Can obstructive intralymphatic granulomas be the cause of cheilitis granulomatosa?

Cheilitis granulomatosa (ChG), also known as Miescher's cheilitis, is an uncommon, immunologically mediated nonnecrotizing granulomatous inflammatory disease characterized by recurrent, painless swelling of the lips. The aim of the study was a pathomorphological and immunohistochemical assessment of cases clinically classified as ChG to investigate potential pathological mechanisms of ChG symptoms and to verify the hypothesis of intravascular granulomas as a cause of lymphatic vessel obstruction and localized edema in ChG. We report 6 patients with ChG who clinically presented localized edema of the lips. Lip biopsy with pathomorphological and immunohistochemical examination was performed in all cases. We found discrete, non-necrotizing granulomas which were adjacent to numerous blood and lymphatic vessels. The lumen of lymphatic channels was dilated and was either empty or contained lymph and few macrophages or was completely occluded by nearby granulomas. All patients demonstrated a characteristic pattern of lymphangiectasia and perivascular lymphatic aggregates with evidence of non-necrotizing granulomas. None manifested intralymphatic granulomas. These results do not support the view that lymphatic vessel obstruction is caused by intravascular histiocytic granulomas described as the main part in the etiology of lymphatic edema in ChG. However, perivascular granulomas and dilation of lymphatic vessels confirm presence of inflammatory lymphostasis in all studied cases of ChG.

Nonsteroidal anti-inflammatory drug hypersensitivity syndrome: a multicenter study. II. Basophil activation by nonsteroidal anti-inflammatory drugs and its impact on pathogenesis.

BACKGROUND: Patients who are clinically hypersensitive to nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes present basophil activation in vitro, and in 50% of cases a parallel response to release of sulfidoleukotrienes (cellular allergen stimulation test) is observed. These phenomena occur not only in clinically hypersensitive patients, but also in some healthy controls who tolerate NSAIDs. MATERIAL AND METHODS: We studied 16 clinically hypersensitive patients, 22 controls tolerating NSAIDs, and 29 healthy blood donors (clinical NSAID status unknown) using 2 different basophil isolation techniques (buffy coat or plasma leukocytes). RESULTS: In a population of 13 aspirin-tolerant healthy controls and 29 healthy blood donors, basophil activation with aspirin, diclofenac, and naproxen was analyzed at 4 different concentrations. The results in the 2 groups were quite similar in qualitative terms. Choosing a cutoff of 5% and a stimulation index >2, the proportion of positive results increased with the concentration. There were more positive results at all concentrations using the plasma leukocyte technique. CONCLUSIONS: The most important finding of this study is that basophil activation by NSAIDs occurs not only in clinically hypersensitive patients but also, to a very variable extent and on an individual basis, in apparently normal healthy individuals who tolerate NSAIDs. The phenomenon is clearly dose-related, and hypersensitive patients seem to react to lower NSAID concentrations.

A new variant of the basophil activation test for allergen-induced basophil CD63 upregulation. The effect of cetirizine.

OBJECTIVE: The aim of our study was to determine the diagnostic usefulness of a newly developed basophil activation test (BAT) in patients allergic to Dermatophagoides pteronyssinus and pollens. We also analyzed the influence of cetirizine on CD63 upregulation. This popular antihistamine strongly inhibits skin tests, but its impact on BAT sensitivity remains unknown and deserves at least preliminary determination. METHODS: The study sample comprised 22 patients allergic to house dust mite and pollens and 19 healthy controls. All participants underwent skin prick testing and the newly developed flow-cytometric basophil activation test. The protocol for allergen-induced basophil CD63 upregulation consisted of whole blood samples that were processed and stained with anti-CCR3/CD63 antibodies added to the buffer at the beginning of stimulation. Skin prick tests and BAT were performed twice--before and 2 hours after ingestion of 10 mg of cetirizine. RESULTS: The new BAT is characterized by its short processing time, easy basophil gating, and strong CD63 upregulation with very high sensitivity and excellent specificity. Our results suggest that allergen-induced CD63 upregulation by higher doses of allergens is not inhibited 2 hours after administration of cetirizine (unlike skin prick tests). CONCLUSION: The BAT is a very useful and precise method for the diagnosis of allergy to aeroallergens. It is not influenced by cetirizine.

Food-dependent exercise-induced anaphylaxis: possible impact of increased basophil histamine releasability in hyperosmolar conditions.

We present a case of anaphylactic shock induced by exercise following celery ingestion. The possible mechanism of food-dependent exercise-induced anaphylaxis (FDEIA) and the laboratory tests for its diagnosis are discussed. We evaluated spontaneous, celery-allergen-induced, and anti-FcepsilonRI-antibody-induced histamine release from basophils obtained from the patient, 2 celery-allergic controls, and 3 healthy controls. Buffers of increasing osmolarity were used to mimic conditions of vigorous physical exercise. Only the patient's basophils showed an increase in spontaneous, anti-FcepsilonRI antibody-induced and allergen-induced histamine release under physiological conditions and with slightly increased medium osmolarity. To our knowledge, this is the first report on the possible role of increased histamine releasability in the pathogenic mechanism of FDEIA. We suggest that FDEIA results from increased histamine releasability triggered by physical effort after exposure to a sensitizing food allergen.

[Pathogenesis of exercise induced asthma]. / Patogeneza astmy wysilkowej.

Exercise induced asthma is an exaggerated airway response to airway dehydration and the following mediators release from the inflammatory cells. The airway narrowing is primarily caused by bronchial smooth muscle contraction, but in milder form mucus production, airway edema and cough can be observed. In this study we have described some previously and currently proposed hypotheses which may explain pathomechanism of this form of bronchial hyperreactivity.

[Oxidation phenotype as a risk factor for development of allergic diseases]. / Fenotyp oksydacji jako czynnik zwiekszajacy ryzyko wystapienia chorób alergicznych.

The relationship between genetically determined polymorphic metabolism and susceptibility to allergic diseases has aroused much interest. The aim of our study was to evaluate whether patients with allergic diseases, like atopic asthma and allergic rhinitis differ from healthy persons in their ability to oxidize sparteine as a model drug. The study was completed by 200 persons, 40 patients with allergic diseases--20 with atopic asthma and 20 with allergic rhinitis and 160 healthy volunteers as a control group. The results of our study revealed a predominance of very extensive metabolizers of sparteine among patients with allergic diseases in comparison with healthy volunteers. The difference in the oxidation metabolic ratio (MR) frequency distribution between patients with allergic diseases and healthy persons was statistically significant. Relative risk (odds ratio) of development of atopic asthma was 3.29 times higher, and that of allergic rhinitis 2.94 times higher for persons with very extensive oxidation phenotype. Our results represent some evidence for a possible relationship between extensive, rapid oxidation phenotype and the higher susceptibility to development of atopic asthma and allergic rhinitis.

[Bronchial hyperreactivity to histamine and levels of serum eosinophil cationic protein in patients with non-atopic asthma]. / Nadreaktywnosc oskrzeli na histamine a stezenie eozynofilowego bialka kationowego w surowicy chorych na astme oskrzelowa nieatopowa.

Pathogenesis of non-atopic bronchial asthma remains still an open question. Until now there have been very few studies concerning relationship between eosinophil activation and nonspecific bronchial hyperreactivity to histamine in this form of asthma. Sixteen subjects with mild nonatopic bronchial asthma entered the study. Evaluations of PC 20 for histamine and serum eosinophil cationic protein (ECP) concentration have been performed in all patients. In spite of fact that all patients were considered as mild asthmatic we have observed wide range of PC 20 and serum ECP concentration. Moreover we were able to find statistically significant inverse correlation between PC 20 for histamine and serum eosinophil cationic protein concentration: r = -0.498, p < 0.05. We conclude that eosinophil activation plays an important role in pathophysiology of nonspecific bronchial hyperreactivity in nonatopic bronchial asthma.

Comparative study between skin prick tests and TOP-CAST allergen leukocyte stimulation in diagnosis of allergic status.

A recently developed CAST-ELISA method was applied to determine allergen-induced leukocyte stimulation. This method is based on the measurement of sulfidoleukotriene secretion by peripheral blood leukocytes previously stimulated with specific allergen in the presence of interleukin 3. 24 patients allergic to different aeroallergens and some food allergens were included in this study. Subjects received no medication 2 weeks before the testing. Leukocytes were isolated by dextran sedimentation. After incubation with allergen at two concentrations, the cells were centrifuged and the concentration of sulfidoleukotrienes in supernatant was determined. The results were expressed in pg/ml after subtraction of values of spontaneous sulfidoleukotriene production in portions incubated without allergen. We observed a wide range of sulfidoleukotriene secretion upon allergen stimulation. Concentrations of leukotrienes ranged from 0 to 5780 pg/ml at lower allergen concentration and from 210 to 5680 at higher allergen concentration. On the basis of observed results, we conclude that the better allergen concentration is the higher one because there was no appearance of negative cell stimulation. In the lower allergen concentration we observed negative results in two cases. Sixteen healthy control subjects were also included in this study. Eleven subjects had negative skin prick tests (SPT) as well as CAST results. In 5 healthy subjects with positive SPT, we also observed positive CAST results in 4 persons. In 1 healthy person with positive SPT results, CAST results were negative. We conclude that TOP-CAST allergen is a valuable mixture of different aero and food allergens for determining the allergic status in patients with suspicious allergic status, although it cannot differentiate between health and disease states.

CAST-ELISA test in diagnosis of mite allergy.

The recently developed CAST-ELISA method was applied to determine allergen-induced leukocyte stimulation. This method is based on the measurement of sulfidoleukotriene secretion by peripheral blood leukocytes stimulated with specific allergen in the presence of interleukin 3.23 patients allergic to Dermatophagoides pteronyssinus were included in this study. All subjects received no medication 2 weeks before the testing. Leukocytes were isolated by dextran sedimentation. After incubation with allergen the cells were centrifuged and the concentration of sulfidoleukotrienes in supernatant was determined. The results were expressed in pg/ml after subtracting the values of spontaneous sulfidoleukotriene production in portions incubated without allergen. We observed a wide range of sulfidoleukotriene secretion upon allergen stimulation. Concentrations of leukotrienes ranged from 0 to 3440 pg/ml. The mean level in the whole group was 1521.3 pg/ml at the optimal allergen concentration. Positive results were observed in 21 subjects. In 2 subjects we could not demonstrate leukotriene secretion by stimulation with allergen. 15 healthy control subjects were also included in this study. 12 subjects had negative skin prick tests (SPT) as well as CAST results. In 2 healthy subjects with positive SPT, we also observed positive CAST results. However, leukotriene secretion was lower than 300 pg/ml in these subjects. We conclude that CAST-ELISA is a valuable method for determining the allergic status in patients with mite allergy.

Is mast cell activation during asthmatic reaction reflected in the circulation?

Allergic asthmatic patients were challenged with specific allergen that resulted in early asthmatic reaction (EAR). Serum tryptase concentration (STC) and neutrophil chemotactic activity (NCA) were measured before and during EAR. A significant increase in neutrophil chemotactic activity was noticed in the 60th min, without an accompanying increase in serum tryptase concentration. The rise in neutrophil chemotactic activity in our study confirms previous observations in this field. However, because of the numerous cellular sources for neutrophil chemotactic activity, it does not seem to be a gold standard for measurement of mast cell activation. Undetectable levels of serum tryptase concentration during EAR in our study do not exclude the role of the mast cell in its pathogenesis. To our knowledge, only massive mast cell degranulation is reflected in the circulation as an increased tryptase concentration. In the case of upper respiratory allergic reactions, mast cell degranulation definitely takes place, but does not result in evident changes in serum tryptase concentration. We conclude that mast cell activation during allergen-induced EAR is poorly represented in the circulation.

[Spontaneous histamine release by basophils and bronchial hyperreactivity in patients with hay fever]. / Spontaniczne uwalnianie histaminy z bazofilów oraz nadreaktywnosc oskrzeli u chorych na pylkowice.

Basophil spontaneous histamine release test was performed in seventeen patients suffered from seasonal allergic rhinitis before, 2 weeks after immunotherapy and during pollen season. During pollen season at the same day non-specific bronchial hyperreactivity to histamine was estimated. Values of spontaneous basophil histamine release before immunotherapy were not different from control group but significantly increased after immunotherapy and during pollen season. There was no correlation between degree of nonspecific bronchial hyperreactivity and values of spontaneous histamine release from basophils.

[Concentration of eosinophil cationic protein in blood serum during early and late asthmatic reaction]. / Stezenie eozynofilowego bialka kationowego w surowicy podczas wczesnej i póznej reakcji astmatycznej.

Eosinophil cationic protein (ECP) was measured in blood serum of 15 atopic asthmatics during early (EAR) and late (LAR) asthmatic reaction triggered by specific allergen provocation. Nonspecific bronchial hyperreactivity was evaluated in histamine provocation test before and 48 hours after the allergen challenge. We observed dual asthmatic reaction (DAR) in 8 and an isolated EAR in 7 patients. The ECP serum level and nonspecific bronchial hyperreactivity were significantly higher (p < 0.05) in the DAR group when compared to EAR responders. An inverse correlation between PC20 for histamine and ECP level was shown before and after the allergen challenge in all examined subjects (R = -0.5472, p < 0.05).

[Spontaneous and allergen induced basophil histamine release and bronchial hyperreactivity]. / Spontaniczne i indukowane alergenem uwalnianie histaminy z granulocytów zasadochlonnych a nadreaktywnosc oskrzeli.

In this study we have measured spontaneous and allergen induced basophil histamine release before and 24 hours after specific allergen bronchoprovocation challenge. Non-specific bronchial hyperreactivity was estimated twice: before and after allergen challenge. 15 atopic asthmatic entered the study. 8 of them developed only early asthmatic reaction and 7 demonstrated dual asthmatic reaction. In dual responders group higher values of spontaneous basophil histamine release before and increase of allergen induced basophil histamine release after specific allergen bronchoprovocation challenge were observed. There was an inverse correlation between values of allergen induced basophil histamine release and values of PC20 for histamine.

[Granulocyte chemiluminescence during early and late asthmatic reaction]. / Chemiluminescencja granulocytów w trakcie wczesnej i póznej reakcji astmatycznej.

Allergic asthmatic patients were challenged with specific allergen resulting in early and dual asthmatic reaction. FMLP induced granulocyte chemiluminescence was measured before and in 10 min, 60 min, 4 hours and 24 hours after allergen challenge. We have observed significant decrease of granulocyte chemiluminescence in both groups. In patient with early asthmatic reaction decrease of luminescence was observed during first hour only. In patients with dual asthmatic reaction decrease of luminescence was observed during 24 hours after allergen challenge.

[Nedocromil sodium in treatment of bronchial asthma]. / Nedokromil sodu w leczeniu astmy oskrzelowej.

Clinical study on efficiency of the nedocromil sodium (Tilade, Fisons) was performed in 20 patients with atopic and nonatopic bronchial asthma. The drug was administrated in dose of 8 mg per day for 2 months which allowed to renounce regular using of Beclocort forte after 7 days of the treatment. In both types of bronchial asthma the positive effect of nedocromil sodium was confirmed, causing increase of pulmonary ventilation and decrease of bronchial hyperactivity. Especially profitably effect was noticed in atopic bronchial asthma in which statistically important increase of peak expiratory flow (PEF) was obtained and decrease of bronchial hyperreactivity by PC20 for histamine was observed (p < 0.05). Mentioned above spirometric parameters did not differ in statistically important pattern in patients with nonatopic bronchial asthma, when Beclocort forte group with Tilade group compared. Neither important differences in general number of cells nor percentage composition of cell smears were observed in bronchoalveolar lavage fluid.