REPORT

FACIAL PYOGENIC GRANULOMA-LIKE LESIONS UNDER ISOTRETINOIN THERAPY JOSEPH HAGLER, M.D., EMMILIA HODAK, M.D., MICHAEL DAVID, M.D., AN13 MIRIAM SANDBANK, M.D.

cystic areas were noticed on the face. No constitutional signs or symptoms were present. Microscopic examination of a puncb biopsy specimen obtained from a pyogenic granuloma-like lesion on the face (hematoxylin and eosinstained) revealed tbat the epidermal layers were absent and tbe upper dermis contained numerous small blood vessels and a dense perivascular cellular infiltrate consisting of lymphocytes, macrophages, plasma cells, and foreign body giant cells. The lower dermis contained increased fibroblasts and collagenous fibers. The dosage of isotretinoin was reduced to 0.5 mg/kg/day with resultant regression and resolution of tbe facial dermatitis and the pyogenic granuloma-like lesions after 2 weeks.

Abstract A male patient witb severe cystic acne was treated with 13cis-retinoic acid in a dosage of 1 mg/kg/day. Early flare-up of bis acne and multiple pyogenic-like lesions on his face appeared during the second week of isotretinoin treatment. Histologic study of the lesions revealed granulation tissue. Possible etiologies for this phenomenon are discussed. Isotretinoin (13-cis-retinoic acid) has been shown to be a highly potent therapeutic agent in the treatment of severe cystic acne.'"-^ Under therapy with 13-cis-retinoic acid mucocutaneous side effects are often found which, though less marked, are similar to those of hypervitamlnosis A. These side effects are largely dose dependent and reversible after reduction or withdrawal of the drug. Cheilitis appears routinely even at a low dose of 0.1 mg/kg/day. Other relatively frequent side effects are: facial dermatitis, dryness of the nasal and buccal mucosa, desquamatioti, and pruritus. Conjunctivitis, nosebleeds, fragility of the skin, and excess granulation tissue occur more rarely.''''"*' We have recently noted the occurrence of facial multiple pyogenic granuloma-like lesions in a patient with severe cystic acne treated with oral isotretinoin.

DISCUSSION

The tissue respotise described herein occurred in twelve previous cases published in the English literature.^"" The reaction in these case reports developed at sites of both ulcerative (75%) and nonulcerative (25%) cystic acne lesions, which were located on the neck, shoulders, upper arms, chest, back, and buttocks. Therefore, erosions can be a marker for greater susceptibility to develop pyogenic granuloma-like lesions during isotretinoin treatment. In the above-mentioned case reports, this reactioti appears after 3 to 12 weeks of therapy. The lesions resolved following curettage, silver nitrate cautery, reductioti or discontinuation of isotretinoin, atid prednisone therapy. Our patient developed pyogenic gratiuloma-like lesions on the face after 2 weeks of 1 mg/kg/day 13-cis-isotretinoin therapy. The dose of isotretinoin was decreased to 0.5 mg/kg/day and the pyogenic granuloma-like lesions spontaneously involuted. Therefore, it seems that the existence of the pyogenic granuloma-like lesions during isotretinoin therapy is a dose-dependent side effect. Our case differs from previously reported cases in two aspects. (1) The location of the pyogenic granulorna-like lesions: on the face. As far as we know no such facial lesions have been described previously in the literature. This rarity is probably due to the predelection of cystic acne to involve the trunk and less frequently the facial area. (2) The earlier appearance of the pyogenic granuloma-like lesions. The exact mechanism of the reactioti is unknown. Possible etiologies for this phenomenon are convincing evidence tbat retinoids have been shown to modulate connective tissue rnetabolism

Case Report A 15-year-old wbite man had severe cystic acne since tbe age of 12 years. He responded poorly to conventional topical and oral antibiotic tberapy. On examination, a severe degree of cystic acne was found, with many large cysts, nodules, pustules, and multiple comedones distributed on the face, upper chest, and upper back. Isotretinoin was started at an initial dosage of 80 mg orally (1 mg/kg/day). After 2 weeks of tberapy, facial dermatitis was noted at follow up. Additional facial, multiple, soft, friable, pyogenic, granuloma-like lesions (0.6 x 0.6 cm), erupting from within From the Department of Dermatology, Beilinson Medical Center, Petah Tiqva, and the Tel Aviv University, Sackler School of Medicine, Israel. Address for correspondence: Joseph Hagler, M.D., Department of Dermatology, Beilinson Medical Center, Petah Tiqva 49100, Israel. 199

International Journal of Dermatology Vol. 31, No. 3, March 1992

in fibroblast cultures and suppression of production of collagenase by isotretinoin.'^ Skin fragility occurs in patients during treatment with isotretinoin and is associated with the loss of desmosomes and desmosomal attachment and with the accumulation of an amorphous material within the epidermis.'^ Moderate to marked increase in vascular proliferation was noted in the upper portion of the reticular dermis after tbe onset of oral isotretinoin. '"^ Early diagnosis of pyogenic granuloma-like lesion under isotretinoin therapy provides the basis for tberapeutic management. Topical treatment of eacb lesion is possible but not generally essential.

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DRUG NAMES

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isotretinoin: Accutane 11. REFERENCES

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Peck GL, Olsen TC, Butkus D, et al. Isotretinoin versus placebo in the treatment of cystic acne. J Am Acad Dermatol 1982; 6:735-745.

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Yobpo EH, Pochi PE. Side effects and long-term toxicity of synthetic retinoids. Arch Dermatol 1987; 123: 1375-1376. Hodak E, David M, Eeuerman EJ. Excess granulation tissue during etretinate therapy. J Am Acad Dermatol 1984; 11:6. Norris J, Cunliffe WJ. The use and long-term benefit of isotretinoin. BrJ Demiatol 1987; 117 (Suppl 32):23-34. Mobayen MM, Copeman PW. Multiple pyogenic granulomas in secondarily infected cystic acne. Clin Exp Dermatol 1983; 8:107-109. Valentic JP, Barr RJ, Weinstein GD. Inflammatory neovascular nodules associated with oval isotretinoin treatment of severe acne. Arch Dermatol 1983; 119: 871-872. Exner JH, Dahod S, Pochi PE. Pyogenic granuloma-like acne lesions during isotretinoin therapy. Arch Dermatol 1983; 119:808-811. Robertson DB, Kubiak E, Gomez EC. Excess granulation tissue responses associated with isotretinoin therapy. BrJ Dermatol 1984; 3:689-694. Blanc D, Zultak M, Wendling D, Lonchampt E. Eruptive pyogenic granulomas and acne fulminans in two siblings treated with isotretinoin. Dermatologica 1988; 177:16-18. Abergill R, Meeker C, Oikarinen H, et al. Retinoid modulation of connective tissue metabolism in keloid fibroblast cultures. Arch Dermatol 1985; 121:632-635. Williams ML, Elias PM. Nature of skin fragility in patients receiving retinoids for systemic effect. Arch Dermatol 1981; 117:611-619. Goldstein JA, Comite H, Mescon H, et al. Isotretinoin in the treatment of acne. Histologic changes, sebum production and clinical observation. Arch Dermatol 1982; 118:555-558.

Patient Communication We live at a time when consumers and patients want to know more about tbe food they consume and the drugs they take, and their appetite for information is growing. Yet the nation is also facing a communications gap that has serious implications for the public health. Tbis gap extends from wbat patients want to know about their medicines to wbat they actually learn from their physicians and pharmacists. The uncertainties of patients, who receive approximately 1.5 billion prescriptions a year, contribute to the failure of many of them to benefit fully from tbeir medications. Evidence suggests that inadequate communication about drugs is one of the principal reasons why 30 to 55 percent of patients deviate from their medical regimens. Patients' misunderstanding of tbe proper use of medications is also an underlying cause of many adverse drug reactions. Now that computers, data banks, and rapid printers are common, we can do much better. Commercial advertising is not a suitable vehicle for educating the public about tbe risks and benefits of drugs. In my view, bridging tbe information gap is a matter of high priority for consumers, providers, and the Food and Drug Administration. From Kessler DA. Communicating with patients about their medications. N EnglJ Med 1991; 325:1650-1652. 200

Facial pyogenic granuloma-like lesions under isotretinoin therapy.

A male patient with severe cystic acne was treated with 13-cis-retinoic acid in a dosage of 1 mg/kg/day. Early flare-up of his acne and multiple pyoge...
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