Early effects of rush immunotherapy with Dermatophagoides pteronyssinus in asthmatics

In this study we assessed the effects of Dermatophagoides pteronyssinus (Dpt) rush immunotherapy in comparison with placebo treatment in our asthmatic patients. Fourteen highly Dpt-susceptible adults were randomized in two groups (immunotherapy and placebo) and treated in single-blind manner. Patients were selected according to the recommendation of the immunotherapy position paper (1993). To minimize side effects we modified the protocol by adjusting allergen doses for each patient separately. Immunologic (total and Dpt-specific serum IgE and IgG antibodies/EIA, Pharmacia) and clinical parameters (spirometry, medication score and skin testing) were recorded before treatment, after 2 weeks, at the second month and after 4 months of immunotherapy onset. None of the patients had life-threatening side effects in the course of the treatment. The results obtained demonstrated significant influence of immunotherapy on Dpt-specific serum IgG synthesis (Kruskal Wallis test, p < 0.05) and on the late phase skin reaction with Dpt (U-test, p < 0.05) at the end of the second month of immunotherapy onset. In the immunotherapy group, we also registered a negative correlation between concentrations of Dpt-specific serum IgE and IgG antibodies (p = -0.83; p < 0.05), at the end of the second month. In addition, diversities among patients, expressed by immunologic parameters, were related to the amount of delivered allergen. There were no significant differences between groups concerning medication score from opposite to better FEV1, PEFR and dPEFR results (Kruskal Wallis, p < 0.05) in the placebo group. In conclusion, Dpt-specific serum IgG concentration, immunologic score and late phase skin reactivity to allergen appeared to be the valid parameters of rush-immunotherapy achievement, while delivered allergen dose also seemed to be an influencing factor

Reaktivnost kože i sistem 'prik-test jednak histaminskom' kod osoba preosetljivih na polene trava

INTRODUCTION Skin prick-test has been accepted as one of diagnostic criteria for atopyc diseases. In accordance with the recommendations of the EAACI (European Academy of Allergy and Clinical Immunology ), the Subcommittee for skin testing, allergen specific skin prick-test should be estimated in relation to positive control (histamine hydrochloride in the HEP system /histamine equivalent prick/) [1 -4]. The purpose of this study was to establish a recording system of skin sensitivity to allergen by using HEP method in our patients. MATERIAL AND METHODS The study was performed in 75 persons (49 females, 26 males, mean age 34.6 years) suffering from atopyc diseases (hay fever, allergic asthma or rhinoconjunctivitis) and susceptible to one of pollen allergens. Skin prick tests were performed and recorded as said before [2-6]. We used a house standardized (Torlak Institute) allergen solution of 5000 AU/mL (pollen of Dactylis glomerata, Lolium perennae, Phleum pratense), 7500 AU/mL (Phleum pratense) and 10 000 AU/mL (Phleum pratense) and histamine-hydrochloride solution (1 mg/mL and 10 mg/mL). Total and allergen specific serum IgE was made before the study by ELISA immunoassay (Pharmacia, Uppsala, EIA RAST Phadesim) in all selected persons and results were recorded in Phadebas RAST unit given by the manufacturer. According to the serum concentration of specific IgE, patients were classified into groups (low susceptibility, intermediate sensitivity and highly susceptible persons). Skin reactions were recorded according to histamine skin sensitivity (as reaction equal or larger in diameter than histamine papule). Additionally, measured allergenic and histamine wheal were sorted and frequency of positive tests was calculated. Skin testing was performed with the approval of the Ethic Committee of our Centre and with the written patients' consent. For statistical analysis we used x2 test, regression analysis and Kolmogar-Smirnov nonparametric test. Results for the confidence of 95% (p lt 0.05), were considered significant. RESULTS In a group of 30 persons, susceptible to Phleum pratense pollen (Table 1, Graph 1 and 2), it was found that the number of positive tests was equally distributed among groups; it was dependent on the allergen concentrations, and was higher when using H1 (p lt 0.01). When H10 was used as reference solution, only allergens of the highest concentration provided a significant number of positive tests (p lt 0.01). There was no difference among groups of patients depending on the concentration of used histamine solution. In all 75 persons, we estimated skin-prick test performed by allergen solution of 5000 AU/mL and compared it with HI reaction. It was calculated that the most frequent histamine papule diameter was 3 mm and this value was farther used as the end-diameter in HEP system. Patients were classified in groups on the basis of serum IgE concentrations (RAST). The estimation of criterion positivity revealed the highest significance by using criterion Ap gt Hp (p lt 0.001). At the same time, if the criterion Ap gt 2Hp was used we were sure that 99% of our patients were highly sensitive to allergen we tested. DISCUSSION In the study it was established that allergen concentration of 5000 AU/mL and histamine solution of 1 mg/mL are sufficient to estimate skin-prick test in the HEP system. We found that the end diameter of histamine-papula was 3 mm. This finding suggests the good utility of HEP system. In addition, it has been proven that absolute value of papula diameter is not a critical parameter for the estimation of positivity or discrimation among patients regarding their susceptibility to allergen. By this system we found that criterion Ap gt Hp, provides a significantly higher number of positive tests (p lt 0.001). The recommended criterion Ap gt Hp gives no discrimination among tested groups of patients, while using the criterion Ap gt 2Hp we diagnosed highly susceptible persons (p lt 0.01). The obtained results are in accordance with the recommendations of the EAACI Subcommittee, giving us the possibility of using a highly valide HEP system in our adult patients.Kod osoba s atopijskom kostitucijom, testiranje kože ubodom ('prik-test') i rastvorom alergena, može se ocenjivati primenom sistema HEP (Histamine Equivalent Prick), što znači reaktivnost kože na test s alergenom jednaka reaktivnosti kože na test s histaminom. Prethodno, međutim, treba utvrditi najmanje koncentracije rastvora histamina i alergena koje izazivaju reakciju kože pri testu ubodom kod najvećeg broja preosetljivih osoba. Zatim, utvrditi koja je najčešća veličina reaktivnosti kože na histamin kod preosetljivih osoba u odnosu na koju se ocenjuje test kože s rastvorom alergena. Kod 75 osoba s jednom od atopijskih bolesti i dokazanim antitelima IgE, specifičnim za polene u serumu (RAST, Pharmacia), testirali smo kožu (ubodom) alergenima polena trava. Rezultate testa smo ocenjivali prema reaktivnosti kože na test s histamiom. Od testiranih 75 osoba, kod 30 je izvršen test s tri različite koncentracije alergena (polena trave Phleum pratense) i dve različčite koncentracije rastvora histamina (od 1 mg/mL i 10 mg/mL). Utvrdili smo da je broj pozitivno ocenjenih rezultata testiranja kože srazmeran koncentraciji primenjenog rastvora alergena, a obrnuto srazmeran koncentraciji rastvora histamina. Najčešća veličina prečnika histaminske papule je 3 mm (rastvor histamina koncentracije 1 mg/mL) i ne zavisi od preosetljivosti bolesnika na alergen. Utvrđeno je da veličina reakcije kože (papula) izazvana alergenom (koncentracija 5000 AJ/mL), koja je veća od histaminske papule, ukazuje sa sigurnošću od 99,9 posto (r lt 0,001) da je ispitivana osoba preosetljiva. Ako je alergenska papula dvostruko veća od histaminske papule ili još veća, reč je o visokopreosetljivoj osobi (r lt 0,01). U graničnim slučajevima treba primeniti rastvor alergena od 7500 AJ/mL

Primary biliary cirrhosis: Report

Chronic non-suppurative destructive cholangitis, the so-called primary biliary cirrhosis, is characterised by changes, which occur in intrahepatic bile ducts in early stages and in hepatic parenchyma as the disease progresses. The disease gradually evolves into the full-blown picture of biliary cirrhosis. Primary biliary cirrhosis predominantly affects women between 35 and 60 years of age in all social classes and in all races. Our patient was a woman, old 78 years old who admitted for treatment of hypertrophie cardiomyopathy. During the routine laboratory exploration signs of cholestasis were noted: higher values of alkaline phosphatase and gamma glutamyl transferase, combined with low level of platelets, probably of autoimmune origin. Hypercholesterolaemia (7.8 mmol/L) associated with normal values of triglycerides was observed. The main criterion for establishing the diagnosis of primary biliary cirrhosis was the titer of antimito-chondrial antibodies in the serum, which was 1:640. At the same time, she had a urinary infection, caused by Escherichia coli, which confirmed possible relationship between primary biliary cirrhosis and occurence of some Gramm negative bacteria, reported elsewhere. On the other hand, biopsy of the liver was just an auxiliary method, serving for the confirmation of diagnosis. Ursodeoxycholic acid was used as the main drug in the therapy of primary biliary cirrhosis. This case of primary biliary cirrhosis is a worth report because of the comorbidity with cardiac symptoms, which were covering symptoms of hepatic disorder

Churg-Strauss syndrome

Churg-Strauss syndrome (CSS) is medium blood vessels vasculitis with predilection for lungs in patients with bronchial asthma, chronic eosinophilic pneumonia and positive ANCA in the sera in 55-67%. This is a case report of a 60 years old female patient with bronchial asthma, peripheral pulmonary infiltrations, blood eosinophilia, xerophtalmia, tachycardia, chronic rhino sinusitis, polyneuropathia and negative immunological tests: CIC (PEG), CRYO, ANA (IIF), RF (agglutination) and ANCA (IIF: pANCA and cANCA; ELISA: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G). Eosinophilic infiltrates in the tissues tested by skin and salivary gland biopsies were not found. The patient had fulfilled five clinical diagnostic criteria and responded well to immunosuppressive therapy, so this case could be classified as the ANCA negative angiitis and granulomatous of CSS type

The influence of a residual group in low-molecular-weight allergoids of Artemisia vulgaris pollen on their allergenicity, IgE- and IgG-binding properties

Background: Reaction of epsilon-amino groups of lysine with potassium cyanate, maleic, or succinic anhydride leads to allergoids of low molecular weight. No study has been performed to compare their properties and investigate the influence of a residual group on allergenicity and human IgE- and IgG-binding of these derivatives. Methods: Allergoids of a pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, and succinic and maleic anhydride. Biochemical properties were investigated by determination of amino groups, enzyme activity, isoelectric focusing IEF and SDS-PAGE. IgE- and IgG-binding was determined using immunoblots and ELISA inhibition. Allergenicity was investigated by skin prick tests (SPT) on a group of 52 patients, of which 6 were control subjects, 30 were patients with no previous immunotherapy (IT), and 16 were patients undergoing immunotherapy. Results: The same degree of amino-group modification (more than 85%), residual enzyme activity (less then 15%), IEF, and SDS-PAGE pattern were noted. In the immunoblots of IgE-binding, there was more pronounced reduction in the succinyl and maleyl derivatives than in the carbamyl one. IgG-binding was less affected by carbamylation than by acid anhydride modification. The SPT showed that the succinylated derivative had the most reduced allergenicity (98% showed a reduced wheal diameter when tested with the succinyl derivative, 87% with the maleyl allergoid, and 83% with the carbamyl allergoid). The most significant difference among allergoids could be seen in the group of patients with high skin reactivity (83% of patients showed no reaction to the succinyl derivative when compared to the value of 28% for the carbamyl derivative or 22% for the maleyl derivative). Conclusions: According to our results, all three modification procedures yielded allergoids with a similar extent of modification. No single biochemical parameter investigated in the study could predict the degree of reduced allergenicity in vivo. The most reduced allergenicity was seen in the succinyl derivative while the preservation of IgG binding epitopes was of the highest degree for the carbamyl derivative