Conjunctival Intraepithelial Lymphocytes, Lacrimal Cytokines and Ocular Commensal Microbiota: Analysis of the Three Main Players in Allergic Conjunctivitis.

Conjunctival intraepithelial lymphocytes, tear soluble molecules and commensal microbiota have important roles in the ocular mucosal immune response in healthy and diseased subjects. For the purpose of this study, the cellular and microbial populations of the conjunctiva and the lacrimal soluble molecules were analyzed to find the main biomarkers in allergic conjunctivitis. A total of 35 healthy subjects, 28 subjects with seasonal allergic conjunctivitis and 32 subjects with perennial allergic conjunctivitis were recruited to obtain peripheral blood, conjunctival brush cytology, tear fluid and microbiota samples. Flow cytometry for lymphocytes, multiplex bead assays for cytokines and high-throughput DNA sequencing for microbiome analysis were used. For perennial allergic conjunctivitis, an increased proportion of Th2 and NKT lymphocytes was found, while CD3+TCRγδ+ lymphocytes and double negative MAIT cells were decreased. In contrast, seasonal allergic conjunctivitis was distinguished by an increase in Th17 and Th22 cell proportions, while the Th1 cell proportion decreased. Among tear fluid, the vast majority of pro-inflammatory cytokines (especially Th2 and Th17 cytokines) in perennial allergies and MMP-9 together with IgA in seasonal allergies were increased. In contrast, TGF-ß2 was decreased in both forms of conjunctivitis. Finally, fungal (Malassezia species) and bacterial (Kocuria and Propionobacterium acnes species) colonization were observed in the perennial allergic conjunctivitis group. These results provide the basis for the development of a disease profile for perennial allergic conjunctivitis and open the door to new therapeutic and diagnostic strategies.

Occupational hypersensitivity pneumonitis caused by fossil-containing rocks.

AIMS: We present a hypersensitivity immune response to inhalation of antigens from fossil soils frequently used in tile manufacture. We found that the soil polished by a worker affected by pneumonitis was a paleosol containing bivalves from the cretaceous period called Hippurites. METHODS: We made a diagnostic study for pneumonitis (analysis, microbiology, radiology, high-resolution CT, bronchoalveolar lavage, pulmonary biopsy. A biochemical study of the polishing materials used (magnesium hexafluorosilicate crystallizer), steel spoilage, washing liquid and Bilbao red limestone) after scraping of the same. Allergy study included skin tests with extracts from fossil soils, determination of IgG and IgE to mollusks, IgE-immunodetection with soil extracts with the patient's serum and non-atopic controls. Histology was made using scanning electron microscopy of the lung biopsy and the fossil soil to determine the presence of remains of mollusks, fungi, pollen or other fossil elements. RESULTS: SDS-PAGE IgE Immunoblotting assay detecting IgE binding in soil extract between 66 and 35 kDa. Likewise, IgE-Immunblotting assay with extracts from bivalve mollusks (razor shell, mussel and scallop) and gastropod (sea snail), detecting IgE binding between 100 kDa - 30 kDa, as well as in some bands with molecular mass between 20 and 14 kDa, proving sensitization to mollusks. CONCLUSIONS: Bivalve proteins preserved in fossil soils may produce an immune hypersensitivity response. This may impact on the precautions exposed workers, in this case fossil soil cutters and polishers, should take.

Adverse Reactions to Illicit Drugs (Marijuana, Opioids, Cocaine) and Alcohol.

Drug allergy has been a research topic within the allergy field for decades. However, many drug reactions presumed to be of allergic nature are not and originate from different mechanisms. Drug-induced reactions can affect numerous organ systems, present with various symptoms, and have more than 1 mechanism of action. In this rostrum article, we want to give an overview of the different allergic and nonallergic reactions that can be expected with the (illicit) use of cannabis, cocaine, opioids, and alcohol. In addition, this article focuses on the different methods available to diagnose allergy related to these 4 drug types and highlight the pitfalls of nonallergic reactions or allergy "mimickers" complicating the diagnosis of true drug allergy. Finally, the impact on current medical practices and future research in support of the allergist in diagnosis and treatment of these medical problems is addressed.

Inhaled corticosteroids may have a protective effect against coronavirus infection.

BACKGROUND: Spain has been severely affected by the COVID-19 epidemic, with 195,944 persons infected and 20,453 deaths at the time of writing. Older people with respiratory or cardiac conditions are most at risk. OBJECTIVE: The aim was to compare respiratory symptoms in nursing home residents and patients with uncontrolled asthma, who are considered vulnerable to COVID-19. METHODS: We studied 134 nursing home residents and 139 patients with uncontrolled asthma, groups vulnerable to COVID-19. Demographic characteristics, clinical manifestations, outcomes, key laboratory results, and radiological images were collected from medical records. COVID-19 infection was detected by polymerase chain reaction (PCR). RESULTS: Thirteen (9.3%) patients with uncontrolled asthma, all receiving inhaled corticosteroids were infected by COVID-19. Eighty (60%) nursing home residents were infected; only 28, all of whom had received inhaled corticosteroids, had a good prognosis. CONCLUSIONS: Early treatment with inhaled corticosteroids may be helpful in COVID-19 infection. Persons with an allergy might have some protective mechanisms against coronavirus.

Inhaled corticosteroids may have a protective effect against coronavirus infection

BACKGROUND: Spain has been severely affected by the COVID-19 epidemic, with 195,944 persons infected and 20,453 deaths at the time of writing. Older people with respiratory or cardiac conditions are most at risk. OBJECTIVE: The aim was to compare respiratory symptoms in nursing home residents and patients with uncontrolled asthma, who are considered vulnerable to COVID-19.METHODS: We studied 134 nursing home residents and 139 patients with uncontrolled asthma, groups vulnerable to COVID-19. Demographic characteristics, clinical manifestations, out-comes, key laboratory results, and radiological images were collected from medical records. COVID-19 infection was detected by polymerase chain reaction (PCR).RESULTS: Thirteen (9.3%) patients with uncontrolled asthma, all receiving inhaled corticoste-roids were infected by COVID-19. Eighty (60%) nursing home residents were infected; only 28, all of whom had received inhaled corticosteroids, had a good prognosis CONCLUSIONS: Early treatment with inhaled corticosteroids may be helpful in COVID-19 infection. Persons with an allergy might have some protective mechanisms against coronavirus

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Una respuesta ética en la atención a residencias de ancianos en la pandemia Covid-19 / An ethical response in the care of nursing homes in the covid-19 pandemic

La llegada de la pandemia COVID-19 puso en evidencia el riesgo de una posible falta de atención de los ancianos de las residencias de mayores. Aportamos la experiencia de un equipo multidisciplinar con profesionales voluntarios de diferentes especialidades que realizó una labor de apoyo a los profesionales sanitarios de las residencias. Este equipo se implementó desde las gerencias de atención primaria y de atención especializada. La sistemática de trabajo se inspiraba en el de hospitalización a domicilio e incluía la atención directa de los pacientes más complejos y el asesoramiento en las medidas de prevención, aislamiento e higiene dentro de la residencia. De este modo fue posible que los ancianos de las residencias con sospecha o diagnóstico de COVID-19 recibieran una atención adecuada por parte de un equipo interdisciplinar, que se descargara parte de la presión de los profesionales de las residencias y que los familiares percibieran que no existía abandono terapéutico. El compromiso desde diversos niveles asistenciales en una labor coordinada ha conseguido evitar que una población vulnerable pudiera quedar desatendido durante la pandemia

With the arrival of the COVID-19 pandemic, the risk of a possible lack of care for the elderly in nursing homes became evident. We summarize the experience of a multidisciplinary team with volunteer professionals from different specialties who carried out support for healthcare professionals in nursing homes. This team was implemented from both Primary and Specialty Care managements. Its work paradigm was proposed by our home hospitalization team, which included direct care of the most complex patients and general counselling on isolation, hygiene and preventive measures within the nursing homes. Thanks to this support, the elderly population placed there, with suspected or diagnosed COVID-19, received adequate care from an interdisciplinary team, which led part of the pressure to be released from their professional workers, and many family members were aware that there was no neglect of the elderly. Commitment from various levels of care in a coordinated effort has prevented a vulnerable population from being left unattended during the pandemic

Occupational airborne contact urticaria, anaphylaxis and asthma in farmers and agronomists due to Bruchus pisorum.

BACKGROUND: Occupational contact urticaria due to inhalation of legume pest allergens has rarely been described. OBJECTIVE: To determine the cause of an outbreak of airborne contact urticaria, asthma, and anaphylaxis in farmers and agronomists studying the disinsectization of dried peas. Peas were treated with aluminum phosphide (EPA). METHODS: Extracts prepared from Bruchus lentis and Bruchus pisorum bodies and from healthy legumes, EPA-treated legumes, and infested legumes, were used for in vivo tests (skin prick testing, oral, and specific bronchial challenge for the diagnosis of asthma and anaphylaxis) in affected patients and in five control patients with severe legume hypersensitivity. Open application, patch testing with the most common legume insecticides, molecular analysis, and IgE immunoblotting were undertaken. RESULTS: We found positive responses (prick, provocation, immune detection) to parasitic pea extracts and B. pisorum. A 25 kDa band was detected in the western blot of all patients who worked with infested EPA-treated peas. Bands from B. pisorum extract were detected in all patients. No responses to pea allergens were found in any patient, unlike in legume allergy controls. Oral provocation tests were negative. CONCLUSION: B. pisorum is a cause of contact urticaria and may cause occupational hives, anaphylaxis, and asthma. The allergen may enter by inhalation or puncture of setae released by B. pisorum.

Mastocytosis and the Fig Wasp (Blastophaga psenes).

BACKGROUND: Mastocytosis involves the abnormal proliferation of mast cells and clinical variability. In the case of anaphylaxis, the triggering antigen, often associated with Hymenoptera allergens, must be identified. The common fig (Ficus carica) requires the fig wasp (Blastophaga psenes) for pollination. OBJECTIVE: We evaluated the ingestion of B. psenes as a trigger of anaphylaxis in patients with mastocytosis. MATERIAL AND METHODS: Skin prick tests (SPTs) and specific immunoglobulin E to the possible involved allergens were carried out in the patient and in 4 controls allergic to Hymenoptera and fig. Given the possibility of hidden allergens, we studied the source (figs of various origins) and possible hypersensitivity to Hymenoptera allergens, including the fig wasp (B. psenes). RESULTS: In all subjects, the SPT resulted in a wheal (larger than with histamine) with the extract of the inferior part of the female fig but not with the male extract (lower pole and stem). Immune detection was made with the stem and inferior part of figs and venom of Polistes and Vespula. Recognition bands were observed at 25 kDa with female fig extracts that were also recognized by the patient with anaphylaxis to Hymenoptera venom. CONCLUSIONS: We cannot exclude the possibility that the ingestion of fig with Blastophaga antigens may have triggered anaphylaxis in our patient.

Component-resolved diagnosis in allergic disease: Utility and limitations.

Component resolved diagnosis (CRD) is a microarray-based diagnostic solution capable of simultaneously analysing specific IgE antibodies against 112 allergenic components, providing sensitivity patterns for multi-sensitised or complex patients. The CRD is indicated for these patients, especially those with concomitant respiratory and food allergies. This study reivews the method, its utility, limitations, and our experience in allergic diseases with difficult etiologic diagnosis (eosinophilic esophagitis, occupational asthma and drug allergy).

Identification and molecular characterization of allergenic non-specific lipid-transfer protein from durum wheat (Triticum turgidum).

BACKGROUND: Common wheat (Triticum aestivum) and durum wheat (T. turgidum) are both involved in Baker's asthma (BA) and food allergy (FA) including wheat-dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have not been described, and the over-expression of T. turgidum non-specific lipid-transfer protein (nsLTPs) is considered to increase resistance to phytopathogens. OBJECTIVE: To identify and assess the allergenicity of nsLTP from T. turgidum. METHODS: Recombinant T. turgidum nsLTP Tri tu 14 was generated and tested for structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE). Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with positive bronchial challenge to wheat flour, and 12 Italian patients (wheat FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T. aestivum) and Pru p 3 (P. persica) were determined by ImmunoCAP testing. Allergenic potency (in vitro mediator release) and IgE cross-reactivity were investigated. RESULTS: Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The correlation between Tri a 14 and Tri tu 14 specific IgE levels was r = 0.97 (BA) and r = 0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed allergenic activity by mediator release from effector cells and IgE cross-reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat nsLTPs varied between individual patients. CONCLUSIONS AND CLINICAL RELEVANCE: Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for patients with nsLTP-mediated FA.

Germination of pollen grains in the oesophagus of individuals with eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and, histologically, by eosinophilic inflammation. There is no a clear aetiologic treatment. EoE exacerbations are often seasonal. We hypothesized that the inflammatory response of the oesophageal mucosa in patients with high levels of antibodies to pollen allergens and worsened seasonal EoE might be due to swallowing airborne pollen and the intrusion into the oesophageal mucosa of pollen allergens and pollen tubes, which encounter a pH and humidity resembling the stigma at pollination. OBJECTIVE: The aim of our study was to demonstrate the possible pathogenic role of environmental allergens in EoE through molecular and anatomopathological studies METHODS: One hundred and twenty-nine patients with EoE were tested for environmental and food allergens. Component resolved diagnosis (CRD), histological and botanical analysis was performed. Microscopic examination of oesophageal biopsies of 129 adults patients with EoE, 82 of them with seasonal exacerbation, and 100 controls, with gastroesophageal reflux without eosinophilic infiltrate, were made to verify the presence of callose (polysaccharide abundant in pollen tubes but absent in animal tissues) in the oesophagus. RESULTS: Component resolved diagnosis detected pollen allergens in 87.6% of patients with EoE. The predominant allergens were group 1 grass (55%), Art v 3 (11.3%) and lipid transfer proteins (LTPs) (19.4%) of common Mediterranean foods such as peach, hazelnuts, walnuts and wheat. Callose from pollen tubes was found in 65.6% of biopsies. CONCLUSION: Alteration of the mucosal barrier in EoE might cause the penetration of pollen grains into the oesophageal tissues. In EoE patients, anatomopathological studies searching for intrusion to plant foods and pollen, and specific-guided diet and immunotherapy after plant structures detection in biopsies, might be effective. CLINICAL RELEVANCE: It is possible to see the intrusion into animal tissues (oesophagus mucosa) of plant structures (pollen grains or pollen tubes) using an adecuate histologic botanical analysis. Molecular and anatomopathological studies can help to demonstrate a possible pathogenic role of environmental allergens in EoE.

Cocaine Allergy in Drug-Dependent Patients and Allergic People.

BACKGROUND: Adverse reactions to local anesthetics (LAs), especially esters, are not uncommon, but true allergy is rarely diagnosed. To our knowledge, currently there is no reliable method of determining IgE-mediated hypersensitivity to LAs and cocaine. OBJECTIVE: To assess the clinical value of allergy tests (prick, IgE, challenges, and arrays) in people suffering hypersensitivity reactions (asthma and anaphylaxis) during local anesthesia with cocaine derivatives and drug abusers with allergic symptoms after cocaine inhalation. METHODS: We selected cocaine-dependent patients and allergic patients who suffered severe reactions during local anesthesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity, and predictive value) of allergy tests using cocaine and coca leaf extracts in determining cocaine allergy was assessed, taking a positive challenge as the criterion standard. RESULTS: After prick tests, specific IgE, and challenge with cocaine extract, 41 of 211 patients (19.4%) were diagnosed as sensitized to cocaine. Prick tests and IgE to coca leaves (coca tea) had a good sensitivity (95.1% and 92.7%, respectively) and specificity (92.3 and 98.8%, respectively) for the diagnosis of cocaine allergy and LA-derived allergy. CONCLUSIONS: Cocaine may be an important allergen. Drug abusers and patients sensitized to local anesthesia and tobacco are at risk. Both prick tests and specific IgE against coca leaf extract detected sensitization to cocaine. The highest levels were related to severe clinical profiles.

Component-resolved diagnostics in vernal conjunctivitis.

PURPOSE OF REVIEW: Conventional diagnostic tests in allergy are insufficient to clarify the cause of vernal conjunctivitis. Component-resolved diagnostic (CRD) by microarray allergen assay may be useful in detecting allergens that might be involved in the inflammatory process. RECENT FINDINGS: In a recent trial in patients suffered from eosinophilic esophagitis, after 2 years of the CRD-guided exclusion diet and specific immunotherapy, significant clinical improvement was observed, and 68% of patients were discharged (cure based on negative biopsy, no symptoms, and no medication intake). Our new objective was to evaluate IgE-mediated hypersensitivity by CRD in tears and serum from patients with vernal conjunctivitis and treat patients with identified triggering allergens by specific immunotherapy. Twenty-five patients with vernal conjunctivitis were evaluated. The identified triggering allergens were n Lol p 1 (11 cases), n Cyn d 1 (eight cases), group 4 and 6 grasses (six cases) and group 5 of grasses (five cases). Prick test and pollen IgE were positive in one case. Clinical improvement was observed in 13/25 vernal conjunctivitis patients after 1-year specific immunotherapy. SUMMARY: CRD seems to be a more sensitive diagnostic tool compared with prick test and IgE detection. Specific CRD-led immunotherapy may achieve clinical improvements in vernal conjunctivitis patients.

Component-resolved diagnostics in vernal conjunctivitis.

BACKGROUND: Conventional diagnostic tests in allergy are insufficient to clarify the origin of vernal conjunctivitis (VC). OBJECTIVES: To evaluate IgE-mediated hypersensitivity by component-resolved diagnosis (CRD) in tears and serum from patients with VC and to evaluate how to treat patients with identified triggering allergens by specific immunotherapy. METHODS: Patients were divided into 3 groups: (1) patients with VC (25 patients), (2) patients allergic to grass pollen with seasonal allergic conjunctivitis (AC) (50 patients), and (3) healthy blood donors (50 patients). If triggering allergens were detected, specific conventional immunotherapy was administered for 1 year. RESULTS: Twenty-five patients with VC were evaluated. The identified triggering allergens were n Lol p 1 (11 patients), n Cyn d 1 (8 patients), group 4 and 6 grasses (6 patients), and group 5 grasses (5 patients). Prick test and pollen IgE test results were positive in one patient. Clinical improvement was observed in 13 of the 25 patients with VC after 1 year of specific immunotherapy. CONCLUSION: CRD seems to be a more sensitive diagnostic tool compared with prick test and IgE detection. Specific CRD-led immunotherapy may achieve clinical improvements in patients with VC.