Abstract We report a case of pyoderma gangrenosum in a 80-yearold woman suffering from ulcerative colitis and treated witb clofazimine. Significant improvement was evident within 5 days following commencement of therapy, complete healing occurred after only 4 weeks of treatment. Clofazimine is a phendimetrazine tartrate derivative having antimicrobial action on mycobacteria, particularly Mycobacterium leprae. Clofazimine possesses an intracellular bactericidal effect and increases neutrophil phagocytosis in vivo and in vitro.'''' Over the past 15 years, this drug has been used with varying degrees of efficacy in the treatment of pyoderma gangrenosum (PG)."*"^ We report its successful use in a patient with ulcerative colitis (uc) suffering from PG resistant to conventional therapy. Case Report An 80-year-old women suffering from ulcerative colitis of 35 years duration presented to our department with multiple painful ulcerations over tbe left leg. Two montbs preceding admission, she bad noted the sudden appearance of small reddish papules over the left calf. Witbin several days these papules had become pustular and subsequently ulcerated. Treatment witb prednisone, 40 mg daily, bad failed to elicit improvement, resulting in ber bospitalization. Thirteen years preceding her current admission, she bad been treated by corticosteroids for PG involving tbe left buttock, and 7 years later bad received corticosteroids, followed by excision and grafting for PG-induced ulcerations at tbfs site. Additionally, 2 years prior to ber current bospitalization, a left hemicolectomy witb a transverse colostomy had been performed, and tberefore, up to and including tbe present bospitalization, tbe patient bad been in remission, as far as the uc was concerned. On admission, cutaneous examination (Fig. 1) revealed multiple irregular ulcers, measuring 1 to 3 cm in diameter, over the left calf. Tbe ulcers, which were discharging a pu-

Figure 1. Multiple irregular ulcers over tbe left calf. rulent and bemorrbagic exudate, bad prominently undermined, erythematous margins. Scarring and postinflammatory byperpigmentation were noted over tbe left buttock. Apart from the presence of a permanent colostomy, the remainder of the physical examination was noncontributory. Laboratory investigations, including full blood count and differential, ESR, and blood cbemistry were witbin normal limits. Culture from the base of one of the ulcers yielded Pseudomonas aeruginosa, whilst bistologic examination revealed ulceration with underlying suppurative dermatitis and collagen degeneration (Fig. 2). Tberapy was commenced with prednisone (in decreasing dosage), cephalexin, 4 x 500 mg/day, and local application of normal saline soaks. After 1 week of treatment, the patient unfortunately developed a drug eruption, and thus cepbalexin was ceased. At tbis stage, owing to lack of clinical improvement and desiring to avoid increasing tbe

From the Department of Dermatology, Cbaim Sheba Medical Center, Tel Hasbomer, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Address for correspondence: Baruch Kaplan, M.D., Department of Dermatology, Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel. 591

International journal of Dermatology Vol. 31, No. 8, August 1992


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Figure 2. Histologic examination of a lesion revealing degeneration of collagen and suppurative dermatitis.

Figure 3. Healing of the lesions following 4 weeks of clofazimine therapy.

dosage of prednisone (and tbus the risks of adverse sequelae), treatment with clofazimine, 3 x 100 mg/day, and sodium colistimetbate soaks was instigated. Witbin 5 days a patently remarkable clinical improvement had occurred. Over tbe following 3 weeks, there was gradual reduction in the dosage of clofazimine, correlating witb the degree of clinical improvement. Complete healing and discontinuation of therapy occurred 4 weeks following clofazimine administration (Fig. 3). There were no adverse clinical or laboratory sequelae during tberapy.

antimicrobial agent that exerts a slow bactericidal effect on Mycobacterium leprae, was initially reported in 1976 by Michaelsson et al. as being beneficial in the treatment of PC, particularly in recalcitrant cases.•* The recommended dosage was 300 to 400 mg/day. The exact mode of action of clofazimine is uncertain. It has clearly been shown to enhance the intracellular killing of bacteria and to increase neutrophil phagocytosis. Additionally, some patients with PG have been shown to have neutrophil function abnormalities, including (1) decreased neutrophil phagocytosis, (2) abnormal bactericidal ability, (3) in vitro inhibition of neutrophil function, (4) decreased neutrophil chemotaxis; and (5) delayed migration.''' It has been postulated that the neutrophil dysfunction may be, at least partially, due to an abnormal T4:T8 cell ratio.''' Clofazimine administration is associated with a number of possible adverse sequelae.'** These include cutaneous pigmentation (from pink to brownish-black in 75-100% of patients within a few weeks of treatment); ichthyosis and xerosis (8-28% of patients); non-specific rashes and pruritus; and discoloration of the hair., conjunctiva, lacrimal fluid, sweat, sputum, urine, and feces. Additionally, gastrointestinal disturbances, particularly epigastric pain, nausea, and vomiting, may occur. ,.





Pyoderma gangrenosum, a rare, destructive ulcerating skin disease of unknown etiology, is often the cutaneous manifestation of an underlying systemic disease, particularly ulcerative colitis,^"" Crohn's disease,'"''^^'^ and rheumatoid arthritis.'^"'' Although a variety of causes, including a derangement of humoral or cell mediated immunity or neutrophil function, have been proposed, the exact mechanism responsible for the development of the lesions has yet to be eludicated. A wide range of therapeutic modalities have been used including corticosteroids, dapsone, cyclosporine, sulfapyridine, minocycline, immunosuppressive agents, and topical sodium cromoglycate.'"' Clofazimine, an 592

Pyoderma Gangrenosum Kaplan et al.


Our case highlights some salient features of PG. It is ktiown that up to 50% of patients with PG have underlying UC.'^'^ Whereas exacerbations of the skiti lesions tend to parallel recurretice of the intestinal inflammation, only rarely is there an acute flare of cutaneous lesions during the quiescent phase of uc, as was the case with out patietit.""^^ In this particular case, owing to lack of improvement with 40 tng daily of prednisone, clofazimine was comrnenced rather than increasing the dosage of prednisone, with its possible adverse reaction. This was followed, withiti a matter of days, by ati impressive irnprovement with total healitig occurring after 4 weeks of therapy. There were no adverse clitiical or laboratory side effects.


It is worthwhile notitig that examinatioti of the literature did not shed light as to the optimal duration of therapy with clofazimine nor to patients' condition at different periods following its discontitiuatioti. In our particular patient, following completion of healitig, the drug was discontinued. Consequently, iti view of our positive experience, the patient's rapid healing and avoidance of possible complications of other therapeutic modalities, we would like to illustrate the successful use of clofazimine in the treattnent of pyoderma gangrenosum.


Struthers GR. Pyoderma gangrenosum, seronegative polyarthropathy and inflammatory bowel disease. J R Soc Med 1979; 72:284-286.


Mir-Madjlessi SH, Taylor JS, Farmer RG. Clinical course and evolution of erythetna nodosum and pyoderma gangrenosum in chronic ulcerative colitis: a study of 42 patients. Am J Gastroenterol 1985; 80:615-620.


Powell PC, Schroeter AL, Su WP, et al. Pyoderma gangrenosum: a review of 86 patients. Q J Med 1985; 55: 173-186.


Samitz MH. Cutaneous vasculitis in association with ulcerative colitis. Cutis 1966; 2:383-387. Samitz MH, Dana AS, Rosenberg P. Cutaneous vasculitis in association with Crohn's disease. Review of statistics of skin complications. Cutis 1970; 6:51-56.



Hickman JG, Lazarus GS. Pyoderma gangrenosum: a reappraisal of associated systemic diseases. Br J Dermatol 1980; 102:235-237.


Lazarus GS, Goldsmith LA, Rocklin RE. Pyoderma gangrenosum, altered delayed hypersensitivity and polyarthritis. Arch Dermatol 1962; 105:46-51.


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Schwaegerle SM, Bergfeld WM, Senitzer D, et al. Pyoderma gangrenosum: a review. J Am Acad Dermatol 1988; 18:559-568. Check IJ, Ellington EP, Moreland A. T-helper-suppressor cell imbalance in pyoderma gangrenosum, with relapsing polychondritis and corneal keratolysis. Am J Clin Pathol 1983; 80:396-399.


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Cline MJ. Drug potentiation of macrophage function. Infect Immun 1970; 2:601-605. Brandt I. Enhancing effect of clofazimine on the phagocytosis of neutrophil leucocytes in vitro. Scand 1 Haematol 1971; 8:265-269. Molin L. Clofazimine enhanced phagocytosis in pustulosis palmaris et plantaris. Acta Derm Venereol (Stockh) 1975; 55:151-153.



Michaelsson G, Molin L, Ohman S, et al. Clofazimine: a new agent for the treatment of pyoderma gangrenosum. Arch Dermatol 1976; 112:344-349. Thomson K, Rothenberg HW. Clofazimine in the treatment of pyoderma gangrenosum. Arch Dermatol 1979; 115:851-852.

Kark EC, Davis BR, Pomeranz JR. Pyoderma gangrenosum treated with clofazimine. J Am Acad Dermatol 1981; 4:152-159. Thornton JR, Teague RH, Low-Beer TS, et al. Pyoderma gangrenosum and ulcerative colitis. Gut 1980; 21: 247-248.

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From the collection of "La Pharmacie Fran^aise," New Orleans, Louisiana, Mr. Ben Bavly, Curator. 593

Treatment of pyoderma gangrenosum with clofazimine.

We report a case of pyoderma gangrenosum in a 80-year-old woman suffering from ulcerative colitis and treated with clofazimine. Significant improvemen...
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