We evaluated the effect of erythromycin therapy on pulmonary function tests and the airway inflammatory response of patients with DPB. The number of neutrophils in BALF obtained from DPB patients was significantly higher than that of healthy volunteers. Treatment with erythromycin (600 mg/day for 12.9+/-9.5 months (mean +/- s.d.)) significantly reduced the total number of cells and neutrophils in the airway, and significantly improved pulmonary function tests. The levels of IL-1beta and IL-8 were significantly higher in DPB compared with healthy volunteers (P<0.05, P<0.05, respectively). IL-1Ra in patients is considered to have a weak inhibitory activity for IL-1beta, with approximately five-fold concentration of IL-1beta compared with that in healthy volunteers (approx. nine-fold concentration of IL-1beta). Erythromycin therapy significantly reduced these cytokines to levels comparable to those of healthy volunteers, and produced a trend toward reduction in the level of IL-1Ra in BALF. The level of IL-1beta correlated significantly with the concentration of neutrophils in BALF (r=0.72, P<0.01), as well as with the level of IL-1Ra (r=0.688, P<0.05) and IL-8 (r=0.653, P<0.05). A nearly significant or significant correlation was observed between the concentration of neutrophils and levels of IL-1Ra or IL-8 in BALF (r=0.526, P=0.053 or r=0.776, P<0.01, respectively). There was also a significant relationship between FEV(1) and the concentration of neutrophils in BALF (r=0.524, P<0.05). Our results suggest that the relative amounts of IL-1beta and IL-1Ra or IL-8 may contribute, at least in part, to the neutrophil-mediated chronic airway inflammation in patients with chronic airway disease, and long-term erythromycin therapy may down-regulate the vigorous cycle between the cytokine network and neutrophil accumulation, with resultant reduction of neutrophil-mediated inflammatory response.

Skin disorders are frequent adverse events after coronavirus disease 2019 (COVID‐19) vaccination. However, the pathogenesis of these disorders is not fully understood. Here, we report a case series of cutaneous adverse events following COVID‐19 vaccination, and the results of our investigation reveal the underlying mechanism. Case 1: a 47‐year‐old female developed a wheal, confined to the COVID‐19 vaccination site, 2 days after her first injection. She was treated with topical steroids and oral antihistamines. Case 2: a 51‐year‐old female showed generalized petechial erythema accompanied by fever, genital bleeding, thrombocytopenia, liver dysfunction, and disseminated intravascular coagulation, 2 days after her second injection. She was diagnosed with vaccine‐induced macrophage activation syndrome and treated with anti‐inflammatory therapy. Immunohistological analysis of the skin eruption, in both these cases, showed infiltration of CD123 + BDCA2 + plasmacytoid dendritic cells (p‐DC). Despite the distinctive clinical features in these two cases, this finding suggests that p‐DC might be involved in different cutaneous adverse events after COVID‐19 vaccination.

IntroductionSweat secretion is controlled by the sympathetic nervous system and is less active during winter than in the summer. Raynaud’s phenomenon is affected by an excessive strain of the sympathetic nerves after exposure to a cold environment, thus reducing the quality of life of patients with collagen disease. Herein, we focus on the eccrine sweat glands that receive both adrenergic and cholinergic innervation. Our hypothesis is that excessive activation of sympathetic nerve in Raynaud’s phenomenon can affect sweating, especially in winter. This study is designed to evaluate the neuroactive sweating responses in patients with collagen disease and to assess its association with skin findings in peripheral circulatory disorders.Methods and analysisThe study will be conducted at a single centre in Japan. Patients with systemic sclerosis, Sjogren’s syndrome, systemic lupus erythematosus, mixed connective tissue disease, and dermatomyositis will be assessed using the quantitative sudomotor axon reflex test. The primary outcomes will be sweat volume and reaction time due to axon reflex and the Raynaud’s condition score. The secondary outcomes will include patient background, skin symptoms (digital ulcers, pernio-like eruptions, subcutaneous calcifications, telangiectasia, nailfold capillary dilatation/bleeding and degree of skin sclerosis) and skin surface temperature. Evaluation will be done two times, during the summer and winter, allowing for the assessment of seasonal differences in sweating responses.Ethics and disseminationEthical approval of this study was certified by the clinical research review board of Nagasaki University Hospital (Reference number: CRB19-001). We will disseminate the findings of this study through peer-reviewed publications and conference presentations.Trial registration numberjRCTs072190009; pre-results.

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Familial Mediterranean fever (FMF) is a rare hereditary autoinflammatory disorder that is caused by pyrin gene mutation associated with aberrance of the interleukin (IL)-1b pathway and characterized by recurrent, self-limiting attacks of fever and other inflammatory symptoms. We report a case of FMF with annular erythema and psoriasis-like lesions, the latter of which demonstrated parakeratosis with neutrophil microabscesses and mild inflammatory mononuclear cell infiltration in the upper dermis. Immunofluorescence staining showed IL-17-positive T-cells. Skin eruption with neutrophil migration in the epidermis may be provoked by T-helper 17 cell activation through the abnormal IL-1b cascade in FMF.