In the last decades, many different computer-assisted management systems for Computer Interpretable Guidelines (CIGs) have been developed. While CIGs propose a “standard” evidence-based treatments of “typical” patients, exceptions may arise, as well the need to cope with comorbidities. The treatment of deviation from “standard” execution has attracted a lot of attention in the recent literature, but the approaches proposed are focused on the treatment either of exceptions or of comorbities. However, this is a clear limitation, since during a CIG execution, both these issues can occur. In this paper, we propose the first approach which supports the integrated treatment of both exceptions and comorbidities. To achieve such a goal, we propose a modular client-server architecture supporting the concurrent execution of multiple guidelines. The architecture proposed has been designed as a further layer building upon “traditional” execution engines for a single CIG. Thus, our methodology is general and can be used to extend the CIG systems in the literature. Finally, we describe our approach in action on a case study, in which a comorbid patient is treated for Peptic Ulcer and for deep Venous Thrombosis and, during the treatment, she manifests a heart failure.