Luca Bianchi

Topical treatment of basal cell carcinoma with tazarotene: a clinicopathological study on a large series of cases.

Background  Basal cell carcinoma (BCC) is the most common cancer in humans. Medical treatment modalities offer cost reductions and clinical advantages in selected cases such as low‐risk areas, surgically inaccessible sites, patients with multiple neoplasms, and older, infirm or anticoagulated subjects. Tazarotene has been proposed for the treatment of BCC; however, data on its efficacy are lacking.

Tazarotene 0·1% gel for psoriasis of the fingernails and toenails: an open, prospective study

SIR, Mycosis fungoides (MF) is characterized by clonal helper ⁄ memory (CD4+ CD45RO+) T-cells in the epidermis, whereas follicular mucinosis or alopecia mucinosis has perifollicular T-cell infiltrates and may clinically resemble alopecia areata. Bexarotene is the first retinoid X receptor (RXR)-selective retinoid shown to be effective for cutaneous T-cell lymphoma. Bexarotene has recently been shown to induce T-cell apoptosis in vitro. Although bexarotene oral and topical gel are effective for MF, this is the first report, to our knowledge, of reversal of associated alopecia. Five patients with alopecia secondary to MF or follicular mucinosis were observed among a cohort of over 90 patients receiving bexarotene therapy at the M.D. Anderson Cancer Center. Their demographic data, degree of hair loss, skin biopsy results and drug administration are shown in Table 1. The location of the hair loss was confined to the scalp in four patients and to the extremities in a fifth. All of the skin biopsy specimens revealed atypical CD4+ CD8+ perifollicular lymphocytic infiltrates, and two showed mucin deposits consistent with follicular mucinosis. Three patients had scaling with negative fungal cultures. Patients with early stage MF were treated with topical bexarotene therapy and advanced stage patients with oral bexarotene. The MF as well as the alopecia improved in all five patients, irrespective of the route of delivery. Hair regrowth began within 2–9 months and full regrowth was evident by 1Æ5 years. Patient 1. A 77-year-old Native American woman presented with a 3-month history of a single patch of alopecia accompanied by pruritus and mild tenderness, generalized xerosis, fatigue and a 4Æ5-kg unintentional weight loss. Asthma and childhood eczema were noted. There was a 4 · 5 cm alopecia areata-like lesion with scaling on the scalp (Fig. 1a) and macular erythema of less than 1%. An atypical CD4+ CD8– clonal lymphocytic infiltrate and mucin deposits were present in the follicular epithelium. After applying 1% bexarotene gel daily to the leg and scalp lesions, partial hair regrowth was present at 3 months (Fig. 1b), with full regrowth of terminal grey hair covering the former patch of alopecia at 5 months (Fig. 1c). Patient 2. A 64-year-old Hispanic man with dermatitis for 30 years developed generalized exfoliative erythroderma, patchy alopecia, and a skin biopsy consistent with MF. He had increased fatigue, chills, night sweats and intense pruritus. On examination, he had generalized exfoliative erythroderma and lymphadenopathy. On the scalp, multiple round alopecia areata lesions, patches of white hair, and exclamation point hairs were observed (Fig. 2a,b). An atypical CD4+ CD8+ dermal infiltrate with epidermotropism and a clonal T-cell receptor gene rearrangement were observed in

Type I lamellar ichthyosis improved by tazarotene 0.1% gel

Summary The efficacy of tazarotene 0.1% gel in a 30‐year‐old woman with type I lamellar ichthyosis is reported. The drug was applied to 15% of the total body surface area as follows: once daily for 2 weeks, three times a week for further 2 weeks, followed by a once weekly maintenance application. During the first week of treatment there was partial improvement obtained and in the next 14 days further reduction of scaling within the tazarotene‐treated areas was observed. After 4 months of maintenance application, there was a marked overall improvement in the treated areas. Side‐effects consisted only of mild pruritus, slight burning and irritation. In essence, the therapeutic benefit obtained was comparable with that of systemic retinoids but without the adverse systemic side‐effects. As noted in other reports, tazarotene 0.1% gel seems to be a valuable and safe therapeutic option for this severe genodermatosis.

Pachyonychia congenita with late onset of nail dystrophy—a new clinical entity?

Pachyonychia congenita syndrome (PCS) is a genetic disease with an autosomal dominant mode of transmission in which the main sign, pachyonychia, usually arises at birth or in childhood together with other disorders of keratinization. A 28‐year‐old woman developed subungual hyperkeratosis of all toe‐nails and thumb‐nails associated with pain on pressure and walking. She had a scrotal tongue with leucokeratotic areas, blister formation, plantar hyperkeratosis, palmoplantar hyperhidrosis and dental cavities since childhood. The present case, interpreted as PCS of late onset, could be a clinical variant of the Jadassohn–Lewandowsky syndrome with the late onset of pachyonychia or else an additional form of PCS due to the expression of a new and different allele.

Intramuscular myxoma of the face: An unusual localization. A clinicopathological study

BACKGROUND Intramuscular myxoma is a rare benign mesenchymal lesion. Only very rare cases of cutaneous localization of this tumor have been described, in particular related to the somatic soft tissues of the face. This unusual localization may clinically mimic nodular or cystic facial lesions having different origins. OBJECTIVE The aim of our work was to well characterize the phenotype of the spindle cells characteristic of intramuscular mixoma. METHODS Tissue samples were processed for morphological and ultrastructural studies. Moreover, immunohistochemical stainings were performed to characterize the expression of different nonmuscular and muscular cytoskeletal proteins. RESULTS The tumor was composed of sparse spindle cells embedded in a prominent mucoid matrix. Besides the predominance of a fibroblast‐like appearance, some neoplastic cells displayed immunohistochemical and ultrastructural features resembling either myofibroblasts or primitive mesenchymal cells, with a modulation of cell actin expression. CONCLUSION The presence of multiple phenotypes of nonmuscular, mesenchymal pathway of differentiation can be considered a peculiar feature of intramuscular myxoma.

Blood MUC-18/MCAM expression in patients with melanoma: a suitable marker of poor outcome

morphology nor the growth rate of the cultured follicles (Fig. 2a,b). In contrast, DHT but not testosterone led to a statistically significant 10 1-fold upregulation of the KRT37 gene, while the gene expression of KRT25 and KRT31 was not affected by the androgens. Indeed, the gene expression of SRD5A1 and SRD5A2 remained lower in cultured occipital hair follicles regardless of androgens (average DCt against RPLP0 by quantitative PCR was 6 2 and 15 2, respectively) (Fig. 2c). Accordingly, at the protein level, a significant K37 induction was clearly demonstrable in the medulla of DHT-treated but not testosterone-treated follicles (compare Fig. 2d, e1–e4, f1, f2), while the constitutive medullar keratin K75 remained insensitive to DHT (Fig. 2g, h1, h2). In line with findings in DHTexposed cultured dermal papilla cells from occipital hair follicles as well as in human beard hair follicles, IIF revealed a slight upregulation of AR expression in the nuclei of cells of the dermal papilla and the lower medulla of DHT-treated hair follicles (Fig. 2i–j′). Taken together, we describe two principal differences between the medulla of androgen-independent occipital and androgen-dependent sexual hairs. Firstly, occipital hairs do not contain genuine cortex cells within their medulla – a feature which is most probably related to the smaller diameter of the occipital hair shaft and its medulla. Secondly, occipital hairs exhibit the same complex keratin pattern as sexual hairs except for the expression of medullar keratin K37. Considering, however, that K37 expression can be induced in medulla cells in vitro through external DHT but not testosterone supply, this suggests that the androgen-insensitivity of occipital hair follicles in vivo goes back to the low expression of 5a-reductases, which results in the inability to synthesize DHT from its precursor testosterone in their dermal papilla and medulla cells. Hair keratin K37 may therefore be ideally suited to serve as a pathfinder for the elucidation of an altered androgen metabolism not only in occipital hairs follicles but also in follicles of other scalp regions.

Loss of CRABP-II Characterizes Human Skin Poorly Differentiated Squamous Cell Carcinomas and Favors DMBA/TPA-Induced Carcinogenesis

Retinol and its derivatives play an important role in epidermal growth and differentiation and represent chemopreventive agents in nonmelanoma skin cancer. Retinoic acid binding protein II (CRABP-II) is a cytoplasmic receptor that critically regulates all-trans-retinoic acid (ATRA) trafficking. We documented the marked reduced expression of CRABP-II and its promoter methylation in human poorly differentiated squamous cell carcinomas. To investigate the role of CRABP-II in skin carcinogenesis we used skin lesion induction by dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate in CRABP-II-knockout C57BL/6 mice. We observed earlier and more diffuse epidermal dysplasia, greater incidence and severity of tumors, reduced expression of cytokeratin 1/cytokeratin 10 and involucrin, increased proliferation, and impaired ATRA inhibition of tumor promotion compared with wild-type animals. CRABP-II-transfected HaCaT, FaDu, and A431 cells showed expression of differentiation markers, retinoic acid receptor-β/-γ signaling, ATRA sensitivity, and suppression of EGFR/v-akt murine thymoma viral oncogene homolog 1 (AKT) pathways in a fatty acid binding protein 5/peroxisome proliferator-activated receptor-β/-δ-independent manner. The opposite was true in keratinocytes isolated from CRABP-II-knockout mice. Finally, CRABP-II accumulation induced ubiquitination-associated reduction of EGFR. Our results showed reduced CRABP-II expression in human poorly differentiated squamous cell carcinomas, and its gene deletion favored experimental skin carcinogenesis and impaired ATRA antitumor efficacy, likely modulating EGFR/AKT pathways and retinoic acid receptor-β/-γ signaling. Therapeutic interventions aimed at restoring CRABP-II-mediated signaling may amplify therapeutic retinoid efficacy in nonmelanoma skin cancer.

Behandlung der multiplen aktinischen Keratose und Feldkanzerisierung mit topischem Piroxicam 0,8% und Sonnenschutz (LSF 50+) bei Organtransplantat-Empfängern: Eine Serie von 10 Fällen

Empfänger von Organtransplantaten (organ transplant recipients, OTR) haben ein hohes Risiko, Hautkrebs wie z.B. ein Plattenepithelkarzinom und ein Basalzellkarzinom zu entwickeln. Die aktinische Keratose (AK) wird als Vorstufe dieser nicht-melanozytären Hautkrebsarten angesehen. Sonnenschutz ist für Patienten mit AK unerlässlich und eine wichtige vorbeugende Maßnahme bei Organtransplantat-Empfängern. Die Behandlung der Feldkanzerisierung ist außerdem entscheidend, um das Risiko für ein Rezidiv der Hautläsionen bei AK und bei Patienten mit nicht-melanozytärem Hautkrebs zu reduzieren. Bei der Pathogenese von Hautkrebserkrankungen spielt die Aktivierung von Cyclooxygenase-1- und -2-Enzymen eine wichtige Rolle. Die topische Anwendung von Cyclooxygenase-Inhibitoren wie Diclofenac und, seit Kurzem, Piroxicam hat sich bei der Verringerung der AK-Läsionen bei immunkompetenten Patienten als wirksam erwiesen. Es wurde gezeigt, dass ein Medizinprodukt, das Piroxicam und Sonnenschutz (LSF 50+) (P+SS) enthält, die AK-Läsionen reduziert und die Feldkanzerisierung verbessert. Wir berichten über den Effekt der Anwendung von P+SS über 16 Wochen in einer Fallserie mit 10 Patienten mit multiplen AK-Läsionen. Die Behandlung mit P+SS führte bei 7 Patienten zu einem klinisch relevanten Rückgang der AK-Läsionen (>75%) (mit vollständiger Abheilung bei 3 Patienten) und zu einer Besserung der Feldkanzerisierung: Dieses Medizinprodukt kann als Erfolg versprechende kurative und präventive Langzeittherapie bei OTR-Patienten mit hohem Risiko für nicht-melanozytären Hautkrebs angesehen werden. Übersetzung aus Case Rep Dermatol 2017;9:211-216 (DOI: 10.1159/000481770)

Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease

IntroductionImmune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and uveitis.MethodsA Delphi consensus-based approach was used to identify a core set of statements. The process included development of initial questions by a steering committee, an exhaustive search of the literature using complementary approaches to identify potential statements and two Delphi voting rounds for finalization of the statements.ResultsConsensus was achieved on the related nature of IMIDs, the existence of a high prevalence of multiple IMIDs in a single patient and the fact that a multidisciplinary approach can result in a more extensive evaluation and comprehensive approach to treatment. The goals of a multidisciplinary team should be to increase diagnosis of concomitant IMIDs, improve the decision-making process, and increase patient satisfaction and adherence. Early referral and diagnosis, early recognition of concomitant IMIDs and optimizing treatment to improve patient quality of life are some of the advantages of using multidisciplinary teams. To be effective, a multidisciplinary team should be equipped with the appropriate tools for diagnosis and follow-up, and at a minimum the multidisciplinary team should include a dermatologist, gastroenterologist and rheumatologist; providing psychologic support via a psychologist and involving an ophthalmologist, general practitioners and nurses in multidisciplinary care is also important.ConclusionThe present Delphi consensus identified a set of overarching principles that may be useful for implementation of a multidisciplinary approach for the management of SpA-related IMIDs.FundingAristea and Hippocrates.