Pedro Jaén

Frontal fibrosing alopecia: A multicenter review of 355 patients

BACKGROUND To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. OBJECTIVE We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. METHODS This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. RESULTS In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). LIMITATIONS The retrospective design is a limitation. CONCLUSIONS Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment.

Topical 5-aminolevulinic acid photodynamic therapy for the treatment of unilesional mycosis fungoides: a report of two cases and review of the literature

Background  Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T‐cell lymphoma (CTCL), characterized clinically by a solitary lesion and by histopathological features indistinguishable from multilesional MF. The photodynamic therapy (PDT) is a new and effective treatment of precancerous lesions and non‐melanoma skin cancers. In recent years it has been used successfully for the treatment of MF.

Pulsed dye laser vs. photodynamic therapy in the treatment of refractory nail psoriasis: a comparative pilot study

Background  Nail psoriasis is often refractory to traditional treatments, and patients with nail psoriasis usually demand a therapeutic option. Both photodynamic therapy (PDT) and pulse dye laser (PDL) have proved effective for plaque‐type psoriasis, but they have not been evaluated in nail psoriasis. On the other hand, delta‐aminolaevulinic acic has been shown to penetrate into the nail matrix and nail bed occluded with bioadhesive patches.

Protoporphyrin IX-dependent photodynamic production of endogenous ROS stimulates cell proliferation.

Photodynamic therapy using methyl 5-aminolevulinate (MAL) as a precursor of the photosensitizing agent protoporphyrin IX is widely used in clinical practice for the treatment of different pathologies, including cancer. In this therapeutic modality, MAL treatment promotes the forced accumulation of the endogenous photoactive compound protoporphyrin IX in target malignant cells. Subsequent irradiation of treated tissues with an appropriate visible light source induces the production of reactive oxygen species (ROS) that, once accumulated above a critical level, promote cell death. Here we demonstrate that a photodynamic treatment with low MAL concentrations can be used to promote a moderate production of endogenous ROS, which efficiently stimulates cell growth in human immortalized keratinocytes (HaCaT). We also show that this proliferative response requires Src kinase activity and is associated to a transient induction of cyclin D1 expression. Taken together, these results demonstrate for the first time that a combination of light and a photoactive compound can be used to modulate cell cycle progression through Src kinase activation and that a moderate intracellular increase of photogenerated ROS efficiently stimulates cell proliferation.

Disorganisation of cytoskeleton in cells resistant to photodynamic treatment with decreased metastatic phenotype

The appearance of cells resistant to photodynamic therapy (PDT) is crucial for the outcome of this antitumoral treatment. We had previously isolated two sublines resistant to PDT derived from the mammary adenocarcinoma LM3 [A. Casas, C. Perotti, B. Ortel, G. Di Venosa, M. Saccoliti, A. Batlle, T. Hasan, Induction of murine tumour cell lines resistant to ALA-mediated Photodynamic Therapy, Int. J. Oncol. 29 (2006) 397-405.]. These clones have severely impaired its metastatic potential in vivo together with decreased general anchorage-dependent adhesion and invasion. In the present work we analyzed the differential expression and distribution of cytoskeleton and adhesion proteins in these cell lines. In both resistant clones, loss of actin stress fibers and disorganization of the actin cortical rim was observed. E-cadherin and beta-catenin and vinculin distribution was also disorganized. However, Western blot assays did not show differential expression of actin, E-cadherin, vinculin or beta-catenin. It was demonstrated that PDT strongly affects cell-cell and cell-substrate adhesion through the reorganization of some cytoskeletal and adhesion proteins. Changes in the metastasis phenotypes previously found are likely to be ascribed to these differences.

Terapia fotodinámica: nuevas indicaciones

Photodynamic therapy (PDT) is approved for the treatment of actinic keratoses, superficial and nodular basal cell carcinomas, and recently, Bowens disease. In the last decade the advances experienced in the study of the photodynamic reaction have expanded the spectrum of application to other cutaneous diseases, neoplastic as well as inflammatory and infectious ones. The experience in psoriasis, acne, common warts and cutaneous T cell lymphoma starts to be broad and interesting, which permits to define its use in these entities. Photodynamic therapy is also been tested for a great variety of dermatoses with different photosensitizers and light sources with variable results. In this paper we review the treatment of Bowens disease and other indications different from non melanoma skin cancer with PDT, providing our experience.

Oncogenic H-Ras and PI3K signaling can inhibit E-cadherin-dependent apoptosis and promote cell survival after photodynamic therapy in mouse keratinocytes

Maintenance of E‐cadherin mediated cell–cell contacts is often required for the survival of epithelial cells and tissues. Here we report that oncogenic activation of H‐Ras in murine keratinocytes can prevent cell death induced by immunological disruption of E‐cadherin adhesion. A similar situation was observed in cells showing constitutive activation of the p110α catalytic subunit of class IA PI3K. This protective effect is associated with β‐catenin‐dependent transcription and with activation of survival factor Akt/PKB. In addition, we induced cell death by employing photodynamic therapy, using Zn‐phthalocyanine as a photosensitizer that targets E‐cadherin adhesion complexes. We have found that cell death based on this photodynamic action is also bypassed in cells showing constitutive activation of H‐Ras and p110α. Taken together, these results indicate that H‐Ras/PI3K/Akt signaling plays a key role in cell survival mediated by E‐cadherin cell–cell contacts. J. Cell. Physiol. 219: 84–93, 2009.

Trichoscopic features of frontal fibrosing alopecia: Results in 249 patients

To the Editor: Currently, dermoscopy constitutes an essential noninvasive tool for dermatologists. It helps discern between different types of alopecia, it provides a more precise follow-up, and it can be used to identify an adequate biopsy site. Frontal fibrosing alopecia (FFA) is a primary lymphocytic scarring alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession and eyebrow loss that mainly affects postmenopausal women. The main objective of our study was to describe the trichoscopic features of FFA in a large series of patients and to correlate these findings with several relevant parameters of FFA. We performed a descriptive, retrospective, observational, multicenter study of digital trichoscopic images, obtained between 1994 and 2013, of 238 women with FFA at 12 Spanish centers. Diagnostic criteria included typical clinical signs and/or histopathologic features consistent with FFA. Images were obtained with either a nonpolarizing or a polarizing dermoscope. Two dermatologists expert in dermoscopy evaluated the images if the registered trichoscopic features of FFA (cicatricial white patches, perifollicular erythema, follicular hyperkeratosis, lonely hairs, and hair diameter diversity) and yellow dots typical of androgenetic alopecia were present on the frontotemporal hairline. Both a descriptive and an analytic study to correlate these parameters with the degree of severity and other clinical variables were performed using SPSS 15.0 software. Clinical and severity variables included female pattern hair loss (FPHL), presence or absence of menopause, FFA severity (I: 1 cm, II: 1-2.99 cm, III: 3-4.99 cm, IV: 5-6.99 cm, and V: [7 cm), and years of evolution, pruritus, trichodynia, facial papules, occipital involvement, eyebrow and eyelash loss, pubis hair loss, and body hair involvement. A bivariate analysis including trichoscopic findings and the aforementioned variables was carried out, and those variables with statistical significance in X test were included in a multivariate logistic regression analysis adjusted for age and excluding lost cases. No new dermoscopic signs were found. Descriptive dermoscopic results are listed in Table I. Both the intraobserver and interobserver agreement for the assignment of a dermoscopic pattern for each lesion were excellent (! 1⁄4 0.82, P\.001; ! 1⁄4 0.80, P\.001, respectively). The trichoscopic features that were statistically significantly associated (P \ .05) with some clinical parameters in the bivariate and multivariate logistic regression analysis are listed in Table II. Dermoscopic features of FFA have previously been described in some isolated studies. Toledo-Pastrana et al retrospectively analyzed the dermoscopic images of 79 patients with FFA. They found that 100% of the patients showed no follicular openings, 72.1% showed follicular hyperkeratosis, 66.3% showed perifollicular erythema, and 44.8% showed follicular plugs. Interestingly, they also found that perifollicular erythema was statistically associated to the activity of FFA. In our study, we correlated the dermoscopic features with another outcome: the severity of the disease in terms of extension of the hairline. Remarkably, we found that the presence of cicatricial white patches was statistically associated with the severity of FFA. This dermoscopic feature correlates with the histopathologic findings of hair follicle destruction and severe tissue fibrosis. Therefore, it

Venous malformation of the eyelid treated with pulsed-dye-1064-nm neodymium yttrium aluminum garnet sequential laser: an effective and safe treatment.

Venous malformations of the skin and subcutaneous tissue are compressible, blue-purple tumors that are present at birth. According to the location and symptoms caused, venous malformations can be treated with surgery, sclerotherapy, or a combination of both. Laser therapy can also be used, especially when surgery is contraindicated. We report the case of a 24-year-old man who presented with a venous malformation on the upper and lower left eyelids, which provoked a mechanical ptosis. Treatment with sequential pulsed-dye neodymium yttrium aluminum garnet (PDL-Nd:YAG) laser was performed. After 2 treatments, a marked reduction of volume and blanching of the venous malformation was observed, with satisfactory cosmetic results. The sequential PDL-Nd:YAG laser seems to be an effective and safe therapy for the treatment of cutaneous venous malformations. It penetrates deeper than pulsed-dye laser alone, and because it allows the use of lower fluencies than Nd:YAG laser alone, it reduces the risk of adverse effects.

Folliculitis decalvans: a multicentre review of 82 patients

Folliculitis decalvans (FD) is a rare neutrophilic scarring alopecia that represents a therapeutic challenge for dermatologists.