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 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.

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.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

Disfunción tiroidea en adultos infectados por el virus de inmunodeficiencia humana

Los pacientes con infección por el virus de inmunodeficiencia humana (HIV) tienen una mayor prevalencia de disfunción tiroidea cuando se los compara con la población general. Las manifestaciones más frecuentemente observadas son: el síndrome del eutiroideo enfermo, la enfermedad de Graves y el hipotiroidismo subclínico. La relación entre el uso de la terapia antirretroviral y el incremento en la prevalencia de alteraciones tiroideas fue demostrada en varias series de pacientes. La enfermedad de Graves se reconoce claramente como una consecuencia del síndrome de restitución inmune. Además, existen estudios que sugieren una relación entre hipotiroidismo y el uso de inhibidores nucleósidos de la transcriptasa reversa, en particular estavudina y el inhibidor no nucleósido de la transcriptasa reversa efavirenz. Nuevos estudios podrán aportar evidencia adicional sobre la necesidad de evaluaciones rutinarias de la función tiroidea en pacientes infectados por HIV.

Patients infected with human immunodeficiency virus (HIV) have a higher prevalence of thyroid dysfunction when compared with the general population. The most frequently observed manifestations are euthyroid sick syndrome, Graves´ disease and subclinical hypothyroidism. The relationship between the use of highly active antiretroviral therapy and the increased prevalence of thyroid dysfunction has been demonstrated in several series of patients. Grave’s disease is recognized as a consequence of immune restitution syndrome. Besides, several studies have suggested an association between hypothyroidism and the use of nucleoside reverse transcriptase inhibitors, particularly stavudine and non-nucleoside reverse transcriptase inhibitors such as efavirenz. Further studies could provide additional evidence of the need for routine assessment of thyroid function in HIV-infected patients.

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 restauração imune associada à histoplasmose / Histoplasmosis-associated immune reconstitution inflammatory syndrome

Paciente masculino, 27 anos, portador de HIV, com quadro de histoplasmose cutânea disseminada. Terapia antirretroviral oral e anfotericina B por via EV (dose total acumulada 0,5g) foram introduzidas, verificando-se rápida cicatrização das lesões após duas semanas. A anfotericina B foi substituída por itraconazol (200mg/dia). O paciente interrompeu voluntariamente os tratamentos. A terapia antirretroviral foi reintroduzida, havendo aumento da contagem de células T CD4-positivas (No restante do texto, a autora usa o símbolo "+" (T CD4+) ao invés da palavra "positiva". O que fazer neste caso? Seguimos o padrão do restante do texto ou acatamos essa opção da autora no resumo?!). Neste momento, diagnosticou-se histoplasmose ganglionar. O aumento da contagem de células T CD4-positivas (de novo aqui), associado à redução da carga viral a níveis inferiores ao limite de detecção após a reintrodução da terapia antirretroviral, sugere que essa piora clínica paradoxal seja uma síndrome de restauração imune.

A 27-year-old HIV-positive male patient with disseminated cutaneous histoplasmosis was treated with both HAART and amphotericin B (total accumulated dose of 0.5g). Amphotericin B was later replaced with itraconazole (200mg/day). Two months after therapy had been started and the cutaneous lesions had healed, the patient interrupted both treatments voluntarily and his health deteriorated. HAART was then re-introduced and CD4+ cell count increased sharply at the same time as lymph node histoplasmosis was diagnosed. This paradoxical response? the relapse of histoplasmosis and concomitant increase in CD4+ cell count and undetectable viral load after resumption of HAART ? suggests that this was a case of immune reconstitution inflammatory syndrome (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 manifesting as disseminated tuberculosis, deep venous thrombosis, encephalopathy and myelopathy.

We describe an unusual case of a 25-year-old human immunodeficiency virus (HIV)-positive male with a pre-treatment CD4 count of 144 cells/microL, who had received highly active antiretroviral therapy (HAART) consisting of lamivudine, stavudine and nevirapine for three months, developing immune reconstitution inflammatory syndrome (IRIS) manifesting as disseminated tuberculosis (TB), myelopathy, encephalopathy and deep venous thrombosis (DVT). In addition to HAART and antituberculosis treatment (ATT), the patient was given non-steroidal anti-inflammatory drugs, oral vitamin B12 and heparin, which was later switched to oral warfarin.

Manifestaciones cutáneas del síndrome de reconstitución inmune (SRI) / Cutaneous manifestations of immune reconstitution inflammatory syndrome

La supresión de la replicación del virus de la inmunodeficiencia humana adquirida (VIH) lograda por la terapia antirretroviral de gran actividad (TARGA) a menudo reestablece la respuesta inmune protectora patógeno-específica; pero en algunos pacientes esta recuperación es inmunopatológica y causa enfermedad. Esta situación es conocida con el nombre de síndrome de reconstitución inmune (SRI). Los pacientes experimentan deterioro clínico debido a la restauración de su capacidad de montar una respuesta inflamatoria inmune contra antígenos infecciosos y no infecciosos preexistentes. Se comunican 3 casos de SRI. En la revisión de la bibliografía se destacan las manifestaciones cutáneas del síndrome...

Síndrome de restauración inmune asociado a tratamiento antirretroviral y criptococosis meníngea: Caso clínico / Inflammatory reconstitution immune syndrome associated to antiretroviral therapy and meningeal cryptococcosis

The objective of high activity antiretroviral therapy (HAART) in patients with AIDS, is to obtain immune restoration. This means a reduction of the viral load and restitution of the CD4 cell count. A decreased rate of HIV replication improves both the number and function of CD4 cells. Nevertheless, this treatment sometimes results in the reappearance of previous symptoms from treated conditions due to opportunistic infections (ie: tuberculosis, criptococcosis, hepatitis, Pneumocystis jirovesi, toxoplasmosis, etc) or non infectious condition such as sarcoidosis, Graves disease or Kaposi sarcoma. This is known as Inflammatory Reconstitution Immune Syndrome (IRIS). We report a 37 year-old woman in stage C3-AIDS with a previous criptococcal meningitis. She was treated, achieving a marked improvement with treatment and subsequent suppressive therapy with fluconazole 200 mg/day. IRIS appeared after 8 months of ongoing antiretroviral therapy with immune restoration with the development of aseptic meningitis and intracranial hypertension. The opportunistic agent could not be identified by cultures. Additional laboratory tests excluded toxoplasmosis, tuberculosis, bacterial cerebral abscesses, syphilitic cerebral gummas, and lymphoma. Brain CT and magnetic resonance studies were compatible with brain vasculitis and leptomeningitis. The patient condition improved with general measures, such as a repeated lumbar punctures and non steroidal anti-inflammatory drugs. We conclude that this patient had an IRIS due to a Cryptococcus neoformans antigen.