Bonnie A. Whisman

Allergic Bipolaris sinusitis: Clinical and immunopathologic characteristics

Allergic Aspergillus sinusitis was first reported in 1983. We present the first three cases of allergic fungal sinusitis caused by the black fungus Bipolaris spicifera. The patients were young, atopic, and immunocompetent. All three patients demonstrated pansinusitis with nasal polyps and underwent multiple surgical procedures. Pathologic features included a characteristic mucoid exudate containing eosinophils, Charcot-Leyden crystals, and fungal hyphae. In two cases there was bony erosion revealed by computed tomography scan but no histologic evidence of direct fungal invasion into the mucosa or bony trabeculae. Immunologic features, including total eosinophil count, total serum IgE, immediate and late-phase skin response to B. spicifera, serum precipitins, and specific IgE and IgG to B. spicifera, are described. B. spicifera is a previously unrecognized cause of allergic fungal sinusitis that may be an underdiagnosed disorder. This diagnosis should be considered in atopic patients with nasal polyps and pansinusitis unresponsive to conventional medical therapy. Diagnostic criteria include characteristic histologic allergic mucin, culture identification of fungus, positive immediate cutaneous reactivity to fungal extract, positive serum precipitins, and elevated specific IgE and IgG antibodies.

Suppression of the late cutaneous response by immunotherapy

In a prospective, double-blind, placebo-controlled study, we examined the effect of mountain cedar (MC) immunotherapy on the MC-induced late cutaneous response (LCR). Fourteen MC-sensitive patients were intradermally skin tested before and after immunotherapy with MC extract. We measured the size of the wheal at 15 minutes and the area of tissue swelling at 6 hours. Patients were matched by the size of the LCR and started receiving either MC immunotherapy or placebo immunotherapy. MC-specific immunoglobulins (MC sIgG, MC sIgG1, MC sIgG4, and MC sIgE) were measured by ELISA. Symptom-medication scores (SMSs) were recorded on a daily basis during the MC season and tabulated at the end of the study. Comparison of the 14 paired patients revealed no significant differences between MC-treated and placebo-treated groups in preimmunotherapy MC sIgG1 and SIgG4. However, when MC immunotherapy was compared to placebo immunotherapy, patients receiving MC immunotherapy developed significantly higher MC sIgG1 (p less than 0.04) and MC sIgG4 (p less than 0.01) after immunotherapy. Patients receiving MC immunotherapy also demonstrated significantly greater suppression of the LCR after immunotherapy (p less than 0.005) with the postimmunotherapy LCR correlating significantly with both MC sIgG4 (rs = 0.715; p = 0.008) and cumulative dose of MC received (rs = 0.808; p = 0.004). MC sIgE was similar in both groups after immunotherapy. The reduction in SMSs in the MC-treated group did not reach significance, nor was there a correlation of SMSs with MC sIgE, sIgG, sIgG1, or sIgG4.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-DR4-associated nonresponsiveness to mountain-cedar allergen

We did human lymphocyte antigen (HLA)-DR and DQ typing on 37 subjects with mountain-cedar (MC) pollinosis as defined by history and a positive skin test. Of these 37 subjects, 31 were subdivided into 18 subjects with a single positive skin test (SPST) and 13 subjects with multiple positive skin tests (MPSTs). We also typed 51 subjects without MC sensitivity or atopy as defined by history and negative skin tests to a battery of aeroallergens. We also typed 116 subjects in whom MC sensitivity had not been determined. Total IgE, Mc-specific immunoglobulin E (sIgE), and MC-sIgE binding bands by immunoblot were also determined on the subjects with SPSTs and MPSTs. No significant differences were found between the subjects with SPSTs and MPSTs for HLA type, total IgE, MC sIgE, or bands bound by MC sIgE by immunoblot. There was a strong negative relationship between HLA-DR4 and subjects with MC pollinosis; chi-square, 14.857; p = 0.0096; and odds ratio, 0.139. These findings suggest that there is no difference in genetic immunoregulation between subjects with SPSTs and MPSTs but that the presence of the DR4 gene product is associated with a decreased risk of an IgE response to MC and protection from MC pollenosis.

The relationships between late cutaneous responses and specific antibody responses with outcome of immunotherapy for seasonal allergic rhinitis

Mountain cedar (MC) (Juniperus ashei) causes a significant and isolated seasonal allergic rhinitis in south-central Texas during the winter months. Retrospective studies have indicated that patients segregate into two categories based on skin test reactions: single positive skin test to MC only and multiple positive skin tests. These two populations differed in age, personal and family history of atopy, levels of both IgE and total MC-specific IgE (sIgE), and symptomatology. It has been speculated that the subjects with only a single positive skin test may actually be nonatopic and develop an IgE response to MC because of some peculiarity of the antigen. In a prospective, randomized, controlled trial, we tested the efficacy of immunotherapy (IT) with MC extract in 51 subjects, 12 single positive skin tests and 39 multiple positive skin tests, to determine if these differences indeed exist and if IT is equally effective in both groups. We failed to demonstrate significant differences in age, sex, MC sIgE, total IgE, initial immediate cutaneous response, initial late cutaneous response, or personal or family history of atopy. IT was equally effective in both groups of subjects with no significant differences noted in response to MC sIgE, MC sIgG1, MC sIgG4, or with suppression of the late cutaneous response. In addition, we found that suppression of the late cutaneous response correlated significantly with cumulative dose of MC extract, postseasonal level of MC sIgG1 and MC sIgG4, and improvement of symptomatology. Suppression of the late cutaneous response may be a clinically useful parameter to follow in monitoring patients during IT. Caution is advised because this procedure may result in systemic reactions.

The effect of immunotherapy on the cutaneous late phase response to antigen

BACKGROUND This study used the skin chamber model to evaluate prospectively the effect of immunotherapy (IT) on the cutaneous early and late phase response (LPR) to epicutaneous antigen challenge. METHODS Nine subjects with allergic rhinitis were studied at three time points: before starting IT, after 3 months of IT, and after 6 months of IT. Skin chamber histamine content was measured hourly for 12 hours, and cell counts performed hourly during hours 6 to 12. An intradermal skin test was placed, and the reaction was measured hourly for 12 hours. Skin biopsy specimens were obtained 8 hours after intradermal placement and evaluated for cellular infiltrate and major basic protein deposition. Serum antigen-specific IgG and IgE levels were measured at each time point to confirm physiologic effect of IT. RESULTS Six months of IT significantly (p < 0.05) decreased both early and LPR skin test reactivity and skin chamber histamine for hours 1 to 3, 4 to 6, and 9 to 12. Skin chamber LPR cellular influx decreased significantly (p < 0.05) for neutrophils only. Decrease in LPR histamine after 6 months of IT was significantly correlated with both decrease in mononuclear cells (R2 = 0.817, p = 0.002) and decrease in neutrophils (R2 = 0.813, p = 0.009). Also significantly correlated were decrease in LPR skin test reactivity, with percent change in skin chamber mononuclear cells (R2 = 0.800, p = 0.009) and decrease in early skin test reactivity (R2 = 0.675, p = 0.01). Biopsy specimens showed no consistent change in either dermal cellular infiltrate or deposition of major basic protein. CONCLUSION IT significantly attenuates cutaneous histamine release and skin test reactivity and is accompanied by a decrease in skin chamber LPR neutrophil influx without significantly altering the dermal infiltrate at 8 hours.

Occupational asthma in a seafood restaurant worker: cross-reactivity of shrimp and scallops.

BACKGROUND The case of a restaurant seafood handler with IgE-mediated occupational asthma and contact urticaria to both shrimp and scallops is presented. Independent hypersensitivity to both seafoods was demonstrated by skin testing, inhalation challenge, and immunoassays. Bronchial challenge with extracts of shrimp and scallops each produced an isolated early asthmatic response. OBJECTIVE To investigate cross-reactivity of shrimp (phylum Arthropoda) and scallops (phylum Mollusca). METHODS Shrimp and scallops extracts were prepared from raw seafood and seafood boiling water. Distillate was collected over boiling shrimp. Specific-IgE ELISA and immunoblot assays were accomplished for shrimp and scallops extracts inhibited by each other. RESULTS SDS-PAGE of shrimp boiling water and distillate showed similar protein patterns. SDS-PAGE and immunoblot demonstrated prominent protein allergens for shrimp boiling water at 21, 26, and 35 to 38 kD; for raw shrimp at 26 and 38 kD; for scallops boiling water at 20, 35 to 39 and 42 kD; and for raw scallops at 36 to 38 and 41 kD. Significant inhibition of the 35 to 39-kD band of each shrimp and scallops extract was demonstrated on immunoblot inhibition by seafood of the opposite phylum. IgE ELISA inhibition demonstrated 17% to 28% inhibition of shrimp by scallops and scallops by shrimp. CONCLUSIONS Seafood allergens aerosolized during food preparation are a source of potential respiratory and contact allergens. Shrimp and scallops demonstrate significant cross-reactivity. These findings confirm that the primary cross-reactive allergen of shrimp (phylum Arthropoda) and scallops (phylum Mollusca) is the 35 to 39 kD heat-stable allergen, previously demonstrated to be muscle topomyosin in both phyla.

Cross-reactivity among conifer pollens

BACKGROUND There are increasing reports of Cupressaceae pollinosis from various geographic areas. Cross-reactivity among a limited number of species within the Cupressaceae family has been suggested. Juniperus ashei (mountain cedar) is the leading cause of respiratory allergy in South Texas. OBJECTIVE This study examines in vivo and in vitro cross-reactivity among 12 Cupressaceae species, one Taxodiaceae species, one Pinaceae species, and an angiosperm. METHODS Cross-reactivity among pollen extracts of mountain cedar (MC) and the other 14 trees was investigated by: (1) prick skin testing of each tree pollen extract in ten patients with MC pollinosis. (2) Ouchterlony gel immunodiffusion employing rabbit antisera to MC. (3) IgE immunoblotting using high-titer MC pooled human sera, and immunoblot inhibition after pre-incubation with MC protein. (4) Monoclonal antibody immunoblotting using a murine monoclonal antibody with strong affinity for the gp40 major allergen of MC. RESULTS Positive skin wheal-and-flare responses occurred to all 12 Cupressaceae and Japanese cedar (the Taxodiaceae), but not to the Pinaceae or the angiosperm. In Ouchterlony gels, lines of identity or partial identity formed between MC and all pollens except the Pinaceae and the angiosperm. Immunoblots demonstrated IgE binding to the 40 to 42 kD protein in each Cupressaceae, and to a parallel band in Japanese cedar at 43 to 46 kD. Immunoblot inhibition by MC pollen was complete for all trees. The monoclonal bound both the 40 to 42 kD protein in 11 of 12 Cupressaceae species and the 46 kD band in Japanese cedar, but bound no protein bands in the Pinaceae or the angiosperm. CONCLUSION Pollen proteins of the 12 Cupressaceae (including MC) and the Taxodiaceae (Japanese cedar) are extensively cross-reactive. In particular, the MC major allergen, gp40, is cross-reactive with 40 to 42 kD proteins of the other Cupressaceae and with the Japanese cedar major allergen of 46 kD. Component-based immunotherapy may someday allow a standard treatment for both Juniper-allergic and C. japonica-allergic patients.

Safety of chitosan bandages in shellfish allergic patients.

BACKGROUND In 2005, the Office of the Surgeon General mandated that every soldier carry a HemCon bandage. Made from chitosan, a polysaccharide derived from shrimp shells, this bandage effectively stops bleeding. There are no studies reporting the safety of this bandage in shellfish allergic patients. METHODS Patients who reported shellfish allergy were recruited. Initial assessment included a detailed history, IgE skin prick testing (SPT), and serum testing to shellfish allergens. Participants who demonstrated specific shellfish IgE underwent a bandage challenge. RESULTS Nineteen participants were enrolled; 10 completed the study. Seven (70%) were male and the average age was 44.8 + 10 years. Nine (90%) reported a shrimp allergy history and five (50%) reported multiple shellfish allergies. All participants completing the study had positive SPT and serum IgE testing to at least one shellfish; eight (80%) had shrimp positive SPT and ten (100%) demonstrated shrimp-specific IgE. No participant had a positive SPT to chitosan powder or experienced an adverse reaction during bandage challenges. No protein bands were visualized during gel electrophoresis analysis of chitosan powder. CONCLUSION All participants tolerated the HemCon bandage without reaction. This is the first study demonstrating the safety of this bandage in shellfish allergic subjects.

Mountain cedar pollinosis: can it occur in non-atopics?

In 1984 Ramirez postulated the existance of two subgroups of patients with Mountain Cedar (MC) pollinosis. One subgroup had a single positive skin test (SPST) to MC only, lacked other atopic diseases, and required prolonged MC exposure to develop the disease. The second subgroup had multiple positive skin tests (MPST) in addition to MC, had other atopic diseases, and developed clinical symptoms after a shorter period of MC exposure. To validate these findings, and to explore the clinical and immunologic differences between these two subgroups, 13 SPST and nine MPST patients underwent immunotherapy with MC pollen extract. Six SPST and ten non-allergic controls did not receive immunotherapy. MC specific IgE (sIgE), MC sIgG, and MC sIgG subclasses were measured by ELISA pre and intra season. Symptom Medication Score (SMS) were measured during the MC season. SPST patients had a significantly lower baseline sIgE than MPST patients, 2.1 IU/ml versus 22.3 IU/ml, p = 0.023, and were also older than MPST patients, 52.4 versus 32.2 years, p less than 0.001. Baseline MC sIgG and MC sIgG subclass antibody levels were similar in both patient groups. SMS were lower in treated SPST patients compared to treated MPST patients, p less than 0.01, but in vitro responses to immunotherapy were not significantly different between the two groups. MC sIgE, MC sIgG, MC sIgG1 and MC sIgG4 rose in both treated groups. MC sIgG1 (but not MC sIgG4) rose during the MC season in both non-immunotherapy groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-reactivity between coconut and hazelnut proteins in a patient with coconut anaphylaxis

BACKGROUND The medical literature reports few cases of severe allergic reactions to coconut. We encountered a patient with anaphylaxis to coconut and oral symptoms to tree nuts. OBJECTIVE To identify cross-reactive antibodies between coconut and other tree nuts. METHODS We performed commercial radioallergosorbent tests to coconut and various tree nuts using the patients serum. Skin prick testing was performed to fresh coconut and commercial extracts of coconut, almond, Brazil nut, cashew, pecan, walnut, and hazelnut. Proteins from fresh coconut, commercial coconut extract, and tree nuts were extracted. Immunoblot and inhibition assays were performed to evaluate for cross-reacting IgE antibodies between similar-sized allergens in coconut and hazelnut. RESULTS Positive skin test results occurred to the coconut and multiple tree nut extracts. In vitro serum specific IgE was present for coconut, hazelnut, Brazil nut, and cashew. Immunoblots demonstrated IgE binding to 35- and 50-kDa protein bands in the coconut and hazelnut extracts. Inhibition assays using coconut demonstrated complete inhibition of hazelnut specific IgE, but inhibition assays using hazelnut showed only partial inhibition of coconut specific IgE. CONCLUSIONS Our study demonstrates the presence of cross-reactive allergens between hazelnut (a tree nut) and coconut (a distantly related palm family member). Because there are many potentially cross-reactive allergens among the tree nuts, we recommend patients with coconut hypersensitivity be investigated for further tree nut allergies.