Ig Therapy Research Articles

Charting a course for global progress in PIDs by 2030 - proceedings from the IPOPI global multi-stakeholders' summit (September 2023).

The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its second Global Multi-Stakeholders' Summit, an annual stimulating and forward-thinking meeting uniting experts to anticipate pivotal upcoming challenges and opportunities in the field of primary immunodeficiency (PID). The 2023 summit focused on three key identified discussion points: (i) How can immunoglobulin (Ig) therapy meet future personalized patient needs? (ii) Pandemic preparedness: what's next for public health and potential challenges for the PID community? (iii) Diagnosing PIDs in 2030: what needs to happen to diagnose better and to diagnose more? Clinician-Scientists, patient representatives and other stakeholders explored avenues to improve Ig therapy through mechanistic insights and tailored Ig preparations/products according to patient-specific needs and local exposure to infectious agents, amongst others. Urgency for pandemic preparedness was discussed, as was the threat of shortage of antibiotics and increasing antimicrobial resistance, emphasizing the need for representation of PID patients and other vulnerable populations throughout crisis and care management. Discussion also covered the complexities of PID diagnosis, addressing issues such as global diagnostic disparities, the integration of patient-reported outcome measures, and the potential of artificial intelligence to increase PID diagnosis rates and to enhance diagnostic precision. These proceedings outline the outcomes and recommendations arising from the 2023 IPOPI Global Multi-Stakeholders' Summit, offering valuable insights to inform future strategies in PID management and care. Integral to this initiative is its role in fostering collaborative efforts among stakeholders to prepare for the multiple challenges facing the global PID community.

Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain Related to Chronic Inflammatory Demyelinating Polyneuropathy: A Proof-of-Concept Study.

Background/Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disease. Neuropathic pain (NP), related to peripheral inflammation, is among its earliest manifestations. This preliminary open-label investigation aimed to evaluate the efficacy of ultramicronized Palmitoylethanolamide (umPEA) in the management of NP. Methods: A total of 14 patients with CIDP, already undergoing immunoglobulin (Ig) therapy, were divided into two groups: Group A received umPEA 600 mg twice daily in addition to Ig for 60 days, followed by Ig alone until the end of the observation (180 days); Group B received Ig alone for 120 days and subsequently umPEA + Ig in the last 60 days of the study. Painful symptom intensity and quality of life were assessed by the Numeric Rating Scale, Neuropathic Pain Symptoms Inventory, and Five Dimensions Health Questionnaire. The safety umPEA profile was evaluated. Results: UmPEA in addition to immunoglobulins allowed for a significant improvement over time in all NP symptoms intensity (p = 0.0007) and in patients' quality of life (p = 0.0036). Conclusions: This study suggests umPEA as a safe and effective treatment in addition to immunoglobulins to improve NP, ameliorating the patient's health status. These results highlight the importance of neuroinflammation modulation in the management of CIDP's painful symptoms, drawing attention to umPEA's potential use also in neuropathies of different etiologies.

Longitudinal evaluation of serum MOG-IgG titers in MOGAD after initiation of maintenance immunoglobulin: A case series.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct demyelinating disease of the central nervous system. Immunoglobulin (Ig) has been used as a maintenance therapy to prevent relapses in MOGAD, but the impact of Ig on serum MOG-IgG titers is unclear. To characterize the variation in serum MOG-IgG titers after initiation of Ig treatment in people with MOGAD. We conducted a retrospective study of 10 patients with a diagnosis of MOGAD and available serum MOG-IgG titers before and after initiation of maintenance Ig treatment. We found that most of the patients remained MOG-IgG seropositive while on Ig treatment with a reduced or unchanged titer, despite a lack of disease activity. This case series suggests that the mechanism of action of Ig therapy in MOGAD is not exclusively dependent on MOG-IgG titer reduction.

Benefits of Immunoglobulin (Ig) Replacement Therapy for Primary and Secondary Immunodeficiency in Chronic Rhinosinusitis.

This is the first study to examine chronic rhinosinusitis (CRS) outcomes after starting immunoglobulin (Ig) replacement therapy for patients with primary (PID) and secondary immunodeficiency (SID). This is a retrospective review of patients diagnosed with CRS from 2018 to 2022 prior to initiating Ig therapy for the treatment of PID or SID. Outcomes included medication use and Sinonasal Outcome Test (SNOT-22) scores. Ten patients met the inclusion criteria. PID and SID patients had a decrease in antibiotics (PID: 9.40 to 3.20, P = .05, SID: 8.20 to 2.00, P = .04) and steroids (PID: (5.40 to 0.60; P = .06; SID: 2.20 to 0.20, P = .047) prescribed in the year after Ig compared to the year prior. Patients with SID had a decrease in mean SNOT-22 scores by 12 months after Ig (47.50 to 20.50, P = 0.03). Patients receiving Ig for PID and SID showed decreased medication use and SID patients experienced subjective improvement in CRS symptoms in year-over-year comparison.

Navigating the management complexity in long-term asymptomatic immunodeficiency

Background: Common variable immunodeficiency disorder (CVID) is a condition associated with recurrent infections and non-infectious outcomes, including lung disease like bronchiectasis and granulomatous and lymphocytic interstitial lung diseases (GLILD), autoimmune disease, enteropathy, and lymphoma. Treatment involves initiation of replacement immunoglobulin (Ig), which is a lifelong commitment. Prior to Ig replacement, life expectancy for patients with CVID was less than 15 years. With replacement Ig, it has improved to over 50 years. In most cases, patients present to a clinician with a history of recurrent infections, and treatment is indicated. However, in patients with asymptomatic disease, the best timing to start treatment can be difficult to determine. Case: We present a case of an otherwise healthy male who had an incidental diagnosis of CVID. Results: Workup revealed hypogammaglobulinemia for over 30 year. Discussion: Though successful in reducing infections, Ig replacement can come with many side effects, as well as a heavy medical burden to the patient and the healthcare system. It is also a big life adjustment, and can greatly affect a patient's quality of life. In the military, a diagnosis of an immunodeficiency, and the need for monthly intravenous immunoglobulin (IVIG) can be detrimental to deployment readiness, and a patient's military career. Risks and benefits need to be weighed prior to initiating Ig therapy.

Netherton Syndrome in a 1-year-old Filipino Female

Abstract Netherton syndrome (NS) is an autosomal recessive genodermatosis characterized by cutaneous and systemic complications (recurrent infections, dehydration, and sepsis). This highlights the urgency of making an accurate diagnosis, especially in infants and children. However, it is important to note that the recognition of NS is usually delayed due to its rarity and similarity to cutaneous disorders with atopiform, erythrodermic, and ichthyosiform presentations. We report a case of a 1-year-old female who was previously diagnosed with a case of infantile psoriasis and was subsequently treated with topical emollients. However, after months of surveillance, the patient developed feeding problems, failure to thrive, recurrent diarrhea, upper respiratory tract, and gastrointestinal infection, leading to repeated hospitalizations. The patient then underwent further clinical examinations and laboratory analysis, which revealed abnormal hair shaft findings, elevated immunoglobulin (Ig) E levels, and normal chromosomal analysis. Multispecialty referrals with other services were done to address the current problems and ensure holistic care for the patient. On her last admission, the patient was given three doses of intravenous Ig therapy with noted improvement in lesion presentation without any systemic symptoms.

Diagnosis of a case of X-linked agammaglobulinemia with juvenile idiopathic arthritis and recurrent pneumonia in Bangladesh

Abstract X-linked agammaglobulinemia (XLA) is a rare hereditary primary immunodeficiency disorder caused by mutation in the Bruton’s tyrosine kinase (BTK) gene located in the Xq22 region of the X chromosome. It is characterized by absolute or marked deficiency of matured B-cells in circulation as well as decreased in all immunoglobulin (Ig) classes. We have reported one case who is a 48-month-old boy and suffering from recurrent pneumonia, skin abscess, otitis media, and swelling of the left knee joint. His serum Ig levels showed an IgM level of <0.169 g/l, IgG 2.43 g/l, and IgA <0.256 g/l. Immunophenotyping of lymphocyte subsets showed an absence of B-cells. Intracellular BTK protein expression in monocytes by flow cytometry showed a markedly reduced mean fluorescence index which confirmed the diagnosis of XLA. Antibiotics with intravenous Ig therapy were started.

A Case Report and Review of Increased IgE in Patients with Transient Hypogammaglobulinemia of Infancy and Atopic Dermatitis after Normalization of IgG

The coexistence of a high IgE level and transient hypogammaglobulinemia of infancy ( THI ) with atopic dermatitis (AD) is well known, but the coexistence with a marked serum IgE level ≥ 1000 IU/mL is a rare finding. Literature is scarce regarding IgE levels in patients with THI and AD after treatment with immunoglobulin (Ig). We reported a female infant 8 months old, with THI and severe AD. She was treated with intravenous immunoglobulin (IVIG) infusion after the failure of conventional therapy. Initially, serum levels of IgE were high, and serum levels of IgG were low. After 4 weeks of treatment with IVIG, patient profile showed normalization of IGE and higher elevation in IgG level. The present article is the first to describe a finding of marked IgE elevation (> 1000 IU/mL) after treatment with IVIG. Furthermore, our finding is supported by our review of increased IgE levels in patients with THI and AD who received IG therapy. According to our review different trend of IgE levels in patients who achieved spontaneous normalization of IgG was found.

Long-Term Host Immune Changes Following Treatment with Venetoclax Plus Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia

Background: Immune dysregulation is a hallmark of chronic lymphocytic leukemia (CLL) and often leads to hypogammaglobulinemia and frequent infections. Treatment with anti-CD20 antibodies (Abs) such as rituximab (R) is a known risk factor for hypogammaglobulinemia. Despite the widespread use of anti-CD20 Abs in combination with venetoclax (Ven), a B cell lymphoma 2 inhibitor, little has been reported on the long-term impact of this therapy on B cell recovery. We report long-term immune changes post treatment in patients (pts) with relapsed/refractory CLL in the MURANO phase 3 trial (NCT02005471) who completed the full VenR course without progressive disease (PD). Methods: Overall, 389 pts were randomized to either VenR (2 years of Ven with R for the first 6 months) or 6 months of bendamustine-R. Minimal residual disease (MRD) status has been previously reported (Kater et al. J Clin Oncol 2020). In the VenR arm, immunoglobulin (Ig) G, A and M, and T, B, and natural killer (NK) cells were measured centrally at baseline (BL), cycle 4 day 1 (C4D1), end of combination treatment (EOCT), end of treatment (EOT), and every 3 months for up to 3 years, then every 6 months until PD. This is a post hoc analysis among evaluable pts; statistics are descriptive only. Results: In total, 130 pts completed 2 years of VenR without PD (27 pts were excluded from this analysis as they received Ig therapy during the study). BL characteristics amongst those included were consistent with the whole population. Median change from BL by visit (EOT, 12 months, and 24 months post EOT) was calculated among pts with paired evaluable BL and visit samples (Table 1). IgG was significantly decreased at EOT vs BL (n=91; median change from BL, -5.9%). At 12 months (n=77; median change from BL, -4.8%) and 24 months (n=58; median change from BL, 1.1%) post treatment, IgG was not significantly different to BL levels. While there was no reduction in IgA from BL at EOT, at 12 and 24 months post treatment, IgA levels were significantly increased (median change from BL, 12.5% and 35.1%, respectively). IgM levels were significantly reduced at EOT vs BL (median change from BL, -32.3%), but returned to BL levels at 12 months post treatment (median change from BL, 11.1%). At 24 months post treatment, IgM had significantly increased by 49.5% compared with BL levels. There was no significant difference in median IgG, IgA and IgM levels at any time point amongst pts who achieved undetectable (u)MRD at EOT vs pts with MRD at EOT. In pts who received VenR the overall infection rate was low; however, there was a non-statistically significant, but numerically higher rate of grade ≥3 infections occurring on treatment in those with uMRD at EOT compared with those who had MRD at EOT (15.2% [10/66] vs 7.1% [2/28]; p=0.5). T, B and NK cell data were available for all 130 pts. A depletion in CD19+ B cells was observed on treatment, which was more pronounced in pts with uMRD at EOT. After EOCT, B cell recovery started ~1 year later, and stabilized ~30 months after EOCT, regardless of EOT MRD status (Figure 1). Given the differences in disease burden at EOT, comparable CD19+ B cell recovery in pts with uMRD and MRD is likely to be representative of a larger relative proportion of normal B cells vs CLL cells. Additional analyses to test this are underway. At BL, total CD3+ T cells were increased (median [range], 1,991 [135-17,334]; reference values as previously reported, 700-2,100/µL [de Weerdt et al. Blood Adv 2019]). Though a reduction of CD3+ T cells was observed during combination treatment (C4D1), the number of CD3+ T cells were maintained within the reference range post treatment. A similar pattern was observed for NK cells. The median (range) CD4/CD8 ratio at BL was 1.10 (0.33-5.77) and was maintained throughout the study. Conclusions: Overall, pts demonstrated immune recovery following fixed-duration treatment with VenR in this post hoc exploratory analysis. This is the first time that post-treatment serial Ig levels have been reported following VenR therapy. Recovery of IgG, IgA and IgM levels post treatment was observed regardless of EOT MRD status. While the overall incidence of grade ≥3 infections was low, the rate was numerically higher in pts with uMRD at EOT compared with pts with MRD. Additional analyses are underway to assess the correlation between infection and MRD state. A normalization of CD3+ T cells during and after VenR is consistent with previous reports. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

RESULTS OF A PHASE 4 STUDY OF IMMUNOGLOBULIN [HUMAN] SUBCUTANEOUS FOR PATIENTS REQUIRING IMMUNOGLOBULIN

<h3>Introduction</h3> Immunoglobulin (Ig) therapy has transformed into the preferred treatment for patients diagnosed with various conditions that attack and disable the immune system. Originally, immunoglobulin therapy could only be administered intravenously, but subcutaneous IgG (SCIg) has become a standard of care. This study compares immunoglobulin [human] subcutaneous 16.5% to other currently marketed SCIg products. <h3>Methods</h3> The study was designed to enroll 150 male or female patients with immune dysfunction in one of 3 study arms. Arm 1 enrolled patients naïve to Ig therapy; arm 2 enrolled patients currently receiving IVIG therapy; and arm 3 enrolled participants receiving other SCIg products. Participants receiving SCIg continued on their current product for Visit 1 and Visit 2, with the option of switching to the test product for Visit 3 – Visit 7. After screening, the length of study participation is approximately 6 months. Data regarding number of infusions, laboratory measurements, rate of infection, and quality of life (using 4 mental health questionnaires) were collected every 4 weeks (±3 days). <h3>Results</h3> The study currently has 45 actively enrolled patients. Patients had an average IgG serum quantitative value of 960.55 in arm 1, 1084.27 in arm 2, and 1231.34 in arm 3. Patients in arm 3 had been on therapy longer, which might explain their higher trough levels, although efficacy was seen in all 3 arms. Additionally, patients reported greater quality of life during the study. <h3>Conclusion</h3> Preliminary results suggest a link between higher IgG levels and greater reported quality of life. Further data is forthcoming.

A nursing primer: immunoglobulin (Ig) therapy for secondary antibody deficiency (SAD) in haematological malignancies

A nursing primer: immunoglobulin (Ig) therapy for secondary antibody deficiency (SAD) in haematological malignancies

SEVERE PAPULAR ECZEMA SKIN REACTION AFTER INTRAVENOUS IMMUNOGLOBULIN INFUSION IN PATIENT WITH CHRONIC LYMPHOCYTIC LEUKEMIA: A CASE REPORT

Hypogammaglobulinemia is a common finding in Chronic Lymphocytic Leukemia (CLL). Their etiology is multifactorial, due to disease-related immune defects and chemo-immunotherapy treatment as Rituximab. It is present in up to 85 % of patients at some point in their disease course. It is therefore important to monitor patients for the development of an antibody deficiency due to being susceptible to infections. Strategies to prevent infections in patients with secondary antibody deficiencies include replacement Immunoglobulin (Ig). However, nearly 6% develop skin reaction Ig associated, a rare adverse event reported only in case reports. A 64 years-old man was diagnosed with CLL in 2011. Despite treatment with Chlorambucil, in July 2013, the patient had therapeutic failure, so he switched to a 2nd-line regimen, with intravenous chemotherapy with cyclophosphamide, vincristine and prednisone for 2 cycles. In September 2013, due to disease progression, he was switched to a 3rd-line regimen with fludarabine and cyclophosphamide. In 2014, he presented an increase in the size of the cervical lymph nodes, so he used 8 cycles of Rituximab. After Rituximab-therapy, hypogammaglobulinemia was detected due to recurrent infections. Then, the patient received Ig monthly with pre-medication. Fifteen days after this Ig infusion, he developed an extensive pruritic, eczematous rash and lichenified skin lesions on the upper limbs. In the following months, 48 hours after the Ig infusion, he presented excoriated eczematous plaques located in the inguinal region and posterior thighs, with follicular pustules (delayed hypersensitivity reaction, type IV). Histological analysis of a skin biopsy specimen revealed subacute spongiotic dermatitis with intraepidermal microvesiculation. The lesions progressively regressed after stopping Ig infusions, oral prednisone, dapsone and topical application of tacrolimus and corticosteroids. Although the Rituximab used in the treatment of patients with CLL is capable of depleting the population of malignant lymphocytes, they lack specificity and further contribute to the significant immune dysfunction that predisposes these patients to a serious risk of infection. As such, the use of Ig therapy is increasing in the treatment of CLL. However, the severity of its rare adverse effects is often poorly recognized. Dermatologic adverse effects of Ig are rare and include urticaria, papules, eczema, pompholyx, lichenoid dermatitis, and desquamation. The underlying mechanism resulting in skin reactions following treatment with Ig is not clear. Most of these reactions develop within 2 weeks after immunoglobulin administration. The rash is managed with topical/systemic steroids and antihistamine treatment. These adverse events can also lead to cessation of therapy. This case report highlights the fact that cutaneous adverse effects of IgIV are more common than previously believed. Although the precise mechanism of this cutaneous eruption remains to be elucidated, its occurrence within days of Ig infusion, its characteristic distribution at onset, and its clinical course should be recognized by hematologists and dermatologists.

Different modalities of the treatment of Rasmussen encephalitis: A systematic review of case reports of a rare disease

Background: Rasmussen’s encephalitis (RE) is a rare chronic neurological disorder that presents with progressive neurological and cognitive deterioration, and intractable seizures that lacks definitive management. We aimed to identify case reports of RE in the literature to assess the treatment based on the symptoms and outcomes after the treatment. Methods: We searched the databases PubMed, Google Scholar, and the Cochrane Library from 1990 to 22nd February 2022 in order to review the case reports that included the treatment options and clinical outcomes of RE. A pre-established protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (ID: CRD42021261999). Results: The mean age of onset of seizure was 31.44 and 6.87 years in adult onset RE and children (below 15 years of age) with RE respectively. A total of four (44.44%) out of nine adult patients and 81 (66.39%) out of 122 children underwent surgery. Tacrolimus was used in 17 (13.93%) and steroid therapy was used in 11 (9.01%) of the children. Conclusions: Large scale-controlled trials are needed to study the beneficial effect of tacrolimus, IV Ig, and plasma therapy. Hemispherectomy should be opted as a treatment modality by assessing the impairment of patients’ motor or language functions following the treatment procedure.

Transition to Subcutaneous Immune Globulin 16.5% Improves Patient-Reported Quality of Life

Subcutaneous immune globulin (IGSC) offers the convenience of self-administration, fewer systemic reactions, and more stable IgG levels compared to intravenous IG (IVIG). The Life Quality Index (LQI) is an instrument to evaluate health-related quality of life (QoL) and treatment satisfaction among patients receiving IG therapy and has been previously applied to product switches. We report QoL survey results for patients transitioned to IGSC 16.5% (Cutaquig®) from IVIG or alternative IGSC in a real-world setting.

Replacement and Immunomodulatory Activities of 20% Subcutaneous Immunoglobulin Treatment: A Single-Center Retrospective Study in Autoimmune Myositis and CVID Patients.

BackgroundImmunoglobulin (Ig) replacement therapy represents a life-saving treatment in primary antibody deficiencies. The introduction of subcutaneous Ig (SCIg) administration brings a major improvement in quality of life for patients, compared to the traditional intravenous administration. In recent years, an additional role has been proposed for Ig therapy for various inflammatory and immune-mediated diseases. Consequently, the use of SCIg has expanded from immunodeficiencies to immune-mediated diseases, such as polymyositis (PM) and dermatomyositis (DM). Given the rarity of these conditions, it is still difficult to evaluate the real impact of SCIg treatment on PM and DM, and additional data are constantly required on this topic, particularly for long-term treatments in real-life settings.AimThis study aimed to increase the knowledge about the anti-inflammatory and immunomodulatory effects of SCIg treatment for myositis. To this aim, a long-term evaluation of the effectiveness of 20% human SCIg treatment (20% SCIg, Hizentra®, CSL Behring) was carried out in patients with PM/DM in care at our Center. In addition, an evaluation of the 20% SCIg therapy in CVID patients was provided. This analysis, beside adding knowledge about the use of SCIg therapy in this real-life setting, was intended as a term of comparison, regarding the safety profile.ResultsResults support the beneficial effect and tolerability of long-term 20% SCIg therapy in PM/DM patients, reporting a significant improvement in creatine kinase levels, muscle strength, skin conditions, dysphagia, disease activity (MITAX score) and disability (HAQ-DI score). None of the patients reported systemic reactions. The duration of the reported local reactions was a few hours in 80% of the patients, and all resolved spontaneously. CVID patients reported an improvement in all the considered effectiveness parameters at the end of 20% SCIg therapy. The frequency of the adverse events reported by PM/DM patients was not different from what reported in CVID patients, where the use of SCIg therapy is more consolidatedConclusionsThis study suggests that 20% SCIg treatment represents a viable and safe treatment for PM/DM patients and a valid therapeutic alternative to IVIg, with important advantages for patients’ quality of life.

Variation in Use of Immunoglobulin and Impact on Survival in Multiple Myeloma: A Report from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR)

Variation in Use of Immunoglobulin and Impact on Survival in Multiple Myeloma: A Report from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR)

Rationale for Polyclonal Intravenous Immunoglobulin Adjunctive Therapy in COVID-19 Patients: Report of a Structured Multidisciplinary Consensus.

Introduction: Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID-19 and the mechanisms of action of Ig led to the consideration of this adjunctive therapy, including in patients with respiratory failure due to the SARS-CoV-2 infection. This manuscript reports the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID-19. Methods: A panel of multidisciplinary experts defined the clinical phenotypes of COVID-19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. Results: Three different phenotypes of COVID-19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune paralysis (late phase) and patients with sepsis due to a hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panelists considered its use in the late phase and patients with sepsis/septic shock by bacterial superinfection appropriate. Conclusion: As with other immunotherapies, IVIg adjunctive therapy may have a potential role in the management of COVID-19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness.

Rapidly Progressive Cognitive Decline and Varicella Zoster Blisters Associated With Teprotumumab in 2 Patients With Graves’ Orbitopathy

Introduction: Teprotumumab, an IGF-1R antagonist, was approved for treatment of Graves’ orbitopathy (GO) in 2020. Common side effects include nausea, diarrhea, muscle spasms, hearing impairment, dysgeusia, headache, dry skin, infusion reactions, and hyperglycemia. We report here 2 cases of unexpected adverse effects. Patient #1 is a 76-year-old man with Graves’ disease diagnosed in 2018, treated with methimazole 2.5mg every other day. His GO manifestations included diplopia, proptosis, and exposure keratopathy. Past history was significant for hypertension, hyperlipidemia, and prostate hyperplasia. He lived independently and walked several miles daily. Teprotumumab was initiated. Between the 4th and 5th doses, his family noted 6-weeks of rapidly progressive cognitive decline characterized by behavioral changes, confabulation, memory deficit, delirium/delusions/mania. He was admitted to neurology service and subsequent doses held. Lumbar puncture was unremarkable. TFT was normal before, during and after stopping teprotumumab. Thyroid antibodies were notable for elevated TSI but normal thyrotropin receptor Ab and TPO/TgAb. Other labs: IL2, IL6, ESR, CRP, heavy metals, IgG, IgM, SARS-CoV-2 IgM/IgGs, vitamins B1, B6, and B12 were all normal. His most recent repeat TPO Ab was 14 IU/mL (increased from <6), TgAb 18.4 IU/mL (increased from <1.0). EEG showed no epileptiform activity. Head MRI/MRA showed cerebral amyloid angiopathy without stenosis or aneurysms in the intracranial arterial vasculature. Symptoms progressed with IV glucocorticoids and IV Ig therapy. He subsequently underwent plasmapheresis with resolution of symptoms. Patient #2 is a 48-year-old man with Graves’ disease and GO diagnosed in 2018, initially treated with methimazole and subsequently underwent total thyroidectomy in 2019. Patient is euthyroid on levothyroxine. Ophthalmic signs and symptoms included significant proptosis and retrobulbar pain. He was started on teprotumumab infusions. After his 4th dose, he noted painful vesicles in a dermatomal distribution on his right posterior thigh. Direct fluorescent antibody stain was positive for varicella zoster, and rashes resolved with valacyclovir therapy. Discussion: Paraneoplastic/autoimmune encephalitis syndromes can be associated with antibodies to neuronal cell surfaces/synaptic proteins and may occur in the presence or absence of cancer. The incidence of varicella-zoster virus infection is associated with the immune status of the patient, disease-related immunocompromised, or iatrogenic immunosuppression, with age being the major risk factor for 90% of adult cases. This could be incidental, or related to other disorders, or perhaps teprotumumab may have activated auto-immunity. The exact mechanisms for rapidly progressive cognitive decline and shingles remains unclear.

Rescue therapy with intravenous immunoglobulin in severe refractory dengue: A pilot study

BackgroundSevere dengue causes more than 22,000 deaths annually worldwide. Complicated dengue has high mortality of 44–72%. Disordered immune system with capillary leak and thrombocytopenia are hallmark of complicated dengue. Intravenous immunoglobulin (IV Ig) therapy has shown to be effective in complicated dengue in pediatric age group with refractory shock, but studies in adults are lacking. Its immunoresuscitative role is not yet fully explored in critically ill patients with severe dengue. MethodsThis is retrospective observational study of patients with complicated dengue fever who were administered IV Ig therapy in a tertiary care hospital of southern India from 01 Jan 2018 to 31 Dec 2019. ResultsA total of 999 patients with dengue were admitted; 754 (75.47%) were males, and 245 (24.53%) were females. A total of 402 (40.24%) patients presented with warning signs. Bleeding was seen in 121 patients (12.11%); 102 (10.21%) had shock; 29 (2.90%) had acute kidney injury and 24 (2.40%) had adult respiratory distress syndrome. Overall, four people died (mortality rate: 0.40%). IV Ig in the dose of 0.4 g/kg for 5 days was used in 13 critically ill patients where standard therapy failed, 9 patients with refractory shock (which included three with myocarditis with refractory shock), 2 with encephalitis, 2 in hemophagocytic lymphohistiocytosis. Two patients died, one with myocarditis with refractory shock and another with refractory shock. ConclusionIV Ig therapy in critically ill patients with complicated dengue can be used as a rescue therapy.

Individualizing Therapy in CIDP: A Mini-Review Comparing the Pharmacokinetics of Ig With SCIg and IVIg.

Immunoglobulin (Ig) therapy is a first-line treatment for CIDP, which can be administered intravenously (IVIg) or subcutaneously (SCIg) and is often required long term. The differences between these modes of administration and how they can affect dosing strategies and treatment optimization need to be understood. In general, the efficacy of IVIg and SCIg appear comparable in CIDP, but SCIg may offer some safety and quality of life advantages to some patients. The differences in pharmacokinetic (PK) profile and infusion regimens account for many of the differences between IVIg and SCIg. IVIg is administered as a large bolus every 3–4 weeks resulting in cyclic fluctuations in Ig concentration that have been linked to systemic adverse events (AEs) (potentially caused by high Ig levels) and end of dose “wear-off” effects (potentially caused by low Ig concentration). SCIg is administered as a smaller weekly, or twice weekly, volume resulting in near steady-state Ig levels that have been linked to continuously maintained function and reduced systemic AEs, but an increase in local reactions at the infusion site. The reduced frequency of systemic AEs observed with SCIg is likely related to the avoidance of high Ig concentrations. Some small studies in immune-mediated neuropathies have focused on serum Ig data to evaluate its potential use as a biomarker to aid clinical decision-making. Analyzing dose data may help understand how establishing and monitoring patients' Ig concentration could aid dose optimization and the transition from IVIg to SCIg therapy.