Noncaseating Granulomatous Disease in Common Variable Immunodeficiency

Patients with common variable immunodeficiency (CVID) are occasionally recognized to have a concurrent noncaseating granulomatous disease. The granulomatous disease (GD) associated with CVID shares many clinical properties typical of sarcoidosis. Some investigators speculate that the GD-CVID is actually sarcoidosis that is expressed atypically because of the patient\u27s immunodeficiency. Clinical differences, however, have led other investigators to speculate that the GD-CVID is a distinct sarcoid-like granulomatous process

Development of granulomatous common variable immunodeficiency subsequent to infection with Toxoplasma gondii

Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency that is accompanied by granulomatous lesions in 5–10% of cases. Why some patients develop granulomatous disease remains unclear. Here we describe a 12-year-old previously healthy girl who presented with pancytopenia and granulomatous lymphoproliferation subsequent to infection with Toxoplasma gondii. Loosely arranged non-fibrosing granulomas were observed in the liver, lymph nodes and lung, but no Toxoplasma tachyzoites could be demonstrated and polymerase chain reaction (PCR) and culture were negative for Toxoplasma and a wide range of other pathogens. While the patient had a normal peripheral B cell status at presentation, the development of CVID could be observed during the following months, leading to a loss of memory B cells. This was accompanied by an increasingly activated CD4(+) T cell compartment and high serum levels of angiotensin-converting enzyme (ACE), tumour necrosis factor (TNF) and sCD25. Steroid therapy reduced pancytopenia, granulomatous lymphoproliferation and cytokine elevations, but did not improve the B cell status. This is the first report of an association of Toxoplasma infection with granulomatous CVID and provides one of the rare examples where the onset of CVID could be documented subsequent to an infectious disease

Cytochrome P450-mediated cardiovascular drug interactions.

Introduction: There are numerous drug-drug interactions (DDIs) related to cardiovascular medications and many of these are mediated via the cytochrome P450 (CYP) system. Some of these may lead to serious adverse events and it is, therefore, essential that clinicians are aware of the important interactions that occur. Areas covered: An extensive literature search was performed to analyze the CYP-mediated cardiovascular DDIs that lead to a loss of efficacy or potential toxicity. Cardiovascular drugs may be victims or act as perpetrators of DDIs. The paper analyzes CYP-mediated drug interactions concerning anticoagulants, antiplatelet agents, antiarrhythmics, beta-blockers, calcium antagonists, antihypertensive medications, lipid-lowering drugs and oral antidiabetic agents. Expert opinion: Cardiovascular DDIs involving the CYP system are numerous. Additionally, the spectrum of drugs prescribed is constantly changing, particularly with cardiovascular diseases and it is not necessarily the case that drugs that had shown safety earlier will always show safety. Clinicians are encouraged to develop their knowledge of CYP-mediated DDIs so that they can choose safe drug combination regimens, adjust drug dosages appropriately and conduct therapeutic drug monitoring for drugs with narrow therapeutic indices