The therapeutic era
Throughout the 19th century, a variety of soaps and patent medicines were touted as cure-alls for a host of skin diseases. Other than their benefits to surface cleanliness and their antiseptic properties, however, they were of little effect.
It wasn’t until the 20th century that truly effective therapeutics entered the dermatologic pharmacopoeia. In their 1989 review, Diane Quintal, MD, and Robert Jackson, MD, discussed the origins of the most important of these drugs and pointed out that, “Until this century, the essence of dermatology resided in the realm of morphology. Early contributors largely confined their activities to the classification of skin diseases and to the elaboration of clinical dermatologic entities based on morphologic features. ... but “in the last 50 years, there have been significant scientific discoveries in the field of therapeutics that have revolutionized the practice of dermatology.“ (Clin Dermatol. 1989;7[3]38-47).
These key drugs comprised:
- Quinacrine was introduced in 1932 by Walter Kikuth, MD, as an antimalarial drug. But it was not until 1940, that A.J. Prokoptchouksi, MD, reported on its effectiveness 35 patients with lupus erythematosus.
- Para-aminobenzoic acid (PABA) came into prominence in 1942, when Stephen Rothman, MD, and Jack Rubin, MD, at the University of Chicago, published the results of their experiment, showing that when PABA was incorporated in an ointment base and applied to the skin, it could protect against sunburn.
- Dapsone. The effectiveness of sulfapyridine was demonstrated in 1947 by M.J. Costello, MD, who reported its usefulness in a patient with dermatitis herpetiformis, which he believed to be caused by a bacterial allergy. Sulfapyridine controlled the disease, but gastrointestinal intolerance and sulfonamide sensitivity were side effects. Ultimately, in 1951, Theodore Cornbleet, MD, introduced the use of sulfoxones in his article entitled “Sulfoxone (diasones) sodium for dermatitis herpetiformis,” considered more effective than sulfapyridine. Dapsone is the active principal ingredient.
- Hydrocortisone. In August 1952, Marion Sulzberger, MD, and Victor H. Witten, MD (both members of the first Skin & Allergy News editorial advisory board), described use of Compound F (17-hydroxycorticosterone-21-acetate, hydrocortisone) in seven cases of atopic dermatitis and one case of discoid or subacute lupus erythematosus, reporting improvement in all of these cases.
- Benzoyl peroxide. Canadian dermatologist William E. Pace, MD, reported on the beneficial effects of benzoyl peroxide on acne in 1953. The product had originally been used for chronic Staphylococcus aureus folliculitis of the beard.
- Griseofulvin, a metabolic byproduct of a number of species of Penicillium, was first isolated in 1939. But in 1958, Harvey Blank, MD, at the University of Miami (also on the first Skin & Allergy News editorial advisory board), and Stanley I. Cullen, MD, administered the drug to a patient with Trichophyton rubrum granuloma, in the first human trial. In 1959, they reported the drug’s benefits on 31 patients with various fungal infections.
- Methotrexate. In 1951, R. Gubner, MD, and colleagues noticed the rapid clearing of skin lesions in a patient with rheumatoid arthritis who had been treated with the folic acid antagonist, aminopterin. And in 1958, W.F. Edmundson, MD, and W.B. Guy, MD, reported on the oral use of the folic acid antagonist, methotrexate. This was followed by multiple reports on the successful use of methotrexate in psoriasis.
- 5-fluorouracil (5-FU). In 1957, 5-FU, an antimetabolite of uracil, was first synthesized. In 1962, G. Falkson, MD, and E.J. Schulz, MD, reported on skin changes observed in 85 patients being treated with systemic 5-FU for advanced carcinomatosis. They found that 31 of the 85 patients developed sensitivity to sunlight and subsequent disappearance of actinic keratoses in these same patients.