Immune-Mediated Hematologic Complications of Checkpoint Inhibitors: A Review of the Literature

Abstract Background: The incidence and types of hematologic complications from immune check point inhibitors are not well known. We conducted this review to describe immune-mediated hematologic complications reported in clinical trials, case series, and case reports. Methods: A pre-defined comprehensive search strategy was used to identify case reports, case series, and clinical trials using PubMed. Any study that reported hematologic complications was included. Data were extracted for demographic characteristics and occurrence of immune-mediated hematologic complications. We pooled the data to calculate the frequency of immune-mediated hematologic adverse effects. Results: A total of 689 of studies were retrieved using the search criteria and 75 were included in the analysis (31 case reports and case series and 44 clinical trials). There were 44 patients reported having immune-mediated hematologic complications, 4 of them in clinical trials. The complications included aplastic anemia, autoimmune hemolytic anemia, cryoglobulinemia, graft versus host disease, hemophilia A (acquired), immune neutropenia, immune thrombocytopenia, macrophage activation syndrome, myelodysplastic syndrome, pure red cell aplasia, and thrombotic thrombocytopenic purpura. However, the overall rates were very low, ranging from 1-2.2% in clinical trials. Immune thrombocytopenia was the most common (29.5%), followed by autoimmune hemolytic anemia (15.9%), and immune neutropenia (13.6%). Immune-mediated hematologic complications were reported in all classes of checkpoint inhibitors including anti-programmed cell death protein 1 (nivolumab and pembrolizumab), anti-programmed death ligand 1 (avelumab and durvalumab), and anti-cytotoxic T-lymphocyte-associated protein 4 inhibitors (ipilimumab and tremelimumab). Among patients reported in case reports and case series, the median age was 57 years (range, 29-85) and most were males (52.9%). The majority of the complications occurred in patients treated with ipilimumab (38.8%), nivolumab (27.7%) and pembrolizumab (16.0%). The onset was usually within the first week of receiving the first dose but could occur up to 17 months after drug initiation. Indefinite discontinuation of the immunotherapy was the mainstay of treatment resulting in resolution of complications in the majority (74.5%) of the patients. Two patients were re-challenged with the same checkpoint inhibitor and one experienced a relapse of immune cytopenia (autoimmune hemolytic anemia). Conclusion: Immune-mediated hematologic complications associated with checkpoint inhibitors are rare. They are usually reversible after discontinuation of such treatment. Relapses may occur with re-challenge. Disclosures No relevant conflicts of interest to declare.

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Safe Start of Ibrutinib in Patients with Chronic Lymphocytic Leukemia and Uncontrolled Autoimmune Hemolytic Anemia

Blood ◽

10.1182/blood-2018-99-120129 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5560-5560 ◽

Cited By ~ 1

Author(s):

Alejandro Garcia-Horton ◽

Rosanne St. Bernard ◽

Alejandro Lazo-Langner ◽

Anargyros Xenocostas ◽

Joy Mangel ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Conflicts Of Interest ◽

Case Reports ◽

Laboratory Data ◽

Case Series ◽

Lymphocytic Leukemia ◽

Positive Direct

Abstract It is estimated that 4-10% of patients with chronic lymphocytic leukemia (CLL) will develop autoimmune hemolytic anemia (AIHA) over the course of their disease. Ibrutinib has proven to be effective in treatment of relapsed, refractory, 17p deleted, and treatment naïve CLL. The effect of ibrutinib on AIHA in the context of CLL has not been established since patients with active hemolysis were excluded from major trials. In this abstract, we present a case series of patients that were actively hemolyzing at the start of ibrutinib therapy and in which their AIHA achieved prolonged response. Patient characteristics and laboratory data are shown in Table. Five patients (3 women, 2 men), median age 61 years (range 57 to 78), with CLL and active, uncontrolled AIHA at the time of ibrutinib initiation were identified. Uncontrolled AIHA was defined as anemia with evidence of hemolysis (at least two of the following: increased reticulocyte count, elevated lactate dehydrogenase, elevated indirect bilirubin, and reduced haptoglobin and a positive direct antiglobulin test (DAT)). Patients had a median hemoglobin of 70 g/L (range 69-96) prior to start of ibrutinib and 3 of them required transfusion support for symptomatic anemia. All patients were receiving prednisone for management of AIHA at the time of ibrutinib initiation and had been on it for a median of 10 days (range 9 - 25) without AIHA resolution. 1 patient received intravenous immunoglobulin concurrently. All patients had received at least one line of therapy for CLL in the past and 3 had experienced previous AIHA responsive to steroids. AIHA in 2 patients was related to previous fludarabine exposure but had responded to a prednisone tapering schedule and were off steroids by the time of the new AIHA flare. Median hemoglobin of 130 g/L (range 113-149) was reached at time of AIHA response. All 5 patients tolerated 420mg oral daily of ibrutinib therapy and AIHA was controlled in a median of 6.5 weeks (range 6-10). Discontinuation of steroids was achieved in all patients at a median of 10 weeks (range 6-17) without evidence of further hemolysis. All patients except one are receiving ongoing follow up and have been followed up for a median of 130 weeks (range 15-150) since ibrutinib start. Patients have not shown evidence of AIHA relapse and continue off AIHA treatment (prednisone). One patient required discontinuation of ibrutinib 6 months after starting due to neutropenia but there was no evidence of AIHA relapse in follow up. The patient has passed away from unrelated GI bleed 2 years after the initial AIHA event. This is the largest case series to our knowledge on the safe start of ibrutinib in CLL complicated by active AIHA. Hemolysis in all patients responded to a short prednisone taper with ibrutinib concurrently and obtained a sustained response at follow up without any flare ups or further AIHA treatment use. These cases suggest that it is safe to start ibrutinib during uncontrolled, active hemolysis in contrast to 2 previous case reports that suggested causal relationship between ibrutinib and onset of severe CLL-associated AIHA (Rider et al, 2015; Hodskins et al, 2014). As previously reported, AIHA occurrence or relapse once ibrutinib has been started is rare (Rogers et al, 2016). Disclosures No relevant conflicts of interest to declare.

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Autoimmune Hemolytic Anemia as a Complication of Congenital Anemias. A Case Series and Review of the Literature

Journal of Clinical Medicine ◽

10.3390/jcm10153439 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3439

Author(s):

Irene Motta ◽

Juri Giannotta ◽

Marta Ferraresi ◽

Kordelia Barbullushi ◽

Nicoletta Revelli ◽

...

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Case Series ◽

Intravenous Immunoglobulins ◽

Point Of View ◽

First Line ◽

Human Erythropoietin ◽

Immune Mediated ◽

Hemolytic Crisis ◽

Life Threatening

Congenital anemias may be complicated by immune-mediated hemolytic crisis. Alloantibodies are usually seen in chronically transfused patients, and autoantibodies have also been described, although they are rarely associated with overt autoimmune hemolytic anemia (AIHA), a serious and potentially life-threatening complication. Given the lack of data on the AIHA diagnosis and management in congenital anemias, we retrospectively evaluated all clinically relevant AIHA cases occurring at a referral center for AIHA, hemoglobinopathies, and chronic hemolytic anemias, focusing on clinical management and outcome. In our cohort, AIHA had a prevalence of 1% (14/1410 patients). The majority were warm AIHA. Possible triggers were recent transfusion, infection, pregnancy, and surgery. All the patients received steroid therapy as the first line, and about 25% required further treatment, including rituximab, azathioprine, intravenous immunoglobulins, and cyclophosphamide. Transfusion support was required in 57% of the patients with non-transfusion-dependent anemia, and recombinant human erythropoietin was safely administered in one third of the patients. AIHA in congenital anemias may be challenging both from a diagnostic and a therapeutic point of view. A proper evaluation of hemolytic markers, bone marrow compensation, and assessment of the direct antiglobulin test is mandatory.

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NUDT15 polymorphism explains serious toxicity to azathioprine in Indian patients with chronic immune thrombocytopenia and autoimmune hemolytic anemia: a case series

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2020-0128 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Anup J. Devasia ◽

Raveen Stephen Stallon Illangeswaran ◽

Infencia Xavier Raj ◽

Biju George ◽

Poonkuzhali Balasubramanian

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Immune Thrombocytopenia ◽

Case Series ◽

Severe Toxicity ◽

Toxic Side Effect ◽

Case Presentation ◽

Oral Ulcers ◽

Asian Patients ◽

Life Threatening

AbstractObjectivesAzathioprine (AZA) is a commonly used immunosuppressant in patients with autoimmune diseases. The toxic side effect to AZA (myelosuppression, hair loss, and oral ulcers) are highly unpredictable which can be life threatening if not identified earlier and dose adjustments made or the drug is withdrawn.Case presentationHere we report a case series of five patients with severe toxicity while on treatment with AZA for autoimmune hemolytic anemia (n=1) and Immune thrombocytopenia (n=4). The common thiopurine methyltransferase (TPMT) variants (TPMT*2, *3A, *3B) were not present in these patients. However, all these patients had the NUDT15 415C>T variant that has been reported to explain serious toxicity to thioguanine in Asian patients.ConclusionsOur report suggests pre-emptive genotype-based dosing of AZA could reduce adverse toxicity and hence better outcome.

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Autoimmune Hemolytic Anemia and Checkpoint Inhibitors: 68 Cases from the FDA Database and Critical Review

Blood ◽

10.1182/blood-2018-99-111724 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2324-2324

Author(s):

Georges Tanios ◽

Peter B Doley ◽

Reinhold Munker

Keyword(s):

Lung Cancer ◽

Malignant Melanoma ◽

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

High Frequency ◽

Conflicts Of Interest ◽

Checkpoint Inhibitors ◽

Chemotherapy Drugs ◽

Aggressive Management ◽

Time Period

Abstract Immune checkpoint inhibitors (CPI) are widely used in modern oncology and have improved the prognosis of lung cancer, bladder cancer, malignant melanoma and other malignancies. Unlike cytotoxic chemotherapy, drugs like nivolumab, pembrolizumab and ipilimumab are associated with a high frequency of immune-related adverse effects. We recently observed a patient with lung cancer who developed a fulminant warm-antibody autoimmune hemolytic anemia (AIHA) and reviewed the literature and public databases of the Food and Drug Administration (FDA) to help understand the association between CPI use and AIHA. A total of 68 cases of AIHA were identified in the FDA database during the time period 2012-2018; 43 associated with nivolumab, 13 with pembrolizumab, 7 with ipilimumab and 5 with atezolizumab administration (see Table 1). All episodes of AIHA were listed as serious. If the total number of adverse effect cases reported to the FDA is taken as a reference, AIHA is rare, but occurred more frequently with PD-1 or PDL1 targeting agents (0.15 to 0.25%) than with CTLA4-inhibitors (0.06%). The underlying cancer diagnoses corresponded mostly to the approved indications for CPI (32 cases of malignant melanoma, 24 cases of lung cancer). In about a quarter of cases with AIHA other immune related side effects were reported. In addition to our case, the literature review identified 10 similar cases. AIHA can occur earlier and later after the administration of CPI (median of 10 weeks, range 2- 78). Most cases of AIHA responded to steroids, but 2/11 were fatal. In conclusion, we describe AIHA as a rare and serious immune-related side effect of checkpoint inhibitors. Because of its seriousness and the underlying comorbidities, early aggressive management is necessary. Disclosures No relevant conflicts of interest to declare.

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Levofloxacin-Induced Autoimmune Hemolytic Anemia

Annals of Pharmacotherapy ◽

10.1345/aph.1c525 ◽

2003 ◽

Vol 37 (7-8) ◽

pp. 1010-1013 ◽

Cited By ~ 17

Author(s):

Young R Oh ◽

Sian M Carr-Lopez ◽

James M Probasco ◽

Peter G Crawley

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Case Reports ◽

Stable Condition ◽

Drug Event ◽

Packed Red Blood Cells ◽

Case Summary ◽

Immune Mediated ◽

Severe Jaundice

OBJECTIVE: To report a case of autoimmune hemolytic anemia (AIHA) secondary to levofloxacin. CASE SUMMARY: An 82-year-old white man was treated with levofloxacin 500 mg/d for cellulitis. Three days following completion of levofloxacin therapy, the patient presented to the emergency department with severe jaundice, dizziness, and loss of vision. He received packed red blood cells (PRBCs) and was discharged home. Two days later at the follow-up visit, he was diagnosed with AIHA secondary to levofloxacin. The patient was hospitalized and treated with a tapering dose of prednisone and additional PRBC infusion. He was discharged from the hospital in stable condition after 3 days. Repeated hematologic laboratory studies following discharge demonstrated that the hemolytic anemia had resolved. DISCUSSION: Hemolytic anemia due to levofloxacin is an extremely rare, but potentially fatal, adverse drug event. An objective causality assessment revealed that the adverse reaction was probable. To our knowledge, this is the first published case of levofloxacin-induced AIHA. However, there are published case reports of hemolytic anemia with other fluoroquinolones including ciprofloxacin (n = 12) and temafloxacin (n = 95). Temafloxacin was withdrawn from the market in 1992 due to this adverse effect. The mechanism by which levofloxacin triggers hemolytic anemia is unknown. We believe that an immune-mediated reaction is most likely. CONCLUSIONS: Levofloxacin-induced AIHA is a rare but serious complication of therapy. Immediate discontinuation of the offending medication and treatment of the hemolytic anemia are essential. Until more information is available, levofloxacin should not be prescribed for patients with previous reactions to any fluoroquinolone.

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Autoimmune Hemolytic Anemia in HIV: A Case Series and Review of the Literature.

Blood ◽

10.1182/blood.v108.11.3858.3858 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3858-3858 ◽

Cited By ~ 1

Author(s):

David P.H. Wu ◽

Joseph Caperna ◽

Erin Reid

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Case Reports ◽

Clinical Manifestations ◽

Case Series ◽

High Dose ◽

Hiv Patients ◽

Latino Male ◽

Positive Direct

Abstract Background: Patients infected with HIV are more likely to have positive direct antiglobulin tests (Toy, Am J of Hem 1985) but there have only been a few reports of HIV-related AIHA (autoimmune hemolytic anemia) in the literature. Here we report three new cases of AIHA in HIV infected patients diagnosed from July 2003 to September 2005 at UCSD. Methods: Patients were identified by clinical presentation to the HIV service. All cases were considered highly likely by hematologists to have AIHA (lab data table 1). Results: Patient #1 was a 43 yo Caucasian male with CD4 < 50 prior ITP and untreated recently diagnosed visceral KS. On presentation, he reported dyspnea and had hepatosplenomegaly. His Hb was 5.2, retic 14%, LDH 459, Ibili 0.7, haptoglobin <7; + microspherocytes on smear. He was started on high-dose glucocorticoids (GC) before PRBC transfusion, and tolerated it well other than one fever to 100F. He received prednisone (pred) 60mg daily with taper. 3 weeks later at follow-up he self-tapered pred to 20mg and Hb was 11.1. Once off pred, his Hb remained stable at 11 when he died from PML approximately 4 months after remission of AIHA. Patient #2 is a 43 yo Latino male presenting with syncope, dizziness, dyspnea and palpations. His Hb was 5.4, retic 8%, LDH 366, Ibili 1.2, haptoglobin < 7, with smears showing extensive microspherocytes. He was treated with high-dose GC and received PRBC with heparin prophylaxis. His Hb recovered to 12. He was tapered off GC over 8 months and remains in remission for the past 2 months with Hb 14. Patient #3 is a 38 yo Latino male with dyspnea. His Hb was 5.7, retic 8%. He symptomatically improved with PRBC, and subsequently had a rapid response to GC. Hb peaked at 13.5 through tapering of pred by 10 mg weekly to 30 mg daily. The patient missed follow-up and continued the rapid taper, hemolysis recurred 1 month after pred cessation. Pred 60mg qd was restarted with resolution of hemolysis; this recurred even with slow taper (2mg/week) below 20mg daily. Pred again increased to 60 mg daily and danazol 600mg bid added with resolution of hemolysis. Pred taper to 20 mg was tolerated. Conclusions: AIHA in HIV patients has been described mainly in single case reports and abstracts (Koduri, Am Jo Hematology 2002). Only a few reports include long-term follow-up and fewer have included precipitants for AIHA. Within 2 years, we have three HIV patients with documented AIHA under different clinical manifestations and responses to treatment. One patient had a recent diagnosis of KS, the 2nd had received penicillin for syphilis and the 3rd had no recent medical complications. All 3 patients tolerated transfusion which resulted in symptomatic improvement and responded successfully to pred. Patient #3 who had a high CD4, was the only one with recurrence of hemolysis upon pred taper; perhaps a higher CD4 count may be associated with more persistent AIHA. In the literature, there are 14 other cases of idiopathic AIHA in adults with HIV (summary table to be presented at meeting). Of the 6 cases with reported CD4 counts, all were less than 200. 4/14 cases had inadequate reticulocyte response demonstrating existence of additional factors contributing to anemia. Most cases (10/14) responded to standard AIHA treatments including GC, IVIG and splenectomy. Overall 5/14 had died at the time of the reports; 2 of these deaths were related to PCP after remission of AIHA. 2/8 cases receiving PRBC died of DIC that occurred after transfusion. Table 1 Case Hb gm/dl Retic % LDH IU/L Hapto mg/dl IBili mg/dl CD4 #/ml 1 5.2 13.9 459 <7 0.9 82 2 5.4 8.1 366 <7 1.2 86 3 5.7 8.1 317 <7 2.1 424

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Autoantibodies Directed Against Moesin C471-577/N1-297 Are Novel and Specific Biomarkers of Immune Thrombocytopenic Purpura (ITP),

Blood ◽

10.1182/blood.v118.21.3301.3301 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3301-3301

Author(s):

Yue Zhang ◽

Hua Mao ◽

Aimin Zhao ◽

Feng Du ◽

Xiaofang Liu ◽

...

Keyword(s):

Hemolytic Anemia ◽

Lupus Erythematosus ◽

Autoimmune Hemolytic Anemia ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

High Serum ◽

Deficiency Anemia ◽

Serum Samples ◽

Hematologic Diseases ◽

Control Subjects

Abstract Abstract 3301 Moesin is a member of the protein 4.1 superfamily and shares structure homology with ezrin and radixin. The phosphorylation of moesin increases the aggregation of Fas, activation of capases, and triggers the apoptotic pathways through the Rho-ROCK pathway. The moesin protein is highly expressed in human platelets and phosphorylation of threonine558 is associated with the activation of platelets. Autoantibodies against moesin have not been evaluated in patients with ITP. Thus, we designed and expressed three polypeptides of moesin: N1-297 terminal, α 298–470 helix domain and C471-577 terminal for ELISA assays. Serum samples from patients with ITP (n=148), patients with non-immune thrombocytopenia (n=32), and other patients with hematologic diseases (n=102) as well as gender-matched healthy control subjects (n=50) were evaluated. All ITP patients clinically met an eligibility of ITP minimal standardized criteria from an international working group.1 The titers of moesin autoanitbodies were significantly elevated in the sera from patients with ITP compared with healthy subjects (Mean of autoantibodies titers = N1-297 0.515/0.155; α298–470 0.252/0.159; C471-577 0.430/0.144, P < 0.01). The levels of moesin autoantibodies against N1-297 and C471-577 in ITP patients were also markedly higher than in patients with non-immune thrombocytopenia (Mean of autoantibodies titers = N-1-297 0.515/0.168; C471-577 0.430/0.103, P < 0.05). However, the titer of autoantibodies against moesin ? 298–470 helix domains was similar in ITP, non-immune thrombocytopenia and in patients with other hematologic diseases. When an autoantibody cut-off value of ±2D in normal control subjects (n=50) was assigned, the serum levels of moesin autoantibodies in ITP patients were found to be elevated in 70% (103/148) positive for N-1-297, 44% (65/148) positive for C471-577 and only 6.1% (9/148) positive for α 298–470. Moreover, patients with non-immune thrombocytopenia (n=9), anaphylactic purpura (n=11) and myelodysplasticsyndrome, MDS (n=12) were all negative for moesin autoantibodies. In other groups of patients with hematologic diseases, multiple myeloma (n=15), pure red cell aplasia (n=2), and autoimmune hemolytic anemia (n=18), only autoimmune hemolytic anemia demonstrated 4.5% (3/18) positive for N-1-297 and all were negative for C471-577. Notably, severe ITP patients with iron deficiency anemia had high serum moesin autoantibodies against N-1-297 and C471-577. We also found 15.6% (6/38) positive moesin autoantibodies against C471-577 in ITP patients with systemic lupus erythematosus (SLE). To validate the ELISA results, we examined the specificity of moesin autoantibodies in ITP by Western blot analysis. Three polypeptides of moesin were run on SDS-PAGE and transferred onto nitrocellulose membrane. The immunoblotting showed autoantibodies against ITP that specifically recognized the moesin C471-577 or N1-297 polypeptide. In conclusion, this is the first study to show the elevation of serum moesin autoantibodies in patients with ITP. We propose that moesin autoantibodies specific for C471-577/N1-297 may be specific serum biomarkers for clinical diagnosis and differentiation of ITP from non-immune thrombocytopenia and other hematologic diseases. Disclosures: No relevant conflicts of interest to declare.

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Safety and Efficacy of Immune Checkpoint Inhibitors in Children and Young Adults with Haematological Malignancies: Review and Future Perspectives

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525719666210510171132 ◽

2021 ◽

Vol 19 ◽

Author(s):

Eleni Tsotridou ◽

Eleni Vasileiou ◽

Elpis Mantadakis ◽

Athanasios Tragiannidis

Keyword(s):

Clinical Trials ◽

Young Adults ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Case Reports ◽

Safety Data ◽

Case Series ◽

Great Promise ◽

Haematological Malignancies

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blockade of inhibitory receptors and have shown great promise in preclinical models and studies in the adult population. However, paediatric malignancies present unique features and so far, experience with these agents remains limited. In the current review we present an overview of efficacy and safety data from case reports, case series and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials.

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Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835921992989 ◽

2021 ◽

Vol 13 ◽

pp. 175883592199298

Author(s):

Orthi Shahzad ◽

Nicola Thompson ◽

Gerry Clare ◽

Sarah Welsh ◽

Erika Damato ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Case Reports ◽

Case Series ◽

Simple Algorithm ◽

Cancer Therapeutics ◽

Management Algorithm ◽

Ocular Symptoms ◽

Systemic Corticosteroids ◽

Permanent Loss

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

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Vitamin C in the Treatment of COVID-19

Nutrients ◽

10.3390/nu13041172 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1172

Author(s):

Gregorio Paolo Milani ◽

Marina Macchi ◽

Anat Guz-Mark

Keyword(s):

Clinical Trials ◽

Vitamin C ◽

Respiratory Infections ◽

Medical Condition ◽

Case Reports ◽

Case Series ◽

Theoretical Background ◽

Current Evidence ◽

Vitamin C Supplementation ◽

Essential Nutrient

Vitamin C is an essential nutrient that serves as antioxidant and plays a major role as co-factor and modulator of various pathways of the immune system. Its therapeutic effect during infections has been a matter of debate, with conflicting results in studies of respiratory infections and in critically ill patients. This comprehensive review aimed to summarize the current evidence regarding the use of vitamin C in the prevention or treatment of patients with SARS-CoV2 infection, based on available publications between January 2020 and February 2021. Overall, 21 publications were included in this review, consisting of case-reports and case-series, observational studies, and some clinical trials. In many of the publications, data were incomplete, and in most clinical trials the results are still pending. No studies regarding prevention of COVID-19 with vitamin C supplementation were found. Although some clinical observations reported improved medical condition of patients with COVID-19 treated with vitamin C, available data from controlled studies are scarce and inconclusive. Based on the theoretical background presented in this article, and some preliminary encouraging studies, the role of vitamin C in the treatment of patients with SARS-CoV-2 infection should be further investigated.

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