scholarly journals Anakinra in the treatment of protracted paradoxical inflammatory reactions in HIV-associated tuberculosis in the United Kingdom: a report of two cases

2020 ◽  
Vol 31 (8) ◽  
pp. 808-812 ◽  
Author(s):  
Alexander J Keeley ◽  
Vivak Parkash ◽  
Anne Tunbridge ◽  
Julia Greig ◽  
Paul Collini ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Therapeutic Option ◽  
Interleukin 1 ◽  
High Dose ◽  
Inflammatory Reactions ◽  
Amyloid A ◽  
The United Kingdom ◽  
First Case ◽  
Life Threatening ◽  
Dose Corticosteroid

Paradoxical reactions, including immune reconstitution inflammatory syndrome (IRIS), are common in patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB). Paradoxical reactions may confer substantial morbidity and mortality, especially in cases of central nervous system (CNS) TB, or through protracted usage of corticosteroids. No high-quality evidence is available to guide management in this scenario. Interleukin-1-mediated inflammation has been implicated in the pathophysiology of TB–IRIS. We describe two cases where anakinra (human recombinant interleukin-1 receptor antagonist) was used as steroid-sparing therapy for life-threatening protracted paradoxical inflammation in HIV-associated TB. In the first case of disseminated TB with lymphadenitis, protracted TB–IRIS led to amyloid A amyloidosis and nephrotic syndrome. In the second case of disseminated TB with cerebral tuberculomata, paradoxical inflammation caused unstable tuberculomata leading to profound neuro-disability. In both cases, paradoxical inflammation persisted for over a year. Protracted high-dose corticosteroid use led to adverse events yet failed to control inflammatory pathology. In both patients, anakinra successfully controlled paradoxical inflammation and facilitated withdrawal of corticosteroid therapy. Following anakinra therapy, nephrotic syndrome and neuro-disability resolved, respectively. Anakinra therapy for protracted paradoxical inflammation in HIV-associated TB may be a viable therapeutic option and warrants further research.

Anakinra as rescue therapy for steroid-dependent idiopathic recurrent pericarditis in children: case report and literature review

2018 ◽  
Vol 29 (2) ◽  
pp. 241-243 ◽  
Author(s):  
Moises Rodriguez-Gonzalez ◽  
Estefania Ruiz-Gonzalez ◽  
Ana Castellano-Martinez
Keyword(s):  
Inflammatory Responses ◽  
Rescue Therapy ◽  
Therapeutic Option ◽  
Interleukin 1 ◽  
High Dose ◽  
Recurrent Pericarditis ◽  
High Dose Corticosteroid ◽  
Steroid Dependent ◽  
Biologic Effects ◽  
Dose Corticosteroid

AbstractIn approximately 5% of patients with idiopathic recurrent pericarditis, the disease usually follows a chronic relapsing course, and children can develop dependence and side effects of prolonged high-dose corticosteroid regimens. In this setting anakinra, a recombinant human interleukin-1 competitive receptor antagonist that blocks the biologic effects of interleukin-1, thereby reducing systemic inflammatory responses, appears to be one of the most promising strategies. We report an adolescent with steroid-dependent idiopathic recurrent pericarditis that was successfully treated with anakinra, highlighting that this therapeutic option seems to be an effective, rapidly acting, steroid-sparing, and relatively safe agent for the treatment of this entity in children.

scholarly journals Etiology and Pathogenesis of Corticosteroid-Associated Osteonecrosis of the Femoral Head

2021 ◽  
Vol 3 (SP1) ◽  
pp. e1-e8
Author(s):  
Yusuke Kubo ◽  
Wolf Drescher ◽  
Thomas Pufe
Keyword(s):  
Femoral Head ◽  
Therapeutic Option ◽  
Joint Destruction ◽  
Preventive Therapy ◽  
High Dose ◽  
Head Region ◽  
Characteristic Finding ◽  
Pathological Mechanism ◽  
Flow Failure ◽  
Dose Corticosteroid

Osteonecrosis of the femoral head (ONFH) is an intractable disease occurring at a relatively young age. The characteristic finding of ONFH – the femoral head collapse with severe hip pain – is observed in many cases, which frequently leads to further joint destruction, requiring surgical treatment. Among the associated factors of ONFH, majority of patients who require high-dose corticosteroid are still challenging due to inevitable therapeutic option regardless of poor prognosis. As a pathological mechanism, ONFH is defined as tissue necrosis in the femoral head region due to occlusion of the nutrient vessels; but the detailed micro-level processes leading to blood flow failure remains unclear. The elucidation of ONFH and the establishment of preventive therapy is desirable for these patients. Here, we discuss the etiology and pathogenesis of corticosteroid-associated ONFH by reviewing current literature.

scholarly journals Efficacy of Rituximab in a Systemic Lupus Erythematosus Patient Presenting with Diffuse Alveolar Hemorrhage

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Gabriela Montes-Rivera ◽  
Grissel Ríos ◽  
Luis M. Vilá
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Therapeutic Option ◽  
Acute Onset ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
High Dose ◽  
Systemic Lupus ◽  
Effective Therapeutic Option ◽  
Life Threatening

Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus (SLE). Although infrequent, its mortality is very high. While there are no established therapeutic guidelines, DAH has been traditionally managed with high-dose intravenous (IV) corticosteroids, cyclophosphamide, and plasma exchange. The efficacy of alternative therapies such as rituximab has been described only in a few cases. Herein, we report a 25-year-old Hispanic man who presented with acute-onset SLE manifested by polyarthralgia, nephritis, seizures, pancytopenia, severe hypocomplementemia, and elevated anti-dsDNA antibodies. His disease course was complicated by DAH. His condition was refractory to high-dose intravenous (IV) methylprednisolone pulses, IV cyclophosphamide, and plasmapheresis. Given the lack of clinical response, he was started on IV rituximab 375 mg/m2 weekly for a total of four courses. He rapidly improved after the first two doses. Over the next seven months, he did not present recurrent pulmonary symptoms. Follow-up chest computed tomography did not show residual abnormalities. This case, together with other reports, suggests that rituximab is an effective therapeutic option for DAH in SLE.

scholarly journals Cervical Pregnancy: Two Cases with Different Treatment Strategies

2016 ◽  
Vol 6 (1) ◽  
pp. 51-54
Author(s):  
Hanan M. Shamrani
Keyword(s):  
Therapeutic Option ◽  
Treatment Strategies ◽  
First Trimester ◽  
Management Options ◽  
Uterine Preservation ◽  
Cervical Pregnancy ◽  
Dilatation And Curettage ◽  
First Case ◽  
Threatening Condition ◽  
Life Threatening

Cervical pregnancy is a rare, potentially life-threatening condition that presents challenging management options. We report the cases of two patients: a 38-year-old, gravida 11 para 8+ 2 who presented with first-trimester vaginal bleeding and a 32-year-old female primigravida who presented in her ninth week of gestation with vaginal spotting and abdominal pain. Radiological and histopathological findings were consistent with cervical pregnancy in both cases, which were managed successfully with different approaches. Conservative management with intra-embryonic injection of potassium chloride was successful in the first case while dilatation and curettage after intramuscular methotrexate administration resolved the second patient's symptoms. Cervical pregnancy, when diagnosed early, can be successfully treated with medical therapy. Surgical intervention may be necessary, but adopting medical treatment as a first-line therapeutic option offers the advantage of uterine preservation.

scholarly journals Nephrotic Syndrome-Associated Hypercoagulopathy is Alleviated by Nuclear Receptor Agonist Therapy with both Pioglitazone and Glucocorticoids

2020 ◽  
Author(s):  
Amanda P. Waller ◽  
Shipra Agrawal ◽  
Katelyn J. Wolfgang ◽  
Jiro Kino ◽  
Melinda A. Chanley ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Nuclear Receptor ◽  
Therapeutic Modality ◽  
High Dose ◽  
Puromycin Aminonucleoside ◽  
Thrombotic Risk ◽  
Steroid Resistant ◽  
Before And After ◽  
Life Threatening ◽  
Steroid Sensitive

ABSTRACTBackgroundThrombosis is a potentially life-threatening nephrotic syndrome (NS) complication. We have previously demonstrated that hypercoagulopathy is proportional to NS severity in rat models and that pioglitazone (Pio) reduces proteinuria both independently and in combination with methylprednisolone (MP), a glucocorticoid (GC). However, the effect of these treatments on NS-associated hypercoagulopathy remains unknown. We thus sought to determine the ability of Pio and GC to alleviate NS-associated hypercoagulopathy.MethodsPuromycin aminonucleoside-induced rat NS was treated with sham, Low- or High-dose MP, Pio, or combination (Pio+Low-MP) and plasma was collected at day 11. Plasma samples were collected from children with steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) upon presentation and after 7 weeks of GC therapy. Plasma endogenous thrombin potential (ETP), antithrombin (AT) activity, and albumin (Alb) were measured using thrombin generation, amidolytic, and colorimetric assays, respectively.ResultsIn a rat model of NS, both High-MP and Pio improved proteinuria and corrected hypoalbuminemia, ETP and AT activity (P<0.05). Proteinuria (P=0.005) and hypoalbuminemia (P<0.001) were correlated with ETP. In childhood NS, while ETP was not different at presentation, GC therapy improved proteinuria, hypoalbuminemia, and ETP in children with SSNS (P<0.001) but not SRNS (P=0.330).ConclusionsBoth Pio and GC diminish proteinuria and significantly alleviate hypercoagulopathy. Both Pio and MP improved hypercoagulopathy in rats, and successful GC therapy (SSNS) also improved hypercoagulopathy in childhood NS. These data suggest that even a partial reduction in proteinuria may reduce NS-associated thrombotic risk.SIGNIFICANCE STATEMENTNephrotic syndrome (NS) is characterized by massive proteinuria and is complicated by a complex, acquired hypercoagulopathy that markedly increases the risk for potentially life-threatening venous thromboembolism (VTE). This study demonstrates a strong correlation between proteinuria reduction and improvement of an established VTE-risk biomarker, in both a well-established animal model and in childhood NS before and after steroid treatment. We show that nuclear receptor agonists with known disparate mechanisms of action successfully reduce proteinuria and simultaneously improve NS-associated hypercoagulopathy. These data suggest that complete or partial proteinuria reduction by any therapeutic modality may concurrently reduce NS-associated thrombotic risk.

Personalized treatment of immune checkpoint inhibitor-related severe hemophagocytic lymphohistiocytosis (HLH).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15079-e15079
Author(s):  
Michel Obeid ◽  
Berna C. Özdemir ◽  
Sofiya Latifyan ◽  
Olivier Michielin
Keyword(s):  
Bone Marrow ◽  
Immune Checkpoint ◽  
Cytokine Profile ◽  
High Dose ◽  
Variable Response ◽  
Centre Hospitalier Universitaire ◽  
Life Threatening ◽  
Melanoma Patients ◽  
Dose Corticosteroid ◽  
Th1 Cytokines

e15079 Background: HLH is a rare but potentially lethal immune related adverse event (irAE) with an incidence of 0.03-0.4 % in cancer patients undergoing immune checkpoint inhibition (ICI). Given the rarity of HLH there are currently no diagnostic or therapeutic guidelines and the majority of the reported cases have been treated with corticosteroids alone with very variable response rates. There is currently no established therapy for corticosteroid resistant HLH occurring in the context of immunotherapies. We investigated the treatment possibility of severe HLH according to the cytokine profile. Methods: We report the clinical presentation, the cytokine profile and the outcome of three melanoma patients with ICI-related HLH not responding to high dose corticosteroid therapy alone who were treated with additional anti-IL-6R at the Centre Hospitalier Universitaire Vaudoise. We collected the following data: treatment setting, ICIs received, duration of each treatment, HLH criteria, bone marrow biopsy, cytokine profile, response to corticosteroid and to anti-IL-6R therapy. Results: We identified a severe HLH in three metastatic melanoma patients treated with ipilimumab and nivolumab for 2 of them and 1 with pembrolizumab. HLH occurred in a median of 10 weeks after initiation of immunotherapy. The patients met at least five of the HLH-2004 criteria including high ferritin levels ( > 100.000 ng/ml). High levels of interferon-gamma (IFNγ), IFNγ-induced chemokines, particularly CXCL9, CXCL10, CXCL13, IL-18 and IL-6 were found in all patients. For 2 of them we identified a highly infiltrated bone marrow by activated CD8+ T and NK cells. Median duration of corticosteroids therapy was 6.5 weeks. The evolution of the three patients was rapidly favorable in a median of 2.5 weeks after the addition of an anti-IL-6R therapy targeting the IFNγ/Th1 axis. Conclusions: HLH is a potentially life-threatening irAE necessitating emergency therapy. CXCL9 and Th1 cytokines are markedly elevated in patients with ICI-related HLH due to the activation of the IFNγ pathway. High CXCL9 and Th1 cytokines levels appear to be potential specific biomarkers for ICI-related HLH diagnosis. Blocking this axis by anti-IL-6 therapy seems a very promising strategy for severe ICI-related HLH allowing rapid resolution of symptoms and normalization of the abnormal laboratory results.

scholarly journals Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults

2020 ◽  
Vol 32 (1) ◽  
pp. 199-210
Author(s):  
Ho Jun Chin ◽  
Dong-Wan Chae ◽  
Yong Chul Kim ◽  
Won Suk An ◽  
ChunGyoo Ihm ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Complete Remission ◽  
Low Dose ◽  
Study Drug ◽  
Minimal Change Nephrotic Syndrome ◽  
Minimal Change ◽  
High Dose ◽  
Once Daily ◽  
High Dose Steroid ◽  
Dose Corticosteroid

BackgroundTacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study.MethodsIn this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5–7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation.ResultsComplete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3–8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences.ConclusionsCombined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

scholarly journals Laryngeal Myofibroblastic Tumor: A New Therapeutic Approach. A Case Report

2020 ◽  
pp. 014556132091874
Author(s):  
Javier Gómez-Hervás ◽  
Manuel Moreno-Romera ◽  
Fabio Hugo Escobar Arias ◽  
Esteban Merino Gálvez
Keyword(s):  
Corticosteroid Therapy ◽  
Therapeutic Approach ◽  
English Literature ◽  
Mass Effect ◽  
The Body ◽  
High Dose ◽  
High Tendency ◽  
Laryngeal Tumors ◽  
Life Threatening ◽  
Dose Corticosteroid

Myofibroblastic tumors are rare lesions which can affect any part of the body. Although benign, their mass effect causes symptoms that can become life-threatening. Supraglottic laryngeal involvement is extremely rare, with only 4 cases described in the English literature. Because the pathophysiology is unknown and the incidence is so low, there is no standardized therapeutic management, although for laryngeal tumors surgery has traditionally been the preferred initial option. Another less common option is intravenous and oral corticosteroid therapy, but this is usually reserved for myofibroblastic tumors in other head and neck sites that are more difficult to access surgically, or patients who cannot undergo surgery. These lesions have a very high tendency to recur, and morbidity rates are therefore also high. We present a case of supraglottic myofibroblastic tumor in which we elected high-dose corticosteroid therapy as the only form of treatment. With this new therapeutic approach, we avoided the undesirable effects of the usual type of surgery. At the 12-month follow-up, the patient is in complete remission.

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.

Intracerebral Abscess Associated With the Camino Intracranial Pressure Monitor: Case Report and Review of the Literature

Neurosurgery ◽  
2011 ◽  
Vol 71 (1) ◽  
pp. E193-E198 ◽  
Author(s):  
Ryan Morton ◽  
Timothy H. Lucas ◽  
Andrew Ko ◽  
Samuel R. Browd ◽  
Richard G. Ellenbogen ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Corticosteroid Therapy ◽  
Exceptional Case ◽  
High Dose ◽  
Icp Monitoring ◽  
Pressure Monitor ◽  
Life Threatening ◽  
Age Appropriate ◽  
Dose Corticosteroid ◽  
Intracerebral Abscess

Abstract BACKGROUND AND IMPORTANCE: Intracranial pressure (ICP) monitoring is a mainstay in the management of traumatic brain injury. Large investigations have validated the safety and efficacy of ICP monitors in comatose patients. Clinically relevant infections are extremely rare and cerebral abscess has never been reported with the Camino device. We describe an exceptional case of a life-threatening intracerebral abscess from an intraparenchymal ICP monitor. CLINICAL PRESENTATION: A 35-month-old child required 7 days of ICP monitoring after a fall from a 2-story window. His hospital course was complicated by severe airway edema treated, in part, with high-dose corticosteroid therapy for a total of 10 days. Two weeks later, the patient deteriorated acutely owing to a large intracerebral abscess under the previous ICP monitor site. Urgent craniotomy with evacuation of the abscess was performed on 2 separate occasions. Cultures grew methicillin-sensitive Staphylococcus aureus, which was treated with long-term antibiotics. At the 3-month follow-up, the patient was meeting age-appropriate milestones without focal deficits. CONCLUSION: To the best of our knowledge, this is the first report describing an intracerebral abscess as a complication from an intraparenchymal pressure monitor. Corticosteroid therapy may have constituted an independent risk factor for the ICP monitor--associated infection, as well as reinsertion of the ICP monitoring device at the same site. That this is the first reported parenchymal infectious complication underscores the safety of this device with respect to infection. When reinsertion of a parenchymal monitor is considered, a new site should be chosen.

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