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.

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 inflamatorio de reconstitución inmune (SIRI) en pacientes pediátricos que acuden a la consulta de VIH/SIDA del servicio de pediatría médica infecciosa del Hospital Universitario de Caracas / Immune reconstitution inflammatory syndrome (IRIS) in pediatric patients attending consultation HIV / AIDS medical service pediatric infectious Hospital Universitario de Caracas

La Organización Mundial de la Salud define al síndrome inflamatorio de reconstitución inmune (SIRI) como un grupo de signos y síntomas que resultan de la recuperación inmunológica del paciente VIH/SIDA después del inicio de la terapia retroviral de gran actividad (TARGA) cuya incidencia es del 10% al 25%. Estudiar los pacientes con diagnóstico de infección por VIH controlados en el Servicio de Pediatría Médica Infecciosa del Hospital Universitario de Caracas que desarrollaron SIRI. Se realizó estudio retrospectivo con revisión de datos de pacientes pediátricos con diagnóstico de VIH que presentaron SIRI. Los mismos fueron recabados de la base de datos de la consulta VIH/SIDA diseñada en Access 2010 y analizados con EPIINFO 3.5.4. El 15% de los pacientes con diagnóstico de VIH presentaron SIRI, siendo del sexo masculino 80%; 60% fueron clasificados inicialmente en estadio C3. La edad media fue de 5,26 años, (SD: ± 4,34). La carga viral de inicio de TARGA 320.318 copias/mL (SD: ± 260 727), contaje de linfocitos T CD4+: 127 células/mm³ (SD:±148) relación CD4/CD8: 0,17 (SD: ± 0,11); TARGA inicial: 90% utilizaron 3TC, 60% AZT, 40% ABC y 80% inhibidores de proteasa. Las manifestaciones clínicas más frecuentemente observadas fueron BCGitis (30%), tuberculosis (30%) y neumocistosis (20%). En un 90% las manifestaciones de SIRI ocurrieron en los primeros 3 meses de iniciado TARGA. Al momento del SIRI se observó en promedio un aumento del contaje de linfocitos T CD4+ en 411 células/mL y disminución de CV en 2 log. El SIRI es frecuente en pacientes pediátricos con VIH/SIDA y debe ser tomado en cuenta cuando se inicia tratamiento en estados severos de inmunodepresión

The World Health Organization defines the Immune Reconstitution Inflammatory Syndrome (IRIS) as a group of signs and symptoms as a result of the HIV/AIDS patients’ immune recovery after initiation of highly active antiretroviral therapy (HAART), being the incidence 10% to 25%. To study patients with HIV infection in control at the Pediatric Infectious Service of University Hospital of Caracas who developed IRIS. Retrospective data review of pediatric patients diagnosed with HIV who presented SIRI was performed. It was collected from 2010 Access - designed HIV/AIDS consultation database and analyzed with EPIINFO 3.5.4. 15% of patients diagnosed with HIV had IRIS, being 80% male, 60% were initially classified C3 stage. The average age was 5.26 years (SD: +4.34). Viral load (VL) starting HAART: 320 318 copies/mL (SD: ± 260,727), CD4 ± count: 127 cells/mm³ (SD: +148), CD4/CD8: 0.17 (SD: +0.11); initial HAART used: 90% 3TC,60% AZT, 40% ABC and 80% protease inhibitors. The most frequently clinical features observed were: BCGitis (30%), tuberculosis (30%) and pneumocystosis (20%). SIRI manifestations occurred, in 90% of cases, in the first 3 months after initiation of HAART. At the moment of IRIS diagnosis, an average CD4 + T count at 411 cells/ml increase and 2 log VL decreases were recorded. SIRI is common in HIV pediatric patients and should be considered when treatment is started in severe immunosuppression state

Síndrome de opsoclonia-mioclonia-ataxia em paciente com AIDS / Opsoclonus-myoclonus-ataxia syndrome in an AIDS patient

É relatado aqui o caso de uma mulher de 38 anos com AIDS que desenvolveu a síndrome de opsoclonia-mioclonia-ataxia em um período diferente dos outros casos já relatados na literatura. A síndrome de opsoclonia-mioclonia-ataxia já tinha sido relatada como manifestação inicial de AIDS, assim como no momento da soroconversão de HIV e na síndrome de reconstituição imune. Este caso é único, uma vez que a paciente tinha contagem elevada de CD4 e carga viral negativa no momento em que a síndrome de opsoclonia-mioclonia-ataxia ocorreu.

We report the case of a 38-year-old woman with AIDS who developed opsoclonus-myoclonus-ataxia syndrome during a period different from other cases reported in literature. Opsoclonus-myoclonus-ataxia syndrome had already been reported as the initial neurological presentation of AIDS, as well as at the time of HIV-seroconversion and immune reconstitution syndrome. Our case is unique since the patient had an elevated CD4 count and negative viral load in the period when the opsoclonus-myoclonus-ataxia syndrome occurred.

Síndrome de reconstitución inmune por BCG en niños tratados por VIH / Immune reconstitution syndrome due to BCG in HIV-treated children

El objetivo del estudio fue describir el perfil clínico del síndrome de reconstitución inmune por Mycobacterium bovis Bacillus Calmette-Guérin (SIRI-BCG) en niños con infección VIH que reciben tratamiento antirretroviral de gran actividad (TARGA) en el Instituto Nacional de Salud del Niño de Lima, Perú. Se realizó un estudio de serie de casos, que incluyó ocho niños con SIRI-BCG, definido como la presencia de linfadenopatía regional o inflamación en sitio de inoculación de BCG con disminución de al menos un logaritmo en la carga viral o mejoría inmunológica. Todos los pacientes tenían estadio SIDA (C3). La mediana de edad de inicio del TARGA fue de 7,2 meses y el evento se produjo entre 3 a 11 semanas luego de haberlo iniciado. En siete casos se produjo adenitis axilar. Al comparar con el grupo sin SIRI-BCG se encontró asociación significativa con la edad de inicio del TARGA de un año, estado de inmunodepresión severa, y carga viral incrementada. Se concluye que el SIRI-BCG está relacionado con una rápida progresión clínica de la infección VIH/SIDA de trasmisión vertical, estadio de inmunosupresión severa, y carga viral alta al momento del inicio del TARGA.

The objective of this study is to describe the clinical profile of the immune reconstitution syndrome due to Mycobacterium bovis Bacillus Calmette-Guérin (IRS-BCG) in children with HIV infection who receive highly active antiretroviral treatment (HAART) at Instituto Nacional de Salud del Niño de Lima (National Children’s Health Institute of Lima), Peru. A case study was conducted, including 8 children with IRS-BCG, defined as the presence of regional lymphadenopathy or inflammation on the BCG vaccination site with at least one less logarithm in the viral load or immune improvement. All patients had AIDS (C3). The starting median age in HAART was 7.2 months and the event occurred 3 to 11 weeks after the treatment was started. 7 cases showed axillary adenitis. When compared with the Non IRS-BCG group, a significant association between the age at which HAART was started at one year, severe immunodepression, and increased viral load was found. It is concluded that IRS-BCG was related to a rapid clinical progression of the mother-to-child transmitted HIV/AIDS infection, severe immunosuppression and high viral load when the HAART began.

Incidence and risk factors of immune reconstitution inflammatory syndrome in HIV-TB coinfected patients

Tuberculosis is one of the leading causes of development of Immune reconstitution inflammatory syndrome (IRIS) in HIV patients receiving antiretroviral therapy (ART). OBJECTIVE: To determine the incidence of IRIS in HIV-TB coinfected patients, and to find out the possible risk factors associated with IRIS. MATERIALS AND METHODS: Study commenced with 96 patients adhered to standard antitubercular therapy (ATT) and ART without defaultering, and followed up for six months. RESULT: The mean (± SD) CD4 count and CD4 percentage at baseline was 59.16 (± 24.63) per mm³ and 4.59 percent (± 1.73) respectively. Only 18.75 percent developed IRIS after 57.05 (± 14.12) days of initiation of ART. Extrapulmonary tuberculosis was the most significant factor associated with IRIS (83.33 percent) than those without IRIS (44.87 percent) (p = 0.0032). Specifically, tubercular lymphadenitis (38.88 percent, p = 0.0364) and disseminated tuberculosis (33.33 percent, p = 0.0217) were significantly associated with IRIS. The other risk factors associated with appearance of IRIS were higher CD4 count (p = 0.0212) at three months after initiation of ART and increment of CD4 count (p = 0.0063) and CD4 percentage (p = 0.0016) during this period. The major manifestations of IRIS were fever (40 percent), followed by lymphadenitis (38 percent). The mortality rate in IRIS was not higher than those without IRIS. CONCLUSION: Patients with extrapulmonary tuberculosis, especially tubercular lymphadenitis, were more likely to develop IRIS and fever was associated in most of them. Higher increment of CD4 count may indicate development of IRIS in presence of new or worsening tuberculosis lesion.

Bronchoscopy and endobronchial disease in patients with human immunodeficiency virus infection.

The natural history of human immunodeficiency virus (HIV) infection has been significantly altered since the advent of antiretroviral therapy (ART). However, lung diseases are still common in these patients. This makes flexible fibreoptic bronchoscopy a valuable diagnostic tool. Knowledge of the visual appearance of various diseases would be of utmost importance to the bronchoscopist. Timely recognition of the endobronchial appearance of these diseases can narrow the differential diagnosis and potentially mitigate an avoidable delay in the diagnosis.

A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition.

Background & objectives: A considerable proportion of patients with HIV associated tuberculosis (TB) started on highly active antiretroviral therapy (HAART) develop immune reconstitution inflammatory syndrome (IRIS), which is difficult to diagnose in a resource-limited setting. In view of the recently proposed consensus case-definitions for TB-IRIS for use in resource-limited settings we undertook this study to describe the incidence and risk factors of TB associated IRIS in a tertiary care hospital and research centre in north India. Methods: Retrospective analysis of antiretroviral treatment (ART) naïve adults started on highly active ART (HAART) from June 2006 to September 2008 was done. Results: Of the 627 patients studied, 237 (38%) had TB at the initiation of HAART. In total, 18 (7.5%) of 237 patients with TB at baseline had paradoxical TB-associated IRIS, and 12 (3%) of 390 patients without TB at baseline developed ART-associated TB. Most IRIS events occurred during the initial 30 days of HAART. Two patients developed TB-associated IRIS after 90 days of HAART. Using univariate analysis, low CD4+ cell count at baseline [64 (28-89) vs. 95 (52-150); P=0.009] and early initiation of HAART [33 (24-41) vs. 48 (35-61) days; P<0.001] were significantly associated with paradoxical TB-associated IRIS. No identifiable risk factors were associated with the development of ART-associated TB. Interpretation & conclusions: A considerable proportion of patients on HAART develop TB-associated IRIS. The consensus case-definition is a useful tool in resource-limited settings for the diagnosis of TB-associated IRIS.

Infección por virus herpes simple 1-2 como manifestación de síndrome inflamatorio de reconstitución inmune: informe de un caso de difícil diagnóstico / Herpesvirus 1 and herpesvirus 2 infection as manifestation of immune reconstitution inflammatory syndrome: a case off difficult diagnosis

Se presenta el caso de un paciente que desarrolló una enorme lesión ulcerada en la cavidad bucal debida a VHS en el contexto de un cuadro de reconstitución inmunitaria asociada a la terapia antirretroviral de gran actividad o de alta eficacia.

Immune reconstitution inflammatory syndrome in acquired immunodeficiency syndrome.

A 33-year-old male presented with a history of fever and cough and was diagnosed to have pulmonary tuberculosis and acquired immunodeficiency syndrome (AIDS). He was started on antituberculosis therapy (ATT) followed by highly active anti-retroviral treatment (HAART) after one week. He developed an immune reconstitution inflammatory syndrome (IRIS) leading to an exacerbation of the tuberculosis disease. After HAART was stopped his condition improved dramatically.

Immune reconstitution inflammatory syndrome in a patient with cryptococcal lymphadenitis as the first presentation of acquired immunodeficiency syndrome.

Immune reconstitution inflammatory syndrome is commonly seen in acquired immunodeficiency syndrome (AIDS) patients having concomitant opportunistic infection, following initiation of highly active anti-retroviral therapy (HAART). We describe IRIS in a young man with unknown human immunodeficiency virus (HIV) status who presented with cryptococcal lymphadenitis as the first manifestation of AIDS. At presentation the patient had features overlapping with tuberculosis (TB) lymphadenitis which was ruled out by fine needle aspiration cytology. The patient responded to antifungal treatment but following the start of HAART, symptoms recurred which were managed conservatively. Though TB is common in India, a thorough workup including histopathology of lymph node should be done before the patient is started on anti-tuberculosis treatment. HIV infected patients having opportunistic co-infection should be closely monitored following initiation of HAART.