Manish Butte

Front Surg. 2023 May 18;10:1200432. doi: 10.3389/fsurg.2023.1200432. eCollection 2023.

ABSTRACT

BACKGROUND: The incidence of spondylodiscitis (SD) and isolated spinal epidural empyema (ISEE) has been increasing in the last decades, but the distinct differences between both entities are poorly understood. We aimed to evaluate the clinical phenotypes and long-term outcomes of SD and ISEE in depth.

METHODS: We performed a chart review and analyzed data from our cohorts of consecutive SD and ISEE patients who were treated and assessed in detail for demographic, clinical, imaging, laboratory, and microbiologic characteristics at a university neurosurgical center in Germany from 2002 to 2021. Between-group comparisons were performed to identify meaningful differences in both entities.

RESULTS: We included 208 patients (72 females: age 75 [75 32-90] y vs. 136 males: 65 [23-87] y, median [interquartile range], p < 0.001), of which 142 (68.3%) had SD and 66 (31.7%) had ISEE. Patients with SD were older than ISEE (ISEE: 62 y vs. SD: 70 y, p = 0.001). While SD was more common in males than females (males: n = 101, 71.1% vs. females: n = 41, 28.9%, p < 0.001), there was no sex-related difference in ISEE (males: n = 35, 53.0% vs. females: n = 31, 47.0%, p = 0.71). Obesity was more frequent in ISEE than in SD (ISEE: n = 29, 43.9% vs. SD: n = 37, 26.1%, p = 0.016). However, there were no between-group differences in rates of diabetes and immunodeficiency. In the entire study population, a causative pathogen was identified in 192 (92.3%) patients, with methicillin-susceptible staphylococcus aureus being most frequent (n = 100, 52.1%) and being more frequent in ISEE than SD (ISEE: n = 43, 65.2% vs. SD: n = 57, 40.1%, p = 0.003). SD and ISEE occurred most frequently in the lumbar spine, with no between-group differences (ISEE: n = 25, 37.9% vs. SD: n = 65, 45.8%, p = 0.297). Primary infectious sources were identified in 145 patients (69.7%) and among this skin infection was most common in both entities (ISEE: n = 14, 31.8% vs. SD: n = 25, 24.8%, p = 0.418). Furthermore, epidural administration was more frequent the primary cause of infection in ISEE than SD (ISEE: n = 12, 27.3% vs. SD: n = 5, 4.9%, p < 0.001). The most common surgical procedure in SD was instrumentation (n = 87, 61%) and in ISEE abscess evacuation (n = 63, 95%). Patients with ISEE displayed lower in-hospital complication rates compared to SD for sepsis (ISEE: n = 12, 18.2% vs. SD: n = 94, 66.2%, p < 0.001), septic embolism (ISEE: n = 4/48 cases, 8.3% vs. SD: n = 52/117 cases, 44.4%, p < 0.001), endocarditis (ISEE: n = 1/52 cases, 1.9% vs. SD: n = 23/125 cases, 18.4%, p = 0.003), relapse rate (ISEE: n = 4/46, 8.7% vs. SD: n = 27/92, 29.3%, p = 0.004), and disease-related mortality (ISEE: n = 1, 1.5% vs. SD: n = 11, 7.7%, p = 0.108). Patients with SD showed prolonged length of hospital stay (ISEE: 22 [15, 30] d vs. SD: 38 [29, 53] d, p < 0.001) and extended intensive care unit stay (ISEE: 0 [0, 4] d vs. SD: 3 [0, 12] d, p < 0.002).

CONCLUSIONS: Our 20-year experience and cohort analysis on the clinical management of SD and ISEE unveiled distinct clinical phenotypes and outcomes in both entities, with ISEE displaying a more favorable disease course with respect to complications and relapse rates as well as disease-related mortality.

PMID:37273827 | PMC:PMC10232866 | DOI:10.3389/fsurg.2023.1200432

BMC Immunol. 2023 Jun 3;24(1):8. doi: 10.1186/s12865-023-00543-6.

ABSTRACT

BACKGROUND: The correlation between primary immunodeficiencies (PIDs) and autoimmunity shows ethnic and geographical diversity. The aim of our study was to accumulate more data in paediatric PID population.

METHODS: 58 children aged 1-17 and with PID (study group) and 14 age-matched immunocompetent individuals (control group) were included in the study. Serum levels of 17 different specific IgG antibodies against autoantigens were measured by means of a quantitative enzyme immunoassay. Immunoglobulin levels were analysed in relation to a detailed medical examination.

RESULTS: Autoantibodies against one or more antigens were detected in the sera of 24.14% (n = 14) subjects in the study group. The most frequent were anti-thyroid peroxidase (anti-TPO) antibodies (n = 8; 13.8%). Anti-TPO antibody levels were elevated more often in PID patients with a positive family history of autoimmune diseases (p = 0.04). The screening for anti-deamidated gliadin peptide (DGP) and anti-tissue transglutaminase (tTG) antibodies in our series allowed identifying two previously undiagnosed cases of coeliac disease in PID patients. There was no statistically significant difference between the study and the control group in terms of the autoantibodies prevalence.

CONCLUSIONS: This study provides data on the prevalence of autoantibodies in paediatric population diagnosed with PID. Selected autoantibodies (i.e. anti-tTG, anti-DGP) might be useful for the screening of PID to avoid the delay of diagnosis of an autoimmune disease.

PMID:37270495 | DOI:10.1186/s12865-023-00543-6

J Clin Immunol. 2023 Jun 2. doi: 10.1007/s10875-023-01482-y. Online ahead of print.

ABSTRACT

Primary immunodeficiency disease (PIDD) comprises a group of disorders of immune function. Some of the most severe PIDD can be treated with hematopoietic cell transplant (HCT). Hizentra® is a 20% liquid IgG product approved for subcutaneous administration in adults and children greater than 2 years of age with PIDD-associated antibody deficiency. Limited information is available on the use of Hizentra® in children following HCT for PIDD. A multicenter retrospective chart review demonstrated 37 infants and children (median age 70.1 [range 12.0 to 176.4] months) with PIDD treated by HCT who received Hizentra® infusions over a median duration of 31 (range 4-96) months post-transplant. The most common indication for HCT was IL2RG SCID (n = 16). Thirty-two patients switched from IVIG to SCIG administration, due to one or more of the following reasons: patient/caregiver (n = 17) or physician (n = 12) preference, discontinuation of central venous catheter (n = 16), desire for home infusion (n = 12), improved IgG serum levels following lower levels on IVIG (n = 10), and loss of venous access (n = 8). Serious bacterial infections occurred at a rate of 0.041 per patient-year while on therapy. Weight percentile increased by a mean of 16% during the observation period, with females demonstrating the largest gains. Mild local reactions were observed in 24%; 76% had no local reactions. One serious adverse event (death from sepsis) was reported. Hizentra® was discontinued in 15 (41%) patients, most commonly due to recovery of B cell function (n = 11). These data demonstrate that Hizentra® is a safe and effective option in children who have received HCT for PIDD.

PMID:37266769 | DOI:10.1007/s10875-023-01482-y

Indian Dermatol Online J. 2023 Apr 4;14(3):379-382. doi: 10.4103/idoj.idoj_472_22. eCollection 2023 May-Jun.

ABSTRACT

Hyper-immunoglobulin E syndrome is a rare primary immunodeficiency syndrome characterized by severe atopic dermatitis, recurrent pulmonary and staphylococcal skin infections. Its diagnosis requires a high degree of suspicion, typical clinical features, and not mere rise in serum IgE levels. Genetic studies are not always possible in a resource poor setting in developing countries. In this case series, all children had recurrent eczematoid rash, secondary infections, multiple episodes of hospitalization for pulmonary infection and raised serum IgE levels. Diagnostic genetic study was feasible in only one of the cases which revealed pathogenic homozygous deletions of exons 15 to 18 (Transcript: NM_203447) in DOCK8 gene. The main goal of management of hyper-immunoglobulin E syndrome is aggressive treatment of infections and optimum skin care. Our case series highlights various characteristic, presentations, and management of this rare syndrome childhood cases. Awareness of these manifestations may facilitate early identification and contribute to optimal care of patients as representative data on the same is limited in literature.

PMID:37266097 | PMC:PMC10231702 | DOI:10.4103/idoj.idoj_472_22

Case Reports Immunol. 2023 May 22;2023:3977739. doi: 10.1155/2023/3977739. eCollection 2023.

ABSTRACT

Patients with primary immunodeficiencies are especially vulnerable to developing severe coronavirus disease 2019 (COVID-19) after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important regulator of immune responses, and patients who suffer from CTLA4 haploinsufficiency have hyperactivation of effector T cells and infiltration of various organs. Overexpression of CTLA4 has been associated with a more severe disease course in patients with COVID-19, but there have only been a few reports on the disease course of COVID-19 in patients with CTLA4 haploinsufficiency. We report on a 33-year-old female with a history of immune thrombocytopenia, autoimmune haemolytic anaemia, granulomatous-lymphocytic interstitial lung disease, and common variable immunodeficiency who developed COVID-19. She was admitted and discharged from the hospital several times in the months thereafter and remained symptomatic and had a positive SARS-CoV-2 PCR for up to 137 days after the first symptoms. No SARS-CoV-2 antibodies were identified in the patients’ serum. The disease was finally controlled after repeated infusions of convalescent plasma and treatment of concurrent bacterial and fungal infections. Genetic analysis revealed a likely pathogenic variant in CTLA4, and CTLA4 expression on regulatory T-cells was low. This case illustrates that patients with primary immunodeficiencies who have a protracted disease course of COVID-19 could benefit from convalescent plasma therapy.

PMID:37260564 | PMC:PMC10228224 | DOI:10.1155/2023/3977739

Clin Respir J. 2023 May 31. doi: 10.1111/crj.13630. Online ahead of print.

ABSTRACT

INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children.

METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed.

RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive.

CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.

PMID:37259267 | DOI:10.1111/crj.13630

J Clin Immunol. 2023 May 29. doi: 10.1007/s10875-023-01511-w. Online ahead of print.

ABSTRACT

BACKGROUND: The human CD19 antigen is expressed throughout B cell ontogeny with the exception of neoplastic plasma cells and a subset of normal plasma cells. CD19 plays a role in propagating signals from the B cell receptor and other receptors such as CXCR4 in mature B cells. Studies of CD19-deficient patients have confirmed its function during the initial stages of B cell activation and the production of memory B cells; however, its role in the later stages of B cell differentiation is unclear.

OBJECTIVE: Using B cells from a newly identified CD19-deficient individual, we investigated the role of CD19 in the generation and function of plasma cells using an in vitro differentiation model.

METHODS: Flow cytometry and long-read nanopore sequencing using locus-specific long-range amplification products were used to screen a patient with suspected primary immunodeficiency. Purified B cells from the patient and healthy controls were activated with CD40L, IL-21, IL-2, and anti-Ig, then transferred to different cytokine conditions to induce plasma cell differentiation. Subsequently, the cells were stimulated with CXCL12 to induce signalling through CXCR4. Phosphorylation of key downstream proteins including ERK and AKT was assessed by Western blotting. RNA-seq was also performed on in vitro differentiating cells.

RESULTS: Long-read nanopore sequencing identified the homozygous pathogenic mutation c.622del (p.Ser208Profs*19) which was corroborated by the lack of CD19 cell surface staining. CD19-deficient B cells that are predominantly naïve generate phenotypically normal plasma cells with expected patterns of differentiation-associated genes and normal levels of CXCR4. Differentiated CD19-deficient cells were capable of responding to CXCL12; however, plasma cells derived from naïve B cells, both CD19-deficient and sufficient, had relatively diminished signaling compared to those generated from total B cells. Additionally, CD19 ligation on normal plasma cells results in AKT phosphorylation.

CONCLUSION: CD19 is not required for generation of antibody-secreting cells or the responses of these populations to CXCL12, but may alter the response other ligands that require CD19 potentially affecting localization, proliferation, or survival. The observed hypogammaglobulinemia in CD19-deficient individuals is therefore likely attributable to the lack of memory B cells.

PMID:37246174 | DOI:10.1007/s10875-023-01511-w

Allergy Asthma Clin Immunol. 2023 May 27;19(1):44. doi: 10.1186/s13223-023-00790-7.

ABSTRACT

BACKGROUND: Primary antibody deficiencies (PAD) are characterized by a heterogeneous clinical presentation and low prevalence, contributing to a median diagnostic delay of 3-10 years. This increases the risk of morbidity and mortality from undiagnosed PAD, which may be prevented with adequate therapy. To reduce the diagnostic delay of PAD, we developed a screening algorithm using primary care electronic health record (EHR) data to identify patients at risk of PAD. This screening algorithm can be used as an aid to notify general practitioners when further laboratory evaluation of immunoglobulins should be considered, thereby facilitating a timely diagnosis of PAD.

METHODS: Candidate components for the algorithm were based on a broad range of presenting signs and symptoms of PAD that are available in primary care EHRs. The decision on inclusion and weight of the components in the algorithm was based on the prevalence of these components among PAD patients and control groups, as well as clinical rationale.

RESULTS: We analyzed the primary care EHRs of 30 PAD patients, 26 primary care immunodeficiency patients and 58,223 control patients. The median diagnostic delay of PAD patients was 9.5 years. Several candidate components showed a clear difference in prevalence between PAD patients and controls, most notably the mean number of antibiotic prescriptions in the 4 years prior to diagnosis (5.14 vs. 0.48). The final algorithm included antibiotic prescriptions, diagnostic codes for respiratory tract and other infections, gastro-intestinal complaints, auto-immune symptoms, malignancies and lymphoproliferative symptoms, as well as laboratory values and visits to the general practitioner.

CONCLUSIONS: In this study, we developed a screening algorithm based on a broad range of presenting signs and symptoms of PAD, which is suitable to implement in primary care. It has the potential to considerably reduce diagnostic delay in PAD, and will be validated in a prospective study. Trial registration The consecutive prospective study is registered at clinicaltrials.gov under NCT05310604.

PMID:37245042 | DOI:10.1186/s13223-023-00790-7

J Allergy Clin Immunol Pract. 2023 May 25:S2213-2198(23)00567-6. doi: 10.1016/j.jaip.2023.05.029. Online ahead of print.

NO ABSTRACT

PMID:37244439 | DOI:10.1016/j.jaip.2023.05.029

Pediatr Blood Cancer. 2023 May 26:e30429. doi: 10.1002/pbc.30429. Online ahead of print.

ABSTRACT

Cytomegalovirus retinitis (CMVR) following hematopoietic stem cell transplantation (HCT) for a primary immunodeficiency is a rare but highly morbid condition with potential irreversible consequences despite optimal antiviral pharmacotherapy. Viral-specific T cells (VSTs) pose a promising and safe approach eradicating intractable viral disease. We describe the case of a 21-month-old male with Wiskott-Aldrich syndrome (WAS) and CMVR post HCT with sustained long-term virologic and clinical response after CMV-specific T-cell therapy. This case highlights the need to consider VST as an adjunct upfront strategy in refractory CMVR and for routine ophthalmologic screening and surveillance in high-risk patients post HCT.

PMID:37243390 | DOI:10.1002/pbc.30429