Validation of plasma microRNAs as biomarkers for myotonic dystrophy type 1.

Non-invasive and simple to measure biomarkers are still an unmet need for myotonic dystrophy type 1 (DM1). Indeed, muscle biopsies can be extremely informative, but their invasive nature limits their application. Extracellular microRNAs are emerging humoral biomarkers and preliminary studies identified a group of miRNAs that are deregulated in the plasma or serum of small groups of DM1 patients. Here we adopted very stringent selection and normalization criteria to validate or disprove these miRNAs in 103 DM1 patients and 111 matched controls. We confirmed that 8 miRNAs out of 12 were significantly deregulated in DM1 patients: miR-1, miR-27b, miR-133a, miR-133b, miR-206, miR-140-3p, miR-454 and miR-574. The levels of these miRNAs, alone or in combination, discriminated DM1 from controls significantly, and correlated with both skeletal muscle strength and creatine kinase values. Interestingly, miR-133b levels were significantly higher in DM1 female patients. Finally, the identified miRNAs were also deregulated in the plasma of a small group (n = 30) of DM2 patients. In conclusion, this study proposes that miRNAs might be useful as DM1 humoral biomarkers.

Combination therapy with hydrogen peroxide (4%), salicylic acid (0.5%) and D-panthenol (4%): efficacy and skyn tolerability in common acne vulgaris during sun exposure period.

OBJECTIVE: Acne vulgaris is a disease of the sebaceous follicle which affects up to 90% of adolescent patients. Topical retinoids, benzoyl peroxide and antibiotics are the main treatments for mild to moderate acne vulgaris. The use of such topical treatments is often associated with local irritation and dryness making the skin more sensitive to the sun. The aim of our study was to assess the efficacy and skin tolerability of a fixed-dose combination therapy with hydrogen peroxide (4%), Salicylic acid (0.5%) and D-panthenol (4%) (HSD) gel, in mild-moderate acne vulgaris, during the period of sun exposure. PATIENTS AND METHODS: We retrospectively observed 30 patients of Central Italy with mild to moderate acne between April and September 2012. All the patients selected underwent only therapy with HSD gel once a day in the evening for 60 days, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale. RESULTS: The mean GES value showed a statistically significant reduction: 2.03 (SD 0.81) at baseline, 1.63 (SD 0.81) and 0.90 (SD 0.71) respectively at 30 and 60 days (p < 0.01). 21 (70%) and 27 patients (90%) did show good or very good tolerability at 30 and 60 days respectively. CONCLUSIONS: Topical treatments with retinoids, antibiotics and antiseptics may increase skin irritation reducing patient adherence to the treatment. HSD gel has shown a good skin tolerability and efficacy in reducing acne lesions, even during the sun exposure period in which traditional treatments should be cautiously used.

Tibialis anterior muscle needle biopsy and sensitive biomolecular methods: a useful tool in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by a CTG repeat expansion in 3'UTR of DMPK gene. This mutation causes accumulation of toxic RNA in nuclear foci leading to splicing misregulation of specific genes. In view of future clinical trials with antisense oligonucleotides in DM1 patients, it is important to set up sensitive and minimally-invasive tools to monitor the efficacy of treatments on skeletal muscle. A tibialis anterior (TA) muscle sample of about 60 mg was obtained from 5 DM1 patients and 5 healthy subjects through a needle biopsy. A fragment of about 40 mg was used for histological examination and a fragment of about 20 mg was used for biomolecular analysis. The TA fragments obtained with the minimally-invasive needle biopsy technique is enough to perform all the histopathological and biomolecular evaluations useful to monitor a clinical trial on DM1 patients.

Combination therapy with retinaldehyde (0.1%) glycolic acid (6%) and efectiose (0.1%) in mild to moderate acne vulgaris during the period of sun exposure--efficacy and skin tolerability.

OBJECTIVES: Acne vulgaris is the most common disease of the adolescence age (70-94%). Main topical treatments for acne vulgaris are retinoids, benzoyl peroxide and antibiotics in mono or combination therapy. Topical retinoids, some antibiotics and antiseptics although effective on acne lesions, can due photosensitivity or make the skin more sensitive to the sun. Our study is aimed to evaluate the efficacy and tolerability of a combination therapy with Retinaldheyde (0.1%), Glycolic acid (6%) and Efectiose (0.1%) (RGE) cream in patients affected by acne vulgaris, during the lasting period of sun exposure. PATIENTS AND METHODS: We retrospectively observed 30 patients of Central Italy with mild or moderate acne between April and September. All the patients selected underwent only therapy with RGE cream once a day in the evening for 8 weeks, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale. RESULTS: The mean GES value showed a statistically significant reduction: 1.83 (SD 0.83) at baseline 1.57 (SD 0.77) and 0.90 (SD 0.76) respectively at 30 and 60 days (p < 0.01). Side effects were very uncommon. CONCLUSIONS: Topical treatments with retinoids, antibiotics and antiseptics can be associated with an increased occurrence of facial dryness and erythema restricting their use in sun exposure period. RGE cream has shown a good skin tolerability and efficacy, so it can be considerate an effective maintaining therapy to treat mild to moderate acne during the sun exposure period in which retinoids, antibiotics or antiseptic treatments are not recommended.

Melanoma detection in Italian pigmented lesion clinics.

AIM: Accuracy in melanoma detection is important to recognize early curable melanomas and to minimize the unnecessary excision of benign lesions. The aim of this paper was to evaluate melanoma screening accuracy of Italian pigmented lesion clinics in terms of number needed to excise (NNE), melanoma thickness, and number of melanomas diagnosed during patient follow-up. METHODS: Information on all skin tumors excised in 2011 were extracted from the databases of the participating centers. Information whether the lesion was excised at the baseline examination or during patient follow-up was recorded, as well as the overall number of patients examined in each center in 2011. RESULTS: After e-mail solicitation, 22 of 40 centers agreed to participate. A total of 8229 excised lesions were collected. The overall number of examined patients was 86.564, thus 9.5% of screened patients had a lesion removed. Of the excised lesions, 866 were diagnosed as melanoma (1% of examined patients) and 5311 (88.9%) were melanocytic nevi. Three NNE were calculated giving values of 7.9 excised lesions to find 1 melanoma, 7.1 melanocytic lesions to find 1 melanoma, and 3.7 lesions to find 1 skin malignancy. The median melanoma thickness was 0.6 mm, with only 15.1% of melanomas ≥ 1 mm of thickness. Melanomas detected over time were 96 (11.1%; mean thickness, 0.3 mm), with 15.6% of lesions excised after short-term follow-up and 84.4% after long-term follow-up. CONCLUSION: The NNE values comparable to those achieved in specialized clinical settings and the high number of early melanomas diagnosed at the baseline examination or during patient follow-up indicate a high level of accuracy in melanoma screening achieved by Italian pigmented lesion clinics.

Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction.

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are multisystemic disorders linked to two different genetic loci and characterized by several features including myotonia, muscle weakness and atrophy, cardiac dysfunctions, cataracts and insulin-resistance. In both forms, expanded nucleotide sequences cause the accumulation of mutant transcripts in the nucleus deregulating the activity of some RNAbinding proteins and providing an explanation for the multisystemic phenotype of DM patients. However this pathogenetic mechanism does not explain some histopathological features of DM skeletal muscle like muscle atrophy. It has been observed that DM muscle shares similarities with the ageing muscle, where the progressive muscle weakness and atrophy is accompanied by a lower regenerative capacity possibly due to the failure in satellite cells activation. The aim of our study is to investigate if DM2 satellite cell derived myoblasts exhibit a premature senescence as reported for DM1 and if alterations in their proliferation potential and differentiation capabilities might contribute to some of the histopathological features observed in DM2 muscles. Our results indicate that DM myoblasts have lower proliferative capability than control myoblasts and reach in vitro senescence earlier than controls. Differentely from DM1, the p16 pathway is not responsible for the premature growth arrest observed in DM2 myoblasts which stop dividing with telomeres shorter than controls. During in vitro senescence, a progressive decrease in fusion index is observable in both DM and control myotubes with no significant differences between groups. Moreover, myotubes obtained from senescent myoblasts appear to be smaller than those from young myoblasts. Taken together, our data indicate a possible role of DM2 premature myoblast senescence in skeletal muscle histopathological alterations i.e., dystrophic changes and type 2 fibre atrophy.

Extragenital lichen sclerosus and atrophicus treated with topical steroids and retinoids in a child with vitiligo.

Lichen sclerosus and atrophicus (LSA) most commonly affects the anogenital region. Extragenital involvement is rare, and women are reported to be affected 6 to 10 times more often than men. The aetiology of LSA is unclear, but genetic, physiological and environmental factors are thought to be involved. Several lines of evidence support the hypothesis of an autoimmune basis for LSA; an increased incidence of tissue-specific antibodies and an association with autoimmune disorders such as vitiligo, alopecia areata, thyroid disease and pernicious anaemia have been reported. We describe a paediatric patient with extragenital LSA associated with vitiligo who was successfully treated with topical steroids and retinoids.

Impetigo herpetiformis occurring during N-butyl-scopolammonium bromide therapy in pregnancy: case report.

Impetigo herpetiformis (IH) is a rare dermatosis arising during the third trimester of pregnancy which is generally considered as a form of pustular psoriasis of unknown aetiology. Clinically it is characterized by erythematous plaques surrounded by sterile pustules associated with fever, diarrhea, sweating and increasing risk of stillbirth for placental insufficiency. We describe a case of developed erythematous plaques surrounded by pustules localised initially to the trunk of a 35-year-old woman at the 34th week of gestation after 5 days of treatment with N-Butyl-Scopolammonium, and which later involved the upper and lower limbs. Skin histology confirmed the diagnosis of generalised pregnancy pustular psoriasis (impetigo herpetiformis). IH is reported to be associated with hypocalcemia, hypoparathyroidism, use of oral contraceptives and bacterial infections. This is the first report suggesting the potential role of drugs other than oral contraceptives in the pathogenetic mechanism of this disease. In this case an adverse cutaneous reaction to BB could be the cause of the development of Koebner isomorphism.