Efficacy of bath-psoralen and ultraviolet A therapy for mycosis fungoides - retrospective analysis of 62 cases.

Photochemotherapy with psoralen and ultraviolet A (PUVA) is widely used for refractory skin diseases. Bathwater delivery of 8-methoxypsoralen (8-MOPS) with subsequent UVA irradiation (bath-PUVA) or oral administration of 8-MOPS with UVA is used to treat mycosis fungoides. We retrospectively analyzed 62 patients with mycosis fungoides (8 stage IA, 30 stage IB, 5 stage IIB, 18 stage IIIA, and 1 stage IVA2) treated with bath-PUVA at the Dermatology Clinic of Nagoya City University Hospital from November 2004 to December 2013. A complete response was achieved in 37 (59.7%) patients, a partial response was achieved in 16 (25.8%), and stable disease was achieved in 6 (9.7%). Progressive disease was observed in 3 (4.8%) patients. Almost all patients in stage IA/IB achieved a complete response. Of the 5 stage IIB patients, 2 achieved a partial response, 1 achieved stable disease, and 2 had progressive disease. The serum concentrations of soluble interleukin-2 receptor and lactate dehydrogenase decreased significantly following treatment with bath-PUVA (p < 0.001). We examined the risk factors of patients whose stage progressed despite PUVA treatment. A multivariate Cox regression analysis of risk factors associated with stage progression yielded a hazard ratio of 28.5 for stage IIb. Treatment with bath-PUVA is highly effective in the early stages of mycosis fungoides, and partially effective in advanced stages.

Wound, pressure ulcer and burn guidelines - 1: Guidelines for wounds in general, second edition.

The Japanese Dermatological Association prepared the clinical guidelines for the "Wound, pressure ulcer and burn guidelines", second edition, focusing on treatments. Among them, "Guidelines for wounds in general" is intended to provide the knowledge necessary to heal wounds, without focusing on particular disorders. It informs the basic principles of wound treatment, before explanations are provided in individual chapters of the guidelines. We updated all sections by collecting references published since the publication of the first edition. In particular, we included new wound dressings and topical medications. Additionally, we added "Question 6: How should wound-related pain be considered, and what should be done to control it?" as a new section addressing wound pain, which was not included in the first edition.

Wound, pressure ulcer and burn guidelines - 6: Guidelines for the management of burns, second edition.

"Wound, pressure ulcer and burn guidelines - 6: Guidelines for the management of burns, second edition" is revised from the first edition which was published in the Japanese Journal of Dermatology in 2016. The guidelines were drafted by the Wound, Pressure Ulcer and Burn Guidelines Drafting Committee delegated by the Japanese Dermatological Association, and intend to facilitate physicians' clinical decisions in preventing, diagnosing and treating burn injury. All sections are updated by collecting documents published since the publication of the first edition. Especially, the recommendation levels of dressing materials newly covered by the Japanese national health insurance are mentioned. In addition, the clinical questions (CQ) regarding the initial treatment of electrical (CQ15) and chemical burns (CQ16), and also the use of escharotomy (CQ22), are newly created.

Wound, pressure ulcer and burn guidelines - 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers.

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.

Adherence to oral and topical medication in 445 patients with tinea pedis as assessed by the Morisky Medication Adherence Scale-8.

BACKGROUND: Adherence is defined as the extent to which a person's behavior corresponds with recommendations from health care providers. Adherence to treatment is an important factor for a good therapeutic outcome. OBJECTIVES: This study aimed to examine the adherence of patients with tinea pedis and to clarify the factors related to it. MATERIALS AND METHODS: We assessed medication adherence for oral and topical drugs using a translated version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with other background factors in 445 Japanese patients with tinea pedis, using a questionnaire in a web-based monitoring system. RESULTS: Overall, high, medium and low adherence rates as assessed by MMAS-8 were 8.7%, 31.7% and 59.6% for oral medication, and 8.6%, 17.4% and 74.0% for topical medication, respectively. The adherence level was significantly higher for oral medication than for topical medication. Subgroup analyses showed that the adherence level for topical medication was significantly higher when topical and oral medications were used in combination than when topical medication was used alone. A low adherence level was shown in employed patients, those for whom their oral medication had not been effective and those with topical medication who had visited their hospital less often than once every six months. CONCLUSION: Patient adherence to therapy can be effectively improved by selecting highly effective medication while considering the prescription of topical and oral antifungal medications concomitantly, by carefully selecting a therapy plan for employed patients and by encouraging patients to visit their doctor regularly.

Characterization of socioeconomic status of Japanese patients with atopic dermatitis showing poor medical adherence and reasons for drug discontinuation.

BACKGROUND: Patients' high adherence to medication is indispensable for the management of skin diseases including atopic dermatitis. We previously showed poor medication adherence in Japanese dermatological patients. OBJECTIVE: This study was conducted to determine the level of adherence to oral or topical medication in Japanese patients with atopic dermatitis, attempting to characterize the socioeconomic status of those patients with poor adherence. METHODS: A web questionnaire survey on demographic data as well as adherence level was conducted on patients registered in the monitoring system. Adherence level was assessed with Morisky Medication Adherence Scale-8 (MMAS-8). Among a total of 3096 respondents with dermatological disorders, data of 1327 subjects with atopic dermatitis were extracted and analyzed. RESULTS: More than 80% of subjects felt that both oral and topical medications were safe and efficacious, while less than 60% of them were satisfied with their treatment. Levels of adherence to oral and topical treatments were evaluated with MMAS-8, giving scores of 4.6 and 4.2, respectively. Demographic factors such as gender, marital status, state of employment, alcohol consumption, frequency of hospital visits, and experience of drug effectiveness had a significant impact on the degree of adherence to treatment. CONCLUSION: Medication adherence level in Japanese subjects with atopic dermatitis was relatively low compared with that of other chronic diseases. Our survey has characterized patients with poor adherence, who are good targets for interventions to maximize potentially limited healthcare resources.

Transient improvement of urticaria induces poor adherence as assessed by Morisky Medication Adherence Scale-8.

Poor adherence to medication is a major public health challenge. Here, we aimed to determine the adherence to oral and topical medications and to analyze underlying associated factors using the translated Japanese version of Morisky Medication Adherence Scale-8 regarding urticaria treatment. Web-based questionnaires were performed for 3096 registered dermatological patients, along with a subanalysis of 751 registered urticaria patients in this study. The adherence to oral medication was significantly associated with the frequency of hospital visits. Variables that affected the adherence to topical medication included age and experience of drug effectiveness. The rate of responses that "It felt like the symptoms had improved" varied significantly among the dermatological diseases treated with oral medications. Dermatologists should be aware that adherence to the treatment of urticaria is quite low. Regular visits and active education for patients with urticaria are mandatory in order to achieve a good therapeutic outcome by increasing the adherence.

Risk factors and treatment responses in patients with vitiligo in Japan--A retrospective large-scale study.

Vitiligo is a refractory skin disease. To investigate the risk factors and treatment responses of patients with vitiligo in Japan, we recorded and analyzed the details of 713 vitiligo patients (comorbidity, treatment responses, family history, age, and sex) who visited the dermatology clinic of the Nagoya City University Hospital, Nagoya, Japan between January 2004 and August 2010 (mean age, 35.2 years; 302 men, 411 women) using logistic regression analysis. The results are expressed as odds ratios (OR) with 95% confidence interval (CI). Patients were diagnosed with vitiligo [n = 644; 338 generalized type (47.4%), 170 segmental type (23.8%), and 136 localized type (19.1%)], nevus depigmentosus (n = 53, 7.4%), halo nevus (n = 14, 2.0%), and hypomelanosis of Ito (n = 2, 0.3%). For generalized and localized types, none of the analyzed factors were statistically significant. For the segmental type, antinuclear antibody (OR = 1.005; 95% CI, 1.00-1.01; p < 0.05) and onset age < 14 years were the significant factors in patients between 15 years and 29 years (OR = 0.246; 95% CI, 0.113-0.538; p < 0.001), 30-54 years (OR = 0.0419; 95% CI, 0.0133-0.132; p < 0.001), and >55 years (OR = 0.0171; 95% CI, 0.00333-0.0879; p < 0.001). The treatment response rates for narrow-band UV-B, topical vitamin D3, and punch graft (1 mm minigraft) were, respectively, as follows: (1) generalized type: 46.3%, 21.1%, and 38.9%; (2) segmental type: 20.3%, 29.0%, and 77.3%; and (3) localized type: 29.2%, 54.8%, and 73.3%. We report the comorbidities and efficacy rates of these treatments. The response data for these treatments, in particular, would be of assistance to the previous explanations, because there were only a few reports on the response data for these treatments. The appropriate treatment should be selected depending on the type of vitiligo.

[A case of abscess of corpus cavernosum as an early symptom of penile pyodermal gangrenosum: we propose the possibility of a new pathogenic finding].

A 76-year-old man with a mass on the penis and a pain during nighttime erection was referred to our institution. T2-weighted magnetic resonance imaging showed a high-intensity area in the dorsal part of corpus cavernosum. We diagnosed him with the abscess of corpus cavernosum. Surgical drainage and chemotherapy had been performed for 3 years. However, it recurred consistently and developed several cutaneous draining fistulae. The abscess culture was sterile. Skin biopsy revealed a diagnosis of penile pyoderma gangrenosum, which was treated successfully with prednisolone and an immunosuppressive drug. Twenty nine cases of the abscess of corpus cavernosum have been reported in the literature. Most of the recurrent cases tend to be idiopathic corpus cavernosum abscess with sterile culture and finally penectomy is performed. Based on this case, we propose a new notion that corpus cavernosum abscess can be an early symptom of pyoderma gangrenosum.

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.

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.

Successful treatment of psoriasis vulgaris with targeted narrow-band ultraviolet B therapy using a new flat-type fluorescent lamp.

Narrow-band ultraviolet B (NB-UVB) therapy is widely used for refractory skin diseases. Targeted phototherapy is now being used to reduce the number of sessions and to avoid exposing normal skin. We developed a targeted NB-UVB therapy using a flat-type lamp emitting a wavelength similar to that of the TL-01 fluorescent lamp. Six Japanese patients with psoriasis were recruited and treated with the flat-type NB-UVB device with an initial dose of 70% of the minimal erythema dose, with a 20% increase at each subsequent session. The plaque severity score was determined. All lesions of the tested patients were responsive to NB-UVB therapy using the flat-type lamp. The mean percent reduction of the lesion was 58.3 ± 17.7%. The mean cumulative dose was 20.8 ± 10.8 J/cm². No side effects were observed during treatment. The flat-type targeted NB-UVB device is compact and convenient, and highly effective for the treatment of limited psoriasis lesions.

Efficacy of 1-mm minigrafts in treating vitiligo depends on patient age, disease site and vitiligo subtype.

Vitiligo vulgaris is a refractory skin disease. Treatment modalities include topical steroids, phototherapy, suction blister roof grafts and cellular grafting techniques. Adverse effects may occur, however, and some cases remain unresponsive to treatment. To evaluate the efficacy of small (1-mm) punch minigraft therapy in relation to patient age, disease site, disease duration and vitiligo subtype. We used a recently developed disposable 1.0-mm punch apparatus to perform minigraft therapy in 20 patients with either generalized (n = 4), segmental (n = 9) or limited (n = 7) vitiligo, and evaluated the area and rate of repigmentation in relation to patient age, disease site, disease duration and vitiligo subtype. The area of repigmentation was significantly greater in patients with segmental vitiligo (n = 9) than in those with generalized vitiligo (n = 4). Repigmentation covered a broader area and occurred more quickly in patients under 15 years of age than in those over 20 years of age (n = 9). Disease duration did not affect the repigmentation rate. The results of the present study suggest that 1-mm minigrafts are effective for treating patients with vitiligo. Better results occurred in patients under 15 years of age, patients with facial grafts, and patients with segmental and limited subtypes.

Safety and efficacy of a fixed-dose cyclosporin microemulsion (100 mg) for the treatment of psoriasis.

Cyclosporin is a second-line modality for the treatment of psoriasis. The long-term efficacy of cyclosporin and potential adverse side-effects, however, are a concern to patients. Therefore, a cyclosporin microemulsion (Neoral), which is steadily absorbed at an ultra-low dosage (1-2 mg/kg per day) or low dosage (2-3 mg/kg per day), is currently recommended. The dose must be calculated based on patient bodyweight and the blood concentration monitored regularly, which is time-consuming. Furthermore, the concentration is related to the safety profile, but not to efficacy. We examined whether a fixed-dose cyclosporin microemulsion (100 mg/day) is effective for treating psoriasis. Enrolled patients (n = 40) were given either 100 mg cyclosporin emulsion once daily (group A) or 50 mg twice daily (group B), regardless of patient weight and condition, before meals in a randomized controlled study. Patient bodyweight ranged 50-80 kg. We assessed the serum cyclosporin concentration 1 h after administrating the medicine (C1 score), Psoriasis Area and Severity Index (PASI) score, quality of life, and the results of regular blood examinations. The improvement rate was 69.4 ± 4.8% in group A and 73.4 ± 4.3% in group B. PASI-50 was achieved by 82% in group A and 84% in group B. At 6 weeks, the number of patients with PASI-50 was significantly higher in group A than in group B. PASI-75 and -90 were also achieved in both groups with no significant difference between groups. Administration of a fixed-dose cyclosporin microemulsion (100 mg/day) is practical for second-line psoriasis treatment.

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±3.30ng/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.

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

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, 7µl/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.

Increased peripheral Th17 in patients with pustulosis palmaris et plantaris.

Pustulosis palmaris et plantaris (PPP) is a chronic recurrent dermatitis characterized by intraepidermal pustules with erythematous scaling on the palms and soles. PPP shares many characteristics with psoriasis, but has a different genetic background. T helper 17 cells (Th17) have an important role in the pathogenesis of psoriasis. In psoriasis, regulatory T cells (Treg) are dysfunctional and circulating Th17 are increased. Whether Th17 are involved in PPP, however, is unclear. Therefore, we examined the Th17 population in peripheral blood mononuclear cells (PBMC) of patients with PPP. Foxp3(+) Treg was also analyzed. We examined circulating Th17 and Treg in the peripheral blood of PPP patients. PBMC were obtained from healthy volunteer controls (n = 26, mean ± SD age 33.11 ± 9.80 years) and PPP patients (n = 24, age 55.00 ± 12.26 years). The proportion of Th17 among the PBMC was 2.52 ± 0.811% (mean ± SD) in healthy controls and 3.23 ± 1.45% in PPP patients. The proportion of Th17 in the PPP patients was significantly higher than that in the healthy controls (p < 0.05, Student's t test). PPP patients had significantly fewer Treg (5.69 ± 1.86%) than healthy controls (7.10 ± 1.78%). Th17 was inversely correlated with Treg.

A surgical approach for stable lesions of linear scleroderma.

A 29-year-old Japanese woman presented with alopecia lesions in her occipital region and was diagnosed as linear scleroderma. Topical steroids along with psoralen and UVA light therapy were applied, but the lesion persisted. A surgical approach was therefore selected to treat the lesion. The resection was successful without any recurrence for 1 year. Sclerotic lesions on the exposed areas can cause cosmetic disfigurement, and surgery may be a useful modality for treating stable linear scleroderma.