The review focuses on clinical and epidemiological characteristics of herpesvirus infection, particularly Human herpesvirus type 8, which is associated with idiopathic Kaposi sarcoma. A new hypothesis of the origin of this disease is discussed. An important paradigm is now gaining influence: assessment and prediction of the integral effect of cumulative various viral infections (in particular, HHV), the so-called infection coalition. We present a clinical case of Kaposi sarcoma (idiopathic, sporadic type) associated with herpesvirus infection in a comorbid patient. The authors suggest that synergistic pathological effects of HSV types 1, 3, and 8 in this comorbid patient may lead to multisystem involvement of skin, mucous membranes, and CNS (presented as herpetic ganglioneuritis as an atypical form of the secondary recurrent disease). In this regard, the authors hypothesize the presence of a viral coalition in herpesvirus infections, including systemic organ and tissue involvement, which warrants further scientific research. The trigger factors for organ damage in the persistence of various types of herpesviruses remain controversial. Perhaps the critical factor for the damage is not just the persistence of HHV but the state of its latency or replication. The specific mechanisms of the systemic effects of mixed herpes virus associations on the human body are currently studied but still far from being finally understood.