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 xenobiotics.

This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

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Hallopeau’s acrodermatitis is characterized by the presence of aseptic pustules on an inflammatory basis of the periungual or subungual region. The cyclic recurrences induce important physical and psychological morbidity. By analogy to the efficacy of TNF-α antagonists in the treatment of generalized pustular psoriasis, our patient illustrates the long-term efficacy and safety of etanercept (Enbrel®) in the treatment of Hallopeau’s acrodermatitis refractory to infliximab (Remicade®). This treatment alternative should in consequence be considered in patients with a recalcitrant form of a potentially debilitating disease.

Background: Necrobiosis lipoidica is a rare granulomatous noninfectious skin disease. Treatment of this chronic debilitating disease is of importance because ulceration of the plaques may induce important psychological and physical morbidity. Objective: Infliximab, an anti-TNF-α chimeric monoclonal antibody used intravenously and intralesionally for other extradermatological granulomatous diseases including Crohn’s disease and sarcoidosis, was administered by intradermal injection in necrobiosis lipoidica. The aim of this study was to evaluate the efficacy and safety profile of a locally delivered drug compared to its systemic use. Patients and Methods: Weekly injections of intralesional infliximab for 3 weeks were followed by a 1-week treatment interruption. This treatment schedule was repeated thrice. Results: Two patients who benefitted from complete treatment experienced almost complete remission for up to 18 months. The third patient, who had treatment interruptions, showed partial improvement. No serious side effects were noticed, although the injections caused pain. Conclusions: This is the first report about the efficacy and safety of a therapy consisting of intralesional injections of infliximab for a granulomatous skin disease. Although this approach was clearly effective for necrobiosis lipoidica, the disease recurred several months after treatment interruption, raising the question of the need for maintenance therapy. Further controlled long-term trials are thus necessary.