Treatment of psoriasis with topical agents: Recommendations from a Tuscany Consensus.

Psoriasis is a chronic and relapsing inflammatory skin disease, clinically characterized by erythematous and scaly plaques. Treatment approach is mainly driven by disease severity, though several factors should be considered in order to identify the optimal therapeutic choice. Mild psoriasis may be treated with a wide array of topical agents including corticosteroids, vitamin D analogs, keratolytics, and calcipotriol/betamethasone propionate compound. Because guidelines may not provide practical indications regarding the therapeutic approach, the use of topical agents in psoriasis is more individually tailored. In order to homogenize the standard of care, at least in a local setting, we collected the real-life-based recommendations for the use of topical therapies from an expert panel, the Tuscany Consensus Group on Psoriasis, representing all leading centers for psoriasis established in Tuscany. With this document, this consensus group sought to define principles guiding the selection of therapeutic agents with straightforward recommendations derived from a real-life setting.

Middermal Elastolysis: Dermal Fibroblasts Cooperate with Inflammatory Cells to the Elastolytic Disorder.

Little is known about the cause and pathophysiology of middermal elastolysis (MDE). In this condition, variable inflammatory infiltrate may be present or not together with loss of elastic fibres in the middermis that spares both papillary and lower reticular dermis. MDE may be a consequence of abnormal extracellular matrix degradation related to an imbalance between elastolytic enzymes released from inflammatory and resident cells and their naturally occurring inhibitors. However, the cause of this imbalance is still an object of investigation. In order to shed light on the role of fibroblasts in MDE, we used fibroblast cultures from MDE and control subjects to evaluate matrix metalloproteinases (MMPs) and their major inhibitor TIMP-1, which in combination with neutrophil or macrophage proteases released in inflamed areas may influence the elastolytic burden. We demonstrate that fibroblasts derived from MDE produce in vitro low levels of TIMP-1, the major inhibitor of MMPs. Elevated levels of MMP-2, MMP-14, and TIMP-2 capable to activate in a cooperative manner pro-MMP-2 are present in MDE tissue samples. Additionally, significant reaction for MMP-1 is present in the same MDE areas. These data all together suggest that ECM changes in MDE are due to cooperation of different cell populations (i.e., inflammatory cells and fibroblasts).

Superficial Acral Fibromyxoma of the Toe: Unusual Location of the Mixoid Variant.

Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor that frequently involves the periungual and subungual regions of acral surfaces. Macroscopically, it appears as a flesh-colored dome-shaped solitary mass; microscopically, it consists of a moderately cellular proliferation of spindle-shaped fibroblast-like cells embedded in a myxocollagenous stroma and arranged in a loose storiform and focally fascicular pattern. The tumor cells are immunoreactive for CD34, epithelial membrane antigen, CD99, and CD10. In this study, we describe a case of SAFM on the fourth toe with predominantly myxoid stroma. Our case, in contrast of those reported in the literature, showed an unusual location for the myxoid variant. SAFM is often not recognized; it may resemble some benign and malignant mesenchymal neoplasm. The gold standard treatment is surgery. The tumor was completely excised, and no recurrence was evident at 1-year follow-up. Awareness of this entity facilitates its diagnosis and management, avoiding unwarranted concerns and additional procedures for the patient.

Crosstalk between platelets and PBMC: New evidence in wound healing.

Platelet-derived products have proven useful in accelerating healing processes and tissue regeneration. However, despite their widespread use in clinical practice, the cellular and molecular mechanisms involved have not yet been completely clarified. Recent studies show that interaction between platelet gel (PG) and peripheral blood mononuclear cells (PBMC) can result in activation of PBMC and production of several cytokines involved in wound healing and tissue repair. The aim of our study was to analyze whether crosstalk between platelets and PBMC can influence wound healing by modulating release of VEGF, bFGF and IL-10 by PBMC. Cultures of PBMC alone and co-cultures with autologous PG of 24 healthy volunteers were incubated under normoxia for 24 h. VEGF, bFGF and IL-10 concentration and expression were then analyzed in supernatants by ELISA and by real-time RT-PCR. We observed a down-regulation of VEGF and bFGF release and an up-regulation of IL-10 release in co-cultures of PBMC and PG. Platelets are not only important in the early stages of the healing process (clot formation, direct release of growth factors), but also can influence the whole process of tissue regeneration by modulating synthesis and release of VEGF, bFGF and IL-10 by PBMC. These effects could give platelets a new key role in the control of healing processes and provide insights into the clinical success of platelet-derived products in many medical fields.

Influence of Ambient Stressors and Time Constraints on Diagnostic Accuracy of Borderline Pigmented Skin Lesions.

BACKGROUND: Health professionals are required to make complex decisions in dynamic contexts involving many variables and factors. Decisions are more difficult in the presence of uncertainty, urgency and high risk. OBJECTIVE: To evaluate the effect of ambient stressors and time constraints on decision making by expert dermatologists faced with borderline pigmented skin lesions (PSL) (early melanoma vs. atypical nevi). METHODS: We performed a retrospective chart review of PSL from the image databases of our department. A total of 321 PSL (219 nevi and 102 melanomas) were randomly assigned to three groups: control group, ambient stress group and time stress group. The diagnostic accuracy of each group was evaluated as sensitivity and specificity. RESULTS: Mean sensitivity and specificity of diagnosis were 69.2 and 90.5% in the control group, 62 and 81.2% in the ambient stress group and 59.6 and 82.5% in the time stress group, respectively. CONCLUSION: Time constraints and stressors negatively influenced the performance of dermatologists in the diagnosis of atypical PSL.

Concordance and time estimation of store-and-forward mobile teledermatology compared to classical face-to-face consultation.

Smartphones have overcome the limitations of image quality seen in older devices and opened a new field of telemedicine called "mobile teledermatology". Technological advances and the need to reduce health service costs will strongly promote the development of telemedicine. For this reason, we evaluated the concordance between store-and-forward mobile teledermatology and the classical face-to-face dermatological visit. We also measured the time taken to submit a teleconsultation using a smartphone. Before conventional face-to-face visit, a final-year resident of the three-year course for general practitioners collected medical history, took digital images of skin diseases with a smartphone and, measuring the time required to complete this operation, transmitted them to an expert teledermatologist. In 391 patients we obtained a concordance between face-to-face and store-and-forward diagnosis of 91.05% (Cohen κ coefficient = 0.906). On average only few minutes needs to be added to a normal visit to transmit the cases to an expert teledermatologist.

Subcutaneous fat necrosis in a newborn after brief therapeutic hypothermia: ultrasonographic examination.

A 7-day-old infant developed erythematous indurated plaques on the back, left shoulder, and arm a few days after therapeutic hypothermia. Ultrasonographic study along with Doppler blood flow analysis of lesional skin areas revealed flogistic fat involvement and calcifications. On the basis of clinical appearance, patient history, and ultrasonographic study, a diagnosis of subcutaneous fat necrosis of the newborn was established.

Rituximab plus liposomal pegylated doxorubicin in the treatment of primary cutaneous B-cell lymphomas.

BACKGROUND: In primary cutaneous B-cell lymphomas (PCBCL), radiotherapy - or surgery in a minority of cases - is the first-line treatment in follicle center lymphoma (PCFCL) and marginal zone B-cell lymphoma (PCMZL). Conversely, patients with multifocal skin involvement or relapsed/refractory disease deserve a systemic chemotherapy. In diffuse large B-cell lymphoma, leg type (PCLBCL-LT), due its poorer outcome, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimens are the most commonly used frontline, although hard to propose in elderly patients. In this regard, the association of rituximab (R) and pegylated liposomal doxorubicin (PLD) can be considered a promising, alternative approach. AIMS: Based on the favorable results reported with R and PLD in several recent trials, we decided to test efficacy and safety of this combination. METHODS: Twelve patients with PCBCL were treated with R plus PLD, and 7 had relapsed disease. Treatment plan consisted of 2 monthly cycles of R 375 mg/m(2) and PLD 20 mg/m(2) day 1;15, followed (in responders) by two cycles given only at day 1. All patients received prophylactic pyridoxine to prevent palmar-plantar erythrodysesthesia (PPE). RESULTS: Ten of 12 patients had a response (eight complete; two partial), remarkably 2/3 with PCLBCL-LT. Two patients did not respond (one progressive disease, PD, and one stable disease). Three patients died after a median follow-up of 56 months, two patients due to PD, and 1 due to a second neoplasm. Two out of 10 responders relapsed after 31 and 32 months, respectively. Hematological toxicity was negligible (one case of grade 2 neutropenia), as well as extra-hematological toxicity (two cases of grade 2 PPE). CONCLUSIONS: These preliminary data suggest that R-PLD is effective and well tolerated in all subsets of PCBCL and may be offered frontline in indolent cases unsuitable for radiotherapy or surgery as well as in more aggressive cases with contraindications to CHOP-like regimens.

Thirty-six cases of epidemic infections due to Trichophyton violaceum in Siena, Italy.

Trichophyton violaceum is an anthropophilous dermatophyte endemic to parts of Africa and Asia, sporadic in Europe. It is an emerging pathogen in Italy due to immigration. We report 36 cases of infections due to T. violaceum, diagnosed in the last 5 years by mycological examination. The source of contagion was 13 children adopted from orphanages.

Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene.

Next-generation sequencing is a straightforward tool for the identification of disease genes in extended genomic regions. Autozygosity mapping was performed on a five-generation inbred Italian family with three siblings affected with Clericuzio-type poikiloderma with neutropenia (PN [MIM %604173]), a rare autosomal-recessive genodermatosis characterised by poikiloderma, pachyonychia, and chronic neutropenia. The siblings were initially diagnosed as affected with Rothmund-Thomson syndrome (RTS [MIM #268400]), with which PN shows phenotypic overlap. Linkage analysis on all living subjects of the family identified a large 16q region inherited identically by descent (IBD) in all affected family members. Deep sequencing of this 3.4 Mb region previously enriched with array capture revealed a homozygous c.504-2 A>C mismatch in all affected siblings. The mutation destroys the invariant AG acceptor site of intron 4 of the evolutionarily conserved C16orf57 gene. Two distinct deleterious mutations (c.502A>G and c.666_676+1del12) identified in an unrelated PN patient confirmed that the C16orf57 gene is responsible for PN. The function of the predicted C16orf57 gene is unknown, but its product has been shown to be interconnected to RECQL4 protein via SMAD4 proteins. The unravelled clinical and genetic identity of PN allows patients to undergo genetic testing and follow-up.

Keratotic horn on left fifth fingertip: congenital ectopic nail misdiagnosed as a common wart.

The term "ectopic nail" refers to nail tissue found in a location other than in the normal nail bed. Here we report a 9-year-old girl with an asymptomatic keratotic "horn" on the tip of her left fifth finger. Present since the age of 1 month, it was misdiagnosed as a common wart and treated using liquid nitrogen cryotherapy without benefit.

Importance of good manufacturing practices in microbiological monitoring in processing human tissues for transplant.

Skin allografts represent an important therapeutic resource in the treatment of severe skin loss. The risk associated with application of processed tissues in humans is very low, however, human material always carries the risk of disease transmission. To minimise the risk of contamination of grafts, processing is carried out in clean rooms where air quality is monitored. Procedures and quality control tests are performed to standardise the production process and to guarantee the final product for human use. Since we only validate and distribute aseptic tissues, we conducted a study to determine what type of quality controls for skin processing are the most suitable for detecting processing errors and intercurrent contamination, and for faithfully mapping the process without unduly increasing production costs. Two different methods for quality control were statistically compared using the Fisher exact test. On the basis of the current study we selected our quality control procedure based on pre- and post-processing tissue controls, operator and environmental controls. Evaluation of the predictability of our control methods showed that tissue control was the most reliable method of revealing microbial contamination of grafts. We obtained 100 % sensitivity by doubling tissue controls, while maintaining high specificity (77 %).

Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian Group of Cutaneous Lymphomas.

BACKGROUND: Mycosis fungoides (MF) is an indolent primary cutaneous T-cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. METHODS: This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor-lymph node-metastasis-blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor-stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. RESULTS: The median follow-up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor-stage (1%-2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T-score was found to be associated with extracutaneous involvement site, tumor-stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . CONCLUSIONS: The data from the current study support the need for a stage-tailored follow-up, suggest that the classification of tumor-stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification.

Photolocalized purpura during levofloxacin therapy.

Side-effects associated with levofloxacin treatment include phototoxicity, hypersensitivity and skin disorders. Purpuric eruptions have rarely been reported. We describe the case of a 75-year-old woman who was prescribed a 15-day course of levofloxacin (500 mg twice a day) for hemorrhagic cystitis. On exposure to sunlight, the patient developed a pruritic purpuric eruption on the lower extremities. The acute reaction differed from a classical sunburn, manifesting as confluent petechiae limited to sun-exposed areas and accompanied by pruritus. This was a rare case of solar capillaritis. Purpuric eruptions on photoexposed skin should be considered another unusual side effect of levofloxacin.

A single centre melanoma thickness trend (1985-2009) in relation to skin areas accessible and non-accessible to self-inspection.

BACKGROUND/OBJECTIVES: Melanoma has become a major public health problem worldwide and its incidence in individuals of Caucasian origin continues to rise. The objective was to determine historical changes in thickness, melanoma proportions and anatomical site of presentation over a 25-year period in our Department. METHODS: This was a historical retrospective study (January 1985 to December 2009). Only patients born and living in Italy were considered. The following parameters were evaluated: age, gender, year of diagnosis, site of primitive lesion (head, back, chest, anterior and posterior upper limbs, anterior and posterior lower limb, and acral sites) and Breslow thickness of the lesion. RESULTS: In the 25-year period, 993 cases of melanoma were diagnosed. The total number of cases per year tripled between 1985-1989 and 1995-1999 and more than doubled between 1995-1999 and 2005-2009. Our results also revealed that thicker melanomas were more frequent in elderly patients and on parts of the body that cannot be readily self-inspected. CONCLUSION: The importance of observation of the posterior parts of the body is stressed, since not only did most melanomas arise in these sites but the diagnosis of lesions in these sites is often delayed.

Retraction: SNHG5 promotes proliferation and induces apoptosis in melanoma by sponging miR-155.

[This retracts the article DOI: 10.1039/C7RA12520H.].