Disease versus disease: how one disease may ameliorate another

Systemic disease, either genetic or acquired, may prevent or decrease the severity of another disease. These observations have led to important therapeutic advances. The best-known examples are Edward Jenner's use in 1798 of cowpox to prevent smallpox and J.B. Haldane's 1942 observation that erythrocyte disorders such as thalassemia and sickle cell disease modify the severity of malaria. Patients with and carriers of cystic fibrosis may have genetic resistance to tuberculosis and/or secretory diarrhea. The beneficial effects of undernutrition have led to therapeutic diets for seizures, celiac disease, type 2 diabetes, and inflammatory bowel disease. Finasteride for prostatic hypertrophy was developed after the observation that patients with male pseudohermaphrodism resulting from 5-alpha-reductase mutations do not develop prostatic hypertrophy. Rh immunoglobulin for Rh hemolytic disease prevention followed the observation that ABO incompatibility prevented Rh sensitization. The natural immunosuppression of measles may cause remission of nephrosis, and that of leprosy prevents psoriasis. Patients with one form of agammaglobulinemia (X-linked) never get Epstein-Barr virus infection, and patients with another form (common variable) are seemingly cured by HIV infection. HIV/AIDS is prevented or modified by co-receptor mutations (notably the CCRDelta32 chemokine mutation), HIV-2, or GB virus C infection. Additional exploration of these genetic, infectious, and metabolic influences on disease severity may provide new therapeutic approaches to HIV and other diseases.