Complications of topical hydrocortisone Jere D. Guin, M.D. Kokomo, IN Chronic and uninterrupted application of I % hydrocortisone was followed by complications in six patients. Three developed a rosacea-I ike eruption for the first time an done also had perioral dermatitis. A11 of these responded to treatment a nd remained clear. Another patient had a severe exacerbation of ros acea following use and withdrawal of 1 % hydrocortisone cream. Two female adults developed atrophy and telangiectasia of the eyelids following long-term application of I % hydrocortisone cream. The severity of the complications reported was generally less than that found following use of more potent topical corticosteroids. However, the complications experienced by these patients wou ld suggest that therapy with any effective topical corticosteroid should be intermittent. Particular care should be used in su sceptible individuals and in vulnerable areas such as the eyelids. (J AM ACAD DERMATOL 4:417-422, ]981.)

Potent topical corticosteroids are known t-o cause a variety of side effects, including seniletype purpura, a rosacea-like eruption, exacerbation of acne, atrophy and atrophic striae, glaucoma, and aggravation of dermatophyte infections.' Lower concentrations of hydrocortisone, on the other hand, are considered sufficiently innocuous to permit their nonprescription sale." In fact, there seems to be some doubt that hydrocortisone could produce such complications even if abused. I report six patients who developed complications following the use of topical preparations containing 1% hydrocortisone. CASE REPORTS

Case 1 A 22-year-old woman presented with hidradenitis suppurati va of the axillae and casually mentioned a scaly eruption lateral to the nasal alae. She denied any previous therapy for either skin condition and the use of From the Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN. Reprint requests to: Dr. Jere D. Guin, 804 South Berkley Road, Kokomo, IN 46901.

0190-9622/81/040417+06$00.60/0 © 1981 Am Acad Derrnatol

any oral medications except Ovulen-28, which she had taken fOT 2 months. Physical examination revealed scars and comedones (and one nodulocystic lesion) of the axillae. A scaly eruption, interpreted as seborrheic dermatitis, was present in the nasofacial groove and laterally on the cheeks. The seborrheic dermatitis was treated with topical 1 % hydrocortisone and 10% sodium sulfacetamide in Acid Mantle creme. One month later, the patient was found to have erythema and multiple pustules over the cheeks and an erythematous and papular eruption in and around the nasofacial groove where she had applied the medication (Fig. 1). She denied any previous history of either eruption. These signs cleared following treatment with oral tetracycline and a topical lotion containing 10% sodium sulfacetamide and 5% sulfur. There was no recurrence when treatment was slowly decreased over a 3-month period.

Case 2 A 67-year-old man, hospitalized for syncopy, bradycardia, diabetes mellitus, and pernicious anemia, was s-een in consultation for an eruption of the face of many years' duration. Examination revealed rosacea of the central portion of the face and seborrheic dermatitis of the eyebrows, eyelid margins, and nasolabial folds.

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Fig. 1. A papular and erythematous eruption which appeared weeks' use of a cream containing 1% hydrocortisone. Treatment consisted of topical clindamycin, sodium sulfacetamide 10% ophthalmic ointment, and a cream containing I % hydrocortisone and 10% sodium sulfacetamide in Acid Mantle creme. Improvement was noted during his hospital stay. The patient was not seen again until 2 months following discharge, at which time the pustular eruption was dramatically worse than it had been when he was originally seen. According to the patient, he had been applying the topical steroid cream regularly to the central portion of the face. He was given oral tetracycline, 250 mg twice daily, but was lost to follow-up when he was hospitalized elsewhere for his primary conditions.

Case 3 A 67-year-old man had been treated for many years for numerous solar keratoses, seborrheic keratoses, and squamous cell carcinomas. He had never had rosacea. In August, 1979, he asked for treatment for a scaly eruption of the glabella and eyebrow areas of recent onset. Examination revealed a plethoric man with multiple areas of slight alteration in pigment from previous superficial surgery in sun-damaged skin. He also had seborrheic dermatitis of the glabella and eyebrows. Three months after he was started on 1 % hydrocortisone cream (Hytone), erythema and multiple pustules appeared in the previously treated area. The patient had been using the hydrocortisone cream regularly rather than only as needed. He was treated with oral tetracycline, 250 mg twice daily, and instructed to

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Patient 1 following 4

avoid use of the 1% hydrocortisone cream. Following a response to treatment in the first 2 weeks, tetracycline was reduced in dosage and discontinued. No recurrence of the pustules occurred during the first 6 months after discontinuance of oral tetracycline.

Case 4 A 72-year-old man was seen in January, 1980, because of seborrheic dermatitis of the face and scalp of long duration. He was under treatment by another physician for cardiac decompensation, gout, and hypertension. Examination of the skin revealed seborrheic dermatitis of the forehead, eyebrows, nasolabial folds, and scalp. There was also a seal ing eruption of the feet and onycholysis and subungual hyperkeratosis of multiple toenails. Multiple hyphae were found on KOH examination of skin scrapings from the feet. Treatment consisted of oral griseofulvin (ultramicrocrystalline), 125 mg three times daily, and topical 2% miconazole cream to the feet. The scalp was treated with 10% sodium sulfacetamide lotion and 0.1 % triamcinolone acetonide in propylene glycol. Lesions on the face were treated with a cream comprising 1% hydrocortisone and 10% sodium sulfacetamide in Acid Mantle creme. One month later, the treated conditions were dramatically improved. However, the patient noted multiple small, tender pustules over the nose. He had faithfully applied the hydrocortisone-sodium sulfacetamide cream to the skin over the nose and involved areas of the cheeks three times daily. He was

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Fig. 2. Thinning of the skin of the upper eyelids in Patient 5 which developed after 12 months' treatment with a cream containing 1% hydrocortisone. asked to stop this practice and was given clindamycin 1% in a hydroalcohol ic vehicle to be used topically. Response was prompt so that after 4 weeks the use of topical clindamycin could be reduced and later discontinued without any recurrence.

Case 5 A 62-year-old woman had been treated since 1972 for chronic seborrheic dermatitis of the scalp and face. In February, 1979, she was given a topical steroid cream containing I % hydrocortisone and 10% sodium sulfacetamide for seborrheic dermatitis of the eyelids. She was not seen again until April 21, 1980, when she sought treatment for another condition. According to the history, the topical corticosteroid had been used on a regular basis for over I year. Examination revealed the formerly involved upper eyelid areas to be quite thin with dermal blood vessels visible on the surface. The atrophic skin of the upper eyelids contrasted with the more normal skin of the lower eyelids, and there was a definite margin approximately 1 cm below the eyebrow on each side (Fig. 2).

Case 6 A 67-year-old woman was seen in December, 1979, because of chronic eczema of the lower eyelids. She had been treated by another physician with topical betamethasone valerate cream 0.1 % three or four times daily to the involved area for 2 weeks. Examination revealed an eczematous eruption of the

medial aspect of the lower eyelids with swelling and scaling. The lateral portions of the lower eyelids were normal. The previous treatment was discontinued. She was started on topical I % hydrocortisone, 10% sulfacetamide in Acid Mantle creme pending the outcome of patch tests. Patch tests to multiple substances revealed a 1+ reaction to a perfume mix and to a moisturizing lotion which had been applied to the area. She was advised to avoid that product, to use fragrance-free cosmetics, and to use the hydrocortisone cream for symptomatic relief. Because of an extended vacation in Florida, she was not seen again until April, 1980. Examination at the time revealed no eyelid dermatitis. However, the patient complained of "dark spots" in the previously involved area. These were first noted in late February or early March, 1980. A close examination revealed atrophy of the medial aspect of both lower eyelids. Blood vessels were easily visible in the skin and there was a difference in thickness of the skin of the medial and lateral aspects of both lower eyelids (Fig. 3). A history of uninterrupted usage of the topical hydrocortisone sulfacetamide cream was obtained and this medication was stopped.

DISCUSSION

Topical 1% hydrocortisone has a relati vely good safety record, but it has not been totally without complications, particularly in children.

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Fig. 3. Telangiectasia and atrophy of the medial aspect of the lower eyelids (more prominent on the left) in Patient 6 . This followed use of a cream containing 1% hydrocortisone for 4 month s.

There are reports of growth arrest, :1.-1 fluid retention and weight gain," and benign intracranial hypertension. -1.6 Some studies of hydrocortisone have shown a relativel y low order of absorption' and little tendency to produce atrophy. H.!J However, in children, when the drug is applied under occlusion to the antecubital fossa, absorption can reach 44% in normal and 50% in eczematous skin as measured by urinary output," Just how absorption in this area in children would compare with nonocclusive use in the central one third of the face or the eyelids in adults is not clear, but it is much greater on the forehead than on the forearm;'? and it would be e xpec ted to increase with long-term use . II Although complications from these agents are thought generally to be a function of potency , IU the tendency for a particular top ical corticosteroid to produce certain side effec ts, e.g. , atrophy , does not always parallel its ant i-inflammatory activity ." However, for a given agent, a compatible vehicle (which should make the preparation more effective) and additives (which increase absorption) might increase complications as well as effectiveness. Not unreasonably, some have warned tha t some side effects usually attributed to more potent topical corticosteroids could possibly occur with prolonged use of hydrocortisone, especially when

appl ied to vulne rable areas 12 and to patients with rosacea . I :! In evaluating the first patient , it is difficult to totally rule out a causative effect from the vehicle. A statistical analys is of Bendl 's I ~ data showed an impressive correlation of the use of creams and cosmetics by patients with perioral dermatitis as compared with a control group. However, of the first four patients, only one patient had that condition, while all had rosacea . Their courses would better fit the rebound phenomenon which has been described following topical corticosteroid therapy. Rosacea can, of course, occur without any pre vious exposure to topical corticosteroids , but it tends to worsen suddenly after their use and withdrawal . !" This was dram atic in Patient 2. Three of the patients who developed rosacea denied having pustules pre viously , although they were all lightcomplexioned and had seborrheic dermatitis. All of these patients were seen both befo re and after the onset of the eruption, which occurred only in or around the areas where the cream was used. All received topical I % hydrocortisone in a van ishing cream base and all but one used the same preparation. One cannot say with certaint y that the use of topical hydrocortisone cau sed the eruption, but the circumstances are suggest ive. Although uncommon, rebound has been previously noted follow -

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ing withdrawal of topical hydrocortisone from patients with rosacea who were initially benefited. 1:1 While perioral dermatitis is often attributed to the use of more potent topical corticosteroids, six patients in one series I-l and two in another" had received prior treatment with hydrocortisone. (Those reporting the latter group denied a causal relationship.) Rebound following hydrocortisone withdrawal is not unreasonable. Perioral dermatitis can even occur without prior therapy with a topical corticosteroid, since the patients reported by Frumess and Lewis!" had not received any such medication. However, that condition is more common since the advent of potent topical corticosteroids, and it is also more severe. The argument that hydrocortisone cannot cause the condition because it is used effectively in its treatment simply will not stand up. The same argument was used for hydrocortisone butyrate, which has now been found to cause or aggravate it. 18 Steroid rosacea is said to occur in those with a rosacea background which is unmasked by steroid therapy, LD and this may also be true when the condition follows topical hydrocortisone therapy. Two patients developed eyelid atrophy where topical hydrocortisone was used. One of them had treated the upper but not the lower eyel ids, while the other treated only the medial aspect of the lower eyelids. In both cases the appearance of the treated areas contrasted with that of the untreated areas. Theoretically, one might expect this complication to occur less commonly from hydrocortisone than from certain other topical corticosteroids, e.g., triamcinolone. n However, hydrocortisone can produce atrophy when administered intradermally.s''-" and perhaps topically, 22 so it is not improbable that it might do so following prolonged application to the skin of the eyel ids. Patient 6 had prominent thinning of only the medial one third of the lower eyelids following treatment of a dermatitis in that area. This followed at least 2 months of continuous usage of topical 1% hydrocortisone. According to her history, she used topical 0.1 % betamethasone valerate for 2 weeks but did not notice the change in the eyelids until 10 or 12 weeks after it was discontinued. Since no atrophy was found 1 month after betamethasone valerate was stopped and the pa-

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tient did not notice the change for over 1 month after that, this product seems unlikely to be the cause. All six patients in this report had used their medication regularly for 3 weeks or longer. Since they were being followed, the complications were found relatively early. One must be concerned about individuals who self-medicate without any supervision, II; as well as those patients in whom close follow-up is not practical. For most situations, it would seem better to avoid uninterrupted and unsupervised topical application of 1% hydrocortisone (as well as the more potent corticosteroids) to vulnerable areas such as the face and eyelids. REFERENCES 1. Stoughton RB: Frost P, Gomez EC, Zaias N, editors: III

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Recent advances in dermatopharmacology. New York, 1977, Spectrum Publications, Inc., pp. 105-112. Rosenberg EW: Hydrocortisone creams over-the-counter: Not a worry. JAM ACAD DERMATOL 1:455, 1979. Fanconi G: Hemmung des Wachstums bei einem Saugling durch die zu intensive Anwendung einer I%igen Hydrocortisonsalbe auf del' Haut bei generalisiertem Ekzem. Helv Paediatr Acta 17:267-268, 1962. Benson PF, Pharoah POD: Benign intracranial hypertension due to adrenal steroid therapy. Guy's Hosp Rep 109:212-218, 1960. Feinblatt BI. Aceto T, Beckham G, Bruck E: Percutaneous absorption of hydrocortisone in children. Am J Dis Child 112:218-224, 1966. Hosking GP, Elliston H: Benign intracranial hypertension in a child with eczema treated with topical steroids. Br Med J 1:550-551, 1978. Malkinson FD, Ferguson EH; Percutaneous absorption of hydrocortisone-d-C'" in two human subjects. J Invest DcrmataI25:28I-283, 1955. Snyder DS, Greenberg RA: Radiographic measurement of topical corticosteroid-induced atrophy. J Invest Derrnatol 69:279-281, 1977. Smith JG, Wehr RF, Chalker DK: Corticosteroidinduced cutaneous atrophy and telangiectasia. Arch Dermatol 112: 1115-1117, 1976. Stoughton RB: A perspective of topical corticosteroid therapy, ill Farber EM, Cox AJ, editors: Psoriasis: Proceedings of the Second International Symposium. New York, 1977, Yorke Medical Books, p. 219. Wester RC, Noonan PK, Maibach HI: Percutaneous absorption of hydrocortisone increases with long-term administration. Arch Dermatol 116:186-188, 1980. Kligman AM, Kaidbey KH: Hydrocortisone revisited. An historical and experimental evaluation. Cutis 22: 232-244, 1978. Sneddon IE: The treatment of steroid-induced rosacea and perioral dermatitis. Dermatologica 152(suppl 1): 231-237,1976.

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14. Bendl BJ: Perioral dermatitis; Etiology and treatment. Cutis 17:903-908, 1976. 15. Sneddon IB: Adverse effect of topical fluorinated corticosteroids in rosacea. Br Med J 1:671-673, 1969. 16. Wilkinson OS, Kirton Y, Wilkinson JO: Perioral de 1'matitis: A l2-year review. Br J Dermatol 101 :245-257, 1979. 17. Frumess GM, Lewis HM: Light-sensitive seborrheid, Arch Dermatol 75:245-248, 1957. 18. Cotterill JA: Perioral dermatitis. Br J Dermatol 101: 259-262, 1979. 19. Leyden Jf , Thew M, Kligman AM: Steroid rosacea. Arch DermatolllO:619-622, 1974.

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20. Guin 10, Knox JM, Chernosky ME, Shapiro EM: Prednisolone acetate. A usefu) steroid preparation for intradermal administration. Arch Dcrmatol 81:438-441, 1960. 21. Baer RL, Witten YH: Editorial comment. Year book of dermatology, 1958-1959. Chicago, 1959, Year Book Medical Publishers, Inc., pp. 45-46,48-49. 22. Weirich EG, Longauer J: Tierexperlmentelle Priifung des epidermal-hypoplastischen Effektes von Externcorticoiden. (Hypoplastic effect of topical corticosteroids on the animal epiderrnis.) Arztl-Forsch 25:292-298, 1971.