Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis

BACKGROUND: Few cases of allergic fungal sinusitis have been systematically evaluated to conclusively confirm working clinical, histopathologic, and serologic diagnostic criteria. OBJECTIVES: The objective of this study was to describe 67 consecutive cases of allergic fungal sinusitis, the largest number of cases yet published. METHODS: Cases from 1 practice over 8 years were evaluated with a consistent protocol, including skin testing, serum chemistries and serologies, and surgical specimen analysis. RESULTS: All patients were atopic (100 %) and had nasal polyposis (100%). They tended to be young (33.3+/-13.1 years, mean +/-SEM), immunocompetent (92 %; remaining 8 % with low quantitative immunoglobulin but normal function), have slight female preponderance (58%), have a history of hypertrophic rhinosinusitis (100%), report nasal cast production (75%), and have developed their disease in the southwestern United States. Bipolaris spicifera was the most prevalent fungus involved (67%). Total serum IgE (mean 668 IU/mL) and fungal-specific IgG were generally elevated, whereas fungal-specific precipitins and specific IgE were generally negative despite positive fungal-specific immediate hypersensitivity skin tests. CONCLUSIONS: Patients with allergic fungal sinusitis tend to have elevated total serum IgE and fungal-specific IgG at diagnosis but not fungal-specific IgE or precipitins. Histopathologic criteria for allergic fungal sinusitis diagnosis are discussed. The southwestern United States appears to be a "hot spot" for the disease, particularly caused by B spicifera.     

Serum eosinophil cationic protein in infants during first wheezing episode

We measured serum ECP levels in infants during first wheezing episode. Serum ECP in these infants are significantly higher than in control infants, although much higher in children with asthma. Serum ECP in these infants with high serum IgE and/or positive RAST score are higher than in infants with normal serum IgE and negative RAST score. In children with bronchial asthma serum ECP is correlated with peripheral eosinophil counts, but in infants during first wheezing episode serum ECP is often elevated not associated with increased peripheral eosinophil counts. These suggest that activated eosinophils could be responsible for bronchoconstriction in wheezing patients with atopic diathesis even in very early phase and that these eosinophilic inflammations could contribute to formation of increased airway reactivity and bronchial asthma.     

Immunologic basis of chronic allergic diseases: clinical messages from the laboratory bench

During the past decade there have been significant advances in our understanding of the mechanisms underlying allergic responses. Immediate hypersensitivity reactions are mediated primarily by mast cells in an IgE-dependent manner. After the local release of various mediators, proinflammatory cytokines, and chemokines, there is a cell-mediated response that is dominated by eosinophils and T lymphocytes. The majority of T cells in early allergic reactions are memory T cells secreting helper type 2 (TH2)-like cytokines, i.e. IL-4, IL-5, and IL-13, but not interferon-gamma. These cytokines regulate IgE synthesis and promote eosinophil differentiation and cell survival, thus contributing to allergic inflammatory responses. Failure to control immune activation early in the course of allergic inflammation may blunt the response to glucocorticoid therapy and contribute to long-term morbidity of disease. The identification of key cells and cytokines involved in the initiation and maintenance of allergic inflammation is likely to become an important therapeutic target in the future management of this important group of diseases.     

Clinical study of children with nasal allergy

Possible factors influencing nasal allergy in children were studied using a questionnaire and allergic examination including eosinophil count of nasal discharge, IgE RAST score to house dust and provocation test. We investigated three groups of children according to the results of allergic examinations. The negative group, the equivocal group and the definite group, respectively, consisted of 40, 49 and 107 children. We found the prediction value of definite group with eosinophil count of nasal discharge, IgE-RAST score and provocation test to house dust were respectively 77.0, 89.2 and 78.1%. Bottle feeding and history of asthma bronchiale occurred more frequently in the definite group. These observations provide epidemiologic and clinical bases for further investigations of children with nasal allergy.     

Quantitative differences between the optic nerve head and peripapillary retina in low-tension and high-tension primary open-angle glaucoma

Anti-IgE antibodies directed against the Fc epsilon RI-binding region on IgE inhibit binding of IgE to IgE receptors without inducing mediator release from IgE sensitized cells. In mice these antibodies selectively reduce serum IgE, inhibit antigen induced skin reactions, cytokine production by lung Th2 cells, and pulmonary eosinophil infiltration. Clinical trials in humans reveal that such antibodies are well tolerated and reduce rhinitis symptoms and early and late phase bronchoconstriction responses. Thus interruption of the allergic cascade at the IgE antibody level with non-anaphylactogenic anti-IgE antibodies is effective and represents an attractive intervention for the treatment of allergic diseases.     

Anti-schistosomal IgE and its relation to gastrointestinal allergy in breast-fed infants of Schistosoma mansoni infected mothers

To study the relationship between presence of gastrointestinal allergic manifestations in breast-fed infants and presence of IgE against Schistosoma mansoni antigens, sixty breast-fed infants of S. mansoni infected mothers were selected. Of them, thirty infants were suffering from manifestations of gastrointestinal allergy (patients) and the other thirty were not suffering from such manifestations (controls). Levels of IgE against S. mansoni adult worm antigen (AWA), soluble egg antigen (SEA) and cercarial antigen (CA) were determined, by ELISA, in sera of these infants. There was significant association between presence of allergic manifestations and presence of IgE against AWA (P = 0.018), SEA (P < 0.001) and CA (P = 0.002). Also, concentration of IgE against AWA was significantly higher in patients group than the control group (P = 0.024). IgE against AWA showed significant negative correlation with haemoglobin concentration (P = 0.009) and serum albumin level (P = 021) and significant positive correlation with absolute eosinophilic count (P = 0.005). Also, IgE against CA showed significant negative correlation with haemoglobin concentration (p = 0.047) and serum albumin level (0 = 0.036). It was concluded that gastrointestinal allergy in breast-fed infants of S. mansoni infected mothers may be due to hypersensitivity of Schistosoma mansoni antigens present in mothers' milk. Schistosoma mansoni should be investigated and treated in mothers from endemic localities when their breast-fed infants are suffering from manifestations suggestive of gastrointestinal allergy.     

Changes in allergic inflammation associated with successful immunotherapy

Allergen injection immunotherapy in selected patients is effective and has wide ranging anti-inflammatory effects. These include modulation of serum (and presumably local) IgE and IgG antibody responses, a reduction in mast cell numbers in the target organ and inhibition of mast cell mediator release. Tissue eosinophilia and eosinophil activation are also reduced. We have compared and contrasted the effects of immunotherapy and topical corticosteroids on allergen-induced late nasal responses. Both treatments inhibit allergen-induced late nasal symptoms and associated CD4+ T cell and eosinophil recruitment, possibly by distinct mechanisms. Whereas topical corticosteroids may act by suppressing cytokine mRNA expression for Th2-type cytokines, particularly interleukin-4, immunotherapy induces a local Th1 response with an increase in interferon-gamma.     

Comparison of basophil histamine release, eosinophil cationic protein and non-specific airway responsiveness between mite-sensitive asthmatic and non-asthmatic children and non-allergic controls

To understand the relevance of allergy to the development of asthma in children, we examined basophil histamine release (HR) with Df antigen, blood eosinophil counts, serum eosinophil cationic protein (ECP) levels, and bronchial responsiveness to methacholine (PC20) in three groups of children, including 36 asthmatics with high RAST titre for Df (group 1), 36 non-asthmatics with similarly high RAST titre for Df (group 2) and 21 non-asthmatics with negative RAST titre for Df (group 3). The amount of Df antigen inducing 50% HR from basophils did not vary significantly between group 1 and 2 (P > 0.05), while none of the cells responded to higher concentrations of Df in group 3. The mean number of blood eosinophils and level of serum ECP were highest in group 1, and lowest in group 3, with group 2 being intermediate, and the differences were significant between all three groups (P < 0.01). The mean PC20 value was the lowest in group 1, intermediate in group 2, and the highest in group 3, and the differences were significant between all three groups (P < 0.01). While correlation studies showed that PC20 values of group 2 subjects significantly correlated with their eosinophil numbers (r = -0.48, P < 0.01) and ECP levels (r = -0.49, P < 0.01), such correlations were not found in group 1 subjects. These results suggest that the degree of the eosinophilic inflammation caused by the allergic reaction to mites is an important factor in determining the clinical expression of asthma in atopic subjects.     

Laboratory diagnosis of allergic inflammation

Monitoring of allergic inflammation includes direct examination of biopsy specimens from mucosa and epithelium, and indirect study by sputum, bronchoalveolar and nasal lavage fluid and peripheral blood. Although, some of these detection assays are not applicable to clinical use, it is now possible to measure a number of inflammatory mediators released from cells participating in allergic disease. The release of performed histamine from peripheral blood basophils challenged with specific antigen remains a valuable in vitro correlate of immediate hypersensitivity reactions. However, other mediators such as LTC4 and IL-4 are also generated by basophils upon IgE dependent activation. Tryptase and PGD2 are released from mast cells upon activation. Eosinophils contain in their granules proteins that cause damage to the bronchial epithelium: MBP and ECP. It is possible to measure soluble markers from other cells (T cells, macrophages, platelets, endothelial cells) involved in allergic inflammation. Detection of mediators have produced data that have significantly added to our understanding of the mechanisms and allowed better pharmacological control of allergic inflammation.     

Codfish allergy in adults. Specific tests for IgE and histamine release vs double-blind, placebo-controlled challenges

BACKGROUND: At present, several in vitro tests for immunoglobulin E (IgE)-mediated food allergy are available. An estimation of the diagnostic accuracy of the various tests used in predicting clinical sensitivity to codfish in a well-characterized allergic material is necessary. OBJECTIVES: To compare the diagnostic value of four specific IgE tests, and histamine release from basophils (HR) in identifying clinical type I allergy to codfish. As a true diagnosis, double-blind, placebo-controlled food challenges (DBPCFC) were employed. METHODS: Eight clinically codfish-allergic adult patients were investigated together with 30 codfish-tolerant control subjects for evidence of codfish-specific reactivity by Phadebas RAST (PHA), Pharmacia CAP System RAST (CAP), Magic Lite (ML) and HR. To characterize the diagnostic properties of a freshly prepared raw codfish extract, experiments were conducted employing an in-house radioallergosorbent test (RAST), the Maxisorp RAST (MAXI) and HR. Finally, protein profile and IgE-reacting allergens were detected by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. RESULTS: The sensitivities of HR with commercial extract and the three commercially available specific IgE analyses were 0.83 and 1.00 respectively. Specificities were 1.00 (HR) and 0.87-1.00 (specific IgE tests). Freshly prepared codfish extracts improved the sensitivity of HR. SDS-PAGE revealed approximately 29 bands (< 14.3-200 kDa) including a band of 12-13 kDa, and in immunoblotting 18 sera identified 17 IgE-binding bands. The protein migrating at 12-13 kDa was identified in the fresh codfish extract tested with sera from all clinical codfish allergics, while no significant reaction was seen in the control subjects. CONCLUSION: Based on the small number of adult patients included in our study, the in vitro assays with commercial and fresh extracts have high sensitivity and are acceptable for screening for codfish allergy. Specificity of Phadebas, CAP, and our in-house RAST was less than unity, whereas ML and strong binding of IgE to a 12-13 kDa protein completely matches DBPCFC results, and thus seems sufficient for establishing the diagnosis.     

In vivo and vitro in diagnosis of latex allergy at Groote Schuur Hospital

OBJECTIVE: The aim of this study was to evaluate the diagnostic utility of skin-prick tests, radio-allergosorbent tests (CAP RASTs), basophil histamine release, sulphidoleukotriene release and Western blotting in the diagnosis of latex allergy at Groote Schuur Hospital. DESIGN: Patients with a history suggesting latex hypersensitivity were recruited via staff health and allergy clinics at Groote Schuur Hospital. A clinical assessment was followed by laboratory investigation and skin-prick testing. A control group consisted of laboratory and hospital staff who had regular latex exposure but were asymptomatic. SETTING: Hospital-based cohort at Groote Schuur Hospital. PARTICIPANTS: Twenty-three patients with suspected latex allergy; 10 control subjects exposed to, but not clinically sensitive to, latex. MAIN OUTCOME: Skin-prick testing was more sensitive than in vitro diagnostic tests for the diagnosis of latex allergy. RESULTS: Eighteen of 21 (85.7%) of the patients tested had a positive skin-prick test with a commercial latex solution (Allerbioprick) and 17/21 (80%) tested skin-prick-positive with an in-house glove extract. CAP RASTs were positive in 13/23 patients (56.5%), sulphidoleukotriene release was positive in 10/23 (43%), histamine release assay was positive in 10/23 (45%) and Western blots were positive in 8/23 (34.7%). All patients with only urticaria were Western blot-negative and CAP RAST-negative, suggesting that they have very little circulating latex-specific IgE. Although patients who were Western blot-positive tended to have multi-organ involvement, both patients with anaphylaxis were Western blot-negative. CONCLUSION: Latex allergy is a significant clinical problem at Groote Schuur Hospital. Titrated skin-prick testing performed in a controlled environment can safely and reliably confirm the diagnosis in patients who do not give a history of anaphylaxis. The CAP RAST was the most sensitive in vitro test for latex allergy locally available, but lacks sensitivity in patients presenting with urticaria only.     

Update on genetics of Huntington''s disease: availability of direct and accurate predictive test

Recently, human leukocyte elastase has been detected in human eosinophils. Reinvestigating these findings, 2.5 pg active human leukocyte elastase (E.C. 3.4.21.37) were found per neutrophil isolated from peripheral blood, whereas the elastase activity of eosinophil preparations was linearly correlated with the content of contaminating neutrophils. Also spontaneous or stimulated release of active elastase was absent in eosinophils. By immunohistochemistry no elastase immunoreactivity could be demonstrated in human eosinophils. Therefore, we conclude that human eosinophils do not contain considerable amounts of human leukocyte elastase.     

Mast cells, neutrophils, and eosinophils in prurigo nodularis

BACKGROUND AND DESIGN: Prurigo nodularis is a disease of unknown cause. To characterize the involvement of mast cells, neutrophils, and eosinophils in lesional tissue, we analyzed seven skin biopsy specimens by an indirect immunofluorescence technique for localization of mast cell tryptase, neutrophil elastase, and eosinophil granule major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin. RESULTS: Mast cells were detected in all of the specimens, with prominent numbers of mast cells in three specimens; there was minimal or no extracellular deposition of tryptase in any of the tissues. Neutrophil infiltration was observed in all specimens, but few cells were observed in four; extracellular elastase was minimal or absent in all but one specimen in which prominent dermal elastase deposition was found. Scanty eosinophil infiltration was present in all specimens; however, extracellular deposition of the eosinophil granule proteins including major basic protein, eosinophil-derived neurotoxin, and eosinophil cationic protein was present in all but one specimen and striking deposition of at least one eosinophil granule protein was present in six of the seven specimens. CONCLUSIONS: These studies suggest that mast cell numbers are increased in prurigo nodularis and that eosinophil degranulation as evidenced by striking extracellular deposition of granule proteins is prominent in lesions. In contrast, extracellular deposition of mast cell and neutrophil proteins is absent. The distinctive proteins of the eosinophil granule have potent effects on tissues; the toxicity of these proteins and their deposition in lesional tissue suggest a pathogenic role for the eosinophil in prurigo nodularis.     

Atopic allergy and immunoglobulins in children with adenoids and recurrent otitis media

From 274 adenoidectomized children 1-16 years of age two groups were selected: children with a history of recurrent otitis media and/or otosalpingitis (middle ear effusion) and those in which nasal obstruction was the main symptom. In all, 154 children were subjected to an allergy investigation including history, skin tests, eye tests, determination of IgE and RAST, blood eosinophils and immunoglobulins G, A and M. No increased incidence of immunoglobulin deficiency was found in either group in comparison with unselected children. A family history of atopic disease and/or otitis media was highly overrepresented, especially in the children with recurrent otitis media as the reason for the adenoidectomy. Atopic diseases had occurred in 24.4% of the children. Furthermore, in both groups there was a high incidence of positive skin and eye tests. An increased incidence of eosinophila, positive RAST tests and elevated IgE levels were also found. In all, 39.6% of the children had two or more laboratory findings characteristic of the atopic state but no significant difference was found between the two groups. Possible connections between atopic allergy and recurrent otitis media are discussed.     

Management of treatment-resistant schizophrenia with olanzapine

BACKGROUND: The term oral allergy syndrome (OAS) describes an IgE-mediated reaction that takes place minutes after ingestion of some food to which the organism is previously sensitised. The clinical manifestations are typically localized to the mouth and throat. Oral allergy syndrome is commonly elicited by fresh fruits and vegetables, especially in subjects with hypersensitivity to pollens. METHODS: We report a patient with OAS following intake of chicken meat. We performed (1) skin prick test to chicken meat, egg, milk, and wheat and to common inhalants, (2) determination of serum specific IgE, (3) histamine release test, and (4) in vitro antigen-specific production of sulphidoleukotrienes and challenge test with chicken meat. RESULTS: Skin prick test was positive only for chicken meat. The patient had serum specific IgE, positive histamine release test, and specific production of sulphidoleukotrienes to chicken meat. We confirmed these findings by means of the challenge test.     

Allergy to pistachio: crossreactivity between pistachio nut and other Anacardiaceae

BACKGROUND: Anaphylaxis against Anacardiaceae nuts is uncommon and the allergens involved still poorly characterized. For this reason two patients with allergy towards pistachio nut (a member of the Anacardiaceae family) have been studied. OBJECTIVE: Identification of immunoallergens present in pistachio nut and analysis of crossreactive antigens in other members of the same plant family, specifically cashew and mango. METHODS: Presence of specific IgE for pistachio and cashew nut and for mango seed and pulp was determined by skin tests and radioallergosorbent assay (RAST). The allergenic profile of pistachio and cashew was analyzed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting. Crossreactivity between pistachio and the other Anacardiaceae was studied by RAST inhibition. RESULTS: Skin tests were positive for pistachio and cashew in the two children and for mango seed in one. RAST was positive for pistachio and cashew in both patients. On immunoblotting, serum from both patients recognized several pistachio and cashew allergens with a molecular weight ranging from < 14.2-70 kDa. RAST inhibition demonstrated common antigenic determinants between pistachio and cashew nut. Crossreactivity was also found between pistachio nut and mango seed but not with mango pulp. CONCLUSION: Pistachio nut contains several protein allergens able to trigger type I hypersensitivity reactions. These allergens can be found also in cashew nut and mango seed but not in mango pulp.     

Effects of PAF, FMLP and opsonized zymosan on the release of ECP, elastase and superoxide from human granulocytes

Platelet-activating factor (PAF) is a potent chemoattractant for human eosinophils and neutrophils and causes eosinophil and neutrophil recruitment into animal airways. Since eosinophils and eosinophil cationic proteins are thought to play an important role in the pathophysiology of asthma, we have examined the hypothesis that PAF may also stimulate eosinophil cationic protein (ECP) release from human granulocytes. Granulocytes (93% neutrophils, 3% eosinophils) were isolated from the blood of normal volunteers, using metrizamide density gradients, and stimulated in vitro with PAF, L-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) or opsonized zymosan (OPZ). Superoxide generation was measured colorimetrically, granulocyte degranulation by a fluorimetric assay for elastase, and eosinophil activation by specific radioimmunoassay (RIA) for ECP. Granulocyte chemotaxis was also measured. Whilst both PAF and FMLP were potent chemoattractants for human mixed granulocytes (concentrations producing half the maximal effect (EC50s) ca 10 nM), PAF at concentrations below 10 microM was a poor stimulus to superoxide generation, elastase release or ECP release from the same cell population. In contrast, FMLP was a potent stimulus to both superoxide generation (EC50 48 nM) and ECP (EC50 ca 100 nM) and elastase release (EC50 ca 1 microM). OPZ was a potent stimulus to superoxide generation, but was a poor stimulus to ECP or elastase release. Thus, although PAF is a potent chemoattractant for human granulocytes, our results suggest that it alone may not stimulate their subsequent activation and release of cytotoxic products.     

Vernal keratoconjunctivitis in the child. Clinical and complementary study apropos of 22 cases

PURPOSE: Vernal kératoconjunctivitis was studied in a population of 22 children aged 3 to 14 years and followed up in an allergy and ophthalmology outpatient clinic. The role of allergy and the severity of inflammation where assessed by a systematic exploration, which combined a detailed allergy evaluation and blood and lacrimal sampling. MATERIALS AND METHODS: Allergy criteria chosen and recorded in 9 cases are: an increase of total IgE over the higher limit for the age, a positive skin prick test to one allergen, a positive serum specific IgE dosage (> 0.35 IU/mL) of specific IgE. Conjunctival allergy was present in 6 of the 9 children with a positive allergenic provocation test, or with a high local production of total IgE and a lacrimal/serum eosinophilic cationic protein ratio greater than one. RESULTS: Criteria used for supporting the IgE mediated hypersensitivity diagnosis are discussed: they have to be very strict to eliminate false positive results. Allergen involvement can only be evidenced by a specific provocation test. When evidenced as described, limbic or palpebral conjunctivitis had the same frequency. Lacrimal ICAM 1 levels seemed to be higher (p < 0.05) in the severe limbal forms (24.7 +/- 3 pg/mL) than in the palpebral ones (8.1 +/- 6.5 pg/mL). Interpretation of biological parameters evidencing conjunctival inflammation is more difficult. CONCLUSION: Allergic involvement in child vernal keratoconjunctivitis can only be assessed through a detailed evaluation, leading to a specialised ophthalmic and allergic management. A specific treatment can then be established, based on allergen eviction and possibly on specific immunotherapy (5 cases). H1 antihistamin treatments are dedicated only to children with a positive allergic evaluation.     

Immediate allergic reactions to amoxicillin

A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.