Histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con virus de la inmunodeficiencia humana / Disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus

Introducción: La histoplasmosis es una micosis profunda o sistémica causada por un hongo dimórfico que se puede diseminar principalmente en pacientes con inmunosupresión, como los que tienen diagnóstico de virus de la inmunodeficiencia humana. El síndrome de reconstitución inmune consiste en un empeoramiento paradójico de una condición conocida o de nueva aparición después del inicio de la terapia antirretroviral. Objetivo: Describir un caso de histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con infección por virus de la inmunodeficiencia humana. Caso clínico: Paciente masculino de 32 años con diagnóstico de infección por virus de la inmunodeficiencia humana, con cuadro clínico de tres semanas de evolución. Este cuadro inició posterior al comienzo de la terapia antirretroviral, que consistió en pápulo-nódulos umbilicados diseminados, con compromiso pulmonar; además, tenía histopatología y cultivo positivos para Histoplasma capsulatum sl. y prueba de antigenuria para histoplasma también positiva. Se consideró un diagnóstico de histoplasmosis diseminada con presentación cutánea, fue la expresión de un síndrome de reconstitución inmune por desenmascaramiento. Se inició manejo con anfotericina B liposomal y se mantuvo la terapia antirretroviral; posteriormente se continuó el tratamiento con itraconazol durante 12 meses con mejoría de las lesiones. Conclusiones: El diagnóstico clínico, histopatológico y microbiológico fue oportuno; el paciente presentó una adecuada respuesta al tratamiento. Esta es una micosis curable e incluso prevenible, si se diagnostica a tiempo, se inicia tratamiento precoz y se mantiene la terapia retroviral(AU)

Introduction: Histoplasmosis is a deep or systemic mycosis caused by a dimorphic fungus which may disseminate mainly in immunocompromised patients, such as those diagnosed with human immunodeficiency virus. Immune reconstitution syndrome is a paradoxical worsening of a known condition or a condition appearing after the start of antiretroviral therapy. Objective: Describe a case of disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus infection. Case report: A case is presented of a male 32-year-old patient diagnosed with human immunodeficiency virus with a clinical status of three weeks' evolution. The current status developed after the start of antiretroviral therapy. It consisted in disseminated umbilicated papular nodules with pulmonary involvement, as well as positive Histoplasma capsulatum sl. histopathology and culture, and a positive histoplasma antigen test. A diagnosis of disseminated histoplasmosis with a cutaneous presentation was considered. It was the expression of immune reconstitution syndrome by unmasking. Treatment was started with liposomal amphotericin B, maintaining the antiretroviral therapy. Management was then continued with itraconazole for 12 months with improvement of the lesions. Conclusions: Timely clinical, histopathological and microbiological diagnosis was performed. The patient displayed an adequate response to treatment. This mycosis is curable and even preventable when a diagnosis is made in time, treatment is started early and the retroviral therapy is maintained(AU)

Síndrome Inflamatorio Multi Sistémico Asociado a COVID-19 en Pediatría / Multi-Systemic Inflammatory Syndrome Associated with COVID-19 in Pediatrics

En Marzo 2020, la Organización Mundial de la Salud declara la pandemia provocada por el coronavirus deno- minado SARS COV-2 causando la enfermedad denomi- nada Covid-19. Esta pandemia tuvo y tiene un impacto planetario nunca visto con un virus que demostró alta transmisibilidad y capacidad de diseminación. Durante varios meses se consideró que los adultos eran el grupo etario más afectado con una alta mortalidad en el adul- to mayor, considerándose que los niños podían conta- giarse pero cursando la enfermedad en forma benigna. Cabe mencionar que, en Argentina, los niños y adoles- centes representan alrededor entre 15 al 17% de los ca- sos de Covid-19 oficialmente reportados por el Minis- terio de Salud. Posteriormente, se observó en los niños que la enfermedad Covid-19 en ocasiones, presentaba complicaciones graves afectando diversos órganos, en otras series, los pacientes padecían cuadros fenotípicos de Kawasaki y en otras oportunidades cuadros mixtos de compromisos múltiples y hallazgos de esta última enfermedad. El cuadro tiene diversas denominaciones según los países pero en Argentina fue descripto por el Ministerio de Salud como "Sindrome Inflamatorio Mul- tisistémico post-Covid" (SIM-C). En realidad el cuadro no siempre es posterior a la enfermedad sino también puede ocurrir dentro del cuadro agudo de los primeros 14 días y se engloba en lo conocido como estados de hiperinflamación, actuando el virus como un superantí- geno y respuesta inmunomediada con impacto en órga- nos importantes como corazón, intestino, y el riesgo de shock. Este cuadro está excelentemente descripto y ac- tualizado en el artículo publicado por las Dras. Alvarez y Espada quienes introducen que estos cuadros forman parte de los síndromes de hiperferritinemias, entidad sindromática poco pensada por los pediatras. Es posible que futuras investigaciones puedan demostrar algunas características genéticas para esta complicación que es poco frecuente en niños y adolescentes. Su mortalidad está estimada en 1,8% por el CDC. Es importante recor- dar que se debe tener confirmación virológica ya sea PCR en tracto respiratorio superior o serología positiva para el SARS CO2 y/o nexo epidemiológico. Este tipo de complicación requiere manejo de equipos multidisci- plinarios y atención en Unidad de Cuidados Intensivos (UCI), si bien algunos autores consideran que los pa- cientes "compensados" pueden manejarse en unidades de internación general, pero debe hacerse en instituciones que tengan UCI.

Meningoencefalitis por herpesvirus varicelazóster como síndrome inflamatorio de reconstitución inmune. Una manifestación clínica infrecuente / VARICELLA-ZOSTER HERPESVIRUS MENINGOENCEPHALITIS AS AN INFLAMMATORY SYNDROME OF IMMUNE RECONSTITUTION. An uncommon clinical manifestation

El uso cada vez más difundido de la terapia antirretroviral de gran actividad (TARGA) en el tratamiento de los pacientes con infección por el virus de la inmunodeficiencia humana (VIH) puede dar lugar a respuestas paradojales, caracterizadas por un empeoramiento de las manifestaciones clínicas o la reactivación de ciertas infecciones oportunistas, hasta ese momento subclínicas, como el Herpes varicela-zóster (HVZ). Este cuadro clínico se conoce desde hace años como síndrome inflamatorio de reconstitución inmune (SIRI). Puede afectar a más del 30% de los pacientes seropositivos para el VIH con un tiempo de aparición promedio de 8 a 12 semanas luego del inicio o cambio de TARGA. El HZ mucocutáneo representa entre el 7% al 12% de los episodios de SIRI en estos pacientes. En este trabajo, se presenta un paciente VIH seropositivo que desarrolló un episodio de HVZ cutáneo monometamérico asociado a compromiso del sistema nervioso central bajo la forma de un síndrome meningoencefalítico

The use of highly active antiretroviral therapy (HAART) in the management of human immunodeficiency virus (HIV) infection has resulted in a paradoxical response associated with the worsening of clinical symptoms of previously subclinical infections, such as herpes varicella-zoster (HVZ). This clinical picture is named as immune reconstitution inflammatory syndrome (IRIS). It may affect up to 30% of HIV-seropositive subjects within a wide range of time after the initiation or change of HAART, but mainly after 8 to 12 weeks. Mucocutaneous HZ accounts for 7%-12% of the diseases associated with HIV infection in patients with immune reconstitution from the administration of HAART. Here we present an HIV seropositive patient that developed an episode of cutaneous metameric eruption of HVZ associated with central nervous system involvement as meningoencephalitis syndrome.

Tuberculosis y síndrome inflamatorio de reconstitución inmunológica. Caso pediátrico / Tuberculosis and immune reconstitution inflammatory syndrome. Pediatric case

La tuberculosis es una enfermedad muy frecuente en nuestro medio. A pesar de que la detección precoz y el tratamiento adecuado logran la curación en la mayoría de los pacientes, la dificultad en el diagnóstico, el abandono del tratamiento y la aparición de resistencia a los fármacos tradicionales generan que, en la actualidad, continúe siendo un importante problema de salud pública. En la Argentina, la tasa de morbilidad es de 25/100 000 habitantes, con un leve aumento en la mortalidad.Se presenta el caso de una paciente pediátrica con tuberculosis, que tuvo múltiples complicaciones asociadas a la enfermedad y a su tratamiento, entre las cuales se incluye el síndrome in-flamatorio de reconstitución inmunológica, también conocido como reacción paradojal al tratamiento antituberculoso. Este representa una consecuencia clínica adversa al restablecimien-to de la inmunidad en el paciente que padece una infección sistémica grave, como la tuberculosis miliar.

Tuberculosis is a very frequent disease in our environment. Although early detection and adequate treatment achieve cure in most patients, the difficulty in diagnosis, the abandonment of treatment and the appearance of resistance to traditional drugs generate that at present it continues to represent an im-portant public health problem. In Argentina, the morbidity rate is 25/100,000 inhabitants, with a slight increase in mortality.We present the case of a pediatric patient with tuberculosis and multiple complications associated with the disease and its treatment. One of these complications was the immune re-constitution inflammatory syndrome or paradoxical reaction to antituberculosis treatment. It represents an adverse clinical con-sequence of the restoration of immunity in the patient suffering from a serious systemic infection such as miliary tuberculosis.

Altered T cell and monocyte subsets in prolonged immune reconstitution inflammatory syndrome related with DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.

Perforación intestinal por citomegalovirus durante un Síndrome de Reconstitución Inmune / Intestinal Perforation for Cytomegalovirus in Immune Reconstitution Syndrome

RESUMEN El síndrome de reconstitución inmune se produce debido a un aumento de la inmunocompetencia en pacientes previamente inmunocomprometidos. La situación es frecuente tras iniciar un tratamiento antirretroviral de alta eficacia, en pacientes con infección por el virus de inmunodeficiencia humana. En determinados casos, puede conllevar un empeoramiento paradójico de una infección previa. El citomegalovirus, es un germen oportunista que, en el seno de un síndrome de reconstitución inmune, puede dar lugar a perforación intestinal multifocal y peritonitis secundaria de difícil tratamiento. Es más frecuente en pacientes con recuento de linfocitos cooperadores inferior a 50 células/mm3 al iniciar el tratamiento antirretroviral. El objetivo es comunicar dicha situación a través, de un caso clínico para facilitar su sospecha lo más pronto posible, y realizar un tratamiento adecuado. Presentamos el caso de un paciente con virus de inmunideficiencia humana de reciente diagnóstico, en tratamiento con terapia antirretroviral de alta eficacia, que acude a urgencias con abdomen agudo secundario a perforación por citomegalovirus. La infección conlleva importante morbimortalidad, siendo imprescindible un diagnóstico temprano e iniciar precozmente el tratamiento antiviral intravenoso, asociado generalmente a tratamiento quirúrgico(AU)

ABSTRACT Immune reconstitution syndrome occurs due to increased immunocompetence in previously immunocompetent patients. The condition is frequent in patients with human immunodeficiency virus infection who have started a highly active antiretroviral therapy. In certain cases, the syndrome can lead to a paradoxical worsening of a previous infection. Cytomegalovirus is an opportunistic germ that, during an immune reconstitution syndrome, can lead to multifocal intestinal perforation and secondary peritonitis, in cases that are difficult to treat. The syndrome is more frequent in patients with CD4 lymphocyte count below 50/mm3 at the time of starting antiretroviral treatment. The objective is to communicate this situation through a clinical case presentation in order to facilitate suspicion as soon as possible, and to carry out appropriate treatment. We present the case of a patient with a recently diagnosed human immunodeficiency virus, under treatment with highly active antiretroviral therapy, who attended the emergency department with an acute abdomen secondary to perforation due to cytomegalovirus. Infection carries significant morbidity and mortality, and early diagnosis is essential and intravenous antiviral treatment should be started early, generally associated with surgical treatment(AU)

Criptococosis cerebral, voriconazol, niveles plasmáticos y síndrome de reconstitución inmune: reporte de un caso / Cerebral cryptococcosis and immune reconstitution inflammatory syndrome: case report

We report a 45-year-old male with AIDS who had a Cryptococcus neoformans central nervous system infection. He was treated with amphotericin B deoxycholate subsequently changed to voriconazole due to systemic toxicity of the former. Plasma levels of voriconazole were insufficient with a standard dose (0.7 μg/mL), therefore, the dose was increased thereafter to reach appropriate levels (4.5 μg/mL). Anti-retroviral therapy was started five weeks after voriconazole initiation with non-interacting drugs and he was discharged after a favorable evolution. He was re-admitted three months later due to seizures; a brain magnetic resonance showed new sub-cortical nodules. After excluding alternative causes and demonstrating fungal eradication, an immune reconstitution inflammatory syndrome (IRIS) event was suspected and treated with a short course of steroids. His evolution was satisfactory.

Assessing endocrine and immune parameters in human immunodeficiency virus-infected patients before and after the immune reconstitution inflammatory syndrome

ABSTRACT Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p < 0.05) in IRIS-P than in non-IRIS-P (3.9 ± 1.0 pg/mL and 461.0 ± 84.4 pg/mL, respectively) BT. Mean T4 plasma level significantly decreased in both groups of patients after treatment (p < 0.05). In both groups cortisol levels were similar before and after ART (p > 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease.

Mycobacterium avium Complex Infection-Related Immune Reconstitution Inflammatory Syndrome Mimicking Lymphoma in an Human Immunodeficiency Virus-Infected Patient

In acquired immunodeficiency syndrome (AIDS) patients, immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium complex (MAC) infection is one of the most difficult IRIS types to manage. We report an unusual case of MAC-associated IRIS. At first the patient was diagnosed human immunodeficiency virus (HIV) infection after he was admitted with pneumocystis pneumonia. After starting antiretroviral therapy he presented unmasked IRIS with MAC infection. Next, he was hospitalized with continuous loose stools and new-onset fever. Investigation included computed tomography (CT), which showed homogeneous enhancement and enlargement of the lymph nodes (LN), elevation of ferritin (>1,650 ng/mL) and lactate dehydrogenase (306 IU/L) levels, and F- fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan, which showed increased FDG uptake. These findings were highly indicative of lymphoma. We performed laparoscopic biopsy of the mesenteric LN, and the biopsy culture grew MAC. So we made a diagnosis of MAC-associated. Therefore, IRIS must be considered as a possible diagnosis when AIDS patients develop new symptoms or exhibit exacerbations of existing symptoms. Furthermore the biopsies should be conducted.

Mycobacterium avium Complex Infection-Related Immune Reconstitution Inflammatory Syndrome Mimicking Lymphoma in an Human Immunodeficiency Virus-Infected Patient

In acquired immunodeficiency syndrome (AIDS) patients, immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium complex (MAC) infection is one of the most difficult IRIS types to manage. We report an unusual case of MAC-associated IRIS. At first the patient was diagnosed human immunodeficiency virus (HIV) infection after he was admitted with pneumocystis pneumonia. After starting antiretroviral therapy he presented unmasked IRIS with MAC infection. Next, he was hospitalized with continuous loose stools and new-onset fever. Investigation included computed tomography (CT), which showed homogeneous enhancement and enlargement of the lymph nodes (LN), elevation of ferritin (>1,650 ng/mL) and lactate dehydrogenase (306 IU/L) levels, and F- fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan, which showed increased FDG uptake. These findings were highly indicative of lymphoma. We performed laparoscopic biopsy of the mesenteric LN, and the biopsy culture grew MAC. So we made a diagnosis of MAC-associated. Therefore, IRIS must be considered as a possible diagnosis when AIDS patients develop new symptoms or exhibit exacerbations of existing symptoms. Furthermore the biopsies should be conducted.

Cutaneous tuberculosis and HIV infection at a referral centre in Rio de Janeiro, Brazil

BACKGROUND Cutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported. OBJECTIVE To describe CTB cases among patients with HIV infection from a cohort with tuberculosis. METHODS We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node. FINDINGS Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome. CONCLUSIONS In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

Síndrome inflamatória de reconstituição imune como causa de hepatite autoimune e insuficiência hepática aguda / Immune reconstitution inflammatory syndrome as a cause of autoimmune hepatitis and acute liver failure

RESUMO A insuficiência hepática aguda é uma síndrome rara com elevada mortalidade e frequentemente reconhecida de forma tardia. Os médicos intensivistas desempenham um papel fundamental na suspeição diagnóstica e no manejo das disfunções múltiplo-orgânicas características desta entidade. A síndrome inflamatória de reconstituição imune é uma entidade que se caracteriza pela piora paradoxal do quadro prévio do paciente, após o início de antirretrovirais, desencadeada contra patógenos presentes no hospedeiro ou autoantígenos. A hepatite autoimune tem sido recentemente descrita como uma destas manifestações autoimunes. Os autores relatam o primeiro caso com evolução à insuficiência hepática aguda e óbito em poucos dias após o desenvolvimento de encefalopatia, revisam os casos de hepatite autoimune descritos e tecem comentários sobre as possibilidades terapêuticas neste contexto.

ABSTRACT Acute liver failure is a rare syndrome with high mortality and is often diagnosed late. Intensivist physicians play fundamental roles in the diagnostic suspicion and the management of the multiple-organic dysfunctions characteristic of this entity. Immune reconstitution inflammatory syndrome is an entity that is characterized by the paradoxical worsening of the patient's previous condition, after the initiation of antiretrovirals, triggered against either pathogens present in the host or autoantigens. Autoimmune hepatitis has recently been described as one of these autoimmune manifestations. The authors report the first case with evolution to acute liver failure and death within a few days after the development of encephalopathy, review the cases of autoimmune hepatitis described and comment on the therapeutic possibilities in this context.

Síndrome de reconstitución inmune / Immune reconstitution syndrome

ResumenEl síndrome inflamatorio de reconstitución inmune se presenta en pacientes con infección por VIH o infección avanzada por el virus, días, semanas o meses después del inicio de la terapia antirretroviral. Se caracteriza por una restauración gradual de la inmunidad patógeno-específica donde el sistema inmune es capaz de reconocer atógenos presentes pero clínicamente ocultos. Característicamente se presenta después de iniciar la TARV cuando el sistema inmunitario comienza a recuperarse. Puede ser leve o potencialmente mortal.

AbstractThe immune reconstitution inflammatory syndrome occurs in patients with advanced HIV infection or HIV infection, days, weeks or months after initiation of antiretroviral therapy. It is characterized by a gradual restoration of pathogen specific immunity where the immune system is able to recognize pathogens presents but clinically occult.Characteristically it occurs after starting antiretroviral therapy when the immune system starts to recover. It can be mild or life threatening.

Voriconazole-refractory invasive aspergillosis

Invasive aspergillosis (IA) is one of the most common life-threatening complications in immunocompromised patients. Voriconazole is currently the drug of choice for IA treatment. However, some patients with IA suffer clinical deterioration despite voriconazole therapy. Management of voriconazole-refractory IA remains challenging; no useful recommendations have yet been made. Voriconazole-refractory IA can be further categorized as disease attributable to misdiagnosis or co-infection with another mold; inadequate blood voriconazole blood; inadequate tissue drug concentrations attributable to angioinvasion; immune reconstitution inflammatory syndrome; or infection with voriconazole-resistant Aspergillus. Hence, when encountering a case of voriconazole-refractory IA, it is necessary to schedule sequential tests to decide whether medical treatment or surgical intervention is appropriate; to adjust the voriconazole dose via drug monitoring; to seek CYp2c19 polymorphisms; to monitor serum galactomannan levels; and to examine the drug susceptibility of the causative Aspergillus species.

Lepromatous leprosy and human immunodeficiency virus co-infection associated with phenomenon of Lucio versus immune reconstitution inflammatory syndrome / Lepra lepromatosa y coinfección con el virus de la inmunodeficiencia humana asociada a fenómeno de Lucio versus síndrome inflamatorio de reconstitución inmune

Diffuse lepromatous leprosy (DLL) is a severe clinical outcome of lepromatous leprosy (LL). The aetiologic cause is believed to be different from Mycobacterium leprae. A new species, Mycobacterium lepromatosis, was identified from a group of Mexican patients with DLL, and severe leprosy reactional state type 3 (Lucio's phenomenon). However, a total sequencing of its genome is necessary to prove the existence of this new species. This is a report on a non-typical Colombian case of leprosy - HIV coinfection, associated with an immune reconstitution inflammatory syndrome clinically compatible with a leprosy reaction type 3 or Lucio's phenomenon.

La lepra difusa (LLD) es una variedad de la lepra lepromatosa (LL), frecuente enMéxico. El agente etiológico se cree que es diferente a Mycobacterium leprae y se considerauna especie nueva denominada Mycobacterium lepromatosis, hecho que no se ha comprobado.El reporte de este caso se realiza para dar a conocer el cuadro clínico atípico que presentóuna paciente colombiana con coinfección VIH---LL variedad difusa (LLD), asociado a síndromede reconstitución inmunológica, compatible clínicamente con una leprorreacción tipo 3 o fenó-meno de Lucio.

Unmasking histoplasmosis immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral therapy

Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution. After 2 weeks of amphotericin B and itraconazole therapy, the scheduled treatment involved fluconazole maintenance therapy, which resulted in an improvement of his skin lesions.

O uso de Modelos de Equações Estruturais na análise dos principais mecanismos de desenvolvimento de lipodistrofia em pessoas vivendo com HIV/AIDS / The use of Structural Equation Modeling analysis of main lipodystrophy development mechanisms in people living with HIV / AIDS

A tese tem por objetivo identificar diferentes padrões: resposta imunológica através das trajetórias da carga viral, CD4 e os regimes de tratamento com antirretrovirais e verificar associação com o desenvolvimento de lipodistrofia (LD). Estudou-se uma coorte prospectiva de 912 pacientes, durante cinco anos, com mensurações repetidas de CD4 e carga viral. Utilizou-se análise de equações estruturais com uso de classes latentes para identificar o modelo com o melhor número de trajetórias de CD4, carga viral, regime tratamento e drogas antirretrovirais com base em parâmetros estatísticos, e a associação dessas trajetórias com o desenvolvimento de LD por meio de regressão logística. A prevalência da LD na primeira reavaliação foi 40,6%, chegando a 77,6%. As trajetórias déficit imunológico temporário, déficit imunológico mantido e carga viral alta mostraram associação com o desenvolvimento de LD na análise univariada; depois de controladas pelos fatores de confusão, apenas déficit imunológico mantido e carga viral alta permaneceram associadas. As variáveis compostas proxy da reconstituição imunológica e da imunodeficiência, apresentaram forte associação com a LD. Agrupando essas duas últimas variáveis em uma categoria, encontra-se uma forte associação com a LD. Na análise do tratamento antirretroviral observou-se que os regimes Inibidor de Transcriptase Reversa análogos de Nucleosídeos (ITRN)+ Inibidor de Transcriptase Reversa não análogos de Nucleosídeos (ITRNN) estavam associados ao desenvolvimento da LD e não havia diferença entre os indivíduos tratados e não tratados. Entre as classes latentes verificou-se associação com o desenvolvimento da LD dos regimes ITRN+ITRNN e das drogas Lamivudina (3TC)+Zidovudina (AZT)+Nevirapina (NVP) e 3TC+Tenofovir (TDF)+Efavirenz (EFV). O uso das trajetórias permitiu identificar padrões de resposta imunológica e o envolvimento do regime ITRNN associados à LD, e esta pode ocorrer devido à exposição à TARV ou apenas pela exposição ao HIV. Os modelos de equações estruturais mostraram superar as ferramentas tradicionais que, apesar de eficientes, muitas vezes não são sensíveis suficiente para detectar possíveis características ou comportamentos implícitos

The thesis aims to identify different patterns: immune response through the paths of viral load and CD4, treatment regimens and antiretroviral drug combinations and verify association with the development of lipodystrophy (LD).This was a cohort of 912 patients followed up over a period of 5years, with repeated CD4 count and viral load measurements. A structural equation analysis was conducted to identify the model with the bestnumber of CD4, viral load, treatment regimen and antiretroviral drugstrajectories, based on statistical parameters (entropy and bic), and through logistic regression, the association of these trajectories with the development of lipodystrophy. The prevalence of LD on the first visit after baseline assessment of cohort was 40.6% reaching 77.6%. The trajectories temporary immune gap, sustainedimmune gapand high viral load were associated with the development of LD in the univariate analysisand, after control for confounders, only sustained immune gap and high viral load remained associated. Composite proxy variables of immune reconstitution and immunodeficiency, suggesting the underlying inflammation, demonstratedanassociation with the LD, despite the wide confidence interval. Grouping the twolastvariables into one category, we encountereda strong association with LD. In the analysisof antiretroviral treatment (ART), it was observed that the Nucleoside reverse transcriptase inhibitors (NRTI) +Non-nucleoside reverse transcriptase inhibitors (NNRTI)regimens were associated with the development of the LD and there was no difference between treated and untreated individuals. Among the latent classes found an association of the NRTI+NNRTI regimens and combination of drugs lamivudine (3TC) +zidovudine (AZT) +nevirapine (NVP)and tenofovir (TDF) +3TC+efavirenz (EFV)with the development of LD. The use of trajectories allowed us to identifythe immunologicalresponse patterns and the involvement of NNRTI regimeassociated with the LD and that LD can occur due to ART exposure or just by HIV virus exposure. The structural equation modeling showed to overcome the traditional tools which although effective, are often not sensitive enough to detect possible features or implied behavior.

Leprosy presenting as immune reconstitution inflammatory syndrome - report of three cases

The introduction of highly active antiretroviral treatment [HAART] has led to the emergence of a new clinical syndrome, immune reconstitution inflammatory syndrome [IRIS]. This syndrome affects human immunodeficiency virus [HIV]- positive patients at an advanced stage of the disease [CD4 lymphocyte counts 200/micro L]. In these patients, clinical signs of inflammation appear mostly in association with opportunistic infection, when HAART triggers a generalized immune activation during the transition phase of viral load suppression and CD4 lymphocyte counts increase. The infectious agent may have been treated previously or may have been present in a latent state, but is always present in the patient's body before the introduction of antiretroviral treatment. In the first situation, the opportunistic infection, which is initially improved by specific treatment, then leads to generalized or localized inflammation. In the second situation, the opportunistic infection is first detected when the CD4 lymphocyte count increases. In the first reported cases of IRIS, in 1998, the infectious agents were mycobacteria [Mycobacterium avium complex and M tuberculosis]. The syndrome has since been described in association with more than a dozen different infectious conditions, with herpes zoster [41 cases], M tuberculosis [37 cases], M avium complex [32 cases], and cytomegalovirus [22 cases] in 73% of the first 182 published cases. In some cases, IRIS appears in the absence of opportunistic pathogens and manifests itself as an autoimmune or granulomatous disease, of which sarcoidosis is the most frequent [10 cases]. The first case of leprosy diagnosed after HAART initiation was reported in 2003. We herewith report three cases of leprosy presenting as IRIS as the first manifestation

Manejo da síndrome de reconstituição imunológica / Immune reconstitution syndrome management

Com o aumento da incidência de pessoas infectadas pelo HIV e também dos portadores de outras condições clínicas que levam à imunossupressão, é fundamental o reconhecimento da Síndrome de Resconstituição Imunológica, bem como o entendimento de seu manejo. O objetivo deste artigo é fazer uma revisão sobre seu manejo, tão pouco discutido.

The Diagnosis of Immune Reconstitution Inflammatory Syndrome as well as the understanding of its management is extremely important considering the increasing incidence of HIV infected patients and of other medical conditions that lead to immunosuppression. The goal of this article is to review the management of this syndrome, sometimes neglected.