scholarly journals P24 The successful use of anakinra to control protracted immune reconstitution inflammatory syndrome in HIV associated tuberculosis: a report of two cases

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Alexander J Keeley ◽  
Vivak Parkash ◽  
Anne Tunbridge ◽  
Julia Greig ◽  
Paul Collini ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Interleukin 1 ◽  
Brain Mri ◽  
Granulomatous Inflammation ◽  
High Dose ◽  
Tb Treatment ◽  
Life Threatening ◽  
Inflammatory Syndrome

Abstract Background Paradoxical inflammatory reactions are well known to complicate tuberculosis (TB) and are observed with greater frequency in patients who are co-infected with HIV. Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical inflammatory reaction following early immune system recovery after initiation of antiretroviral therapy. IRIS complicates one in five cases of HIV-associated TB. Most cases of IRIS respond to short courses of corticosteroids; however, morbidity and mortality is increased in central nervous system TB or with protracted reactions. There are no evidence-based treatment guidelines but montelukast, thalidomide and anti-tumour necrosis factor agents have been used to treat protracted paradoxical TB IRIS. Interleukin-1 mediated inflammation has been implicated in TB IRIS. We describe two cases using anakinra (recombinant human interleukin-1 receptor inhibitor) to control protracted, life-threatening inflammation in HIV associated TB. Methods The cases are presented in the results section. Results Case 1: A 33-year-old female from Ethiopia presented with sub-acute onset of fever, malaise with massive abdominal and thoracic lymphadenopathy. She was diagnosed with HIV (CD4=60 cells/mm3) and fully sensitive TB from lymph node aspirate. Despite two courses of TB treatment she developed a 3-year protracted IRIS with fevers, malaise and multiple cold abscesses and was unable to wean below 20mg prednisolone. AA amyloidosis developed with nephrotic range proteinuria and renal amyloid deposition on biopsy. Inflammation failed to respond to montelukast or colchicine, prompting anakinra initiation (100mg daily) with rapid clinical response, resolution of proteinuria, normalisation of inflammatory markers and successful weaning of corticosteroids. She is maintained on 100mg alternate-daily anakinra having failed an attempt to withdraw the treatment at seven years. Case 2: A 41-year-old Zimbabwean teacher with HIV (stable on antiretroviral therapy, complete viral suppression, CD4=245 cells/mm3) presented with one month of fever, weight-loss and headache with no neurological deficit. He was diagnosed with isoniazid mono-resistant miliary TB with tuberculomata in his medulla, pons and both cerebral hemispheres on magnetic resonance imaging (MRI). Following initiation of TB treatment, he developed worsening headaches, left sided weakness and dysphasia with increasing size and surrounding oedema of his tuberculomata on brain MRI. Brain biopsy demonstrated necrotic granulomatous inflammation with visible acid-fast bacilli but no mycobacterial growth, compatible with paradoxical inflammation. He required protracted and high dose dexamethasone. After 18 months without successfully weaning steroids, with cognitive and functional impairment and unstable tuberculomata on serial brain MRI, anakinra was initiated with significant clinical, functional and radiological improvement. He is maintained steroid-free on 100mg alternate-daily anakinra at four years. Conclusion This is the first published report using anakinra to control severe and life-threatening protracted paradoxical inflammation and reduce steroid exposure in HIV-associated tuberculosis. Disclosures A.J. Keeley None. V. Parkash None. A. Tunbridge None. J. Greig None. P. Collini None. R.S. Tattersall None.

Immune Reconstitution Inflammatory Syndrome

2011 ◽  
Vol 23 (1) ◽  
pp. 90-96 ◽  
Author(s):  
A.R. Tappuni
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
T Regulatory Cells ◽  
Clinical Presentation ◽  
Early Recognition ◽  
Clinical Intervention ◽  
Suppressor Cell ◽  
Life Threatening ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon observed in patients recovering from immunodeficiency. The clinical presentation of IRIS involves the unmasking of covert infections or the worsening of overt conditions. Several causes and pathways have been suggested, most recognizing an inflammatory flare component occurring in the context of rapid immune reconstitution. In HIV-infected patients, IRIS inadvertently occurs as the consequence of successful antiretroviral therapy, and it is affiliated with improvement of the immune function, complicating the course of the disease and presenting treatment challenges to clinicians. The pathogenesis of IRIS is poorly understood, but in recovering HIV patients, its initiation and progression seem to be primarily linked to an increase in CD4+ T-helper and CD8+ T-suppressor cell count and a reduction in T-regulatory cells, all endorsed by exaggerated cytokine release and activity. The clinical presentation of IRIS is usually atypical. The manifestations depend on the trigger antigen, which can be an infective agent (viable or nonviable), a host antigen, or a tumor antigen. Most IRIS cases are self-limiting, but a few cases can be overwhelming and life-threatening; hence, early recognition is important. In most cases, there is no need to discontinue the antiretroviral therapy, although in the more severe cases, other clinical intervention may be necessary.

scholarly journals Cryptococcal Lymphadenitis in an HIV-Infected Patient: A Rare Manifestation of Immune Reconstitution Inflammatory Syndrome

Diseases ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 70
Author(s):  
Jose Gonzales Zamora ◽  
Yogeeta Varadarajalu
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
Granulomatous Inflammation ◽  
Highly Active ◽  
Rare Manifestation ◽  
Previously Treated ◽  
Immunodeficiency Syndrome ◽  
Inflammatory Syndrome

Cryptococcosis is a fungal infection that is typically associated with acquired immunodeficiency syndrome (AIDS). The advent of highly active antiretroviral therapy has decreased the frequency of this infection, but has led to the emergence of atypical cases of immune reconstitution inflammatory syndrome (IRIS). Here, we describe the case of a 40-year-old man who was diagnosed with HIV infection and cryptococcal meningitis. He was successfully treated with antifungals and then started antiretroviral therapy. The patient returned to the hospital 15 months later complaining of fever, pain, and neck swelling. A computed tomography (CT) scan revealed a conglomerate of necrotic lymph nodes in the supraclavicular region. He underwent biopsy and histology showed granulomatous inflammation with fungal elements, consistent with Cryptococcus. He tested positive for serum cryptococcal antigen. The patient was treated with liposomal amphotericin and flucytosine. After induction therapy, he was re-started on fluconazole. The final fungal cultures were negative. We attributed our patient’s clinical presentation to “paradoxical” IRIS, which was associated with his previously treated cryptococcosis. Near resolution of the supraclavicular mass was noted at the 3-month follow-up.

scholarly journals Thyroid Eye Disease due to Immune Reconstitution Inflammatory Syndrome as a Consequence of Antiretroviral Therapy in the Setting of AIDS

2020 ◽  
Vol 2020 ◽  
pp. 1-3 ◽  
Author(s):  
Ravali Nallu ◽  
Parvathy Madhavan ◽  
Lisa Chirch ◽  
Pooja Luthra
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Early Recognition ◽  
Thyroid Eye Disease ◽  
Eye Disease ◽  
High Dose ◽  
Thyroid Function Tests ◽  
Graves Orbitopathy ◽  
Inflammatory Syndrome

We describe a case of worsening Graves’ orbitopathy due to immune reconstitution inflammatory syndrome (IRIS) in a 38-year-old HIV-infected male after beginning ART (antiretroviral therapy). Two years after initiation of ART, the patient developed symptoms of hyperthyroidism and thyroid eye disease (TED) or Graves’ orbitopathy (GO). Thyroid iodine uptake scan was consistent with Graves’ disease. The CT scan of the orbits revealed minimal right-sided proptosis, consistent with GO. He was treated with methimazole and a short course of high-dose prednisone for GO. Thyroid function tests normalized, and eye symptoms eventually stabilized. This case demonstrates the importance of awareness and early recognition of IRIS in its many forms, as it has significant therapeutic implications.

scholarly journals Graves’ disease associated with HIV disease and late immune reconstitution inflammatory syndrome following the initiation of antiretroviral therapy

2021 ◽  
Vol 2021 ◽  
Author(s):  
S Ludgate ◽  
S P Connolly ◽  
D Fennell ◽  
M F Muhamad ◽  
I Welaratne ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Cd4 Count ◽  
Graves Disease ◽  
High Dose ◽  
List Type ◽  
Delayed Presentation ◽  
Hiv Disease ◽  
Inflammatory Syndrome

Summary Both human immunodeficiency virus (HIV) and antiretroviral therapy (ART) are associated with endocrine dysfunction (1). The term 'immune reconstitution inflammatory syndrome' (IRIS) describes an array of inflammatory conditions that occur during the return of cell-mediated immunity following ART. Graves’ disease (GD) occurs rarely as an IRIS following ART. In this study, we describe the case of a 40-year-old Brazilian female who was diagnosed with HIV following admission with cryptococcal meningitis and salmonellosis. At this time, she was also diagnosed with adrenal insufficiency. Her CD4 count at diagnosis was 17 cells/µL which rose to 256 cells/µL over the first 3 months of ART. Her HIV viral load, however, consistently remained detectable. When viral suppression was finally achieved 21 months post diagnosis, an incremental CD4 count of 407 cells/µL over the following 6 months ensued. Subsequently, she was diagnosed with a late IRIS to cryptococcus 32 months following initial ART treatment, which manifested as non-resolving lymphadenitis and resolved with high-dose steroids. Following the initiation of ART for 45 months, she developed symptomatic Graves’ hyperthyroidism. At this time, her CD4 count had risen to 941 cells/µL. She has been rendered euthyroid on carbimazole. This case serves to remind us that GD can occur as an IRIS post ART and typically has a delayed presentation. Learning points Endocrinologists should be aware of the endocrine manifestations of HIV disease, in particular, thyroid pathology. Endocrinologists should be aware that IRIS can occur following the initiation of ART. Thyroid dysfunction can occur post ART of which Graves' disease (GD) is the most common thyroid manifestation. GD as a manifestation of ART-induced IRIS can have a delayed presentation. Infectious disease physicians should be aware of endocrine manifestations associated with HIV and ART.

Immune Reconstitution Inflammatory Syndrome

2017 ◽  
Author(s):  
Dagan Coppock ◽  
William R. Short
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Immunologic Function ◽  
Appropriate Treatment ◽  
Life Threatening ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is associated with either worsening of a recognized infection (paradoxical IRIS) or an unrecognized infection (unmasking IRIS), which occurs in the setting of improved immunologic function. Most patients presenting with IRIS should be maintained on antiretroviral therapy (ART) along with treatment for the associated infection. Screening for latent tuberculosis infection should be undertaken in all HIV-infected patients. In paradoxical IRIS, it is crucial to exclude alternate diagnoses and ensure the patient is receiving appropriate treatment for the condition. In the majority of cases, ART is continued, but on rare occasions cessation of ART is warranted in severe IRIS, particularly when it is life-threatening.

scholarly journals Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

2012 ◽  
Vol 54 (4) ◽  
pp. 231-233 ◽  
Author(s):  
Walter de Araujo Eyer-Silva ◽  
Maria Cecília da Fonseca Salgado ◽  
Jorge Francisco da Cunha Pinto ◽  
Fernando Raphael de Almeida Ferry ◽  
Rogério Neves-Motta ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
Gouty Arthritis ◽  
Infected Male ◽  
Acute Gouty Arthritis ◽  
Highly Active ◽  
History Of ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

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.

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