Wheat can cause both immediate and delayed reactions. Immediate, IgE-mediated reactions may be triggered, after eating foods that contain this cereal, or by inhalation of wheat flour (WF), as in baker's asthma (BA).1,2 The delayed reactions are not IgE-mediated, cause digestive symptoms, as it happens in eosinophilic esophagitis (EoE).3–6
We describe a 49-year-old man who worked as a baker for 30 years. He was referred to the allergology clinic by nasoocular itching, watery eyes, sneezing, runny nose, nasal obstruction, dry cough and dyspnea. His symptoms began after handling WF in his workplace, improving during weekends or holidays. He was treated with antihistamines and inhaled budesonide (400μg/day), with good control for 10 years. In the last 5 years he worsened, needing to increase the dose of inhaled corticosteroids and adding salbutamol as rescue medication.
Simultaneously, he began with symptoms of esophageal dysfunction (SED) (dysphagia, chocking and heartburn). He was treated with omeprazole, 40 daily/20 years, with improvement and resolution of his symptoms but was never studied by a gastroenterologist.
Allergy study, skin prick tests (SPT) and specific IgE (sIgE) were negative (mean SPT wheal <3×3mm and sIg E <0.35kU/L) to pollens (grass, Olea europaea and Salsola kali), mites (D. pteronyssinus, D. farinae and L. detructor), molds (A. alternata, Cladosporum and Aspergyllus) and animal dander (cat, dog). SPTs were positive with WF commercial extract (ALK-Abelló, Madrid) and in prick by prick test. Total serum IgE: 135kU/L. and specific IgE to WF 2.5kU/L. Specific IgE to gluten, r-ω-5-gliadin, α-amylase and Tri a 14 were all negative (ImmunoCAP, ThermoFisher, Uppsala, Sweden).
The basal spirometry was normal. The methacholine bronchial test with an abbreviated method7 was positive (PD20: 0.20mg cumulative dose) while he was working, but, after 3 months of sick leave, it was negative. Chest X-ray was normal.
A specific bronchial test was carried out with WF, tipping it from one tray into another for 15min. Spirometries were performed at baseline and at 2, 5, 10, 15, 20, 30, 45 and 60min after the exposure to WF. Peak expiratory flow was measured at baseline and over a period of 24h (respecting sleeping patterns). A 23% fall in FEV1 was observed 15min after exposure to WF. The patient did not have any late reaction. A bronchial control test with saline carried out on the previous day was negative.
A sodium dodecyl sulphate polyacrylamide gel electrophoresis immunoblot analysis with WF extract was performed using the Laemmle method.8 A specific binding was detected between 37 and 70kDa. Glutenins in within the range of these molecular weights.
Endoscopy (E)1: without taking omeprazole, during a working period and ingesting WF. E2: working, ingesting WF and omeprazole; E3: without ingesting neither WF nor omeprazole and without exposure (sick leave); E4: without omeprazole, without exposure but with ingestion of WF; E5: without omeprazole, working, and without ingesting WF. E6: without omeprazole, without exposure and ingesting a gluten-free diet (Table 1). The diagnosis was made according to the updated international consensus diagnostic criteria for EoE: AGREE conference.3 Remission is confirmed <15eos/cga (total and partial remission: <5 and 5–14eos/hpf, respectively).
In E1, >15eosinophils/hpf were detected in the esophagus and <3eosinophils/hpf in the stomach and duodenum. Table 1 shows the patient's responses to omeprazole, to a wheat-free diet, and to the environmental exposure to WF. The avoidance of WF, both by the digestive and the bronchial route, were capable to solve the EoE.
The patient was diagnosed with occupational allergic respiratory disease (OARD)9 and occupational EoE5,6 caused by WF. The evolution of the patient has been very good; after being retired from his job and on a wheat-free diet, he is asymptomatic.
EoE and OARD are frequently found as comorbidities along with other atopic manifestations. These two conditions have similar T helper type 2 responses-driven pathophysiology and share common management strategies10; this case is a clear example of the multiorganic clinical manifestations of atopy.
EoE experts have so far questioned whether this disease could be caused by the inhalation of allergens. The case described suggests that the answer would be affirmative.5,6 The small number of reported cases caused by aeroallergens could be justified because, until now, some doctors who treat atopic patients have little experience in the diagnosis and management of EoE.
In Spanish bakers, sensitization to grass pollen and to rTria 14 is frequent, however, our patient is only sensitized to WF. The positive methacholine test, confirms that patient has bronchial asthma and the positive specific bronchial challenge test indicates that it is an OARD by WF.6
OARD to wheat proteins is very frequent and its prevalence does not seem to be declining. The researchers on BA point out the strong limitations of its diagnosis and treatment; they think that the isolation and characterization of cereal allergens associated with BA, particularly from WF would allow us to better define major and minor allergens, what would help to provide an adequate diagnostic panel of molecular markers.2
The EoE responded to omeprazole3 but the patient had to follow a gluten-free cereal exclusion diet and to avoid WF inhalation simultaneously to achieve remission. Neither diet nor being off-work separately were sufficient for the resolution of the EoE.
In patients with SED, it is important to study if they have EoE or gastroesophageal reflux disease or both, because can worsen asthma.
We present an unusual case in which WF triggers EoE and an occupational OARD in the same patient, in which the inhalation of WF triggered the two diseases and EoE is caused by the oral and inhalation routes. When we diagnose an OARD, we should ask the patient for SED, since an early diagnosis and treatment will improve the prognosis and the quality of life of these patients.
