[Calciphylaxis, risk factors, treatment and outcomes. Retrospective study of 39 patients]. / Calcifilaxis, factores de riesgo, tratamiento y evolución. Estudio retrospectivo de 39 pacientes.

INTRODUCTION: Calciphylaxis is a serious vascular disorder characterized by calcification of tunica media, intimal hyperplasia, thrombosis, and skin necrosis. It was described in patients with renal failure (UC), although it can occur in its absence (NUC). Its risk factors are under study and its diagnosis can be complex. Over a decade ago, its mortality was estimated at 60-80%. Recent studies indicate that it has decreased (40%). METHODS: A retrospective study was carried out in the period between January 1, 2011 and December 31, 2019. The past medical record, clinical characteristics, laboratory and histopathological findings, and evolution of all patients with calciphylaxis evaluated at the Hospital Italiano de Buenos Aires were reviewed. RESULTS: Thirty-nine patients were included. Sixtyone percent were men and 39% were NUC cases. Eightytwo percent had arterial hypertension, 66% obesity and 46% diabetes. Of those, 49% received coumarin anticoagulants. All patients with NUC and 75% with UC presented ulcers with necrosis, located more frequently on the legs. In 72% of the cases the histological diagnosis was made with one biopsy. In all the treatment was multimodal and mortality at one year was 42%. CONCLUSION: We observed a high proportion of patients with NUC, in relation to what is reported in the literature, and that half received vitamin K antagonists. The histological diagnosis was made with one biopsy in most of the cases, as the surgical technique for taking the sample, the Von Kossa staining and the evaluation by an expert pathologist were the key of it.

Introducción: La calcifilaxis es un trastorno vascular grave caracterizado por depósito de calcio en túnica media arteriolar, trombosis y necrosis cutánea. Se describió en pacientes con insuficiencia renal (CU), aunque puede producirse en su ausencia (CNU). Sus factores de riesgo están en estudio y su diagnóstico puede ser complejo. Su mortalidad se estimaba en 60-80%, aunque trabajos recientes indican que ha disminuido (40%). Métodos: Estudio retrospectivo entre el 1/1/2011 y el 31/12/2019. Se revisaron los antecedentes, las características clínicas, los hallazgos de laboratorio e histopatológicos, y la evolución de todos los pacientes con diagnóstico de calcifilaxis evaluados en el Hospital Italiano de Buenos Aires. Resultados: Se incluyeron 39 pacientes. El 61.5% (24) eran hombres y 38.5% (15) fueron casos de CNU. De éstos, 82% presentaba hipertensión arterial, 66% obesidad y 46% diabetes. El 49% recibía anticoagulantes dicumarínicos. Todos los pacientes con CNU y 75% con CU presentaron úlceras de fondo necrótico, localizadas con mayor frecuencia en las piernas. En 72% de los casos el diagnóstico histológico se efectuó con una toma de biopsia. En todos, el tratamiento fue multimodal y la mortalidad al año fue de 42%. Conclusión: Observamos una elevada proporción de pacientes con CNU, en relación con lo comunicado en la literatura, y la mitad recibía anticoagulantes dicumarínicos. El diagnóstico histológico se efectuó por biopsia en la mayor parte de los casos, para lo cual la toma quirúrgica de la muestra, la tinción con Von Kossa y la evaluación por un patólogo experto fueron claves.

Genetic diversity and phylogeographic analysis of human herpesvirus type 8 (HHV-8) in two distant regions of Argentina: Association with the genetic ancestry of the population.

BACKGROUND: The genetic diversity of persistent infectious agents, such as HHV-8, correlates closely with the migration of modern humans out of East Africa which makes them useful to trace human migrations. However, there is scarce data about the evolutionary history of HHV-8 particularly in multiethnic Latin American populations. OBJECTIVES: The aims of this study were to characterize the genetic diversity and the phylogeography of HHV-8 in two distant geographic regions of Argentina, and to establish potential associations with pathogenic conditions and the genetic ancestry of the population. STUDY DESIGN: A total of 101 HIV-1 infected subjects, 93 Kaposi's Sarcoma (KS) patients and 411 blood donors were recruited in the metropolitan (MET) and north-western regions of Argentina (NWA). HHV-8 DNA was detected by ORF-26 PCR in whole blood, saliva and FFPE tissues. Then, ORF-26 and ORF-K1 were analyzed for subtype assignment. Mitochondrial DNA and Y chromosome haplogroups, as well as autosomal ancestry markers were evaluated in samples in which subtypes could be assigned. Phylogeographic analysis was performed in the ORF-K1 sequences from this study combined with 388 GenBank sequences. RESULTS: HHV-8 was detected in 50.7%, 59.2% and 8% of samples from HIV-1 infected subjects, KS patients and blood donors, respectively. ORF-K1 phylogenetic analyses showed that subtypes A (A1-A5), B1, C (C1-C3) and F were present in 46.9%, 6.25%, 43.75% and 3.1% of cases, respectively. Analyses of ORF-26 fragment revealed that 81.95% of strains were subtypes A/C followed by J, B2, R, and K. The prevalence of subtype J was more commonly observed among KS patients when compared to the other groups. Among KS patients, subtype A/C was more commonly detected in MET whereas subtype J was the most frequent in NWA. Subtypes A/C was significantly associated with Native American maternal haplogroups (p = 0.004), whereas subtype J was related to non-Native American haplogroups (p < 0.0001). Sub-Saharan Africa, Europe and Latin America were the most probable locations from where HHV-8 was introduced to Argentina. CONCLUSIONS: These results give evidence of the geographic circulation of HHV-8 in Argentina, suggest the association of ORF-26 subtype J with KS development and provide new insights about its relationship with ancient and modern human migrations and identify the possible origins of this virus in Argentina.

Potential predictive value of cofilin-1 for metastasis occurrence in a small cohort of Argentinian patients with mid-low Breslow thickness melanoma.

Nowadays, histopathological criteria for melanocytic lesions are the mainstay prognostic factors for melanoma. However, there are cases in which these parameters fall short to predict melanoma spread. We recently demonstrated a correlation of cofilin-1 levels, a key protein for tumor invasion, with different histopathological parameters associated with melanoma malignancy as well as a negative correlation with survival. In order to broaden our previous findings, we aim to estimate the probability of a melanoma to metastasize as a function of both a conventional histopathological parameter (Breslow thickness, BT) and cofilin-1's immunohistochemical expression levels, which we propose as a potential marker for metastasis. We used a Bayesian approach to analyze clinical and cofilin-1 datasets formerly obtained from a patients' small cohort diagnosed with malignant melanocytic lesions since 2000 until 2008; classified at different tumor stages with or without detected metastasis and with at least 5 years of clinical follow-up. Low BT values exhibited wide variance to predict metastasis occurrence, while the differential diagnostic value of cofilin-1 confirmed BT diagnosis or resulted more precise to predict outcome. Particularly, the probability of metastasis estimation improved when cofilin-1 was combined with BT for specific cases, where BT displayed large uncertainties. Our analysis and the cofilin-1 determination provided statistically significant prognostic value in mid-low BT melanomas, which could complement further evaluation criteria to assist diagnosis and treatment decision-making. Moreover, the combined use of cofilin-1 with BT, if validated in follow-up studies, would be feasible to help patients' selection for treatment and optimize health resources.

Nodular fasciitis, a forgotten entity.

BACKGROUND: Nodular fasciitis is a benign pseudosarcomatous, self-limited, and reactive process. Based on its clinical and histological features - a fast-growing, solitary tumor with high cellularity and mitotic count - nodular fasciitis is considered to be a benign mimic of sarcoma. METHODS: We present four cases of nodular fasciitis and a review of the literature. RESULTS: The cases we present were initially misdiagnosed as sarcoma; two as dermatofibrosarcoma protuberans, one as atypical fibroxanthoma, and one as leiomyosarcoma. CONCLUSION: Awareness of this entity among dermatologists is important as misdiagnosis may lead to unnecessary treatments associated with increased morbidity.

Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients.

Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.

Cutaneous phaeohyphomycosis.

BACKGROUND: Phaeohyphomycosis is an infrequent infection in human beings. However, in recent years, its prevalence has augmented in immunosuppressed patients (mostly in solid organ transplanted patients). Infection can be mucocutaneous or disseminated. In the former, the fungus inoculation occurs mainly through traumatism. Lesions may be polymorphic and asymptomatic, isolated or multiple, and are usually localized in exposed areas of the limbs and head. Treatment is not standardized. When possible, surgical resection of the lesion is combined with systemic antifungals. METHODS: We communicate three phaeohyphomycosis cases with cutaneous compromise. RESULTS: The cases we present show diverse clinical characteristics and varied severity and evolution. CONCLUSION: It is important for dermatologists to recognize this cutaneous fungus infection because the diagnosis using microscopic examination and mycological culture depends on the clinical suspicion.

Lingual ulceration associated with retinoic acid syndrome during treatment of acute promyelocytic leukemia.

BACKGROUND: All-trans retinoic acid (ATRA) is routinely associated with chemotherapy for the treatment of acute promyelocytic leukemia (APL). Several reports of scrotal ulceration induced by this agent have been made in the recent years. AIMS: The aim of this article was to report the first case of a lingual ulceration associated with retinoic acid syndrome (RAS). MATHERIALS AND METHODS: We presented a 32-year-old man with a diagnosis of acute promyelocytic leukemia who received treatment with ATRA. He presented with febrile neutropenia and a lingual ulcer that did not respond to antibiotic and antifungal regimens. He developed weight gain, lower limb edema, polyserositis, and acute renal failure. Retinoic acid syndrome syndrome was diagnosed. RESULTS: An exhaustive attempt to exclude infectious causes was made performing repeated cultures, histologic examinations, and direct immunofluorescence for HSV. No causative agent was identified. Re-epithelialization of the ulcer was achieved with ATRA cessation and treatment with systemic steroids. DISCUSSION: As far as we are concerned, we report the first case of a lingual ulceration associated with RAS. CONCLUSION: It is important for dermatologists to recognize this cutaneous complication of ATRA as it poses many differential diagnoses in neutropenic patients.

[Toxic epidermal necrolysis associated with acute infection by Mycoplasma pneumoniae]. / Necrólisis epidérmica tóxica asociada a infección aguda por Mycoplasma pneumoniae.

Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis represent different manifestations of the same spectrum of severe idiosyncratic cutaneous reactions to drugs and to a lesser extent are associated with infectous agents. Among these, Mycoplasma pneumoniae is one of the most frequent. We report the case of a female patient aged 5 years, with a toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection, which begins with a fever accompanied by a generalized rash with involvement of the mucous membranes. IgM serology for Mycoplasma pneumoniae was positive and initial biopsy was compatible with erythema multiforme major. The patient was treated with corticosteroids, intravenous immunoglobulin, plasmapheresis and strict care to prevent superinfection and sequels. After 31 days of hospitalization the patient was discharged from hospital.

Necrólisis epidérmica tóxica asociada a infección aguda por Mycoplasma pneumoniae / Toxic epidermal necrolysis associated with acute infection by Mycoplasma pneumoniae

El eritema multiforme, el síndrome de Stevens-Johnson y la necrólisis epidérmica tóxica representan diferentes manifestaciones de un mismo espectro de graves reacciones cutáneas idiosincrásicas a fármacos y, en menor medida, están asociados a agentes infecciosos. De estos últimos, Mycoplasma pneumoniae es uno de los más frecuentes. Se presenta el caso de una niña de 5 años, con una necrólisis epidérmica tóxica asociada a infección aguda por Mycoplasma pneumoniae, que comenzó con un cuadro febril acompañado de un exantema generalizado y compromiso de todas las mucosas. Se obtuvo serología IgM positiva para Mycoplasma pneumoniae y una biopsia inicial compatible con eritema multiforme mayor. La paciente fue tratada con corticosteroides, gammaglobulina intravenosa, plasmaféresis y estrictos cuidados para la prevención de sobreinfección y posibles secuelas. Después de 31 días de internación fue dada de alta hospitalaria.

Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis represent different manifestations of the same spectrum of severe idiosyncratic cutaneous reactions to drugs and to a lesser extent are associated with infectous agents. Among these, Mycoplasma pneumoniae is one of the most frequent. We report the case of a female patient aged 5 years, with a toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection, which begins with a fever accompanied by a generalized rash with involvement of the mucous membranes. IgM serology for Mycoplasma pneumoniae was positive and initial biopsy was compatible with erythema multiforme major. The patient was treated with corticosteroids, intravenous immunoglobulin, plasmapheresis and strict care to prevent superinfection and sequels. After 31 days of hospitalization the patient was discharged from hospital.

Rituximab en pénfigo, ¿una alternativa terapéutica? / Rituximab in pemphigus, a therapeutic option?

El rituximab es un anticuerpo monoclonal humanizado anti-CD20, proteína presente en la superficie de los linfocitos B, células productoras de autoanticuerpos que originan el pénfigo. Se considera un fármaco de segunda línea en el tratamiento de dicha enfermedad cuando fallan los corticoides y otros inmunosupresores de uso habitual. Se presentan cuatro pacientes con diagnóstico de pénfigo vulgar, refractarios a los tratamientos convencionales que recibieron rituximab, tres de los cuales presentaron remisión completa de la enfermedad...

Reactivation of Chagas' disease: cutaneous manifestations in two immunosuppressed patients.

BACKGROUND: Chagas' disease is a zoonosis caused by a protozoan agent, Trypanosoma cruzi. Patients undergoing immunosuppressive treatment due to organ transplant, malignancies, infections, or chemotherapy may reactivate a preexisting chronic or indeterminate Trypanosoma cruzi infection. METHODS: We present two transplant patients who underwent reactivation of Chagas' disease with cutaneous manifestations after an augmentation in their immunosuppressive therapy. A 38-year-old man was hospitalized on day 69 after receiving an allogeneic bone marrow transplant; he developed multiple painful erythematous plaques with diffuse borders, confined to the right cheek, trunk, thigh, elbows, and feet. A 59-year-old woman with a 14-year history of Chagasic cardiomyopathy presented one month after heart transplantation with a painful infiltrated purpuric plaque on the back of her right leg. RESULTS: In both cases, histologic examination of skin biopsies showed dermal infiltration with intrahistiocytic amastigotes. In one of the reported cases, the Strout method detected parasitemia. Treatments with nifurtimox (600 mg/d) in case 1 and benznidazole (400 mg/d) in case 2 were started. Fever and cutaneous lesions resolved immediately after seven days of treatment. CONCLUSIONS: Reactivation of Chagas' disease is a serious complication that usually occurs in immunocompromised patients. Clinical manifestations include febrile illness occasionally associated with painful skin lesions. Early diagnosis and proper treatment can significantly improve these patients' outcome.

Púrpura de Schõnlein- Henoch en adultos / Henoch-Schõnlein purpura in adults

La púrpura de Schõnlein-Henoch es una vasculitis sistémica mediada por inmunoglobulina A, caracterizada clínicamente por púrpura palpable, dolor abdominal, artralgias y hematuria o proteinuria en el laboratorio. La inmunofluorescencia directa de las lesiones cutáneas, así como la del riñón, revelan la presencia de depósitos perivasculares de este anticuerpo, dato de valor para confirmar el diagnóstico. Se presentan cinco pacientes adultos con PSH, insuficiencia renal aguda y neoplasias malignas en tres de ellos.

Henoch-Schönlein Purpura is a systemic vasculitis mediated by Ig A, clinically characterizedby non-thrombocytopenic palpable purpura, abdominal pain, arthritis and proteinuria orhematuria. Histologically, it is characterized by deposition of immunoglobulin A in the skinand kidneys, being these features essential for the diagnosis. We report five adult patientswith Henoch-Schönlein purpura with acute kidney failure, and malignant neoplasms onthree of them.

Niño de cuatro meses de vida con lesiones ampollares / Child of four months with bullous lesions

Presentamos un niño de 4 meses de edad con un cuadro clínico típico de PA, con las ampollas características y en localizaciones habituales en menores de un año, (predominio en palmas y plantas y respeto de la zona del pañal), con leucocitosis y eosinofilia en los exámenes de laboratorio y con histopatología correspondiente a las lesiones urticarianas del PA e IFD que confirmó el diagnóstico presuntivo clínico. El mismo tuvo muy buena respuesta al tratamiento con corticoides sistémicos, con remisión completa rápida y sin secuelas cicatrizales ni recaídas hasta el momento

We present a 4-month-old with a typical clinical picture of PA, with the characteristic blisters and usually located in less than one year (predominantly on palms and soles and respect for the diaper area) with leukocytosis and eosinophilia laboratory tests and histopathology for the PA urticarial lesions and IFD confirmed clinical presumptive diagnosis. He himself had very good response to treatment with systemic corticosteroids, with complete remission quickly and without sequelae or relapse scarring so far