History of iatrogenic disease

Perhaps the earliest association of iatrogenics relates to toxicity of the many remedies. Here, primum non nocere (“do no harm”) was not the norm. Many of the early physical modalities—leeches, bleeding, heat, water therapy—all had toxic side effects. Overuse of spas, excessive mineral concentrations, and related treatments also created problems in the nineteenth century. Hunter, in his lectures, graphically documents the complications of therapy for this portion of dermatology and syphilology.1 The complications of physical treatment of the strictures, fistula formation, the use of bougies forming new urethral openings, all are directly related to medical surgical intervention. Injections or systemic therapy for the various venereal diseases had many long-term side effects. Mercury was foremost among them, and Hunter, in his usual style, applied mercury on his skin and noted the mucous membrane side effects with severe oral symptoms that were commonly noted in patients treated with mercurial ointments for their chancres. Perhaps in some of these patients the evolution of acrodynia occurred. It is of interest that in his lectures Hunter has a section (p. 119) on “operations of mercury on the virus.” William Heberden, M.D. (in his commentaries, The History and Cure of Diseases)2 compares his thoughts and concerns with those of Hunter. He documents the widespread use of mercury, the dysgeusia associated and the problems with decreased appetite, wasting, erythema, and acrodynia. His recommended treatment is shown in Table 1. This was said to be beneficial for the problems of acrodynia. The development in the understanding of acrodynia was further documented by Kaposi in his book Pathology and Treatment of Diseases of the Skin.3 Acrodynia was noted by Alibert, with the epidermal symptoms in 1828. In 1829 and 1830, further added symptoms included erythema, vesicles, a pellagra-like picture, progressing to gangrene and “tingling” of the peripheral nervous system. At that time acrodynia was assumed to be analogous to pellagra, a similarly poorly understood syndrome. This was a time of increased use of various serums, both animal and human, progressing to the problem of serum sickness, which became well documented in the nineteenth century. The urticaria component of serum sickness was well known, and it was attributed often in Kaposi’s work to food, berries, and seafoods such as saltwater fish and lobsters. The medications associated with urticaria were quinine, copaiba, and mineral water. The problem of urticaria, documented at the close of the nineteenth century, remains a serious medical syndrome to this day. Other heavy metals were used prior to the advent of antibiotics, along with their concomitant side effects, which could be considered either as toxic reactions or iatrogenic disease. Many of these remedies had a very low therapeutic ratio, thereby greatly increasing the possibility of toxic side effects. At the turn of the twentieth century, Darier’s treatise4 focused on the similar problem of sorting out the disease “de novo” versus toxicities and drug-induced diseases from many treatment modalities. Darier attempted to organize these toxicodermas into internal and external causes, thus helping to broaden the understanding of drugs and disease. In Darier’s approach to toxicodermas, he considered external causes as the most common; this was because there were few systemic medications for skin disease at the time. The medicinal and counter-irritant approach to many skin diseases resulted in many clinical problems, including induced maceration from soaks, with secondary infection; toxic reactions to the antiseptics, such as boric acid, other borates and carbolic acid; and skin changes related to formol and other formalin derivatives. Salol, which is a carbolic salicylic acid combiFrom Department of Dermatology, Tulane University Medical Center, New Orleans, Louisiana. Address correspondence to Dr. L. E. Millikan, Dept. of Dermatology SL73, Tulane University Medical Center, 1430 Tulane Ave., New Orleans, LA 70112-2699. Table 1. Early Therapy for Iatrogenic Skin Disease