Disseminated coccidioidomycosis in a patient who is immunocompromised in the setting of immune reconstitution inflammatory syndrome

2021 ◽  
Vol 14 (4) ◽  
pp. e227217
Author(s):  
Hamid Yaqoob ◽  
Muhammad Mohsin Munawar ◽  
Omer Salih ◽  
Anand Deonarine
Keyword(s):  
Bone Marrow ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Airborne Spores ◽  
Systemic Fungal Infection ◽  
Art Initiation ◽  
Paradoxical Worsening ◽  
Inflammatory Syndrome

Coccidioidomycosis is a systemic fungal infection first described in 1892. More than 95% of annual cases occur in Arizona and California. It is an opportunistic infection (OI) transmitted via inhalation of airborne spores (arthroconidia) and rarely via percutaneous inoculation into a tissue or solid organ transplantation in patients who are immunocompromised and with HIV. With the advent of antiretroviral therapy (ART), the incidence of OIs has markedly reduced; however, OIs continue to occur, particularly in patients who present late for medical care or delay ART initiation. In rare cases, immunodeficient individuals may experience a paradoxical worsening or unmasking of OI symptoms, known as the immune reconstitution inflammatory syndrome (IRIS). We present a case of a 31-year-old man with disseminated coccidioidomycosis affecting the spleen, lymph nodes, lungs, bone marrow, and adrenals who developed IRIS after the initiation of ART.

scholarly journals Immune Reconstitution Inflammatory Syndrome Occurring in a Kidney Transplant Patient with Extrapulmonary Tuberculosis

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Jose Iglesias ◽  
Kandria Jumil Ledesma ◽  
Paul J. Couto ◽  
Jessie Liu
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
Extrapulmonary Tuberculosis ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
High Risk Group ◽  
Kidney Transplant Patient ◽  
Solid Organ ◽  
Inflammatory Syndrome

Tuberculosis (TB) occurring in solid organ transplantation (SOT) is associated with significant morbidity and mortality usually due to delays in diagnosis, drug toxicity encountered with antimycobacterial therapy, and drug-drug interactions. TB in SOT patients may mimic other infectious and noninfectious posttransplant complications such as posttransplant lymphoproliferative disorder (PTLD) and systemic cytomegalovirus infection. Immune reconstitution inflammatory syndrome (IRIS) is a host response resulting in paradoxical worsening of an infectious disease which occurs after the employment of effective therapy and reversal of an immunosuppressed state. We describe the development of immune reconstitution inflammatory syndrome (IRIS), a unique complication occurring during the treatment of extrapulmonary tuberculosis occurring after transplant which resulted from decreasing immunosuppression in a patient who received Alemtuzumab induction therapy. Although (IRIS) has been originally described in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART), solid organ transplant recipients with diagnosed or occult TB whose immune system may undergo immune reconstitution during their posttransplant course represent a new high risk group.

scholarly journals High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Control Group ◽  
Hiv Patients ◽  
Art Initiation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Α Level ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

scholarly journals Immune Reconstitution Inflammatory Syndrome with Recurrent Paradoxical Cerebellar HIV-Associated Progressive Multifocal Leukoencephalopathy

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 813
Author(s):  
Paola Frattaroli ◽  
Teresa A. Chueng ◽  
Obinna Abaribe ◽  
Folusakin Ayoade
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
People Living With Hiv ◽  
Rare Presentation ◽  
Diagnosis And Management ◽  
Art Initiation ◽  
Cerebellar Lesions ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Progressive multifocal leukoencephalopathy (PML), presenting as immune reconstitution inflammatory syndrome (IRIS), is a known complication of antiretroviral therapy (ART) in people living with HIV (PLWH). Typically preceded by ART initiation, IRIS may appear simultaneously/unmasked (PML-s-IRIS) or as a delayed/worsening/paradoxical (PML-d-IRIS) presentation of known PML disease. Primary cerebellar tropism continues to be a rare presentation, and paradoxical cerebellar involvement of PML-IRIS syndrome can be a challenge for both diagnosis and management. Steroids have been suggested as a possible therapy in severe cases but the duration of steroid therapy remain elusive. Our case is that of a 34-year-old man with newly diagnosed HIV simultaneously found to have cerebellar PML. His PML lesions however worsened after initiation of ART (PML-d-IRIS) with evidence of increased intracranial pressure. Despite initial favorable response to a short duration of steroids, he had multiple recurrence of his PML lesions after steroids were discontinued. The presence of predominant cerebellar lesions and the question of how long steroids should be provided to prevent or minimize PML recurrence is the highlight of our case. This report emphasizes the need for more controlled studies to assist clinicians in the optimal diagnosis and management of PML-IRIS in PLWH.

scholarly journals Cardiovascular Biomarker Profile on Antiretroviral Therapy Is Not Influenced by History of an IRIS Event in People With HIV and Suppressed Viremia

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Aurelie Gouel-Cheron ◽  
Martha Nason ◽  
Adam Rupert ◽  
Virginia Sheikh ◽  
Greg Robby ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Antiretroviral Therapy ◽  
Chronic Inflammation ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Art Initiation ◽  
History Of ◽  
Cardiovascular Biomarker ◽  
Inflammatory Syndrome

Abstract Immune reconstitution inflammatory syndrome (IRIS) is characterized by release of proinflammatory cytokines and tissue inflammation occurring early after antiretroviral therapy (ART) initiation. The role of previous IRIS events in persistent chronic inflammation in people with HIV is currently unclear. In this retrospective analysis of 143 participants who maintained suppression of HIV viremia, we compared biomarkers related to inflammation, coagulation, and cardiovascular risk after 3 years on ART in participants with and without a history of IRIS. There was no evidence of higher levels of persistent chronic inflammation in people with HIV who had a history of an IRIS event. ClinicalTrials.gov Identifier . NCT00286767.

scholarly journals Clinical and immunologic predictors of Mycobacterium avium complex immune reconstitution inflammatory syndrome in a contemporary cohort of patients with HIV

2020 ◽  
Author(s):  
Kimberly F Breglio ◽  
Caian L Vinhaes ◽  
María B Arriaga ◽  
Martha Nason ◽  
Gregg Roby ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
T Cell Activation ◽  
Mycobacterium Avium ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Mycobacterium Avium Complex ◽  
Subsequent Development ◽  
Art Initiation ◽  
Increased Risk ◽  
Inflammatory Syndrome

Abstract Background Patients with HIV (PWH) can present with new or worsening symptoms associated with Mycobacterium avium complex (MAC) infection shortly after antiretroviral therapy (ART) initiation as MAC immune reconstitution inflammatory syndrome (MAC-IRIS). In this study, we assessed the utility of several laboratory tests as predictors of MAC-IRIS. Methods PWH with clinical and histologic and/or microbiologic evidence of MAC-IRIS were identified and followed up to 96 weeks post-ART initiation within a prospective study of 206 ART-naïve patients with CD4 <100 cells/µL. Results Fifteen (7.3%) patients presented with MAC-IRIS within a median interval of 26 days after ART initiation. Patients who developed MAC-IRIS had lower BMI, lower hemoglobin levels, a higher alkaline phosphatase and increased CD38 frequency and MFI on CD8 + T-cells, at the time of ART initiation compared to non-MAC IRIS patients. A decision tree inference model revealed that stratifying patients based on levels of alkaline phosphatase and D-dimer could predict the likelihood of MAC-IRIS. A binary logistic regression demonstrated that higher levels of alkaline phosphatase at baseline were associated with increased risk of MAC-IRIS development. Conclusions High alkaline phosphatase levels and increased CD8 + T-cell activation with low CD4 counts at ART initiation should warrant suspicion for subsequent development of MAC-IRIS.

scholarly journals Left hand extensor tenosynovitis due to <i>Histoplasma capsulatum</i> complicated by immune reconstitution inflammatory syndrome

2021 ◽  
Vol 6 (8) ◽  
pp. 355-361
Author(s):  
Talha Riaz ◽  
Mark Collins ◽  
Mark Enzler ◽  
Marco Rizzo ◽  
Audrey N. Schuetz ◽  
...  
Keyword(s):  
Antifungal Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Histoplasma Capsulatum ◽  
Surgical Debridement ◽  
Left Hand ◽  
Paradoxical Worsening ◽  
Inflammatory Syndrome

Abstract. We describe a case of left hand extensor tenosynovitis due to histoplasmosis in a patient with dermatomyositis on chronic immunosuppression. Treatment involved surgical debridement and antifungal therapy. The patient experienced paradoxical worsening of tenosynovial inflammation during de-augmentation of immunosuppression felt to be immune reconstitution inflammatory syndrome.

scholarly journals The Epidemiology of IRIS in Southern India: An Observational Cohort Study

2017 ◽  
Vol 16 (5) ◽  
pp. 475-480 ◽  
Author(s):  
Nisha Thambuchetty ◽  
Kayur Mehta ◽  
Karthika Arumugam ◽  
Umadevi G. Shekarappa ◽  
Jyothi Idiculla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
South India ◽  
Significant Risk ◽  
Southern India ◽  
Art Initiation ◽  
Incidence Risk ◽  
Observational Cohort ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an uncommon but dynamic phenomenon seen among patients initiating antiretroviral therapy (ART). We aimed to describe incidence, risk factors, clinical spectrum, and outcomes among ART-naive patients experiencing IRIS in southern India. Among 599 eligible patients monitored prospectively between 2012 and 2014, there were 59.3% males, with mean age 36.6 ± 7.8 years. Immune reconstitution inflammatory syndrome incidence rate was 51.3 per 100 person-years (95% confidence interval: 44.5-59.2). One-third (31.4%) experienced at least 1 IRIS event, at a median of 27 days since ART initiation. Mucocutaneous infections and candidiasis were common IRIS events, followed by tuberculosis. Significant risk factors included age >40 years, body mass index <18.5 kg/m2, CD4 count <100 cells/mm3, viral load >10 000 copies/mL, hemoglobin <11 g/dL, and erythrocyte sedimentation rate >50 mm/h. Immune reconstitution inflammatory syndrome–related morality was 1.3% (8 of 599); 3 patients died of complicated diarrhea. These findings highlight the current spectrum of IRIS in South India and underscore the importance of heightened vigilance for anemia and treatment of diarrhea and candidiasis during ART initiation.

scholarly journals Understanding Pathogenesis and Care Challenges of Immune Reconstitution Inflammatory Syndrome in Fungal Infections

2018 ◽  
Vol 4 (4) ◽  
pp. 139 ◽  
Author(s):  
Sarah Dellière ◽  
Romain Guery ◽  
Sophie Candon ◽  
Blandine Rammaert ◽  
Claire Aguilar ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Immunosuppressive Agents ◽  
Fungal Species ◽  
Invasive Fungal Infections ◽  
Solid Organ ◽  
Mortality And Morbidity ◽  
Inflammatory Syndrome

Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS.

scholarly journals Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

2018 ◽  
Vol 5 (7) ◽  
Author(s):  
Irina Vlasova-St. Louis ◽  
Christina C Chang ◽  
Samar Shahid ◽  
Martyn A French ◽  
Paul R Bohjanen
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Cryptococcal Meningitis ◽  
Immune Reconstitution ◽  
Clinical Manifestations ◽  
Predictive Biomarkers ◽  
Proinflammatory Response ◽  
Antiviral Immune Response ◽  
Art Initiation ◽  
Genomic Studies ◽  
Inflammatory Syndrome

Abstract Background Paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) affects ~25% of human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (CM) after they commence antiretroviral therapy (ART) resulting in significant morbidity and mortality. Genomic studies in cryptococcal meningitis and C-IRIS are rarely performed. Methods We assessed whole blood transcriptomic profiles in 54 HIV-infected subjects with CM who developed C-IRIS (27) and compared the results with control subjects (27) who did not experience neurological deterioration over 24 weeks after ART initiation. Samples were analyzed by whole genome microarrays. Results The predictor screening algorithms identified the low expression of the components of interferon-driven antiviral defense pathways, such as interferon-inducible genes, and higher expression of transcripts that encode granulocyte-dependent proinflammatory response molecules as predictive biomarkers of subsequent C-IRIS. Subjects who developed early C-IRIS (occurred within 12 weeks of ART initiation) were characterized by upregulation of biomarker transcripts involved in innate immunity such as the inflammasome pathway, whereas those with late C-IRIS events (after 12 weeks of ART) were characterized by abnormal upregulation of transcripts expressed in T, B, and natural killer cells, such as IFNG, IL27, KLRB1, and others. The AIM2, BEX1, and C1QB were identified as novel biomarkers for both early and late C-IRIS events. Conclusions An inability to mount effective interferon-driven antiviral immune response, accompanied by a systemic granulocyte proinflammatory signature, prior to ART initiation, predisposes patients to the development of C-IRIS. Although early and late C-IRIS have seemingly similar clinical manifestations, they have different molecular phenotypes (as categorized by bioinformatics analysis) and are driven by contrasting inflammatory signaling cascades.

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