Immune Reconstitution Inflammatory Syndrome Research Articles

Immune reconstitution is the trigger of herpes zoster with lymphopenia and high neutrophil-to-lymphocyte ratio (NLR) in a retrospective cohort study

Abstract Background Herpes zoster (HZ) rarely results in later death, but predictive biomarkers for mortality necessitates further elucidation. Objective To investigate immune dynamics prior to HZ event, risk factors for HZ onset, and immune status at initial HZ. Methods This retrospective study extracted the absolute neutrophil and lymphocyte counts (ANC and ALC, respectively) at the initial HZ date and up to 30 days before HZ. A follow-up survey was completed within 180 days of the onset of illness. Results Patients with HZ showed higher neutrophil-to-lymphocyte ratio (NLR) and lower ALC than the control at the initial date and had poorer prognosis. In the pre-onset examination, the maximum and minimum ALC values were significantly lower in patients with HZ than in the control, and the maximum ALC value in patients with HZ was lower than the minimum value in the control. The lowest ALC value was observed 7 days before the onset of HZ. An NLR value of 4.53 or more and ALC value of 0.64 × 109 cells/L or less were predictive markers of HZ development within 30 days. Patients who died after HZ had lower minimum ALC than those who survived longer. Limitations The study had small population size, varying age distribution, and retrospective nature. The pre-onset data might have been exaggerated. Conclusion HZ develops in a state of immune reconstitution with immunocompromised conditions, as part of the unmasking immune reconstitution inflammatory syndrome (IRIS). Lymphopenia prior to HZ onset is one of the most crucial factors in its pathogenesis and vital prognosis.

An Uncommon Cause of Elevated Liver Transaminases: Immune Reconstitution Inflammatory Syndrome from Unmasking of Occult Mycobacterium Avium Complex Infection in an HIV Infected Patient

Abnormal liver chemistry from the development of immune reconstitution inflammatory syndrome (IRIS) may reflect an unmasking of subclinical disease. We present the case of a 37-year-old female with a mixed pattern of liver injury from disseminated mycobacterium avium complex infection after starting antiretroviral therapy (ART). Presenting symptoms were fever, confusion, dysphagia, and abdominal discomfort for one week. Exam revealed a fever of 103.2°F, hypotension, encephalopathy, and abdominal tenderness. Lab work was significant for acute normocytic anemia, leukopenia, absolute CD4 count 28 cells/cmm, HIV viral load 276 viral copies/ml (vc/ml), ALT 267 U/L, AST 484 U/L, alkaline phosphatase 342 U/L, and normal total bilirubin. Imaging revealed hepatomegaly with steatosis and mesenteric and retroperitoneal lymphadenopathy. Percutaneous liver biopsy demonstrated noncaseating granulomas with AFB-positive organisms, with AFB blood cultures growing Mycobacterium avium complex (MAC), consistent with disseminated MAC infection. Clinicians must have a high index of suspicion for IRIS when determining the etiology of elevated liver transaminases in patients with HIV.

Severe BCG immune reconstitution inflammatory syndrome lymphadenitis successfully managed with pre-antiretroviral counseling and a non-surgical approach: a case report

BackgroundBacillus Calmette-Guérin (BCG) reactions are the most common cause of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive infants who initiate antiretroviral therapy (ART). There is limited evidence regarding the incidence of BCG-IRIS; however, reports from outpatient cohorts have estimated that 6–9% of infants who initiated ART developed some form of BCG-IRIS within the first 6 months. Various treatment approaches for infants with BCG-IRIS have been reported, but there is currently no widely accepted standard-of-care.Case PresentationA 5-month-old male HIV-exposed infant BCG vaccinated at birth was admitted for refractory oral candidiasis, moderate anemia, and moderate acute malnutrition. He had a HIV DNA-PCR collected at one month of age, but the family never received the results. He was diagnosed with HIV during hospitalization with a point-of-care nucleic acid test and had severe immune suppression with a CD4 of 955 cells/µL (15%) with clinical stage III disease. During pre-ART counseling, the mother was educated on the signs and symptoms of BCG-IRIS and the importance of seeking follow-up care and remaining adherent to ART if symptoms arose. Three weeks after ART initiation, he was readmitted with intermittent subjective fevers, right axillary lymphadenopathy, and an ulcerated papule over the right deltoid region. He was subsequently discharged home with a diagnosis of local BCG-IRIS lymphadenitis. At six weeks post-ART initiation, he returned with suppurative lymphadenitis of the right axillary region that had completely eviscerated through the skin without signs of disseminated BCG disease. He was then started on an outpatient regimen of topical isoniazid, silver nitrate, and oral prednisolone. Throughout this time, the mother maintained good ART adherence despite this complication. After 2.5 months of ART and one month of specific treatment for the lymphadenitis, he had marked mass reduction, improved adenopathy, increased CD4 count, correction of anemia, and resolution of his acute malnutrition. He completely recovered and was symptom free two months after initial treatment without surgical intervention.ConclusionsThis case details the successful management of severe suppurative BCG-IRIS with a non-surgical approach and underlines the importance of pre-ART counseling on BCG-IRIS for caregivers, particularly for infants who initiate ART with advanced HIV.

150 From pancytopenia to hyperleukocytosis, an unexpected presentation of immune reconstitution inflammatory syndrome in an infant with methylmalonic acidemia

150 From pancytopenia to hyperleukocytosis, an unexpected presentation of immune reconstitution inflammatory syndrome in an infant with methylmalonic acidemia

Unmasked Kaposi and sarcoidosis immune reconstitution inflammatory syndrome in a patient with AIDS.

Unmasked Kaposi and sarcoidosis immune reconstitution inflammatory syndrome in a patient with AIDS.

Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.

People with HIV (PWH) have a higher age-adjusted mortality due to chronic immune activation and age-related comorbidities. PWH also have higher rates of clonal hematopoiesis (CH) than age-matched non-HIV cohorts, however, risk factors influencing the development and expansion of CH in PWH remain incompletely explored. We investigated the relationship between CH, immune biomarkers, and HIV-associated risk factors (CD4, CD8 T-cells, nadir CD4 count, opportunistic infections [OIs], and immune reconstitution inflammatory syndrome [IRIS]) in a diverse cohort of 197-PWH with median age of 42-years, using a 56-gene panel. Seventy-nine percent had a CD4 nadir < 200, 58.9% had prior OIs, and 34.5% had a history of IRIS. The prevalence of CH was high (27.4%), even in younger individuals, and CD8 T-cells and nadir CD4 counts strongly associated with CH after controlling for age. A history of IRIS was associated with CH in a subgroup analysis of ≥ 35-years-old patients. Inflammatory biomarkers were higher in CH carriers compared to non-carriers supporting a dysregulated immune state. These findings suggest PWH with low nadir CD4 and/or inflammatory complications may be at high risk of CH regardless of age and represent a high-risk group that could benefit from risk reduction and potentially targeted immunomodulation.

Immune reconstitution inflammatory syndrome (IRI S) in reproductive health

Immune reconstitution inflammatory syndrome (IRI S) in reproductive health

Hypercalcemia as a rare manifestation of immune reconstitution inflammatory syndrome (IRIS) in a person living with Human Immunodeficiency Virus (HIV) with disseminatednontuberculous mycobacteriosis.

Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV). A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8kg within the last 2weeks. Laboratory findings included serum hypercalcemia of 3.27mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18Fluoro-D-glucose positron emission computed tomography (18FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered. Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment.

Advances in Antiretroviral Therapy for Patients with Human Immunodeficiency Virus-Associated Tuberculosis.

Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.

Steroid-Induced Progressive Multifocal Leukoencephalopathy (PML) in HIV Patient: A Paradoxical Effect

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the central nervous system predominantly found in patients with acquired human immunodeficiency syndrome (AIDS). Case Presentation: This report details a case involving a male HIV-positive patient with PML who discontinued his highly active antiretroviral therapy (HAART) treatment 10 days after being diagnosed with HIV. The patient had no history of neurological symptoms either before or after his HIV diagnosis until he was administered corticosteroids. Notably, he began experiencing ataxia shortly after starting dexamethasone. Progressive multifocal leukoencephalopathy was diagnosed through polymerase chain reaction (PCR) testing for the John Cunningham virus (JCV) in the cerebrospinal fluid (CSF). The PML lesions were confined to the cerebellum. Conclusions: The occurrence of neurological symptoms (activation of JCV) after administering corticosteroids to a patient with HIV-who had not received any antiretroviral treatment for 4 years-raises a critical question: Is the use of corticosteroids, which are a primary treatment for immune reconstitution inflammatory syndrome (IRIS), a double-edged sword in CNS-IRIS?

Mycobacterial spindle cell pseudotumor of the spinal cord: Case report and literature review

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.

Skin and mucosal manifestations of immune reconstitution inflammatory syndrome in people living with HIV: a review.

Opportunistic infections have significantly decreased in individuals living with human immunodeficiency virus and receiving antiretroviral therapy. However, in approximately 10%-25% of patients, severe skin reactions during immune reconstruction are constantly increasing. This may manifest as either an exacerbation of a chronic disease or the development of a new disorder, referred to as immune reconstitution inflammatory syndrome. This review focuses on the current knowledge regarding the dermatological symptoms of immune reconstitution inflammatory syndrome observed in recent years. These symptoms encompass various pathogens, neoplasms, and certain autoimmune diseases. In addition to the most common skin reactions, attention is directed towards conditions not previously described in any review, such as psoriasis.

Meningitis and Tuberculosis: A Correlation along with Diagnosis and Management of Tuberculosis Meningitis

Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), is a communicable disease and a leading cause of death globally, especially in developing countries. It exists in active and latent forms, affecting both pulmonary and extrapulmonary sites. The pathophysiology of TB involves interactions with various immune cells, particularly T cells, in defense against the infection. On the other hand, meningitis is the inflammation of the membranes surrounding the brain and spinal cord, and it can be caused by bacteria or viruses. Bacterial meningitis, associated with high mortality and risk of disability. The article highlights the promulgation of TB into the brain and the immune responses within the brain, shedding light on the migration of M. tb into the central nervous system (CNS) and the innate immune responses involving microglia and cytokine secretion. The diagnostic methods for TB meningitis encompass neuroimaging, adenosine deaminase measurement in cerebrospinal fluid (CSF), microscopy, polymerase chain reaction (PCR) techniques, and enzyme-linked immunosorbent assay (ELISA). Moreover, it discusses the treatment of TB meningitis, emphasizing traditional antimicrobial therapies, systemic corticosteroid therapy, adjunctive therapy, fluid management, surgical intervention for hydrocephalus, and considerations for patients co-infected with HIV. The treatment approaches stress the importance of timely and empirical treatment, the use of newer generation fluoroquinolones, systemic corticosteroids as adjunctive therapy, and surgical interventions for hydrocephalus. The article also addresses the potential challenges and considerations for patients co-infected with HIV, such as the risk of immune reconstitution inflammatory syndrome (IRIS), drug interactions, and the efficacy of adjunctive corticosteroids. Overall, the document provides a comprehensive overview of the correlation between TB and meningitis, covering their pathophysiology, diagnostic methods, and treatment approaches. It emphasizes the complexity of managing TB meningitis and the importance of considering various factors, including immune responses, diagnostic accuracy, and tailored treatment strategies, particularly in the context of HIV co-infection.

Immune recovery uveitis: a focus review.

Immune recovery uveitis (IRU) is an intraocular inflammation that typically occurs as part of immune reconstitution inflammatory syndrome (IRIS) in the eye. Typically, it affects human immunodeficiency virus (HIV)-infected patients with recognized or unrecognized cytomegalovirus (CMV) retinitis who are receiving highly active antiretroviral therapy (HAART). IRU is a common cause of new vision loss in these patients, and it manifests with a wide range of symptoms and an increased risk of inflammatory complications, such as macular edema. Recently, similar IRU-like responses have been observed in non-HIV individuals with immune reconstitution following immunosuppression of diverse etiologies, posing challenges in diagnosis and treatment. This review provides an updated overview of the current literature on the epidemiology, pathophysiology, biomarkers, clinical manifestations, diagnosis, differential diagnosis, and treatment strategies for IRU.

Fatal form of immune reconstitution inflammatory syndrome (IRIS) developed post pneumonia in a solid organ transplant recipient

BackgroundImmune reconstitution inflammatory syndrome (IRIS) is a complex phenomenon commonly diagnosed with human immunodeficiency virus (HIV). However, rarely, IRIS can develop with other diseases outside of HIV. We are discussing a rare presentation of IRIS following a pseudomonal infection.Case presentationWe present a 79-year-old Hispanic male who completed a course of cefepime for Pseudomonas aeruginosa hospital-acquired pneumonia. The patient had a 21-year history of solid organ transplant and immunosuppressive therapy, and he developed a fatal form of IRIS post-Pseudomonas aeruginosa.ConclusionsIRIS may occur in any immunocompromised patient who develops an insidious onset of unexplained clinical and serological deterioration.

Paradoxical and Unmasking HIV Immune Reconstitution Inflammation Syndrome in Antiretroviral-Naïve Pregnant Women: A Prospective Cohort Study.

Following antiretroviral therapy (ART) initiation, HIV-associated immune reconstitution inflammatory syndrome (IRIS), indicated by an array of opportunistic infections, may occur, presenting as either paradoxical, a worsening of a previously treated infection, or unmasking, a flare-up of an underlying, previously undiagnosed infection. The impact of ART as the backbone of HIV treatment and prevention has prolonged the survival of people living with HIV. In pregnancy, benefits have been shown by slowing HIV progression and preventing perinatal transmission; however, there have been risks of adverse reactions with ART, including immune responses to both the fetus and mother. This study sought to estimate the incidence of HIV-IRIS cumulatively and by type either paradoxical or unmasking IRIS, determine the baseline maternal and HIV clinical markers as predictors of, and analyze the log-rank test for survival time to IRIS outcome assessed by relying on an increase in CD4 count and/or a rapid decrease in viral load. An active records study was conducted between June 2019 and March 2020 among ART-naïvepregnant women attending the antenatal care units (ANCu) at the Kenyatta National and MbagathiHospitals, Nairobi, Kenya. Participants were aged between 20 and 49 years and had a confirmed HIV-positive test. To ascertain a true case of IRIS, the diagnosis was adjudicated for accuracy and consistency by an independent review committee. Plasma HIV viral load, CD4 counts, and routine laboratory evaluations (hemoglobin, white blood cell count (WBC)) were performed by each hospital's clinical laboratory. The IRIS incidence was assessed using the International Network for Studies Against HIV-Associated IRIS (INSHI) during the first three months after ART initiation. Multivariate Cox regression with IRIS as the outcome, using the SPSSSurvival package, examined the relationship between baseline maternal characteristics and HIV clinical markers before ART initiation and IRIS, and finally, decision-tree analysis for predicting IRIS was performed. From a pool of 532 ART-naïvepregnant women, 133 (25%) developed IRIS, and 97 (72.9%) were in the unmasking category. The accumulated risk of experiencing IRIS symptoms increased from week two (hazard ratio (HR)=0.0287) to week 12 (HR=3.6158). Participants with a maternal BMI (MBMI) of 25-29.9 kg/m2 at baseline were at a higher risk of unmasking IRIS (HR=2.478; P=0.010). The WHO-HIV clinical stages 1 and 2 skewed towards paradoxical IRIS (regression coefficients =-0.111 and -0.276 (P<0.05)), while stage 4 skewed towards unmasking IRIS (regression coefficient=0.047, HR=1.048, P=0.941). A CD4 count > 500 cells/mm^3 skewed towards unmasking IRIS (regression coefficient=0.192, HR=1.211, P=0.416), while RNA-HIV viral loads >50 copies/ml towards paradoxical IRIS (regression coefficient=-0.199, HR=0.820, P=0.360. On decision tree analysis, 85% (P=0.001) of ART-naïve pregnant women with a baseline CD4 count below 500 copies/mm^3 presented with unmasking IRIS. For ART-naïvepregnant women, unmasking IRIS is the most common type, and an MBMI of 25-29.9 kg/m2, advanced HIV infection, a CD4 count <500 cells/mm^3, and a higher parity at baseline may be clinically useful predictors. The higher proportion of ART-naïvepregnant women experiencing unmasking as compared to paradoxical IRIS supports the need for earlier assessment based on potential predictors.

The nature and origin of immunosuppressive disorders

This publication reflects modern ideas about the main aspects of etiology, pathogenesis and the latest achievements of clinical practice in the field of the most common primary and secondary immunodeficiency. The features of laboratory diagnostics of congenital immunodeficiency, risk factors and early clinical guidelines that allow the patient to suspect an immunosuppressive state are considered. Special attention is paid to the problem of secondary immunodeficiency, their prevalence and polyetiology. When covering immunopathogenesis, infection caused by the human immunodeficiency virus (HIV), attention is paid to the multimorbidity of clinical manifestations of HIV-associated immunosuppression and concomitant diseases, the importance of timely administration of antiretroviral therapy (ART) and its role in the development of immune reconstitution syndrome (IRS). The criteria for the diagnosis of SVI based on their own experience and the opinion of foreign colleagues, the tactics of patient management are presented in detail.

Recent advances in understanding the human host immune response in tuberculous meningitis.

Tuberculous meningitis (TBM), the most severe form of tuberculosis, causes death in approximately 25% cases despite antibiotic therapy, and half of survivors are left with neurological disability. Mortality and morbidity are contributed to by a dysregulated immune response, and adjunctive host-directed therapies are required to modulate this response and improve outcomes. Developing such therapies relies on improved understanding of the host immune response to TBM. The historical challenges in TBM research of limited in vivo and in vitro models have been partially overcome by recent developments in proteomics, transcriptomics, and metabolomics, and the use of these technologies in nested substudies of large clinical trials. We review the current understanding of the human immune response in TBM. We begin with M. tuberculosis entry into the central nervous system (CNS), microglial infection and blood-brain and other CNS barrier dysfunction. We then outline the innate response, including the early cytokine response, role of canonical and non-canonical inflammasomes, eicosanoids and specialised pro-resolving mediators. Next, we review the adaptive response including T cells, microRNAs and B cells, followed by the role of the glutamate-GABA neurotransmitter cycle and the tryptophan pathway. We discuss host genetic immune factors, differences between adults and children, paradoxical reaction, and the impact of HIV-1 co-infection including immune reconstitution inflammatory syndrome. Promising immunomodulatory therapies, research gaps, ongoing challenges and future paths are discussed.

Therapeutic effectiveness on early and delayed treatment of antiretroviral in TB-HIV patients: a literature review

Introduction: Indonesia is one of the countries with a high TB-HIV prevalence. Antiretroviral treatment (ART) is only being administered to approximately 42% of TB-HIV patients. The low utilization of ART can be attributed, in part, to the delayed initiation of treatment. Nonetheless, starting ART in these people at an early stage poses risks, owing to the increased likelihood of drug-drug interactions and the manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) side effects when combined with anti-TB medication. Postponing ART, on the other hand, can hasten illness progression and increase the risk of death. Methods: A literature review was conducted to assess the effects of early ART (within four weeks of getting anti-TB) against delayed ART initiation (at least eight weeks after receiving anti-TB) in individuals co-infected with TB and HIV. The data was obtained by a comprehensive electronic search using the PubMed and Science Direct databases. Results: The findings of our study suggest that there was no statistically significant disparity in mortality rates between the early ART group and the delayed ART group. The initial ART cohort had a markedly elevated susceptibility to encountering an IRIS occurrence, particularly among individuals with a CD4 count below 50 cells per cubic millimeter. Conclusion: In summary, the strategy of delaying the initiation of ART in patients co-infected with TB-HIV is seen as preferable when compared to the approach of early treatment. The frequency of IRIS events is a significant determinant in determining the optimal timing of ART initiation in individuals co-infected with TB-HIV.

Stroke, HIV and the Immune Reconstitution Inflammatory Syndrome in the absence of opportunistic infections

IntroductionStroke in people living with HIV (PLWH) has been described to occur soon after the initiation of antiretroviral therapy (ART) possibly related to the Immune Reconstitution Inflammatory Syndrome (IRIS). We sought to investigate whether there was a temporal association between stroke and recent ART initiation in the absence of opportunistic infections (OIs), and to identify risk factors for this. MethodsThis cross-sectional study recruited PLWH with new-onset stroke at a hospital in Johannesburg, South Africa, from 2014 to 2017, excluding all patients with OIs. Patients were assessed for ART duration, CD4 count, HIV viral load, inflammatory markers and cardiovascular risk factors. Results77 PLWH were recruited, of which 35 were on ART at the time of stroke. Of the patients with confirmed ART duration (n = 28), 9 (32.1%) had a stroke within the first 6 months of starting ART (crude incidence rate of 0.73 cases per patient year). In the period beyond 6 months, 19 strokes occurred (crude incidence rate of 0.21 cases per patient year), translating to a 3.5 times greater risk in the first 6 months (p = 0.0002). There were no clearly identified risk factors when comparing those who had strokes in the first 6 months to those after 6 months and ART-naïve patients. ConclusionAlmost a third of strokes in PLWH may be related to IRIS, with a crude incidence rate 3.5 times higher in the first 6 months following ART-initiation compared to beyond 6 months. This appears to be independent of OIs. Risk factors are unclear.