Utako Kimura

Long-pulsed 1064-nm neodymium:yttrium–aluminum–garnet laser treatment for refractory warts on hands and feet

Common warts (verruca vulgaris) are the most commonly seen benign cutaneous tumors. However, warts in the hands and feet regions often respond poorly to treatment, some are resistant to more than 6 months of treatment with currently available modalities, including cryotherapy, being defined as refractory warts. We investigated the usefulness of long‐pulsed neodymium:yttrium–aluminum–garnet (LP‐Nd:YAG) treatment for refractory warts. The clinical trial was conducted on 20 subjects (11 male, nine female) with a total of 34 lesions (periungual/subungual areas, plantar areas, fingers and/or toes). All the subjects suffered from refractory warts despite conventional treatments for more than 6 months. The patients were administrated up to six sessions of treatment, at intervals of 4 weeks between sessions, with an LP‐Nd:YAG at a spot size of 5 mm, pulse duration of 15 msec and fluence of 150–185 J/cm2. Evaluation of the treatment results at 24 weeks after the initial treatment showed complete clearance of the refractory warts in 56% of the patients. Histological evaluation showed separation of the dermis and epidermis at the basement membrane with coagulated necrosis of the wart tissue in the lower epidermis, as well as coagulation and destruction of the blood vessels in the papillary dermis following the laser irradiation. No scarring, post‐hyperpigmentary changes or serious adverse events were documented. Our preliminary results show that LP‐Nd:YAG treatments are safe and effective for refractory warts of hands and feet, causing minimal discomfort, and is a viable treatment alternative.

Tinea faciei caused by Trichophyton mentagrophytes (molecular type Arthroderma benhamiae ) mimics impetigo : a case report and literature review of cases in Japan.

A 36-year-old female elementary schoolteacher presented with aggregated serous papules surrounded by mild erythema, extending from both nasal wings/nostrils down to the upper lip. No improvement was seen following treatment of the lesions with topical antibiotics for impetigo. Potassium hydroxide (KOH) direct microscopy confirmed the presence of mycelia, and the infection was diagnosed as tinea faciei. The isolate was identified as Trichophyton mentagrophytes using morphological analysis and as Arthroderma benhamiae using genetic analysis. Here we describe that case and summarize the clinical features of other cases of A. benhamiae infection in Japan that have been reported in the literature.

Successful treatment with adalimumab in a patient with psoriatic arthritis and generalized pustular psoriasis

Dear Editor, Tumor necrosis factor (TNF)-a inhibitors are used in treating intractable diseases including rheumatoid arthritis. Their dermatological application has started in patients with moderate to severe psoriasis vulgaris in Japan, followed by other psoriasis types including psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP). We present a case of a 36-year-old woman with multiple scaly erythematous keratotic plaques of up to 7 cm on the head, trunk and limbs. She simultaneously had tenderness and swelling of the distal interphalangeal joints of bilateral ring fingers, right wrist, right foot and left knee. She had been treated with topical corticosteroids and calcipotriol ointments under the diagnosis of psoriasis vulgaris for 7 years. Because she had experienced redness and swelling of the other joints 6 months ago, we diagnosed her as having PsA. The condition worsened to the degree that she had difficulty in walking. The value of the Disease Activity Score 28–Creactive protein (DAS28-CRP) was 4.40. X-ray revealed no bone deformity of the fingers, suggesting that the arthritis was of non-rheumatic origin. Additionally, she had repeated episodes of pyrexia of 38 C or higher, and multiple small pustules on psoriatic eruptions. Several of those pustules were in a ring arrangement, and others continued to spread, resulting in the formation of “lakes of pus’’ (Fig. 1a–c). Blood test showed increases in white blood cell count (11 500/lL), erythrocyte sedimentation rate (56 mm/ h), CRP (1.9 mg/dL) and matrix metalloproteinase-3 of 109 ng/ mL (normal range, 17.3–59.7), but the other major blood data were normal. The severity score evaluated by Japan GPP guidelines was 9/17, consisting of 5/9 of skin evaluation and 4/8 of systemic conditions. Histological findings obtained from her abdomen revealed a spongiform pustule of Kogoj in the upper spinous layer, consistent with pustular psoriasis (Fig. 1f). Taken together, her PsA was complicated by GPP. We considered systemic therapy because topical clobetasol propionate ointments and oral celecoxib at 400 mg/day were ineffective for 7 days. The use of oral methotrexate or etretinate was avoided due to her childbearing desire. Because she strongly opposed the infusion, 80 mg adalimumab was administrated s.c. as recommended by the Japanese package insert. Her arthralgia significantly improved after 2 days of injection, resulting in the decrease of DAS28–CRP to 2.16. All of the multiple pustules resolved within 5 days. The initial dose was decreased to 40 mg every other week, resulting in complete resolution of the arthralgia, a negative CRP test and a decrease of DAS28-CRP to 2.06 at 10 weeks of treatment (after the sixth injection) (Fig. 1d,e). The Psoriasis Area and Severity Index score decreased from 20.2 at the initial presentation to 4.2 at 10 weeks. No relapses or adverse drug reactions have been observed subsequently. Because infliximab has rapid onset of action and high efficacy in GPP, it would be a preferred choice among the available TNF-a antagonists. Additionally, to our knowledge, the

Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis

BACKGROUND Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H1-antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. OBJECTIVE This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. METHODS Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. RESULTS Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. CONCLUSION Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD.

The Excimer Lamp Induces Cutaneous Nerve Degeneration and Reduces Scratching in a Dry-Skin Mouse Model

Epidermal hyperinnervation, which is thought to underlie intractable pruritus, has been observed in patients with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. Previously, we showed that the excimer lamp has antihyperinnervative effects in nonpruritic dry-skin model mice, although epidermal expression of axonal guidance molecules was unchanged. Therefore, we investigated the antipruritic effects of excimer lamp irradiation and its mechanism of action. A single irradiation of AD model mice significantly inhibited itch-related behavior 1 day later, following improvement in the dermatitis score. In addition, irradiation of nerve fibers formed by cultured dorsal root ganglion neurons increased bleb formation and decreased nerve fiber expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting degenerative changes in these fibers. We also analyzed whether attaching a cutoff excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA damage marker, in dry-skin model mice. Irradiation with COF decreased CPD production in keratinocytes, as well as having an antihyperinnervative effect, indicating that the antipruritic effects of excimer lamp irradiation with COF are due to induction of epidermal nerve degeneration and reduced DNA damage.

Importance of tryptophan nitration of carbonic anhydrase III for the morbidity of atopic dermatitis

The nitration of proteins results from the vigorous production of reactive nitrogen species in inflammatory disease. We previously reported the proteomic analysis of nitrated tryptophan residues in in vitro model cells for inflammatory diseases using a 6-nitrotryptophan-specific antibody. In this paper, we applied this method to the analysis of a disease model animal and identified the 6-nitrotryptophan-containing proteins in the skin of atopic dermatitis model mice (AD-NC/Nga mice). We found three nitrotryptophan-containing proteins, namely, carbonic anhydrase III (CAIII), α-enolase (α-ENO), and cytoskeletal keratin type II (KTII), and identified the positions of the nitrotryptophan residues in their amino acid sequences: Trp47 and Trp123 in CAIII, Trp365 in α-ENO, and Trp221 in KTII. Among these, the nitration of CAIII was increased not only in the lesional skin of AD-NC/Nga mice but also in the mice that did not present any symptoms. The in vitro nitration of purified CAIII by peroxynitrite reduced its CO2 hydratase activity in a dose-dependent manner. In addition, we found that CAIII was induced during the differentiation of normal human epidermal keratinocytes. Furthermore, we found the presence of CAIII and the formation of 6-nitrotryptophan-containing proteins in both the lesional and the nonlesional sections of the skin of patients with atopic dermatitis through immunohistochemical staining. This study provides the first demonstration of the formation of 6-nitrotryptophan in human tissues and disease.

Generalized pustular psoriasis-like eruptions induced after the first use of adalimumab in the treatment of psoriatic arthritis

Dear Editor, A 35-year-old man was diagnosed as having psoriasis at a different hospital, on the basis of the clinical features of scaly, red, dry skin patches on the trunk and extremities, pitting of fingernails, and histological confirmation of psoriasiform hyperkeratosis in the lesions. His recent primary clinical concerns included inflamed and swollen proximal interphalangeal (PIP) joints and deformities of the distal interphalangeal (DIP) finger joints. Radiographically, joint space narrowing and joint erosions were observed. Hematological and biochemical parameters, chest radiography and serological tests

Mating type gene for isolates of Trichophyton mentagrophytes from guinea pigs.

Trichophyton mentagrophytes were isolated from 19 of 20 guinea pigs in a childrens corner of a zoo. The nucleotide sequence identity of the internal transcribed spacer region among 19 guinea pig isolates was 99%, including the reference strain of animal type 3 of T. mentagrophytes. The genomic DNA of all isolates were investigated for the mating (MAT) gene by specific polymerase chain reaction. The alpha‐box gene was detected in all 19 isolates, while the high‐mobility‐group (HMG) gene was detected in only one of 19 isolates. Therefore, the guinea pig population harbored at least 2 MAT types of Arthroderma vanbreuseghemii. The T. mentagrophytes that was prevalent in this population may constitute a constant source of infection for persons coming into contact with guinea pigs.

Laser Therapies for Onychomycosis in Japan

Various treatment methods other than oral and topical antifungal medications have been employed to treat onychomycosis. Treatment methods include mechanical removal of the affected part of the nail plate by using a toenail cutter or grinder and chemical removal by using occlusive dressing therapy with salicylic acid plaster or urea cream. In recent years, laser therapies have received attention as modalities for treatment of onychomycosis. Favorable outcomes in patients with onychomycosis have been reported in Japan from treatment combining carbon dioxide laser and topical antifungal drug, treatment with photodynamic therapy, and treatment with Nd:YAG laser. However, irradiation conditions, number of irradiation sessions, and efficacy evaluation methods vary among institutions and studies; thus, there is no established evidence to support these outcomes. In addition, a study reported that a combination of Nd:YAG laser and external antifungal drugs was more effective than each of the treatments alone. Future studies are required to provide clinical evidence on the effectiveness of laser therapies, on the enhancement of effect from the combination of laser and external antifungal drugs, and on the possibility of shortening treatment duration using laser therapies in the management of patients with onychomycosis.

Trial of hyperthermic treatment for Bowen's disease with disposable chemical pocket warmers: A report of two cases

Dear Editor, Bowen’s disease (BD) is a common form of squamous cell carcinoma in situ of the skin. In 2000, Hiruma et al. reported the efficacy of local hyperthermic treatment (HTT) for this disease, and HTT is also recommended in the UK guidelines for BD. However, no trials have examined this treatment. Therefore, we report two cases of local HTT for BD. Case 1: Three years ago, a 35-year-old Japanese man developed a brown plaque on the posterior surface of his left thigh, which did not respond to topical steroid treatment. The original plaque was 18 mm in diameter, well-circumscribed, oval, flat, dark-reddish brown and had slightly elevated margins (Fig. 1a). The diagnosis of BD was based on a slightly thickened epidermis, enlarged tumor cell nuclei and cell clumping (Fig. 1b). The patient elected to delay surgery for 2 months and was instructed to perform HTT at home by applying a disposable chemical pocket warmer for 6 h/day. The lesion subsequently flattened before the surgery, leaving only mild erythema (Fig. 1c). Hematoxylin–eosin staining revealed that the number of tumor cells had decreased, with mild atypia in the residual tumor cells (Fig. 1d). Case 2: Eight years ago, an 81-year-old Japanese woman developed hyperkeratotic erythema on the posterior surface of her right leg. The erythema did not respond to topical steroid therapy. The initial hyperkeratotic erythema was oval and 18 mm in diameter, with mild scaling and crusting (Fig. 1e), and the biopsy findings were the same as those in case 1 (Fig. 1f). The patient declined surgery but consented to undergo HTT using the same method as in case 1. Only mild infiltration was present 8 months later (Fig. 1 g); the follow-up biopsy findings were similar to those in case 1, and the histopathological efficacy was considered partial elimination (Fig. 1 h). The lesion was removed 18 months later because of partial persistence. Treatment for BD is determined based on lesion size, number of lesions, presence/absence of spontaneous regression tendency, functional disorder and systemic conditions. The treatments include 5-flucytosine, imiquimod, cryotherapy, curettage, excision, photodynamic therapy, radiation and laser treatment. Murata et al. have reported pathologically normal interlesional skin regression tendency in 34 of 90 BD cases (38%), which suggests that partial spontaneous regression is possible. Subsequent reports have also described a trend towards or actual spontaneous regression. Hiruma et al. administrated HTT for 4–5 months in eight cases of BD, and the UK guidelines also recommend HTT as an alternative treatment. Because both of our patients were unwilling to undergo surgery at the time of diagnosis, we tried HTT which provided good outcomes after 2 and 8 months, respectively. Although spontaneous regression is possible, we believe that HTT is one of the treatment options for BD, the number of which is increasing due to population aging.