Yoichi Shintani

Tobacco smoke is related to Th17 generation with clinical implications for psoriasis patients

Abstract:  Environmental factors contribute to the increased prevalence of autoimmune diseases via T helper type‐17 cell (Th17) activation. Tobacco smoking increases the risk of psoriasis, but the mechanisms are not clear. We evaluated the percentage of circulating Th17 among CD3+ cells in peripheral blood mononuclear cells (PBMC) obtained from 27 healthy volunteers (2.58 ± 0.80%), 33 smoker (3.55 ± 1.33%) and 21 non‐smoker (3.10 ± 1.14%) patients with psoriasis to elucidate the relation between smoking and psoriasis. More smokers (19/33) than non‐smokers (6/21) had high Th17 levels (Th17/CD3 > 3.38%, mean + 1 SD of healthy volunteers). Tobacco smoke extract (TSE, 7 μl/ml) induced Th17 generation from central memory T cells in vitro. TSE increased interleukin 17 and 22 expression. These findings demonstrate the relation between tobacco smoke and IL‐17 and IL‐22, which exacerbate psoriasis.

Successful treatment with topical tacrolimus in four cases of discoid lupus erythematosus.

Discoid lupus erythematosus (DLE), a cutaneous form of lupus erythematosus, is characterized as atrophic and scaly erythema and the lesions are often refractory to a wide range of topical or systemic therapies. Herein, we present four cases of DLE that were successfully treated with topical tacrolimus. Tacrolimus ointment (0.1%) was applied to DLE lesions twice daily and the erythematous plaques readily diminished after 4–8 weeks. Adverse effects, such as burning sensation or irritations, were not observed. These results indicate that topical tacrolimus might be an effective and alternative treatment to control DLE.

Role of the aryl hydrocarbon receptor in tobacco smoke extract–induced matrix metalloproteinase‐1 expression

Findings from large epidemiologic studies indicate that there is a link between smoking and extrinsic skin ageing. We previously reported that matrix metalloproteinases (MMPs) mediate connective tissue damage in skin exposed to tobacco smoke extracts. Tobacco smoke contains more than 3800 constituents, including numerous water‐insoluble polycyclic aromatic hydrocarbons (PAHs) that trigger aryl hydrocarbon receptor (AhR) signalling pathways. To analyse the molecular mechanisms involved in tobacco smoke–induced skin ageing, we exposed primary human fibroblasts and keratinocytes to tobacco smoke extracts. Hexane‐ and water‐soluble tobacco smoke extracts significantly induced MMP‐1 mRNA in both human cultured fibroblasts and keratinocytes in a dose‐dependent manner. To clarify the involvement of the AhR pathway, we used a stable AhR‐knockdown HaCaT cell line. AhR knockdown abolished the increased transcription of the AhR‐dependent genes CYP1A1/CYP1B1 and MMP‐1 induced by either of the tobacco smoke extracts. Furthermore, the tobacco smoke extracts induced 7‐ethoxyresorufin‐O‐deethylase activity, which was almost completely abolished by AhR knockdown. Likewise, treating fibroblasts with AhR pathway inhibitors, that is, the flavonoids 3‐methoxy‐4‐nitroflavone and α‐naphthoflavone, blocked the expression of CYP1B1 and MMP‐1. These findings suggest that the tobacco smoke extracts induce MMP‐1 expression in human fibroblasts and keratinocytes via activation of the AhR pathway. Thus, the AhR pathway may be pathogenetically involved in extrinsic skin ageing.

Narrowband ultraviolet B radiation suppresses contact hypersensitivity

Background/purpose: A main mechanism responsible for the efficacy of narrowband ultraviolet (UV)B is thought to be the induction of apoptosis in pathogenetically relevant cells. Narrowband UVB therapy, however, generally induces a relatively long remission period. Recently, evidence that UVB radiation induces regulatory T (Treg) cells was reported. Based on these findings, we examined whether narrowband UVB suppresses contact hypersensitivity (CHS) by inducing Treg cells.

Poor adherence to medication as assessed by the Morisky Medication Adherence Scale-8 and low satisfaction with treatment in 237 psoriasis patients

Previously we assessed the medication adherence for oral and topical remedies by a translated Japanese version of the Morisky Medication Adherence Scale‐8 (MMAS‐8) together with socioeconomic backgrounds in 3096 Japanese dermatological patients, and found the medication adherence, especially to topical drugs, was poor in these patients. In order to elucidate the disease‐specific sociomedical factors, we further sub‐analyzed the medication adherence in 237 psoriasis patients and compared it with that in other dermatological diseases such as atopic dermatitis, urticaria or tinea. This study was conducted among patients registered in monitoring system and 3096 eligible patients were enrolled. Our web‐based questionnaire included the following items such as age, sex, annual income, main health‐care institution, experience of effectiveness by oral or topical medication, overall satisfaction with treatment, and MMAS‐8 for oral or topical medication. Mean adherence score by MMAS‐8 was 5.2 for oral and 4.3 for topical medication. More patients with psoriasis used a university hospital and fewer used a private clinic compared with those with the other skin disease patients. Experience of drug effectiveness by oral medication and overall satisfaction with treatment was lower in psoriasis patients than in other patients. In oral medication, significantly better adherence was observed in those of higher age and with higher annual income. The adherence to medication, especially to topical drugs, was poor in 237 psoriasis patients. We speculated that some severe psoriasis patients were not sufficiently treated systemically and were resistant to topical therapy, leading to poor adherence.

Phototherapy reduces serum resistin levels in psoriasis patients

This study investigated phototherapy‐induced changes in certain adipokine levels in patients with psoriasis. Patients with psoriasis (n=36) were recruited and body mass index (BMI) and disease severity (Psoriasis Area and Severity Index) were recorded. Serum resistin and leptin levels before and after bath‐psoralen and ultraviolet (UV) A or narrow‐band UVB therapy were examined by enzyme‐linked immunosorbent assay. Serum leptin levels correlated positively with BMI. Phototherapy induced no remarkable change in the leptin levels, but significantly decreased serum resistin levels from 9.02±8.83 to 4.86±3.30 ng/ml. Serum resistin levels might be involved in insulin resistance and inflammation, and correlate with disease severity in patients with psoriasis. The reduction in serum resistin induced by phototherapy might be related to the clinical efficacy of this treatment for psoriasis.

Comparison of the efficacy of calcipotriol and maxacalcitol in combination with narrow-band ultraviolet B therapy for the treatment of psoriasis vulgaris

Background: Combination treatment with topical vitamin D3 and narrow‐band ultraviolet B (UVB) radiation is effective against psoriasis vulgaris. We compared the efficacy of the topical vitamin D3 derivatives calcipotriol and maxacalcitol in combination therapy.

Feasibility and accuracy of a newly developed hand-held device with a flat-type fluorescent lamp for measuring the minimal erythema dose for narrow-band UVB therapy

Background: Narrow‐band ultraviolet B (NB‐UVB) for the treatment of refractory skin diseases, such as psoriasis and atopic dermatitis, requires an adequate irradiation protocol based on the minimal erythema dose (MED) to establish an optimal dosage schedule. Although MED can be measured using a systemic‐type irradiation unit, there are difficulties associated with this device. There is no standardized device available to determine the MED for NB‐UVB. Here, we compared a conventional device with a newly developed device for measuring MED.

The development of a filter to enhance the efficacy and safety of excimer light (308 nm) therapy

Background: Excimer light (308 nm) therapy is a new ultraviolet (UV) B phototherapy for which the efficacy and resulting DNA damage are not well established.

Case of unilateral focal dermal hypoplasia (Goltz syndrome)

Focal dermal hypoplasia (FDH) is a rare multisystem condition in which developmental defects of the skin are associated with ocular, dental and skeletal abnormalities. Herein, we report an 8‐year‐old girl with FDH. Her body halves were asymmetric and she had linear cutaneous atrophy with yellow nodules on her extremities. Syndactylies of the third and fourth fingers of the right hand and second and third toes of the right foot were also observed. Histological examination revealed dermal hypoplasia and upward extension of the adipose tissue. Based on these observations, she was diagnosed with unilateral FDH.