Acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome: prevalence, main characteristics, and outcomes in a Brazilian center.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) - immune reconstitution inflammatory syndrome (IRIS) in people living with HIV/AIDS (PLWHA) has been rarely described in low- and middle-income countries. OBJECTIVE: To describe the prevalence of PML-IRIS among PLWHA with PML and its main features in a tertiary hospital in Brazil. METHODS: We performed a retrospective cohort study. We included PLWHA with PML-IRIS patients admitted at Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, between 2011 and 2021. We retrieved information on neurological manifestations, neuroimaging findings, treatments, and outcomes. RESULTS: We identified 11 (11.8%) PML-IRIS cases among 93 patients with definite PML. Eight (73%) cases were men and had a median (IQR) age of 41 (27-50) years. Seven (63.6%) patients developed unmasking PML-IRIS and 4 (36.4%) had paradoxical PML-IRIS. The median (IQR) time from initiation of combined antiretroviral therapy (cART) to IRIS diagnosis was 49 (30-70) days. Ten (90.9%) patients received corticosteroids. There were 4 (36%) in-hospital deaths and 3 were associated with hospital-acquired pneumonia. Among the 7 (64%) patients who survived, 5 (71.5%) had sequelae at discharge. One year after the PML-IRIS diagnosis, 6 (54.5%) patients were alive. CONCLUSION: The prevalence of PML-IRIS was 11.8%. Most patients had unmasking PML-IRIS. In-hospital mortality and morbidity were high. One-year survival was similar to that described in some high-income countries.

ANTECEDENTES: A síndrome inflamatória de reconstituição imune (SIRI) da leucoencefalopatia multifocal progressiva (LEMP) em pessoas vivendo com HIV/Aids (PVHA) foi raramente descrita em países de baixa e média renda. OBJETIVO: Descrever a prevalência da SIRI-LEMP- em PVHA com LEMP e suas principais características em um hospital no Brasil. MéTODOS: Foi realizado um estudo de coorte retrospectivo. Incluímos PVHA com SIRI-LEMP admitidos no Instituto de Infectologia Emílio Ribas, São Paulo, Brasil, entre 2011 e 2021. Recuperamos informações sobre manifestações neurológicas, neuroimagem, tratamento e desfecho. RESULTADOS: Identificamos 11 (11,8%) casos de SIRI-LEMP entre 93 pacientes com LEMP definitiva. Oito (73%) casos eram homens e a mediana de idade (amplitude interquartile - AIQ) foi de 41 (27­50) anos. Sete (63,6%) pacientes desenvolveram SIRI-LEMP "desmascarada" e 4 (36,4%) casos apresentaram SIRI-LEMP "paradoxal". A mediana de tempo (AIQ) desde o início da terapia antirretroviral combinada (cART) até o diagnóstico de SIRI foi de 49 (30­70) dias. Dez (90,9%) pacientes receberam corticoide. Houve 4 (36%) óbitos intra-hospitalares e 3 foram associados à pneumonia hospitalar. Dos 7 (64%) pacientes que sobreviveram, 5 (71,5%) ficaram com sequelas na alta. Um ano após o diagnóstico de SIRI-LEMP, 6 (54,5%) pacientes estavam vivos. CONCLUSãO: A prevalência de SIRI-LEMP foi de 11,8%. A maioria dos pacientes apresentava SIRI-LEMP "desmascarada". A mortalidade e morbidade hospitalar foram altas. A sobrevida em 1 ano foi semelhante à descrita em alguns países de alta renda.

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.

Immune Reconstitution Syndrome with Initiation of Treatment of HBV/HIV Co-infection: Activity Flare associated with E antigen Seroconversion.

Immune reconstitution syndrome is a recognized complication with initiation of highly active antiretroviral therapy for acquired immune deficiency syndrome patients co-infected with hepatitis B. Hepatitis B flares are seen in 20%-25% of patients after initiation of highly active antiretroviral therapy, an estimated 1%-5% of whom develop clinical hepatitis. We present a case of highly active antiretroviral therapy initiation for HIV that led to a flare of HBV activity despite antiviral therapy directed towards both. Liver biopsy and longitudinal serologic evaluation lend support to the hypothesis that the flare in activity was representative of IRIS. Importantly, we document eAg/eAb seroconversion with the IRIS phenomenon.

Immune reconstitution inflammatory syndrome associated with secondary syphilis: dermatologic, neurologic and ophthalmologic compromise in an HIV patient.

The presentation of syphilis as a manifestation of immune reconstitution inflammatory syndrome in patients with human immunodeficiency virus (HIV) infection is rare and can be associated with the varied clinical expression of unusual syphilitic manifestations. We report a case of immune reconstitution syndrome with dermatologic, ophthalmologic and neurologic compromise of secondary syphilis in a patient with HIV infection.

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

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.

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.

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.

Clinical characteristics, predictors of immune reconstitution inflammatory syndrome and long-term prognosis in patients with Kaposi sarcoma.

OBJECTIVE: To investigate the predictive factors for the development of Kaposi sarcoma-related immune reconstitution inflammatory syndrome (KS-IRIS) and long-term prognosis in patients starting combined antiretroviral therapy (cART). METHODS: We studied a retrospective-cohort of consecutive antiretroviral-naïve patients with KS initiating cART from January 2005 to December 2011 and followed through June 2013. KS-IRIS was defined as ≥2 of the following: abrupt increase in number of KS lesions, appearance or exacerbation of lung-opacities or lymphedema, concomitantly with an increase in CD4+ cell-count ≥50 cells/mm3 and a decrease of >1 log in viral-load once started cART. We compared individuals who met KS-IRIS criteria with those that did not and described the long-term follow-up. RESULTS: We included 89 patients, 88 males; 35 (39%) developed KS-IRIS at a median of 10 weeks (IQR 4-16). KS-IRIS patients had more pulmonary-involvement (60% vs. 16.6% of patients; p < 0.0001), eight died attributed to pulmonary-KS. Thrombocytopenia <100,000/mm3 at follow-up occurred in 36% of KS-IRIS vs. 4% in non-KS-IRIS patients (p = 0.0002), 45% KS-IRIS patients with thrombocytopenia died, non without KS-IRIS. Chemotherapy (bleomicyn-vincristine) was more frequently prescribed in KS-IRIS patients (88.6% vs. 29.6%) with no differences in outcome; 80% of all patients achieve KS complete remission, 52% of them never received chemotherapy. No difference between groups in the long-term follow-up (mean 52.4 ± 27.4 months) was found, only one patient developed a secondary malignancy (1.12%). CONCLUSIONS: Lung-involvement was predictive of IRIS development. Thrombocytopenia in KS-IRIS patients at week 12 follow-up after cART initiation was associated with high mortality. Over a third of patients with KS achieve remission without chemotherapy. Individuals that survive the initial period of KS-IRIS adhere to cART had a good long-term prognosis.

Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

BACKGROUND: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. CASE PRESENTATION: A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. CONCLUSIONS: Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.

Immune response to Leishmania antigens in an AIDS patient with mucocutaneous leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome (IRIS): a case report.

BACKGROUND: After the onset of HAART, some HIV-infected individuals under treatment present a exacerbated inflammation in response to a latent or a previously treated opportunistic pathogen termed immune reconstitution inflammatory syndrome (IRIS). Few reports of tegumentary leishmaniasis have been described in association with IRIS. Moreover, the immunopathogenesis of IRIS in association with Leishmania is unclear. CASE PRESENTATION: The present study reports on a 29-year-old HIV-infected individual who developed mucocutaneous leishmaniasis associated with immune reconstitution inflammatory syndrome (IRIS) five months following highly active antiretroviral therapy (HAART). Severe lesions resulted in the partial destruction of the nasal septum, with improvement observed 15 days after treatment with Amphotericin B and corticosteroids. The immune response of this patient was evaluated before and after the lesions healed. IRIS was diagnosed in association with high levels of TNF-α and IL-6. Decreased production of IFN-γ and a low IFN-γ/IL-10 ratio were also observed in response to Leishmania antigens. After receiving anti-leishmanial treatment, the individual's specific Th1 immune response was restored. CONCLUSION: The results suggest that the production of inflammatory cytokines by unstimulated T-lymphocytes could contribute to occurrence of leishmaniasis associated with IRIS.

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

Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

BACKGROUND: Cytomegalovirus (CMV) retinitis has been extensively described in patients with advanced or late human immunodeficiency virus (HIV) disease under ineffective treatment of opportunistic infection and antiretroviral therapy (ART) failure. However, there is limited information about patients who develop active cytomegalovirus retinitis as an immune reconstitution inflammatory syndrome (IRIS) after successful initiation of ART. Therefore, a case definition of cytomegalovirus-immune recovery retinitis (CMV-IRR) is proposed here. METHODS: We reviewed medical records of 116 HIV-infected patients with CMV retinitis attending our institution during January 2003-June 2012. We retrospectively studied HIV-infected patients who had CMV retinitis on ART initiation or during the subsequent 6 months. Clinical and immunological characteristics of patients with active CMV retinitis were described. RESULTS: Of the 75 patients under successful ART included in the study, 20 had improvement of CMV retinitis. The remaining 55 patients experienced CMV-IRR; 35 of those developed CMV-IRR after ART initiation (unmasking CMV-IRR) and 20 experienced paradoxical clinical worsening of retinitis (paradoxical CMV-IRR). Nineteen patients with CMV-IRR had a CD4 count of ≥50 cells/µL. Six patients with CMV-IRR subsequently developed immune recovery uveitis. CONCLUSIONS: There is no case definition for CMV-IRR, although this condition is likely to occur after successful initiation of ART, even in patients with high CD4 T-cell counts. By consequence, we propose the case definitions for paradoxical and unmasking CMV-IRR. We recommend close follow-up of HIV-infected patients following ART initiation.

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.

Opsoclonus-myoclonus-ataxia syndrome in an AIDS patient.

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.