Success of intravenous immunoglobulin and steroids in managing severe COVID-19 following lung transplantation:A case report

BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised patients.This case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung transplantation.CASE SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung transplantations.Postoperatively,he developed COVID-19 pneumonia,severe septic shock,and ARDS.He recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse steroids.CONCLUSION IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 infection.We aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant setting.With further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.

Pembrolizumab-induced Guillain-Barrésyndrome in triple-negative breast cancer:A case report

BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.

Correlation of IL-1, IL-6, IL-10 Concentrations to Ovarian Hyperstimulation Syndrome and Effect of Intravenous Immunoglobulin on Ovarian Hyperstimulated Rats

Objective To investigate the correlation of interleukin（IL）-1,IL-6 and IL-10 concentrations to ovarian hyperstimulation syndrome（OHSS） and whether intravenous immunoglobulin（IVIG） has the effects on ovarian hyperstimulated rats. Methods Immature female Wistar rats were divided into control group, OHSS group （n=13） and IVIG group（n=13）. For the latter two groups, pregnancy mare serum gonadotropin（PMSG）and human chorionic gonadotropin（hCG） were given to induce OHSS, and rats in IVIG group were treated with immunoglobulin. Forty-eight hours after administration of hCG, capillary permeability was evaluated from the Evans blue dye（EB） concentration in the ovaries and the EB concentration in peritoneal irrigated fluid at 30 min after the intravenous injection of EB. Rats＇ blood samples and ovaries were obtained to be measured for IL-1, IL-6 and IL-10 by ELISA. Results In OHSS group, total weights of bilateral ovaries and the ovarian EB concentration were significantly higher than those in others（P〈0.05）. Both serum and ovarian concentrations of IL-1 were significantly higher in OHSS and IVIG groups than those in control group （P〈0.05）. The ovarian concentrations of IL-6 and IL-10 in IVIG group were significantly lower than those in control group（P〈0.05）. Furthermore, the ovarian IL-10 concentration in IVIG group was significantly lower than that in OHSS group（P〈0. 05）. Conclusion Inflammation involved IL-1 in OHSS rats plays an important role. Vascular permeability was mostly increased in ovaries of hyperstimulated rats. It appears that ovaries of OHSS rats may be the primary places of inflammation. IVIG treatment resulted in statistically significant reductions in ovaries＇ weights and ovarian vascular permeability of OHSS rats, with a decreased level of ovarian IL-10. It implys that IVIG have a beneficial effect in reducing the severity of OHSS in the experimental model maybe by restrainning IL-10.

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure

BACKGROUND： The established procedure for ABO-incompatible liver transplantation（ABO-I LT） was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin（IVIG） for ABO-I LT in patients with acute liver failure（ALF）.METHODS： The data from 101 patients who had undergone liver transplantation（LT） for ALF were retrospectively analyzed.The patients were divided into two groups： ABO-compatible liver transplantation group（ABO-C LT, n=66） and ABO-I LT group（n=35）. All the patients in the ABO-I LT group received a single dose of rituximab（375 mg/m2） and IVIG（0.4 g/kg per day） at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol.Quadruple immunosuppressive therapy including basiliximab,corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression.RESULTS： The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%,respectively（P〉0.05）, and the graft survival rates were 80.0%and 86.3%, respectively（P〉0.05）. Two patients（5.7%） suffered from antibody-mediated rejection in the ABO-I LT group.Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups.CONCLUSIONS： The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Role of intravenous immunoglobulin in suspected or proven neonatal sepsis

Neonatal sepsis remains the major cause of mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay in newborn infants. Despite of advances in technology and optimal antibiotic treatment,incidence of neonatal sepsis and its complications remains unacceptably high especially in developing countries. Premature neonates in particular are at higher risk due to developmentally immature host defence mechanisms. Though not approved by Food and Drug Administration(FDA) U. S. A,off label use of intravenous immunoglobulin as prophylactic or adjuvant agent in suspected or proven neonatal infections continues in many countries. In a recent large multicenter clinical trial by International Neonatal Immunotherapy Study(INIS) group, the use of polyvalent IgG immune globulin was not associated with significant differences in the risk of major complications or other adverse outcomes in neonates with suspected or proven sepsis. Hence,use of intravenous immunoglobulin in suspected or proven neonatal sepsis is not recommended. The expense of prophylactic use of intravenous immunoglobulin administration for both term and preterm newborn population,given the minimal benefit as demonstrated by many individual studies and by meta-analysis is not justified.

Intravenous Immunoglobulin Treatment of Recurrent Miscarriage:an Update of Placebo-controlled Trials

Background Immunological disturbances which may be treated with intravenous immunoglobulin (IvIg) play a significant role in the majority of patients with recurrent miscarriage (RM). The present study aimed to review the current knowledge about IvIg treatment in RM primarily based on results from published placebo controlled trials. Seven placebo controlled trials were identified comprising a total of 343 patients. The background variables, the treatment protocols and the results were extremely different between the trials. Among the patients with secondary RM, a meta analysis showed that the pooled odds ratio for live birth among IvIg treated women compared with women infused with placebo was 1.69 (95 % CI = 0.72～3.96, not significant). IvIg also seemed to be efficacious in patients with repeated second trimester intrauterine fetal deaths. A new big placebo controlled trial should be conducted which focus on RM patients with secondary RM or recurrent second trimester fetal deaths. Sufficient IvIg doses should be given with optimal time intervals.

Haemolytic Anaemia Following High Dose Intravenous Immunoglobulin Treatment for Epidermolysis Bullosa Acquisita

Background: Epidermolysis bullosa aquisita (EBA) is a severe acquired blistering skin disease that is often resistant to prednisolone but can respond well to intravenous immunoglobulin infusion (IVIg). Main Observations: We describe the case of a 35 years old male patient with EBA who developed clinically significant haemolytic anaemia with a drop in Hb from 15.3 g/dL to a nadir of 8.4 g/dL within 5 days post IVIg infusion. The patient was blood group A and the IVIg batch was found to have a high titre of anti-A immunoglobulin. Conclusions: IVIg is an effective treatment for EBA. Haemolysis associated with IVIg has not previously been reported in the dermatology literature but review of data from other specialties shows that the problem is well recognised. Dermatologists using IVIg should be aware of this potential complication and patients should be consented appropriately and warned about this potential side effect.

Evaluation of the Immunoglobulin Use in Inflammatory Systemic and Immuno-Mediated Illnesses in a Tertiary Hospital

The object of this study is to assess the Ivlg （intravenous immunoglobulin） use in inflammatory systemic and immune-mediated illnesses, in patients older than 18 years in a tertiary hospital. The assessment also intends to ensure if the clinical indications matched with the evidence-based clinical guidelines recommendations of use. Analytical, observational, transversal and retrospective study carried out during 2012. Patients with inflammatory systemic and immuno-mediated illnesses, older than 18 years old, were included. The data collected were： age, sex, number of administrations, dosage, frequency, commercial brand and the indication for what the Ivlg treatment has been prescribed. As a reference guide the British Health Department Clinical Guidelines for Immunoglobulin Use （2nd edition, 2008, and 2nd edition update 2011） and its Spanish adaption were used. The lvlg treatment was justified by a grade of recommendation A, B or C in 41% of the indications. Thus in 59% （grey indications or unclear diagnosis） the IvIg use would be questionable because of its weak evidence. It was found one indication for what the prescription of IvIg was clearly not recommended. The inflammatory systemic and immune-mediated diseases include many pathologies for what the IvIg use has not been properly studied. There is a need of consensus guidelines for IvIg use to guide doctors and pharmacists in their clinical practice. Moreover, it is important to prioritize which indications and circumstances are of first importance to have their supply guaranteed.

A Systematic Review Incorporating Meta-Analysis on the Effectiveness of Intravenous Immunoglobulin Versus Corticosteroids in the Treatment of Pediatric Myocarditis

Background:Concerns have been raised about the efficacy of intravenous immunoglobulin and corticosteroids in pediatric myocarditis;however,the relationship between the risk and efficacy of these two therapies in children with myocarditis varies.Methods:A systematic review on seventeen studies was conducted in July 2020,which included 1,960 subjects at the baseline,with 788 receiving intravenous immunoglobulin and 142 receiving corticosteroids.The mean difference(MD)or odds ratio(OR)with 95%confidence intervals(Cis)was calculated to assess the prognostic role of both treatments using dichotomous and continuous methods with random or fixed-effect models.Results:The use of intravenous immunoglobulin was significantly associated with a lower mortality rate or heart transplantation in children with myocarditis(OR,0.55;95%CI,0.40-0.77,^<0.001)compared with the control group.However,corticosteroids were not significantly associated with the same parameters(OR,0.72;95% CI,0.31-1.63,p=0.43).The use of intravenous immunoglobulin was not significantly related to improving left ventricular ejection in children with myocarditis(OR,2.30;95% CI,-9.65-14.25,p=0.71)and so were corticosteroids(MD,5.17;95% CI,-0.26-10.60,p=0.06).Conclusion:The use of intravenous immunoglobulin might have an independent risk relationship with a lower mortality rate or heart transplantation and is recommended in children with myocarditis to prevent complications.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Pure red cell aplasia due to parvovirus B19 infection after liver transplantation:A case report and review of the literature

Pure red cell aplasia （PRCA） due to parvovirus B19 （PVB19） infectiori after solid organ transplantation has been rarely reported and most of the cases were renal transplant recipients, Few have been described after liver transplantation. Moreover, little information on the management of this easily recurring disease is available at present. We describe the first case of a Chinese liver transplant recipient with PVB19-induced PRCA during immunosuppressive therapy. The patient suffered from progressive anemia with the lowest hemoglobin level of 21 g/L. Bone marrow biopsy showed selectively inhibited erythropoiesis with giant pronormoblasts. Detection of PVB19-DNA in serum with quantitative polymerase chain reaction （PCR） revealed a high level of viral load. After 2 courses of intravenous immunoglobulin （IVIG） therapy, bone marrow erythropoiesis recovered with his hemoglobin level increased to 123 g/L. He had a lowlevel PVB19 load for a 5-too follow-up period without recurrence of PRCA, and finally the virus was cleared. Our case indicates that clearance of PVB19 by IVIG in transplant recipients might be delayed after recovery of anemia.

Human parvovirus B19-associated early postoperative acquired pure red cell aplasia in simultaneous pancreas-kidney transplantation:A case report

BACKGROUND Acquired pure red cell aplasia(aPRCA)related to human parvovirus B19(HPV B19)is rarely reported in simultaneous pancreas-kidney transplantation(SPKT)recipients;there has yet to be a case report of early postoperative infection.In this current study,we report the case of a Chinese patient who experienced the disease in the early postoperative period.CASE SUMMARY A 63-year-old man,with type 2 diabetes and end-stage renal disease,received a brain dead donor-derived SPKT.Immunosuppression treatment consisted of tacrolimus,prednisone,enteric-coated mycophenolate sodium(EC-MPS),and thymoglobulin combined with methylprednisolone as induction.The hemoglobin(Hb)level declined due to melena at postoperative day(POD)3,erythropoietinresistant anemia persisted,and reticulocytopenia was diagnosed at POD 20.The bone marrow aspirate showed decreased erythropoiesis and the presence of giant pronormoblasts at POD 43.Metagenomic next-generation sequencing(mNGS)of a blood sample identified HPV B19 infection at POD 66.EC-MPS was withdrawn;three cycles of intravenous immunoglobulin(IVIG)infusion therapy were administered;and tacrolimus was switched to cyclosporine.The HPV B19-associated aPRCA resolved completely and did not relapse within the 1-year follow-up period.The diminution in mNGS reads was correlated with Hb and reticulocyte count improvements.CONCLUSION HPV B19-associated aPRCA can occur at an early period after SPKT.An effective therapy regimen includes IVIG infusion and adjustment of the immunosuppressive regimen.Moreover,mNGS can be used for the diagnosis and to reflect disease progression.

Modern approaches to incompatible kidney transplantation

The presence of human-leukocyte antigen （HLA）-antibodies and blood group incompatibility remain a large barrier to kidney transplantation leading to increased morbidity and mortality on the transplant waiting list. Over the last decade a number of new approaches were developed to overcome these barriers. Intravenous immunoglobulin （IVIG） remains the backbone of HLA desensitization therapy and has been shown in a prospective, randomized, placebo controlled trial to improve transplantation rates. Excellent outcomes with the addition of rituximab （anti-B cell） to IVIG based desensitization have been achieved. There is limited experience with bortezomib （anti-plasma cell） and eculizumab （complement inhibition） for desensitization. However, these agents may be good adjuncts for patients who are broadly sensitized with strong, complement-fxing HLA antibodies. Excellent short and long-term outcomes have been achieved in ABO incompatible transplantation with the combination of antibody removal, B cell depletion, and pre-transplant immunosuppression. Kidney paired donation has emerged as a reasonable alternative for programs who cannot provide desensitization or in conjunction with desensitization. Future therapies directed toward cytokines that alter B cell proliferation are under investigation.

An effective initial polytherapy for children with West syndrome

Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.

Kawasaki disease without changes in inflammatory biomarkers:A case report

BACKGROUND Kawasaki disease(KD)is diagnosed based on clinical features.Blood tests and other tests are auxiliary diagnostic tools.Since KD is a disease caused by arterial inflammation,many patients with KD have elevated levels of inflammatory biomarkers,such as C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and serum amyloid A protein(SAA)in blood tests.We report our experience of a patient with KD who did not have elevated levels of inflammatory biomarkers.CASE SUMMARY A 1-year-old boy presented with a 3-day history of fever.Five of the six symptoms of KD were observed,except for changes in the lips and oral cavity.Blood tests revealed no elevation in CRP,ESR,or SAA levels.Although the blood test results were atypical,the patient was diagnosed with KD based on clinical symptoms and was admitted to the hospital for treatment.The patient was administered intravenous immunoglobulin(IVIG)and aspirin.Despite commencing treatment,the fever persisted;therefore,additional IVIG was administered,the dosage of aspirin was increased,and ulinastatin was added.Three doses of IVIG were administered and the fever resolved on day 11 of KD symptoms started.Blood tests performed during hospitalization showed normal levels of inflammatory biomarkers.We examined leucine-rich alpha-2-glycoprotein 1-a protein that is elevated during the acute phase of KD.The protein levels did not increase during hospitalization.CONCLUSION This case suggests the need to identify criteria and biomarkers for detecting KD conditions that do not require KD treatment.

Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

AIM:To compare the prevalence of Helicobacter pylori (Hpylon)infection in autoimmune thrombocytopenic purpura (AITP)patients with that of nonthrombocytopenic controls, and to evaluate the efficacy of the treatment in H pylori(+) and H pylor(-)AITP patients. METHODS:The prevalence of gastric H pylori infection in 38 adult AITP patients(29 female and 9 male;median age 27 years;range 18-39 years)who consecutively admitted to our clinic was investagated. RESULTS:H pylori infection was found in 26 of 38 AITP patients(68.5%).H pylori infection was found in 15 of 23 control subjects(65.2%).The difference in H pylori infection between the 2 groups was not significant.Thrombocyte count of H pylori-positive AITP patients was significantly lower than that of H pylori-negative AITP patients(P<0.05). Thrombocyte recovery of H pylori-positive group was less than that of H pylori-negative group(P<0.05). CONCLUSION:H pylori infection should be considerecd in the treatment of AITP patients with H pylori infection.

Hematologic diseases: High risk of Clostridium difficile associated diarrhea

AIM: To investigate the incidence and clinical outcome of Clostridium difficile (C. difficile) associated diarrhea (CDAD) in patients with hematologic disease.

Granulomatosis with polyangiitis presenting as high fever with diffuse alveolar hemorrhage and otitis media: A case report

BACKGROUND Granulomatosis with polyangiitis is a necrotizing inflammation of small andmedium-sized vessels accompanied by formation of granuloma, involvement ofprimary granulomatous upper and lower respiratory tracts, glomerulonephritis,and vasculitis of small vessels.CASE SUMMARY Herein, we described a case of a 52-year-old man admitted with pulmonarynodules and high fever. Autoantibody workup revealed that the patient waspositive for c-anti-neutrophil cytoplasmic antibodies and proteinase-3 antineutrophilcytoplasmic antibodies. Pulmonary biopsies revealed a localgranulomatous structure. The patient received therapy with methylprednisoloneand intravenous immunoglobulin, and his clinical symptoms improved.CONCLUSION Intravenous immunoglobulin may act on granulomatosis with polyangiitis similarto immunosuppressants.

Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies:A case report

BACKGROUND Paraneoplastic neurological syndrome(PNS)is a rare complication in patients with cancer.PNS can affect the central,peripheral,autonomic nervous system,neuromuscular junction,or muscles and cause various neurological symptoms.Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibodypositive neurological paraneoplasms are common,but coexistence of both types has not been described in the literature.CASE SUMMARY Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers.A 55-year-old woman was admitted to our hospital with unsteadiness while walking.The patient had a history of breast cancer two years previously.Chest computed tomography revealed a 4.6 cm×3.6 cm mass in the right lung,which was diagnosed as small-cell lung cancer(SCLC).Blood test was positive for anti-Yo antibodies,and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies,and the neurological symptoms were considered to be related to the paraneoplasm.The patient was treated with a course of intravenous immunoglobulin,without noticeable improvement.After being discharged from hospital,the patient underwent regular chemotherapy for SCLC and periodic reviews.The patient’s neurological symptoms continued to deteriorate at the follow-up visit in April 2021.CONCLUSION This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies.The clinical appearance of two or more paraneoplastic tumors requires additional attention.

Immune thrombocytopenia in adults

Immune thrombocytopenia is an autoimmune disease resulting in the destruction of platelets.It is classified as acute,thrombocytopenia occurring for < 6 mo and usually resolving spontaneously,and chronic,lasting >6 mo and requiring therapy to improve the thrombocytopenia.The underlying defects leading to autoantibody production are unknown.Molecular mimicry appears to play a role in the development of self-reactive platelet antibodies after vaccination and certain viral infections.Platelet life span is reduced as a consequence of antibody-mediated clearance by tissue macrophages in essentially all patients.Diagnosis is based on the exclusion of the other causes of thrombocytopenia.Steroid is the first choice of the treatment,often followed by splenectomy in unresponsive cases.Intravenous immunoglobulin,anti-Rho(D) immune globulin,azathioprine,cyclosporine A,cyclophosphamide,danazol,dapsone,mycophenolate mofetil,rituximab,thrombopoietin receptor agonists and vinca alkaloids are other choices of treatment.