Matteo Auriemma

Cytokines and T cells in atopic dermatitis

Atopic dermatitis (AD) is an inflammatory disorder of the skin characterized by an impaired immune response. Several effector T cell subsets, such as pro-inflammatory cells like Th9, Th17 and Th22 cells, expressing high levels of IL-9, IL-17 and IL-22, together with the anti-inflammatory, immuno-modulating Treg cells constitutively producing IL-10, seem to play a role in this condition. IL-9 and IL-9 receptors are significantly increased in lesional AD skin compared to normal control skin. In addition, some polymorphisms in IL-9 and IL-9r genes have been associated with AD. The role of IL-17 and IL-17-producing T cells remains under debate and conflicting data are available. IL-22-producing T-cells seem to correlate with the severity of the AD. The number and function of Treg cells, producing IL-10, have been widely investigated in AD with conflicting results. Other studies suggest that high levels of IL-31 or low levels of IL-21 might be involved in the pathogenesis of AD. This review was undertaken in order to provide a better understanding of the relevance of certain cytokines in AD. We have analysed the new insight into the pathogenesis of AD, with special attention to those cytokines produced by the different T cell subpopulations.

Treatment of Cutaneous Calciphylaxis with Sodium Thiosulfate

Cutaneous calciphylaxis is a potentially fatal condition characterized by calcium deposition in dermal arterioles and the subsequent development of livedo reticularis, plaques, and extremely painful ulcers. This condition may be present in up to 4% of end-stage renal disease patients. Several treatments, which mainly attempt to control calcium phosphate metabolism, are available for this condition.We describe two patients treated with sodium thiosulfate with good results. Moreover, we also performed a PubMed literature search of sodium thiosulfate treatment for calciphylaxis. We found 41 cases of which most (>90%) presented a rapid and sustained resolution, indicating this drug is a very good candidate for the treatment of this condition.

UV Induced Skin Immunosuppression

It is well estabilished that ultraviolet radiations from sunlight are carcinogenetic for skin cells. These radiations at different wavelength induce damage in the skin manly through two mechanisms : direct DNA alteration and alteration of the immune system. The skin immune system is composed by a complex network of cells and soluble mediators that help to maintain the homeostasis of the skin. UV induced immunosuppression is mediated through different photoreceptors present in the skin that lead to either: the production of immunosuppressive cytokines such as IL-10, TNF-α and TGF-β or the development of suppressive T regulatory cells or to the migration in the skin of CD11+ leukocytes in the skin that ultimately lead to the suppression of immune responses. The aim of this short review is to summarize the general knowledge in the field of UV-induced immunosuppression. The knowledge of the exact mechanism involved in this mechanism is important in order to develop strategies aimed at reducing skin cancer induction.

Polypodium leucotomos supplementation in the treatment of scalp actinic keratosis: could it improve the efficacy of photodynamic therapy?

BACKGROUND Actinic keratoses (AKs) are a common premalignant skin condition. Many treatments are available for AKs. Photodynamic therapy (PDT) is one of the most effective treatments. However, major concerns exist on the possibility of PDT-induced DNA-mutagenesis/immunosuppression, leading to AKs recurrence/treatment failure. An extract (PLE) from the fern polypodium leucotomos reduces UV-induced immunosuppression and mutagenesis. OBJECTIVE To assess the ability of PLE to enhance the efficacy of PDT treatment, reducing AKs recurrence on the scalp. MATERIALS AND METHODS Thirty-four bald patients presenting at least two AKs on the scalp were alternatively assigned to two groups. Both groups underwent two PDT-sessions one-week apart. The first group began oral PLE supplementation one week after the last PDT session. Evaluation of the effect of PLE supplementation was performed by direct inspection of the bald areas, lesions count, and photodynamic diagnosis assessment at 2 and 6 months. RESULTS Both groups were homogeneous in terms of skin phototype and previous UV exposure. Mean age was 75.7 ± 7.8 years and 76.5 ± 5.5 years, respectively. Both treatment modalities were successful in reducing AKs number (p < .001). However, PLE supplementation increased clearance rate compared with PDT alone (p = .040). CONCLUSION Polypodium leucotomos improves PDT clearance and decreases AK recurrence rate at 6 months, suggesting its use as a complementary agent in the treatment of field cancerization.

The Antinflammatory Effect of Alpha-MSH in Skin: A Promise for New Treatment Strategies

MCs are peptide hormones involved in the regulation of an increasing list of processes: pigmentation, cortisol production, food intake, energy and metabolism homeostasis, sexual behaviour, exocrine gland function and inflammation. One of the most important players of this system is αMSH, a neuroimmunomodulatory tri-decapeptide derived from POMC; while it has been demonstrated in melanocytes, monocytes, B-cells, NK, a subset of cytotoxic T-cells, epithelial cells and in keratinocytes, the skin is one of the most relevant extrapituitary sources of αMSH expression and secretion. The key role of MCs in skin/hair colour regulation has been widely figured out in man and animal models. UV-light induces the production of MCs; additionally other skins produced cytokines and parakrine factors (CRH, IL-1, TNF-α, and TGF-β) regulate MC production and MC-1R activity. Moreover MCs and their autoAbs are involved in grooming behaviour, antipyretic and antinflammatory responses, learning, reproductive function, appetite regulation, eating disorders, energy homeostasis, ethanol consumption and violent conduct. A strong and not well understood association between skin malignancies and the CRH-POMC axis has been shown. The MCs bind to five MC-Rs. Each MC-R binds several MCs with the exception of MC-2R, strongly selective for ACTH, unlike the expression of MC-R which is tissue specific, MC-5R being the most widespread. The discovery of the influence of MC in the inflammation modulation, food intake behaviour, lipid metabolism, sex activities, neoplasm development and autoimmune diseases is attracting more and more attention to define new therapeutic strategies and drugs like αMSH and the related tripeptide KPV and K(D)PT.

Mole modifications following controlled ovarian stimulation for assisted reproduction technologies

The role of estrogens on moles biology remains undefined although estrogenic receptors have been found on melanocytes. It has been postulated that supraphysiological estrogen levels could promote the progression of moles to melanoma. Women undergoing controlled ovarian stimulation (COS) for assisted reproductive technologies (ART) are exposed to high levels of estrogens, produced by the ovary in response to exogenous gonadotropin administration. The aim of this study is to assess whether COS for ART may have an impact on mole structure and/or characteristics.

Skin toxicity evaluation in patients treated with cetuximab for metastatic colorectal cancer: a new tool for more accurate comprehension of quality of life impacts

Objectives The effectiveness of evaluation of the severity of epidermal growth-factor receptor inhibitor (EGFRI)-associated dermatological toxicities remains a topic of debate. This study was designed to assess the correlation between quality of life (QoL) and severity of dermatological toxicity, evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) and our novel scale, the Eruption Scoring System (ESS), in metastatic colorectal cancer (CRC) patients treated with first-line chemotherapy combined with cetuximab. Methods Cutaneous toxicity was evaluated, by oncologists and dermatologists, in patients (n=30) with histologically confirmed metastatic CRC who were scheduled to begin first-line chemotherapy combined with the EGFRI, cetuximab, using the NCI-CTCAE and ESS tools. Health-related QoL (HRQoL) was evaluated using the Skindex-29 and Skindex-17 dermatology-specific instruments. Correlations between QoL and skin toxicity severity were assessed using Spearman’s rank tests. Interclass correlation coefficients were used to assess interoperator agreement for ESS and NCI-CTCAE v4.0 scoring. Results A positive correlation was identified between dermatology HRQoL and the severity of dermatological toxicities assessed using the NCI-CTCAE v4.0 scale for cutaneous papulopustular acneiform rash; however, a stronger correlation was observed between HRQoL and toxicities evaluated using the ESS tool. Both NCI-CTCAE v4.0 and ESS tools demonstrated good interobserver agreement for grading of skin toxicity. Conclusion There is a strong correlation between the scores generated by the ESS and NCI-CTCAE tools to grade cutaneous toxicity related to treatment with the anti-EGFR monoclonal antibody, cetuximab. ESS can be considered a valid instrument for identification and grading of the severity of skin toxicity induced by cetuximab, with some advantages over the standard NCI-CTCAE scoring system.

MSH peptides and applications to treatment of hair

The proopiomelanocortin (POMC) system is an evolutionary conserved regulatory module representing one of the best characterized neuropeptide networks which can be considered as an equivalent of the hypothalamic-pituitary-adrenal axis. POMC contains within its structure the amino acid sequences of several hormonal products (ACTH, alpha-melanocyte-stimulating hormone (αMSH), βMSH, and γMSH, the endogenous opioids α-, β- and γ-endorphin). While originally identified as regulators of pigmentation, the POMC system is responsible for the balance of several physiologic processes. One of the most important players of the melanocortin (MC) system is αMSH, a neuro immunomodulatory peptide. In addition to its pigmentary capabilities, αMSH has been addressed as potent anti-inflammatory protein downregulating proinflammatory cytokines. αMSH can be detected in: melanocytes, monocytes, B cells, natural killers, a subset of cytotoxic T cells, epithelial cells and in keratinocytes. The MCs mediate their biological effects by binding to five different MC receptors (MC-Rs) belonging to the superfamily of G protein-coupled receptors. Distibution of each MC-Rs varies among the different tissues, cell type and during cell differentiation. The hair follicle is a typical stress-responding mini organ with a peculiar immune system in which the human follicle bulge meets all key criteria of an immunoprivileged tissue site. This immune privilege is characterized primarily by a low expression of major histocompatibility (MHC) class I antigens. Moreover, the anagen hair bulb lacks a lymphatic system and almost devoid of intraepithelial T cells. Indeed, anagen hair bulbs locally generate potent immunosuppressants. Thereafter immune privilege collapse may favor autoimmune disease development like alopecia areata. Due to its anti-inflammatory and immunomodulatory activity and to its highly favorable safety profile, αMSH has already been exploited as a promising candidate for immune privilege restoration in several immune diseases. In addition to αMSH, follicular cells produce other POMC-derived peptides such as ACTH and β-endorphin; those molecules, as well as αMSH and its related peptides, k(D)PT and KPV, may assist in the maintenance or restoration of the unique immune system of the hair follicle and could be eventually considered as potential therapeutic agents for immune hair disorders.