Preliminary and Short Report DECREASE OF URINARY CORTICOSTEROIDS FOLLOWING APPLICATION OF FLUOCINOLONE ACETONIDE UNDER AN OCCLUSIVE DRESSING* ROBERT B. SCOGGINS, M.D. Since the advent of topical corticosteroidrange occurred on this regimen, indicating suffi- therapy, numerous studies of possible systemiccient absorption of fluocinolone to cause suppres- effects have appeared in the literature. Mostsion of endogenous adrenocorticosteroid produc- have demonstrated no absorption with the mate-tion. Clinical response was excellent. Return of rials and methods used (1—6). In one study ab-urinary steroids to normal levels occurred upon sorption of hydrocortisone-4-C'4 but in smallcessation of topical applications. The procedure amount and in a possibly inert form was shownwas repeated in the patients at a time when each (7). Convincing evidence of fludrocortisonewas experiencing a moderate recrudescence of acetate absorption was reported in 1955 (8).skin lesions similar to that frequently seen in One report presented radioautographic evidencepsoriatics upon discontinuance of systemic cor- of hydro cortisone-C14 absorption (9). Anotherticosteroid therapy. Again, 17-hydroxycorti- showed a decrease in circulating eosinophilscosteroid and 17-ketosteroid excretion fell following meticortelone application (10). Theabruptly and significantly. In patient 2, the present widespread use of topical corticoste-occlusive wrapping was then discontinued, this roids with occlusive plastic film dressings (11)at a time when his skin disease was notably prompted an investigation of the possibility ofimproved. Urinary steroid excretion promptly percutaneous absorption when applied over largeincreased despite continued application of fluo- body areas. cinolone without occlusive dressing. During this Methods final treatment period the skin lesions remained improved. Two patients with severe generalized psoriasis were treated with fluocinolone acetonide (6z, Discussion 9a difluoro-16a hydroxyprednisolone 16, 17 The above data provide sufficient basis to acetonide) 0.025% cream which was appliedsuggest that the same precautions be observed every 12 hours in an amount sufficient to coverin the use of potent corticosteroid preparations the entire body, followed by Saran Wrap (Dowunder plastic film dressings over large areas of Chemical Co.) dressing of the whole body exclud-diseased skin that are observed in the adminis- ing head and genitalia. tration of corticosteroids by any other route. Patient 1 was a 48-year-old obese white femaleThe complications of systemic corticosteroid without other significant disease; 60 g. of creamadministration, both those immediately related (15 mg. fluocinolone) was applied twice daily.to greater-than-physiologic dosage and those of Patient 2 was a 44-year-old white male chronic potential adrenal insufficiency following with- alcoholic with evidence of early Laennec's cirrho-drawal of exogenously administered preparations, sis; 45 g. of cream (11.25 mg fluocino]one) wasneed not be reiterated here. applied twice daily. Neither had recently re- Further studies are in progress in an effort ceived corticosteroids in any form. Levels of 17-to clarify the dose-response relationship, to hydroxycorticosteroids were measured by aconfirm and extend the data by these and other modified Porter-Silver method (12) and 17-parameters in patients and subjects with normal ketosteroids were determined by the Vester-skin, and to determine the percutaneous absorp- guard method (13) in 24-hour urine specimens. tion of certain other preparations. Abandonment Results of this useful therapy is not suggested at the present time, but caution is indicated in its As shown in the table, marked depression ofuse until its pharmacology is better understood. urinary steroid excretion to below the normal Summary *Fromthe Department of Dermatology, Har- vard Medical School, and the Dermatology Serv- Significant percutaneous absorption of physio- ice, Massachusetts General Hospital, Boston, Massachusetts. logically active drug is shown with fluocinolone Received for publication October 25, 1962. acetonide application over large body areas with 473 474 THEJOURNAL OF INVESTIGATIVE DERMATOLOGY TABLE that the same precaution should be exercised Alterations in urinary steroids (mg/24 hrs.) inin the use of this therapeutic modality* that would psoriatic patients during fluocinolone therapy be used in the administration of cortieosteroids by oral or parenteral routes. Patient I Patient 2 Day REFERENCES 17— Keto 1. DANTO, J. L. AND MADDEN, S.: The eosino- philie response in normal subjects following __llHOH the inunction of cortisone ointment. J. Control 0 4.5 5.5 0 4.1 5.1 Invest. Derni., 18: 381, 1952. 1 1.4 2. WITTEN, V. H., SHAPIRO, A. J. AND SaBER, ++ 1.5 0.9 ++ 3.7 H. H.: Attempts to demonstrate absorption 2 ++ 3.5 0.4 ++ 1.5 1.9 of hydrocortisone by new chemical test 3 ++ 1.8 0.2 ++ 1.2 1.7 following inunction into human skin. Proc. 4 ++ L2 0.5 ++ — 1.7 Soc. Exp. Biol. Med., 88: 419, 1955. 5 1.1 3. SMITN, C. C.: Urinary excretion of 17-ketoste- ++ 0.5 0.5 ++ 0.3 roids and 17-hydroxycorticosteroids after 6 ++ 0.7 0.5 ++ 1.2 1.9 inunetion of hydrocortisone ointment. J. 7 ++ 0.7 0.7 ++ 1.3 1.5 Invest. Derm., 25: 67, 1955. 8 0 0.6 0.4 ++ 0.7 1.7 4. CEMZELL, C. A., HARD, S. AND NJLZ4N, A.: 9 0 1.1 The effect of hydrocortisone, applied lo- 2.5 0.8 ++ 0.4 cally to the skin, on the eosinophil count and 10 0 2.8 0.7 ++ 0.7 2.0 the plasma level of 17-hydroxycorticoste- 11 0 — — 0 — roids. Acta Dermat. vener., 35: 327, 1955. 12 0 — 0.4 0 2.7 1.7 5. FLEIsCHMAJER, H.: The lack of systemic hy- 13 0 5.0 4.5 0 4.9 4.2 drocortisone effects after massive and pro- — longed external applications. J. Invest. 14 0 — 0 6.8 5.2 Derm., 35: 11, 1961. 15 0 3.0 1.8 0 6.3 6.2 6. GOLDMAN, L. AND COHEN, W.: Total body in- 16 0 — — 0 7.0 3.1 unction as topical corticosteroid therapy. 17 0 — — 0 3.1 8.1 A.M.A. Arch. Derm., 85: 146, 1962. — 7. MALKIN5ON, F. D. AND FEROU5ON, E. H.: 18 0 — 0 4.0 2.0 Perautaneous absorption of hydrocortisone 19 0 4.0 1.5 ++ 3.8 5.4 4-C14 in two human subjects. J. Invest. 20 0 3.2 1.0 ++ 2.1 6.0 Derm., 25: 281, 1955. 21 8. FITxPATEICK, T. B., GRIswoLD, H. C. AND ++ 2.7 0.2 ++ 1.7 2.9 HIcKs, J. H.: Sodium retention and edema 22 ++ 1.3 0.0 ++ 1.4 2.0 from percutaneous absorption of fludro- 23 ++ 2.7 0.0 ++ 1.6 2.6 cortisone acetate. J.A.M.A., 158: 1149, 1955. 24 ++ 1.4 0.0 ++ 1.4 2.1 9. Scorr, A. AND KALZ, F.: The penetration and 25 3.8 distribution of C'-hydrocortisone in human ++ 1.2 skin after its topical application. J. Invest. End of Study Derm., 26: 149, 1956. 26 + 1.0 1.7 10. T5CHAN, D. N. AND Aoom, L.: Effect of per- 27 + 1.5 5.0 cutaneous absorption of meticortelone on 28 + 2.4 11.0 the eosinophile count. J.Invest.Derm., 28: 29 385, 1957. + 5.4 7.3 11. SULZBEEOEN,M.B. ANDWITTEN, V.H.: Thin 30 + 4.5 8.0 pliable plastic films in topical dermatologie 31 + 6.2 16.5 therapy. A.M.A. Arch. Derm., 84: 1027, 1961. 32 +4.9 12.8 12. SILBEE,R.H. ANDPORTER, C.C: The deter- mination of 17,21 -dihydroxy-20-ketoste- 33 + 5.5 9.0 roids in urine and plasma. J. Biol. Chem., 210:923, 1954. ++ Fluoeinolone with wrap 13. VE5TEEOAAED,P.:Rapid micro-modification + Fluocinolonewithout wrap of the Zimmermann/Callow procedure for 1No the determination of 17-ketosteroids in therapy urine. Acta Endocr. 8: 193, 1951. *Twopatients with atopic dermatitis treated an occlusive dressing in two patients with ex- in the same way with triamcinolone acetonide tensive psoriasis, with repeated confirmation in 0.1% cream and flurandrenolone 0.05% cream in 45 gm. amounts b.i.d. showed similar depression eachpatient. These preliminary data suggest of urinary steroid levels..