This article, written in response to receiving the academic conference award from the 72nd annual meeting of the Japanese society of allergology, reviews the author's research on allergic conjunctivitis, discusses its significance, and outlines future research directions.

Previously, we reported that repeated topical application of pollen to the conjunctiva without prior systemic sensitization induced eosinophilic conjunctivitis and found that particulate matters like pollen shells were required for the development of local ocular allergy. To track the localization of antigens, we administered fluorescently labeled protein antigen to mouse conjunctiva together with pollen shells. Histological examination revealed that goblet cell associated antigen passages (GAPs) were rapidly formed upon stimulation of pollen shells. The antigen acquisition by the cells in the stroma was highly correlated with GAP formation.

Kinetic experiments revealed that rapid antigen transport through GAPs played an important role in the development of the allergic conjunctivitis. Furthermore, topical anesthetics and electric ablation of the trigeminal nerve suppressed the pollen shell-stimulated GAP formation and antigen uptake in the conjunctiva. These results indicated that the pollen shell stimuli induced the GAP formation through a nerve-goblet cell association, which contributed to the development of allergic conjunctivitis.

A 30-year-old man who had worked in the painting industry for the past year was referred to our hospital after developing progressive exertional dyspnea. A chest computed tomography scan showed a diffuse, random pattern of ground-glass opacities in the lungs. Bronchoalveolar lavage fluid (BALF) was predominantly lymphocytic (49.2%), and bronchoscopic cryobiopsy showed fibrotic interstitial proliferation around the small bronchi and Masson's bodies. The drug-induced lymphocyte stimulation test (DLST) for isocyanate (hexamethylene diisocyanate [HDI]) reagent was positive in blood and the BALF samples. The patient was diagnosed with hypersensitivity pneumonitis, and isocyanates (HDI) were suspected as the allergen based on the effectiveness of antigen avoidance, occupational history, DLST results, and a multidisciplinary discussion. Avoiding the antigen with a leave of absence and changing jobs, along with corticosteroids and mycophenolate mofetil treatment resulted in partial improvement of both the reticular shadows in the lungs and respiratory function. In recent years, isocyanate-induced hypersensitivity pneumonitis has become rare, probably because of improvements in working environments, but healthcare providers must still be aware of it as an occupational allergy. Although DLST alone cannot definitively diagnose hypersensitivity pneumonia, when combined with other findings it may serve as a useful adjunct diagnostic tool, as in this case.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with chronic rhinosinusitis (CRS) and bronchial asthma. Mepolizumab, an anti-IL-5 monoclonal antibody, has been used in the treatment of EGPA. We report two cases of MPO-ANCA-positive EGPA with CRS that exhibited differing responses to mepolizumab. In Case 1, nasal symptoms persisted despite mepolizumab treatment, and CRS recurred early after endoscopic sinus surgery (ESS). In contrast, Case 2 developed EGPA following dupilumab administration, but nasal symptoms improved with mepolizumab and remained well controlled. These cases suggest that the efficacy of mepolizumab for CRS in ANCA-positive EGPA varies among patients. Even in cases that respond well to treatment, recurrence may still occur, underscoring the importance of continuous follow-up in close collaboration with internal medicine specialists.

We report a rare case of toxic epidermal necrolysis (TEN) in a 10-year-old boy with no significant past medical history, triggered by the use of over-the-counter antibacterial eye drops. Seven days prior to the first visit, the patient experienced ocular pruritus and conjunctival hyperemia for which he applied an over-the-counter antibacterial eyedrops. The following day, erythematous plaques appeared all over his body, gradually enlarging. Two days prior to his initial visit, he started taking amoxicillin due to a positive throat swab for group A streptococcal infection. On the day of the first consultation, he was referred to our hospital with a diagnosis of Stevens-Johnson syndrome (SJS). At our initial assessment, marked conjunctival hyperemia, hemorrhagic erosion of the oral mucosa, and multiple flat atypical targets were present on almost the entire body. By the second day, the erythema had largely evolved into flaccid blisters, with epidermal detachment involving more than 30% of the body surface area. The pathological findings confirmed the full-thickness necrosis of the epidermis, leading to a diagnosis of TEN. Treatment with steroid pulse therapy and high-dose intravenous immunoglobulin therapy was successful in complete re-epithelialization of the skin. The severity-of-illness score improved from 26 points at admission to 0 points at discharge. While cases of SJS and TEN caused by glaucoma eye drops are documented, TEN in children associated with over-the-counter antibacterial eye drops has only been reported once previously worldwide, and this is the first such case reported in Japan, highlighting its clinical significance.

As needed therapy with inhaled corticosteroid plus fast onset acting β₂ agonist only when symptomatic (as needed FABA/ICS) is recommended for the management of patients with mild asthma in the various foreign countries based on solid evidence. However, this treatment is currently not recommended in Japan. Therefore, we conducted a systematic review (SR) to determine whether this treatment is beneficial for patients with mild asthma in Japan. We extracted randomized controlled trials (RCTs) that met the following criteria: patients with mild asthma receiving as needed FABA/ICS and assessed at 54 weeks. RCTs were selected from a previously published SR, and the search was up-to-date as of March 2021. In addition, RCTs published until June 2022 were searched. We selected five RCTs from a previously published systematic review and did not select any additional RCTs. As needed FABA/ICS therapy significantly reduced the number of exacerbations requiring systemic steroid and the annual exacerbation rate compared to as needed FABA therapy (p≤0.01), but there was no significant difference with regular ICS therapy. In addition, as needed FABA/ICS therapy significantly reduced the number of exacerbations requiring hospital admission or emergency department / urgent care visit compared to as needed FABA therapy and regular ICS therapy (p≤0.01). The frequency of serious adverse events was not significantly different from as needed FABA therapy and regular ICS therapy. It was suggested that as required FABA/ICS is a useful treatment option in Japanese patients with mild asthma.