Background: Histamine H1 receptor antagonists (antihistamines) are recommended as adjunctive therapy for atopic dermatitis (AD). However, their long-term usefulness and the effect of updosing have not been clarified.

Purpose: To analyzed the long-term usefulness and the effect of updosing of rupatadine, a second generation antihistamine, for patients with AD.

Methods: Efficacy and safety of rupatadine were evaluated in 66 AD patients, including 50 patients with dose escalation by post hoc analysis of the phase III trial of rupatadine for Japanese patients with pruritus associated with skin diseases.

Results: The mean score at baseline total pruritus score (TPS) was 4.682. It decreased to 3.885 at 2 weeks, and 2.376 at 52 weeks by rupatadine administration. The change (of one week after baseline TPS) was significant. Baseline TPS of dose escalation groups, either after 2 weeks or after week 4, were higher than those of 10mg maintenance dose cases, but no significant difference was shown in the change from baseline TPS among the groups at 52 weeks. The occurrence of adverse drug reactions and somnolence were observed in 19.7% and 15.2% of the subjects.

Conclusion: These results suggest the long-term usefulness of rupatadine for pruritus in AD.

Background: In order to determine the optimal breathing method for childhood lung sound analyses, it is important to study the effect of airflow on the parameters of lung sounds.

Methods: Sixty-one well-controlled children with atopic asthma (median; 12 years) participated. After confirming that there was no wheezing or respiratory symptoms, the lung sound spectrums of the inspiratory flow before and after inhalation of a β₂ stimulant were analyzed. At the same time, their lung function was measured by a spirogram and the forced oscillation technique.

Results: Before β₂ agonist inhalation, the area under the entire curve (A_T) and 99% frequency (F₉₉) in the lung sound of inspiratory flow around 2.0L/s due to slightly strong breathing were significantly higher than the lung sound of inspiratory flow around 1.0L/s due to rest breathing. However, no marked differences were observed in the lung sound parameters based on the lung sound spectrum. The improvement in the lung sound parameters after β₂ agonist inhalation was clearer at an inspiratory flow around 1.0L/s than that around 2.0L/s.

Conclusion: The present study showed that changes after β₂ agonist inhalation and the correlation with the lung function parameters were clear during resting breathing. This method may be used for the long-term montoring of children with asthma.

Background: Hereditary angioedema (HAE) is associated with recurrent, painful, and potentially lifethreatening attacks characterized by swelling of subcutaneous or submucosal tissues.

Purpose: To investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of repeat-use C1 inhibitor (C1-INH) replacement therapy for long-term prophylaxis and treatment of breakthrough attacks in the management of Japanese patients with HAE type I or II.

Methods: An open-label, single-arm, Phase 3 study was conducted in Japanese patients with HAE (NCT 02865720). For patients 6 years of age or older, 1000U were administered biweekly (by a healthcare professional or self-administered) via intravenous infusion.

Results: In 8 enrolled patients, the mean number of attacks normalized per month was lower during C1-INH treatment than during the 3 months prior (1.826 vs. 3.375). Clinically meaningful mean change from baseline in the angioedema-quality of life (AE-QoL) total score was shown during treatment with C1-INH. Pharmacokinetic data showed markedly higher and enduring post-baseline plasma levels of C1-INH functional activity and C1-INH antigen concentration, starting from 0.5h after first dose of C1-INH and lasting up to 72 hours. C1-INH was well tolerated with no new safety signals identified in this population of Japanese patients with HAE.

Conclusion: C1-INH was effective for long-term prophylaxis and treatment of breakthrough attacks with favourable safety profile in Japanese patients with HAE.

A 5-year-old girl living in Koriyama, Fukushima Prefecture was admitted in April with cough persisting for 1 month and fever. Chest X-ray showed diffuse ground-glass shadows in both lungs. After treatment with antibiotics, her fever went down on the 2^nd day, and her cough subsided gradually. She was discharged on the 7^th day, but her symptoms relapsed on the 8^th day. Due to her worsening symptoms, she was readmitted on the 16^th day. Chest CT scans showed enhancement of interstitial density. Serum anti-Trichosporon asahii antibody was positive. Her symptoms rapidly improved on a steroid regimen, and she was discharged on the 23^th day. She was diagnosed as having summer-type hypersensitivity pneumonitis (SHP). She was instructed not to use a moldy humidifier and not to go to her grandmother's 57 years old wooden house. She has had no symptom after discharge. However, suspected mold was not found at her grandmother's house, and a provocation test there was negative. The HLA typing of the patient showed HLA-DQ8, which was previously described as SHP-sensitive.

A 28-year-old man was transferred to our emergency room for dyspnea and wheals on the entire body. He had eaten landlocked ayu fish (Plecoglossus altivelis) the so-called “koayu fish”, from Lake Biwa, and had immediately experienced a stomachache. Wheals and dyspnea developed one hour later and were successfully treated with intravenous corticosteroids. The patient was examined for koayu fish and related allergens by skin prick and allergen-specific immunoglobulin E (IgE) (ImmunoCAP^®) tests. Positive skin prick results were obtained for Lake Biwa koayu fish (raw and heated) as well as for standard skin test allergens (prepared by Torii pharmaceuticals) including shrimp, crab, and squid. Negative prick test results were observed for regular ayu fish and other fish such as horse mackerel, sardine, salmon, mackerel, codfish, and tuna. Allergen-specific IgE tests (ImmunoCAP ^®) showed positivity for shrimp, crab, ticks, moths, and mosquitoes, while ImmunoCAP^® tests were negative for the allergen components rGad c 1 (pollackparvalbumin) and rPen a 1 (shrimp tropomyosin). Moreover, enzyme-linked immunosorbent assay (ELISA) tests were negative for mackerel parvalbumin and collagen. We considered this case to be of anaphylaxis caused by koayu fish from Lake Biwa and speculated that a novel koayu-specific antigen might have been the cause of the condition.

Background: Prurigo nodularis is a chronic disease characterized by a hard dome-like or wart-like nodule which is solitary and does not fuse. Prurigo nodularis presents as one of the symptoms of atopic Dermatitis (AD).

Cases: We present three cases of AD children with intractable prurigo nodularis. 1) a 9-Year-Old Boy, 2) an 11-Year-Old Girl, and 3) an 8-Year-Old Boy. The Eczema Area and Severity Index (EASI) in the first visit was 27.7, 30.6, and 49.0, respectively. All patients had been treated with very strong or strongest potency topical steroids for 3-9 years. Quality of life (QOL) had declined due to severe pruritus, and they had striae and secondary adrenal suppression as side effects of steroids. Case 1 and 2 were treated with Cyclosporine A (CyA), case 3 was treated with Duplimab when he was 15 years old; all patients improved.

Discussion: CyA and Duplimab are not indicated for children in Japan, however, it is necessary to consider not only topical medicine but also other additional treatments when faced with adrenal suppression as a side effect of steroids or loss of QOL.

Conclusion: CyA and Duplimab, that were effective in AD with intractable prurigo nodularis, are expected to become indications for AD children.