Clinical impact of immunotherapy in Merkel cell carcinoma patients: A systematic review and meta-analysis.

BACKGROUND: Immunotherapy is emerging as an alternative treatment for Merkel cell carcinoma, but its long-term effects on response, survival, and safety are not well established. High-quality evidence is needed to estimate the efficacy of this treatment and to review the characteristics of patients and tumors that might improve outcomes. OBJECTIVE: To summarize efficacy and safety of immunotherapy in patients with Merkel cell carcinoma. METHODS: A systematic review was performed for studies published in MEDLINE, Web of Science, Scopus, and EMBASE. Two reviewers examined the literature and data extraction in duplicate. We estimated the proportions for objective responses, progression-free survival, overall survival, and treatment-related adverse events. Associations between objective response rate and immunobiologic markers were analyzed. RESULTS: Six clinical trials of 201 patients treated with immunotherapy were included. The objective response rate was 51% (95% confidence interval, 0.40-0.62; I2 = 37.1%) and grade ≥3 treatment-related adverse events were observed in 18% (95% confidence interval, 0.11-0.29; I2 = 49.5%) of patients. No significant difference was observed between response rates and immunobiologic characteristics. CONCLUSIONS: A significantly reduced tumor diameter with durable response rates and a safe profile are obtained with immunotherapy. Similar response rates achieved on either subgroup of viral status or programmed death ligand 1 expression suggests that it might act on multiple, unexplored pathways.

Giant congenital fibroepithelial polyp of the scrotum.

Fibroepithelial polyps are common tumors of mesodermal origin. However, only a few case reports of giant fibroepithelial polyps have been published, and they have mainly involved adults. This case report describes a 3-month-old boy with a pedunculated mass in the scrotum. To our knowledge, this is the first report of a giant congenital fibroepithelial polyp on this location.

Commentary on Dermoscopy as a complementary tool for positive margin demarcation on the Mohs' map.

Mohs micrographic surgery (MMS) is a technique that allows removal of complex or ill-defined skin cancer, combining tissue preservation and complete microscopic margin control. One of the main challenges of Mohs surgery is to illustrate the exact location of the tumour detected by light microscope. Using a dermoscope allows a fast, easy, reproducible way to accurately illustrate the location of a positive tumour on the Mohs map and ultimately transpose it to the surgical defect of the patient in a more precise way.

Balloon Cell Melanoma and Its Metastasis, a Rare Entity.

Balloon cell melanoma (BCM) with metastasis is a rarely occurring neoplasia. The incidence of BCM is low, and hence, the frequency of these lesions presenting metastasis is even less frequent. This review exposes the balloon cell metastasis cases that have been published and a new case. These cases share the histopathological features but the location of initial melanoma, age and sex vary. It is relevant for the dermatologist and dermatopathologist to keep in mind the diagnosis of BCM and consider the possibility of it metastasizing as nonpigmented skin lesions.

Acrodermatitis Enteropathica: A Novel SLC39A4 Gene Mutation in a Patient with Normal Zinc Levels.

Acrodermatitis enteropathica (AE) is a rare disease that results from a defective gene, SLC39A4, and is characterized by dermatitis, alopecia, and diarrhea. We report a case of AE presenting with only periorificial and acral dermatitis in which genetic testing revealed two novel compound heterozygous missense mutations for SLC39A4. This case demonstrates that not all AE mutations alter zinc transporters in the same manner and highlights the phenotypic variability of AE.

[Current treatments for advanced stage melanoma]. / Actualidades en el tratamiento del melanoma en etapas avanzadas.

Melanoma has shown a greater increase in frequency as compared to other neoplasms, demonstrated by a 619% incidence increase in the USA from 1950 to the year 2000. Its treatment has always been a challenge, and once it has metastasized, there are no available curative regimens. In recent years considerable progress in the understanding of its pathophysiology and progression has been achieved; with the description of the genetic, molecular, and immunologic changes, new and specific drugs have been developed, with better response rates than conventional chemotherapy. Currently, a broad scope of therapeutic choices is available, although only eight are approved by the FDA. In the following literature review we present some of the better-known systemic treatment options for melanoma, from conventional chemotherapy, molecular (MAPK inhibitors) and immunomodulatory (interleukin-2, tumor necrosis factor alpha, cytotoxic T lymphocyte antigen-4 and programmed death-1 inhibitors) therapies, to miscellaneous options, among which are angiogenesis inhibitors, apoptosis modulators, vaccines, and radiotherapy.

Ciliary Madarosis Secondary to Intra-Arterial Chemotherapy for Retinoblastoma Treatment.

Background: Retinoblastoma is the most common intraocular tumor in the pediatric population. Its main therapeutic objectives are to avoid fatal outcomes and preserve vision as much as possible. Intra-arterial chemotherapy (IAC) improves drug delivery and reduces possible systemic adverse effects. This modality allows direct administration of chemotherapeutic agents to intraocular malignancies via the ophthalmic artery (OA), proving to be a feasible and effective method for globe salvage. Most side effects of IAC are local, including eyelash loss of the nasal portion of the eyelid. Summary: We performed a comprehensive review to analyze data regarding ciliary madarosis in patients diagnosed with retinoblastoma treated with IAC. We describe 9 studies with a total of 637 eyes with retinoblastoma that underwent IAC, of which 45 cases presented madarosis. In chemotherapy-induced alopecia, there is hair shaft thinning and breakage. On trichoscopy, the remaining end of the fractured hair will be observed as black dots. Differential diagnoses must include alopecia areata and trichotillomania. Key Messages: Ciliary madarosis secondary to IAC, although transitional, may cause discomfort in patients and family members. Physical examination, as well as a trichoscopic evaluation of the affected area, can help in reaching a prompt diagnosis and prognosis for this particular alopecia.

[Scleroderma: an update on the pathogenesis and treatment]. / Etiopatogenia y tratamiento de la esclerodermia. Conceptos actuales.

Scleroderma is a multiorganic disease characterized by inflammatory, vascular and sclerotic changes in skin and internal organs. It is considered as a tripartite disease, associated to autoimmune, fibroblast and endothelial defect, due to genetic, environmental and infectious factors. This disease can be classified in systemic and localized form. The Raynaud phenomenon occurs in 90% of the patients with the diagnosis. It explains the microcirculation involvement and the reduction in the number of capillaries. Malformation of nail bed capillaries is readily demonstrated by nail bed microscopy and has been shown to correlate both with disease severity and with degree of internal organ involvement. The MRSS-51 validates the skin involvement and has the main predictive value to determine the patient survival. MRSS-51 should not be considered as an activity disease parameter or used to validate the effectiveness of treatment. Nowadays, multiple treatment alternatives exist for scleroderma disease; however these treatments offer poor results for the cutaneous manifestations.

Anagen Effluvium after Neurointerventional Radiation: Trichoscopy as a Diagnostic Ally.

Minimally invasive procedures for vascular brain lesions are being performed more frequently. Radiation exposure caused by endovascular embolization of cerebral aneurysms may give rise to nonscarring scalp alopecia located in the treated area. Clinical and trichoscopic features of this type of alopecia are similar to alopecia areata (AA). Herein, we performed a comprehensive review to describe the clinical and trichoscopic characteristics of radiation-induced anagen effluvium. Predominant trichoscopic findings include black dots, yellow dots, short vellus hairs, and absence of exclamation marks hairs. It is important to consider this diagnosis in patients who have recently undergone such procedures that can easily be misdiagnosed as AA.

Psoriasis and Cardiovascular Disease: A Narrative Review.

Psoriasis is a chronic, autoimmune, and inflammatory disease that affects 2% of the world's population. In recent years, it has been demonstrated that psoriasis confers a 25% increase in relative risk of cardiovascular disease, independent of factors such as hyperlipidemia, smoking, and obesity. The objective of this review was to analyze and describe the association between psoriasis and cardiovascular disease. In this review, we describe the epidemiological association of psoriasis and cardiovascular disease, pathophysiology, mechanisms, and its association with the well-known cardiovascular risk calculators. In addition, we describe diagnostic tools, such as imaging techniques and novel biomarkers, that are useful in the evaluation of atherosclerotic cardiovascular disease. Finally, we present different systemic therapies that are used in patients with psoriasis and their effect on atherosclerotic cardiovascular disease. This article provides an overview of the current literature on psoriasis and cardiovascular risk, which can be useful for primary care physicians in their daily clinical practice.

Cryotherapy plus low-dose oral isotretinoin vs cryotherapy only for the treatment of anogenital warts: a randomized clinical trial.

BACKGROUND: Anogenital warts are a common human papillomavirus infection. They cause emotional distress, especially when they are in the anogenital region. Cryotherapy is a first-line treatment. Previous clinical trials and case series have reported variable results with retinoids (isotretinoin) as adjuvant therapy. OBJECTIVE: To determine the safety and efficacy of low-dose oral isotretinoin as adjuvant treatment of anogenital warts. METHODS: Forty-six patients with anogenital warts were randomly assigned to isotretinoin + cryotherapy (n = 23) or only cryotherapy (n = 23). Patients were allocated via an interactive web-based randomization system. Evaluators were blinded to treatments. Isotretinoin 20 mg/daily + cryotherapy or cryotherapy were prescribed for 6 weeks. Patients were followed for 4 months. Genotyping of lesions was performed before treatment started. Dermatology Life Quality Index (DLQI) and Columbia-Suicide Severity Rating Scale (C-SSRS) were measured at the beginning and end of therapy. All patients completed the study. RESULTS: Both Groups had 50% clearance at the end of treatment. Recurrence in the combined group was not significantly lower than in the cryotherapy group (P = 0.59). Improvement was observed in the DLQI of all patients in both groups (P = 0.001). No suicidal intention was detected with the C-SSRS. Two patients (one in each group) had liver function test abnormalities after treatment. CONCLUSION: Combined therapy showed a slight not significant efficacy for anogenital warts in Hispanic patients. Low-dose isotretinoin seems to be safe even when it is used with cryotherapy on anogenital warts. TRIAL REGISTRATION: On April 25, 2019 with registration number DE19-00004, CONBIOÉTICA-19-CEI-001-20160404. Prospectively registered.

Subcutaneous alemtuzumab plus cyclosporine for the treatment of aplastic anemia.

Aplastic anemia (AA) is most frequently due to autoimmune attack on its own stem cells. Alemtuzumab is a monoclonal antibody which recognizes the CD52 antigen on the surface of T and B cells. It has proved useful in autoimmune diseases, lymphoproliferative conditions, and graft versus host disease. Based on its immunosuppressive properties, we treated 14 AA patients with alemtuzumab. Median age was 23 years. Ten milligrams of alemtuzumab were injected subcutaneously each day for five consecutive days. Cyclosporine A was also administered orally at a dose of 2 mg/kg every 12 h for 3 months, and then gradually tapered. Response to alemtuzumab was followed for a median of 20 months. There were eight responses (57.1%), two complete and six partial. Whereas six (42.8%) patients were non-responders. Median complete blood count values on alemtuzumab responders were Hb 13.1 mg/dL, absolute neutrophil count 2.4 x 10(9)/L, and platelets 97.5 x 10(9)/L. A good response was produced in 57% of AA patients with the administration of alemtuzumab, who lacked a stem cell donor.

Pigmented purpura and cutaneous vascular occlusion syndromes.

Purpura is defined as a visible hemorrhage in the skin or mucosa, which is not evanescent upon pressure. Proper classification allows a better patient approach due to its multiple diagnoses. Purpuras can be categorized by size, morphology, and other characteristics. The course varies according to the etiology, as do the diagnostic approach and treatment. This review discusses pigmented purpuras and some cutaneous vascular occlusion syndromes.

Dermoscopic features of acral melanocytic nevi in a case series from Mexico.

BACKGROUND: Pigmented lesions on acral sites are common; clinical differentiation of nevi and early melanoma can be challenging. In these cases, dermoscopy can provide a more accurate diagnosis. Most dermoscopic patterns on acral skin have been described in Asian and European populations, while there are few studies in Latin American populations OBJECTIVES: To determine the frequency of pigmented lesions in volar skin and their dermoscopic patterns in a Mexican population. Methods: An observational, descriptive, cross-sectional study was performed in Hispanic patients with the presence of at least one pigmented lesion on acral skin. Clinical and dermoscopic images were obtained. These were subsequently evaluated independently by two dermatologists trained and experienced in dermoscopy RESULTS: A total of 582 pigmented lesions on volar skin were diagnosed in 321 patients. Overall, prevalence of acral pigmented lesions on volar skin was 6.8%. For both observers, parallel furrows were the most frequent pattern described, but for observer 2, a lattice-like pattern was prevalent on the toes and a homogeneous pattern on the sides of the feet. There was lower inter-observer agreement, with a kappa index of 0.144 STUDY LIMITATIONS: The lesions were not biopsied, so clinical-histological correlation could not be performed. The study did not correlate dermoscopic patterns with age CONCLUSIONS: As previously reported by other authors, parallel furrows were the most frequently found dermoscopic pattern on palmoplantar skin

An Update on Calciphylaxis.

Calciphylaxis, also known as calcific uremic arteriolopathy and uremic small artery disease with medial wall calcification and intimal hyperplasia, is a multifactorial cutaneous vascular disease characterized by chronic, painful, non-healing wounds that occur frequently in patients with chronic kidney disease, predominantly in those with end-stage renal disease. The pathogenesis remains unclear, and the development of calciphylaxis lesions depends on medial calcification, intimal fibrosis of arterioles and thrombotic occlusion. Despite an increase in reports of calciphylaxis in the literature and clinical recognition of demographic characteristics and risk factors associated with calciphylaxis, it remains a poorly understood disease with high morbidity and mortality. In this review, we analyze and summarize the clinical manifestations, pathogenesis and pathophysiology, histopathology, differential diagnosis, diagnostic workup and treatment modalities for calciphylaxis. Because of the lack of consensus regarding the optimal approach to and treatment of this disorder, a high degree of clinical suspicion, early diagnosis, and multimodal and multidisciplinary treatment in collaboration with dermatology, nephrology, wound care, nutrition and pain management specialties may improve survival in patients with calciphylaxis.

Basal cell carcinoma treated with Mohs micrographic surgery in young Ibero-American patients.

BACKGROUND: The incidence of basal cell carcinoma (BCC) in younger individuals has increased in recent decades. However, the characteristics of BCCs in this population, especially in Ibero-Latin American countries, have not been completely defined. OBJECTIVE: To describe the demographic, clinical, and histopathological characteristics of BCCs in patients younger than 40 treated with Mohs Micrographic Surgery (MMS). MATERIALS AND METHODS: A multicenter, retrospective study conducted between January 2009 and December 2014, in five Ibero-American countries, included biopsy-proven BCCs in patients younger than 40 that were treated with MMS. Demographic, clinical, histopathological, and surgical characteristics were described. RESULTS: The study included 301 tumors in 241 patients, of whom 61% were female. The most common Fitzpatrick phototype was III. The most common histological subtypes were nodular (37.5%) and infiltrative (18.9%). Perineural invasion was encountered in 1.7%, and tumor clearance was achieved in 87.4% within two stages of MMS. CONCLUSIONS: This is the first Ibero-Latin American transnational study describing the characteristics of BCCs in young patients treated with MMS. Despite darker skin phototypes in this population, BCCs can occur in early ages and may present with aggressive features. Therefore, MMS may be considered an appropriate first-line treatment option in this population.