Effects of Neuropeptides In The Development Of The Atopic Dermatitis Of Mouse Models

Background: Neuropeptides are considered to be factors that trigger, exacerbate or modulate allergic diseases and inflammatory skin reactions. In addition, it has been indicated that allergic diseases are highly correlated with stress. Methods: 2,4,6-Trinitrochlorbenzene (TNCB) and crowding stress were applied to mouse atopic dermatitis (AD) models for the purpose of provoking chronic dermatitis. In addition, TNCB-sensitized mice were given olopatadine hydrochloride (10 or 3 mg/kg), an anti-allergic agent, orally. The neuropeptide content in the skin tissues and serum IgE levels were measured in these mice. Results: Repeated local application of TNCB solution induced itching skin lesions, together with an increase in levels of substance P, a decrease in calcitonin generelated peptide levels and early augmentation of IgE production. Treatment with crowding stress brought about a transient increase in substance P. Furthermore, we observed significant decreases in substance P and serum IgE levels when the administration of olopatadine hydrochloride was started before the elicitation of chronic dermatitis caused by repeated application of TNCB solution. These changes were more definite in the group administered a higher dose of the drug (10 mg/kg). Conclusions: It is suggested that repeated contact allergic dermatitis or mental stress may promote the development and exacerbation of AD and that substance P has a role in this response. In addition, it seems that an anti-allergic drug, such as olopatadine hydrochloride, possibly downregulates substance P, thereby suppressing the development of AD. In the future, the development and clinical application of a drug that strongly influences the release of neuropeptides, such as substance P, and the expression of neuropeptide receptors would be expected for the treatment of AD

Efficacy of combination therapy of steroid and methotrexate for refractory pemphigus

Abstract The first line of treatment for pemphigus is systemic corticosteroids. When steroids alone do not result in remission, additional immunosuppressants are recommended. Twenty‐two patients with pemphigus vulugris were treated with steroids and other immunomodulators. However, they were refractory, and hence, methotrexate (MTX) was administered. The efficacy of MTX was assessed for 16 patients who were able to continue MTX therapy for 1 year. Steroid dose reduction was possible in 11 patients. One patient with severe infections had diabetes and was elderly. Our results suggested that MTX was useful as a steroid‐sparing agent in treating recalcitrant pemphigus, when an initial immunosuppressant treatment had failed. However, adverse effects should be closely monitored

Late-onset Anaphylaxis after Ingestion of Bacillus Subtilis-fermented Soybeans (Natto): Clinical Review of 7 Patients

Background: Allergic reactions after ingestion of fermented soybeans have rarely been reported. Fermented soybeans were recently reported to be a causative food of IgE-mediated, late-onset anaphylaxis without early phase responses. The objectives of our study are to clarify the clinical and laboratory features and to characterize the allergens in allergy due to fermented soybeans. Methods: Seven patients with suspected hypersensitivity to fermented soybeans, from whom informed consent had been obtained, underwent skin prick-prick tests with fermented soybeans and challenge test with fermented soybeans. Additionally, specific IgE against fermented soybeans and the allergens of fermented soybeans were detected by ELISA and IgE-immunoblotting, respectively. Results: Seven male patients, aged 26 to 42 years (mean age, 33.1 years), participated. All patients reported generalized urticaria and dyspnea; 5, loss of consciousness; 2, collapse; 2, vomiting; and 2, diarrhea after fermented soybean ingestion. The interval between fermented soybean ingestion and onset of symptoms was 5 to 14 hours (mean, 9.6 hours). All patients were positive on skin prick-prick tests with fermented soybeans. In 2 patients, oral challenge with fermented soybeans was positive 5.5 and 13 hours after ingestion. In ELISA, all 5 patients tested showed elevated IgE levels to the fermented soybean extract. Furthermore, IgE-immunoblotting using 5 patients' sera showed six bands, of which three bands at 38, 28, and 26-kd were bound to sera from 4 patients. Conclusions: Cases with hypersensitivity after ingestion of fermented soybeans most frequently correspond to IgE-mediated, late-onset anaphylactic reactions due to fermented soybeans

Retrospective analysis of Stevens–Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients – Treatment and outcome

Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. Methods: To present the clinical characteristics of SJS and TEN in Japan and evaluate the efficacy of treatments, we retrospectively analyzed cases of SJS and TEN treated in 2 university hospitals during 2000–2013. Results: Fifty-two cases of SJS (21 males and 31 females; average age, 55.1 years) and 35 cases of TEN (17 males and 18 females; average age, 56.6 years) were included in this study. Twenty-eight cases of SJS (53.8%) and all cases of TEN were caused by drugs. Hepatitis was the most common organ involvement in both SJS and TEN. Renal dysfunction, intestinal disorder, and respiratory disorder were also involved in some cases. The major complication was pneumonia and sepsis. All cases except for 3 cases were treated systemically with corticosteroids. Steroid pulse therapy was performed in 88.6% of TEN. Plasmapheresis and/or immunoglobulin therapy was combined with steroid therapy mainly in TEN after 2007. The mortality rate was 6.9% and the rates for SJS and TEN were 1.9% and 14.3%, respectively. These were much lower than predicted mortality according to a severity-of-illness scoring system for TEN prognosis (SCORTEN) score. When comparing the mortality rate between 2000–2006 and 2007–2013, it was decreased from 4.5% to 0.0% in SJS and from 22.2% to 5.3% in TEN. Conclusions: Treatment with steroid pulse therapy in combination with plasmapheresis and/or immunoglobulin therapy seems to have contributed to prognostic improvement in SJS/TEN

Serum levels of squamous cell carcinoma antigens 1 and 2 reflect disease severity and clinical type of atopic dermatitis in adult patients

Background: Recent studies have indicated that serum levels of squamous cell carcinoma antigen (SCCA) 1 and 2 induced by type 2 cytokines such as IL-4 and IL-13, are increased in patients with atopic dermatitis (AD). However, no clinical studies have analyzed serum levels of SCCA2 in larger series of AD patients or their association with various clinical characteristics. This study was performed to clarify whether serum levels of SCCA2 are associated with disease severity and clinical phenotypes of adult AD patients. Methods: An enzyme-linked immunosorbent assay was performed to examine serum SCCA2 levels in 240 adult patients with AD and 25 healthy controls in this study. Serum SCCA2 levels were analyzed with clinical characteristics and laboratory parameters including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophils, total IgE, and specific IgE (Japanese cedar pollen, Dermatophagoides farina, Candida, malassezia, Staphylococcal enterotoxin B). Expression of SCCA2 in AD eruption was examined by immunohistochemistry. The effect of treatment on serum SCCA2 was also assessed. Results: Serum SCCA2 level showed a positive correlation with disease severity, levels of TARC, LDH, eosinophil counts, and IgE levels. Robust expression of SCCA2 was detected in the supra basal keratinocytes in the epidermis of AD patients. Serial measurements of serum SCCA2 revealed decreased levels of SCCA2 after treatment for AD. Conclusions: Serum SCCA2 levels reflected disease severity and clinical type of AD. Serum SCCA2 may thus be a relevant biomarker for AD