Alteration of microbial composition in the skin and blood in vasculitis.

Vasculitis is a systemic autoimmune disease characterized by leukocyte infiltration into blood vessels. Various microorganisms have been associated with the pathogenesis of vasculitis; however, the causal microbial agents and underlying mechanisms are not fully understood, possibly because of the technical limitations of pathogen detection. In the present study, we characterized the microbiome profile of patients with cutaneous vasculitis using comprehensive metagenome shotgun sequencing. We found that the abundance of the SEN virus was increased in the affected skin and serum of patients with vasculitis compared to healthy donors. In particular, the abundance of SEN virus reads was increased in the sera of patients with cutaneous arteritis. Among the bacteria identified, Corynebacteriales was the most differentially associated with vasculitis. Linear discriminant analysis effect size also indicated differences in the microbial taxa between patients with vasculitis and healthy donors. These findings demonstrate that vasculitis is associated with considerable alteration of the microbiome in the blood and skin and suggest a role for the infectious trigger in vasculitis.

Three cases of perioral dermatitis related to fusobacteria treated with ß-lactam antibiotics.

BACKGROUND: The oral tetracyclines, especially minocycline hydrochloride, are often used as an effective treatment for perioral dermatitis; however, they are sometimes difficult to use, especially in children, because of the side effects. OBJECTIVE: The effectiveness of ß-lactam antibiotics was evaluated in three cases of perioral dermatitis. METHODS: Three Japanese patients with perioral dermatitis were treated with cefcapene pivoxil hydrochloride hydrate per os 100-300 mg/day. They were one girl (aged 10 years) and two adult women (aged 32 and 37 years respectively). One of the adult patients had a past history of Meniere's disease and the other had had a side effect, vertigo, from minocycline hydrochloride treatment. The presence of fusobacteria before and after the treatment was examined using the tape-stripping toluidine blue method. RESULTS: These patients showed the improvement in 1-2 weeks and were much improved or cured after 2-5 weeks. No side effects were found during the treatment. Fusobacteria were positive before treatment but became negative after the treatment in all of them. CONCLUSION: The ß-lactam antibiotics might be a useful treatment for perioral dermatitis, especially in cases who cannot take tetracyclines.

Possible involvement of chemokine-induced platelet activation in thrombophilic diathesis of antiphospholipid syndrome.

Among the heterogeneous antiphospholipid antibodies, many studies suggest that those directed to beta2-glycoprotein I (beta2GPI) are the major pathogenic antibodies in antiphospholipid syndrome (APS). They have been shown to activate the coagulation pathway via several mechanisms, activate platelets via thrombin formation, and suppress fibrinolysis. Additionally, we propose another possible mechanism that involves certain chemokines and results in platelet activation. This hypothesis is based on the observations that anti-beta2GPI antibodies stimulated monocytes to secrete inflammatory cytokines such as IL-1beta and TNF-alpha, which in turn stimulated vascular endothelial cells to express chemokines such as CX3CL1 and CCL5. CX3CL1 increased the ability of normal platelets to adhere to collagen at a high shear rate, while CCL5 induced platelet aggregation. Expression of tissue factor, IL-1beta, and TNF-alpha by monocytes stimulated with anti-beta2GPI antibodies, as well as CX3CL1 and CCL5 by vascular endothelial cells stimulated with IL-1beta or TNF-alpha were all suppressed by the NF-kappaB-specific inhibitor DHMEQ. These results suggest that the NF-kappaB pathway may be a potential therapeutic target relating to both the coagulation pathway and platelet activity.

Effect of vitamin D3 on the increased expression of Bcl-xL in psoriasis.

Psoriasis is a chronic skin disease characterized by epidermal hyperproliferation, which may be regulated by several mechanisms including apoptosis. In this study, we detected DNA fragmentation by the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) method and immunohistochemically examined the expression of Bcl-x and Bax in psoriasis. We determined the expression of bcl-xL mRNA by RT-PCR, and also determined the effect of vitamin D(3) (VD3) on bcl-xL mRNA expression in cultured normal human keratinocytes by RT-PCR, and the expression of Bcl-xL in psoriatic lesions before and after topical application of VD3. A large number of TUNEL-positive cells as well as Bcl-xL - and Bax-positive cells were observed throughout the epidermis in psoriatic lesions. Whereas, in nonlesional and normal skin, only a few TUNEL-positive cells were observed and only the lower epidermis showed positive staining for Bcl-x and Bax. We also observed higher expression of bcl-xL mRNA in psoriatic lesions than in nonlesional and normal skin. The expression of bcl-xL mRNA in cultured normal human keratinocytes stimulated or not with IFN-gamma and PMA was suppressed by VD3 in a dose-dependent manner, and the expression of Bcl-xL, but not Bax, in psoriatic lesional skin decreased after topical application of VD3 for 4 weeks. In conclusion, it is suggested that the apoptotic process in psoriatic lesions is in part regulated by Bcl-xL, and decreasing the expression of Bcl-xL by treatment with VD3 might ameliorate psoriatic lesions by contributing to the completion of the apoptotic process.