Journal of the Royal Society of Medicine Volume 75 December 1982 963 treated with topical minoxidil'

David A Fenton MB MRCP John D Wilkinson MB MRCP Department of , Wycombe General Hospital, Bucks HPJ 1 2TT

Summary: Two cases of long-standing treated with topical minoxidil are described. The mechanism of minoxidil is discussed. Introduction Many treatments have been suggested for alopecia areata. Most have relied on the natural history of the disease or on inducing an inflammatory response. To date no single treatment has been universally successful and patients have tended to relapse on discontinuing therapy. Two patients are described with long-standing alopecia totalis who regrew scalp within two months of treatment with topical minoxidil. Case reports Case 1: A 52-year-old woman had developed alopecia totalis one month after the birth of her third child in 1953. There was no previous history of alopecia and no family history. Various treatments, including topical and intradermal , application of thorium-X, iodine and phenol, failed to produce regrowth. In 1961 diffuse regrowth of occurred after exposing the scalp to ultraviolet radiation. Full regrowth of hair ensued and this lasted for two years, but for the past 15 years she has had alopecia totalis. Treatment with 1% minoxidil in Unguentum Merck was commenced in February 1982. This was applied to the scalp thinly once daily. There was new vellus hair after six weeks treatment, and after four months therapy long, white vellus and terminal could be seen. Case 2: A 70-year-old womanx with a 64-year history of alopecia areata had developed at 6 years of age, after an episode of pneumonia. Minimal regrowth of hair occurred at 12 years of age, but subsequent complete loss had required her to wear a wig since she was 14. Complete regrowth of hair occurred during pregnancy at 21 years of age but this was followed by alopecia universalis in the puerperium. She has had alopecia universalis ever since. There is no family history of alopecia and no personal history of atopy, hypertension or organ-specific . Treatment with 1% minoxidil in Unguentum Merck was commenced in February 1982, and applied thinly to the scalp and once daily. After one month some vellus hair on the scalp was apparent. After four months she had grown long, white, fine vellus and all over her scalp (Figure 1) and had also noticed that her had regrown for the first time in forty years. Discussion Several drugs are known to produce hypertrichosis: benoxaprofen, cyclosporin, diazoxide, diphenylhydantoin, minoxidil, penicillamine, psoralens, corticosteroids, and streptomycin. Minoxidil is a potent peripheral vasodilator used to control severe hypertension. Dermatological interest was aroused when it was noticed that hypertrichosis was produced in virtually all patients receiving therapeutic doses of the drug (Dargie et al. 1977). Burton & Marshall (1979) described hypertrichosis involving the forehead, ears, temples, eyebrows and 1 Based on case presentations to Section of Dermatology, 17 June 1982. Accepted 18 August 1982 0141-0768/82/120963-03/$O1.00/0 (D 1982 The Royal Society of Medicine 964 Journal of the Royal Society of Medicine Volume 75 December 1982

Figure 1. Hair regrowth after 4 months treatment with topical minoxidil forearms in a 50-year-old man receiving minoxidil 15 mg daily for hypertension. They suggested that a topical formulation might stimulate local hair growth in early male-pattern alopecia. Reversal of male-pattern baldness has been described in a patient receiving minoxidil for hypertension (Zappacosta 1980). Systemic minoxidil appears to convert vellus hair to terminal hair and also darkens the colour of the hair. As treatment is continued, however, some of the hypertrichosis may disappear. Normal plasma testosterone levels and normal urinary hydroxy- and ketosteroids have been found in minoxidil-treated patients with hypertrichosis (Earhart et al. 1977); androgenic stimulation is therefore unlikely. Weiss et al. (1981), in the United States, have treated alopecia areata patients with topical minoxidil as a 1% lotion in ethanol, propylene glycol and water. The lotion was applied thinly to the scalp twice daily, the evening application being occluded with a thin layer of white petrolatum. Local hair regrowth was observed in 2 out of 3 patients within four to six weeks. We have treated several patients with alopecia areata using the 1% minoxidil lotion as used by Weiss and colleagues, and also 1% minoxidil in Unguentum Merck. Regrowth of hair has been observed in two-thirds of patients treated. This is seen at an earlier stage in the patients receiving the Unguentum Merck preparation, presumably due to its occlusive effect. Regrowth of eyebrows and eyelashes (as in Case 2) has been observed in some patients when only the scalp is being treated. This would suggest that there is some absorption via the scalp and that growth of hair in sites distant from those being treated is due to a systemic effect. No other systemic effects have been noted during therapy; in particular, there has been no fall in blood pressure and no contact . Many treatments can induce vellus hair growth, but regrowth of terminal hair has always been more elusive. Both vellus and terminal hair growth is seen with topical minoxidil treatment and long, white, fine 'intermediate-type' hairs have also been observed. At present it is not possible to say if the hair growth will be permanent or if it will persist even if treatment is continued. But the use of topical minoxidil therapy is obviously more acceptable than topical sensitization with allergens. The hypertrichosis seen with minoxidil bears close resemblance to that seen with diazoxide (Burton & Marshall 1979) and although they are not related chemically, they are both potent peripheral vasodilators. An increased cutaneous perfusion has previously been suggested as a mechanism for the hypertrichosis (Burton et al. 1975), and systemic minoxidil markedly increases the blood flow Journal of the Royal Society of Medicine Volume 75 December 1982 965 to the skin (Humphrey et al. 1974). The regrowth seen with topical minoxidil may be due to absorption via the scalp, producing local vasodilatation. This would also explain the regrowth occurring at sites near those areas treated. Occlusive preparations would be expected to enhance this effect. Topical minoxidil therapy would seem to be a fairly innocuous treatment for alopecia areata, but the eventual cosmetic acceptability of the regrowth remains to be assessed. References Burton J L & Marshall A (1979) British Journal of Dermatology 101, 593-595 Burton J L, Schutt W H & Caldwell I W (1975) British Journal of Dermatologr, 93, 707 Dargie J H, Dollery C T & Daniel J (1977) Lancet ii, 515 Earhart R N, Ball J, Nuss D D & Aeling J L (1977) Southern Medical Journal 70, 442 Humphrey S J, Wilson E & Zins G R (1974) Federation Proceedings 33, 583 Weiss V C, West D P & Mueller C E (1981) Journal of the American AcademY of Dermatology, 5, 224-226 Zappacosta A R (1980) New England Journal of Medicine 303, 1480-1481