[Show abstract][Hide abstract] ABSTRACT: Epidermal Langerhans cells (LCs) extend dendrites through tight junctions (TJs) to survey the skin surface, but their immunological contribution in vivo remains elusive. We show that LCs were essential for inducing IgG(1) responses to patch-immunized ovalbumin in mice that lacked skin dendritic cell subsets. The significance of LC-induced humoral responses was demonstrated in a mouse model of staphylococcal scalded skin syndrome (SSSS), a severe blistering disease in which the desmosomal protein Dsg1 (desmoglein1) is cleaved by Staphylococcus aureus-derived exfoliative toxin (ET). Importantly, ET did not penetrate TJs, and patch immunization did not alter epidermal integrity. Nevertheless, neutralizing anti-ET IgG(1) was induced after patch immunization and abolished upon LC depletion, indicating that antigen capture through TJs by LCs induced humoral immunity. Strikingly, the ET-patched mice were protected from developing SSSS after intraperitoneal ET challenge, whereas LC-depleted mice were susceptible to SSSS, demonstrating a vital role for LC-induced IgG(1) in systemic defense against circulating toxin in vivo. Therefore, LCs elicit humoral immunity to antigens that have not yet violated the epidermal barrier, providing preemptive immunity against potentially pathogenic skin microbes. Targeting this immunological process confers protection with minimal invasiveness and should have a marked impact on future strategies for development of percutaneous vaccines.
Full-text · Article · Dec 2011 · Journal of Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: Herlitz junctional epidermolysis bullosa (H-JEB) is an extremely rare genodermatosis characterized by lethality owing to severe blister formation. We report two unrelated Japanese patients with H-JEB. Genetic analyses detected a single nonsense mutation on the LAMC2 gene in these two patients.
To identify the mutation involved and describe the first reported Japanese recurrent mutation in the LAMC2 gene.
Direct sequencing was performed of DNA from either peripheral blood or fetal cells in amniotic fluid. Reverse transcriptase PCR was used to confirm that an aberrant transcript resulted from the splice site mutation. A haplotype analysis was performed to define the origin of the recurrent mutation.
Both patients had blisters and erosions on the trunk and limbs at birth, with nail dystrophy. Patient 1 died as a result of sepsis at 30 weeks of age, and patient 2 died as a result of disseminated intravascular coagulation at 20 weeks of age. Mutation analysis of the LAMC2 gene revealed that patient 1 was compound heterozygous for a nonsense mutation (p.Cys553X) and a novel splice site mutation (c.2868+1delG), and patient 2 was a homozygous for p.Cys553X. Prenatal diagnosis performed during a subsequent pregnancy in family 2 revealed that this second child was heterozygous for p.Cys553X, and was thus not affected. Haplotype analysis suggested that a p.Cys553X allele derived from the same origin had been independently inherited by these two unrelated families.
p.Cys553X in the LAMC2 gene may be a Japanese-specific recurrent mutation as a result of a founder effect, and it may therefore be useful for initial screening in the mutation analysis of H-JEB.
No preview · Article · Dec 2010 · Clinical and Experimental Dermatology
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2010 · The American Journal of dermatopathology
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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 Birbeck's 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 Birbeck's 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.
No preview · Article · Jun 2008 · Clinical and Experimental Dermatology
[Show abstract][Hide abstract] ABSTRACT: Pseudallescheria boydii is a ubiquitous filamentous fungus. We report a case of cutaneous P. boydii infection of the left knee in a 79-year-old Japanese man who was receiving oral predonisolone (25 mg/day) for radiation pneumonitis after radiation therapy on left breast cancer. He presented with a 2-week-history of a lesion on the left knee. A biopsy specimen from the skin lesion revealed granulomatous inflammation with hyphae. Culture of the pus from the skin specimen confirmed the diagnosis of cutaneous P. boydii infection. rDNA ITS sequence was analyzed to confirm the mycological diagnosis. The patient was treated orally with 200 mg/day of itraconazole. The lesion was gradually cured and left a hypertrophic scar. Cutaneous injury may be responsible for an incidence of localized infection. Such rare fungus infection in immunocompromised patients who have a persistent traumatic skin ulcer needs to be ruled out. An opportunistic infection in immunocompromised patients can be life-threatening and prompt treatment based on accurate diagnosis is important.
No preview · Article · Feb 2008 · Nippon Ishinkin Gakkai Zasshi
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2006 · The Journal of Dermatology
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Aug 2005 · The Journal of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Trichophytia profunda acuta of the glabrous skin (TPAGS) arose in a 67-year-old Japanese man. The patient presented indurated erythematous plaques and nodules on his left forearm. Direct microscopic examination of the scale in KOH preparation was negative for fungal elements, and culture for dermatophytes was also negative. Although fungal infection could not be proven in hematoxillin-eosin stained sections, deep-cut sections of the biopsied skin lesion with PAS stain revealed the ectothrix presence of fungal elements. Nested PCR was done with Trichophyton specific primers directed to internal transcribed spacer gene 1 (ITS1), using template DNA obtained from formalin fixed, paraffin embedded skin sections. A single band corresponding to T. rubrum was obtained, and the etiological agent was thus identified. KOH tests and cultures may often turn out unsuccessful, perhaps reflecting the hair follicle dominant fungus growth in TPAGS. Although these tests are most important for diagnosis of TPAGS, nested PCR using paraffin embedded skin sections may be an alternative method to identify the etiological agent.