Montserrat Molgó

Uso de inmunoglobulina humana endovenosa en pacientes con necrolisis epidérmica tóxica y síndrome de sobreposición Stevens Johnson necrolisis tóxica epidérmica

BACKGROUND Toxic epidemial necrolysis (TEN) is an acute adverse drug reaction, that has an unpredictableprogression and a 30% mortality. The incidence of TEN in the general population is approximately 0.4 to 1.2 cases/million/year. It is characterized pathologically by keratinocyte apoptosis which leads to epidemial detachment. Keratinocyte apoptosis is triggered by activation of the Fas-FasL, pathway and could be prevented by the use of intravenous immunoglobulin (IVIG). AIM To report the experience with the use of IVIG in TEN. MATERIAL AND METHODS Retrospective study of 15 patients with a diagnosis of Stevens-Johnson/TEN overlap (SJS/TEN) or TEN, that received a total dose of 23 +/- 0.6 mg/kg ofIVIG over aperiod of 3 to 4 days. The infusión was initiated during thefirst 24 hours after diagnosis and was associated with standard care for burn victims. Steroids were avoided if the patient was not in chronic steroidal therapy. RESULTS Allpatients responded to IVIG in a lapse of 46.4 +/- 14.2 hours from the beginning of infusión. Eighty percent of patients survived, but one developed acute renal failure due to IVIG, and another became blind due to corneal opacities, a complication of TEN. Those who survived were discharged after a lapse of 19-8 +/- 6.6 days from the beginning ofthe disease. CONCLUSIONS Despite the lack of blind, multicentric and randomized triáis, we agree with some international studies that TVIG is beneficial as a treatment for SSJ/NETand TEN .

Necrolisis epidérmica tóxica. Terapia en UCI con inmunoglobulinas intravenosas en un caso

We report a 27 years old homosexual male with AIDS that was admitted to the ICU dehydrated, with fever and severe malaise. He had irregular bullae, an extensive purpuric exanthema and a zone of epidermic detachment in the right arm. A toxic epidermal necrolysis was diagnosed and therapy with i.v. immunoglobulins was started. After four days of treatment, bullous lesions disappeared and the extension of exanthema decreased. Toxic epidermal necrolysis is a potentially fatal disease and the use of intravenous immunoglobulins for this condition has been reported as successful (Rev Med Chile 2000; 128: 1343-48).

Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma

Purpose:CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America.Methods:CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained.Results:Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients.Conclusion:The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727–736.

Tanning salons in Santiago, Chile: the knowledge of the staff in charge and the quality of information provided to potential clients before and after a new regulatory law

Introduction: In recent years, the use of artificial tanning devices has become very popular in Chile. In April, 2007, a new law was established to regulate the non‐medical use of tanning beds and tanning booths. The aim of this study was to evaluate the level and quality of information provided by tanning salon staff to clients before deciding on using the services. This information was collected before and 6 months after the law was enacted by researchers visiting tanning salons posing as potential clients.

Vitamin D axis and its role in skin carcinogenesis: a comprehensive review

Vitamin D (VD) is a secosteroid hormone that is mainly synthesized in the skin upon exposure to UVB radiation. VD is widely known for its role in calcium metabolism; however, multiple endocrine, paracrine and autocrine functions of VD have been described, including a prominent role on carcinogenesis. In recent years, multiple associations between VD deficiency and different types of cancer have been described, supported by evidence of anti-proliferative, anti-angiogenic, pro-apoptotic, cell-differentiating and anti-invasive effects of this hormone. An immunomodulatory role of VD associated to cancer microenvironment has also been suggested. Regarding skin cancer, it has been shown that VD inhibits tumor development in basal cell carcinoma, squamous cell carcinoma, and melanoma in vitro. Some studies have suggested that lower VD levels may be a risk factor for skin cancer, while others have shown the opposite; there is also preliminary evidence on the role of VD supplementation for the prevention of melanoma in vivo. In this review, we explore the mechanisms of VD effects on carcinogenesis and the available scientific evidence of the interplay between VD and the genesis of both non-melanoma and melanoma skin cancer.

Immunohistochemical expression of vitamin D receptor in melanocytic nevi and cutaneous melanoma. A case‐control study

Vitamin D deficiency is associated with higher risk of cancer, possibly due to its antiproliferative, antiangiogenic, proapoptotic, cell‐differentiating and anti‐invasive effects. The anticarcinogenic role of vitamin D in melanoma is still a matter of debate. Loss of nuclear and cytoplasmic vitamin D receptor (VDR) expression in melanoma cells has been reported.

Abstract LB-223: An open-label, exploratory phase II study of oral itraconazole for the treatment of basal cell carcinoma

Purpose: Itraconazole is an FDA-approved antifungal drug that has been recently shown to antagonize the Hedgehog (Hh) signaling pathway, a crucial driver of basal cell carcinoma (BCC) tumorigenesis. As oral itraconazole reduced BCC growth in mice, we assessed itraconazole9s efficacy in treating human BCC tumors in an open-label, exploratory phase II study. Patients and Methods: Patients with at least one BCC tumor greater than 4 mm in diameter and with no co-morbidities were eligible to enroll. Patients were enrolled in 2 cohorts to receive oral itraconazole 200 mg twice-daily for one month (Cohort A) or 100 mg twice-daily for a longer duration (Cohort B). The primary endpoint was to determine changes in tumor size, proliferation (Ki67 levels), and a target gene of the Hh pathway (GLI1 mRNA). Results: Of the 29 patients that enrolled in the clinical trial, 19 patients were treated with itraconazole. Itraconazole caused 2 treatment-related adverse events (grade 2 fatigue and grade 4 CHF). Tumors treated with itraconazole showed a 23% reduction in clinical tumor area (95% CI: 17.2% to 28.1%), a 45% reduction in cell proliferation (P=0.04), and a 65% reduction in Hedgehog activity (P=0.03). Eight subjects with multiple tumors were assessed for clinical size changes: 4 subjects had partial response and 4 had stable disease. Tumors from control patients and patients previously treated with other Hedgehog inhibitors saw no significant changes in cell proliferation or Hedgehog activity. Conclusion: Itraconazole reduced BCC tumor size, tumor proliferation, and Hedgehog pathway activity in this exploratory study. Additional studies with larger numbers of patients are needed to validate these findings, however this proof-of-concept study demonstrates the possibility of repurposing FDA approved drugs for the treatment of cancers driven by the Hedgehog signaling pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-223. doi:1538-7445.AM2012-LB-223

Extranodal Natural Killer/T-Cell Lymphoma, nasal-type with primary cutaneous involvement. A case report

INTRODUCTION Extranodal natural killer/T-cell lymphoma (NK/T), nasal type, is an infrequent neoplasm with a high lethality, characterized by bone destruction around the sinus, nasal septum or obstruction of the airway. Also, may be primary skin involvement, airway and other organs. Objecti ve: Submit a rare condition in the pediatric population, in order to facilitate the diagnostic suspicion and quick recognition from specialists. CASE REPORT a 14-year-old girl, who presented arm and leg lesions, painless, suggestive of subcutaneous panniculitis, which evolve to ulcerated purple maculae. Skin biopsy showed lesion compatible with NK/T lymphoma, nasal type. She was referred to pedia tric oncology, where she received chemotherapy treatment. Despite medical efforts, the patient died eight months after due to a serious pulmonary infection secondary to immunosuppression. Conclu sions: Extranodal NK/T-cell lymphoma, nasal type, is a rare neoplasm that behaves aggressively, with high mortality without treatment, therefore, its recognition has a high importance for early diagnosis and prompt referral to Hematology-Oncology.

Porfiria cutánea tarda. Caso Clínico

Porphyria cutanea tarda (PCT) is the most common type of porphyria: it is characterized by blistering lesions, erosions and crusts on the back of the hands, associated with photosensitivity and facial hypertrichosis. It is produced by acquired or hereditary deficiency of the enzyme UROD, fifth enzyme in the chain of production of the Heme group. This causes accumulation of porphyrins in the liver, which are subsequently mobilized to the skin, where lesions are generated by photosensitivity. This deficiency can be exacerbated by multiple causes. We report a 51-year-old female presenting with the characteristic dermal lesions described above, which disappeared when she discontinued her hormone replacement therapy with estradiol and dydrogesterone. Urinary and blood uroporphyrin and hexacarboxyl porphyrins were elevated and plasma ferritin was 479 ng/ml. Hormone replacement therapy was discontinued and phlebotomies were attempted but not tolerated by the patient. The dermic lesions have not relapsed.

Sospecha diagnóstica de síndrome de Ehlers Danlos tipo vascular: Reporte de un caso y revisión de literatura

Ehlers Danlos Syndrome comprises a heterogeneous group of genetic disorders of the connective tissue, due to defects in collagen or its modifying enzymes. We report a 21 years old male presenting with translucent skin revealing the subcutaneous venous pattern. He had a thin face, large-appearing eyes, thin lips, thin nose, joint hypermotility and history of hip dysplasia. A vascular Ehlers Danlos Syndrome was suspected. However, the genetic study to confirm the diagnosis was not done.