Common variable immunodeficiency associated enteropathy: A diagnostic enigma in developing countries.

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency disorder with different phenotypes and aetiologies. It is characterised by hypogammaglobulinaemia, defects in specific antibody response, erroneous activation and proliferation of T cells, leading to increased risk of recurrent infections. In CVID, "Variable" refers to the heterogeneity of clinical presentations, which include recurrent infections, autoimmunity, enteropathy, and increased risk of malignancies. This wide spectrum of disease manifestations and being a diagnosis of exclusion poses a diagnostic challenge. It is pertinent to mention that CVID along with associated complications is the commonest symptomatic primary antibody deficiency but is scarcely mentioned in local literature. The main aim of presenting this case is to impress upon the importance of systematic immunological workup in cases of suspected immunodeficiency to prevent morbidity and mortality.

Pathogenic TNFRSF13B Variant in an Adult Japanese Patient with Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is a primary B cell immunodeficiency disorder. Symptoms do not develop immediately after birth, and patients are often diagnosed in childhood and adulthood. These patients often develop autoimmune diseases and malignant tumors. We herein report a 50-year-old woman with severe hypogammaglobulinemia and recurrent respiratory tract infections who was diagnosed with CVID. Target sequencing showed a TNFRSF13B heterozygous frameshift variant. The patient had many comorbidities, probably caused by a CVID-induced immune imbalance. Physicians who treat adult patients are often unaware of CVID. CVID should be recognized as a differential diagnosis in hypogammaglobulinemia and recurrent infections.

Changes in health-related quality of life in common variable immunodeficiency: an eight-year journey, including the COVID-19 pandemic.

BACKGROUND: Personalized medicine requires the assessment of the impact of health care interventions on Health-Related Quality of Life. RESEARCH DESIGN AND METHODS: We run an observational study of HRQoL in 140 CVID patients with biannual assessments over 8 years using a disease-specific tool, the CVID_QoL, and the GHQ questionnaires. Factors influencing changes in HRQoL scores were identified using multiple linear regression models with a stepwise procedure. RESULTS: Infections frequency, female gender, and chronic enteropathy were associated with worse global CVID_QoL scores. The presence of permanent organ damage and older age contributed to the perception of being at risk of health deterioration, while chronic enteropathy was associated with fatigue. The presence of permanent organ damage was also associated with perceived difficulties in usual activities. The frequency of infections was the main risk factor for difficulties in long-term planning and perceptions of vulnerability. Before COVID-19, improved HRQoL scores were associated with reduced respiratory infections and changes in immunoglobulin replacement route and setting. The COVID-19 pandemic caused a sudden deterioration in all HRQoL dimensions, and a further deterioration in the emotional dimension was observed during the pandemic period. Patients who died during the study had worse CVID_QoL scores at all time points, confirming that HRQoL performance is strongly related to patient outcome. CONCLUSIONS: Periodic HRQoL assessments are needed to capture relevant issues that change over time in patients affected by long-term chronic conditions such CVID, possibly identifying areas of intervention.

Case Report: Common variable immunodeficiency phenotype and granulomatous-lymphocytic interstitial lung disease with a novel SOCS1 variant.

Common variable immunodeficiency is a heterogeneous symptomatic group of inborn errors of immunity that mainly affects antibodies production and/or function, predisposing patients to recurrent and severe infections. More than half of them usually develop autoimmunity, lymphoproliferation, enteropathy, and malignancies. Among these conditions, chronic lung disease such as granulomatous-lymphocytic interstitial lung disease is one of the leading causes of death in these patients. Recently, many genes that play a key role in B and T cells' development, maintenance, and/or cytokines signaling pathways have been implicated in the pathogenesis of the disease. Here, we describe the first Argentinian patient presenting with common variable immunodeficiency and granulomatous-lymphocytic interstitial lung disease, harboring two in cis heterozygous variants in the SOCS1 gene.

The clinical and immunological characteristics of common variable immunodeficiency in adults and older adults.

OBJECTIVE: The aim of this study was to determine the clinical and immunological characteristics of older adults with common variable immunodeficiency (CVID). METHODS: Patients aged ≥18 years who were followed up with the diagnosis of CVID between 2015 and 2020 were included in the study. The patients were separated into two age groups according to the age at diagnosis: the adult group, aged 18-65 years (n=49) and the older adult group, aged ≥65 years (n=11). RESULTS: Splenomegaly (55.1% vs. 9.1%, p=0.006), bronchiectasis (53.0% vs. 9.1%, p=0.008), and autoimmunity (42.8% vs. 9.1%, p=0.036) were determined to be more common in the adult group than in the older adults. A similar frequency of malignancy was seen in both groups (6.1% vs. 9.1%, p=0.721). There were significantly more patients with no comorbidity in the older adult group than in the adult group (45.5% vs. 16.3%, p=0.034). Serum IgG and IgA levels were determined to be significantly higher in the older adult group than in the adult group (p=0.001 for all). The CD19+ B-cell count at the time of diagnosis was determined to be lower and the CD19+CD27+IgD- switched memory B-cells and CD16+CD56+ natural killer cell counts were higher in the older adults than in the adult group (p=0.016, p=0.032, p=0.044, respectively). CONCLUSION: Knowledge of clinical and immunological differences in older adult CVID patients may be of benefit in polyclinic follow-up and in respect of changes to be made to the treatment plan.

Small Bowel Villous Atrophy in a Young Patient: A Challenging Diagnosis.

Common variable immunodeficiency enteropathy is a sprue-like disease, which may manifest as a severe malabsorption syndrome with nutritional deficits and cachexia. The authors report a case of a 33-year-old Afghan man, who presented to the emergency department due to chronic watery diarrhea and severe malnourishment. He had been previously misdiagnosed with celiac disease in his early adulthood; however, this was based on inconclusive findings. After a thorough diagnostic workup, the final diagnosis of common variable immunodeficiency enteropathy with symptomatic norovirus infection of the gut was obtained during his prolonged hospitalization. A slow but progressive improvement was observed with immunoglobulin replacement therapy, corticotherapy, and ribavirin treatment. This is a noteworthy case of a rare malabsorption disorder, and it reviews important aspects concerning the differential diagnosis of small bowel villous atrophy of unknown etiology, as well as gastrointestinal manifestations of common variable immunodeficiency disorder.

A Enteropatia associada à Imunodeficiência Comum Variável é uma entidade com características clínicas e endoscópicas semelhantes à doença celíaca. Por vezes apresenta-se como um síndrome de malabsorção, levando a défices nutricionais e caquexia severa. Os autores relatam o caso de um homem de 33 anos de idade de naturalidade afegã, que recorreu ao serviço de urgência por um quadro de diarreia aquosa crónica e desnutrição severa. O doente teria sido diagnosticado erroneamente com doença celíaca no início da vida adulta, com bases em dados clínicos inconclusivos. Após um estudo exaustivo durante um internamento prolongado, o doente foi diagnosticado com uma Enteropatia associada à Imunodeficiência Comum Variável com sobreinfeção por Norovirus. Foi observada uma melhoria lenta e progressiva com instituição de terapêutica substitutiva com imunoglobulina, corticoterapia e ribavirina. Este caso retrata uma causa rara de malabsorção, abordando pontos essenciais no diagnóstico diferencial da atrofia vilositária do intestinal delgado, bem como das manifestações gastrointestinais da Imunodeficiência Comum Variável.

Increased risk of gastric cancer in relation with pernicious anaemia in patients with primary antibody deficiency: A nationwide case control study.

BACKGROUND/AIM: We aimed to assess gastrointestinal cancers risks in a large cohort of individuals with primary antibody deficiency (PAD) and their association with risk of autoimmune and inflammatory gastrointestinal diseases. METHODS: Investigating a French national database of inpatient admissions between 2010 and 2018, we identified 12,748 patients with PAD and 38,244 control non-exposed individuals. We performed multiple exposed-non-exposed studies using conditional logistic regression. RESULTS: In comparison with non-exposed patients, PAD patients had increased risk of in situ gastric carcinoma (Odds Ratio (OR) =10.5 [95 % CI 2.2; 50.5]), malignant gastric tumor (OR=3.2 [95 % CI 2.2; 4.4]) and colorectal cancer (OR=1.2 [95 % CI 1; 1.5]). PAD patients had also increased risk of pernicious anaemia (OR=8 |95 % CI 5.6; 11.5]), Crohn's disease (OR= 4.4 [95 % CI 3.5; 5.6]), ulcerative colitis (OR=2.9 [95 % CI 2.4; 3.6]) and coeliac disease (OR=13.3 [95 % CI 9.1; 19.5]). Within patients with gastric cancer, those with PAD had increased risk of pernicious anaemia (OR=8.4 [95 % CI 1.5; 215]; p = 0.01) but not of H. pylori infection. CONCLUSIONS: Risk of gastric cancer is particularly high in PAD patients and notably risk of in situ gastric carcinoma in association with pernicious anaemia. It supports indication of early endoscopic screening in these patients.

Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Campylobacter jejuni Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion.

Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic, epigenetic, microbiota, and environmental factors. We present the case of a 46-year-old Caucasian male patient with CVID and an immune dysregulation phenotype. The particular elements of the case consisted of an atypical clinical course, which undoubtedly demonstrates the great variability of clinical manifestations that these types of patients can suffer from, including bacterial and viral infections, autoimmune phenomena, and neoplasia. Notably, the patient suffered from recurrent gastrointestinal infection with macrolide-resistant Campylobacter jejuni and gastroduodenal disease and viraemia by cytomegalovirus (CMV). In addition, CMV was postulated as the main pro-oncogenic factor contributing to the development of early-onset intestinal-type gastric adenocarcinoma, for which the patient underwent gastrectomy. The patient's evolution was difficult, but finally, as a result of the multidisciplinary approach, clinical stabilization and improvement in his quality of life were achieved. Based on our brief literature review, this is the first reported case of this clinical complexity. Our experience could help with the management of future patients with CVID and may also update current epidemiological data on CVID.

Proof-of-concept study evaluating humoral primary immunodeficiencies via CJ:KREC ratio and serum BAFF level.

Humoral primary immunodeficiencies are the most prevalent form of primary immunodeficiency (PID). Currently, there is no convenient method to quantify newly formed B cells. The aim of this proof-of-concept study was to quantitate the ratio of coding joints (CJs) to Kappa-deleting recombination excision circles (KRECs) and serum B cell activating factor (BAFF) in patients with humoral primary immunodeficiency and assess if they correlate with disease severity. This IRB-approved study was conducted at one academic children's hospital. Patients with humoral PIDs and healthy controls were included. CJ and KREC levels were measured via qPCR. Serum BAFF levels were measured using Mesoscale. 16 patients with humoral PID and 5 healthy controls were included. The mean CJ:KREC ratio in the CVID, antibody deficiency syndromes, and controls groups, respectively were 13.04 ± 9.5, 5.25 ± 4.1, and 4.38 ± 2.5 (p = 0.059). The mean serum BAFF levels in CVID, antibody deficiency syndromes and controls were 216.3 ± 290 pg/mL, 107.9 ± 94 pg/mL and 50.9 ± 12 pg/mL, respectively (p = 0.271). When the CVID patients were subdivided into CVID with or without lymphoproliferative features, the BAFF level was substantially higher in the CVID with lymphoproliferation cohort (mean 372.4 ± 361 pg/mL, p = 0.031). Elevated CJ:KREC ratio was observed in CVID, although statistical significance was not achieved, likely due to the small sample size. Serum BAFF levels were significantly higher in CVID patients with lymphoproliferative features. We speculate that the CJ:KREC ratio and serum BAFF levels can be utilized in patients with humoral PID, once more extensive studies confirm this exploratory investigation.

18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency.

Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4+ and/or CD8+ cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.

Oropharyngeal microbial ecosystem perturbations influence the risk for acute respiratory infections in common variable immunodeficiency.

Background: The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients' gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited. Objective: This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections. Methods: Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients. Results: Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order Lactobacillales, including the family Streptococcaceae. Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of Haemophilus and Streptococcus genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of Haemophilus and Anoxybacillus was associated with acute respiratory infections within six months. Conclusions: CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis.

The Horse with Recurrent Fevers and Infections: Approach to Common Variable Immunodeficiency.

Equine common variable immunodeficiency (CVID) is a rare, late-onset, nonfamilial humoral deficiency characterized by B-cell depletion and/or dysfunction resulting in inadequate antibody production and predisposition to recurrent infections. Serum immunoglobulin concentration and peripheral blood lymphocyte immunophenotyping are required to diagnose and characterize CVID in horses. Early recognition of the disease by the equine practitioner is paramount to managing the quality of life for these patients, for whom specific treatment is not yet available and long-term prognosis remains poor. An approach to the diagnosis, identification of complicating factors, and management of horses with CVID are discussed.

Heterozygous SERPINA1 Defects and Their Impact on Clinical Manifestations of Patients with Predominantly Antibody Deficiencies.

Patients with predominantly antibody deficiencies (PADs) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes, display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate the possible contribution to PAD clinical phenotype. Ten CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474), which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD in order to identify patients with a higher risk for liver disease.

Granulomatous Lymphocyte Interstitial Lung Disease: A Rare Complication of Common Variable Immunodeficiency Managed With Azathioprine and Rituximab.

Granulomatous lymphocytic interstitial lung disease (GL-ILD) is a rare, non-infectious pulmonary manifestation of common variable immunodeficiency (CVID). Diagnosing and managing GLILD remains challenging due to its poorly understood pathogenesis and high mortality. We present a complex case of a young female with CVID associated with lung and spinal cord involvement managed with azathioprine and rituximab.

The Etiologic Landscape of Lymphoproliferation in Childhood: Proposal for a Diagnostic Approach Exploring from Infections to Inborn Errors of Immunity and Metabolic Diseases.

Lymphoproliferation is defined by lymphadenopathy, splenomegaly, hepatomegaly, or lymphocytic organ and tissue infiltration. The most common etiologies of lymphoproliferation are represented by infectious diseases and lymphoid malignancies. However, it is increasingly recognized that lymphoproliferative features can be the presenting sign of rare conditions, including inborn errors of immunity (IEI) and inborn errors of metabolism (IEM). Among IEI, lymphoproliferation is frequently observed in autoimmune lymphoproliferative syndrome (ALPS) and related disorders, common variable immunodeficiency (CVID), activated phosphoinositide 3-kinase δ syndrome, and Epstein-Barr virus (EBV)-related disorders. Gaucher disease and Niemann-Pick disease are the most common IEMs that can present with isolated lymphoproliferative features. Notably, other rare conditions, such as sarcoidosis, Castleman disease, systemic autoimmune diseases, and autoinflammatory disorders, should be considered in the differential diagnosis of patients with persistent lymphoproliferation when infectious and malignant diseases have been reasonably ruled out. The clinical features of lymphoproliferative diseases, as well as the associated clinical findings and data deriving from imaging and first-level laboratory investigations, could significantly help in providing the correct diagnostic suspicion for the underlying etiology. This paper reviews the most relevant diseases associated with lymphoproliferation, including infectious diseases, hematological malignancies, IEI, and IEM. Moreover, some practical indications to orient the initial diagnostic process are provided, and two diagnostic algorithms are proposed for the first-level assessment and the approach to persistent lymphoproliferation, respectively.

Reference values of lymphocyte subsets from healthy Polish adults.

The flow cytometry method could support physicians' decisions in the diagnosis and treatment monitoring of immunodeficient patients. Most clinical recommendations are focused on the search for alterations in T- and B-lymphocyte subsets, less commonly natural killer (NK) cells and granulocytes. While reference values for clinically meaningful lymphocyte subsets have been published ubiquitously among numerous countries, we have not found significant data for a population of adult Polish habitats; thus we determined reference values for T, B, and NK subsets according to sex and age. The female group showed a higher percentage of lymphocytes (CD45++), T helper lymphocytes with a higher absolute count, as well as CD4/CD8 ratio, marginal zone-like B cells, class-switched B cells, and CD21low B cells than the male group. The male group was found to have elevated percentages of naïve B lymphocytes, transitional B cells, and plasmablasts. A weak positive correlation with age was found among double positive T lymphocytes, natural killer T cells (NKT) lymphocytes, and CD21low B cells. A negative correlation with age for double negative T lymphocytes, marginal zone-like B cells, and plasmablasts was noted. The results indicated the importance of creating distinct reference ranges regarding sex and age concerning immunophenotype.

A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece.

Background and Objectives: Predominantly antibody deficiencies (PAD) represent the most common type of primary immunodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifestations, and outcome. Considering that the prevalence of PAD in Greece is unknown, and there is limited knowledge on the clinical and laboratory characteristics of affected patients, we conducted a nationwide study. Materials and Methods: 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed, and followed-up between August 1979 to September 2023. Furthermore, we classified our cohort into five groups according to their medical history, immunoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficiency (CVID), 12 patients with "secondary" hypogammaglobulinemia due to a previous B-cell depletion immunotherapy for autoimmune or malignant disease several years ago (median: 9 years, range 6-14) displaying a typical CVID phenotype, 7 with combined IgA and IgG subclass deficiencies, 5 patients with CVID-like disease due to CTLA4-mediated immune dysregulation syndrome, and 6 patients with unclassified hypogammaglobulinemia. Results: We demonstrated a remarkable delay in PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). A family history of PAD was only present in 11.8%, with the majority of patients considered sporadic cases. Most patients were diagnosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant autoimmune cytopenias. Interestingly, 10 patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%), while 39 patients (25.5%) developed bronchiectasis, and 16 (10.5%) granulomatous disease. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Conclusion: Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and the appropriate management of affected patients.

Role of B Cells beyond Antibodies in HBV-Induced Oncogenesis: Fulminant Cancer in Common Variable Immunodeficiency-Clinical and Immunotransplant Implications with a Review of the Literature.

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially affected by oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted a previously introduced clinical model of host-virus interaction (i.e., infectious process in immunodeficiency) for analysis of B cells and the specific IgG role (an observational study of a CVID patient who received intravenous immunoglobulin (IVIG). Suddenly, the patient deteriorated and a positive results of for HBs and HBV-DNA (369 × 106 copies) were detected. Despite lamivudine therapy and IVIG escalation (from 0.3 to 0.4 g/kg), CT showed an 11 cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs were positive in time-lapse analysis (range 111-220 IU/mL). Replacement therapy intensification was complicated by an immune complex disease with renal failure. Fulminant HCC in CVID and the development of a tumor as the first sign is of interest. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HB substitution has not been proven to be effective, oncoprotective, nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, and patient selection more precise with the exclusion of HBV-positive donors. Our clinical model showed an HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g., chronic hepatitis). The lack of cell cooperation as well as B cell deficiency observed in CVID play a crucial role in high HBV replication, especially in carcinogenesis.

Granulomatous Lymphocytic Interstitial Lung Disease Associated With Common Variable Immunodeficiency Presenting With Respiratory Failure.

This case study presents a rare occurrence of acute respiratory failure in a 17-year-old male diagnosed with common variable immunodeficiency (CVID) and granulomatous lymphocytic interstitial lung disease (GLILD), which typically have a gradual onset. The patient initially exhibited nonspecific symptoms such as dry cough and fever but quickly progressed to severe respiratory failure despite conventional treatments. Imaging showed extensive lung abnormalities, and blood tests revealed significantly low immunoglobulin levels, indicating an underlying immunodeficiency. Treatment with high-dose steroids and immunoglobulin replacement therapy resulted in a rapid and remarkable recovery of lung function. Lung biopsies confirmed the dual diagnoses of CVID and GLILD, emphasizing the challenge of diagnosing and managing GLILD in CVID patients. This case underscores the importance of early and aggressive intervention in improving outcomes for GLILD patients with acute respiratory distress.

Common Variable Immunodeficiency and Hodgkin Lymphoma in a 50-Year-Old Male.

Common variable immunodeficiency (CVID) is a primary immunodeficiency with the involvement of B cells, T cells, and antigen-presenting cells. Patients with CVID are more susceptible to malignancies and bacterial infections in the gastrointestinal and respiratory tracts. We discuss a case of a 50-year-old male who presented to the emergency department with a history of intermittent abdominal pain, diarrhea, night sweats, fever, nausea, and weight loss of 40 pounds over six months. A CT of the abdomen revealed splenomegaly with several infiltrated solid nodules as well as enlarged mediastinal, hilar, periesophageal, cervical, and left supraclavicular lymph nodes, findings suggestive of lymphoma. The diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma was confirmed by immunohistology, which revealed that CD20 and CD3 were both positive in small lymphocytes. Immunoglobulin (Ig) levels were low for IgG and IgM, findings highly suggestive of CVID. We want to shed light on the importance of performing the clinical workup for CVID when Hodgkin lymphoma and recurrent infections are present, as the immunodeficiency remains underdiagnosed and underreported.