A Case of Pemphigus Vulgaris Improved by Cigarette Smoking

THE CUTTING EDGE

SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: LYNN A. CORNELIUS, MD; JON STARR, MD A Case of Pemphigus Vulgaris Improved by Cigarette Smoking

Jessica N. Mehta, MD; Ann G. Martin, MD; Washington University School of Medicine, St Louis, Mo

The Cutting Edge: Challenges in Medical and Surgical Therapeutics

ported that he stopped smoking at the time of disease ex- Editorial Comment: An inverse relationship be- acerbation. When his disease flared again, he was treated tween cigarette smoking and the activity of cer- with intramuscular injections of aurothioglucose (75 mg tain diseases, most notably ulcerative colitis, has weekly), without improvement. been recognized. Similarly, nicotine patches have Examination revealed a 4 ϫ 4-cm erosive plaque with been used in the treatment of pyoderma gangreno- yellow crusting on the patient’s right cheek and a 2 ϫ 2- sum. Although the exact mechanism of the “ben- cm area of erosion on his left cheek (Figure 1, left). A eficial” effect of smoking and/or nicotine on the ac- punch biopsy specimen from the lesion on the right cheek tivity of these diseases has not been definitively demonstrated an epidermis with a split that extended to elucidated, nicotine has been found to affect the adnexal structures, as well as mild acute and chronic in- production of certain proinflammatory cyto- flammation in the superficial dermis (Figure 2). Indi- kines. rect immunoflorescence was positive for epidermal an- As physicians, we must not forget the posi- tibodies at a titer of 1:240. tive association of smoking with lung carcinoma The dosage of prednisone was increased to 80 mg/d, and cardiac and peripheral vascular disease, as well and cyclophosphamide was added to the regimen at a dos- as with impaired wound healing; therefore, im- age of 25 mg/d. Because of the lack of clinical effect, the provement in certain inflammatory diseases can- dosage of cyclophosphamide was increased to 100 mg/d, not be used as a rationale for smoking. Rather, as and dapsone was added to the regimen at a dosage of 75 new inverse associations, such as the one re- mg/d. Despite this aggressive regimen, our patient’s con- ported by Mehta and colleagues, are found, they dition failed to improve. should foster further investigations toward deter- mining the exact factors involved and the mecha- THERAPEUTIC CHALLENGE nisms responsible for the effect, and ultimately result in more specific clinical interventions. The dangerous adverse effects of immunosuppressive Lynn A. Cornelius, MD drugs largely limits their long-term use. Our patient experienced hyperglycemia, cushingoid facies, and leuko- cytosis, and was unable to continue taking oral steroids at high dosages. Our challenge was finding another thera- REPORT OF A CASE peutic modality. A 27-year-old white man presented to our clinic with a 3-year history of pemphigus vulgaris. The initial treat- SOLUTION ment for erosions of the buccal mucosa and blisters on his face and body included oral prednisone, intramus- The patient reported an inverse relationship between cular gold salts, and oral auranofin. After the patient was smoking and pemphigus flares. He observed a worsen- given a course of aurothioglucose (Solganol) by intra- ing of the pemphigus when he stopped smoking. Nico- muscular injection, treatment with oral prednisone (100 tine patches were prescribed, but he began smoking ciga- mg every other day) and oral auranofin (6 mg/d) was ini- rettes again instead. On average, he smokes 15 cigarettes tiated, during which all blisters cleared. Eventually, this per day. One week after he began smoking again, his pem- regimen proved ineffective. In retrospect, the patient re- phigus rapidly started to clear. The dosages of predni- called that he began to smoke cigarettes because of stress sone and cyclophosphamide were tapered, and treat- prior to the improvement of his disease. He also re- ment with both drugs was discontinued over a 2-month

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Figure 1. Left, Large erosive plaque during gold therapy. Right, Patient’s condition is much improved after discontinuation of all therapy and initiation of smoking.

eficial for patients who are resistant to conventional therapy.1 Recently, a case report described a 35-year-old man with inflammatory bowel disease and pyoderma gangrenosum. While his bowel disease improved during treatment with steroids and immunosuppressive agents, his cutaneous lesions were unaffected. Therapy with a 10-mg nicotine patch directly applied to the ulcer caused dra- matic improvement of the cutaneous lesions; interest- ingly, this patient was also an ex-smoker, as are a sig- nificant number of patients with inflammatory bowel disease.2 Another condition reported to have a negative association with smoking is aphthous stomatitis. The cause Figure 2. Hematoxylin-eosin staining shows a suprabasilar split extending to is unclear, but may be the result of increased keratin- the adnexal structures. There is mild acute and chronic inflammation in the superficial dermis (original magnification ϫ10). ization of the oral mucosa making the surface more resistant to formation of ulcers. It is possible that the byproducts of combustion act together to increase kera- period. Dapsone therapy was discontinued immedi- tinization of the epithelial surface in the mouth, which, ately. Figure 1, right, shows the patient 5 months after in turn, may prevent antigenic substances from penetrat- he began smoking again and 3 months after treatment ing and activating the immune system to form aphthous with all medications had been discontinued. He was un- ulcers.3 able to directly apply the nicotine patch to the lesion be- Immune effects associated with smoking include cause of the proximity of the lesion to his eyes. reduced immunoglobulins, helper-suppressor T-cell ratio, lymphocyte transformation, and natural killer COMMENT cytotoxic activity.4 By stimulating the hypothalamic- pituitary-adrenal axis, nicotine may elevate levels of To our knowledge, there are no reports in the literature endogenous glucocorticoids, thus producing an immu- regarding the improvement of pemphigus vulgaris with nocompromised state.5 Also, benzopyrine, a tobacco- cigarette smoking. Other diseases, however, have dem- related polycyclic aromatic hydrocarbon, has been noted onstrated this negative association. In a double-blind, to suppress B-cell lymphopoeisis6 and cytotoxicity in lym- placebo-controlled, randomized, multicenter trial, Pul- phokine-activated killer cells.7 These immune- lan et al1 compared the effects of nicotine transdermal mediated mechanisms may play some role in the effect patches and placebo on 72 patients with ulcerative coli- of smoking on pemphigus. tis. These patients had been receiving routine medicines We find these results surprising and desire further for ulcerative colitis but had experienced recurrences of evaluation of the active therapeutic agent in cigarette their colitis during treatment. The dosage of nicotine smoke that facilitates this immune response. was increased in 5-mg increments to a maximum of 15 mg, or 25 mg if a clinical benefit was not observed at 15 mg. Seventeen of the 35 patients in the nicotine group were able to achieve complete remission of their disease, Accepted for publication July 22, 1999. compared with only 9 in the placebo group. Although Corresponding author: Ann G. Martin, MD, Division the mechanism of action of nicotine in this disease is of Dermatology, Washington University School of Medi- still unknown, it is plausable that this treatment is ben- cine, 4570 Children’s Pl, St Louis, MO 63110.

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1. Pullan RD, Rhodes J, Ganesh S, et al.Transdermal nicotine for active ulcerative Clinicians, local and regional societies, residents, and fel- colitis. N Engl J Med. 1994;330:811-815. lows are invited to submit cases of challenges in man- 2. Wolf R, Ruocco V. Nicotine for pyoderma gangrenosum. Arch Dermatol. 1998; agement and therapeutics to this section. Cases should 134:1071-1072. follow the established pattern. Submit 4 double-spaced 3. Axell T, Henricsson V. Association between recurrent aphthous ulcers and to- copies of the manuscript with right margins nonjusti- bacco habits. Scand J Dent Res. 1985;93:239-242. fied and 4 sets of the illustrations. Photomicrographs and 4. Meliska CJ, Stunkard ME, Gilbert DG, Jensen RA, Martinko JM. Immune func- illustrations must be clear and submitted as positive color tion in cigarette smokers who quit smoking for 31 days. J Allergy Clin Immunol. transparencies (35-mm slides) or black-and-white prints. 1995;95:901-910. 5. Wilkins JN, Carlson HE, Van Vunakis H, Hill MA, Gritz E, Jarvik ME. Nicotine from Do not submit color prints unless accompanied by origi- cigarette smoking increases circulating levels of cortisol, growth hormone, and nal transparencies. Material should be accompanied by prolactin in male chronic smokers. Psychopharmacology. 1982;78:305-308. the required copyright transfer statement, as noted in “In- 6. Hardin JA, Hinoshita F, Sherr DH. Mechanisms by which benzo(a)pyrene, an en- structions for Authors.” Material for this section should vironmental carcinogen, suppresses B-cell lymphopoiesis. Toxicol Appl Phar- be submitted to George J. Hruza, MD, Laser and Der- macol. 1992;117:155-164. matologic Surgery Center, Inc, 14377 Woodlake Dr, Suite 7. Lindemann RA, Park NH. The effects of benzo(a)pyrene, nicotine, and tobacco- III, St Louis, MO 63017. Reprints are not available. specific N-nitrosamines on the generation of human lymphocyte-activated killer cells. Arch Oral Biol. 1989;34:283-287.

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