Gene Expression Profiling of the Intact Dermal Sheath Cup of Human Hair Follicles.

Cells that constitute the dermal papillae of hair follicles might be derived from the dermal sheath, the peribulbar component of which is the dermal sheath cup. The dermal sheath cup is thought to include the progenitor cells of the dermal papillae and possesses hair inductive potential; however, it has not yet been well characterized. This study investigated the gene expression profile of the intact dermal sheath cup, and identified dermal sheath cup signature genes, including extracellular matrix components and bone morphogenetic protein-binding molecules, as well as transforming frowth factor beta 1 as an upstream regulator. Among these, gremilin-2, a member of the bone morphogenetic protein antagonists, was found by in situ hybridization to be highly specific to the dermal sheath cup, implying that gremlin-2 is a key molecule contributing to maintenance of the properties of the dermal sheath cup.

The usefulness of measuring tear periostin for the diagnosis and management of ocular allergic diseases.

BACKGROUND: Chronic ocular allergic diseases such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are accompanied by serious comorbidities; however, the underlying pathogenesis remains obscure. Furthermore, diagnosing conjunctival lesions in patients with atopic dermatitis and estimating the severity in AKC are important for the treatment of ocular allergic diseases. OBJECTIVE: We addressed whether periostin, a novel mediator and biomarker in allergic inflammation, is involved in the pathogenesis of ocular allergic diseases and whether periostin can be a biomarker for these diseases. METHODS: We investigated tear periostin in patients with seasonal allergic conjunctivitis (SAC), VKC, and AKC and allergic patients without conjunctivitis and compared it with tear IL-13 and serum periostin. Furthermore, in patients with AKC, we measured tear periostin before and after topical treatment with tacrolimus. RESULTS: Tears from patients with ocular allergic disease showed significantly high periostin levels than did tears from allergic patients without conjunctivitis and from patients with AKC, VKC, and SAC in descending order. Tear periostin was associated with serious comorbidities such as large papilla formation and corneal damage in AKC, although both tear IL-13 and serum periostin had little to no such abilities. Furthermore, after topical tacrolimus treatment, tear periostin tended to decrease in most patients with AKC along with their clinical improvement. CONCLUSIONS: Periostin produced in conjunctival tissues stimulated by IL-13 may contribute to the pathogenesis of ocular allergic diseases. Furthermore, tear periostin can be potentially applied as a biomarker to diagnose conjunctivitis in allergic patients and to evaluate disease severity as well as the efficacy of treatments in AKC.

Novel and recurrent ATP2A2 mutations in Japanese patients with Darier's disease.

Darier's disease (DD, keratosis follicularis: OMIM#124200) is an autosomal dominant skin disorder characterized by multiple dark brown keratotic plaques and warty papules covered by thick crusts. Most cases of DD are caused by mutations in ATP2A2, which is expressed in both the skin and the brain. ATP2A2 encodes the cardiac muscle SERCA2a protein and the ubiquitously expressed SERCA2b. SERCA2 plays an important role as a calcium pump. It is thought that a mutation in ATP2A2 causes dyskeratosis and abnormality of cell-cell adhesion. Here, we report five DD patients from five independent families who presented or were referred to the Nagoya University Hospital in the past five years. We detected five mutations in ATP2A2, including a previously unreported mutation. We observed no apparent genotype/phenotype correlation between types and sites of the ATP2A2 mutations and DD phenotypes in the present series of DD patients. Genetic diagnosis from ATP2A2 mutation search is useful for the definite diagnosis of DD, although it is difficult to predict the severity and prognosis of skin symptoms from the results of the ATP2A2 mutation analysis in DD patients.

Establishment of a novel model of onychomycosis in rabbits for evaluation of antifungal agents.

We developed a novel model of onychomycosis in which we observed fungi in the deep layer of the nail, and we used the model to evaluate the efficacy of two topical antifungal drugs. To establish an experimental, in vivo model of onychomycosis, we applied Trichophyton mentagrophytes TIMM2789 to the nails of the hind limbs of rabbits that underwent steroid treatment. The nails were taken from the rabbits' feet at 0, 2, and 6 weeks after a 2-week infection. The localization of the fungi was evaluated histopathologically. Some fungi were seen to penetrate to the nail bed, and the infection rate in the sample at 0, 2, and 6 weeks after infection was 57, 87, and 93%, respectively. In addition, fungi proliferated and moved proximally into the nail plate in a manner that depended on the duration of infection. Second, using this model we evaluated antifungal efficacy both by the culture recovery method and histopathological examination. Two topical antifungal drugs, 8% ciclopirox nail lacquer and 5% amorolfine nail lacquer, were applied to the nail for 4 weeks in each group. On histopathological examination, two antifungal treatment groups showed no significant difference against the nontreated control group. However, there were a significantly low fungus-positive rate and intensity of the recovery of fungi on culture between antifungal treatment and nontreated control groups. We therefore suggest that we have established an in vivo model of onychomycosis that is useful for the evaluation of the efficacy of antifungal agents.

Lymphocutaneous type of nocardiosis caused by Nocardia brasiliensis: a case report and review of primary cutaneous nocardiosis caused by N. brasiliensis reported in Japan.

Nocardiosis is a mixed suppurative and granulomatous inflammatory disease caused by infection with Nocardia organisms, a group of aerobic actinomycetes. We recently encountered a 25-year-old woman with posttraumatic nocardiosis of the lower extremities. The clinical symptoms noted during her first visit included erythematous swelling of the right knee accompanied by white maceration of the center of the knee and erosions, shallow ulcers and satellite pustules. In addition, multiple erythematous areas (up to the size of the tip of the thumb) were linearly distributed on the right thigh. These lesions were painful, and right inguinal lymphadenopathy was also noted. No lesion was found in internal organs such as the lungs. Histopathologically, signs of nonspecific granulomatous inflammation were observed, as well as several filamentous branching bacilli positive on Grocott stain. The organisms isolated from culture of pus were acid-fast, Gram-positive long rods. The isolated strain was finally identified as Nocardia brasiliensis. The patient was therefore diagnosed with lymphocutaneous type of primary cutaneous nocardiosis caused by N. brasiliensis. Drip infusion of flomoxef sodium was initially performed to treat her condition. Because of exacerbation of erythematous swelling of the right knee and an increase in number of pustules, treatment was switched to oral minocycline hydrochloride therapy. The disease healed 9 weeks after the start of oral minocycline hydrochloride therapy. Our patient was free of systemic immunosuppression and was neither under 10 nor over 65 years of age. She may therefore be considered a rare case of lymphocutaneous type of nocardiosis. We present this case and discuss reported cases of primary cutaneous nocardiosis due to N. brasiliensis in Japan.

Clinical significance of neutrophil gelatinase-associated lipocalin and galectin-7 in tape-stripped stratum corneum of acne vulgaris.

The usefulness of stratum corneum neutrophil gelatinase-associated lipocalin and stratum corneum galectin-7 as biomarkers of acne vulgaris was studied. A comparison of neutrophil gelatinase-associated lipocalin levels on the cheeks of patients with acne vulgaris at the start of the study and at the time of symptom improvement showed a significant decrease. On the other hand, the galectin-7 levels at the time of symptom improvement were significantly higher than those at the start of the study. Therefore, because the inflammation in the epidermis and hair follicles was reduced after therapy, as a result of the solution of the inflammatory eruptions caused by acne vulgaris, the neutrophil gelatinase-associated lipocalin level also showed a significant decrease after therapy. These results suggest that stratum corneum neutrophil gelatinase-associated lipocalin may be useful as an objective biomarker of changes in acne vulgaris symptoms.

Zosteriform skin involvement of nodal T-cell lymphoma: a review of the published work of cutaneous malignancies mimicking herpes zoster.

A 77-year-old Japanese woman initially presented with non-Hodgkin's lymphoma involving her neck, axillary and inguen lymph nodes. She had edematous erythema and nodules limited to the skin in zosteriform distribution on the left side chest wall along the T4-5 dermatome. In addition, since 1970, we have mainly been collecting English-language articles on malignant skin tumors and skin metastasis described as zosteriform in the title, and we have reviewed a total of 29 cases, including our own. It should be mentioned that 59% of the cases reported had been diagnosed with herpes zoster at the time of the initial examination and that many of them had received drug therapy (e.g. acyclovir). We wish to add the dermatomic eruption mimicking zoster sine herpete to the list of possible presentations of cutaneous malignancies.

Giant Hidroacanthoma Simplex Mimicking Bowen's Disease.

Hidroacanthoma simplex is a benign tumor of the skin, macroscopically resembling seborrheic keratosis or Bowen's disease and histologically mimicking clonal-type seborrheic keratosis. We observed a plaque of 70 × 50 mm on the right flank part. From clinical appearance, we suspected Bowen's disease; however, based on immunohistochemical findings, we made a diagnosis of hidroacanthoma simplex.

Multiple primary syphilis on the lip, nipple-areola and penis: An immunohistochemical examination of Treponema pallidum localization using an anti-T. pallidum antibody.

Primary syphilis caused by Treponema pallidum usually develops after sexual contact as an initial solitary sclerosis or hard chancre in the genital region. We describe a case of primary syphilis at three sites in genital and extragenital regions of a man who had sex with men. A 29-year-old man visited our hospital for skin lesions on his lower lip, nipple-areola and penis. A positive syphilis serological test for rapid plasma reagin had a titer of 1:16; the patient also tested positive for specific antibodies against T. pallidum, with a cut-off index of 39.0. Histopathological examination of a nipple-areola biopsy specimen revealed a thickened epidermis and dense infiltration of inflammatory cells extending from the upper dermal layers to the deep dermis. The inflammatory cells were composed of abundant lymphocytes, plasma cells, histiocytes and neutrophils. Immunohistochemical staining for T. pallidum using an anti-T. pallidum antibody showed numerous spirochetes in the lower portion of the epidermis, scattered inside inflammatory cell infiltrate and perivascular sites throughout the dermis. Based on these findings, the patient was diagnosed with primary syphilis. Treatment with oral amoxicillin hydrate was started. Five days after starting treatment, a diffuse maculopapular rash (syphilitic roseola) occurred on his trunk and extremities. Perivascular cuffing due to T. pallidum was present throughout the dermis in the biopsy specimen of a localized lesion of primary syphilis. Moreover, syphilitic roseola, which indicates generalized dissemination of T. pallidum, developed during the course of treatment for primary syphilis. Therefore, we considered perivascular cuffing to be indicative of the dissemination phase.

[Analysis of facial lesions on adult type atopic dermatitis with anti-fungus drug (terbinafine hydrochloride) -- analysis of serum anti-Malassezia IgE antibody titers and histamine release test].

Malassezia furfur has been described as an aggravating factor in facial lesions of atopic dermatitis, and oral antifungal agents have been reported to be effective against these lesions. We used terbinafine hydrochloride to treat 15 patients with adult-type atopic dermatitis and evaluated its efficacy by measuring the improvement in facial skin manifestations, serum IgE values, and serum anti-Malassezia IgE antibody titers. A histamine release test (HRT) for Malassezia. was also performed in 6 of the 15 patients. The facial skin manifestations improved in 8 (53.3%) of the 15 patients, and there were significant simultaneous decreases in their serum IgE values. The serum anti-Malassezia IgE antibody titer decreased significantly in all 15 patients. However, no significant correlation was observed between the HRT and the facial skin manifestations. We concluded that oral terbinafine hydrochloride is effective against the facial lesions of atopic dermatitis patients and this is possibly caused by decrease of Malassezia antigen in the facial lesions.

Efficacy of inpatient treatment for atopic dermatitis evaluated by changes in serum cortisol levels.

When dealing with patients with severe atopic dermatitis (AD), inpatient treatment is useful for alleviating skin symptoms in short periods of time. We previously found that many severe AD patients had low serum cortisol levels at admission. The present study was undertaken to evaluate the efficacy of inpatient treatment in 29 adults with AD through comparisons of serum cortisol, plasma adrenocorticotropic hormone (ACTH), serum thymus and activation-regulated chemokine (TARC), and serum lactate dehydrogenase (LDH) levels at admission with those at the time of discharge. Serum cortisol and plasma ACTH levels were significantly higher at discharge. On the other hand, serum TARC and serum LDH were significantly lower at discharge. We examined whether the suppression of hypothalamic-pituitary-adrenocortical function that was seen at admission was attributable to disturbed circadian rhythms due to sleep disorders by analyzing hypothalamic-pituitary-adrenocortical function in relation to the presence/absence of sleep disorders, serum cortisol levels and daily urinary free cortisol. Of the 17 patients with low serum cortisol levels upon admission, 15 (88.2%) had sleep disorders upon admission. However, the daily urinary free cortisol increased significantly from 8.0 ± 5.5 µg/day (at admission) to 18.5 ± 17.2 µg/day (at discharge). These results suggested that the suppression of endocrine function seen at admission was not attributable to disturbed circadian rhythms due to sleep disorders but represented true suppression of the endocrine system. These results indicated that inpatient care was useful for treating patients with severe AD, enabling efficient improvement of the skin condition and recovery from suppressed endocrine function.