The Cutaneous Lesions of Dioxin Exposure: Lessons from the Poisoning of Victor Yushchenko

Several million people are exposed to dioxin and dioxin-like compounds, primarily through food consumption. Skin lesions historically called "chloracne” are the most specific sign of abnormal dioxin exposure and classically used as a key marker in humans. We followed for 5 years a man who had been exposed to the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), at a single oral dose of 5 million-fold more than the accepted daily exposure in the general population. We adopted a molecular medicine approach, aimed at identifying appropriate therapy. Skin lesions, which progressively covered up to 40% of the body surface, were found to be hamartomas, which developed parallel to a complete and sustained involution of sebaceous glands, with concurrent transcriptomic alterations pointing to the inhibition of lipid metabolism and the involvement of bone morphogenetic proteins signaling. Hamartomas created a new compartment that concentrated TCDD up to 10-fold compared with serum and strongly expressed the TCDD-metabolizing enzyme cytochrome P450 1A1, thus representing a potentially significant source of enzymatic activity, which may add to the xenobiotic metabolism potential of the classical organs such as the liver. This historical case provides a unique set of data on the human tissue response to dioxin for the identification of new markers of exposure in human populations. The herein discovered adaptive cutaneous response to TCDD also points to the potential role of the skin in the metabolism of food xenobiotic

New therapeutic targets in dermatoporosis

Dermatoporosis is a novel term proposed to describe the chronic cutaneous insufficiency/fragility syndrome characterized by an extreme skin atrophy. Dermatoporosis is principally due to chronological aging and long-term and unprotected sun exposure, but it may also result from the chronic use of topical and systemic corticosteroids. We have recently proposed a membrane organelle, hyalurosome, composed of molecules involved in hyaluronate (HA) metabolism and cell signaling in the keratinocytes, such as principal HA receptor CD44, heparin-binding epidermal growth factor (HB-EGF), HB-EGF receptor erbB1 and HA synthase 3 (HAS3), which is functionally defective in dermatoporosis and may be a target for intervention. Several lines of evidence suggest that hyalurosome is located in keratinocyte filopodia, thin, actin-rich plasma membrane protrusions implicated in cell motility. We have recently shown that keratinocyte filopodia are downregulated by corticosteroids in vitro. Intermediate size HA fragments (HAFi) inhibited the downregulation of filopodia induced by corticosteroids. Topical HAFi prevented the skin atrophy induced by topical corticosteroids in mice without interfering with their anti-inflammatory effect. Topical treatment with HAFi 1% of atrophic forearm skin of dermatoporosis patients for 1 month resulted in a significant clinical improvement and induced the expression of hyalurosome molecules. Topical retinaldehyde (RAL) and HAFi showed a synergy in HA production and pro-HB-EGF expression in mouse skin and in the correction of skin atrophy in dermatoporosis patients. Uncovering the molecular mechanisms implicating hyalurosome seems to be crucial to better understand the pathogenesis of dermatoporosis and to develop new therapeutic strategies

The Leading Impact Journal in Dermatopathology

As the Editor-in-Chief ofDermatopathologyand the President of the European Society of Dermatopathology (ESDP), I have the great pleasure of celebrating the 10th anniversary ofDermatopathology, the only online journal in the field of cutaneous pathology and the official journal of the ESDP [...]

A Case of Adrenergic Urticaria Associated with Vitiligo

Adrenergic urticaria is a rare form of urticaria, induced by a stress-induced concomitant release of epinephrine and norepinephrine. Here we describe the case of a 60-year-old female patient presenting with disseminated erythematous papules surrounded by a white halo and vitiligo lesions on the hands, arms, and feet. Histological examination of one of the erythematous papules showed a dermal inflammatory infiltrate composed of lymphocytes and eosinophils of perivascular and interstitial localization. After 2 weeks of treatment with antihistamines, the lesions disappeared completely

A New Case of Hybrid Epidermoid and Apocrine Cyst

We described a new case of a hybrid epidermoid and apocrine cyst, known to be a rare histopathological entity. The cyst was located in the axillary region and completely excised, without complication. The diagnosis was made at the histological analysis, where we found a cystic lesion in the dermis, lined with both epidermoid and apocrine epithelium

Cutaneous adnexal cysts revisited: what we know and what we think we know

Cutaneous cysts have been classified by dermatopathologists in many different ways. Here, we propose a novel classification of cutaneous adnexal cysts according to their origin in the folliculosebaceous unit and the sweat glands. By examining the lining of the cystic structure, its origin can be easily identified. Epidermal cysts have an epithelial wall containing a granular layer with lamellar keratinization, indicating an infundibular origin. Tricholemmal cysts have an undulating epithelial wall with no granular layer and a compact keratinization, showing an isthmic origin. In steatocystoma, dermoid cyst, and folliculosebaceous hamartoma, the epithelial lining shows a crenulated appearance which is seen in the sebaceous duct. Hidrocystoma shows the characteristic cuboidal epithelial lining of sweat glands with decapitation secretion in its apocrine forms. The hair matrix cyst wall is composed of basaloid cells maturing to squamoid cells, as seen in the normal hair matrix and shadow cells in the lumen. Metabolizing acquired dioxin-induced skin hamartoma (MADISH) is a cystic lesion with lamellar keratinization, and no sebaceous glands. The classification proposed here aims to simplify the complexity of cutaneous adnexal cysts, and to facilitate a better understanding of the origin of cystic lesions of the skin

Multiple Eruptive Sebaceous Hyperplasia Secondary to Cyclosporin in a Patient with Bone Marrow Transplantation

Many cutaneous complications have been described in patients treated with cyclosporin. Alterations of the pilosebaceous unit such as hypertrichosis are particularly frequent. However, the occurrence of sebaceous hyperplasia is exceptional. These lesions seem to be specific to cyclosporin rather than secondary to immunosuppression. Here, we report an exceptional case of eruptive and disseminated sebaceous hyperplasia arising in a bone marrow transplant recipient only a few months after starting immunosuppressive treatment with cyclosporin

Dermatoporosis: clinical features, molecular mechanisms and novel therapeutic targets - a literature review

‘Dermatoporosis’ is a term proposed 15 years ago to describe an extreme cutaneous insufficiency/fragility syndrome beyond cosmetic aspects. Individuals suffering from this condition are usually elderly, with a history of chronic sun exposure and/or chronic topical or systemic corticosteroid use. The preliminary clinical aspect is skin atrophy, which may be complicated by skin tears and deep dissecting haematoma, a severe complication of dermatoporosis that requires immediate medical attention. We reviewed the literature on dermatoporosis in the PubMed and CINAHL databases from 2006 to 2022 and present here the current knowledge about this emerging skin condition with potential molecular mechanisms and novel therapeutic targets. Background Dermatoporosis is a particular form of skin atrophy/ fragility proposed for the first time in 2007. It has a clear link not only to skin tears, but also to deep dissecting haematomas and pressure ulcers in older adults. Aim To review the literature published on the subject since its first description. Method A literature search between 2006 and May 2022 using the keyword ‘dermatoporosis’ was performed on PubMed and CINAHL databases. Findings A total of 46 papers were identified in the initial search. They describe different aspects of dermatoporosis. From an epidemiological perspective, some papers report its prevalence to be around 30% among elderly hospitalised subjects. Beyond the usual clinical features of dermatoporosis (purpura, pseudoscars, skin tears and deep dissecting haematomas), some papers statistically link dermatoporosis to osteoporosis and pressure ulcers. Other studies describe the histological aspects and molecular mechanisms of dermatoporosis. Implications for clinical practice These observations should help clinicians to identify patients at risk of developing dermatoporosis and al low them to benefit from global prevention. For those patients already showing the clinical complications of dermatoporosis, an understanding of the underlying process should lead to a better patient care.</p