The article presents brief historical information on generalized pustular psoriasis (GPP), features of its clinical course, and development of potential complications that threaten the patient’s life. A clinical case of a sudden development of generalized pustular psoriasis of von Zumbusch complicated by acute deep vein thrombosis of the lower limbs in a 52-year-old male is described. A detailed description of the past medical history of development and course of the disease and the clinical and laboratory parameters are presented. The occurrence of pathogenic staphylococci and colon bacillus in the pustule content on the mucous membrane of the oral pharynx is noteworthy, because it indicates an important role of the infection in the development and course of GPP. In addition, detection of a high IgE level (966 IU/mL) confirms the immunoreactive nature of skin lesion. Combined therapy with the systemic glucocorticosteroids and acitretin provided a positive clinical effect with reduction of the PASI index from 57.6 to 12.5.