed that allergic skin diseases occurred more frequently in 1992-94 and allergenic respiratory diseases were more frequent in 1995-96. Industrial dust containing metals (nickel, chrome, iron, cooper) turned out to be the main allergic factor. The highest prevalence was observed in the Rolling-Mill Department, Chemistry of Coke Department and Incombustible Materials Department. 33% of patients suffering from allergic respiratory diseases and 10% suffering from allergic skin diseases had a family predisposition to allergy (features of atopy).

[The efficacy of subterranean therapy in the salt chamber of Kinga Spa in Wieliczka for patients suffering from allergic rhinitis]. / Skutecznosc leczenia subterraneoterapia alergicznego niezytu nosa w komorach solnych Szpitala Uzdrowiskowego Kinga w Wieliczce.

42 patients (27 women and 15 men aged 14-65 years) suffering from atopic and non atopic rhinitis were submitted for 24 days to the subterraneo-therapy in salt chambers of Kinga Spa in Wieliczka during the exacerbation of their illness. 20 patients suffered from pollen or dust mites allergy and the next 22 patients from non atopic rhinitis with recurrent nasal polyposis. In the first week and at the end of the therapy rhinoscopy, peak nasal inspiratory flow and smell were evaluated as well as daily symptoms score was noted in each treated patient. The results of performed observations indicate that unrelatively to the type of the rhinitis: 1. the nasal symptoms (running nose, sneezing, block of the nose) resolved directly during the stay of the patient in the salt chamber but the more constant effect was visible with the time of the therapy. 2. an increase in the peak nasal expiratory flow was connected with the decrease of nasal mucosal edema, 3. the smell disturbances disappeared in the patients together with the decrease of mucosal edema. The observed changes seem to be connected with the influence of the salt chambers' microclimate on the cells osmolarity disturbances in the nasal mucosa provoked by the non infectious chronic inflammation.

Induction of allergy to new aeroallergens during specific immunotherapy (SIT) in grass pollen sensitive patients.

In the group of 50 patients suffering from grass pollen allergy and successfully treated with SIT for three consecutive years, we observed in 5 persons after the end of this treatment the induction of allergy to new allergens (to weeds, mites or tree) manifested by the change of the symptoms season. The induction of the new kind of allergy was confirmed by revealing of the positive skin prick tests to new allergens and by an increase of the specific IgE serum level to them. Despite disappearance of the symptoms of the illness during grass pollen season in all 5 patients we noted the higher total IgE as well as specific to grasses IgE serum level, in comparison to the value at the start of SIT. In the paper the possible mechanisms of this phenomenon are discussed, which seems to be not connected with the natural development of allergy and which confirms once more that during SIT individual changes in humoral and cellular immunity of the patient take place, sometimes very difficult to be predicted. They may among others switch clinical profile of allergy, what indicates that patient during SIT should be under the careful immunological supervision.

[Latex allergy in health services workers]. / Alergia na lateks u pracowników sluzby zdrowia.

The studies were performed in 20 workers from the Health Service (13 women and 7 men in the age 25-57) suffering from hand urticaria (6 persons) and hand dermatitis (14 persons) suspected of the allergy to latex gloves. In all patients the familial and personal predispositions to allergy were evaluated by the anamnesis, the estimation of total IgE serum level and the skin prick tests (SPT) with inhalant allergens. The latex allergy was diagnosed by SPT and contact test with standardized extract of the natural latex allergen in the concentration 1000 PNU/ml (Nexter-Allergopharma) and by estimation of specific to latex IgE serum level. In addition to this, contact tests with glove's material as well European standard contact allergens (Hermal) were done and the one with antiseptic substances to which the patient was exposed at his work. The allergy type I to latex gloves was confirmed in all 6 cases with contact urticaria. The SPT with standard extract of the natural latex was more valuable than latex specific IgE in the serum. Contact allergy (type IV) to latex gloves was confirmed in 10 from 14 suspected cases. In the next 4 the allergy to antiseptic substances was the reasons of the illness. The allergy to latex gloves appears more often in women. No case showed the familial predisposition to allergy and only 4 patients additionally suffered from the allergy to pollen and mites. Moreover in both groups of patients we showed the presence of the additional contact allergy to different allergens (to metals and antiseptic substances).

Obstruction of the small airways in the spirometric diagnosis of occupational bronchial asthma.

The aim of this study was to evaluate spirometric changes after inhalation challenge in steel and tobacco factory workers suffering from bronchial asthma suspected to be of occupational origin. In 49 patients the spirometric changes were analyzed immediately after and 24 h (delayed reaction) after inhalation challenge at work. A decrease in spirometric parameters of 20% compared to baseline was considered significant. The suspicion of occupational bronchial asthma was based on anamnesis and skin patch tests. The atopy features in examined patients were evaluated according to anamnesis, skin prick tests with aeroallergens, as well as total IgE serum level and blood eosinophils. The significant decrease in spirometric parameters after the inhalation challenge at work was confirmed in 25 (51%) patients. In 16 of them (64%), the decrease of FEV1 value together with the decrease of the MEF 25-75% VC values were noted. A significant isolated decrease in the FEV1 was observed in only four (16%) patients. However, in five (20%) patients a significant decrease in MEF 25-75% VC values was only found as a confirmation of airways obstruction. The studies emphasize the diagnostic value of small airways obstruction in the evaluation of inhalation challenge tests in patients suspected of occupational bronchial asthma.

[Some clinical symptoms and allergens on asthma-prurigo syndrome]. / Niektóre objawy kliniczne oraz alergeny w zespole asthma-prurigo.

The group of 146 patients suffering from asthma-prurigo syndrome (85 adults and 64 children) have been inquired in many various clinical centers. It was established that in 79.6% of the patients the first symptoms of illness appeared already in infancy and only 28.2% of the patients had negative familiar anamnesis on the allergy. In 73.2% of the patients with asthma-prurigo syndrome the symptoms of atopic dermatitis persisted longer than asthma symptoms and in 89.9% of them asthma-prurigo symptoms accompanied other form of allergic diseases. The most important causal allergens provoking asthma-prurigo symptoms were: house dust (in 64.4% of the patients), chocolate (in 42.2%), cat epithelia (in 40.2%) and cow milk proteins (in 29.5% of the patients).

[Changeability of respiratory tract and skin symptoms in patients with asthma-prurigo syndrome under the influence of emotional and environmental factors]. / Zmiennosc nasilenia objawów ze strony dróg oddechowych i skóry u chorych z zespolem asthma-prurigo pod wplywem czynników emocjonalnych i srodowiskowych.

In a group of 228 patients suffering from asthma-prurigo syndrome the influence of emotional state, permanent residence and season time on dynamic of the clinical symptoms were studied. The evaluation of emotional state in 80 adult patients was carried-out by means of Eysenck Personality Inventory. The emotional state had less negative influence on the exacerbation of the symptoms upon children then in adults (especially on their skin symptoms). It was confirmed that the patients with high level of neurotic symptoms revealed easier the exacerbation of asthma and skin disorders under the influence of emotional stress. The climatic treatment on the sea-side was more efficient for them than any mountain climatic cure, especially in the treatment of airways symptoms. Similarly, the summer season brought the relief of their symptoms from both the respiratory and skin symptoms.

[Respiratory and skin diseases among school children in the industrial and rural regions]. / Choroby alergiczne dróg oddechowych i skóry u uczniów szkól podstawowych w rejonie uprzemyslowionym i wiejskim.

The studies were done among the school-children in 3 grammar schools (2 in the industrial and 1 in rural regions). Allergological examination (anamnesis, physical exam and skin prick tests with inhalants) were performed among the pupils suspected of the allergic disorders on the basis of the questionnaire analysis made in all school-children. The results were compared to the environmental air pollution in the school region. The frequency (4.9-7%) and the type of the allergic diseases were similar in all 3 schools. The most frequent allergens were pollen, mites and animal epithelia. In rural region familial predisposition to allergy was 2 times higher in pupils suffering from allergy. 70% of pupils suffering from allergy in the industrial regions had no familial predisposition to allergy.

Double-blind, randomised, placebo-controlled study of two concentrations of azelastine eye drops in seasonal allergic conjunctivitis or rhinoconjunctivitis.

This double-blind, randomised, placebo-controlled study was carried out to assess the efficacy and safety of 0.025% and 0.05% azelastine eye drops twice daily administered for 14 days to patients with seasonal allergic conjunctivitis or rhinoconjunctivitis. A total of 278 patients were recruited and 226 patients were evaluable for per protocol analysis. The target parameter was the response rate. Four eye symptoms, including the main symptom (itching) were recorded by patients in diaries and eight symptoms were assessed by physicians before and after seven and 14 days of treatment. Severity of symptoms was measured on a four-point scale. The response rates for itching (improvement of at least one score point within the first three days) according to patient assessment were 43% for placebo, 52% for 0.025% and 56% for 0.05% azelastine (NS). However, a more objective assessment of the three main eye symptoms by physicians showed a concentration-dependent improvement in response rate compared with placebo (a decrease of > or = 3 points from a baseline total score of > or = 6), which reached statistical significance for 0.05% azelastine on Day 7 (p < 0.002). In the evaluable patient population, the scores of the three main eye symptoms as well as of all eight recorded eye symptoms, as assessed by the physician, were significantly (p < 0.05) lower in the 0.05% azelastine eye drops group in comparison with the placebo group at Day 7. Inefficacy was the cause of withdrawal in five and three patients on 0.025% and 0.05% azelastine, respectively, and in six patients on placebo. Adverse drug effects, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported by 14% (0.025%), 20% (0.05%) and 15% (placebo) of the patients. No serious side-effects occurred. Azelastine eye drops are effective and well tolerated at a concentration of 0.05% for the treatment of seasonal allergic conjunctivitis.

[Clinical characterization of "asthma-prurigo" syndrome with emphasis on risk factors]. / Charakterystyka kliniczna zespolu "asthma-prurigo" z uwzglednieniem czynników przyczynowych.

In a group of 228 patients with Asthma-Prurigo syndrome in 82.5% of patients the onset of skin lesions was earlier than the onset of asthma. It was found that the early onset of atopic dermatitis suggests the greater probability of subsequent asthma. In 88.6% of patients also other allergic diseases were diagnosed, and rhinitis allergica was observed most frequently. In the investigated group of patients urticaria chronica idiopathica or physical urticarias were not observed. Among 228 patients with Asthma-Prurigo syndrome, 74.6% of patients pointed to house dust as one of the most frequent causative factors. The house dust similarly to other inhalant allergens, somewhat more frequently had influence on the course of atopic dermatitis than on the course of asthma. Contrary to this observation according to patients food allergens (milk, eggs, fish, chocolate) aggravated or induced the relapses of skin lesions much more frequently than asthma. It was shown how often patients noticed adverse reactions due to penicillin and sulphonamides.

[Catalet--vaccine against hay fever]. / Catalet--szczepionka pylkowa.

Catalet is the Polish vaccine against pollinosis. It contains pollens of 13 species (mainly grass) and is used in the treatment of pollinosis. It is standardized in protein units. Allergen adsorption on aluminium hydroxide prolongs its absorption and decreases a number of the necessary injections. A four-year investigations in 30 patients (including 5 children) showed that Catalet tolerability is comparable with that of foreign-made preparations such as Alavac P, Desalerga F, and Allpyral-5 Grass mix.

Air pollution and pollen allergy.

Pollen allergy is the most typical form of allergic diseases. The increase in its frequency during recent years is most evident. The disease was rare when it was first described 150 years ago as summer hay fever. In 1876 Blackley wrote that the frequency of pollen allergy was increasing, especially in industrialized countries. Nowadays the prevalence of pollen allergy is well above 10%. Among the patients predominate the inhabitants of large cities, but not rural residents. Allergy develops as a result of multiple interactions between the human immune system and the environment. The current state of knowledge does not permit precision about the importance of genetic and environmental factors. It appears that although genetic control is very important, the environmental influences seem most important in determining the specific allergens to which a person will develop hypersensitivity. The adjuvant factors of the environment play an important role in the increasing problem of pollen allergy in large cities. Air pollution such as sulphur dioxide, ozone, nitrogen oxides, occupational dust, organic and inorganic suspended particulate matter, tobacco smoke, etc., can cause an increase in airway reactivity through mechanisms dependent on or independent of specific IgE antibodies. By irritating the airways and skin, pollen grain penetration into the human body can increase. Defective permeability of tissue surface can increase the risk of infection. Air pollution may also increase the development of pollen allergy through a direct influence on the pollen grains (on their enzymes, plant growth etc.). Lastly, the pollen grains may carry on their surfaces the various substances which are known as environmental allergens.(ABSTRACT TRUNCATED AT 250 WORDS)

[New possibilities of treating acute angioedema caused by C1-inhibitor deficiency]. / Nowe mozliwosci leczenia ostrych obrzeków naczynioruchowych u chorych z niedoborem inhibitora C1-esterazy.

The authors discuss diagnostic difficulties in 12 cases of hereditary angioneurotic edema due to C1-esterase inhibitor (C1-INH deficiency). Emphasis is on the treatment of the acute attacks with intravenous infusions of C1-inhibitor concentrate (Boehring, West Germany). This proved to be a very efficient and safe therapy, leading to a prompt disappearance of all clinical symptoms. Throughout 12 months following the infusions, indices of the liver function remained within the normal range, and anti-Hbs and anti-HIV tests were negative.