Giuseppe Pistone

Unusual clinical variants of cutaneous leishmaniasis in Sicily

Background  The term “leishmaniasis” defines a group of vector‐borne diseases caused by species of the genus Leishmania and characterized by a spectrum of clinical manifestations. Parasite properties (infectivity, pathogenicity, virulence), host factors, and host responses regulate heterogeneous disease expression. Sicily is one of the major islands of the Mediterranean Basin and is considered to be a hypo‐endemic area for cutaneous leishmaniasis. Leishmania infantum is the most common species on the island.

Achilles tendon ultrasonography may detect early features of psoriatic arthropathy in patients with cutaneous psoriasis.

Psoriatic arthropathy is a progressive and debilitating disease involving reduction of functional activity of the articulations with consequent deterioration of the patients quality of life. The entheses represent the initial site of articular inflammation and the enthesis of the Achilles tendon is the first to be affected. In some patients with psoriasis, enthesitis may not be diagnosed because it is still asymptomatic.

Adalimumab for treatment of moderate to severe psoriasis and psoriatic arthritis

ABSTRACT:  Psoriasis and psoriatic arthritis are common diseases associated with considerable morbidity and disability. Their pathophysiology comprises similar processes leading to inflammation of skin, entheses, and joints.

ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis

P63 is a transcription factor belonging to the family of p53, essential for the development and differentiation of epithelia. In recent years, it has become clear that altered expression of the different isoforms of this gene can play an important role in carcinogenesis. The p63 gene encodes for two main isoforms known as TA and ΔN p63 with different functions. The role of these different isoforms in sustaining tumor progression and metastatic spreading however has not entirely been clarified. Here we show that breast cancer initiating cells express ΔNp63 isoform that supports a more mesenchymal phenotype associated with a higher tumorigenic and metastatic potential. On the contrary, the majority of cells within the tumor appears to express predominantly TAp63 isoform. While ΔNp63 exerts its effects by regulating a PI3K/CD44v6 pathway, TAp63 modulates this pathway in an opposite fashion. As a result, tumorigenicity and invasive capacity of breast cancer cells is a balance of the two isoforms. Finally, we found that tumor microenvironmental cytokines significantly contribute to the establishment of breast cancer cell phenotype by positively regulating ΔNp63 and CD44v6 expression.

Enteric-coated mycophenolate sodium in the treatment of refractory pemphigus

Background  One of the major goals of pemphigus therapy is to reduce the patient’s cumulative exposure to systemic corticosteroids. To investigate the efficacy of enteric‐coated mycophenolate sodium (EC‐MPS), 10 patients with active, refractory pemphigus vulgaris (PV) or foliaceous (PF) were treated with EC‐MPS (1440 mg daily) and prednisone (75 mg daily) over 18 months.

Naevus comedonicus immunohistochemical features in two cases.

Sir, Naevus comedonicus was first described by Kofmann in 1895 (1). It was arranged in groups or linear patterns along Blaschko’s line and located on the face, neck, upper arms, chest and abdomen. It has been well documented that naevus comedonicus occurs as a single entity but occasionally in association with other disorders. The objective of this study was to analyse the clinical and immunohistochemical features of two patients with extensive naevus comedonicus arranged in groups and linear patterns without non-cutaneous abnormalities.

Omalizumab for the treatment of chronic spontaneous urticaria in clinical practice

Chronic spontaneous urticaria (CSU) is a skin disease that predominantly affects adults, especially women aged 20 to 40 years, and is characterized by the recurrent appearance of localized or widespread wheals, angioedema or both, without apparent external trigger.1,2 Severe CSU has a detrimental effect on the quality of life and is a frequent cause of absenteeism from school and work.3 The pathogenesis of CSU is not well understood, and it appears to have an autoimmune cause in approximately one-third of patients.4 Guidelines for themanagement of CSU recommend the use of second-generation antihistamines, with the addition of leukotriene receptor antagonists, cyclosporine, or omalizumab.1 A short course (10 days maximum) of oral corticosteroids may also be included for acute exacerbations. Omalizumab is a humanizedmonoclonal antibody that results in a rapid and substantial reduction in serum levels of IgE with subsequent down-regulation of FcεRI on mast cells and circulating basophils, making these cells insensitive to stimulation by incoming allergens.5 It is approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of CSU in adults and adolescents ( 12 years old) with inadequate response to antihistamine treatment. However, the clinical experience with omalizumab is limited, and data regarding its use in patients with CSU in real-life practice are lacking. We present a case series of patients with CSU refractory to antihistamines and other recommended therapies who initiated omalizumab treatment. All patients included in the study received300mgofomalizumab (Xolair;Novartis, Basel, Switzerland) injection subcutaneouslyevery 4 weeks at 8 dermatology and allergy clinics in southern Italy from July 2014 to November 2015. The response to treatment was evaluated at each monthly visit using the Urticaria Activity Score (UAS) and the ItchSeverity Score (ISS). TheUAS rated the severityofwheals and prurituswith scores from0 to3 (0, none; 1,mild; 2,moderate; 3, intense; total score ranging from 0 to 6), whereas the ISS evaluated pruritus on a 4-point scale (0, none; 1, mild; 2, moderate; and 3, severe) or on an 11-point visual analog scale (0, no itch; to 10, most intense itch). TheUAS in the last 7days (UAS7) evaluated the severity of wheals and pruritus during the past week and was a sum of the scores for each day of the past week (maximum score, 42), which relied on entries in the patient diaries. Adverse events associated with the treatmentwere recorded, and all patientswere followedup for a variable period after treatment discontinuation. The studywas conducted in accordance with the ethical standards of the institutional and national committee on human experimentation and the Declaration of Helsinki. All patients included in the study provided a written informed consent.

Gender differences in adverse drug reactions in dermatological patients in west Sicily: an epidemiological study

Purpose: The purpose of this study was to show that gender also plays an important role in pharmacokinetics, pharmacodynamics, and drug toxicity. It is only fair to take into account the so-called “gender-based medicine.” Methods: We again selected admission for cutaneous adverse drug reaction (CADRs), from January 2012 to July 2012, in order to detect and verify, in an analytical way, the substantial gender differences in adverse drug reactions in term incidence, clinical manifestations, severity and drugs involved. Results:In the period January–July 2012, at the Department of Dermatology and Sexually Transmitted Disease of A.O.U.P. “Paolo Giaccone” Palermo, 384 patients were admitted, of which 192 were females (50%) and 192 males (50%). Out of a total of 384 patients, 34 cases of CADRs (8.9%) were identified including 24 females (71%) and 10 males (29%). Conclusions: The female gender is an important predisposing factor for the RAF: a large case series showed that in the RAF female/male ratio is 1.7:1.

Tuberculoid leprosy and Type 1 lepra reaction.

A patient is described with tuberculoid leprosy and Type 1 (lepra) reaction from Sicily a non-endemic region, who lived previously in Manila from 2000 to 2005. The skin lesions became acutely inflamed and edematous. The plaques were painless to touch or pinprick, and there was swelling of the nerves in the fibro-osseous tunnels under the surface of the skin, including both the ulnar nerve at the elbow, and the posterior tibial nerve (medial malleolus). During the course of electro-neurographic studies, conduction velocity in the motory nerves indicated a slowing-down. The diagnosis of leprosy was confirmed by residence in an endemic area for about 5 years, by simultaneous skin lesions and peripheral nerve abnormalities, and by skin biopsy. Outside of endemic areas, diagnosis remains a challenge for physicians for mainly two reasons. Firstly, the incubation period of leprosy is uniquely long among bacterial diseases and varies from a month to over 40 years. Secondly, outside leprosy-endemic areas, the diagnosis of leprosy is usually not considered, and patients are likely to be examined by a wide range of specialists. Physicians outside endemic areas should consider leprosy as a possible differential diagnosis if a patient from leprosy-endemic regions presents with painless skin lesions, nerve enlargement, or persistent skin lesions.

Efficacy of a film-forming medical device containing sunscreen (50+) and piroxicam 0.8% in actinic keratosis and field cancerization: a multicenter, assessor-blinded, 3 month trial

Abstract Introduction: Sunscreen protection in subjects with actinic keratosis (AK) is highly recommended to prevent clinical evolution of this in situ skin cancer condition. Use of topical anti-cyclooxygenase drugs such as diclofenac and piroxicam reduces the number of lesions and improves the cancerization field. A film-forming medical device in a cream formulation containing organic and inorganic sun-filters (50+ SPF) and piroxicam 0.8% (ACTX) has shown in a pilot, single-center, open trial to reduce AK lesions improving the cancerization field. Aim: We evaluated in a multicenter, assessor-blinded, 3 month trial the efficacy of ACTX in AK. Methods: A total of 70 subjects with at least three AK lesions on the scalp or face were enrolled after written informed consent. Primary outcomes of the study were the clinical evolution of number of AK lesions on a target zone area and the evolution of dermoscopy features of the target lesion, assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score (from 0 to 4; maximum score: 16). Lesion count and dermoscopy score were evaluated in a blind fashion assessing digital color high definition coded images. A secondary outcome was the Investigator Global Score (IGS) of clinical evolution of the target area using a 7 point scale from −2 (significantly worse) to +4 (completely cured). IGS was evaluated in an open fashion. Subjects were instructed to apply the cream twice daily on the target area, using one finger-tip unit for the treatment of a 35 cm2 area. Results: All but one subject (40 men and 30 women, mean age 73 years) concluded the study period. At baseline the mean (±SD) number of AK lesions in the target area were 7.0 (5.9) with a median value of 5 and the dermoscopy score of the target lesion was 7.0 (2.3) with a median value of 7.0. ACTX treatment reduced AK lesions to 3.2 (2.9), (p = .0001; Wilcoxon Test), representing a 55% relative reduction. Dermoscopy score was reduced to 3.3 (2.6) (p = .0001) (a reduction of 53%). The IGS after ACTX treatment was +1.9 (1.1), with a median of 2.0. A total of 86% of subjects showed a clinical improvement of IGS (≥1) with a very significant/complete clearance (score +3 or +4) in 42% subjects. No change or a worsening of AK lesions was observed in 14% of the subjects. The product was well tolerated. No serious adverse events were reported during the duration of the trial. Conclusion: In this multicenter, assessor-blinded trial, the use of a film-forming medical device with sun protection and anti-inflammatory actions was effective in reducing AK lesions and improving the dermoscopy aspect of the target lesion in 86% of treated subjects. A head-to-head trial evaluating the efficacy of this medical device in comparison with diclofenac is warranted to establish whether this therapeutic approach could offer additional advantages in term of AK lesion reduction compared to an established topical treatment. (Trial ID: ISRCTN72020277).