Minocycline for acne vulgaris: efficacy and safety.

BACKGROUND: Minocycline is an oral antibiotic used for acne vulgaris. Its use has lessened due to safety concerns (including potentially irreversible pigmentation), a relatively high cost, and no evidence of any greater benefit than other acne treatments. A modified-release version of minocycline is being promoted as having fewer side-effects. OBJECTIVES: To assess new evidence on the effects of minocycline for acne vulgaris. SEARCH METHODS: Searches were updated in the following databases to November 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched trials registers and checked reference lists for further references to relevant randomised controlled trials (RCTs).The Cochrane Skin Group's Trials Search Co-ordinator undertook searches exploring minocycline's adverse effects in EMBASE and MEDLINE in February 2012. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) comparing minocycline, at any dose, to an active or a placebo control, in participants with inflammatory acne vulgaris. For adverse effects, we selected additional studies that reported the number of adverse effects and the number of participants treated. DATA COLLECTION AND ANALYSIS: Outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and participants' global assessments, adverse effects, and dropout rates. Two authors independently assessed the quality of each study. Effect sizes were calculated, and meta-analyses were undertaken where possible.Sixteen studies met the inclusion criteria for the review of adverse effects. MAIN RESULTS: We included 12 new RCTs for this update, giving a total of 39 RCTs (6013 participants). These additional 12 RCTs have not changed the original conclusions about the clinical efficacy of minocycline.The identified RCTs were generally small and poor quality. Meta-analysis was rarely possible because of the lack of data and different outcome measures and trial durations. Although minocycline was shown to be an effective treatment for moderate to moderately-severe acne vulgaris, there was no evidence that it is better than any of the other commonly-used acne treatments. One company-sponsored RCT found minocycline to be less effective than combination treatment with topical erythromycin and zinc. No trials have been conducted using minocycline in those participants whose acne is resistant to other therapies. Also, there is no evidence to guide what dose should be used.The adverse effects studies must be interpreted with caution. The evidence suggests that minocycline is associated with more severe adverse effects than doxycycline. Minocycline, but not other tetracyclines, is associated with lupus erythematosus, but the risk is small: 8.8 cases per 100,000 person-years. The risk of autoimmune reactions increases with duration of use. The evidence does not support the conclusion that the more expensive extended-release preparation is safer than standard minocycline preparations. AUTHORS' CONCLUSIONS: Minocycline is an effective treatment for moderate to moderately-severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly-used therapies. This review found no reliable evidence to justify the reinstatement of its first-line use, even though the price-differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines.

Epithelial-Mesenchymal Transition in Skin Cancers: A Review.

Epithelial-mesenchymal transition (EMT) is involved in physiologic processes such as embryogenesis and wound healing. A similar mechanism occurs in some tumors where cells leave the epithelial layer and gain mesenchymal particularities in order to easily migrate to other tissues. This process can explain the invasiveness and aggressiveness of these tumors which metastasize, by losing the epithelial phenotype (loss of E-cadherin, desmoplakin, and laminin-1) and acquiring mesenchymal markers (N-cadherin). Complex changes and interactions happen between the tumor cells and the microenvironment involving different pathways, transcription factors, altered expression of adhesion molecules, reorganization of cytoskeletal proteins, production of ECM-degrading enzymes, and changes in specific microRNAs. The purpose of this review is to determine particularities of the EMT process in the most common malignant cutaneous tumors (squamous cell carcinoma, basal cell carcinoma, and melanoma) which still have an increasingly high incidence. More studies are required on this topic in order to establish clear correlations. High costs related to skin cancer therapies in general as well as high impact on patients' quality of life demand finding new, reliable prognostic and therapeutic markers with significant public health impact.

Matrix metalloproteinases expression in lentigo maligna∕lentigo maligna melanoma - a review of the literature and personal experience.

Cutaneous melanoma is the most aggressive type of skin cancer, with high invasive potential. Lentigo maligna melanoma (LMM) is a relatively rare type, accounting for about 10% of all melanomas, while the most common subtype of melanoma on the face, typically on chronically sun-exposed skin of elderly people. Its in situ stage is lentigo maligna (LM). During the process of transformation from LM to LMM, tumor cells secrete or induce the release from neighboring cells of large amounts of matrix metalloproteinases (MMPs) that degrade the extracellular matrix. Some MMPs, as MMP3 and MMP9 expressed melanoma cells is associated with statistical significance in both in vitro and in vivo studies, with an invasive phenotype. Unfortunately, there is scarce data published about MMPs expression in LM∕LMM, as majority of research on melanoma refer to superficial spreading and nodular melanoma. Our personal, unpublished yet fully data is an attempt to complete a specific panel of immunohistochemical markers that could explain the slow growing rate of LMM.

Efficacy of methotrexate as anti-inflammatory and anti-proliferative drug in dermatology: Three case reports.

Methotrexate (MTX) is a folic acid analog with anti-proliferative (anti-neoplastic, cytotoxic), immunosuppressive and anti-inflammatory properties, which has been used in the treatment of various cutaneous disorders, such as psoriasis, keratoacanthoma, pityriasis rubra pilaris, atopic dermatitis, mycosis fungoides, bullous skin diseases, systemic sclerosis, morphea, lupus erythematosus, dermatomyositis and crusted scabies. Inhibition of cell proliferation is explained through its role in blocking DNA/RNA synthesis, by inhibiting dihydrofolate reductase, necessary for the production of pyrimidine and purine nucleotides. An anticancer effect can be related to α-oxoaldehyde metabolism (MTX increases methylglyoxal levels). Its anti-inflammatory property is based on the inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase, thus increasing intracellular and extracellular adenosine, a purine nucleoside with anti-inflammatory effect. This drug can limit inflammation by scavenging free radicals and decreasing malondialdehyde-acetaldehyde protein-adduct production. Moreover, the anti-proliferative and anti-inflammatory effects can also be related to inhibition of the DNA methylation pathway, thus inhibiting methionine formation. The aim of the present study was to report various dermatological cases from our daily practice that demonstrate the efficacy of MTX in the treatment of cutaneous diseases, highlighting different mechanisms of action: its anti-inflammatory effect in psoriasis and its anti-proliferative, and anti-neoplastic effect in well-differentiated squamous cell carcinoma or in keratoacanthoma. Moreover, different administration pathways and doses are addressed. Assessment of the treatment plan, clinical improvement of cutaneous lesions, biologic evaluation, final aesthetic result, quality of life, as well as potential adverse effects and drug tolerance related to each case mentioned.

Morphological features of melanocytic tumors with depigmented halo: review of the literature and personal results.

Halo (Sutton's) phenomenon has been described as a depigmented halo that is associated most commonly with acquired melanocytic nevi; but it may be associated with various types of melanocytic skin tumors, melanoma being the most concerning. Different authors have been preoccupied with elucidating morphological features of melanocytic tumors associated with a depigmented halo. We reviewed the literature and discussed the main features of melanocytic halo tumors regarding histopathological, immune microenvironment profile and dermatoscopic appearance. We highlighted similarities and differences between Sutton's nevus and halo melanoma, also presenting relevant aspects of our results. Depigmented halo must be regarded as a phenomenon that may be associated with different types of melanocytic tumors and with a broad spectrum of histopathological atypia degree. Certain correlations between the shape, diameter, symmetry observed in clinical examination, histopathological appearance, dermatoscopic aspect of peritumoral halo and central tumor type could not be established due to insufficient data and contrasting results. Further studies are expected to add valuable information regarding the depigmented halo tumors features.