Ilaria Proietti

Correlations between Psoriasis and Inflammatory Bowel Diseases

For a long time the relationship between inflammatory bowel diseases (IBDs) and psoriasis has been investigated by epidemiological studies. It is only starting from the 1990s that genetic and immunological aspects have been focused on. Psoriasis and IBD are strictly related inflammatory diseases. Skin and bowel represent, at the same time, barrier and connection between the inner and the outer sides of the body. The most important genetic correlations involve the chromosomal loci 6p22, 16q, 1p31, and 5q33 which map several genes involved in innate and adaptive immunity. The genetic background represents the substrate to the common immune processes involved in psoriasis and IBD. In the past, psoriasis and IBD were considered Th1-related disorders. Nowadays the role of new T cells populations has been highlighted. A key role is played by Th17 and T-regs cells as by the balance between these two cells types. New cytokines and T cells populations, as IL-17A, IL-22, and Th22 cells, could play an important pathogenetic role in psoriasis and IBD. The therapeutic overlaps further support the hypothesis of a common pathogenesis.

BRAF and NRAS Mutations are Heterogeneous and Not Mutually Exclusive in Nodular Melanoma

Inhibitors of RAF inhibit the MAPK pathway that plays an important role in the development and progression of those melanoma carrying the V600E BRAF mutation, but there’s a subset of such patients who do not respond to the therapy. Various mechanisms of drug resistance have been proposed which include the clonal heterogeneity of the tumor. We have studied a population of nodular melanoma to investigate the intratumor and intertumor heterogeneity by Laser Capture Microdissection (LCM) analysis. Our results showed that BRAF and NRAS mutations were detected in 47% and 33% of nodular melanoma, respectively, and that there is a discrepancy in mutational pattern of tumoral sample because in the 36% of patients a different mutation, in at least 1 area of the tumor, was found by LCM analysis, giving evidence of the presence of different clonal cells populations. Moreover, we found that mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens and we observed that when the 2 different mutations were present one is a high-frequency mutation and the other is a low-frequency mutation. This was more evident in lymphonodal metastasis that resulted from wild type to mutational analysis, but showed different mutations following LCM analysis. Therefore, we believed that, when primary tumoral sample results negative to mutational analysis, if it is possible, metastases should be investigated to verify the presence of mutations. Generally, it should be searched for other mutations, in addition to BRAF V600E, so as to better understand the mechanism of drug resistance.

Mediterranean diet and familial dysmetabolism as factors influencing the development of acne

Aim: To investigate the effects of adherence to the Mediterranean diet and familial dysmetabolisms on acne development. Methods: A community-based case–control study was carried out in Italy enrolling cases as acneic outpatients of a dermatological ambulatory service and controls as clinically healthy acne-free subjects. Food consumption were evaluated with a validated food-frequency questionnaire, exploring the consumption of pasta, meat, cheese, fish, fruit, vegetables, and olive oil. Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean diet scale that incorporated the main characteristics of this diet. A logistic regression analysis estimated the variables who predicted the odds of being case, using those variables that at the univariate analysis yielded a p-value <0.25. Results are presented as odds ratio (OR) or adjusted OR (AOR). Results: The study included 93 cases (36.6% males, median age 17 years) and 200 controls (32% males, median age 16 years). The Mediterranean diet score ≥6 revealed a protective effect towards acne (crude OR 0.22, 95% CI 0.08–0.64). Logistic regression analysis showed that familial hypercholesterolaemia, diabetes, and hypertension are strong risk factors for acne (AOR 8.79, 95% CI 1.67–46.22; 3.32, 95% CI 1.27–8.63; and 2.73, 95% CI 1.07–6.96, respectively), while the Mediterranean diet represents a protective factor (score ≥6, AOR 0.31, 95% CI 0.11–0.89). Conclusions: The odds for familial dysmetabolisms was higher in cases than in controls, confirming their role in determining or maintaining acne. Moreover, this is the first study demonstrating a protective role of the Mediterranean diet in the pathogenesis of acne.

Recombinant interferon α-2b and coenzyme Q10 as a postsurgical adjuvant therapy for melanoma: A 3-year trial with recombinant interferon-α and 5-year follow-up

Early surgical intervention remains the most successful therapy for melanoma. Despite better outcomes observed in soft tissue and lymph node metastases, the results of pharmacological therapies are still disappointing. Currently, there is no standard adjuvant therapy for melanoma. Low concentrations of coenzyme Q10 have been demonstrated in melanoma cell lines and in sera of melanoma patients. These data and the results of clinical trials of patients with other advanced cancers prompted this study of the long-term administration of an optimized dose of recombinant interferon &agr;-2b and coenzyme Q10 to patients with stage I and II melanoma. A 3-year trial envisaging uninterrupted treatment with low-dose recombinant interferon &agr;-2b (9 000 000 000 IU weekly) administered twice daily and coenzyme Q10 (400 mg/day) was conducted in patients with stage I and II melanoma (American Joint Committee on Cancer criteria 2002) and surgically removed lesions. Treatment efficacy was evaluated as incidence of recurrences at 5 years. All patients completed the treatment and the follow-up. Significantly different rates of disease progression were observed in the interferon+coenzyme Q10 and the interferon group for both stages. No patient withdrew from the study owing to side effects. Long-term administration of an optimized dose of recombinant interferon &agr;-2b in combination with coenzyme Q10 seemed to induce significantly decreased rates of recurrence and had negligible adverse effects. A survival study could not be undertaken owing to the small patient sample and the short duration of follow-up.

Celiac disease: from gluten to skin

Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of the intestinal villi that improves after a gluten-free diet. CD is often associated with extraintestinal manifestations. In the past few years, growing evidence has documented the involvement of skin diseases among the extraintestinal manifestations of CD. This association could be related to the impairment of intestinal absorption and motility, other than to immunological and hormonal changes. The aim of this review is to report all CD-associated skin manifestations described in the literature and to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed.

Acitretin in management of diffuse common warts: a case report

Warts are among the most commonly observed dermatological diseases, caused by human papilloma virus (HPV), usually HPV1‐2 subtypes; HPV4‐7 are rarely found and mostly related to professional exposure (butchers and dairy workers). Different therapeutical approaches are possible, depending on extension and severity of lesions. The present authors describe the case of 32‐year‐old Caucasian man, who came to our attention for the presence of numerous exophytic papules on the back of both hands and over periungual regions, which appeared about 6 months before. Histological examination confirmed the clinical suspicion of common warts (HPV4). The patient underwent therapy by acitretin for 12 weeks, obtaining during the 8th week of therapy complete resolution of skin lesions. The present authors present this case for the unusual local aggressiveness of viral warts in an immunocompetent patient successfully treated with acitetrin.

Isotretinoin for the treatment of squamous cell carcinoma arising on an epidermoid cyst.

A 63‐year‐old man showed multiple concentric erythemato‐nodular lesions of approximately 1.5–3 cm in diameter, located in the parietal and temporal region. The skin biopsy allowed histological diagnosis of infundibular epidermal cyst associated with chronic granulomatous flogosis; in one of these, a well‐differentiated squamous cell carcinoma arising from the cyst wall was found. The patient received isotretinoin at the daily dosage of 0.5 mg/kg/day for 5 months. During 1‐year follow‐up, laboratory tests, computed tomography scans, and control histology were all in the normal range, with a good improvement of the lesions. Epidermal cysts and squamous cell carcinoma are both commonly encountered in practice. However, the association of epidermal inclusion cysts and squamous cell carcinoma in the skin is very rare. In some cases, including the present one, more potent chemopreventive strategies, such as the use of systemic retinoids, must be considered. Systemic retinoids are the most heavily researched chemopreventive agents and have shown promise for multiple types of cancer, including bladder and head and neck carcinomas. We would like to recommend the possibility to administer retinoids in a squamous cell carcinoma, achieving very satisfactory results; in our case, a complete remission of malignant lesion and an improvement of epidermal cysts were made, without the development of side effects associated with retinoids.

INTESTINAL MALABSORPTION AND SKIN DISEASES

Several skin manifestations were described in patients affected by intestinal disorders. The development of skin diseases in these patients could be related to the impairment of intestinal absorption and motility, other than to immunological and hormonal changes. The growing evidence of the association between skin disorders and intestinal diseases suggests that the skin could be considered the ‘mirror of the gut’.

Cardiovascular Risk in Psoriatic Patients Detected by Heart Rate Variability (HRV) Analysis

Postmarketing Phase IV

Acitretin for treatment of familial porokeratosis palmaris et plantaris disseminate

ejd.2012.1826 Auteur(s) : Nevena Skrozaa, Ilaria Proiettia proiettilaria@gmail.com, Nicoletta Bernardinia, Francesca Nicoluccia, Ersilia Tolinoa, Giorgio La Violaa, Diego Orsinia, Sara Zubera, Concetta Potenzaa UOC of Dermatology “Daniele Innocenzi”, Faculty of Medicine and Surgery, University of Rome “Sapienza”, Polo Pontino, A.Fiorini Hospital, Via Firenze, 04019, Terracina, Italy a All authors contributed equally to this work A 65-year-old Caucasian man was referred to our department [...]