Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study.

BACKGROUND: Treatment of moderate-to-severe atopic dermatitis (AD) in the elderly may be challenging, due to side-effects of traditional anti-inflammatory drugs and to comorbidities often found in this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known. OBJECTIVES: A multicentre retrospective, observational, real-life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65 years and affected by severe AD. Their main clinical features were also examined. METHODS: Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P-NRS, S-NRS and DLQI) scores at baseline and after 16 weeks of treatment. RESULTS: Two hundred and seventy-six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16-week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18-64 years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty-one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event. CONCLUSIONS: Therapy with dupilumab led to a significant improvement of AD over a 16-week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly.

An unusual case of mammary Paget’s disease in a woman with psoriasis.

Mammary Paget’s disease (MPD) is a malignant breast tumor, which is characterized by intraepidermal infiltration from malignant glandular epithelial cells. Often it may include an underlying ductal carcinoma in situ or an invasive ductal carcinoma. Clinically it appears as an erythematous patch, moist or crusted, with or without desquamation that in some cases becomes ulcerated, causing infiltration and inversion of the nipple. We report the clinical case of a 60-year-old woman, treated in our department for psoriasis, presenting with erythema of nipple and areola with nipple erosion, ulceration and poor secretion. Suspecting Paget’s disease of the nipple, radiological exams (mammography and breast MRI) were performed. A biopsy for histological examination was carried out and confirmed the diagnosis of mammary Paget’s disease. MPD is sometimes difficult to diagnose both clinically and radiologically, therefore it is important to distinguish from other conditions: in literature MPD is reported in differential diagnosis with psoriasis given its similar clinical features, and in some cases MPD has been treated with topical and systemic steroids due to a wrong diagnosis. However, the concomitance, in the same individual, of mammary Paget’s disease and psoriasis has never been described.

Investigating psoriasis awareness among patients in Italy: validation of a questionnaire.

OBJECTIVE: Psoriasis can have a profound impact on quality of life (QoL) and an awareness of the processes of the disease and its treatment is important in coping with symptoms. Patients do not always understand the potential consequences of their disease and the wide range of effective treatment strategies now available. We designed and validated a questionnaire to investigate patient awareness and understanding of psoriasis including pathogenesis, diagnosis, prognosis and treatment. PATIENTS AND METHODS: This was a multicentre, cross-sectional investigation involving 14 psoriasis referral centres in Italy. The focus group technique was used by a panel of experts in psoriasis, to draw-up a list of questions exploring pathogenesis, diagnosis, prognosis, factors influencing clinical course of psoriasis as well as QoL issues and sources of information on their condition. Psychometric properties of the questionnaire were tested on a sample of 240 adult patients with psoriasis (including treatment-naïve and -experienced patients). RESULTS: The mean age of patients was 50.3±14.9 years and 34.2% were female. The median time from diagnosis was 13.7 years (IQR 7.3-23.2). The Cronbach alpha was 0.77 and all items showed higher correlations within their own dimensions than to other dimensions. Each domain of awareness was well represented by a single dimension. Mean overall awareness was 59.7±13.1 on a 100-point scale. CONCLUSIONS: Our questionnaire was valid in assessing patient awareness in five relevant areas of psoriasis, and can be useful in both the clinical setting and research studies to evaluate patients' knowledge of psoriasis better, with the final aim of reducing the burden of this chronic condition.

Ink spot lentigo: singular clinical features in a case series of patients.

Ink spot lentigo, also known as reticulated black solar lentigo, is a melanotic macula commonly described in fair-skinned individuals on sun-exposed areas of the body. Clinically it is a darkly pigmented type of solar lentigo; herein the term ink spot lentigo. In contrast to common solar lentigines, ink spot lentigo is reported as a unique lesion. However usually ink spot lentigo appears among several common solar lentigines. We report a series of 5 patients who presented ink spot lentigo with typical dermoscopic pattern but singular clinical features.

PEL, Kaposi's sarcoma HHV8+ and idiopathic T-lymphocitopenia CD4+.

We described a case report of a 36-year-old woman with a 10-year-history of idiopathic CD4+ T-lymphocitopenia and Kaposi's sarcoma HHV8+ who developed recurrent pleural effusion. Laboratory and instrumental tests with morphologic, immunophenotypic and molecular analysis of pleural sediment suggest us the diagnosis of primary effusion lymphoma (PEL). The term primary effusion lymphoma defines an extranodal non-Hodgkin's lymphoma HHV8-related, usually classified as a B-cell lymphoma, that grows in liquid-phase within body cavities. The case reported by the Authors appears to be of great interest for its epidemiological and clinical features.

Lisch nodules of the iris in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease. The Lisch nodule represents one of the most common NF1 ocular manifestations. Several studies have reported that the Lisch nodule is a melanocytic hamartoma but its pathogenesis is still debated. We have studied the histopathological and ultrastructural features of a Lisch nodule of a 50-year-old woman biopsied during an intracapsular cataract extraction. Our researches revealed that it was composed of three main cytotypes: pigmented cells, fibroblast-like cells and mast cells, showing a pattern similar to a neurofibroma. Furthermore, we hypothesize that Lisch nodules are compatible with neurofibromas.

The N-termini of the alpha and beta subunits at the top of F1 stabilize the energy-transfer function in the mitochondrial F1Fo ATP synthase.

Limited trypsin digestion of isolated F1 removed 15 and 7 amino acids from the N-termini of the alpha and beta subunits respectively and left other subunits untouched as shown by electrophoresis, immunoblotting and protein sequencing. The cooperativity for ATP hydrolysis by soluble F1 was impaired by trypsin digestion. The Km2 obtained from Eadie-Hofstee plots apparently decreased in trypsin-digested F1 but the affinity for adenosine 5'-[beta,gamma-imido]triphosphate (AdoPP[NH]P) and GTP hydrolysis was not influenced. The inhibition of ATP hydrolysis by ADP was attenuated by trypsin digestion. Trypsin digestion of F1 did not affect its capacity to bind to Fo nor did it alter the sensitivity of ATP hydrolysis in the F1Fo reconstituted system to oligomycin and N,N'-dicyclohexylcarbodiimide. The cleavage of the alpha and beta subunits did, on the other hand impair: (a) the ATP-driven proton pumping in the reconstituted F1Fo complex: (b) the inhibition by F1 of passive proton conduction in Fo; (c) the inhibition of passive proton conduction in Fo by AdoPP[NH]P binding to F1. These results show that the limited cleavage of the N-termini of the alpha and beta subunits, located on the top of F1, results in decoupling of catalysis from proton transport. The possible relationship of these observations with the binding change rotatory model of the F1Fo ATP synthase is discussed.