Gastric cancer is the leading cause of death in Italian adult patients with common variable immunodeficiency

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7\u20133.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4\u201322.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2\u201312.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2\u201344.4 and HR: 4.2, 95%CI: 2.8\u201344.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines

Health-Related Quality of Life in Patients with CVID Under Different Schedules of Immunoglobulin Administration: Prospective Multicenter Study

We assessed the health-related quality of life (HRQoL) in CVID adults receiving different schedules of immunoglobulin replacement therapy (IgRT) by intravenous (IVIG), subcutaneous (SCIG), and facilitated (fSCIG) preparations. For these patients, IgRT schedule was chosen after a period focused on identifying the most suitable individual option

Heart failure not responsive to standard immunosuppressive therapy is successfully treated with high dose intravenous immunoglobulin therapy in a patient with Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Glucocorticoids and immunosuppressive drugs represent the first-line treatment of eosinophilic granulomatosis with polyangiitis (EGPA, former Churg-Strauss syndrome), even though the combined therapy is not successful in achieving the disease remission in some patients with neurological or cardiac involvement. We describe a case of an EGPA male patient with impaired left ventricular function not responsive to glucocorticoid and immunosuppressive therapy. We observed that high-dose (2g/kg/4weeks) intravenous immunoglobulin (IVIG) therapy significantly improved cardiac function, which was deteriorated after reducing IVIG dose at 0.5g/kg/4weeks, and was restored increasing again IVIG dose to 2g/kg/4weeks. The finding highlights the relevance of IVIG as treatment of choice in EGPA patients with cardiac involvement not responsive to the standard glucocorticoid and immunosuppressive therapy. Moreover, at a follow-up of 24months, the continuance of high dose IVIG therapy was required to maintain a sustained remission of the heart failure

Chronic Diarrhea in Common Variable Immunodeficiency: a Case Series and Review of the Literature

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced immunoglobulin serum levels and absent or impaired antibody production. Clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies, also involve various segments of the gastrointestinal tract. Chronic diarrhea is one of the most common gastrointestinal symptoms and may cause a wide spectrum of potentially life-threatening conditions as malabsorption and protein-energy malnutrition. We describe three female CVID adult patients presenting with chronic diarrhea, weight loss, and protein-energy malnutrition due to different underlying conditions. Our review of the literature explores the various gastrointestinal involvements in CVID and points out several histopathological findings proper of the disease, thus highlighting the relevance of the endoscopic and histological assessment in CVID patients presenting with chronic diarrhea

Psoriasis in a cohort of patients with common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. CVID is characterized by reduced serum levels of IgG, IgA, and/or IgM, recurrent bacterial infections, autoimmune and inflammatory diseases and malignancies. According to literature, autoimmune diseases occur in 20-30% of CVID patients. Dermatological involvement has occasionally been reported in CVID and includes alopecia totalis, lichen planus, and vitiligo. Data regarding the frequency and features of psoriasis in CVID are scant. This article is protected by copyright. All rights reserved

Gastroduodenal Disorders in Patients with CVID Undergoing Immuno-globulin Therapy

Background: Common variable immunodeficiency (CVID) encompasses a heterogeneous group of primary antibody deficiency disorders characterized by recurrent infections, autoimmunity and malignancies. Gastrointestinal manifestations are frequently associated with CVID. Objective: In this cross-sectional study, we evaluated gastric and duodenal involvement in a cohort of adult patients with CVID. Methods: Upper gastrointestinal endoscopy was performed in 58 patients (26 males, mean age 47.8±15.6 years), diagnosed with CVID according to 2014 ESID criteria. Random biopsies were collected from gastric antrum and descending duodenum for the all enrolled subjects. Intraepithelial lymphocytosis in descending duodenum was defined as the presence of 25 lymphocytes per 100 enterocytes. Results: The major histopathological findings that we found were: a) chronic active gastritis (44.8%), Helicobacter pylori-associated (8.6%), b) chronic duodenitis (39.6%) with intraepithelial lymphocytosis (31%) and absence of plasma cells (18.9%) and c) autoimmune atrophic gastritis (5.2%). Three patients (5.2%) presented Intestinal Metaplasia (IM) of the gastric antrum. This finding was associated with H. pylori infection and persisted after the eradication in one patient. IM was associated with autoimmune atrophic gastritis in two cases. Giardia lamblia infection was observed in the duodenum samples from three patients (5.2%). A diagnosis of Gastric adenocarcinoma was made in a 58-year-old woman diagnosed with gastric dysplasia one year earlier. Conclusion: In our cohort of CVID patients, gastro-duodenal histopathological findings, including malignancies, are frequent and can affect long-term prognosis. A rigorous endoscopic follow-up is needed in CVID patients irrespective of the gastrointestinal symptoms

Electrocardiographic characteristics of right-bundle-branch-block premature ventricular complexes predicting absence of left ventricular scar in athletes with apparently structural normal heart

Background and aims: Left ventricular scar is an arrhythmic substrate that may be missed by echocardiography and diagnosed only by cardiac magnetic resonance (CMR), which is a time-consuming and expensive imaging modality. Premature ventricular complexes (PVCs) with a right-bundle-branch-block (RBBB) pattern are independent predictors of late gadolinium enhancement (LGE) but their positive predictive value is low. We studied which electrocardiographic features of PVBs with a RBBB pattern are associated with a higher probability of absence of an underlying LGE. Methods and results: The study included 121 athletes (36±16 years; 48.8% men) with monomorphic PVCs with a RBBB configuration and normal standard clinical investigations who underwent CMR. LGE was identified in 35 patients (29%), predominantly in those with PVCs with a superior/intermediate axis (SA-IntA) compared to inferior axis (IA) (38% vs 10%, p=0.002). Among patients with SA-IntA morphology, the contemporary presence of qR pattern in lead aVR and V1 was exclusively found in patient without LGE at CMR (51.0% vs 0%, p< 0.0001). Among patients with IA, the absence of LGE correlated to a narrow ectopic QRS (145±16 vs 184±27 msec, p< 0.001). Conclusions: Among athletes with apparently idiopathic PVCs with a RBBB configuration, the presence of a concealed LGE at CMR was documented in 29% of cases, mostly in those with a SA-IntA. In our experience, the contemporary presence of qR pattern in lead aVR and V1 in PVCs with RBBB/SA-IntA morphology or, on the other hand, a relatively narrow QRS in PVCs with an IA, predicted absence of LGE