Eosinophilic sialodochitis: An emerging atopic condition.

OBJECTIVE: To report the clinical characteristics of the largest single centre cohort of patients with eosinophilic sialodochitis. METHODS: Analysis of data relating to 37 patients seen in a dedicated multidisciplinary clinic was performed. Demographic, clinical, haematological, cytological, histological and radiological features were collated. Response to trials of allergy treatment was assessed. RESULTS: Thirty-seven patients (30 female, seven male) were identified, 42% of whom were of Afro-Caribbean origin, with a mean age of 50.4 years (range 28-80 years). Mean symptom duration at presentation was 10 years (range 2-33 years). Parotid and submandibular gland involvement was equally reported. The most commonly reported symptoms were swelling (97%), itching of the overlying skin (92%), salivary gland discomfort (84%) and "string-like" mucus discharge from salivary duct orifices (76%). Twenty-three patients (62%) demonstrated atopic disease and serum IgE level elevated in 57%. All 37 patients had eosinophils present in aspirated duct contents samples while raised peripheral eosinophil count was seen in 41%. Anecdotal symptom improvement was reported with antihistamine, antileukotriene or steroid treatment. CONCLUSION: Eosinophilic sialodochitis should be considered in any patient presenting with recurrent salivary gland swelling. Further studies are needed to evaluate treatments directed at a likely allergic pathogenesis.

Clinical evaluation and diagnosis of aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) is a condition composed of chronic rhinosinusitis with nasal polyposis and asthma that is defined by respiratory hypersensitivity reactions to the cyclooxygenase 1-inhibitory effects of nonsteroidal anti-inflammatory drugs. It is diagnosed in 5% to 15% of patients with asthma and is even more common in those with comorbid nasal polyposis. Diagnosis is confirmed after an aspirin challenge procedure, yet many patients present with all components and can reliably be diagnosed by history. Patients with AERD commonly experience severe uncontrolled nasal polyposis and require multispecialty evaluation to properly stage and treat this condition. The presence of nasal polyposis plays a large component in the diminished quality of life in patients with AERD. In the last decade, multiple new therapeutic areas have been approved for type 2 airway diseases, offering patients with AERD many more options for control. This makes an early and accurate diagnosis of AERD important in the care of the larger population of type 2 airway diseases.

Inhaled long-acting ß2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD.

BACKGROUND: Combination inhaled therapy with long-acting ß2 agonists (LABAs) and corticosteroids is beneficial in treating asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: In asthma, LABAs enhance glucocorticoid receptor (GR) nuclear translocation in the presence of corticosteroids. Whether this biological mechanism occurs in COPD, a relatively corticosteroid-resistant disease, is uncertain. METHODS: Eight patients with mild/moderate COPD participated in a double-blind, placebo-controlled, crossover study and inhaled single doses of fluticasone propionate (FP) 100 µg, FP 500 µg, salmeterol xinafoate (SLM) 50 µg, and combination FP 100 µg + SLM 50 µg. One hour postinhalation, sputum was induced, nuclear proteins isolated from purified macrophages, and levels of activated nuclear GR quantified by using a GR-glucocorticoid response element ELISA-based assay. RESULTS: Nuclear GR significantly increased after the inhalation of FP 500 µg (P < .01), but not after the inhalation of FP 100 µg or SLM 50 µg, compared with placebo. Interestingly, SLM in combination with FP 100 µg increased nuclear GR levels equivalent to those of FP 500 µg alone. This was significantly greater than either FP 100 µg (P < .05) or SLM 50 µg (P < .01) alone. In vitro in a human macrophage cell line, SLM (10(-8) mol/L) enhanced FP (10(-9) mol/L)-induced mitogen-activated protein kinase phosphatase-1 mRNA (5.8 ± 0.6 vs 8.4 ± 1.1 × 10(-6) copies, P < .05) and 2 × glucocorticoid response element-luciferase reporter gene activity (250.1 ± 15.6 vs 103.1 ± 23.6-fold induction, P < .001). Addition of SLM (10(-9) mol/L) to FP (10(-11) mol/L) significantly enhanced FP-mediated suppression of IL-1ß-induced CXCL8 (P < .05). CONCLUSIONS: Addition of SLM 50 µg to FP 100 µg enhanced GR nuclear translocation equivalent to that seen with a 5-fold higher dose of FP in sputum macrophages from patients with COPD. This may account for the superior clinical effects of combination LABA/corticosteroid treatment compared with either as monotherapy observed in COPD.

A Patch Testing Initiative for the Investigation of Allergic Contact Dermatitis in a UK Allergy Practice: A Retrospective Study.

BACKGROUND: Patch testing is the gold standard diagnostic tool for investigating allergic contact dermatitis (ACD). In the United Kingdom, patch testing has been historically confined to the dermatologist's office. Furthermore, detailed studies on patch testing by allergists are significantly underrepresented at the international level. OBJECTIVE: The objective of this study was to undertake a comprehensive evaluation of a patch testing initiative from an allergy practice; we report on various patient characteristics, prevalence and relevance data, in addition to immediate hypersensitivity testing. METHODS: We undertook a retrospective analysis of 156 patients suspected of having contact dermatitis seen in our UK allergy practice between October 2016 and April 2018. RESULTS: Of the 156 patients patch tested (mean age 36.9 years, female 88%, white ethnicity 71.8%, atopy 68.6%), ACD was diagnosed overall in 49% of the cohort and ACD of current relevance was assigned to 31%. Our extended British standard series alone detected the responsible allergen in 87% of patients, and the remaining 13% were detected from supplementary or own material testing alone. Most prevalent contact allergens were nickel (28.2%), p-phenylenediamine (8.3%), cobalt (8.3%), methylisothiazolinone (5.8%), and hydroperoxides of linalool (4.5%) and limonene (4.5%). A history of occupationally related dermatitis (P = .004) and initial (pretest) diagnosis of ACD (P < .001) were both significantly associated with relevant positive patch test reactions (atopy status was not associated P > .05). CONCLUSIONS: ACD was detected in almost 50% of assessed patients, and we highlight the importance of assessing relevance. Hydroperoxides of limonene and linalool are notable additions to the prevalence data. Patch testing should be incorporated into more allergy practices, although availability of training is a limiting factor.

Rare presentation of anaphylaxis: pancake syndrome.

A 43-year-old woman presented with oral discomfort, sneezing, urticaria, eyelid angioedema, abdominal pain, diarrhoea, dyspnoea and wheeze soon after eating a Japanese flour pancake (okonomiyaki, containing wheat, egg, yam, pork, prawn and squid). Subsequent analysis of the flour used in the pancake revealed the presence of Dermatophagoides farinae (4500 mites/g). The patient tested positive for specific IgE to D. farinae (15.2 kU/L) and D. pteronyssinus (14.0 kU/L) with negative responses to other ingredients in the pancake. Oral ingestion of dust mite in poorly stored foods can cause anaphylactic reactions in patients with allergy.

Identifying Low-Risk Beta-Lactam Allergy Patients in a UK Tertiary Centre.

BACKGROUND: There are marked geographical as well as temporal differences in patient sensitization profiles to ß-lactams (BL). OBJECTIVE: To determine the utility of skin test reagents and identify a cohort of patients where skin testing can be safely omitted in a cohort of patients referred to a UK tertiary referral center. METHODS: A retrospective study of the clinical characteristics of 1092 patients referred for BL allergy testing was analyzed using multivariate regression analysis. The effectiveness of skin test reagents was also evaluated. RESULTS: Multivariate logistic regression identified that a history of anaphylaxis (odds ratio [OR] 10.98, P = .001) and the patients' recall of the index drug (apart from ampicillin and meropenem, OR 3.51-12.43, P < .05) were independent predictors of type I BL allergic status and a time of less than 1 year elapsed since index reaction significantly increasing the odds of a patient with a history of anaphylaxis, having a type I BL allergy (OR 38.66, P = .003). An absence of anaphylactic severity, unknown name of the index drug and a reaction occurring more than 1 year before testing, has a negative predictive value (NPV) of 98.4%, which was similar to the NPV of skin testing of 98.9% for type I BL allergy. The NPV of skin testing with benzylpenicillin + amoxicillin ± index BL was similar with (98.9%) or without (98.1%) the use of benzylpenicillin polylysine and minor determinant for type I BL allergy. CONCLUSION: We identified a "low risk" cohort of patients where the history is of similar reliability to skin testing in predicting nonallergic status for BL allergy.

Chronic idiopathic cough: a discrete clinical entity?

STUDY OBJECTIVES: Despite the success of specialist cough clinics, there is increasing recognition of a subgroup of chronic coughers in whom a diagnosis cannot be made even after thorough, systematic investigation. We call this condition chronic idiopathic cough (CIC). The aim of this study is to compare the clinical characteristics of CIC patients with those of coughers in whom a diagnosis has been established (non-CIC) to see if there is a recognizable clinical pattern that distinguishes CIC from non-CIC. DESIGN: Retrospective analysis of the medical records of chronic cough patients. SETTING: The Royal Brompton Hospital Chronic Cough Clinic, London. PATIENTS: One hundred patients with chronic cough referred to the Royal Brompton Hospital Cough Clinic between October 2000 and February 2004. RESULTS: Seventy-one percent of all patients were female. Median age was 57 years (range, 19 to 81 years), with a median duration of symptoms of 48 months (range, 2 to 384 months). The primary diagnoses were CIC (42%), postnasal drip syndromes (22%), gastroesophageal reflux disease (16%), asthma (7%), and others (13%). In CIC patients, the median age at referral, age at onset of cough, and proportion of females did not differ significantly from non-CIC patients. CIC patients had a longer median duration of cough (72 months vs 24 months, p = 0.002), were more likely to report an upper respiratory tract infection (URTI) as the initial trigger of their cough (48% vs 24%, p = 0.0014), and had a significantly lower cough threshold in response to capsaicin (log concentration of capsaicin required to induce five or more coughs, - 0.009 vs 0.592, p = 0.032) than non-CIC patients. CONCLUSIONS: Patients with CIC commonly describe a URTI that initiates their cough, which then lasts for many years, and they demonstrate an exquisitely sensitive cough reflex. We believe that CIC may be a distinct clinical entity with an as-yet unidentified underlying pathology.