Abundance of interstitial heparan sulfate in granuloma annulare but not in other mucinous skin diseases

BACKGROUND: Heparan sulfate (HS), unlike other glycosaminoglycans, is mainly located on cell surfaces but can be shed into the interstitium by a regulated process. It has been found in interstitial fluid drained from cutaneous wounds, but otherwise the conditions under which the release of HS from the cell surface occurs are unknown. To better characterize this process, we have investigated the presence of interstitial HS in various skin diseases with glycosaminoglycan accumulation. METHODS: Histologic routine material was stained immunohistochemically using an antibody recognizing HS. RESULTS: Heparan sulfate immunoreactivity is present in the interstitium of young cutaneous scars and in the interstitium of the inflammatory infiltrate of granuloma annulare. No reactivity was found in a number of non-inflammatory skin diseases with mucin deposition. CONCLUSIONS: The selective presence of interstitial HS in only two of the investigated skin conditions supports the existence of a regulated mechanism to release HS from the surface of cells into the interstitium. It is suggested that HS modulates the biologic actions of growth factors and cytokines not only during wound repair but possibly also in inflammatory skin diseases such as granuloma annulare.     

T-zone histiocytes in granulomatous skin diseases

We investigated the distribution of T-zone histiocytes by immunohistochemical demonstration of S-100 protein in granulomatous skin diseases (granuloma annulare, 8 cases; necrobiosis lipoidica, rheumatoid nodule, sarcoidosis, lupus vulgaris, and foreign-body granuloma; 5 cases each). T-zone histiocytes were regularly found in the lymphohistiocytic mantle, but also occasionally between epitheloid cells. Our results show that, besides the monocyte-macrophage system, T-zone histiocytes consistently contribute to the formation of cutaneous granulomas. These findings may indicate a role of delayed-type hypersensitivity.     

Interstitial granulomatous dermatitis associated with chronic inflammatory demyelinating polyneuropathy

A 44-year-old man presented with an eruption of pruritic erythematous plaques on his lower extremities of 6 months' duration that were unresponsive to antifungal cream or topical corticosteroid. His medical history was notable for chronic inflammatory demyelinating polyneuropathy (CIDP), which was diagnosed 1 year prior to presentation and was associated with lower extremity weakness and imbalance of 3 years' duration. Punch biopsy of lesional skin showed a superficial and deep perivascular and interstitial lymphohistiocytic infiltrate with abundant interstitial neutrophils and rare eosinophils. He was diagnosed with interstitial granulomatous dermatitis (IGD), and the eruption improved with the initiation of oral dapsone 50 mg twice daily.     

Histologic features of granulomatous skin diseases

Granulomatous disorders affecting the skin belong to a heterogeneous group of diseases, which were predominantly classified based on pathogenetic features. In infections diseases a granuloma is formed if an agent could not be eliminated by the immune system. Typical agents which cause granulomatous reactions are mycobacteria, fungal infections, especially extra European agent, which could effect the skin by, dissemination (e.g. histoplasmosis) or parasites, like leishmaniasis.     

Interstitial granulomatous dermatitis

A 59-year-old woman with arthritis presented to the Skin Institute of New York with a 2-month history of asymptomatic, small, skin-colored papules that erupted symmetrically on the chest, back, and proximal extremities. Histopathologic examination of a biopsy specimen showed findings of interstitial granulomatous dermatitis. Clinical correlation suggested a diagnosis of interstitial granulomatous dermatitis with arthritis. No change in the lesions resulted from application of clobetasol 0.05 percent ointment to the affected areas.     

Differential diagnosis of granulomatous skin diseases]

The case histories of two female patients with granulomatosis disciformis and necrobiosis lipoidica are reported. Widespread skin manifestations, also in face and neck, with peculiar anular lesions complicated the differential diagnostic discrimination from sarcoidosis. The aspects of the cases and their progress are discussed in regard to the necessity of permanent checking of diagnostic preconditions during therapy.     

Chemokine networks in inflammatory skin diseases

The superfamily of chemokines comprises numerous small, cytokine-like chemotactic proteins, which have a fundamental role in the regulation of leukocyte trafficking. The chemokine-chemokine receptor system is highly redundant and promiscuous, and forms a complex network relevantly involved in the expression of chronic inflammatory skin diseases, including allergic contact dermatitis, atopic dermatitis and psoriasis. The pattern of chemokine expression shows overlapping features but also important differences in these diseases due to distinct sources and types of pro-inflammatory signals involved in chemokine induction, and the inherent capacity of resident skin cells to produce chemokines. Chemokine receptors (G-protein coupled receptors) rather than chemokines appear the appropriate therapeutic targets as they are more chemically tractable and play less redundant functions.     

Exosomes in chronic inflammatory skin diseases and skin tumors

Exosomes are membrane vesicles of endocytic origin that can mediate communication between cells and the transport of cellular components such as microRNAs, mRNAs, proteins and DNA. Recently, exosomes have been under investigation for their significant roles in both healthy physiology and disease states. Herein, we review the role of exosomes in chronic inflammatory skin diseases and skin tumors, especially focusing on systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous pemphigoid and melanoma. Moreover, we emphasize the involvement of changes in exosome cargo in the regulation of these diseases.     

Interstitial granulomatous dermatitis with plaques

BACKGROUND: Interstitial granulomatous dermatitis is a histopathologic pattern with variable clinical appearance associated with autoimmune systemic diseases. The frequency of its different cutaneous expressions and its association with autoimmune diseases are not known. OBJECTIVE: We describe the clinical, serologic, and histologic features in 17 patients with interstitial granulomatous dermatitis with a clinical presentation consisting of large erythematous plaques. METHOD: Skin biopsy specimens fulfilling criteria for diagnosis of interstitial granulomatous dermatitis were selected and correlated with the clinical and laboratory findings. RESULTS: The study included 1 man and 16 women with multiple, asymptomatic, round to oval, erythematous plaques, most often on folds of the skin, in a bilateral and somewhat symmetric distribution. Most of patients had rheumatoid polyarthralgias along with various serologic abnormalities, often connected to collagen vascular diseases. Histologic examination disclosed a distinctive interstitial granulomatous dermatitis characterized by a diffuse infiltration of the interstitium by histiocytes with piecemeal fragmentation of collagen and formation of small granulomas around degenerative areas in concert with variable numbers of polymorphonuclear leukocytes sprinkled within the infiltrate. Churg-Strauss granulomas in miniature and flame figures were occasionally observed and indicated continued or increased activity of the associated autoimmune disease(s). CONCLUSIONS: Interstitial granulomatous dermatitis with plaques is a distinct entity with highly reproducible clinical and histopathologic features; recognition of these features identifies a patient who may have an underlying systemic autoimmune disorder.     

microRNA在炎症性皮肤病中作用的研究进展

【摘要】 microRNA（miRNA）是一类转录后调控基因表达的非编码RNA分子,参与皮肤各种病理生理过程。近年来,miRNA表达谱的变化已被报道与部分炎症性皮肤病相关,例如miR-203、miR-146a、miR-21在银屑病皮损中表达上调;miR-155、miR-146a在特应性皮炎皮损中表达上调;miR-21、miR-223、miR-142-3p、miR142-5p在过敏性接触性皮炎皮损表达上调;而miR-146a、miR-155在系统性红斑狼疮患者外周血表达下调;miR-223在皮肌炎皮损中表达下调等。本文综述miRNA与部分炎症性皮肤病发生、发展之间的联系。     

炎症性皮肤病的DNA异常甲基化

DNA甲基化是一种重要的不改变DNA序列,但可影响基因表达水平并遗传的表观遗传学事件.随着DNA甲基化检测方法的日趋完善,有越来越多的研究表明,DNA异常甲基化与炎症性皮肤病相关.有研究证实或提示,DNA异常甲基化可能与多种炎症性皮肤疾病的发病机制密切相关,如银屑病、系统性红斑狼疮、特应性皮炎、系统性硬皮病,其他尚包括雄激素性脱发、慢性湿疹和天疱疮等,但研究并不能清楚地解释异常的甲基化模式如何在疾病中发挥具体的生物学作用.随着研究的深入,可对相关疾病的研究提供新的思路.     

Neuropeptides: role in inflammatory skin diseases

The cutaneous nervous system recently has been demonstrated to interact with multiple target cells in the skin and to mediate actions important in inflammatory conditions. Neuropeptides released by cutaneous neurons such as substance P (SP), vasointenstinal peptide (VIP), calcitonine gene regulated peptide (CGRP), proopiomelancortin (POMC) peptides and others modulate the function of immunocompetent and inflammatory cells as well as epithelial and endothelial cells. They have been found to function as mediators of cell proliferation, cytokine and growth factor production as well as adhesion molecule and cell surface receptor expression. In addition many cells including keratinocytes, fibroblasts, endothelial cells and inflammatory cells have been shown to release several neuropeptides and they express their corresponding receptors. These findings indicate that neuropeptides participate in the complex network of mediators that regulate cutaneous inflammation, hyperproliferation and wound healing.     

Bacterial superantigens and inflammatory skin diseases

Bacteria seem to play an important role in the induction and maintenance of inflammatory skin diseases such as psoriasis and atopic dermatitis. Toxins from bacteria including Streptococcus and Staphylococcus aureus, have been shown to function as a new type of allergen termed 'superantigen'. Superantigens bypass the normal control of T-cell activation and activate all T-cell clones bearing certain types of variable chain on the T-cell receptor: this leads to vigorous T-cell activation and cytokine release. These bacterial superantigens may be involved in induction and aggravation of inflammatory skin diseases. Guttate psoriasis is often preceded by a streptococcal throat infection and T cells specific for streptococcal superantigens have been identified in the skin of patients. The skin of patients with atopic dermatitis is often colonized with superantigen-releasing Staph. aureus, and application of a staphylococcal superantigen to human skin induces an eczematoid reaction.     

Helicobacter pylori and inflammatory skin diseases

Throughout the history of mankind, infections have been the major cause of diseases. Over the last decades, not only the incidence of emerging infectious diseases have increased, but also tremendous strides have been made in understanding the biology of several pathogenic microorganisms. Helicobacter pylori(H. pylori) is a spiral-shaped, gram-negative bacterium, which infects over the half of the world's population. H. pylori has been implicated in the pathogenesis of a number of gastrointestinal disorders. However, new researches have demonstrated that H. pylori is also involved in the pathogenesis of various extragastric diseases. The difference in the clinical outcome of H. pylori infection may be explained, at least in part, by host response to the infection and H. pylori virulence factors. It is obvious that as developments in the research on H. pylori spring up, an understanding of the pathophysiology of H. pylori infection will continue to be identified. Here in this review, we summarize the current knowledge about H. pylori and its association with inflammatory skin diseases.     

内源性大麻素系统与炎症性皮肤病

内源性大麻素系统包括内源性大麻素受体和内源性大麻素以及一系列参与内源性大麻素系统生物合成和代谢的酶类以及膜转运受体.近年来,在角质形成细胞、皮肤成纤维细胞、皮脂腺细胞等多种皮肤细胞中发现了具有生物学效应的内源性大麻素系统.越来越多的研究发现,内源性大麻素系统参与正常皮肤生理生化活动和炎症反应,并在多种炎症性皮肤病中起作用.目前内源性大麻素系统的临床应用尚不成熟,但内源性大麻素系统的研究为临床炎症性皮肤病的治疗提供了新视角和新策略.     

Lysozyme-positive cells and ultrastructural findings in granulomatous and histiocyte-proliferative skin diseases

Immunohistochemically, the presence of lysozyme (LZ) has been detected by the antibody against human LZ in cytoplasm of cells from granulomatous and histiocyte-proliferative skin diseases. To detect LZ in these cells morphologically, I have done electron microscopic observations of the following skin diseases; sarcoidosis, lupus vulgaris, lupus miliaris disseminatus faciei (LMDF), tattoo granuloma, lichen nitidus, foreign body granuloma, granuloma annulare, xanthelasma, xanthoma tuberosum, xanthoma planum, juvenile xanthogranuloma, giant cell tumor of tendon sheath, dermatofibroma, malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, granulation tissue of burn, hypertrophic scar, and histiocytosis X. From both the immunohistochemical and the electron microscopic features it was concluded that a) immunohistochemically LZ-positive cells from lesions of sarcoidosis, lupus vulgaris, LMDF and tattoo granuloma had a number of electron-lucent bodies (ELB) or microvesicles in their cytoplasm, b) lichen nitidus and xanthoma tuberosum had few LZ-positive cells and the ELB were not observed, and c) the other diseases were LZ-negative, and the ELB were also absent. It is suggested that LZ is present in the ELB which are observed electron microscopically.