Sindrome de Atra / Atra syndrome

La leucemia promielocítica aguda (APL) es el subtipo de leucemia mieloide aguda de mejor pronóstico en niños. Su incidencia es menor a 10%. Desde el punto de vista citogenético se observa una translocación t (15;17). En la terapéutica la incorporación del ácido transretinoico ha logrado altas tasas de remisión completa debido a la rápida desaparición de la coagulopatía y, en consecuencia, disminución de la tasa de recaídas, en comparación con el tratamiento de monoterapia. En general es un fármaco bien tolerado pero puede tener reacciones adversas; el más grave es el síndrome de ácido transretinoico (ATRA), potencialmente mortal. Las manifestaciones clínicas son: fiebre, ganancia de peso, infiltrados pulmonares, síndrome de dificultad respiratoria, derrame pleural o pericárdico, hipotensión, insuficiencia hepática y renal. El tratamiento es con suspensión del ácido transretinoico, medidas de apoyo y altas dosis de esteroides. Se presenta un caso clínico del hospital del Niño DIF con APL y Síndrome de ATRA.

The leukemia promyelocytic acute (APL) is the subtype of leukemia myeloid acute of better prognosis in children. Its incidence is less than 10%. From the point of view cytogenetic is observed a translocation t (15; 17). The addition of the acid transretinoico has achieved high rates of complete remission because of the rapid disappearance of the coagulopathy and, consequently, decrease in the rate of relapses, compared with monotherapy treatment. In general it is a well-tolerated drug but can have adverse reactions; the most serious is transretinoico acid (ATRA), potentially fatal syndrome. The manifestations are: fever, weight gain, pulmonary infiltrates, syndrome of shortness of breath, hypotension, pleural effusion or pericardial, hepatic and renal insufficiency. The treatment is with suspension of the acid transretinoico, measures of support and high doses of steroids. It presents a case clinical of the Hospital del Niño DIF with APL and syndrome of ATRA.

Acute promyelocytic leukemia: An experience from a tertiary care centre in north India.

Background: There are very limited data reported about acute promyelocytic leukemia (APL) from developing countries. We reviewed the clinical course and treatment outcome of APL patients treated at our center. Materials and Methods: Between January 1997 and December 2007, 33 patients with APL received induction therapy using ATRA + daunorubicin (n = 26), As = 26), As2O3 (n = 4) or daunorubicin + cytosar ( n = 3). Results: Median age was 30 years with a male to female ratio of 1.68. Twenty seven patients (82%) achieved CR. Complications during induction therapy were febrile neutropenia (33%), ATRA syndrome (30%), bleeding (58%), and diarrhea in (6%) patients. During induction and follow up, 8 (24.24%) patients died, 6 (18.18%) during induction, 1 (3%) during maintenance, and 1 (3%) after relapse. Median OS is 128 months while median EFS is 61 months. Four patients relapsed at a median time of 61 months. At the time of censoring, 25 patients were alive at a median follow up of 13 months (range 0.6 -127 months); 21 in CR1, 3 in CR2, 1 in CR3. Comparisons among the risk groups (CR and relapse rate and survival statistics) were not statistically significant. Conclusions: APL is a highly curable malignancy. Our results confirm the findings of the published literature from larger cooperative studies from the West. We may further improve outcome with quicker diagnosis and more efficient supportive care system.

Eficacia y seguridad del retinaldehido y el Ácido retinoico tópico en el tratamiento del fotoenvejecimiento / Efficacy and safety of retinaldehyde and topical retinoic acid in the treatment of photoaging

El ácido retinoico tópico es eficaz para el tratamiento del fotoenvejecimiento. Sin embargo la irritación cutánea secundaria a su uso es un factor limitante del tratamiento. El retinaldehído es un precursor inmediato del ácido retinoico que posee actividad biológica en la piel, con menos efectos secundarios. Objetivo: comparar la eficacia y tolerancia del retinaldehido y el ácido retinoico tópicos en el tratamiento del fotoenvejecimiento, mediante perfil profilométrico y análisis clínico - fotográfico y determinar los efectos secundarios de estos medicamentos. Métodos: se incluyeron 126 mujeres colombianas (35 a 60 años), quienes no habían recibido tratamientos previos, no estaban embarazadas, ni lactando. En total 119 pacientes completaron las 24 semanas de seguimiento: a 61 pacientes se les aplicó retinaldehído y a 58, ácido retinoico. Se realizó un seguimiento clínico (que evaluó mejoría y tolerancia), en las semanas 4, 8, 16 y 20, y además se realizó profilometría del área de la pata de gallina y seguimiento fotográfico al ingreso y en la semana 24.

Topical retinoic acid has been effectively used to treat photo aging; nevertheless, cutaneous irritation as a side effect is a limiting factor for treatment. Retinaldehyde is an immediate precursor of retinoic acid that has biologic activity in the skin, with few side effects. The objective of this investigation was to compare efficacy and tolerability of topical retinoic acid and retinaldehyde in the treatment of photo aging, by means of profilometry and clinical-photographic analysis and to determine side effects from both medications. Methods: were included 160 colombian women (aged 35 to 60 years), who hadn't had previous treatments and weren't pregnant or breast feeding. A total of 119 patients completed 24 weeks of treatment. Of these, 61 used retinaldehyde and 58 retinoic acid. Clinical evaluation was carried out on weeks 4, 8, 16 and 20, and profilometry of the “crow's feet” area was done at the beginning and at week 24.

Comparative study on the effect of retinoic acid, glycolic acid and salicylic acid on the thin skin of adult female guinea pig. light and electron microscopic study

Many products had been used as chemical peeling agents to renew thin skin. Retinoic, Glycolic and Salicylic acids were used in many dermatological diseases with hypdrkeratinization and/or hyperpigmentation. To evaluate and compare the effects of these acids on the thin skin of adult female guinea pig. Twenty animals were used and were divided into four equal groups. Group I served as the control group, whereas the other treated groups were topically applicated daily on shaved area of back skin with Retinoic [0.05%], Glycolic [12%] and Salicylic [10%] acids in Groups II, III and IV, respectively. Thin skin specimens were processed for light and transmission electron microscopic studies. Morphometric and statistical studies were done. Groups II, III and IV showed high significant increase in mean thickness of epidermal nucleated keratinocytes as compared to Control group. Group II showed proliferation hyperkeratosis and acanthosis and shrinkage of the sebaceous glands with decreased sebum production. Group III showed skin peeling by removing superficial layers of epidermis, cytoplasmic and nuclear degeneration with disruption of intercellular junctions and degeneration in melanocytes with marked decrease of melanin. Both Retinoic and Glycolic acids apparently increased the production of collagen and elastic fibers as compared to control. Group IV showed skin peeling mainly by direct action on intercellular cement substance and partially by inducing proliferation hyperkertosis. Both Retinoic and Glycolic acids showed complementary actions in treatment of hyperpigmentation and as chemical peeling agents. Salicylic acid also is a peeling agent, but its effects could be covered by either Retinoic or Glycolic acids. It is recommended to use combination of both Retinoic and Glycolic acids to give better effects on various skin disorders with hyperkeratinization and hyperpigmentation

Embriopatía por isotretinoína: Un daño evitable / Isotretinoin embryophaty: Report of one case

Retinoic acid is a widely used drug in the treatment of cystic acné. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months of female whose mother was exposed to retinoic acid in both pregestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms ofthe teratogenic effeets of retinoic acid.

Embriopatia do ácido retinóico: relato de dois casos associados ao uso da isotretinoína / Retinoic acid embryopathy: report of two cases associated with the use of isotretinoin

Os autores apresentam dois casos associados ao uso da isotretinoína antes ou durante o período gestacional, com seus aspectos característicos e variações, sendo uma criança do sexo feminino e outra do sexo masculino. Descritos para divulgação no meio médico das possíveis complicações do uso da isotretinoína nas mulheres em idade fértil levando em conta a gravidade das malformações nos diferentes sistemas do corpo humano.

Successful treatment of retinoic acid syndrome with dexamethasone: a case report.

Retinoic acid syndrome (RAS) is the clinical syndrome that occurs after treatment of acute promyelocytic leukemia with all-trans-retinoic acid (ATRA). The patients experience fever, dyspnea, hypotension, respiratory distress, edema and weight gain. Chest x-ray will show pulmonary infiltrates and pleuropericardial effusion. The onset of this syndrome is usually 5-21 days after ATRA treatment when white blood cell counts are rising more than 10,000/cu.mm. The authors have reported a case of RAS. The patient was a 29-year-old man who had been working in a battery manufacturing factory for 7 years. He presented with easily bruising for one month. The initial blood test showed hematocrit of 36.2%, white blood cells count of 3,200/cu.mm with 28% neutrophils, 20% lymphocytes, 2% eosinophils and 50% promyelocytes and platelet of 20,000/cu.mm. Peripheral blood smear revealed numerous fragmented red blood cells. Bone marrow examination showed hypercellularity with abnormal promyelocytes of 95% and bone marrow cytogenetics was translocation of chromosome 15 and 17 [t (15;17)(q22;q12)]. The diagnosis was acute promyelocytic leukemia and the patient was treated with ATRA 45 mg/m2/day per oral starting on day 1 and intravenous idarubicin 10 mg/n2 on day 4, 5 and 6. On day 13, he had a body temperature of 39 degrees C and a dry cough. The white blood cells were rising to 7,400/cu.mm with 16% neutrophils. On day 18, he had oliguria, high grade fever, hypotension, cough with chest pain and white blood cells rose to 21,300/cu.mm with 65% neutrophils and rising of blood urea nitrogen and creatinine. Chest x-ray showed enlarged cardiac shadow with pleural effusion. Echocardiogram revealed moderate amount of pericardial effusion. The diagnosis of RAS was made and ATRA was withdrawn. Intravenous dexamethasone 4 mg every 6 hours and hemodialysis was started. The patient's symptoms improved dramatically and bone marrow examination was in complete remission. He was subsequently given cytarabine and idarubicin as consolidation. This patient had clinical manifestation consistent with RAS, which improved after prompt treatment.

Síndrome del ácido transretinoico: Reporte de un caso y revisión de la literatura / All-Trans retinoic acid Syndrome: Case Report and a Review of the Literature

Se describe el caso de una enferma con leucemia aguda promielocítica (LAP) que desarrolló síndrome del ácido transretinoico (SATRA) y se revisa la literatura. El SA TRA se presenta en enfermos con LAP tratados con ácido transretinoico (ATRA). Tiene incidencia de 5% a 27% con mortalidad de hasta 29%. Es secundario al efecto del ATRA sobre la diferenciación de los promielocitos, lo que desencadena respuesta inflamatoria sistémica, daño endotelial con síndrome de fuga capilar y obstrucción de la microcirculación e infiltración tisular. Clínicamente se manifiesta con fiebre, hipotensión, insuficiencia respiratoria, renal y hepática, infiltrados pulmonares, derrame pleural y pericárdico, y edema generalizado. El tratamiento es a base de suspensión del ATRA, medidas de apoyo y esferoides.

We described a patient with acute promyelocytic leukemia (APL) who developed all-trans retinoic acid syndrome (ATRAS) and reviewed the literature. ATRAS presents in patients with APL treated with all-trans retinoic acid (ATRA). It has an incidence from 5%-27% with mortality of 29%. It is secondary to ATRA effect on promyelocyte differentiation, which causes systemic inflammatory response syndrome, endothelium damage with increase in capillary permeability, microcirculation obstruction, and tissue infiltration. ATRAS clinical manifestations are fever, hypotension, respiratory, renal and hepatic insufficiency, lung infiltrates, pleural and pericardic efussion, and generalized edema. Treatment is based on ATRA suspension, support measures, and steroids.

Características hematológicas e perfil de expressão de antígenos mielóides de pacientes com leucemia promielocítica aguda: análise de fatores prognósticos para o desenvolvimento da síndrome do ácido retinóico / Hematological features and expression profile of myeloid antigens of acute promyelocytic leukemia patients: analysis of prognostic factors for development of the retinoic acid syndrome

OBJETIVO: A leucemia promielocítica aguda (LPA) apresenta uma boa resposta ao tratamento com o ácido all trans retinóico (ATRA). Entretanto, alguns pacientes desenvolvem uma complicação grave chamada síndrome do ácido retinóico (SAR). O objetivo deste estudo foi comparar as características hematológicas e imunofenotípicas de pacientes com LPA que desenvolveram a SAR com as daqueles que não a desenvolveram. MÉTODOS: Foram analisados retrospectivamente os prontuários, exames radiológicos, lâminas de esfregaço de sangue e medula óssea de 71 pacientes com LPA, dos quais a análise imunofenotípica havia sido realizada em 56 casos. Foram identificados oito casos de SAR que, do ponto de vista clínico, caracterizaram-se por insuficiência respiratória (n=8), insuficiência renal (n=2), febre (n=5), ganho ponderal (n=3), edema periférico (n=3) e derrame pleural (n=5). As seguintes variáveis foram comparadas entre pacientes com e sem SAR: dosagem de hemoglobina, contagens de leucócitos e plaquetas no sangue periférico, distribuição dos subtipos hipergranular e variante, percentagens de blastos CD33+, CD13+, CD117+ na medula óssea, intensidade e variação dos valores de fluorescência destes antígenos nas células leucêmicas, expressas através dos canais medianos (CMFs) e dos coeficientes de variação (CVs) de fluorescência, respectivamente. RESULTADOS: A incidência da SAR foi de 11,26 por cento e o tempo médio para seu desenvolvimento 11,5 dias do início do tratamento. Todos os pacientes apresentaram desconforto respiratório agudo, por vezes associado à febre, ganho de peso, edema e insuficiência renal. Os achados radiológicos mais comuns foram: opacidades em vidro fosco, derrame pleural, espessamento peribrônquico e aumento da trama vascular pulmonar. Nenhuma das variáveis laboratoriais analisadas correlacionou-se significativamente ao risco de desenvolvimento da SAR, entretanto as Odd Ratios para CMF para o CD117 > 30 ua e CV para o CD33 < 50 foram de 7,14 (P=0,08) e de 7,86 (P=0,06), respectivamente. CONCLUSAO: A incidência e as características da SAR neste grupo de pacientes brasileiros foi semelhante à descrita na literatura. Nenhum dos parâmetros estudados correlacionou-se significativamente a um maior risco de desenvolvimento desta complicação.

Embriopatía por isotretinoína / Isotretinoin-induced embryopathy

El ácido retinoico es un conocido teratógeno. Con el advenimiento de la isotretinoína para el tratamiento acné, su uso se ha incrementado ampliamente y con ello el peligro de marformaciones fetales. Se comunica un caso fatal de embriopatía inducida por isotretinoína, indicada para el tratamiento del acné en una mujer de 23 años. Se realiza una revisión bibliográfica y se remarca la importancia de las medidas de prevención cuando se prescriben retinoides sistémicos a una mujer en etapa fértil

Sweet's syndrome during the treatment of acute promyelocytic leukemia with all-trans retinoic acid

All-trans retinoic acid (ATRA) is the standard induction treatment for acute promyelocytic leukemia (APL). Quite many ATRA-related side effects, including retinoic acid syndrome, were reported. So far, it has rarely been reported that Sweet's syndrome, characterized by fever, neutrophilia, painful erythematous cutaneous plaques, dense dermal infiltrates of mature neutrophils and rapid response to steroid therapy, is associated with ATRA. In the case that Sweet's syndrome associated with ATRA is found, physicians will have to face a great challenge over the possibility of infectious conditions. We present here a case of Sweet's syndrome associated with ATRA. A 35-year-old female with APL developed fever, painful erythematous cutaneous plaques on both cheeks, right wrist and both shins during induction chemotherapy with ATRA. A skin biopsy revealed a dense dermal infiltrate, consisting of mature neutrophils without vasculitis or cutaneous immunoglobulin deposits, which is compatible with Sweet's syndrome. Oral prednisone was administered and the lesions started to improve within 48 hours

Pseudotumor cerebri caused by all-trans-retinoic acid: a case report.

Pseudotumor cerebri is a condition characterized by increased intracranial pressure with normal cerebrospinal fluid composition. It is usually associated with many medical conditions and drugs. It has been reported that all-trans-retinoic acid can induce pseudotumor cerebri. The authors report a 35-year-old patient diagnosed with acute promyelocytic leukemia who developed pseudotumor cerebri after receiving all-trans-retinoic acid. The patient was treated with 60 mg/day of all-trans-retinoic acid. Two weeks later, she had severe headache and blurred vision. The neurological examination revealed papilledema and decreased visual acuity. Other physical examinations were unremarkable. Brain CT was normal. Additionally, lumbar puncture was performed and the CSF finding was normal except for high CSF pressure. According to modified Dandy criteria, the diagnosis was pseudotumor cerebri. The patient's symptoms disappeared after all-trans-retinoic acid was discontinued. To our knowledge, this is the first case report in Thailand.

Carcinoma de mama y síndrome de Sweet / Breast carcinoma and Sweet's syndrome

El síndrome de Sweet es una entidad dermatológica poco frecuente, definida como una dermatosis neutrofílica febril aguda. Esta patología presenta características clínicas bien definidad, y en un porcentaje minoritario de pacientes está asociada a neoplasias sólidas. Presentamos el caso de una paciente de 71 años de edad que consulta debido a la aparición de placas eritemato-edematosas infiltradas y dolorosas en miembro superior y región mamaria derechas, extendiéndose a hemiabdomen homolateral y dorso, precedidas por fiebre y escalofríos. Como antecedentes personales de importancia destaca haber padecido cáncer de mama 4 años antes de la aparición de la dermatosis

Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

Thirty-seven patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR) was achieved, defined as: a) presence of less than 5 percent blasts in the bone marrow, with b) white blood cells >103/mm3, c) platelets >105/mm3 and d) hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7 percent) patients achieved CR by day 50, and 75 percent of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days), was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82 percent of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS) were observed in 7 (19 percent), 6 (16 percent) and 4 (11 percent) patients, respectively. Thirteen (35 percent) patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3) and six of these presented with new signs of coagulopathy after chemotherapy. Four (11 percent) patients died secondarily to intracerebral hemorrhage (IH) and two (5.4 percent) dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity). RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients

All trans retinoic acid in acute promyelocytic leukemia: case series and review of literature

Over the past few years All Trans-Retinoic Acid [ATRA] has been increasingly used to induce remission in Acute Promyelocytic Leukaemia [APL]. ATRA is thought to restore the structural integrity of the nuclear bodies whic are disrupted by the transcribed chimeric protein [APL-RAR alpha] formed as a result of a specific non-random chromosomal translocation [15:17].Six patients of APL with ATRA were treated at a dose of 45 mg/m[2] orally. There were five female and one male patient. Five patients presented with pancytopenia while all had a picture of disseminated intravascular coagulation [Dic]. Four out of six patients entered into complete remission either on ATRA alone or with the addition of cytotoxic chemotherapy. The other two patients developed serious side effects and the treatment with ATRA had to be stopped. One of these patients subsequently entered into remission with standard chemotherapy. The mean time to remission was 39 days. Since ATRA does not induce cytotoxicity, the problem of marrow suppression and exacerbation of Dic were largely alleviated. The patients remained at home for the most part of their treatment. Relevant literature is reviewed

A importância do ácido trans-retinóico no tratamento da leucemia promielocítica aguda e suas complicaçöes / The importance of trans-retinoic acid in the acute promyelocytic leukemia treatment and its complications

Os autores apresentam uma revisao da literatura relacionada à utilizaçäo do ácido trans-retinóico na Leucemia Mielóide Aguda M3. Apresentam ainda os principais parâmetros para a sua utilizaçäo, bem como os cuidados no reconhecimento e tratamento da síndrome do Acido all-transretinóico. Os autores ilustram tal revisäo com um caso em que ocorreram as mais importantes complicaçöes com a utilizaçao do Acido all-transretinóico. Os modificadores da resposta biológica têm sido cada vez mais usados no tratamento de neoplasias, e a utilizaçäo do Acido all-transretinóico tem sido altamente significativa no tipo de LMA-M3.