Generalidades de un paciente afebril con hepatoesplenomegalia en pediatría / Overview of an afebrile patient with hepatosplenomegaly in pediatrics

Introducción: La hepatoesplenomegalia es el agrandamiento simultaneo del hígado y del bazo, aunque es frecuente en edad pediátrica su literatura se centra en causa infecciosa, siendo también importante otras causas sobre todo en el paciente afebril Método: revisión de literatura actual confrontando con artículos de revisiones de temas en búsqueda electrónica en bases de datos de RIMA, MEDLINE, PUB-MED, MEDSCAPE, de 1981 a 2018. Resultados: La hepatomegalia en paciente afebril se puede encontrar en afectación sistémica o enfermedades hereditarias, algunas prevalentes o extremadamente raras, por lo cual se desarrolló esta revisión para agrupar las causas de esta en un paciente pediátrico afebril.

Introduction: Hepatosplenomegaly is the simultaneous enlargement of the liver and spleen, although it is frequent in pediatric age, its literature focuses on an infectious cause, and other causes are important, especially in the afebrile patient. Method: review of current literature comparing articles from subject reviews. in electronic search in RIMA, MEDLINE, PUB-MED, MEDSCAPE databases, from 1981 to 2018. Results: Hepatomegaly in afebrile patient can be found in systemic involvement or hereditary diseases, some prevalent or extremely rare, for which reason developed this review to group the causes of this in an afebrile pediatric patient.

Enfermedades autoinflamatorias / Autoinflammatory diseases

Las enfermedades autoinflamatorias monogénicas son desórdenes raros que resultan en defectos del sistema inmune innato, originando excesiva respuesta a señales de peligro, activación espontánea de vías inflamatorias o pérdida de reguladores inhibitorios. En los últimos 15 años un creciente número de enfermedades inflamatorias monogénicas han sido descriptas y sus respectivos genes responsables identificados. Las proteínas codificadas por estos genes están involucradas en las vías regulatorias de la inflamación y están expresadas fundamentalmente en las células del sistema inmune innato. Si bien un grupo de pacientes exhibe inflamación sistémica episódica (fiebres periódicas), estos desórdenes están mediados por una continua sobreproducción y liberación de mediadores pro-inflamatorios -especialmente la interleucina 1beta- y su conceptualización como enfermedades autoinflamatorias es preferible por sobre la de fiebres periódicas. Las enfermedades más frecuentes son fiebre mediterránea familiar (FMF), TRAPS, deficiencia de mevalonatocinasa/síndrome de hiper IgD (MKD/HIDS) y los síndromes periódicos asociados a criopirina (CAPS). Sus características clínicas frecuentemente incluyen fiebre, erupciones cutáneas, compromiso de serosas y reactantes de fase aguda. Los autoanticuerpos están usualmente ausentes pero pueden observarse en ciertos síndromes. El diagnóstico es clínico y se basa en las características fenotípicas. El diagnóstico genético es muy importante pero debe ser realizado de manera juiciosa e interpretado con cautela. El tratamiento con agentes biológicos que bloquean citocinas pro-inflamatorias, particularmente IL-1, ha demostrado ser efectivo en muchos pacientes. Sin embargo, en otros tantos casos no se descubren anormalidades genéticas y el tratamiento es subóptimo, planteando la posibilidad de mutaciones patogénicas en genes y vías aún no explorados.

The monogenic autoinflammatory diseases are rare, genetic disorders resulting in constitutive innate immune defects leading to excessive response to danger signals, spontaneous activation of inflammatory mediators or loss of inhibitory regulators. During the past 15 years, a growing number of monogenic inflammatory diseases have been described and their respective responsible genes identified. The proteins encoded by these genes are involved in the regulatory pathways of inflammation and are mostly expressed in cells of the innate immune system. Although a group of patients exhibit episodic systemic inflammation (periodic fevers), these disorders are mediated by continuous overproduction and release of pro-inflammatory mediators, notably IL-1β, and are best considered as autoinflammatory diseases rather than periodic fevers. The most common autoinflammatory diseases are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS) and the cryopyrin-associated periodic syndromes (CAPS). Clinical features often include fever, cutaneous rash, serosal involvement and acute phase reactants. Autoantibodies are usually absent but may accompany certain syndromes. Diagnosis remains clinical and is based on the different phenotypic features. Genetic diagnosis is of utmost importance, but must be performed judiciously and interpreted cautiously. Treatment with biologic agents that block proinflammatory cytokines, particularly IL-1, has proved to be dramatically effective in many patients. Still, in many cases of autoinflammation no genetic abnormalities are detected and treatment remains suboptimal, raising the question of novel pathogenic mutations in unexplored genes and pathways.

DRESS syndrome in ophthalmic patients / Síndrome DRESS em pacientes oftalmológicos

ABSTRACT Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal adverse drug reaction associated with skin rash, fever, eosinophilia, and multiple organ injury. A number of pharmacological agents are known to cause DRESS syndrome such as allopurinol, anticonvulsants, vancomycin, trimethoprime-sulfamethoxazole, and pyrimethamine-sulfadiazine. Here, we describe two patients who developed DRESS syndrome during ocular treatment. The first case was being treated for late postoperative endophthalmitis with topical antibiotics, intravenous cephalothin, meropenem, and intravitreal injection of vancomycin and ceftazidime before symptoms developed. We were unable to identify the causal drug owing to the large number of medications concurrently administered. The second case presented with DRESS syndrome symptoms during ocular toxoplasmosis treatment. In this case, a clearer association with pyrimethamine-sulfadiazine was observed. As a result of the regular prescription of pharmacological agents associated with DRESS syndrome, ophthalmologists should be aware of the potentially serious complications of DRESS syndrome.

RESUMO Síndrome DRESS (drug reaction with eosinophilia and systemic symptoms) é uma reação adversa a medicamentos rara e potencialmente fatal, associada à rash cutâneo, febre, eosinofilia e lesão de múltiplos órgãos. Algumas drogas podem desencadeá-la, como: alopurinol, anticonvulsivantes, vancomicina, sulfametoxazol-trimetoprim, sulfadiazina-pirimetamina, entre outras. Descrevemos dois casos que desenvolverem DRESS síndrome durante tratamento ocular. O primeiro caso apresentou os sintomas durante tratamento para endoftalmite pós-operatória tardia com antibióticos tópicos, cefalotina e meropenem intravenosos e injeção intravítrea de vancomicina e ceftazidima; não podemos identificar a droga causadora, pois múltiplas medicações foram utilizadas. O segundo caso desenvolveu os sintomas durante tratamento clássico para toxoplasmose ocular, então a associação com sulfadiazina-pirimetamina foi mais clara. Como muitos oftalmologistas prescrevem regularmente drogas que podem desencadear a síndrome DRESS, esse diagnóstico deve ser lembrado já que pode levar a sérias complicações.

Sweet Syndrome in childhood

AbstractSweet syndrome or acute febrile neutrophilic dermatosis is a recurrent and rare skin disease caused by the release of cytokines, with diverse possible etiologic causes. It presents clinically with polymorphic skin lesions, fever, arthralgia, and peripheral leukocytosis. In general, it is associated with infections, malignancy and drugs. It usually regresses spontaneously and treatment is primarily to control the basic disease. The authors report the case of a child of 1 year and 11 months who developed Sweet syndrome.

Tuberculosis pericárdica / Pericardial tuberculosis

La tuberculosis pericárdica es una presentación poco frecuente de infecciones causadas por especies de Micobacterias. Se presenta el caso de una paciente femenina de 43 años de edad con antecedentes de Leucemia linfocítica aguda en remisión completa, en fase de mantenimiento con Dasatinib durante cuatro años: había derrame pleural derecho como efecto secundario, y consultó por presentar disnea progresiva, concomitante fiebre de 39ºC precedida por escalofríos, sin patrón horario asociándose a las 72 horas exacerbación del patrón de disnea hasta la ortopnea y disminución del volumen urinario motivo por el cual es traída a nuestro centro. Durante su estancia hospitalaria se realiza TC de tórax hallándose de manera incidental la existencia de derrame pericárdico, se realiza ecoscopia donde se visualiza derrame pericárdico importante a predominio posterior, de 27 mm de volumen con colapso de cavidades cardíacas derechas, estableciéndose el diagnóstico de taponamiento cardíaco. Se realiza pericardiocentesis con obtención de 720 cc de liquido pericárdico turbio. 72 horas posterior al procedimiento presenta nuevo episodio de taponamiento cardíaco realizándose ventana pleuropericárdica; el ADA de líquido pericárdico reportó valores 2 veces superior a limite de corte; el resultado de la biopsia de pericardio reportó fibrosis pericárdica. En vista de hallazgos clínicos y paraclínicos se planteó el diagnóstico de Pericarditis tuberculosa.

Pleuropericardial tuberculosis is a rare presentation of infections caused by Micobacterias. The case of a 43 years - old female patient with a history of acute lymphocytic leukemia in complete remission in the maintenance phase with dasatinib for four years with right pleural effusion is presented. She consulted for progressive dyspnea; there was also fever (39ºC) and chills. Within 72 hours orthopnoea and decreased urine volume appeared. During her hospital stay a chest CT showed the existence of pericardial effusion, and endoscopy confirmed severe pericardial effusion of 27 mm with right-sided heart collaps, and because the diagnosis of cardiac taponade was made pericardiocentesis was performed, obtaining 720 cc of pericardial turbid fluid; after s 72 hours after a new episode of cardiac taponade occurred, so that a pleuropericardial window was done. ADA values reported 2 times higher cutting; pericardial biopsy reported pericardial fibrosis. In view of these findings, clinical and laboratory diagnosis of tuberculous pericarditis was established.

Fiebre Chikungunya / Chikungunya fever

La fiebre Chikungunya es una enfermedad viral causada por el virus de Chikungunya (VCHIK), la palabra "Chikungunya" se deriva de la lengua Makonde, hablada por un grupo étnico en el sureste de Tanzania y el norte de Mozambique, es la raíz del verbo "kungunyala", que significa "secarse o retorcido". La infección fue descrita por primera vez en Tanzania, África del Este, en los años 1952-1953, posteriormente se han descrito epidemias y brotes en diferentes áreas geográficas, particularmente África, Asia y otros lugares. Desde 2005 los casos se han incrementado y se le considera una enfermedad reemergente. El 06 de diciembre 2013 fue descrita por primera vez la fiebre Chikungunya en las Américas, informándose brotes autóctonos en las islas de San Martin (parte francesa) y Dominica, la enfermedad ya se ha extendido a otras islas del Caribe. La infección se transmite principalmente por la picadura del mosquito Aedes aegypti y A. albopictus, transmisores de dengue, también se transmite de madre a hijo (sobre todo cuando la madre adquiere la enfermedad en la culminación del embarazo), por trasplante de órganos y accidentes de laboratorio en trabajadores de la salud. La infección en los recién nacidos suele ser grave. El VCHIK, es un Alphavirus, de la familia Togaviridae y se han descrito tres genotipos; una mutación del virus en 2005 permitió una transmisión más eficiente por A. albopictus en el continente asiático. El PCR en tiempo real es el método recomendado para diagnóstico de la fase aguda de la infección. Las manifestaciones clínicas de la enfermedad son similares al dengue: fiebre elevada de inicio abrupto, dolor de espalda, cefalea y erupción cutánea. Las manifestaciones dermatológicas y oculares (tales como conjuntivitis) son frecuentes. Chikungunya se acompaña de una intensa artralgias y/o artritis incapacitante que puede durar semana, meses o años. La mayoría de los pacientes se recuperan después de dos a tres semanas. No hay tratamiento...

The chikungunya fever is a viral disease caused by Chikungunya virus (VCHIK). The word "chikungunya" is derived from the Makonde language, spoken by an ethnic group in southeast Tanzania and northern Mozambique, and is the root of the verb "kungunyala" meaning "dry or to become twisted". The infection was first described in Tanzania, East Africa in the years 1952-1953; after this outbreak, epidemics have been described in different geographical areas, particularly in Africa and Asia. Since 2005, cases have increased and Chikungunya is considered a reemerging disease. On December 6th, 2013 Chikungunya fever was first described in the Americas. There have been autochthonous outbreaks in St Martin and Dominica islands and the disease has already spread to other islands in the Caribbean. The infection is primarily transmitted by the bite of Aedes aegypti and A. albopictus, transmitters of dengue; it is also transmitted from mother to child, organ transplantation and accidents in health care workers. Pregnant women transmit the disease to the baby, especially when the disease is acquired in the culmination of pregnancy and the infection in newborns is usually severe. The etiologic agent is the Chikungunya virus, Alphavirus of the Togaviridae family. Three genotypes have been described, a mutation of the virus in 2005 allowed a more efficient transmission by A. albopictus in the Asian continent. In the acute stage the real-time PCR is the most recommended method. Clinical manifestations of the disease are very similar to dengue, sudden onset of high fever, arthralgia, back pain, headache and rash. Dermatological and ocular manifestations (such as conjunctivitis) are frequent. Chikungunya is accompanied by intense incapacitating arthralgia and/or arthritis, which can last for weeks, months or years. Most patients recover two to three weeks after the symptoms start. There is no specific treatment, neither a vaccoine for the prevention of disease...

Infección experimental de aislados humanos de Blastocystis sp. en ratones inmunosuprimidos con dexamentasona / Experimental infection using human isolates of Blastocystis sp. in dexamethasone immunosurpressed mice

Blastocystis sp. es un protozoario controversial en cuanto a su papel patogénico, asociado a enfermedad gastrointestinal, con alta prevalencia. A fin de evaluar signos, síntomas y hallazgos de laboratorio producidos por Blastocystis sp., ratones inmunosuprimidos con dexametasona fueron infectados con morfologías del parásito obtenidos de pacientes sintomáticos y asintomáticos. Los parásitos se aislaron empleando gradiente de densidad con lymphoprep™, se realizó semicuantificación de las morfologías presentes en las muestra de heces, y se inocularon 1,6 × 105 parásitos en ratones Balb/c, vía intragástrica. En heces de pacientes sintomáticos se encontraron seis veces más vacuolares que granulares, mientras que en asintomáticos la relación fue apenas dos veces mayor. Los síntomas más frecuentes en los pacientes fueron: flatulencia (85%), dolor de cabeza(62%), dolor abdominal (55%), fiebre (30%) y estreñimiento (8%). La semicuantificación de parásitos por campo en humanos no encontró relación directa entre carga parasitaria y sintomatología gastrointestinal, mientras que en la cuantificación de parásitos por gramo de heces si existió. Los ratones presentaron signos variables luego de la infección, todos aquellos infectados con muestras de pacientes sintomáticos presentaron signos, mientras que solo algunos de los infectados con muestras de pacientes asintomáticos los desarrollaron. Se demostró que no existe relación estadísticamente significativa (p= 0,8) entre la morfología del parásito y los signos manifestados por el ratón; sin embargo hubo una relación estadísticamente significativa (p=0,02) entre las formas vacuolares del parásito y la aparición de síntomas en los pacientes. Se concluye que Blastocystis sp. tiene capacidad de producir signos sugestivos de patología en ratones.

Blastocystis sp. is a controversial protozoan in terms of its pathogenic role associated with high-prevalence gastrointestinal disease. To evaluate signs, symptoms and laboratory findings produced by Blastocystis sp., dexamethasone immunosuppressed mice were infected with parasite morphologies obtained from symptomatic and asymptomatic patients. The parasites were isolated using density gradient with lymphoprep™, semi-quantification of the morphologies present in the stool sample was performed and 1.6 × 105 parasites were inoculated into Balb/c mice, intragastrically. In the faeces of symptomatic patients, vacuolar morphology was six times greater than granular morphology, whereas the ratio in asymptomatic patients was only two times greater. The most common symptoms in patients were flatulence (85%), headache (62%), abdominal pain (55%), fever (30%) and constipation (8%). The semi-quantification of parasites per field in humans evidenced no direct relationship between parasite burden and gastrointestinal symptoms, while in parasite quantification per gram of feces, a direct relationship was found. The mice showed variable signs after infection; all those infected with samples from symptomatic patients showed signs, while only some of those infected with samples from asymptomatic patients developed them. It was demonstrated that no statistically significant (p = 0.8) relationship exists between the morphology of the parasite and the signs manifested by the mouse; nevertheless, there was a statistically significant (p = 0.02) relationship between the vacuolar forms of the parasite and onset of symptoms in patients. Conclusions are that Blastocystis sp. is capable of producing signs suggestive of pathology in mice.

Clinical Features of Polyarteritis Nodosa in Korea

Polyarteritis nodosa (PAN) is a systemic vasculitis characterized by multi-organ involvement with protean manifestations. We evaluated the clinical features of PAN in Korea. Twenty-seven patients were diagnosed as PAN at Seoul National University Hospital between January 1990 and July 2003. The male-to-female ratio was 1.7:1 and mean age at onset (+/-SD) was 47.4+/-20 yr. Their presenting features at diagnosis were similar to those reported previously, i.e., myalgia, muscle weakness or leg tenderness (70%), fever (52%), weight loss >4 kg (44%), skin rash (44%), peripheral edema (33%), abdominal pain (33%), and arthralgia/arthritis (30%). However, the prevalence of testicular pain or tenderness was higher (24%) than reported previously and only three (11.5%) had HBsAg positivity without liver enzyme elevation. Nine patients (33%) had a five-factor score (FFS) of 2. Fourteen patients (52%) responded to treatment, 2 patients relapsed and 4 died within 1 yr of diagnosis. During a median follow-up of 55.5 months, three of the four PAN-related deaths had an initial FFS of 2. The clinical features of PAN were not significantly different from those reported previously. However, testicular pain or tenderness was more frequent and patients with a high FFS tended to have a poorer prognosis.

Parasitic infections presenting as prolonged fevers

Over 2 successive years, out of 187 cases of fevers of undetermined origin [FUO], 30 [16%] cases proved to be of parasitic origin. 10 within normal subjects were taken as controls. Complete blood picture, repeated stool examination, rectal snip by transparency technique, ELISA for specific IgM antibodies for S. mansoni, indirect hemagglutination test for S. mansoni, Fasciola, hydatid, amoebic liver abscess and toxoplasmosis, indirect fluorescent antibody test for toxoplasmosis and abdominal ultrasonography were performed whenever indicated. Cases comprised 8 [26%] acute S. mansoni, 7 [24%] acute fascioliasis, 3 [10%] hydatid cyst, 8 [26%] amoebic liver abscess, 2 [7%] toxoplasmosis and 2 [7%] malaria cases. The clinical picture of acute S. mansoni and acute fascioliasis were similar in the form of prolonged fever, diarrhea, hepatomegaly and leucocytosis with high eosinophilia. Serology [ELISA and IHAT] was essential in differentiating them. Abdominal ultrasonography is an easy, sensitive cheap, noninvasive technique aiding in the diagnosis of amoebic liver abscess, liver hydatid cysts and fascioliasis, but serology was essential in their differentiation

Malignant histiocytosis: a case report and review of the literature

Malignant histiocytosis [MH] is a rare hematologic malignancy, especially in the first decade of life. The disease is clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia and jaundice, and histologically by systemic proliferation of malignant histiocytes and hemophagocytosis. The prognosis is poor and often the diagnosis is not made before death. Because of the rarity of this disease, it is unusual for practitioners to diagnose it by bone marrow aspiration [BMA] alone

Malaria trends in general practice in Karachi, Pakistan

Malaria has been a common protozoal disease since times prehistoric. It has regained global importance after the emergence of drug-resistant strains of plasmodia and resistance of mosquitoes to commonly used insecticides. This study was done to assess the magnitude of malaria as a cause of febrile illness in Karachi and trends of malaria treatment in general practice. The malarial parasite was found present in peripheral blood of 456 out of 50.000 febrile patients [0.91%] and plasmodium falciparum was the predominant species [52%]. Trends in general practice regarding treatment of malaria are inappropriate and need to be brought in line and practiced according to the recommendations of W.H.O. Pharmaceutical drug promotion pressures must not be allowed to influence the principles and practice of scientific medical care in clinical practice

Thioguanine as single agent to achieve partial remission in adult acute non-lymphocytic leukaemia in poor risk patients

Ten adult patients with acute nonlymphoblastic leukemia of poor risk presented with either low platelet or low white blood cell count. We treated with single drug 6-thioguanine. There were 7 male and 3 females with mean age 35 years. Age ranged from 14 to 70 years. The majority of patients presented with anaemia, fever, petechial and haemorrhage, gum hypertrophy, splenomegaly. According to the French-American-British classification, 6 [60%] had differentiated myelopblastic leukemia [M2], 2 [20%] had acute promyelocytic leukemia [M3] one [10%] had acute myelomonocytic leukemia [M4] and one [10%] had acute monoblastic leukemia [M5]. They were treated with 6-thioguanine therapy. The Median leucocyte/platelet and blast were 12x10[9]/L, 24x10[9]/L and 62% respectively before the therapy. After the 6-thioguanine [2-3 courses], median leucocyte/platelet and blast were 3.7x10[9]/L. 105x10[9]/L and 14% respectively complete remission was not achieved in any of these patients, but they achieved good partial remission. Then they were subsequently received conventional D.A.T. regimen. There were minimal side effects. We found that the thioguanine is a safe, effective drug in acute non-lymphoblastic leukemia. When patient presents with low WBC/platelet count and no facility for blood component or growth factors available

Immunogenicity and reactogenicity of VI-typhoid vaccine in 2-10 years old children

A cohort of 200 children grouped according to the age: 2-1-3b months, 3G-17 months, 18-59 months and 5 years through 9 years and 11 months was studied for immunogenicity and reactogenicity. Each child received a single intramuscular injection of the Vi capsular polysaccharide typhoid vaccine [Typhim Vi]. Specific Vi antibodies were measured by passive haemagglutination on two blood samples a month before and after immunization. For each age group, results were expressed as an inverse of dilution and compared with one another. There was excellent seroconversiun in 98% of cases. Local and systemic reactions were evaluated at days 2 and 30. Among the 158 children who completed the study, 1.6% showed local reactions such as redness and pain at the site of injection and 3. 1% had a temperature of more than 38 §C. All reactions subsided within 18 hours and were mild. This study shows that Vi capsular polysaccharide typhoid vaccine is significantly immunogenic in children between 2-10 years of age and showed very few reactions. No reactions were observed on day 30

Typhus fevers in Iraq

Fourty patients with febrile illness without apparent cause that were admitted to Baghdad Teaching Hospital during a period of one year were screened for Rickettsia Conori and Rickettsia typhi infections. Six cases, R conori and one case with R. typhi were documented