Fatal pulmonary hemorrhage, pneumothorax and skin necrosis caused by IRIS to an Aspergillus flavus infection in a young patient with metamizole associated agranulocytosis.

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management.

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

Pathology for severe inflammatory PML with PD1/PD-L1 expression of favorable prognosis: What's a prognostic factor for PML-IRIS?

A 72-year-old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1-hypointense area. Multiple T2/FLAIR-hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of "suspicious of malignant lymphoma." Owing to emergent clinical conditions, high-dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR-hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4+ and CD8+ T cells, and the CD4+ /CD8+ ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20+ B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti-viral response. Variable inflammatory cells were observed, including CD4+ and CD8+ T cells, plasma cells, and a small amount of perivascular CD20+ B cells. PD-1 and PD-L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8+ T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD-1/PD-L1 immune-checkpoint regulation.

Cryptococcal meningitis with atypical paradoxical inflammatory reactions after antifungal treatment in acquired immune deficiency syndrome: A case report.

Cryptococcal meningitis (CM) is a life-threatening disease that primarily affects patients with human immunodeficiency virus (HIV). Antifungal therapy with antiretroviral treatment (ART) usually leads to the clinical remission of CM; however, in some cases, these treatments exacerbate intracranial inflammation because of paradoxical inflammatory reaction or immune reconstitution inflammatory syndrome (IRIS). Here we report two CM cases that presented atypical clinical courses attributed to paradoxical inflammatory reactions. The first case was a 43-year-old man with headache and vertigo diagnosed with CM and HIV. The patient's CM not only was refractory to the antifungal combination therapy of liposomal amphotericin B (L-AMB) and fluconazole (FLCZ) but suddenly worsened because of a paradoxical inflammatory reaction after 18 days of treatment. He passed away from brain herniation on day 23. The second case was a 43-year-old man diagnosed with CM and HIV. After receiving antifungal therapy and ART, the patient's status was stable for more than 3 years with undetectable HIV-RNA. He suddenly presented with brain inflammation and was diagnosed with IRIS due to CM (CM-IRIS). His brain lesions were migratory and refractory to various antifungal therapies such as L-AMB, FLCZ, flucytosine, and intrathecal amphotericin B. Although the cryptococcal antigen in the patient's cerebrospinal fluid gradually diminished after continuous antifungal therapies, his cognitive function declined, and right hemiparesis persisted. These two cases of CM presented atypical clinical courses, presumably because of paradoxical inflammatory reactions. It should be noted that the onset of CM-IRIS may not necessarily depend on the timing of ART initiation.

Immune reconstitution inflammatory syndrome (IRIS) in a patient with neuro pulmonary nocardiosis following hematopoietic cells transplantation (HCT).

Immune reconstitution inflammatory syndrome (IRIS) is increasingly reported in various HIV negative patients with immunosuppression, but the relationship with hematopoietic cell transplantation (HCT) is not well defined. We report a case of IRIS in a patient infected with pulmonary and CNS Nocardiosis following HCT due to primary myelofibrosis.

An Inflammatory Composite Score Predicts Mycobacterial Immune Reconstitution Inflammatory Syndrome in People with Advanced HIV: A Prospective International Cohort Study.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management. METHODS: Plasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model. RESULTS: We identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort. CONCLUSIONS: Systemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART. CLINICAL TRIALS REGISTRATION: NCT00286767.

Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living With Human Immunodeficiency Virus and Severe Lymphopenia.

BACKGROUND: Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. METHODS: We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/µL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models. RESULTS: We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/µL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P = .004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P = .031). Being female (P = .004) and having a lower body mass index (BMI; P = .003), higher white blood cell count (P = .005), and higher D-dimer levels (P = .044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 µg/mL and BMI <15.6 kg/m2 as predictive of death. CONCLUSIONS: For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk.

Increased Th17 activation and gut microbiota diversity are associated with pembrolizumab-triggered tuberculosis.

INTRODUCTION: A hypersensitivity response akin to immune reconstitution inflammatory syndrome (IRIS) has been proposed as a mechanism responsible for anti-PD-1 therapy-induced tuberculosis. IRIS is associated with enhanced activation of IL-17A-expressing CD4 + T cells (Th17). Gut microbiota is thought to be linked to pulmonary inflammation through the gut-lung axis. MATERIALS AND METHODS: We used ImmuCellAI to investigate the T cell population in lung cancer and tuberculosis samples. Then, we applied flow cytometry to monitor the expression levels of the Th17 cell activation marker CD38 in the peripheral blood of a patient experiencing adverse events, including tuberculosis, in response to pembrolizumab. The gut microbiome was examined by 16S rRNA sequencing to examine the alterations caused by pembrolizumab. RESULTS: The percentage of Th17 cells was increased in both lung cancer and tuberculosis. FACS analysis showed that pembrolizumab induced substantial CD38 expression in Th17 cells. The patient's fecal samples showed that the diversity of the gut microbiota was significantly increased in response to the pembrolizumab cycle. One enriched genus was Prevotella, which has previously been linked to lung inflammation and Th17 immune activation. DISCUSSION: The observed Th17 activation in our patient was consistent with a role of Th17-mediated IRIS in pembrolizumab-triggered tuberculosis. Pembrolizumab might trigger airway inflammation with a Th17 phenotype through microbiota interactions in the gut-lung axis.

Cryptococcal meningitis and immune reconstitution inflammatory syndrome in a pediatric patient with HIV after switching to second line antiretroviral therapy: a case report.

BACKGROUND: Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published. CASE PRESENTATION: A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free. CONCLUSIONS: We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.

A case of immune reconstitution syndrome complicating progressive multifocal leukoencephalopathy after kidney transplant: Clinical, pathological, and radiographic features.

Progressive multifocal leukoencephalopathy (PML) is a life-threatening central nervous system (CNS) disorder, most commonly described in patients infected with the human immunodeficiency virus (HIV). Limited data exist on its natural history and treatment in solid organ transplant (SOT) recipients. A complication of PML is the immune reconstitution inflammatory syndrome (IRIS), which develops after T cell reconstitution and can have severe consequences when it occurs in the CNS. While well described in HIV-infected individuals, its clinical features, diagnosis, and treatment after SOT are largely unknown. We report a case of a kidney transplant recipient who was diagnosed with PML and developed significant worsening of her symptoms upon reduction of immunosuppression. Thallium SPECT showed avid uptake suggestive of lymphoma, but the diagnosis of PML-IRIS was ultimately established by brain biopsy. She survived with nearly complete restoration of her functional status after a prolonged steroid taper.

HIV infection and its effects on the development of autoimmune disorders.

More than 35 years have elapsed since the initial outbreak of the HIV/AIDS epidemic and the status of a considerable number of patients has changed from a fatal disorder to a chronic one where comorbidities including sarcoidosis and autoimmune diseases have become relevant and dominant. HIV targets the immune system leading to a state of immunodeficiency in a setting of immune activation in which CD4+ T cell depletion plays a critical role. The onset, natural history and course of HIV-associated autoimmune disease has dramatically changed according to the stage of HIV infection and since the introduction of combined anti-retroviral therapy. There are some issues that need further study regarding therapy, especially when immunosuppressive drugs and biologic agents are under consideration. Currently, biologic agents and others immunosuppressive agents are recommended when patients have CD4+ T cell counts above 200 cells/mm3 and the HIV viral activity is completely suppressed.

Multiple immune disorders after natalizumab discontinuation: After the CIRIS, the SIRIS?

Natalizumab (NTZ) is an effective treatment for patients with highly active relapsing remitting multiple sclerosis (MS). However, when the therapy must be interrupted, it is important to anticipate the withdrawal to avoid reactivation or disease rebound. Described here is the case of a 35-year-old woman, with a past history of beta thalassemia, bulimia and asthma, who was diagnosed with MS at age 26. She was treated initially with first-line subcutaneous (sc) immunomodulatory treatments. However, due to liver toxicity, interferon beta-1a sc was interrupted and replaced by glatiramer acetate treatment, which was well tolerated and used for several years. Unfortunately, disease progression with numerous relapses and contrast enhancement on brain MRI led to initiation of NTZ treatment. After more than 2 years of treatment, NTZ was interrupted because of pregnancy, and the patient was again put on glatiramer acetate. Eight weeks after interruption of NTZ therapy, the first signs of diabetes were observed, together with an increase in blood levels of hepatic enzymes, skin reactions such as angioedema and giant urticaria, and hypothyroidism requiring hormone supplementation. The patient delivered her baby without complications, and NTZ was reintroduced several months later. At the present time, the patient's hypothyroidism, diabetes and increased blood levels of hepatic enzymes persist, although no new skin reactions have been observed. Withdrawal of NTZ can not only lead to reactivation of the disease or its rebound, but also to autoimmune manifestations within the framework of immune reconstitution inflammatory syndrome (IRIS). This risk needs to be considered when therapy has to be interrupted, especially when a personal and/or familial past history of autoimmune disease is present.

Robust Reconstitution of Tuberculosis-Specific Polyfunctional CD4+ T-Cell Responses and Rising Systemic Interleukin 6 in Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.

BACKGROUND: The immunopathogenesis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains unclear. We determined the association between pathogen-specific T-cell responses and development of paradoxical TB-IRIS on antiretroviral therapy (ART). METHODS: This study was nested within a prospective cohort study of HIV-infected patients with active pulmonary tuberculosis and baseline CD4 counts ≤125 cells/µL initiating ART. T-cell immune activation (CD38, HLA-DR, and PD-1 expression), phenotype, and polyfunctional pathogen-specific cellular immune responses prior to and 4 weeks after ART initiation were determined by flow cytometry. Patients with TB-IRIS were compared to non-IRIS controls using χ(2) and rank-sum tests and logistic regression. RESULTS: TB-IRIS patients and controls had similar CD4 counts, levels of T-cell-associated immune activation, frequencies of T-cell memory subsets, and frequencies of interferon gamma (IFN-γ(+))/interleukin 2 (IL-2(+))/tumor necrosis factor alpha (TNF-α(+)) CD4(+) T-cells prior to ART initiation. After ART initiation, cellular immune activation and T-cell subsets also were similar in TB-IRIS patients and controls. In contrast, TB-IRIS patients had significantly greater early increases in the frequency of tuberculosis-specific polyfunctional IFN-γ(+)/IL-2(+)/TNF-α(+) CD4(+) T-cells on ART (P = .02); each quartile increase in the percentage of these cells was independently associated with a 2.8-fold increased risk of TB-IRIS (95% confidence interval, 1.1 to 7.5-fold). In a secondary analysis, patients with TB-IRIS had rapid, concomitant increases in tuberculosis-specific adaptive immune responses and interleukin 6 (IL-6) levels, whereas controls with similarly rapid increases in cellular immune function had IL-6 levels that tended to decrease on ART. CONCLUSIONS: Rapid expansion of tuberculosis-specific polyfunctional CD4(+) T-cell responses, likely linked to increases in IL-6, is associated with development of paradoxical TB-IRIS.

Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda.

Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.

Reactivation of herpes simplex virus type 2 after initiation of antiretroviral therapy.

BACKGROUND: The association between initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection and possible herpes simplex virus type 2 (HSV-2) shedding and genital ulcer disease (GUD) has not been evaluated. METHODS: GUD and vaginal HSV-2 shedding were evaluated among women coinfected with HIV and HSV-2 (n = 440 for GUD and n = 96 for HSV-2 shedding) who began ART while enrolled in a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Monthly vaginal swabs were tested for HSV-2 shedding, using a real-time quantitative polymerase chain reaction assay. Prevalence risk ratios (PRRs) of GUD were estimated using log binomial regression. Random effects logistic regression was used to estimate odds ratios (ORs) of HSV-2 shedding. RESULTS: Compared with pre-ART values, GUD prevalence increased significantly within the first 3 months after ART initiation (adjusted PRR, 1.94; 95% confidence interval [CI], 1.04-3.62) and returned to baseline after 6 months of ART (adjusted PRR, 0.80; 95% CI, .35-1.80). Detection of HSV-2 shedding was highest in the first 3 months after ART initiation (adjusted OR, 2.58; 95% CI, 1.48-4.49). HSV-2 shedding was significantly less common among women receiving acyclovir (adjusted OR, 0.13; 95% CI, .04-.41). CONCLUSIONS: The prevalence of HSV-2 shedding and GUD increased significantly after ART initiation, possibly because of immune reconstitution inflammatory syndrome. Acyclovir significantly reduced both GUD and HSV-2 shedding and should be considered to mitigate these effects following ART initiation.

Fulminant Type 1 Diabetes Caused by DIHS Could Be Affected by the Reactivation of HHV-6.

CONTEXT: In the previous issue of this journal, we reported that the incidence of fulminant type 1 diabetes (FT1D) due to the drug-induced hypersensitivity syndrome (DIHS) in Japan is higher than that in the general population and is associated with HLAB62. On the other hand, the reactivation of human herpesvirus 6 (HHV-6), which has been reported to be associated with DIHS, was observed at a higher frequency, but its association with the development of FT1D was unclear. OBJECTIVE: We aimed to clarify the relationship between the onset of FT1D and the reactivation of HHV-6. METHODS: We conducted a literature search for cases of DIHS-induced FT1D in addition to previously reported cases and investigated the changes in the HHV-6 antibody titer before and after the onset of FT1D. RESULTS: The HHV-6 antibody titer was increased just before or after the onset of FT1D in all 8 cases. In 1 case, HHV-6 DNA was also identified shortly before the onset of FT1D. CONCLUSION: These results indicate for the first time that the reactivation of HHV-6 is associated with the onset of FT1D caused by DIHS.

Immune-related neurodegeneration in the midbrain causes pulmonary dysfunction in murine cryptococcal IRIS.

Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) is a condition that affects immunosuppressed individuals recruited to antiretroviral therapy. In a recent publication, Kawano and colleagues used a mouse model to demonstrate that pulmonary dysfunction, one of the fatal complications of C-IRIS, is caused by T cell-driven neurodegeneration in a vital medullary nucleus of the brain responsible for respiratory control.

Radiological abnormalities in progressive multifocal leukoencephalopathy: Identifying typical and atypical imaging patterns for early diagnosis and differential considerations.

Progressive multifocal leukoencephalopathy (PML) is a rare viral central nervous system (CNS) demyelinating disease primarily associated with a compromised immune system. PML is seen mainly in individuals with human immunodeficiency virus, lymphoproliferative disease, and multiple sclerosis. Patients on immunomodulators, chemotherapy, and solid organ or bone marrow transplants are predisposed to PML. Recognition of various PML-associated typical and atypical imaging abnormalities is critical for early diagnosis and differentiating it from other conditions, especially in high-risk populations. Early PML recognition should expedite efforts at immune-system restoration, allowing for a favorable outcome. This review aims to provide a practical overview of radiological abnormalities in PML patients and address differential considerations.

[Differential diagnosis of immune reconstitution inflammatory syndrome and progressive multifocal leukoencephalopathy after natalizumab withdrawal]. / Differentsial'naya diagnostika vospalitel'nogo sindroma vosstanovleniya immuniteta i progressiruyushchei mul'tifokal'noi entsefalopatii pri otmene natalizumaba.

The appearance of new foci on MRI, the increase in neurological deficits, including the appearance of cognitive disorders and disturbances in the level of consciousness in patients with multiple sclerosis during the «washing period¼ when transferring from natalizumab (NZ) to another drug, may be due to both progressive multifocal leukoencephalopathy (PML) and exacerbation of the disease in the absence of therapy. Discontinuation of NS is fraught not only with a resumption, but with an increase in disease activity, the development of an immune reconstitution inflammatory syndrome (IRIS) due to the opening of the blood-brain barrier. Often, the processes of differential diagnosis of IRIS and natalizumab-associated PML are complex and require the use of additional methods of examination and monitoring of the dynamics of the patient's condition. However, the severity of the condition and the severity of the consequences caused by incorrect therapeutic tactics significantly reduce the time for diagnosis and require an immediate decision. The difficulties of differential diagnosis of IRIS and PML are reflected in the clinical case.