Eur Ann Allergy Clin Immunol. 2024 Apr 5. doi: 10.23822/EurAnnACI.1764-1489.340. Online ahead of print.
NO ABSTRACT
PMID:38578199 | DOI:10.23822/EurAnnACI.1764-1489.340
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Stanford Alliance for Primary Immunodeficiency
Stanford University
By Manish Butte
Eur Ann Allergy Clin Immunol. 2024 Apr 5. doi: 10.23822/EurAnnACI.1764-1489.340. Online ahead of print.
NO ABSTRACT
PMID:38578199 | DOI:10.23822/EurAnnACI.1764-1489.340
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By Manish Butte
J Investig Med High Impact Case Rep. 2024 Jan-Dec;12:23247096241239544. doi: 10.1177/23247096241239544.
ABSTRACT
Citrobacter koseri (formerly classified as Citrobacter diversus) is a gram-negative bacillus (GNB) that occurs as an opportunistic pathogen in neonates and immunocompromised patients. Citrobacter species have been implicated in nosocomial settings leading to infections involving the urinary tract, respiratory tract, liver, biliary tract, meninges, and even in rarer conditions-blood stream infection and infective endocarditis (IE). Gram-negative bacilli are responsible for 3% to 4% of all IE cases and have been traditionally associated with intravenous drug users. Patients with non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kinglella species) GNB IE have poor clinical outcomes with higher rates of in-hospital mortality and complications. The American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) both recommend the use of combination antibiotic therapy with a beta-lactam (penicillins, cephalosporins, or carbapenems) and either an aminoglycoside or fluoroquinolones for 6 weeks (about 1 and a half months) to treat IE due to non-HACEK GNB. Citrobacter koseri is becoming more recognized due to its inherent resistance to ampicillin and emerging drug resistance to beta lactams and aminoglycosides requiring carbapenem therapy. Our case is of a 75-year-old male with no previously reported history of primary or secondary immunodeficiency disorders who developed C koseri blood stream infection. His infectious work-up revealed mitral valve IE and septic cerebral emboli resulting in ischemic infarcts. This case illustrates the importance of recognizing GNB organisms as rising human pathogens in IE cases even without active injection drug use or nosocomial exposure.
PMID:38577758 | DOI:10.1177/23247096241239544
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By Manish Butte
J Med Access. 2024 Mar 28;8:27550834241236596. doi: 10.1177/27550834241236596. eCollection 2024 Jan-Dec.
ABSTRACT
BACKGROUND: Secondary immunodeficiency (SID) disorders are known to occur in patients with haematological malignancies (HM) due to immunosuppressive treatments. Recurring infections causing subsequent morbidity and mortality commonly occur in this patient cohort. Immunoglobulin replacement therapy (IgRT) benefits patients with primary antibody deficiencies. However, evidence supporting their therapeutic role is not as explicit in SID-associated antibody deficiencies, which raises the questions regarding its use in SID and the knock-on effects of this use on its access and availability more generally.
OBJECTIVES: This study aimed to learn about the use of immunoglobulins in SID, identify themes concerning its use and access and suggest methods for improving access.
DESIGN: This study included a thematic analysis of a published data set of 43 articles concerning immunoglobulin use and access in SID.
DATA SOURCES AND METHODS: The data set used to perform the thematic analysis is based on research articles identified from Excerpta Medica Database (EMBASE) and PubMed databases, published as part of a systematic review and part 1 of this two-part publication series.
RESULTS: A thematic synthesis was conducted to identify recurrent themes. The three primary themes included (1) the context for IgRT prescription, which included patient characteristics and cost burden of IgRT administration, and its use in different countries; (2) factors contributing to inappropriate IgRT use, including health care professionals’ awareness of IgRT, disparity between guidelines and actual clinical practice, and the effect of shortages on prescription and chemotherapy-induced hypogammaglobulinemia (HGG); and (3) measures identified to improve IgRT use and access, which included multidisciplinary involvement, improved diagnostic tools and safer withdrawal and stewardship protocols.
CONCLUSIONS: IgRT use is increasing in HM as a supportive therapy but without comprehensive clinical guidelines and appropriate prescribing recommendations, medication wastage may occur with consequences for immunoglobulin access.
PMID:38559466 | PMC:PMC10981255 | DOI:10.1177/27550834241236596
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By Manish Butte
Cent Eur J Immunol. 2023;48(4):350-357. doi: 10.5114/ceji.2023.133949. Epub 2023 Dec 21.
ABSTRACT
Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described disease characterized by recurrent infections, lymphoproliferation with a high risk of malignancy, early-onset cytopenia, and a propensity for autoimmune diseases. Hematopoietic stem cell transplantation (HSCT) has proven to be an effective treatment method; however, the recovery process after HSCT is prolonged and accompanied by complications. In this study, we present the case of a patient with APDS type 1. Despite showing signs of immunodeficiency at the age of 6 months, it took almost 6 years to reach a definitive diagnosis. The patient experienced recurrent infections, often accompanied by anemia requiring transfusions, and multifocal nonmalignant lymphoproliferation. Only after receiving the appropriate diagnosis was it possible to implement proper and accurate treatment. HSCT was performed when the patient was 6 years old, leading to significant improvement in his condition. At the 17-month post-HSCT follow-up, the boy is asymptomatic and in good general health, although close monitoring continues due to mixed chimerism and delayed humoral immune recovery. Applying HSCT before the patient develops malignancy contributes to expanding the use of HSCT as a treatment option for APDS type 1.
PMID:38558560 | PMC:PMC10976654 | DOI:10.5114/ceji.2023.133949
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By Manish Butte
J Allergy Clin Immunol. 2024 Mar 29:S0091-6749(24)00326-9. doi: 10.1016/j.jaci.2024.03.014. Online ahead of print.
ABSTRACT
BACKGROUND: Prior studies have reported that renal insufficiency occurs in a small percentage of patients with predominantly antibody deficiency (PAD) and in about 2% of patients with common variable immunodeficiency (CVID).
OBJECTIVE: The goal of our study was to understand and evaluate the prevalence and type of renal complications in PAD patients in the United States Immunodeficiency Network (USIDNET) cohort. We hypothesized there is an association between certain renal complications and severity of immunophenotype in patients with PAD.
METHODS: We performed a query of patients with PAD from the USIDNET cohort with renal complications. Patients with documented renal disease such as chronic kidney disease (CKD), nephrolithiasis, nephritis, and renal failure syndrome were included. We compared immunophenotype, flow cytometry and immunoglobulin (Ig) levels of PAD patients with renal complications to the total PAD USIDNET cohort.
RESULTS: We identified that 140/2071 (6.8%) of PAD patients had renal complications. Of these 50 (35.7%) had CKD, 46 (32.9%) had nephrolithiasis, 18 (12.9 %) had nephritis, and 50 (35.7%) had other renal complications. Compared to the total USIDNET cohort of patients with PAD, patients with CKD had lower ALCs, CD3+ T-cells, CD4+ T-cells, CD19+ B-cells, CD20+ B-cells and CD27+IgD- B-cells (p<0.05 for all). Patients with nephritis had lower ALCs, CD19+ B-cells, CD27+ B-cells and IgE levels (p<0.05 for all) compared to PAD patients without renal disease.
CONCLUSIONS: We identified that 6.8% of PAD patients in the USIDNET cohort had a documented renal complication. The patients with nephritis and CKD had a more severe immunophenotype compared to the overall PAD cohort.
PMID:38555979 | DOI:10.1016/j.jaci.2024.03.014
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By Manish Butte
Front Med (Lausanne). 2024 Mar 14;11:1381492. doi: 10.3389/fmed.2024.1381492. eCollection 2024.
ABSTRACT
BACKGROUND: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are skin-derived carcinomas. The literature strongly connects SCC with acquired immunosuppression. Current data regarding BCC’s association with immunosuppressive comorbidities are vague. The primary objective of this study was to establish the correlations between BCC and immunosuppressive comorbidities of patients. Materials and methods: We conducted a retrospective cohort study on 275 patients with a histopathological proven diagnosis of BCC from October 2019 to October 2023. Demographic data, BCC characteristics, and patients’ comorbidities were analyzed. Comorbidities were classified as non-immunosuppressant and immunosuppressant (primary and secondary immunodeficiencies).
RESULTS: We recorded 292 BCCs from 275 patients (142 females, 133 males), with equally distributed skin phototypes. 66.44% of the BCCs were detected in patients with various comorbidities (p < 0.001), of which 81.44% had immunosuppressive comorbidities (p < 0.001). All the immunosuppressive comorbidities were secondary and included diabetes mellitus (47.55%), history of solid or hematogenous cancer in the last 5 years (26.57%), chronic kidney disease (8.39%), chronic infections (9.09%), and antirheumatic immunosuppressive therapies (8.39%) (p < 0.001). BCC patients with immunosuppressive comorbidities did not develop larger BCCs (p = 0.2577) or more aggressive subtypes (p = 0.4269) and BCC did not arise earlier in their life (p < 0.001). BCC on the nasal pyramid was frequent in cancer history patients (p = 0.008). The ulcerated form of BCC is more confined to patients with chronic kidney disease (p = 0.006). Multiple BCCs are more frequent in patients with secondary immunodeficiencies (p = 0.027).
CONCLUSION: BCC represents a clinical indicator of secondary immunodeficiency. Further research should establish if cancer screening campaigns may be beneficial in BCC patients.
PMID:38549869 | PMC:PMC10977600 | DOI:10.3389/fmed.2024.1381492
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By Manish Butte
Tunis Med. 2024 Jan 5;102(1):1-6. doi: 10.62438/tunismed.v102i1.4503.
ABSTRACT
Autoimmune cytopenias are defined by autoantibodies’ immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune thrombocytopenia or both that define Evans syndrome. It may be secondary to infection or to underlying pathology such as systemic autoimmune disease or primary immunodeficiency, especially when it becomes chronic over several years. Primary Immunodeficiencies or inborn errors of immunity (IEI) are no longer defined solely by infections: autoimmunity is part of the clinical features of several of these diseases. It is dominated by autoimmune cytopenias, in particular, immune thrombocytopenia (ITP) and autoimmune hemolytic anaemia (AIHA). The challenges for the clinician are the situations where autoimmune cytopenias are chronic, recurrent and/or refractory to the various long-term therapeutic options. Most of these therapies are similar in action and generally consist of non-mediated immune suppression or modulation. In these situations, primary Immunodeficiencies must be diagnosed as soon as possible to allow the initiation of a targeted treatment and to avoid several ineffective therapeutic lines.
PMID:38545722 | DOI:10.62438/tunismed.v102i1.4503
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By Manish Butte
J Allergy Clin Immunol Glob. 2024 Feb 20;3(2):100234. doi: 10.1016/j.jacig.2024.100234. eCollection 2024 May.
ABSTRACT
BACKGROUND: Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied.
OBJECTIVE: We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response.
METHODS: We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes.
RESULTS: The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [P < .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis.
CONCLUSIONS: In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.
PMID:38544577 | PMC:PMC10965812 | DOI:10.1016/j.jacig.2024.100234
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By Manish Butte
Australas J Dermatol. 2024 Mar 27. doi: 10.1111/ajd.14258. Online ahead of print.
ABSTRACT
Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.
PMID:38544290 | DOI:10.1111/ajd.14258
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By Manish Butte
J Clin Med. 2024 Mar 16;13(6):1717. doi: 10.3390/jcm13061717.
ABSTRACT
Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID’s relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients’ heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.
PMID:38541942 | DOI:10.3390/jcm13061717
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