Takeshi Ouchi

Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome.

Epidermal LCs but not dermal DCs take up skin surface protein through intact tight junctions and mediate IgG1 antibody responses to bacterial antigen, conferring protective immunization.

Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex

Plectin is a cytoskeletal linker protein that has a dumbbell‐like structure with a long central rod and N‐ and C‐terminal globular domains. Mutations in the gene encoding plectin (PLEC1) cause two distinct autosomal recessive subtypes of epidermolysis bullosa (EB): EB simplex with muscular dystrophy (EBS‐MD), and EB simplex with pyloric atresia (EBS‐PA). Here, we demonstrate that normal human fibroblasts express two different plectin isoforms including full‐length and rodless forms of plectin. We performed detailed analysis of plectin expression patterns in six EBS‐MD and three EBS‐PA patients. In EBS‐PA, expression of all plectin domains was found to be markedly attenuated or completely lost; in EBS‐MD, the expression of the N‐ and C‐terminal domains of plectin remained detectable, although the expression of rod domains was absent or markedly reduced. Our data suggest that loss of the full‐length plectin isoform with residual expression of the rodless plectin isoform leads to EBS‐MD, and that complete loss or marked attenuation of full‐length and rodless plectin expression underlies the more severe EBS‐PA phenotype. These results also clearly account for the majority of EBS‐MD PLEC1 mutation restriction within the large exon 31 that encodes the plectin rod domain, whereas EBS‐PA PLEC1 mutations are generally outside exon 31. Hum Mutat 30:1–9, 2010.

Indeterminate cell histiocytosis successfully treated with ultraviolet B phototherapy

Indeterminate cell histiocytosis (ICH) is a rare disorder, characterized by infiltration of the skin by neoplastic cells that are characteristically positive for S‐100 and CD1a, but lack Birbecks granules. A 75‐year‐old man presented with a 4‐year history of multiple papules on the trunk, limbs, face and neck. Skin biopsy revealed dense infiltration of histiocytic cells that were CD1a+/S100+, but lacked Birbecks granules. No other abnormality was seen during a general examination including a computed tomography scan of the body, gallium scintigraphy, and an abdominal sonography. Broadband ultraviolet B (UVB) treatment was used for the skin lesions, and partial but almost complete remission was obtained. The case suggests that UVB phototherapy is an option for treatment of ICH.

Granuloma caused by subcutaneous injection of leuprorelin acetate product: Case report and histopathological findings

Leuprorelin acetate is a luteinizing hormone‐releasing hormone (LH‐RH) analog, which is used for chemical castration. Chemical castration treatment has an especially important role for prostate cancer. To ensure ongoing chemical castration, a novel sustained‐action injection system using spherical microcapsules has been developed. We report a patient who had granuloma caused by administration of the 11.25 mg leuprorelin acetate product. Histological examination revealed many giant cells with vacuoles. On the basis of reported cases, these vacuoles are characteristic for the granuloma caused by leuprorelin acetate product. The vacuoles in the granuloma are the same size as the microcapsules, and their shape is almost spherical. We assume that the vacuoles in the granuloma are actually the microcapsules. We expect that there will be investigations regarding the procatarctic cause of granuloma formation.

Trichophyton Tonsurans Infection Manifesting as Multiple Concentric Annular Erythemas

We report a case of dermatophytosis in a Judo wrestler caused by Trichophyton tonsurans (T. tonsurans) with clinical features that mimicked the concentric rings of tinea imbricata. Tinea imbricata is a unique dermatophytosis caused by Trichophyton concentricum (T. concentricum), observed endemically in subtropical to torrid zones and characterized by impressive concentric rings. We found three similar cases of the dermatophytosis in the literature that were reported as tinea pseudoimbricata or tinea indecisiva. All of these cases were associated with systemic or local immunosuppression, perhaps simulating the mechanism of tinea imbricata, which is known to involve the lack of delayed type hypersensitivity to T. concentricum. These cases imply that iatrogenic immunosuppression may perhaps play an important role in the development of the unique clinical features mimicking tinea imbricata. Furthermore, three of the four cases, including the presented case, were caused by T. tonsurans. It may be necessary to consider T. tonsurans infection when multiple concentric erythemas are encountered.

A case of blastomycosis-like pyoderma caused by mixed infection of staphylococcus epidermidis and trichophyton rubrum

Blastomycosis-like pyoderma (BLP) is a type of chronic pyoderma characterized histologically by specific epidermal changes namely: pseudoepitheliomatous hyperplasia and intraepithelial abscesses. These epidermal changes are also seen in blastomycosis (referred to as deep dermatophytosis in North America). Here, we describe the case of a 53-year-old male with prurigo nodularis, diabetes, and chronic lymphocytic leukemia who presented with multiple yellowish-red colored papules that coalesced to form a vegetating plaque. In addition to the typical features of BLP, spores with budding were seen histopathologically in a biopsy specimen. Cultures of a skin specimen grew Staphylococcus epidermidis and Trichophyton rubrum. Antibiotic therapy was effective but failed to eliminate the lesion until antifungal therapy using terbinafine was administered concurrently. Past reports suggest that BLP is mainly caused by bacterial infection, but our case suggests that fungal infection can also be involved as the causative organism in BLP.

Polypoid basal cell carcinoma on the scrotum

Dear Editor, Basal cell carcinoma (BCC) is seen exclusively on hair-bearing skin that is frequently exposed to the sun, especially that on the face. We report here the case of a patient who presented with a black pedunculated nodule on the left scrotum, which was found to be polypoid BCC. A 54-year-old male patient was referred to us with a 2-week history of a rapidly growing tumor on the left scrotum. The lesion had first appeared as a small red nodule 6 months earlier on the site that had been previously injured. The detail of injury is uncertain. An elastic hard, 17-mm, pedunculated black nodule with a smooth surface was found on the left scrotum (Fig. 1). A few small telangiectatic vessels could be seen on its surface without ulceration. Study of an excisional biopsy sample revealed the nodule to be a symmetrical and pedunculated neoplasm. The covering epidermis was thinning, and the neoplasm was composed of solid and cystic aggregations of basaloid cells. The tumor aggregations were restricted to the pedunculated zone. The masses were of various shapes and sizes. Cystic spaces containing hyalinized tissues formed as a result of tumor necrosis (Fig. 2a). The basaloid cells

Acquired dermal melanocytosis of the face and extremities.

Acquired dermal melanocytosis (ADM) is a relatively rare, but well‐described disease among adolescent to middle‐aged East Asian women, particularly those of Japanese and Chinese descent. Clinically, ADM manifests as multiple punctate and greyish‐brown pigmented areas 1–3 mm in diameter occurring on both sides of the forehead and zygomatic region. The subtype of ADM affecting the face and extremities is extremely rare even in East Asian women. We describe three patients with ADM of the face and extremities (ADMFE) and their characteristic clinical features. All patients were Japanese women, and showed multiple greyish‐brown pigmentations on both nasal wings and on the extensor surface of the extremities. We found that the clinical features were strikingly uniform, and that a pigmented lesion on the nasal wing can be an important clue to distinguish ADMFE from other hyperpigmented diseases of the hands and feet. One patient was treated with Q‐switched ruby laser with excellent outcome. Increased awareness of ADMFE can lead to earlier diagnosis and potential treatment.

Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells

Langerhans cells (LCs) are antigen-presenting cells in the epidermis whose roles in antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3) is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen in the autoimmune blistering disease pemphigus. Although antibody-mediated disease mechanisms in pemphigus are extensively characterized, the T cell aspect of this autoimmune disease still remains poorly understood. Herein, we utilized a mouse model of CD4+ T cell-mediated autoimmunity against Dsg3 to show that acquisition of Dsg3 and subsequent presentation to T cells by LCs depended on the C-type lectin langerin. The lack of LCs led to enhanced autoimmunity with impaired Dsg3-specific regulatory T cell expansion. LCs expressed the IL-2 receptor complex and the disruption of IL-2 signaling in LCs attenuated LC-mediated regulatory T cell expansion in vitro, demonstrating that direct IL-2 signaling shapes LC function. These data establish that LCs mediate peripheral tolerance against an epidermal autoantigen and point to langerin and IL-2 signaling pathways as attractive targets for achieving tolerogenic responses particularly in autoimmune blistering diseases such as pemphigus.

Hapten-induced lymphadenosis benigna cutis secondary to squaric acid dibutylester sensitization for alopecia areata

severely painful ulcers, which started to spread from the left leg 1.5 month prior to her visit, was referred to our clinic. Her medical history included rheumatoid arthritis (RA) treated with MTX 5 mg/week, mizoribine 100 mg/day and prednisolone 5 mg/day for 20 years and four episodes of HZ. On physical examination, multiple, hemorrhagic and vesicular/bullous lesions with gangrenous ulcers were observed on her bilateral lower extremities (Fig. 1a–c). Similar lesions were noticed on the left arm, left buttock and face. Laboratory tests detected moderately decreased white cell count (3300/lL), including lymphocytes (211/lL) and mild anemia (hemoglobin 11.0 g/dL). Serum Immunoglobulin G level was normal, however, anti-VZV antibody titer was not increased. The swabs obtained from vesicles detected VZV. A biopsy specimen of a bulla on the thigh demonstrated intraepidermal blister with ballooning degeneration and acantholysis (Fig. 1d). Perivascular dense neutrophilic infiltration with extravasation and fibrin deposition on blood vessel walls were observed in the mid-dermis (Fig. 1f). The diagnosis of disseminated HZ was made. Acyclovir 500 mg/day was administrated i.v. for 5 days, followed by 750 mg/day for an additional 4 days. As the spread of lesion stopped, acyclovir was terminated. One week after, most lesions remained unchanged and blood test detected atypical lymphocytes (2205/lL) and VZV DNA (290 copies/10 peripheral blood mononuclear cells by real-time polymerase chain reaction), indicating viremia. Cytomegalovirus antigenemia tests were negative and no sign of Epstein–Barr virus reactivation was detected during the course. Additional administration of vidarabine (300 mg/day) reduced atypical lymphocytes but failed to recover her general condition. Eventually, she died on day 38. Decline of VZV-specific memory T cells has been reported in relation to age, RA and immunosuppression. In our case, anti-VZV antibody titer was not elevated despite recurrent HZ episodes, suggesting impaired immunity against VZV secondary to long-term RA and its treatment. Virological investigation denied possible contribution of acyclovir-resistant VZV clone. A previous study elucidated that VZV could trigger leukocytoclastic vasculitis. However, a case of HZ with similar manifestations was not found in the published work, implying that impaired immunity against VZV alone is insufficient to explain the condition of our case. Indeed, immunohistochemical study failed to detect VZV antigen in vessel walls (data not shown). An additional mechanism causing damage to vasculature, such as rheumatoid vasculitis, might have contributed to the pathophysiology. The Advisory Committee on Immunization Practices recommended the administration of VZV vaccination to autoinflammatory disease patients receiving low-dose steroids and immunosuppressives. Preemptive vaccination sufficient to elicit immunity may be encouraged, especially to RA patients before immunosuppressive therapy is started.