Relationship of Bone Mineral Density with CD4+ T Cell Counts and Association of Muscle Mass with B Cells in Common Variable Immunodeficiency Patients

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by chronic/recurrent respiratory infections, bronchiectasis, autoimmunity, inflammatory, gastrointestinal diseases and malignancies associated with a chronic inflammatory state and increased risk of osteoporosis and muscle loss. AIM: The aim of this study was to evaluate bone mineral density (BMD), body composition and their relationship with lymphocyte subpopulations in CVID patients. METHODS: Dual-energy X-ray absorptiometry was performed to assess BMD, lean mass, and fat mass in CVID patients. Peripheral blood CD4+, CD8+, and CD19+ cells were measured using flow cytometry. RESULTS: Thirty-three patients (37.3 ± 10.8 years old) were examined. Although only 11.8% of the individuals were malnourished (BMI <18.5 kg/m2), 27.7% of them had low skeletal muscle mass index (SMI), and 57.6% of them had low BMD. Patients with osteopenia/osteoporosis presented lower weight (p=0.007), lean mass (p=0.011), appendicular lean mass (p=0.011), SMI (p=0.017), and CD4+ count (p=0.030). Regression models showed a positive association between CD4+ count and bone/muscle parameters, whereas CD19+ B cell count was only associated with muscle variables. Analysis of ROC curves indicated a cutoff value of CD4+ count (657 cells/mm3; AUC: 0.71, 95% CI 0.52-0.90) which was related to low BMD. Weight (p=0.004), lean mass (p=0.027), appendicular lean mass (p=0.022), SMI (p=0.029), total bone mineral content (p=0.005), lumbar (p=0.005), femoral neck (p=0.035), and total hip BMD (p<0.001) were found to be lower in patients with CD4+ count below the cutoff. CONCLUSION: CVID patients presented with low BMD, which was associated with CD4+ count. Moreover, low muscle parameters were correlated with B cell count.

Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms.

Common variable immunodeficiency (CVID) is one of the inborn errors of immunity that have the greatest clinical impact. Rates of morbidity and mortality are higher in patients with CVID who develop liver disease than in those who do not. The main liver disorder in CVID is nodular regenerative hyperplasia (NRH), the cause of which remains unclear and for which there is as yet no treatment. The etiology of liver disease in CVID is determined by analyzing the liver injury and the associated conditions. The objective of this study was to compare CVID patients with and without liver-spleen axis abnormalities in terms of clinical characteristics, as well as to analyze liver and duodenal biopsies from those with portal hypertension (PH), to elucidate the pathophysiology of liver injury. Patients were divided into three groups: Those with liver disease/PH, those with isolated splenomegaly, and those without liver-spleen axis abnormalities. Clinical and biochemical data were collected. Among 141 CVID patients, 46 (32.6%) had liver disease/PH; 27 (19.1%) had isolated splenomegaly; and 68 (48.2%) had no liver-spleen axis abnormalities. Among the liver disease/PH group, patients, even those with mild or no biochemical changes, had clinical manifestations of PH, mainly splenomegaly, thrombocytopenia, and esophageal varices. Duodenal celiac pattern was found to correlate with PH (p < 0.001). We identified NRH in the livers of all patients with PH (n = 11). Lymphocytic infiltration into the duodenal mucosa also correlated with PH. Electron microscopy of liver biopsy specimens showed varying degrees of lymphocytic infiltration and hepatocyte degeneration, which is a probable mechanism of lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes. In comparison with the CVID patients without PH, those with PH were more likely to have lymphadenopathy (p < 0.001), elevated ß2-microglobulin (p < 0.001), low B-lymphocyte counts (p < 0.05), and low natural killer-lymphocyte counts (p < 0.05). In CVID patients, liver disease/PH is common and regular imaging follow-up is necessary. These patients have a distinct immunological phenotype that may predispose to liver and duodenal injury from lymphocyte-mediated cytotoxicity. Further studies could elucidate the cause of this immune-mediated mechanism and its treatment options.

Common variable immunodeficiency: an important but little-known risk factor for gastric cancer.

INTRODUCTION: although it is a rare disease, common variable immunodeficiency (CVID) stands out as the most frequent primary symptomatic immunodeficiency. Carriers are prone to a variety of recurrent bacterial infections, in addition to the risk of developing autoimmune diseases and neoplasms including gastric cancer (GC). Despite the recognized risk, there are no specific standardized protocols for the management of GC in these patients, so the reported oncological results are varied. Thus, this study aims to describe the clinicopathological characteristics and prognosis of patients with CVID undergoing surgical treatment of GC. METHODS: all patients with GC undergoing surgical treatment between 2009 and 2020 were retrospectively evaluated. Later, patients diagnosed with CVID were identified and this group was compared with the remaining patients without any immunodeficiency. RESULTS: among the 1101 patients with GC evaluated in the period, 10 had some type of immunodeficiency, and 5 were diagnosed with CVID. Patients with CVID had younger age, lower BMI, and smaller lesions compared to those without CVID. Four patients underwent curative gastrectomy and one patient underwent jejunostomy. Two patients died (1 palliative and 1 curative) and one patient had disease recurrence. There was no statistically significant difference regarding the incidence of postoperative complications and survival between the evaluated groups. CONCLUSION: the CVID incidence in patients with GC undergoing surgical treatment was 0.5%, occurring at a less advanced age, but with no difference regarding surgical and oncological results.

Enteropatia perdedora de proteína relacionada a criptococose: um diagnóstico diferencial de imunodeficiência secundária / Protein-losing enteropathy related to cryptococcosis: a differential diagnosis of secondary immunodeficiency

A criptococose é uma doença oportunista que ocorre com maior frequência em pacientes imunossuprimidos, ocasionando piora clínica e imunológica importante. Porém, é raro quando a doença ocorre em pacientes imunocompetentes. Relatamos aqui um caso de paciente previamente hígido que evoluiu com enteropatia perdedora de proteína, hipogamaglobulinemia secundária causada por criptococose disseminada.

Cryptococcosis is an opportunistic disease that occurs more frequently in immunosuppressed patients, causing important clinical and immunological deterioration. However, the disease rarely occurs in immunocompetent patients. We report a case of a previously healthy patient who progressed with protein-losing enteropathy, secondary hypogammaglobulinemia caused by disseminated cryptococcosis.

Hipogamaglobulinemia secundária reversível causada por terapia anticonvulsivante em adultos: relato de três casos / Reversible hypogammaglobulinemia secondary to anticonvulsant therapy in adult patients: report of three cases

A redução dos níveis de imunoglobulina relacionada ao uso de anticonvulsivantes e que cursa com infecções de repetição tem sido descrita nas últimas quatro décadas. O objetivo deste estudo é relatar três casos de pacientes adultos que evoluíram para hipogamaglobulinemia quando foram tratados com anticonvulsivantes. Os níveis de imunoglobulinas e a população de linfócitos se normalizaram quando as drogas foram suspensas. Deficiências de IgA e IgM relacionadas ao uso de anticonvulsivantes resultam em infecções de repetição, apesar de níveis baixos de IgG terem sido relatados em poucos estudos e relatos de casos isolados. Os mecanismos patofisiológicos da hipogamaglobulinemia secundária a essas classes de drogas não estão completamente elucidados, mas diversos estudos mostram a possibilidade de reversão da imunodeficiência depois da suspensão da medicação, principalmente na infância.

Reduced immunoglobulin (Ig) levels related to anticonvulsant therapy and resulting in recurrent infections have been described in the past 4 decades. The objective of this study is to report three cases of adult patients who progressed with hypogammaglobulinemia after anticonvulsant therapy. Normalization of Ig levels and lymphocyte populations was achieved after drug suspension. IgA and IgM deficiencies related to anticonvulsant therapy lead to recurrent infections, although decreased serum IgG levels have been reported in few studies and isolated clinical cases. The pathophysiological mechanisms of hypogammaglobulinemia secondary to these types of drugs have not been completely understood, but several studies show the possibility of immunodeficiency reversion after drug suspension, especially in childhood.

Dermatite de contato por cloreto de benzalcônio / Contact dermatitis from benzalkonium chloride

O cloreto de benzalcônio é um conservante encontrado em produtos de higiene pessoal e preparações farmacêuticas há mais de seis décadas. Antes tido como irritante; porém, evidências crescentes apontam que ele possa induzir alergia de contato em uma taxa mais elevada do que o previsto. Os autores apresentam um caso de um adulto de 71 anos, com reação alérgica ao cloreto de benzalcônio contido em solução tópica oftalmológica. Pretende-se, com este caso, alertar sobre as possíveis hipersensibilidades aos conservantes de medicamentos e cosméticos.

Benzalkonium chloride is a preservative found in personal care products and pharmaceutical preparations for over six decades. It was previously thought to be an irritant, but a growing body of evidence suggests that it may induce contact allergy at a higher rate than anticipated. The authors describe the case of a 71-yearold male patient with allergic reaction to benzalkonium chloride present in a topical ophthalmic solution. With this case report we intend to warn about possible hypersensitivity reactions to preservatives contained in medicines and cosmetics.