Another characteristic feature predictive of an autoimmune process in patients with CVID is the presence of granulomatous infiltrations in the lungs, nodes or other organs. CVID patients with autoimmune diseases are treated using higher doses of immunoglobulin replacement therapy (IRT), and when immune suppressive drugs are administered, it is advised that lower doses and shorter courses are given to prevent the development of opportunistic infections considering the underlying PIDD. Malignancy The lifetime risk of all types of malignancies in adults with CVID is around 6 – 9%.[33] CVID patients are at tenfold increased risk of developing solid or haematological malignancies.[33] Patients with lymphoma typically have a childhood onset and those with gastric Bavisant dihydrochloride hydrate tumours present later in adulthood, particularly in the fourth decade of life. progress to ZNF35 obstructive or restrictive disease given time. Asthma has been observed in 9 – 15% of patents with CVID. The actual aetiology of asthma in patients with CVID is largely unknown. Mediastinal lymphadenopathy is common in CVID. Nonnecrotising granulomas have been described in 8 – 22% of patients with CVID; these non-necrotising granulomas differ from those from sarcoidosis as they are not located peri-lymphatically. Sarcoidosis is usually associated with hyper-gammaglobulinaemia. [25C27] Lymphocytic interstitial pneumonitis has also been reported. Gastrointestinal disease There is a high incidence of inflammatory and infectious gastrointestinal disorders in patients with CVID.[28] Mild watery diarrhoea is common and occurs periodically. More severe clinical disease with malabsorption and weight loss are well described and occur in 10% of cases. Gastrointestinal pathology may include nodular lymphoid hyperplasia and autoimmune hepatitis progressing to portal hypertension. A challenging form of chronic small bowel inflammation and CVID-associated autoimmune enteropathy (AIE) occurs in up to 12% of patients presenting with unexplained persistent diarrhoea, malabsorption of minerals and fat-soluble vitamins, steatorrhoea, and weight loss. These patients often have vitamin A deficiency with added suppression of Ig production. Mild hepatomegaly and an elevated level of alkaline phosphatase is also seen in CVID.[29C31] Granulomatous or polyclonal lymphocytic infiltrative complications Some patients (10 – 25%) with CVID develop granulomatous or lymphoproliferative diseases. The mean age of diagnosis is 20 – 40 years. Granulomatous lesions can affect any region of the body, but most commonly affect the lungs. Patients present with chronic shortness of breath and cough, which is not related to asthma.[8] Autoimmunity It has been suggested that up to 30% of patients with CVID will experience an autoimmune process. Autoimmune disease was the sole clinical finding at the time of diagnosing CVID in 2.3% of patients.[29] Common autoimmune entities seen in CVID patients include autoimmune cytopaenias such as immune thrombocytopaenic purpura (ITP), autoimmune haemolytic anaemia (AIHA), combination of ITP and AIHA Bavisant dihydrochloride hydrate (Evans syndrome), seronegative rheumatoid arthritis (RA), pernicious anaemia, inflammatory bowel disease, Sj?grens syndrome, uveitis, vasculitis, thyroiditis, alopecia, vitiligo, primary biliary cirrhosis, and sicca syndrome or systemic lupus erythematosus.[5,29] Common autoimmune diseases such as type I diabetes mellitus, seropositive RA, psoriasis, celiac and hypothyroidism are not increased in patients with CVID. Not only is the underlying pathogenesis of CVID poorly understood, but the management of concurrent autoimmunity often becomes a challenging task. It is very important to emphasise that autoimmunity may be the presenting feature of CVID without any evidence of recurrent infections characteristic of a PIDD.[32] There seems to be a higher prevalence of autoimmune processes in patients with a paucity of switched memory B cells (CD27+, IgMCIgDC). Another characteristic feature predictive of an autoimmune process in patients with CVID is the presence of granulomatous infiltrations in the lungs, nodes or other organs. CVID patients with autoimmune diseases are treated using higher doses of immunoglobulin replacement therapy (IRT), and when immune suppressive drugs are administered, it is advised that lower doses and shorter courses are given to prevent the development of opportunistic infections considering the underlying PIDD. Malignancy The lifetime risk of all types of malignancies in adults with CVID is around 6 – 9%.[33] CVID patients are at tenfold increased risk Bavisant dihydrochloride hydrate of developing solid or haematological malignancies.[33] Patients with lymphoma typically have a childhood onset and those with gastric tumours present later in adulthood, particularly in the fourth decade of life. The most common type of malignancy reported in patients with CVID is non-Hodgkins lymphoma.[34] Making a diagnosis There is no single test or biochemical marker available to diagnose CVID. The diagnosis is made by a constellation of clinical features and several laboratory investigations. It is the combined result of these tests from which a diagnosis can be made. There are more common genetic disorders that manifest with CVID. Testing for this is possible but expensive. However, diagnosis is not dependent on genetic testing only. Bavisant dihydrochloride hydrate The diagnosis of CVID rests on exclusion of other causes of hypogammaglobulinaemia (Table 2). Table 2 Secondary Bavisant dihydrochloride hydrate causes of hypogammaglobulinaemia[4,13] thead Drug-induced Antimalarial agents /thead Captopril br / Phenytoin, carbamazepime br / Anti-CD20 mAbs: Rituximab br / Glucocorticoids br / Sulfasalazine Single gene and other defects Ataxia telangiectasia br / AR forms of SCID and other combined immunodeficiency br / .
