Red grape (Vitis vinifera L.) flavonoids down-regulate collagen type III expression after UV-A in primary human dermal blood endothelial cells.

Red grape (Vitis vinifera L.) flavonoids including flavan-3-ols (eg, catechin and epicatechin), flavonols (eg, quercetin) and anthocyanins (eg, malvidin) exert anti-inflammatory and antioxidant activities. In the skin they also have a photoprotective action, and their effects have been extensively investigated in keratinocytes, melanocytes and fibroblasts. Despite their known effects also on blood vasculature, little is known on their activities on human dermal blood endothelial cells (HDBECs), which are critically involved in skin homeostasis as well as in the pathogenesis of neoplastic and inflammatory skin diseases. We sought to study the biological effects of selected red grape flavonoids in preventing the consequences of ultraviolet (UV)-A irradiation in vitro. Our results show that red grape flavonoids prevent UV-A-induced sICAM-1 release in HDBECs, suggesting that this cell type could represent an additional target of the anti-inflammatory activity of flavonoids. In addition, flavonoids effectively inhibited UV-A-induced synthesis of collagen type III at both RNA and protein level, indicating that dermal blood microvasculature could be actively involved in ECM remodelling as a consequence of skin photo-ageing, and that this can be prevented by red grape flavonoids.

Narrow-band UVB phototherapy and psoralen-ultraviolet A photochemotherapy in the treatment of cutaneous mastocytosis: a study in 20 patients.

BACKGROUND: In mastocytosis, the skin is almost invariably involved, and cutaneous symptoms deeply affect patients' quality of life. METHODS: A retrospective observational analysis of patients affected by cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM) treated with phototherapy/photochemotherapy (PUVA or NB-UVB) has been conducted. For each patient, total numbers of PUVA or NB-UVB exposures, the cumulative UV dose (J/cm2 ), serum tryptase profile, and pruritus, before and after treatment, according to the visual analogue scale (VAS) were considered. Skin lesions of each patient were assessed, before and after treatment, according to a cutaneous scale score. RESULTS: Twenty patients affected by CM and ISM were studied; in particular, 10 patients received NB-UVB therapy, and other 10 patients received PUVA. A statistically significant mean reduction of pruritus in both groups (P < 0.01) was observed. The number of treatments necessary to obtain symptom relief was significantly lower in the PUVA group, but the mean exposure dose was significantly higher, if compared to the NB-UVB group. Serum tryptase levels showed a downward trend. The cutaneous score improved in both groups. LIMITATIONS: This study was a retrospective study with a small sample size and without a control group. CONCLUSION: This work provides evidence that both NB-UVB and PUVA represent a safe and useful second-line therapy of the cutaneous symptoms in mastocytosis.

Pseudoepitheliomatous changes in a case of vegetating Darier­White disease: a unique histopathological finding.

Darier­White disease (DWD) is a rare autosomal dominant genodermatosis, characterized by constant and typical histopathological findings, such as hyperkeratosis, dyskeratosis with corps ronds and grains and papillary microvilli formation with suprabasal clefting. Despite its nearly constant histopathological presentation, unusual clinical variants are reported, such as the vegetating and cornifying ones. These variants share the same histopathological features of the classic type, except for the striking hyperkeratosis and acanthosis. Here, unreported pseudoepitheliomatous features are described in an elderly male patient with a long history of vegetating and verrucous papules and nodules of DWD, associated with typical nail involvement. These unique histolopathological changes were closely in conjunction with the characteristic microscopic features of DWD. Differential diagnosis with other pseudoepitheliomatous and acantholytic conditions such as reticulated seborrheic keratosis, inverted follicular keratosis, and acantholytic squamous cell carcinoma is also considered. Pseudoepitheliomatous features, in this case of vegetating DWD, could be regarded as a reactive epidermal phenomenon because of different stimuli, i.e. maceration, bacterial superinfection, and chronic scratching.

An unusual case of transient neonatal pustular melanosis: a diagnostic puzzle.

UNLABELLED: A newborn's skin may exhibit a variety of changes during the first weeks of life, and rashes are extremely common in the neonatal period, representing a significant source of parental concern. In particular, a variety of skin eruptions can present as pustules. Most of them are innocuous and self-limiting, while others can be the manifestation of an infectious disease or even indicative of serious underlying disorders. Transient neonatal pustular melanosis is an uncommon vesiculopustular rash characterized by small pustules on a non-erythematous base, noted at birth or during the first day of life, without systemic symptoms. The lesions rupture spontaneously, leaving hyperpigmented macules that usually fade within few weeks. Clinical recognition of this disease can help physicians avoid unnecessary diagnostic testing and treatment for infectious etiologies because no specific therapy is recommended. The clinical aspect and time of onset are generally sufficient to make the correct diagnosis. Nevertheless, peculiar clinical presentations may require additional work-up to rule out life-threatening conditions, and dermatological consultation and histological examination are required for the final diagnosis. CONCLUSION: We report an exceedingly unusual presentation of transient neonatal pustular melanosis, suggesting the importance of a systematic diagnostic approach to allow a confident recognition of this benign condition.

Is there a role for the detection of autoantibodies in the clinical practice of treating infants with bullous pemphigoid? A case report.

We present a case of infantile bullous pemphigoid (BP) triggered by primary infection with varicella zoster virus and we analyze the correlation between autoantibody levels and disease activity. With this report we suggest that serum autoantibody titers may not necessarily mirror the clinical course of the disease or represent a helpful tool in guiding therapeutic decisions in infantile BP.

A retrospective analysis of dermatological lesions in kidney transplant patients.

BACKGROUND & OBJECTIVES: Kidney transplantation is the best option for patients with end-stage renal disease (ESRD) failure. Prolonged use of immunosuppressive drugs often causes opportunistic infections and malignancies of skin and mucosae, but due to lack of a careful dermatological screening in several transplantation centers the diagnosis and the treatment of dermatological lesions in kidney transplant patients are underestimated. In addition after the introduction of interleukin (IL)-2 -receptor antagonists (basiliximab/daclizumab), mTOR inhibitors and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) in new immunosuppressive protocols only a few studies have analyzed the skin and mucosal lesions in kidney transplant patients. This study was undertaken to evaluate the cutaneous and mucosal diseases after kidney transplantation, and to investigate the association between these and different immunosuppressive protocols and/or demographic features. METHODS: A retrospective analysis was done using medical records of kidney transplantation between 2000 and 2009 at the Transplant Unit of Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. The study included 183 patients (M 57.3%, F 42.7%) aged 51.5 ± 11.8 yr) with transplant age 52.3 ± 34.9 months. Induction therapy was basiliximab and steroids based; maintenance therapy included combination-regimes from cyclosporine, tacrolimus, steroids, mycophenolate mofetil (MM), mycophenolic acid (MPA), rapamycin, everolimus. Anti-rejection therapy was steroid and/or thymoglobulines based. Diagnosis of cutaneous disease was made through examination of skin, mucous membranes, nails and hair evaluation. Skin biopsies, specific cultures and serological tests were done when required. RESULTS: Skin and mucosal diseases were reported in 173 (95.7%) of patients; 88 (50.81%) showed viral lesions; 92 (53.01%) immunosuppression-related lesions; 28 (16.39%) benign tumours; 26 (15.3%) precancers /neoplastic lesions; 24 (14.21%) mycosis; 16 (9.29%) cutaneous xerosis, 15 (8.74%) dermatitis, while absence of cutaneous disease was evident only in 8 (4.37%) cases. An association between drug side effects and anti-rejection treatment ( P ≤ 0.01) and/or calcineurin-inhibitors (CNI) exposure ( P ≤ 0.01) was found. Longer exposure to immunosuppressive drugs (>60 months) was associated with pre-malignancy and malignancy lesions. INTERPRETATION & CONCLUSIONS: Cutaneous diseases are frequent in kidney transplanted patients. Continuous skin monitoring is necessary to make an early diagnosis and to start appropriate treatment.

Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate.

BACKGROUND: Imatinib mesylate (IM) is a phenylaminopyrimidine that represents the first-line treatment for chronic myeloid leukemia (CML), Philadelphia chromosome-positive. It acts as a potent and selective inhibitor of the bcr-abl fusion protein by a competitive inhibition at the adenosine triphosphate-binding site of the enzyme, which leads to the inhibition of tyrosine phosphorylation of the proteins involved in bcr-abl signal transduction. IM is generally well tolerated and usually provokes only mild side effects consisting of nausea, myalgia, edema and muscle cramps. OBSERVATION: This is a report of a patient affected by CML, who developed a photoinduced dermatitis and an oral lichenoid reaction associated with IM treatment. The lesions were resolved, thanks to the withdrawal of the therapy, and they relapsed after the reintroduction of IM, confirming the drug-induced pathogenesis. CONCLUSION: Skin changes are the most common non-hematologic side effects to IM treatment and are usually dose dependent. In particular, patients with IM therapy reported a lightening and depigmentation of the skin, that may alter the skin protection against ultraviolet exposure, with a possible subsequent intolerance to sun exposure, as reported in our patient, and higher risk of skin cancer. They are frequently self-limited or easily managed; nevertheless, in some cases, the therapy needs to be discontinued or may only be continued with concomitant oral steroid.

Sporotrichoid metastases to the skin from cutaneous squamous cell carcinoma in an immunocompetent patient.

Squamous cell carcinoma (SCC) of the skin may metastasize in more than 5% of cases. Metastases usually involve the primary regional lymph nodes in 85% of cases. The skin is rarely involved by metastases of SCC of the skin. The presence of multiple cutaneous metastases in a figurate array is a very rare occurrence, mostly reported in SCC occurring in immunocompromized patients. The case of a 70-year-old immunocompetent patient, with an ulcerated primary SCC on his right palm and 3 nodules in a linear array on his right arm is described. He also presented with homolateral axillary lymphadenopathy. Histopathologic examination from the 3 nodules revealed SCC of variable grading, with focal fusion of the metastases with the overlying epidermis. The patient had been previously treated with chemotherapy and radiotherapy in another Department, with no benefit. Despite right arm amputation and homolateral axillary lymphadenectomy, the patient died 4 months after a procedure, for pulmonary embolism.

Erythema ab igne induced by laptop computer: an emerging disease among adolescents?

Erythema ab igne (EAI) was a very common disease in the past, when it occurred mainly among people who worked with fire, or in people who had used heat sources in contact with the skin for warming purposes for long time. In the last decades, with the introduction of central heating in the buildings, EAI incidence was remarkably decreased in Western Countries, and it was found almost exclusively among elderly, and in people affected by defects in thermoregulation or alteration of periphery circulation. Recently, a new slight increase of EAI prevalence has been observed, although with some new features. Here, we describe three cases of adolescents who presented with brownish, reticulated patch on the anterior surface of their thighs. An accurate medical questioning revealed that the patients used to place the lower surface of laptop computer on the extensor side of their thighs in a cross-legged position for many hours (about 6-8 hours) every days. In particular, the patients supported the laptop computer always on the same leg. Laptop computer-induced EAI was diagnosed. Only a few cases of laptop computer-induced EAI have been reported in the literature. Although EAI is poorly symptomatic and it generally evolve to complete remission after an early discontinuance of heat source exposure, chronic lesions of EAI have been regarded as precancerous lesions. Therefore, it is important to implement diagnosis and prevention measures of this disease. Dermatologists should consider new causal agents for old diseases.

Multidisciplinary focus on methotrexate in psoriatic disesase.

The aim of this focus is to establish the role of methotrexate (MTX) in the treatment of psoriatic disease (PD). Despite the lack of hard evidence, MTX can be regarded as the nonbiological drug of choice for the treatment of peripheral psoriatic arthritis, although its effect on psoriatic dactylitis, enthesitis, and spondylitis needs to be further studied by means of well conducted clinical trials. MTX is effective in improving the skin involvement of PD, and can be used in moderate to severe psoriasis before starting a biological agent. Although rheumatologists consider it relatively safe in PD, dermatologists are very concerned about its toxicity and so, until more definite data are available, precautions should be taken to prevent MTX-induced liver fibrosis and cirrhosis.

Zosteriform connective tissue nevus in a pediatric patient.

We report an 8-year-old girl affected by hypochromic, asymptomatic, acquired lesions with a paving-stone aspect on the right lumbosacral area and proximal right leg. The results of serum and urine biochemical screening were normal, as was the bone survey A biopsy was performed. The clinical and histologic aspects led to the diagnosis of connective tissue nevus with zosteriform distribution.

Linear Darier's disease successfully treated with 0.1% tazarotene gel "short-contact" therapy.

We report the case of a 25 year old man affected by linear Darier's disease. The patient presented with brownish keratotic papules involving the trunk in a linear pattern. These lesions were successfully treated within 6 weeks with 0.1% tazarotene gel "short contact". The good response that was obtained suggests that the use of "short contact" tazarotene could be useful in the treatment of linear Darier's disease.

Efficacy of propranolol for cutaneous hemangiomas in premature children.

BACKGROUND: The purpose of the present study is to evaluate the efficacy and safety of propranolol for problematic infantile hemangiomas (IH), showing our experience on 24 children, with special focus on premature infants. METHODS: A retrospective observational study considered 24 patients who were given oral propranolol for the treatment of "problematic" IH. A multidisciplinary team, composed of a dermatologist, a pediatrician, a pediatric cardiologist, and a neonatologist, took part in the indication for propranolol and follow-up on all the patients. Propranolol was administered orally at the starting dose of 0.5-1 mg/kg/die and was gradually increased to the target dose of 2 mg/kg/die. A clinical gravity score, based on color, major diameter, thickness and texture was calculated for each IH, giving a numeric score before (t0) and after (tf) propranolol therapy. Improvement rate was evaluated in terms of score percentage difference between t0 and tf. RESULTS: All of the IH except one (96%), showed a variable grade of improvement, with a median score improvement of 69.1%. Median initial score in premature and term infants did not show any significant difference (P=0.38). Otherwise the two subgroups showed a significant difference in final scores: medium percentage improvement in premature and term infants, was respectively 80.9% and 49.6% (P<0.01). No significant side effects were reported during the treatment period. CONCLUSIONS: As pointed out in our study, IH in premature children showed a significantly better response to propranolol treatment.

Sun exposure and melanoma prognostic factors.

Previous studies have reported an association between sun exposure and the increased survival of patients with cutaneous melanoma (CM). The present study analyzed the association between ultraviolet (UV) light exposure and various prognostic factors in the Italian Clinical National Melanoma Registry. Clinical and sociodemographic features were collected, as well as information concerning sunbed exposure and holidays with sun exposure. Analyses were performed to investigate the association between exposure to UV and melanoma prognostic factors. Between December 2010 and December 2013, information was obtained on 2,738 melanoma patients from 38 geographically representative Italian sites. A total of 49% of the patients were >55 years old, 51% were men, 50% lived in the north of Italy and 57% possessed a high level of education (at least high school). A total of 8 patients had a family history of melanoma and 56% had a fair phenotype (Fitzpatrick skin type I or II). Of the total patients, 29% had been diagnosed with melanoma by a dermatologist; 29% of patients presented with a very thick melanoma (Breslow thickness, >2 mm) and 25% with an ulcerated melanoma. In total, 1% of patients had distant metastases and 13% exhibited lymph node involvement. Holidays with sun exposure 5 years prior to CM diagnosis were significantly associated with positive prognostic factors, including lower Breslow thickness (P<0.001) and absence of ulceration (P=0.009), following multiple adjustments for factors such as sociodemographic status, speciality of doctor performing the diagnosis and season of diagnosis. Sunbed exposure and sun exposure during peak hours of sunlight were not significantly associated with Breslow thickness and ulceration. Holidays with sun exposure were associated with favorable CM prognostic factors, whereas no association was identified between sunbed use and sun exposure during peak hours of sunlight with favorable CM prognostic factors. However, the results of the present study do not prove a direct causal effect of sun exposure on melanoma prognosis, as additional confounding factors, including vitamin D serum levels, may have a role.

Pityriasis rosea-like eruption during treatment with imatinib mesylate: description of 3 cases.

Imatinib mesylate (IM) represents the first-line treatment for chronic myeloid leukemia (CML). We hereby relate 3 cases of an IM-induced pityriasis rosea (PR)-like cutaneous eruption. Patients developed an erythematous, slightly pruritic, macular skin eruption, with many lesions having a peripheral collarette of desquamation, confined to the trunk, limbs, and arms with a vaguely dermatomal diffusion. The histologic findings suggested a reactive process to the drug. Full dermatological recovery was obtained after IM discontinuation, but lesions reappeared upon restoring therapy, suggesting the drug-related nature of the rash. To our knowledge this is the first reported PR-like cutaneous eruption to IM.