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.

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.

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.

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.

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.

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.