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Cogan's syndrome (CS) is defined by the combination of hearing loss, vertigo, and ocular inflammation of uncertain cause, and can be associated with variable vessel vasculitis. Vasculitic manifestations may include arteritis (affecting large, medium or small arteries), aortitis, and aortic and mitral valvulitis. Cutaneous manifestations including erythema, papules, subcutaneous nodules, and purpura sometimes occur; however, to date, only six cases have been histologically confirmed to have genuine vasculitis. Here, we report two cases of CS, one of which involved a patient who developed the typical symptoms of Takayasu arteritis and purpuric lesions in the legs, with histologic findings consistent with small vessel vaculitis in the dermis. The second case involved a patient who developed subcutaneous nodules in the legs and the axilla, and histologic findings revealed a necrotizing vasculitis of the small arteries in the interlobular area. Both cases were successfully treated with systemic steroid therapy. Based on the clinical features and the examination data, there is a possibility that a Chlamydia trachomatis infection played a pivotal role in the pathogenesis of those vasculitides.

The proposal by the 1994 International Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitides (CHCC1994) and by the CHCC2012 markedly influenced the classification and way of considering cutaneous vasculitis. In the proposal by the CHCC1994, hypersensitivity angiitis was defined as an equivalent pathological condition to microscopic polyangiitis or cutaneous leukocytoclastic angiitis (CLA), and it was not adopted as a disease name. However, CLA which was positioned as a type of small-vessel vasculitis is only a pathological name. In the proposal by the CHCC2012, a new category of single-organ vasculitis included CLA and cutaneous arteritis. Vasculitis allergica cutis (Ruiter) corresponded to CLA and cutaneous polyarteritis nodosa corresponded to cutaneous arteritis. The Japanese Dermatological Association (JDA) prepared guidelines for the management of vasculitis and vascular disorders in 2008 based on the proposal by the CHCC1994 and their original viewpoint of dermatology. The JDA subsequently revised the 2008 edition guidelines in 2016 following publication of the proposal of the CHCC2012 in Japanese. We presented the outline of the 2016 edition guidelines and propose a treatment algorithm for primary vasculitides based on the evaluation of the cutaneous symptoms for cases suspected as primary cutaneous vasculitides, which integrates the 2008 JDA guideline and CHCC2012 classification. This is the secondary English version of the original Japanese manuscript for the guideline for management of vasculitis and vascular disorders published in the Japanese Journal of Dermatology 127(3); 299-415, 2017.

The atypical protein kinase C (aPKC)-partition-defective (PAR) complex regulates the formation of tight junctions and apico-basal epithelial polarity. To examine the role of this complex in the epidermis, we generated mutant mice harboring epidermal-specific deletion of aPKCλ (conditional knock-out (cKO)), a major component of the aPKC-PAR complex. The mutant mice exhibited abnormal hair follicle (HF) cycling, progressive losses of pelage hairs and vibrissae, and altered differentiation into the epidermis and sebaceous gland. We found that in the aPKCλ cKO mice HF stem cell (HFSC) quiescence was lost, as revealed by the decreased expression level of quiescence-inducing factors (Fgf18 and Bmp6) produced in Keratin 6-positive bulge stem cells. The loss of quiescence dysregulated the HFSC marker expression and led to the increase in Lrig1-positive cells, inducing hyperplasia of the interfollicular epidermis and sebaceous glands, and drove an increase in Lef1-positive matrix cells, causing a prolonged anagen-like phase. Persistent bulge stem cell activation led to a gradual depletion of CD34- and α6 integrin-positive HFSC reservoirs. These results suggest that aPKCλ regulates signaling pathways implicated in HFSC quiescence.

A 63-year-old Japanese man with non-Hodgkin B-cell lymphoma presented with erythematous skin lesions on his entire body, with oral, ocular and anal mucosal lesions. The patient was diagnosed with paraneoplastic pemphigus. Immunofluorescence showed both immunoglobulin (Ig)G and IgA antibodies to keratinocyte cell surfaces. Various immunoblot and enzyme-linked immunosorbent assays showed both IgG and IgA antibodies to various autoantigens, including desmogleins, desmocollins, envoplakin, periplakin and bullous pemphigoid antigens. This was a unique case with a very rare autoantibody profile in paraneoplastic pemphigus.

Extranodal natural killer/T-cell lymphoma (ENK/TCL) is most often in the nose or the nasopharynx but can present elsewhere. We report a rare case of ENK/TCL that presented as swelling of an upper eyelid without ocular involvement. A 76-year-old man visited our hospital with a swollen lesion of the left upper eyelid which had appeared 2 months earlier. A biopsy of the upper eyelid revealed slight perivascular and periadnexal infiltration of mononuclear cells with dermal edema. Treatment with oral prednisolone at a dosage of 20 mg/day decreased the eyelid swelling. However, 5 months later, exacerbation of the swelling and nasal congestion were observed. A second biopsy of the upper eyelid revealed a diffuse dermal infiltrate composed of mononuclear cells with an angiocentic growth pattern. Immunohistochemical studies and in situ hybridization showed natural killer-lineage antigens (CD56, granzyme B, and T-cell intracellular antigen 1) with expression of Epstein-Barr virus. These findings lead to the diagnosis of ENK/TCL. We treated the patient with radiation therapy (50 Gy) and 3 courses of a regimen including dexamethasone, carboplatin, etoposide, and ifosphamide. This case suggests that ENK/TCL can present with swelling of an upper eyelid as the primary sign of the skin lesion. Swelling of an upper eyelid should be considered in the differential diagnosis of ENK/TCL.

A 72-year-old man was referred to our hospital for treatment of an ulcer that had been growing on his back for 10 years. Physical examination showed an ulcerated tumor from the neck to the back and swollen cervical lymph nodes. The tumor size was 12×9 cm. Histology of the biopsy showed a nodular and morpheic basal cell carcinoma (BCC). A chest computed tomography (CT) scan showed multiple lung tumors. CT-guided biopsy of the lung and the cervical lymph node revealed metastatic basal cell carcinoma (MBCC). The primary skin tumor was resected and a total of 10 courses of cisplatin (25 mg/m2/day×75%) and adriamycin (50 mg/m2×75%) were administered for metastatic basal cell carcinoma (MBCC). The patient died 5 years and 3 months after his first visit. Autopsy revealed MBCC in the lung, kidney, pancreas, several lymph nodes, liver and bone. A portion of the tumor cells were composed of squamoid cells with eosinophilic cytoplasm, large nuclei, lack of the characteristic peripheral palisading and retraction artifacts, and variable cytoplasmic keratinization. These pathological findings were compatible with basosquamous cell carcinoma. Chemotherapy was effective for MBCC in this patient.

Objective To prepare a dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (CHCC2012) to address vasculitides affecting the skin (D-CHCC). The goal was to standardize the names and definitions for cutaneous vasculitis. Methods A nominal group technique with a facilitator was used to reach consensus on the D-CHCC nomenclature, using multiple face-to-face meetings, e-mail discussions, and teleconferences. Results Standardized names, definitions, and descriptions were adopted for cutaneous components of systemic vasculitides (e.g., cutaneous IgA vasculitis as a component of systemic IgA vasculitis), skin-limited variants of systemic vasculitides (e.g., skin-limited IgA vasculitis, drug-induced skin-limited antineutrophil cytoplasmic antibody–associated vasculitis), and cutaneous single-organ vasculitides that have no systemic counterparts (e.g., nodular vasculitis). Cutaneous vasculitides that were not included in the CHCC2012 nomenclature were introduced. Conclusion Standardized names and definitions are a prerequisite for developing validated classification and diagnostic criteria for cutaneous vasculitis. Accurate identification of specifically defined variants of systemic and skin-limited vasculitides requires knowledgeable integration of data from clinical, laboratory, and pathologic studies. This proposed nomenclature of vasculitides affecting the skin, the D-CHCC, provides a standard framework both for clinicians and for investigators.

We present a woman with squamous cell carcinomas on both feet in long-standing eczematous lesions. Histopathological examination of biopsies from the both feet revealed highly atypical cells invading the reticular layer of the dermis in the hyperkeratotic lesion and they were associated with surrounding dermatitis with spongiosis. Although the cause and etiology of eczema in our case is unclear, we speculate that the exceptionally long-lasting dermatitis might have induced double SCCs on bilateral feet with an unusual constitution. To the best of our knowledge, this is a first case of SCC on bilateral feet arising in long-standing eczematous lesions.

Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. The lumican expression correlates with pathological conditions and the growth and metastasis of various malignancies. In cutaneous neoplasms, the lumican expression is lower in advanced-stage malignant melanomas that invade the dermis than in early-stage melanomas. Furthermore, we have recently reported that the expression pattern of lumican is different from that of actinic keratosis and the Bowen disease. Lumican is positive in the poroid cells of intraepidermal sweat ducts; therefore, we examined the expression patterns of lumican in acanthotic-type seborrheic keratosis and Pinkus-type poroma followed by clonal-type seborrheic keratosis and hidroacanthoma simplex. The neoplastic cells of acanthotic-type seborrheic keratosis exhibited positive immunostaining in only 1 of 31 cases (3.23%), whereas the poroid cells of Pinkus-type poroma exhibited positive immunoreactivity in 26 of 28 patients (92.8%). In the hidroacanthoma simplex cases, lumican was expressed in poroid cells forming intraepidermal nests in 22 of 28 patients (78.6%), whereas the neoplastic cells in most cases of clonal-type seborrheic keratosis were negative for lumican. In some seborrheic keratosis cases that were positive for lumican in neoplastic cells, lumican was observed in squamoid cells but not in basaloid cells. Therefore, it is necessary to evaluate the immunoreactivity of lumican in seborrheic keratosis and in basaloid cells. These findings suggest that lumican is a potent differential diagnostic marker that distinguishes hidroacanthoma simplex from clonal-type seborrheic keratosis.

Skin eruption with mild itching of the hands and feet developed in a man in his 90s 1 month after he was hospitalized following a traffic accident. Scabies was diagnosed in an attending nurse 3 months after the patient's hospitalization, and infection from the patient was suspected. Cornification of the patient's soles and marked hypertrophy of the nails of both feet were observed. After a large number of scabies mites were detected on microscopic examination, crusted scabies was diagnosed. The patient was given oral ivermectin, 6 mg, once per week for 3 weeks, and crotamiton topical ointment containing 30% benzyl benzoate was applied on the body from the neck down. However, because a large number of scabies mites were detected again on microscopic examination, the dose of ivermectin was increased to 12 mg and administered 3 times. One week after the sixth dose of ivermectin was administered, hemorrhagic scabs around the mouth and erosion of the tongue developed. Mucosal drug eruption was suspected, and eruptions around the mouth and on the tongue resolved within 1 week after ivermectin being discontinued. 1% gamma-benzene hexachloride ointment was applied topically on the body from the neck down once a week, crotamiton ointment containing benzyl benzoate was applied daily, and the hypertrophic parts of the nails were removed. The patient subsequently achieved a full recovery.

Treating chronic wounds is challenging. Despite standard wound care, some chronic wounds fail to heal. Therefore, hyperbaric oxygen therapy (HBOT) was developed as an adjunct to standard wound care.To evaluate the efficacy of HBOT for treating chronic wounds due to a variety of causes at our institution.We reviewed the medical records of patients with chronic wounds treated with HBOT in addition to standard wound care at the Department of Dermatology, Nippon Medical School Hospital, from 2009 through 2012. Twenty-nine patients were reviewed (14 men and 15 women; mean age, 64.1±14.4 years). The cause of chronic wounds was diabetes mellitus (DM) in 13 patients, venous stasis in 10, polyarteritis nodosa cutanea in 2, and livedoid vasculopathy, pyoderma gangrenosum, chronic renal failure, and systemic sclerosis in 1 patient each. The patients underwent HBOT for 60 minutes with 100% oxygen delivered via a mask in a hyperbaric chamber pressurized to 2.8 atmospheres of absolute pressure. The response of the chronic wounds to HBOT was evaluated according to the following criteria: "excellent": more than 90% wound healing; "good": a greater than 30% reduction in wound size, and wound healing was confirmed on follow-up visits within 6 weeks; "fair": wound healing was achieved with a combination of further invasive interventions; and "poor": the wound showed a less than 30% reduction or worsened during HBOT, or wound healing had not been completed by follow-up visits within 6 weeks.The response to HBOT was "excellent" in 6 patients, "good" in 8, "fair" in 11, and "poor" in 4. All 4 patients with a "poor" response had DM and had undergone hemodialysis.HBOT is an effective treatment for patients with chronic wounds, due to a variety of causes, when used in combination with conventional standard therapy or further interventions. However, HBOT is less effective in patients with DM than in patients with venous stasis because hemodialysis, which is more common in patients with DM, has negative effects on wound healing.

Tenosynovial giant cell tumor (TSGCT) is a benign soft tissue tumor arising from the synovial membrane that composes the lining of joints, tendons and bursae. TSGCT is a common tumor occurring in the hands and fingers, and also consecutively in the knees, ankles, feet and hips. It is rarely found in the scapular region. To the best of our knowledge, only 2 cases arising on the upper back have been reported. This report presents the case of a 44-year-old Japanese female with a TSGCT arising on her right scapular region.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem vasculitis of small- and medium-sized vessels and approximately 40% of patients with EGPA have circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent studies have demonstrated that ANCA-negative EGPA patients have cardiac involvement and tissue eosinophilic infiltration more frequently than ANCA-positive patients. However, a causative relationship between cardiac involvement and tissue eosinophilic infiltration remains to be elucidated. Here we report two cases of ANCA-negative EGPA with microscopic eosinophilic thromboembolism as well as cardiac impairment. Although the cutaneous manifestations of the two cases were quite different, skin specimens from both patients demonstrated that the vessels in the mid- to deep dermis were occluded with fibrin materials and surrounded by marked eosinophilic infiltration without overt leukocytoclastic vasculitis or extravascular necrotizing granuloma. The thrombogenic potential of the eosinophil was revealed by the strong expression of major basic protein, which is thought to be involved in the inhibition of natural anti-coagulation activity and activation of platelets, in the walls of the occluded vessels. The implication of microscopic eosinophilic thromboembolism in EGPA without vasculitic or granulomatous lesions is discussed.

Complete deficiency of the fourth component of complement (C4) is an extremely rare condition. However, it has been reported that partial C4 deficiency can occur in normal subjects, and is associated with several immune diseases. We report a 44-year-old woman who developed slight oedema and punctate purpura on her lower legs after a common cold. She was noted to have persistent microscopic haematuria and proteinuria, and her C4 level was undetectable. On histological examination of a skin biopsy specimen, leucocytoclastic vasculitis was seen, with granular deposition of IgG, IgM, C3 and C1q on the vessel walls in the upper dermis. A renal biopsy showed mild mesangial proliferative glomerulonephritis with slight damage to the capillary loops, and granular deposits of IgM and C4 mainly in the mesangium. The patient was systemically well and needed no medication. The C4 level remained low during the observation period, but neither genotyping nor allotyping analysis identified a C4 deficiency.

Permanent waving is very popular in Japan. Polypeptide chains (main chains) form the principal components of hair, and they are lined up longitudinally. Hair relaxation is also called straight permanent waving, and there are methods that change curly or wavy hair into straight hair. Hair damage as a result of winding, combing, and using high-temperature hairdressing irons is also often seen. By using scanning electron micrographs (SEM) we showed broken hairs and hair damage caused by permanent wave solutions. The hair damage is obvious when comparisons are made with the condition of the hair surface, condition of the cuticle, etc. Hair swelling by permanent wave solutions, manipulations such as winding, etc., inadequate rinsing with water, procedures on injured hair at the outset, etc., are considered possible reasons for any of these types of injury.

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.

E-cadherin is best known as a central molecule in adherens junctions, joining adjacent epithelial cells together, thereby safeguarding epithelial barrier function. However, recent findings have uncovered an immunological role for this adhesion molecule, linked to its expression in dendritic cells (DCs) and alternatively activated macrophages (MPHs) and its impact on intracellular signaling pathways. In this respect, E-cadherin has been shown to influence the immunogenicity/tolerogenicity of DCs through the regulation of β-catenin functionality. For Langerhans cells (LCs), the DC type found in the skin epidermis, E-cadherin is known to mediate interactions with keratinocytes (KCs), thereby immobilizing immature LCs in the epidermis and preventing their maturation. In this issue of the European Journal of Immunology, a study by Mayumi et al. [Eur. J. Immunol. 2013. 43: 270-280] now describes a role for E-cadherin in the final steps of LC differentiation from human peripheral blood monocytes. Although TGF-β induces LC-like cells, these intermediates still express the dermal DC marker DC-SIGN along with Langerin; E-cadherin ligation is sufficient to induce the full LC phenotype in these cells. Here, we place these findings in the context of current knowledge and propose new avenues for future research.

In vivo reflectance confocal microscopy (RCM) provides high-resolution, real-time optical sections of the skin in a non-invasive manner, allowing visualization of the skin in its native state. Highly reflective skin components including melanin, collagen and keratin appear bright (white) in RCM images. RCM examination of solar lentigines is known to show features that correlate well with histologic findings such as supranuclear melanin caps, but there are a limited number of reports on melanocyte dendrites. In this study, we utilized RCM to investigate the melanocyte dendricity and distribution within solar lentigines. Seventeen healthy Japanese females who had fairly large solar lentigines on their faces were recruited to join our clinical study, and we examined them by using RCM on their non-lesional areas, and the inside and the outer rim of the lesional areas. As a result, we discovered that dendritic melanocytes were rarely seen in the center of a solar lentigo (SL), but were seen at a very high frequency in the outer rim of a SL. The results suggest that the melanocytes are more active at the edge of a SL, produce more melanin, and often spread their dendrites widely in a horizontal direction. The findings in this report might shed light on the dynamic pathomechanisms of solar lentigines in vivo.

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in similar outcomes or not. In this article, we reviewed the effect of peeling or peeling agents on the skin in relation to ultraviolet (UV) radiation. The pretreatment of peeling agents usually enhance UV sensitivity by inducing increased sunburn cell formation, lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers. However, this sensitivity is reversible and recovers to normal after 1-week discontinuation. Using animals, the chronic effect of peeling and peeling agents was shown to prevent photocarcinogenesis. There is also an in vitro study using culture cells to know the detailed mechanisms of peeling agents, especially on cell proliferation and apoptotic changes via activating signalling cascades and oxidative stress. It is important to understand the effect of peeling agents on photoaged skin and to know how to deal with UV irradiation during the application of peeling agents and treatment of chemical peeling in daily life.

We present the case of a 64-year-old woman who has suffered from pustulosis palmaris et plantaris for 10 years. At the first examination, many erythematous lesions with purpura, blood crusts, and blisters were present in the lower legs and dorsum of the feet. Painful swelling in the sternal region and dorsal pain were also noted. Elevation of the CRP and myogenic enzyme levels, and liver and renal dysfunctions were noted on blood testing. Histopathologically, leukocytoclastic vasculitis was noted in small blood vessels in the whole dermal layers, and deposition of IgM and C3 in the vascular wall was detected by the direct immunofluorescence techniques. Based on these findings, cutaneous small vessel vasculitis was diagnosed. Because the patient complained of a toothache during the clinical course, an X-ray examination was performed. On pantomography, a radicular cyst and apical periodontitis were noted. The tooth symptoms changed with exacerbation and remission of the skin symptoms. These findings indicate that odontogenic infection is very likely to be a cause of cutaneous small vessel vasculitis in a manner similar to pustulosis palmaris et plantaris.

Ber-EP4 is a monoclonal antibody that recognizes 34-kDa and 39-kDa non-covalently linked glycopolypeptides expressed by most human epithelial cells and carcinomas. In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen's disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co-lesions of both neoplasms. In normal skin tissue, Ber-EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber-EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma also reacted positively in at least 5% of neoplastic cells. No cases of poroma, seborrheic keratosis, AK or Bowen's disease were immunohistochemically positive for Ber-EP4 in neoplastic cells. In all six cases with co-lesions of BCC and AK, neoplastic cells of BCC reacted positively with Ber-EP4 and those of AK were negative. Immunohistochemical examination using the Ber-EP4 antibody is a useful tool for diagnosing neoplasms with follicular germinative differentiation, such as TB, TE or BCC, and for differentiating those from squamous cell carcinoma in situ, poroma or seborrheic keratosis.

Background: Melasma still presents as a difficult entity to treat, especially in the Asian skin phe-notype. Recently laser toning with the Q-switched Nd:YAG has attracted attention. The present study investigated the efficacy of Q-switched Nd:YAG laser toning for melasma, with a histopathological comparison with the Q-switched ruby laser. Subjects and Methods: Eight Japanese females (41–57 yr, mean 52.5 yr) with Fitzpatrick skin type III and bilateral melasma participated in the study. One half of each subject's face (randomly chosen) was treated with Q-switched 1064 nm Nd:YAG laser toning (pulse width 5–20 ns; spot size, 6 mm diameter; fluence, 3.0 J/cm2, 5–7 passes, once/week, 4 weeks: QS:YAG group), and the contralateral half with a single treatment using a Q-switched ruby laser (694.5 nm, pulse width 20 ns, spot size 4 mm diameter; fluence 4.0 J/cm2, 1 pass with approximately 20% overlap: QS:Ruby group). Skin biopsies were taken immediately after the 4th Nd:YAG session and the single ruby session, and histopathological comparison was performed with light- and transmission electron microscopy (TEM). Results: Improvement in melasma pigmentation was seen in both the QS:YAG- and QS:Ruby-treat-ed sides, and this was well-maintained in the QS:YAG group. Ultrastructurally, melanin granules were destroyed in both groups, but there was considerably more morphological epidermal and dermal damage in the QS:Ruby specimens compared with minimal epidermal disruption and cellular damage in the QS:YAG specimens. Conclusions: Q-switched 1064 nm Nd:YAG laser toning offered superior results in the treatment of melasma in the Japanese skin type compared with the Q-switched ruby laser, both ultrastructurally with less immediately post-treatment cellular damage and macroscopically, and a longer recurrence-free interval.

Summary Background Numerous reports have been published on skin rejuvenation by the so-called fractional laser device that delivers a laser beam in a dot form over a grid pattern. Aims In this study, we characterized the effects of a fractional CO2 laser on atrophic acne scars at the clinical and ultrastructural levels. Methods Seven healthy adult Japanese volunteers (aged 32–46 years, mean 37.6, five men and two women of Fitzpatrick skin type III) were recruited for this study. A fractional CO2 laser device, SmartXide DOT (DEKA, Florence, Italy), was used with irradiation parameters set as follows: output power 10 W, pulse width 600 μs, dot spacing 800 μm, and stack 2 (irradiation output power 0.91 J/cm2). A clinical examination and punch biopsy of each subject was performed before and just after the irradiation, and also at week 3 after three irradiation sessions. The biopsy specimens were stained with toluidine blue and were examined ultrastructurally. Results Clinical improvement of the atrophic acne scars was observed at week 3 after the third irradiation session in all cases compared with the condition before treatment. Histologically, outgrowths of many degenerated elastic fibers were observed as irregular rod-shaped masses in the superficial dermis prior to the treatment in the region of the acne scars. At week 3 after the third irradiation, the degenerated elastic fibers were no longer observed, and the elastic fibers were elaunin-like. Conclusions The fractional CO2 laser is considered to be very effective for treating atrophic acne scars.

Background and Objectives Wide application of ALA-PDT for acne is limited due to relative strong side effects, such as pain and erythema. The objective of this study was to establish a protocol for ALA-PDT that would provide specific destruction of sebaceous glands at the lowest concentrations and shortest contact times of ALA. Materials and Methods The rhino (hrrhhrrh) murine model, an experimental acne model, was used in this study. A freshly prepared hydrophilic ALA hydrochloride ointment (2.5%, 5%, and 20%) was applied to the backs of 16-week-old male rhino mice. The fluorescence intensity (FI) of ALA-induced protoporphyrin IX (ALA-PpIX) on the skin was measured by spectrofluorometry. Skin samples were taken at 1, 2, and 4 hours after ALA application to determine the tissue distribution of ALA-PpIX by fluorescence microscopy. Light irradiation was also performed with a broadband light source (600–1100 nm, 15 J/cm2, 60 mW/cm2) with subsequent histological examination 1 day after treatment. Results Prominent increases of ALA-PpIX were observed 1 hour after application of 5% and 20% ALA, while no increase was observed with 2.5% ALA until 2 hours. A direct correlation was found between ALA concentration and ALA-PpIX FI. While no fluorescence was detected 1 hour after application of 2.5% or 5% ALA, 20% ALA produced a strong fluorescence in the epidermis, utricle walls, and sebaceous glands. Histological evaluation showed no damage to skin treated with 2.5% ALA-PDT incubated for 1 hour. Damage was still focused within the sebaceous glands with longer incubation times. Increased ALA concentrations resulted in more prominent damage to the epidermis and sebaceous glands, with deeper damage to the dermis when longer incubation times were used. Conclusion Focused damage of sebaceous glands can be achieved with ALA-PDT when low concentrations of ALA (2.5–5.0%) and short incubation times (to 2 hours) were used. Lasers Surg. Med. 43:376–381, 2011. © 2011 Wiley-Liss, Inc.

This study examined immunohistochemical findings of sebaceous carcinoma and sebaceoma. An immunohistochemical study using 13 anti-cytokeratin (CK) antibodies (anti-CK1, 5-8, 10 and 14-20) and 35 cases of sebaceous carcinoma (16 cases on ocular and 19 cases on extraocular regions) and 10 cases of sebaceoma (no cases arose on the eyelids) was performed. Overall, those in ocular lesions were almost the same as those for extraocular lesions in sebaceous carcinoma other than CK8. The findings in sebaceous carcinoma were almost equal to those of sebaceoma. Over 75% of cases with sebaceous carcinoma were positive with anti-CK5 and anti-CK14 antibodies and negative with anti-CK1, CK10, CK15, CK17, CK18 and CK20 antibodies. Most cases (50-75%) of those were positive with CK7 and negative with CK6, CK16, CK19 and CK8. The sensitivity and specificity of immunohistochemical detection of sebaceous carcinoma using the panel of anti-cytokeratin antibodies were lower than those of other antibodies. Immunohistochemical detection of cytokeratins in diagnosing sebaceous carcinoma should be considered to be ancillary to conventional microscopic findings and those of other antibodies.

Image fusion software can derive a fusion image from single photon emission computed tomography and computed tomography scans. We applied a three-dimensional fusion image to detect sentinel lymph nodes (SLNs) in 3 patients with malignant melanomas of the lumbar, vulvar and head region, respectively. During each operation, we detected SLNs at the expected site, as indicated by the fusion images. The three-dimensional image fusion could thus be confirmed as a simple and helpful method for precisely localizing SLNs in these patients.

A variety of laser or light-based devices have been developed for skin rejuvenation. This study evaluates the efficacy (at the microscopic level) of a combination of pneumatic energy, broadband light, and profusion tip-delivered epidermal growth factor (EGF).Healthy adult Japanese volunteers were recruited for this study. The posterior parts of the left and right arms were treated with a device that combines pneumatic energy and broadband light (Isolaz device). The left arms were also treated with EGF through a tip. Each subject received four treatments at 10-day intervals. Biopsy specimens obtained 3 weeks after the second treatment and 3 weeks after the fourth treatment were examined for histological study.After two treatments, elastin fibers and fibroblasts in the dermal papillary layers of the left arms were increased compared to the right arms. A mean of 173.9 cells positive for proliferating cell nuclear antibody (PCNA) were observed on the left arm compared to 101.0 on the right arm. After the fourth treatment, angiogenesis and increased collagen fibers were observed in the dermal papillary layers of both arms.Four treatments with the addition of the profusion tip appear to hasten new collagen and elastin fiber formation, and the increase of PCNA positive cells so that dermal remodeling begins at an earlier stage than with the Isolaz alone.

BACKGROUND Various laser therapies have been used to treat viral warts, and numerous successful results have been reported, but plantar warts are notoriously difficult to treat and eradicate. MATERIALS & METHODS This study included 35 lesions in 31 patients (17 female, 14 male) with plantar warts. We used a carbon dioxide (CO2) laser for incisions, and the defect was covered with artificial dermis. Follow-up periods ranged from 3 to 12 months. Overall, we examined the presence or absence of human papillomaviruses (HPVs) DNA in the lesional skin of all cases and at the excisional site after treatment in 20 cases. RESULTS Thirty-one of 35 lesions (88.6%) achieved complete clearance after one treatment session. We observed local recurrence in four lesions (11.4%). The application of salicylic acid was effective in treating minor recurrent cases. After complete remission, HPV DNA was not detected in the upper epidermis of the postoperative site. No significant scars or severe pain were seen in any patients. CONCLUSION A combination of CO2 laser therapy and artificial dermis application effectively treated the majority of plantar warts after one treatment, with complete and rapid clearance and no persistent pain. The authors have indicated no significant interest with commercial supporters.

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT) using intense pulsed light (IPL) as a light source (IPL-ALA-PDT) has been used for photorejuvenation, but it is unclear if this protocol can be applied to darker skin types. We performed this study to assess our IPL-ALA-PDT protocol for photorejuvenation in Asian skin. To determine an appropriate dose, ALA ointment (0-20%) was applied to the upper arm of five healthy volunteers and the fluorescence intensity (FI) was measured using a spectrofluorometer. Non-linear regression analysis of FI 2 h after ALA application with global fitting gave a typical sigmoid dose-response curve with R 2 = 0.9705 and saturation after 5% ALA. The entire faces of 16 Japanese women with photodamage were then treated with IPL (500-670 and 870-1400 nm, 23-30 J/cm 2 ) 2 h after application of 5% ALA to one side of the face. Three treatments were delivered at 4-week intervals with follow-up visits. Comparative analysis of photorejuvenation showed noticeable improvements on both sides of the face, although the reduction in the photoaging score from baseline did not differ significantly between the two sides in all subjects. Despite this finding, 75% of the patients felt that the IPL-ALA-PDT-treated side of the face showed greater improvement than the IPL-treated side. However, all IPL-ALA-PDT-treated sides showed adverse effects such as erythema and pain. Therefore, we conclude that the IPL-ALA-PDT protocol requires optimization for photorejuvenation in Asians.

Summary Background. Atopic dermatitis (AD) can be aggravated by mental stress. We recently showed that pretreatment with tandospirone citrate (TC), a serotonin (5-HT) agonist for the 5-HT1A receptor subtype, significantly inhibits stress-induced degranulation of mouse dermal mast cells. Aims. To evaluate the efficacy of TC in treatment of AD. Methods. Changes in anxiety levels, depression symptoms and the clinical severity of AD after administration of TC were examined. Data were collected for 20 patients with AD who received TC 30 mg/day for 4 weeks and 17 patients with AD who did not receive the drug. Profile of Mood States (POMS) scores were used to meaure several types of mental stress. Severity of AD was evaluated using the SCORAD Index, and the patients’ level of stress and sleeping status were evaluated using visual analogue scales. Results. Before TC administration, all scores were markedly different in the 37 patients compared with 37 normal healthy controls matched for age and gender. POMS scores for tension–anxiety (T-A) and the SCORAD Index decreased signficantly in patients who received TC, but did not change significantly in the untreated patients. The two groups had significantly different treatment responses based on changes in T-A scores. There was a significant correlation between changes in the T-A score and SCORAD Index. Conclusion. These data suggest that anxiolytic drugs such as 5-HT1A agonists are useful in the clinical management of stress-associated aggravation of AD. Inhibition of stress-induced mast cell degranulation may be one of the mechanisms underlying the clinical efficacy.

Herein, we report a case of paraneoplastic pemphigus with mild skin features of pemphigus foliaceus and lichenoid stomatitis associated with B-cell lymphoma. A 49-year-old man presented with scattered blisters and erosions on the trunk along with mucosal blisters and erosions. Skin biopsy showed subcorneal acantholytic bulla and oral mucosal biopsy demonstrated lichenoid dermatitis. Direct immunofluorescence showed cell surface deposits of IgG and C3. Indirect immunofluorescence identified circulating IgG autoantibodies to the cell surfaces of normal human skin and also on the transitional epithelium of rat bladder. Enzyme-linked immunosorbent assay using recombinant baculoproteins showed positive antidesmoglein 1 autoantibodies (index 46) but negative antidesmoglein 3 autoantibodies (index 8). Immunoblot analysis using normal human epidermal extract detected BP230 and the 190 kDa periplakin, while immunoprecipitation using radiolabeled cultured keratinocyte immunoprecipitated BP230 and the 210 kDa envoplakin. We consider that the skin lesion was produced by humoral immunity whereas the oral lesion was produced by cellular immunity.

Porocarcinomaとの病理組織学的鑑別が問題となった皮膚原発性上皮性悪性腫瘍の5例を報告した。2例は基底細胞癌であり，3例は有棘細胞癌であった。Porocarcinomaの典型的病理組織像から考えて，病理像でporocarcinomaと鑑別が問題になるのは，基底細胞様細胞と有棘細胞様細胞が混在する例，腫瘍病変内に管腔と鑑別を要する裂隙を形成する例，汗管上皮内に腫瘍細胞の進展がある例であることを示した。