Elisa Moliterni

Paraneoplastic pemphigus: Insight into the autoimmune pathogenesis, clinical features and therapy

Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed “paraneoplastic pemphigus”. We included also papers in French, German, and Spanish. We found 613 papers for “paraneoplastic pemphigus”. Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.

Prognostic factors in head and neck melanoma according to facial aesthetic units

BACKGROUND Head and neck melanoma is a clinical challenge. Indeed, cutaneous head and neck melanoma shows a worse prognosis in comparison to melanomas of other body sites. Although the emphasis on facial cosmetic preservation plays a pivotal role in comparison to other body areas, specific facial aesthetic units could also play a key role in the prognostic evaluation of the malignancy. METHODS The aim of the current study was to evaluate the general outcome and clinicopathological features of head and neck melanoma and to detect prognostic differences according to each facial aesthetic unit. The KaplanMeier product was used to calculate survival curves, while Cox proportionalhazard regression was performed to evaluate the predictive value of each facial aesthetic unit. RESULTS A total of 221 head and neck melanoma patients was included in our analysis. In the nasal facial aesthetic unit, we found a high rate of local recurrence, which affected significantly disease free survival. The worse prognosis was observed in melanoma of the scalp, which showed a greater tendency to skip metastases in internal organs. Moreover, we found that scalp showed a low incidence of nonmelanoma skin cancers, if compared to other facial aesthetic unit, highlighting that the scalp local milieu might play a more prominent role in melanoma biology than chronic UV exposition. CONCLUSIONS Although facial aesthetic units have an aesthetic function, they could also play a role in the evaluation and followup of melanoma.

Marked pseudoepitheliomatous hyperplasia secondary to a red‐pigmented tattoo: a case report

References 1 Limmathurotsakul D, Golding N, Dance DA et al. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 2016; 1: 125–139. 2 Dan M. Melioidosis in travelers: review of the literature. J Travel Med 2015; 22: 410–414. 3 Cheng AC, Currie BJ. Melioidosis: epidemiology, pathophysiology, and management. Clin Microbiol Rev 2005; 18: 383–416. 4 Gibney KB, Cheng AC, Currie BJ. Cutaneous melioidosis in the tropical top end of Australia: a prospective study and review of the literature. Clin Infect Dis 2008; 47: 603–609. 5 Suntornsut P, Kasemsupat K, Silairatana S et al. Prevalence of melioidosis in patients with suspected pulmonary tuberculosis and sputum smear negative for acid-fast bacilli in northeast Thailand. Am J Trop Med Hyg 2013; 89: 983–985. 6 Dance DAB. Melioidosis. Curr Opin Infect Dis 2002; 15: 127–132. 7 Pitman MC, Luck T, Marshall CS, Anstey NM, Ward L, Currie BJ. Intravenous therapy duration and outcomes in melioidosis: a new treatment paradigm. PLoS Negl Trop Dis 2015; 9: 35–36. 8 Yeo B, Lee J, Alagappan U, Pan JY. Cutaneous melioidosis with unusual histological features. Clin Exp Dermatol 2016; 41: 272–274. 9 White NJ. Melioidosis. Lancet 2003; 361: 1715–1722.

An uncommon localization of black heels in a free climbing instructor

Black heels, also known as talon noir or calcaneal petechiae, are asymptomatic superficial cutaneous haemorrhages of the feet, mostly seen as post‐traumatic lesions in young athletic individuals who practice sports such as tennis, football, or gymnastics. Here, we present a case of black heels in a young male rock climber.

Sequential methyl-aminolevulinate daylight photodynamic therapy and diclofenac plus hyaluronic acid gel treatment for multiple actinic keratosis evaluation

Actinic keratosis (AK) is a chronic-relapsing skin lesion, considered as an early stage of invasive squamous cell carcinoma (iSCC) on chronically sun damaged skin (Cantisani et al. 2016a; Cantisani et al. 2016b). AK places a significant burden on health care system (Cantisani, Paolino, Bottoni, & Calvieri, 2015; Tolley, Argenziano, CalzavaraPinton, Larsson, & Ryttig, 2017). Consequently, guidelines recommend that all AKs need to be adequately treated (Lucena et al., 2015; Patel & Stockfleth, 2007). The aim of our work was to evaluate the sequential efficacy of diclofenac 3% in 2.5% hyaluronic acid (DHA) and methyl aminolevulinate-daylight photodynamic therapy (MAL-DL-PDT) on multiple AKs on sun exposed areas. Data were derived by randomized controlled monocentric trial from AK patients, who were assigned to MAL-DL-PDT or MAL-DL-PDT plus DHA; DHA have been applied 30 days before or after MAL-DL-PDT. Patients were evaluated by gender, age, anatomic site of the lesion, systemic therapies, medical history, number of the lesions (≤1 or ≥2). An independent investigator, who was blinded to the assigned treatment modality and was not involved in the treatment, evaluated the tumors 3 and 12 months after the last treatment. Treatment failure was defined as residue or recurrence within 1-year post-treatment. Since DHA is an important anti-inflammatory agent, we evaluated the local inflammation in both groups after the treatment with MAL-DL-PDT. The inflammation intensity was staged as follows: 0 (0–19% of inflammation in the treated area), 1 (20–39% of inflammation in the treated area), 2 (40–59% of inflammation in the treated area), 3 (60–79% of inflammation in the treated area), and 4 (80–100% of inflammation in the treated area). The inflammation was evaluated during second or third MAL-DL-PDT session (3–6 months later). Effectiveness was defined as the probability that complete tumor clearance was achieved 12 months after treatment. A total of 125 patients with multiple AK KIN I and II according to Olsen classification on sun exposed areas and treated with MAL-DL-PDT have been included in the analysis. Patients have been evaluated for 12 months. Mean age of the patients was 73 10 years, with 52 females and 73 males. From this sample of patients, we have considered those treated with MAL-DL-PDT or MAL-DL-PDT plus DHA, 30 days later. They were respectively 93 (52 male and 41 female; mean age 72) and 32 (21 male and 11 female; mean age 75) patients (Table 1). T-test on the ages of the two sample did not show significant differences. The main associated internal diseases in MAL-DL-PDT group were arterial hypertension (n = 5), diabetes (n = 2), malignancies (n = 2; 1 breast cancer and 1 prostatic cancer); while in MAL-DL-PDT plus DHA group the main associated disease was arterial hypertension (n = 3). After 12 months, we did not observe a significant difference in resolution of the AK between MAL-DL-PDT and MAL-DL-PDT plus DHA (p = .5). A mean response of 90% in MAL-DL-PDT plus DHA versus 91.2% in MAL-DL-PDT group have been observed (Figure 1). Finally, at each follow-up we evaluated the presence of inflammation between the two groups and we found that MAL-DL-PDT plus DHA showed a reduced inflammation compared to MAL-DL-PDT alone, without any gender variation. Local skin reaction score was between 2 and 3 (40–79%, median 61%) in MAL-DL-PDT group, while in MAL-DLPDT plus DHA group was between 0 and 1 (0-19-39%, median 11%). The score was arbitrarily performed. Mann–Whitney showed a significant result with a p < .0001 (Figure 2). Only 1% of patients showed photoallergic reaction. Since complete lesion clearance is rarely achieved in real-life practice (Faragnoli, in press), the suggested treatment goals are to reduce the number of lesions, to achieve long-term disease control and to prevent disease progression to iSCC (Faragnoli, in press). Our study showed that the sequential treatment may reduce the inflammation rate and number of MAL-DL-PDT session, increasing patients compliance and consequent quality of life.

Vitamin D and melanoma: state of the art and possible therapeutic uses

Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun-exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

Serum tryptase levels in melanoma patients: case-control study and review of the literature

BACKGROUND Serum tryptase results from the constant release of the enzyme from mast cells and serum tryptase levels are commonly considered to be related to the total number of mast cells. They are increased in several malignancies, as pancreatic carcinoma, angiosarcoma, hepatic carcinoma and proliferative and/or non-proliferative hematological disorders. Contrariwise, it has been reported that the number of tryptase- and chymase-positive mast cells was lower in deeply invasive melanoma compared to in-situ melanoma and dysplastic nevi. Considering the underlying pathophysiological linkages between mast cells and melanocytes and that serum tryptase is related to angiogenesis, tissue-degrading proprieties and metastatization, we have decided to evaluate serum tryptase levels in melanoma patients and in a healthy control. METHODS We performed a case-control study evaluating serum tryptase in melanoma and in healthy group. Starting from an initial general analysis, we have performed a sub-analysis for each sample. RESULTS In general population serum tryptase was statistically higher in elderly patients. Generally, in melanoma patients, median serum tryptase was in lower normal range. We found a decreasing of serum tryptase levels from the healthy control to thin (≤1.00 mm Breslow thickness), reaching the lowest levels in thicker melanoma (≥1.01 mm Breslow thickness), in ulcerated and metastatic melanoma. CONCLUSIONS Tryptase may have a protective role in melanoma or in the early stage of the tumorigenesis. Serum tryptase is an easy and useful biomarker to better investigate melanoma biology.