Background: Generalized granuloma annulare (GGA) is a benign skin disorder of an unknown etiology. Though some cases of GGA have been reported, few systemic reviews of the clinical and pathological features of GGA have been performed. Objective: The purpose of this study is to analyze and correlate the clinical and pathological characteristics of GGA in Korean patients. Methods: We conducted a retrospective study that included 54 biopsy specimens of Korean GGA patients, and the clinical and pathological features of GGA were reviewed and analyzed for their correlation. Results: The cutaneous lesions could be divided into the annular (24, 44%) and nonannular types (30, 56%), and the lesions were more common in males than in females (29 males and 25 females). The incidence of GGA showed a bimodal age distribution. The number of patients who presented within the first decade was 24 cases (44%), and 24 cases (44%) were over the fifth decade. Eight patients (15%) had systemic diseases. Especially, diabetes mellitus (DM) occurred only in the adult GGA patients over forty years old. The pathological findings showed dermal granulomatous lesions that consisted of either a palisading pattern (28, 52%) or an interstitial pattern (26, 48%). Conclusion: In contrast to the previously reported studies, the age of GGA onset showed a bimodal distribution, and GGA was observed more often in males. The prevalence of DM in the GGA affected individuals was higher than that found in the general Korean population. Therefore, it is recommended to perform a work-up for DM in the GGA affected patients who are over forty years old. (Ann Dermatol 21(2) 113∼119, 2009)
Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction involving extensive keratinocyte death in the epidermis. Histologically, the skin from TEN patients exhibits separation at the dermo-epidermal junction and accompanying necrosis of epidermal keratinocytes. Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an essential part of the cellular machinery that executes "programmed", or "regulated", necrosis and has a key role in spontaneous cell death and inflammation in keratinocytes under certain conditions. Here we show that RIP3 expression is highly upregulated in skin sections from TEN patients and may therefore contribute to the pathological damage in TEN through activation of programmed necrotic cell death. The expression level of mixed lineage kinase domain-like protein (MLKL), a key downstream component of RIP3, was not significantly different in skin lesions of TEN. However, elevated MLKL phosphorylation was observed in the skin from TEN patients, indicating the presence of RIP3-dependent programmed necrosis. Importantly, in an in vitro model of TEN, dabrafenib, an inhibitor of RIP3, prevented RIP3-mediated MLKL phosphorylation and decreased cell death. Results from this study suggest that the high expression of RIP3 in keratinocytes from TEN patients potentiates MLKL phosphorylation/activation and necrotic cell death. Thus, RIP3 represents a potential target for treatment of TEN.
Background: Repeated exposure to ultraviolet radiation from the sun results in premature photoaging. Photodynamic therapy (PDT) has been shown to be effective for treatment of photoaging, although the data from most studies have been based on clinical observation.Objectives: We investigated whether 5-aminolevulinic acid (ALA)-PDT induced histologic changes suggesting photorejuvenation.Methods: Fourteen patients with one to three actinic keratoses on the face were treated twice with ALA-PDT by using a 1200 W metal halogen lamp at 1-month intervals. Skin biopsy before and 1 month after the PDT was performed. Twenty-five pairs of specimens were obtained. We examined the specimens with routine and immunohistochemical staining and evaluated the parameters associated with photoaging by using image analysis.Results: After ALA-PDT, the mean epidermal thickness and dermal inflammatory infiltrate were reduced. The total collagen volume in the dermis significantly increased with expression of type I and III procollagen. The level of transforming growth factor b and transforming growth factor b type II receptors in the epidermis also increased. The elastotic material with co-localizing fibrillin-1 and tropoelastin expression in the dermis decreased after treatment. The expression of matrix metalloproteinases-1, -3, and -12 also decreased.Limitations: The study was limited by the small sample size.Conclusions: ALA-PDT resulted in histological changes indicating restoration of photoaged skin. These data suggest that ALA-PDT could be effective for photorejuvenation. ( J Am Acad Dermatol 2010;62:85-95.)
Sarcoidosis is a multisystem disease of unknown etiology. The demonstration of polarizable foreign bodies in cutaneous granulomas is generally thought to exclude a diagnosis of sarcoidosis. Nevertheless. some investigators have reported systemic sarcoidosis with cutaneous manifestations in which polarizable particles were associated with granuloma formation in the skin. We searched the biopsy specimens of granulomatous lesions from 50 patients with cutaneous sarcoidosis using polarization microscopy to estimate the frequency of polarizable foreign bodies in cutaneous lesions of sarcoidosis. Using electron probe microanalysis, we sought to determine what elements compose these foreign bodies. Polarizable foreign bodies were found in the granulomatous skin lesions of 12 of 50 patients with cutaneous sarcoidosis. All 12 patients also had at least one other granulomatous systemic lesion, and 4 had biopsy specimens of a systemic lesion available for review. Polarizable foreign bodies were found in two cases. The elements identified were calcium, phosphorus, silicon, and aluminum. Polarizable foreign bodies were found in cutaneous sarcoidosis far more often than expected. Foreign bodies were also found in granulomatous systemic lesions. The foreign body may serve as an inciting stimulus for granuloma formation in selected cases of sarcoidosis.
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