Acetic acid treatment for toe web infection caused by Pseudomonas Aeruginosa combined with fungal infection: A case series of ten patients

Gram‐negative bacterial toe web infection (GNBTWI) caused by Pseudomonas Aeruginosa combined with fungal infection has variety of treatments. However, these treatments have been poorly described in the literature. Our retrospective study describes patients that had been treated in our medical center with acetic acid combined with local antifungal treatment, to evaluate evidences for the appropriateness of this treatment. Ten patients with evidence of GNBTWI caused by Pseudomonas Aeruginosa combined with local fungal infection which have been treated with acetic acid in Emek Medical Center were identified. Eight patients (80%) had a complete response while two patients (20%) showed only a partial response. Side effects were minimal and included temporary stinging sensation. Acetic acid is a relatively cheap ingredient with minimal side effect profile and highly effective outcomes as a treatment for GNBTWI caused by Pseudomonas Aeruginosa and should be considered as an adjuvant treatment.     

Portable negative‐pressure wound therapy for pyoderma gangrenosum: Report of two cases

Pyoderma gangrenosum is a chronic non‐infectious neutrophilic dermatosis that causes undermining ulcers. Topical therapies for the deep ulcers of pyoderma gangrenosum have not been established. To investigate whether negative‐pressure wound therapy is effective for a pyoderma gangrenosum ulcer, we used the PICO single use negative‐pressure wound therapy system (Smith & Nephew, London, UK) for two pyoderma gangrenosum patients. In these cases, the ulcers decreased in size and necrolytic tissue was removed notably. Moreover, there were no secondary infections nor was there Koebner phenomena. Our cases suggest that portable negative‐pressure wound therapy can be a treatment option for deep, intractable ulcers caused by pyoderma gangrenosum. Because portable negative‐pressure wound therapy devices afford increased mobility to patients, they can give the patient a better quality of life than standard negative‐pressure wound therapy systems do.     

Negative‐pressure closure was superior to tie‐over technique for stabilization of split‐thickness skin graft in large or muscle‐exposing defects: A retrospective study

Skin grafts are frequently used for the reconstruction of skin defects, and optimal stabilization of the graft is essential for successful reconstruction. Although the tie‐over technique has been widely used as a standard method in Japan, we sometimes encounter cases with significant graft loss due to suboptimal stabilization of the graft. Reported risk factors for increased graft loss include the following: defects of a large size, with muscle exposure, and located in the trunk and extremities. Recent studies have demonstrated the usefulness of negative‐pressure closure (NPC) for the stabilization of skin grafts due to the uniform pressure it provides across the graft. Therefore, since March 2017, we have used NPC for skin graft stabilization in patients with defects in the trunk and extremities of more than 10 cm in size or with muscle exposure. We carried out a retrospective comparative study of the outcome of the conventional tie‐over technique versus NPC. Mann–Whitney U‐test revealed that NPC showed significantly higher graft survival rate than tie‐over method (P = 0.0012). In addition, NPC showed a tendency toward shorter operative times (from skin graft harvest to the completion of the graft stabilization) than the tie‐over method (P = 0.0931). These results suggest that NPC may be superior to the tie‐over method for stabilization of skin grafts especially in large or muscle‐exposing defects in the trunk or extremities.     

Evaluation of sentinel node biopsy for cutaneous squamous cell carcinoma

Sentinel lymph node biopsy (SLNB) is a standard care for cutaneous melanoma but its role in cutaneous squamous cell carcinoma (SCC) has not been established. Clinical data was obtained from 54 patients with SCC who received SLNB with the usage of blue dye and radioisotope colloid methods. The positive rate of SLNB in SCC was 7.4%. If the cases were limited to more than T2, the positive rate was 12.9%. Three of 41 patients who was estimated negative LN metastasis by the preoperative tests had micrometastasis (7.3%). Among 13 patients who were suggested to have metastasis in the preoperative tests, only one patient had histological metastasis. One patient with SCC located in the lower lip showed negative SLNB and subsequently developed node recurrence. In conclusion, the efficacy of SLNB in SCC is comparable to that of melanoma in the positive rate. There are two kinds of benefit, avoidance of unnecessary complete lymph node dissection and early detection of metastasis.     

Negative feedback regulation of phosphatidylinositol 3-kinase/Akt pathway by over-expressed cyclooxygenase-2 in human epidermal cancer cells

While enhanced expression of cyclooxygenase (COX)-2 has been observed in human skin epidermal cancer, the mechanisms underlying COX-2 expression have not been completely elucidated. Recently, a role for the phosphatidylinositol-3 (PI3) kinase pathway in COX-2 expression has attracted attention. We investigated COX-2 expression, PI3 kinase activity, and the phosphorylation level of Akt, a downstream effector of PI3 kinase, in the human skin cancer cell line HSC-5. Compared to the nontumorigenic keratinocyte HaCaT, in HSC-5 cells, COX-2 protein expression and PI3 kinase activity were increased. The PI3 kinase inhibitor LY294002 reduced COX-2 expression in HSC-5 cells and, contrary to our expectation, the phosphorylation of Akt was significantly decreased. The expression of Bcl-2, which is regulated by Akt, was reduced, and apoptosis was induced in HSC-5 cells compared to HaCaT cells. COX-2 inhibitor NS398 up-regulated Akt phosphorylation. These results imply that constitutively over-expressed COX-2 down-regulates the Akt phosphorylation through a negative feedback mechanism.     

Multiple plaques on the back: S-100 negative benign granular cell tumor

Granular cell tumor is a rarely seen disease characterized by a gradually developing nodular lesion, which is difficult to diagnose. It has been thought to originate from Schwann cells. The tumor usually appears in the 4th-6th decades of life, more frequently in women and blacks, and has a multifocal location in 10-25% of the cases. The malignancy potential is 1-3%, with 70-74% of the cases in women. Ninety-eight percent of the cases are S-100 positive. The present paper describes an 18-year-old female patient with benign granular cell tumor. This rarely seen type of tumor was S-100 negative and has been detected in biopsies taken from multiple asymptomatic plaques and maculopapular lesions. They were 0.5-4 cm in diameter, light brown in color, and with clear contours and had been gradually growing on her back the last nine years.     

On the significance of negative‐pressure wound therapy with instillation in dermatology

Methods used in the treatment of acute and chronic wounds undergo constant evolution, reevaluation, and innovation. While negative‐pressure wound therapy (NPWT) is an established treatment modality, the combination of NPWT and instillation of normal saline as well as solutions with active antiseptic components for topical treatment of the wound bed represents a novel approach. The well‐known effects of NPWT may thus be combined with those of local antisepsis. They include a decrease in wound area, induction of granulation tissue, and reduction in bacterial colonization. To date, studies have focused on NPWT with instillation for orthopedic/surgical indications, whereas clinical data in dermatosurgery is limited to case reports or small case series. There are as yet no randomized prospective studies investigating NPWT with instillation in the treatment of skin disorders. The goal of this review is to present the method of NPWT with instillation, to highlight its mode of action as well as possible complications and contraindications, and to review the recent literature. In summary, there is increasing evidence that both simple and complicated wounds may be effectively treated with NPWT with instillation, resulting in markedly accelerated tissue granulation and thus earlier defect closure.     

Effects of different negative pressures on reduction of wounds in negative pressure dressings

Negative pressure dressings stimulate the healing of tissue-deficient wounds by applying continuous or intermittent negative pressure. This study was designed to determine the most effective negative pressure level for the reduction of the wound by using negative pressure dressings in animal studies. Fifty male Wister rats weighting 200-250 grams were used throughout the study. The animals were divided into five groups of ten animals each as follows: group 1: no negative pressure and a closed dressing method using a polyurethane foam and an adhesive drape. Group 2-5: 25, 50, 75 and 125 mmHg negative pressure and a closed dressing method using a polyurethane foam and an adhesive drape. The wounds were measured along the vertical and horizontal lengths of the body axis and the wound area was calculated. The reduction of the wound area was weaker in the group with a negative pressure of 25 mmHg, and similarly higher among the groups with negative pressures of 50, 75, or 125 mmHg. There were no significant differences in the reduction of the wound area among the latter three groups.     

Tetra‐arsenic tetra‐sulfide ameliorates lupus syndromes by inhibiting IL‐17 producing double negative T cells

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra‐arsenic tetra‐sulfide (As₄S₄), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus‐prone mice treated with As₄S₄ has showed improved monocytosis, decreased serum interleukin (IL)‐6 and suppressed skin, liver and renal lesions with well‐tolerance. In this study, we explored the effect and mechanism of As₄S₄ on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As₄S₄ treatment groups and dosed with As₄S₄ or placebo for 8 weeks. We found that As₄S₄ prevented the skin, renal and lung lesions of MRL/lpr mice. As₄S₄ significantly decreased the double negative T (DN T) cells and reduced the serum levels of IL‐17, IL‐10, and antinuclear antibodies titer. Further results revealed that the FasL was decreased, and activated caspases elevated in DN T cells in As₄S₄ treated MRL/lpr mice. Taken together, As₄S₄ could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL‐17, which may be produced by DN T cells. As₄S₄ may represent a new therapy for SLE.     

Patch testing with 2.0% (0.60 mg/cm2) formaldehyde instead of 1.0% (0.30 mg/cm2) detects significantly more contact allergy

Background. The currently used patch test concentration for formaldehyde is 1.0% (wt/vol) in water. However, clinical experience and previous studies suggest that 1.0% might be insufficient for detecting an optimized number of clinically relevant cases of contact allergy to formaldehyde. Objectives. To validate earlier patch test results for comparison of 1% (wt/vol) and 2% (wt/vol) formaldehyde in water, and to investigate co‐reactivity with quaternium‐15. Materials and methods. In 12 dermatology clinics, 3591 patients were routinely patch tested simultaneously with 2.0% (wt/vol) (0.60 mg/cm²) and 1.0% (wt/vol) (0.30 mg/cm²) formaldehyde. Micropipettes were used for delivering the exact dosage of the allergen. Results. Significantly more patients reacted to 2.0% formaldehyde than to 1.0% (3.4% versus 1.8%, p < 0.001). Overall, there were no sex differences between those reacting positively to 2.0% and 1.0%. Of 25 quaternium‐15‐positive patients, 4 (0.1%) reacted positively without reacting to formaldehyde. Conclusion. On the basis of the results of this multicentre study, as well as of previous studies, it can be suggested that 2.0% (wt/vol) in water formaldehyde should be used in routine patch testing in the baseline series.     

Functional studies for a dominant mutation in the EDAR gene responsible for hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X‐linked recessive, autosomal dominant or autosomal recessive inheritance traits. The X‐linked form of HED is caused by mutations in the EDA gene, while autosomal forms result from mutations in either EDAR or EDARADD genes. Regarding recessive mutations in the EDAR gene, the pathomechanisms have been well characterized. However, it has remained largely unknown how dominant mutations in the EDAR cause HED. In this study, we performed in vitro analyses for a dominant EDAR gene mutation, p.F398*, as a representative. We showed that the p.F398* mutant EDAR completely lost its affinity to EDARADD, and suppressed the downstream nuclear factor‐κB activation induced by wild‐type EDAR in a dominant‐negative manner. Furthermore, we demonstrated that the mutant EDAR was capable of binding with the wild‐type EDAR, which led to reduced interaction between the wild‐type EDAR and EDARADD. Our findings not only underscore an essential role of the interaction between EDAR and EDARADD in ectodermal development, but also disclose, in part, the molecular basis of autosomal dominant HED.     

Skin graft fixation with negative-pressure dressings

The tie-over bolster dressing is the most commonly used method for securing skin grafts. However, it requires surgical skill and experience to make a skin graft adhere closely to a grafting site when the site has a complicatedly curved surface. The lack of appropriate tension and pressure on the skin graft may produce hematoma, dislocation, or wrinkles in the graft. The grafting site for the dorsum of a hand is particularly complicated and irregular and requires delicate changes in pressure when the tie-over bolster dressing is used for sites supported and not supported by bones. We have obtained a high survival rate at such difficult sites by managing skin grafts with negative-pressure dressings. This paper describes the details of the technique with case reports. We have used this technique for skin graft fixation in 10 patients and confirmed its high utility as evidenced by a survival rate of 95% or higher of the grafted areas. Unlike existing techniques that apply pressure on skin grafts, this technique applies a negative pressure to the space between the skin graft and the grafting site to remove hematomas and pull the whole skin graft onto the grafting site with uniform force for adhesion.     

Skin microbiome differences relate to the grade of acne vulgaris

The skin microbiome plays important roles in the pathogenesis and development of acne. We aimed to investigate the facial skin microbiome of acne and microbiome differences related to different grades of acne. Skin swabs from nine healthy controls and 67 acne patients were collected, and the skin microbiomes were analyzed using 16S rRNA gene sequencing. Compared with healthy controls, acne patients harbored significantly altered skin microbiomes. The skin microbiomes of patients with grade 1–3 acne were similar, but patients with grade 4 acne showed a significantly different skin microbiome compared with grade 1–3 acne, including increased alpha diversity and increased proportions of four Gram‐negative bacteria (Faecalibacterium, Klebsiella, Odoribacter and Bacteroides). In conclusion, acne patients harbored an altered skin microbiome, and more significant dysbiosis was found in patients with grade 4 acne (severe acne). Our findings may provide evidence for the pathogenic mechanisms of acne and microbial‐based strategies to avoid and treat acne, especially grade 4 acne.     

Cutaneous Disseminated Actinomycosis in a Patient with Acute Lymphocytic Leukemia

Actinomycosis is an uncommon infectious disease caused predominantly by Actinomyces israelii. The cutaneous disseminated form is usually caused by hematogenous dissemination from a primary extra-cutaneous lesion. We report here cutaneous disseminated actinomycosis without any detectable extra-cutaneous lesions in a 42-year-old Japanese woman with acute lymphocytic leukemia. Multiple soft nodules developed on her upper and lower extremities. Histopathological examination revealed “sulfur granules”, which are a specific finding for actinomycosis. Cultures from biopsy specimens were not successful. There were no cervicofacial, thoracic, nor abdominal lesions. These findings suggest that cutaneous disseminated actinomycosis in our patient developed primarily in the skin. Although the patient was immunocompromised, antibiotic treatment with minocycline was effective.     

Local reinfusion of B10 cells is effective in the treatment of pustular psoriasis

Psoriasis is a common chronic skin disease characterized by epidermal proliferation and inflammation. Pustular psoriasis (PP) is one of the most serious and refractory. The number, differentiation, and function of B10 cells in patients with PP were analyzed, and the relationship between B10 cells and PP, an autoimmune disease, was explored. We established an Imiquimod psoriasis mouse model and subcutaneously injected B10 cells as treatment. We found that the proportion of B10 cells in the peripheral blood of patients with PP was lower than that of the normal controls. However, the number of B10 precursor cells increased. B10 cells in the peripheral blood may be mobilized to effector sites, such as the skin. In patients with PP, B10 cells do not display evident developmental disorders under the CD40 and TLR9 pathways. Normal human B10 cells were found to inhibit the secretion of IFN‐γ and TNF‐α by lymphocytes significantly. Whereas the function of B10 cells in patients with PP is impaired, and the inhibition is not apparent. Treatment with a B10 cells injection displays a certain therapeutic effect on PP. This study enriched the etiology and pathogenesis of PP. It provides a foundation for cell therapy for the treatment of autoimmune diseases.     

Availability of sentinel lymph node biopsy for cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty‐nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow‐up period were included. Forty‐nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false‐negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post‐treatment metastases. The metastasis‐free and disease‐specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2–T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis‐free and disease‐specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging.     

Negative-pressure dressings in the treatment of pressure ulcers

Applying negative pressure to wounds may speed the formation of granulation tissue, decrease the amount of localized edema, increase blood flow, and accelerate healing. In the present study, we treated ten patients with stage IV chronic pressure ulcers using this negative pressure dressing technique. The long (A) and short (B) diameters of each ulcer were measured to determine size, and the vertical distance from the skin to the deepest point of the ulcer was measured to determine depth. Lesions were measured initially and at weekly intervals. The area of each lesion was taken to be 3.14 x A/2 x B/2 (cm(2)). When we compared the area of ulcer before and after the treatment, the area had been reduced in all cases, and the average reduction was 55.1%. The depth of ulcer also decreased in all cases, and the average reduction was 61.2%. Over the period of evaluation, the method was considered markedly effective in reducing the size and depth of ulcers.