Histopathologic and dermoscopic features of 42 cases of folliculitis decalvans: A case series.

BACKGROUND: Folliculitis decalvans (FD) is a form of inflamed primary cicatricial alopecia (PCA). FD is classified as a neutrophilic PCA; however, only a few previous studies have described its histopathology, including the assessment of systematically evaluated and quantified follicular changes in horizontally sectioned biopsy specimens with clinical and dermoscopic findings of the early and advanced stages. OBJECTIVE: We aimed to clarify the histopathologic and dermoscopic features of early and advanced active stage FD. METHODS: We conducted a case series study of 42 patients with FD by dermoscopy and both horizontally and vertically sectioned biopsy specimens. RESULTS: The histopathologic findings of the early-stage lesions included loss of sebaceous glands; interfollicular acanthosis; and fibrosis with depressed, fused follicular infundibula showing thickened interfollicular keloid-like areas with tufted hairs on dermoscopy. Active lesions showed a greater number of hair clusters, clefting, and fused infundibula with dense inflammation predominantly in the upper follicles. Neutrophil-predominant infiltrates were observed in fewer than half of the patients, including those with early-stage lesions. LIMITATIONS: This was a retrospective study. CONCLUSION: FD has the features of mixed-cell PCA. The features of early-stage FD are thickened interfollicular keloid-like areas with tufted hairs and loss of sebaceous glands.

IL-17-positive mast cell infiltration in the lesional skin of lichen planopilaris: Possible role of mast cells in inducing inflammation and dermal fibrosis in cicatricial alopecia.

Lichen planopilaris (LPP) is a primary cicatricial alopecia characterized by the infiltration of lymphocytes in the upper portion of hair follicles. Inflammation around the bulge region of hair follicles induces destruction of hair follicle stem cells and tissue fibrosis, resulting in permanent hair loss. Treatment is still challenging, and the precise pathophysiology of this disorder is unknown. To clarify the pathogenesis of LPP, we performed histological and immunohistochemical analysis on specimens obtained from LPP patients. Formalin-fixed and paraffin-embedded samples were evaluated by staining with haematoxylin and eosin (HE), toluidine blue stain, immunohistochemistry and immunofluorescence. The immunohistochemical analysis demonstrated that CD4-positive T cells preferentially infiltrated into the follicular infundibulum in the LPP lesions. Toluidine blue stain detected a large number of mast cells in the inflammatory lesions of LPP. Interestingly, immunohistochemical analysis demonstrated that the mast cells harboured IL-17A- and IL-23-producing activity and expressed the IL-23 receptor. The number of IL-17A-positive mast cells was significantly higher in the LPP lesions than in normal scalp. Moreover, the IL-17 receptor was expressed exclusively in the follicular epithelial cells in the LPP lesions. These results suggested that mast cells infiltrating hair follicles might play a role in the pathogenesis of LPP via the IL-23/IL-17 axis.

Mutations in SERPINB7, encoding a member of the serine protease inhibitor superfamily, cause Nagashima-type palmoplantar keratosis.

"Nagashima-type" palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266(∗)) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK.

Multivariate analysis of prognostic factors in patients with rapidly progressive alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common acquired hair disorder showing variable hair loss. Although various prognostic factors have been reported, no evident factors for determining prognosis and appropriate treatment are known. OBJECTIVE: To identify prognostic factors in AA patients, especially those with positive results for the hair-pull test on the first visit or with a history of rapidly progressive AA (RPAA) within 6 months prior to the first visit. METHODS: One thousand thirty (1030) patients diagnosed with AA at Tokyo Medical University Hospital were retrospectively examined for 3 years, and their prognosis was assessed on the basis of various indices using multivariate analysis. RESULTS: Patients with regenerated vellus hairs showed a significantly higher improvement or cure rate regardless of severity. Early onset and lengthy duration were significantly associated with lower cure, and higher relapse, rates. RPAA patients tended to show a good prognosis regardless of the treatment employed. LIMITATIONS: The present study is retrospective, and treatment modalities were chosen according to clinical and social circumstances. CONCLUSION: RPAA patients tend to show a favorable prognosis regardless of treatment modality. Furthermore, the presence of regenerated vellus hairs may indicate a good prognosis.

Primary cicatricial alopecia: Recent advances in evaluation and diagnosis based on trichoscopic and histopathological observation, including overlapping and specific features.

Primary cicatricial alopecia (PCA) is a form of alopecia in which inflammatory cells target follicles, including the bulge region containing follicular stem cells, leading to permanent alopecia. New classifications of PCA subtypes have recently been proposed, including those that account for novel trichoscopic and histopathological features of PCA, enabling greater precision in the evaluation and diagnosis of this condition. Nonetheless, diagnosis remains challenging clinically and histopathologically because the etiology of PCA is multifactorial. Inconsistent use of terminology, overlapping disease concepts, and changes in the clinical or histopathological severity of inflammation in the disease course in the same patient also make diagnosis quite challenging. The present study comprehensively reviews recent progress in diagnostic techniques, including the use of clinical, trichoscopic, and histopathological features, in evaluating each PCA subtype, containing overlapping and specific features. Elucidating the features of PCA, including those that are common to multiple subtypes as well as specific to each in both early and advanced-stage lesions, is important for accurate diagnosis. Improving the evaluation and treatment of this disease depends on having a broader clinical understanding that takes into account not only the features of the disease at a given point in time, but also the changes that occur during the entire disease course.

Rotaxane-type resorcinarene tetramers as histone-sensing fluorescent receptors.

Rotaxane-type receptors, which were composed of anionic cyclophane-based resorcinarene tetramers as the wheel and a 2,6-disubstituted naphthalene derivative having two fluorophore moieties, such as fluorescein and rhodamine residues, as the axle ( and , respectively), were prepared. Rotaxane-type receptors and bound histone, a small basic protein component of eukaryotic chromatins, with binding constants of 2.3 x 10(6) and 9.0 x 10(5) M(-1), respectively. The rotaxane-type receptors showed fluorescence sensing ability with remarkable histone selectivity. Moreover, fluorescence resonance energy transfer (FRET) between the fluorescein residues of and the rhodamine residues of took place in the presence of histone, which was a useful method for the detection of histone.

Family with Legius syndrome (neurofibromatosis type 1-like syndrome).

Legius syndrome (Online Mendelian Inheritance in Man no. 611431) or neurofibromatosis type 1 (NF1)-like syndrome was first reported by Legius et al. in 2007. We herein report the first instance of Legius syndrome occurring in two female siblings in Japan. Both individuals presented cafe-au-lait macules and freckling. Mutation analysis revealed a mutation of c.349C>T resulting in p.Arg117* in the SPRED1 gene as the cause of the Legius syndrome. The National Institutes of Health criteria for NF1 are insufficient to rule out the condition. For this reason, and because the clinical course of each condition is quite different, we stress the need to differentiate Legius syndrome from NF1 clearly.

A Case of Inflammatory Generalized Type of Peeling Skin Syndrome Possibly Caused by a Homozygous Missense Mutation of CDSN.

A 54-year-old Japanese woman had repetitive superficial skin peeling and ensuing erythematous changes in the sites since infancy. Her parents had a consanguineous marriage, and she was the only individual affected in her family tree. The erythematous changes seemed to worsen in the summer. Histologically, hyperkeratosis and splitting of the epidermis within the stratum corneum was noted, and electron microscopy revealed shedding of corneal cells in the horny layer and normal-looking corneodesmosomes. Gene analysis revealed a homozygous missense mutation at c.1358G>A in CDSN. Electron microscopic examination of the length and number of corneodesmosomes revealed statistically significant shortness and sparsity in the affected individual (mean ± SD 386.2 ± 149.5 nm) compared with that of an age- and site-matched control (406.6 ± 182.3 nm). We speculate that this size shrinkage of corneodesmosomes might be the result of a missense mutation of CDSN and that this could be one of the factors contributing to the pathological process of skin peeling.

Elderly cases of Churg-Strauss syndrome: case report and review of Japanese cases.

Churg-Strauss syndrome (CSS) is a vasculitis usually thought to affect comparatively young individuals, however, elderly cases of CSS are being reported increasingly. We report two elderly cases of CSS and review 123 cases of CSS reported in Japan between 2003 and 2010. The two patients showed typical features of CSS such as asthma, chronic sinusitis, purpura and mononeuritis multiplex. The biopsy specimens demonstrated leukocytoclastic vasculitis with infiltration of eosinophils. Both patients responded well to oral prednisolone. The age of the CSS cases we reviewed ranged from the teens to the 80s, with 47.2% of the patients aged 60 years or older. These patients tended more frequently to have complications such as gastrointestinal involvement, and a higher mortality rate. Elderly cases of CSS are not rare. Correct diagnosis at an earlier stage and careful, long-term follow up are of particular importance in preventing a fatal outcome.

Eosinophilic pustular folliculitis (Ofuji's disease) without macroscopic pustules.

BACKGROUND: Eosinophilic pustular folliculitis (EPF), first described by Ofuji et al. in 1970, is a rare dermatosis characterized by pruritic papules and pustules on circinate erythematous plaques with eosinophilic infiltration in and around the hair follicle. METHODS AND RESULTS: We report three cases of EPF that showed no macroscopic pustules during the total observation period. Histopathological examination revealed eosinophilic infiltration in and around the hair follicle in the lower dermis and subcutis. CONCLUSIONS: EPF consists of clinical variants, one of which lacks obvious pustules.

Oral finasteride improved the quality of life of androgenetic alopecia patients.

Although androgenetic alopecia (AGA) is not a systemic disease, some patients suffer from anxiety about the progression of their condition. This study was conducted in order to ascertain whether treatment by oral finasteride can improve the quality of life (QOL) of these patients. Twenty-seven male AGA patients aged 19-76 years (average, 33.8) answered the Visual Analog Scale (VAS), Dermatology Life Quality Index (DLQI), WHO/QOL-26 and State-Trait Anxiety Inventory (STAI) questionnaires before and after the administration of finasteride (1 mg/day) for 6 months. Patients assessed by physicians as "excellent" or "good" were defined as "high responders"; those assessed as "moderate" or "no change" were "low responders". The changes in QOL before and after the treatment were statistically analyzed, and the improved value of each QOL index of the high responders and low responders from baseline were compared. There was a statistical difference in the VAS (P < 0.0001) and DLQI (P < 0.01) indices before and after the administration of finasteride. No significant changes occurred in the WHO/QOL-26 and STAI indices. Comparison of the high responders (11 cases) and low responders (16 cases) revealed no statistical difference in the improvement of VAS and DLQI scores. Oral finasteride improves the QOL of these patients, and VAS and DLQI are useful for the evaluation of patients' QOL because of the high sensitivity of these tests. However, oral finasteride did not alleviate the patients' anxiety nor did its efficacy correlate with the level of reported anxiety.

Case of localized scleroderma successfully treated with bath psoralen and ultraviolet A therapy.

The patient was a 12-year-old girl with linear scleroderma distributed on the right abdomen, dorsal aspect of the right thigh, lower leg and foot. The initial regimen of oral prednisolone and methotrexate, or i.v. methylprednisolone failed in the treatment of the scleroderma. Then bath psoralen and ultraviolet A therapy (bath-PUVA) therapy of 0.2 J-4.0 J/cm(2) daily to total doses 62.8 J/cm(2) combined with oral prednisolone was started. After bath-PUVA therapy, regression of the skin sclerosis was observed, the possible mobile range of the right ankle was increased and histological examination confirmed improvement of the sclerosis. The successful results of bath-PUVA therapy in this case suggest its utility for localized scleroderma.

Athlete's nodule.

Three cases of athlete's nodule on the feet are reported. In case 1, a 30-year-old man, who had been an amateur football player, presented with nodules on the lateral side of the feet and on the right lateral malleolus with a duration of 1 year. In case 2, a 22-year-old man, who had participated in karate and track-and-field, presented with nodules on the lateral side of the feet and on the right lateral malleolus with a duration of 10 years. In case 3, a 25-year-old man, who had skied, presented with a nodule on the right lateral malleolus with a duration of 4 years. The biopsy specimens from the lesion demonstrated hyperkeratosis, acanthosis of the epidermis and thickness of the dermis. In 1991, Cohen et al. proposed the concept of athlete's nodule which indicated an acquired cutaneous nodule caused by chronic stimuli with sports. Histopathology of the athlete's nodule shows hypertrophy of the epidermis and dermis. To the best of our knowledge the term "athlete's nodule" has not been used in Japan, but it is a useful term to refer to the lesion induced by athletics or the use of sporting equipment.