Abu-Elmagd, K

Ackerman, CD

Fung, JJ

Jegasothy, BV

Nikolaidis, N

Rilo, H

Starzl, TE

Thomson, AW

Todo, S

Van Thiel, D

English

PubMed

D-Scholarship@Pitt

Efficacy of FK 506 in the Treatment of Recalcitrant Pyoderma Gangrenosum K. Abu-Elmagd, B.V. Jegasothy, C.D. Ackerman, A.W. Thomson, H. Rilo, N. Nikolaidis, D. Van Thiel, J.J. Fung, S. Todo, and T.E. Starzl I N THIS STUDY the efficacy and safety of systemic FK 506 therapy was evaluated in four patients with severe recalcitrant pyoderma gangrenosum unresponsive to con-ventional therapy. CASE MATERIAL The clinical features in these four cases are summarized in Table 1. The patients were males between the ages of 26 and 34 years. The duration ofthe disease ranged from 3 to 28 years. All patients were referred to our center with well-established clinical and histopathological diagnosis of the disease. Multiple large necrotic ulcers existed in the lower extremities (n = 4). trunk (n = 2). and face (n = 2) prior to FK 506 treatment. The associated clinical conditions. which had also resisted different kinds of therapy. are summarized in Table I. Interestingly, all four patients had con-comitant inflammatory arthritis, regional enteritis (two examples), andlor connective tissue diseases (Table I). Patient 4 was the first patient ever reported with streaking leukocyte factor syndrome, published in 1975 by Jacobs and Goetz!.' FK 506 was started orally at a dose of 0.15 mg/kg twice daily. Dose adjustments were guided by FK 506 plasma levels or by clinical evidence of incomplete disease control or drug toxicity. Twelve-hour FK 506 trough plasma levels were measured with an enzyme-linked immunoassay. 2 Pre-existing steroid therapy (Table I) was tapered in all patients after starting FK 506 and completely discontinued in three patients. Other previously used immunosup-pressive agents were discontinued before initiation of FK 506 therapy. Dennatologic and medical examinations were performed re-peatedly. Assessments included pain, erythema. and drainage from pyoderma gangrenosum lesions. The arthritic manifestations were completely evaluated by a rheumatologist. Renal function. serum cholesterol. blood glucose, and electrolytes were moni-tored. If it developed, hyperkalemia was controlled with the mineralocorticoid fludrocortisone acetate. Hypomagnesemia was seen but did not require correction. RESULTS Response of the Skin Lesions All four patients had a dramatic initial response to treat-ment with a marked reduction in pain. erythema. and drainage by one week. Complete clinical remission and healing of the disfiguring open sores was achieved in patients 2 through 4 within 4 to 8 weeks after initiation of FK 506 therapy (Fig 1). FK 506 plasma trough levels were maintained in these patients at 0.5 to 1.5 ngimL. Patient I was removed from the study after 4 weeks and returned to cyclosporine (Cy A) because of his refusal to undergo rehabilitation for street-drug addiction. He com-mitted suicide a few weeks later. He had been improved by FK 506. The remission has been sustained in the other three patients for 3 to 16 months. In patient 2. efforts to reduce FK 506 dosage by half resulted in low drug plasma From the Departments of Surgery (K.A.-E., A.W.T .• H.R .• N.N., D.V., J.J.F., S.T., T.E.S.) and Dermatology (B.V.J .• C.D.A.). Uni-versity Health Center of Pittsburgh, University of Pittsburgh, and the Veterans Administration Medical Center, Pittsburgh, Pennsyl-vania. This work was aided by research grants from the Veterans Administration and Project Grant OK 29961 from the National Institutes of Health. Bethesda. Maryland. Address reprint requests to Thomas E. Starzl. MD, Dept. of Surgery,3601 Fifth Ave .• University of Pittsburgh. Pittsburgh, PA 15213. © 1991 by Appleton & Lange 0041-1345191/$3.001 +0 Table 1. Patients With Pyoderma Gangrenosum Treated With FK 506* Creatinine Duration of Data (mg%) Age/Sex Disease Associated Clinical FK506 No. (y) (y) Disease Previous Treatment Started Remission Before Alter 2B1male 3 ulcerative colitis arthritis steroids*, Daposone. Azathio- 12/22/89 partialt 1.5 1.7 prine. Leukeran. CyA 2 29/male 11 Crohn's disease with perianal steroids*, Dapsone. 6-mereap- 4/4190 complete 0.5 1.2 fistulae polyarthritiS Sjogren topurine CyA syndrome 3 34/male 7 ankylosing spondylitis scleritis steroids', Dapsone 10/29190 complete 0.7 1.2 4 311male 28 erosive polyarthritis streaking Thalidomide. steroids*, Dapsone, 5/9191 complete 0.7 1.4 leukocyte factor Tetracycline. Colchicine "Follow-up 10 August 20, 1991. tPatient was noncompliant and stopped taking FK 506. *The preexISting prednisone doses were 65 :!: 35 (S.D.) mgld. In patients 2--4 the values were 40,100. and 100 mgld. These were reduced to 0,0 and 5 mgld after 2103 weeks. 3328 Transplantation Proceedings, Vol 23. No 6 (December), 1991: pp 332B-3329 Q ------- -----FK 506 IN PYODERMA GANGRENOSUM 3329 Fig 1. (A) This picture shows a large necrotic ulcer on the medial aspect of the left knee region of patient 2 before starting FK 506 therapy. (8) Marked improvement and healing of the ulcer was noted within 1 week after initiation of FK 506 treatment. levels and consequently in beginning reappearance of the skin lesions and the arthritis, which completely disap-peared after returning to the full dose. Overall, the pro-ductivity and the quality of life of patients 2--4 were significantly improved. Effect on Extra-Dermal Lesions Improvement of arthritis occurred simultaneously in pa-tients 2 through 4. Discontinuance of steroids was consid-ered a godsend by all patients and was particularly impor-tant for patient 4, who has osteoporotic lesions and bone deformity. Two patients with concomitant inflammatory bowel disease became asymptomatic within 4 weeks after FK 506 treatment. One of these patients had complete healing of mUltiple perianal fistulae within 6 weeks. Patient 3 had complete disappearance of scleritis within 1 week after starting FK 506 treatment. FK 506 Adverse Effects Toxicity, including hyperkalemia and hypomagnesemia, was similar to that in the psoriasis patients. 3 There were increases in the current serum creatinine and B UN (Table 1) despite careful dose contro!' -N;pne of the patients developed systemic arterial hypertension after initiation of FK 506 therapy. DISCUSSION AND CONCLUSION This study has shown the efficacy of FK 506 as monother-apy for patients with severe pyoderma gangrenosum. The response was complete in all three patients who continued to receive the drug. The doses and plasma levels needed to maintain remission were in the same range as those re-quired to prevent allograft rejection. Attempts at dose reduction in one patient resulted in temporary reactivation of the skin lesions. The long-term riskibenefit ratio of FK 506 therapy remains to be determined. However. the results of the current report are unequivocally encourag-ing. REFERENCES I. Jacobs Je, Goetzl EJ: Pediatrics 56:570, 1975 2. Tamura K, Kobayashi M. Hashimoto K. et a1: Transplant Proc 19:23. 1987 3. Abu-Elmagd K. Van Thiel D, Jegasothy BV. et al: Trans-plant Proc (this issue) I 1 

Efficacy of FK 506 in the treatment of recalcitrant pyoderma gangrenosum

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Efficacy of FK 506 in the treatment of recalcitrant pyoderma gangrenosum

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