Download pdf - Pyoderma gangrenosum and Crohn's disease

Pyoderma Gangrenosum and Crohn's Disease Eight Cases and a Review of the Literature

DAVID J, SCHOETZ, JR., M.D., JOHN A. COLLER, M.D., MALCOLM C. VEIDENHEIMER, M.D.

Schoetz DJ Jr., Coller JA, Veidenheimer MC. Pyoderma gangrenosum and Crohn's disease: eight cases and a review of the literature. Dis Colon Rectum 1983;26:155-158.

Pyoderma gangrenosum is an ulcerative cutaneous lesion of unknown cause that has been associated with chronic diseases. Its association with inflammatory bowel disease has classically been with chronic ulcerative colitis; however, scattered cases have appeared in which pyoderma gangrenosum has accompanied Crohn's disease. Collected series have indicated an incidence varying between 0.16 per cent in the Mayo Clinic Series of 1954 to 1.5 per cent in the Cleveland Clinic series of 1975. We have reviewed the records of eight patients with pyoderma gangrenosum and Crohn's disease who were seen at the Lahey Clinic between 1957 and 1980. During this period, 961 patients with Crohn's disease were seen (an incidence of 0.8 per cent). The ages of the patients ranged between 16 and 65 years. In two of the eight patients, the onset of pyoderma gangrenosum was coincident with the onset of the bowel symptoms; in the remaining six patients, the onset of pyoderma gangrenosum averaged 7.3 years after the onset of bowel disease. The diagnosis of Crohn's disease was made histopathologically for five patients; for the rest, the diagnosis was clinical Lesions of pyoderma gangrenosum were seen on the legs of all eight patients; two patients had additional lesions of the trunk. In five patients, the activity of the skin lesions paralleled that of the bowel disease. Distribution of Crohn's disease in patients with pyoderma gangrenosum is similar to that previously reported--five with ileocolitis, two with colitis, and one with ileitis. Other extraintestinal manifestations of Crohn's disease in this group of patients were perianal disease in two, erythema nodosum in one, arthritis i n one, and iritis in one. The diagnosis of pyoderma gangrenosum was confirmed pathologically in only one patient, emphasizing the subjective clinical nature of this diagnosis. This report represents the largest detailed series of patients with pyoderma gangrenosum and Crohn's disease to date. [Key words: Pyoderma gangrenosum; Crohn's disease, extraintestinal]

PYODERMA GANGRENOSUM i s a n u n c o m m o n progTes- sive ulcerative cutaneous lesion of obscure cause, which has been associated with a number of chronic debilitating systemic diseases. Since the original description by Brunsting et al. t in 1930, pyoderrna has classically been considered an extraintestinal manifestation of chronic ulcerative colitis. In the largest single series~ of patients with pyoderrna gangrenosurn, 31 of 69 patients (50 per cent) had ulcerative colitis. Another review 3 of a number of series of patients with ulcerative colitis revealed an

Read at the meeting of the American Society of Colon and Rectal Surgeons, San Francisco, California, May 2 to 6, 1982.

Address reprint requests to Dr. Schoetz: Section of Colon and Rectal Surgery, Lahey Clinic Medical Center, 41 Mall Road, Box 541, Burlington, Massachusetts 01805.

From the Section of Colon and Rectal Surgery, Lahey Clinic Medical Center,

Burlington, Massachusetts

overall incidence of pyoderma of from 1 to 5 per cent. Occurrence of pyoderma gangrenosurn in patients with Crohn's disease, however, has been considered such an oddity that only isolated case reports 4-7 have appeared. Recent experience with a patient at the Lahey Clinic, who had both pyoderma gangrenosum and Crohn's disease, has prompted an inquiry into this association. Results of the investigation form the basis of this report.

Methods

A computer ized search was made for the records of all patients with the diagnosis of Crohn ' s disease at the Lahey Cl in ic between 1957 a nd 1980, inclusively. In addi t ion, the records of all pat ients who were d iagnosed as h a v i n g pyoderma gangrenosurn d u r i n g that same period were obtained. Charts of pat ients hav ing both diseases were reviewed carefully by the p r imary au thor with regard to age of the pa t ien t at the t ime of d iagnosis of Crohn ' s disease, me thod of diagnosis of Crohn ' s disease, distr ibu- t ion of Crohn ' s disease, onset of pyoderrna g a n g r e n o s u m in re la t ion to Crohn ' s disease, parallel between the activity of Crohn ' s disease and pyoderma, d i s t r ibu t ion and method of diagnosis of pyoderma, other extraintes t inal manifes ta t ions of Crohn ' s disease, and methods of treat- men t of pyoderrna.

R e s u l t s

At the Lahey Cl in ic between 1957 a nd 1980, 961 pat ients were diagnosed as hav ing Crohn ' s disease. Of these, eight were found to have pyoderma g a n g r e n o s u m also, for an overall incidence of 0.8 per cent. T h e average age of these eight pat ients at the t ime of d iagnosis of

Crohn ' s disease was 30 years, with a range of 16 to 65 years. T w o of the eight pat ients presented wi th both Crohn ' s disease a nd pyoderma at the t ime of in i t ia l diagnosis; pyoderma developed in the r e m a i n i n g six an average of 7.3 years after the onset of Crohn ' s disease. Five of the eight pat ients were men.

0012-3706/83/0300/0155/$01.00 (~) American Society of Colon and Rectal Surgeons

155

156 SCtlOETZ, E T A L . l)i~. (&)l. gc Rect. .Malch 1983

disease by a combination of surgery, systemic corticosteroids, and Azulfidine~. All patients were treated with local measures to prevent the development of secondary infection. For four of the eight patients, intralesional steroids were added to systemic corticosteroids with moderate success.

FIG. 1. Pyoderma gangrenosum. Note punctate ulcerations surrounding the larger necrotic ulcers and di~oloration of the skin.

Diagnosis of Crohn's disease was established histopathologically from either resected small bowel or colon in five of the eight patients. In the remaining three patients, the diagnosis was based on clinical and radiographic criteria. Five patients had ileocolitis, two had colitis, and one had ileitis.

Pyoderma gangrenosum was diagnosed clinically in all eight patients. Lesions were found on the legs of all patients and were the only site of involvement in six patients. One patient also had lesions in the groin, and another patient had a lesion on the back. A definite history of trauma preceding the development of pyoderma was elicited from only one patient. Histopathologic con- firmation of pyoderma gangrenosum was obtained for only two patients; biopsy of skin lesions was obtained from three patients, while for the remaining five patients disease was diagnosed by clinical criteria alone. Activity of the pyoderma paralleled that of the bowel disease in five of the eight patients; in two of the five, the development of pyoderma prompted radiographic evaluations, which led to the diagnosis of recurrent asymptomatic Crohn's disease.

Extraintestinal manifestations of Crohn's disease were relatively common in this group of eight patients. Erythema nodosum was seen in one patient, diffuse polyarthritis in one patient, and iritis in one patient. In addition, anal Crohn's disease was seen in two patients. Consequently, three of the eight patients exhibited extraintestinal lesions associated with Crohn's disease, and two exhibited Crohn's involvement of the anus.

Treatment of pyoderma was varied. The most important factor in the ultimate success of patients with active Crohn's disease was the control of the underlying bowel

Discussion

Pyoderma gangrenosum is macroscopically described as a deep, discrete ulcer with a necrotic center, an under- mined border, and violaceous skin surrounding a lesion that most often is seen involving the pretibial region; individual lesions evolve from small pustules that coalesce into the classic painful ulcer, frequently in a matter of days (Fig. 1). Histopathologic de~ript ion 8 of these lesions indicates that the primary process is nonspecific and parafollicular in location, with polymorphonuclear infiltration and edema in the epidermis associated with inter- stitial and perivascular infiltration with lymphocytes, mononuclear cells, and plasma cells in the dermis. Early suggestions 9 that the lesion was confined to the epidermis have been disproved by biopsies of lesions before ulceration in which the inflammation is limited to the dermis9 ~ Most authors now accept that the chronic dermal inflammatory process results in thrombosis of blcx)d vessels and dermal hemorrhage, leading to ischemia of the overlying epidermis and secondary ulceration. None of the histologic changes are pathognomonic of pyoderma gan~enosum; the single most cogent reason for biopsy is to exclude vasculitis as a diagnostic consideration. The present series supports the observation that the diagnosis of pyevderma is clinical. Biopsies were obtained from three of the eight patients and were considered consistent with pyoderma for only two of the three patients.

Although the lesions may be seen in otherwise healthy individuals, most often an associated debilitation condition is present. Besides the inflammatory bowel disease, pyoderma has been described in patients with various blood dyscrasias, chronic active hepatitis, paraproteine- mia, Hodgkin's disease, polyarthritis, and many other indolent illnesses.Z,s,u, xz In the 20 to 30 per cent of pat ients without identifiable associated disease states, pyoderma gangrenosum may precede the development of the predisposing condition by a considerable period of time. Thus, all patients presenting with pyoderma must undergo thorough investigation of the gastrointestinal tract and hematopoietic system and then be followed up carefully, even after the skin lesions have healed.

T h e pa thophysio logy of pyoderma gangrenosum remains unknown. Brunsting et al . , 1 in their original description, mislabeled the process "pyoderma" because of their conviction that the lesion was primarily of bacterial origin; this has subsequently been demonstrated to be

Volume 26 Number 3 P Y O D E R M A G A N G R E N O S U M 157

a misconception, with bacterial colonization representing a secondary phenomenon. Rostenberg 13 has suggested that pyoderma is an example of the Shwartzman phenomenon , an altered tissue reactivity requiring cutaneous sensitization to an antigen from some other source that has manifested as a hypersensitivity reaction in the skin. More recently, many investigators 8,l~ have presented evidence support ing an alteration in either cellular immuni ty or neutrophil function as the pr imary causa- tive mechanism. Whether the defect is specifically directed at the skin or is a result of the underlying disease process is not clear from currently available data.

In an early report of 19 cases of pyoderma gangrenosum reported by Perry and Brunsting, x4 o n e patient was reported to have coincident regional enteritis and pyoderma. Although two early series 15,~6 of patients with Crohn 's colitis did not include pyoderma as a cutaneous manifestation of granulomatous disease of the large bowel, later studies with more intensive examinat ion of associated skin lesions confirmed the rare association of these two conditions. McCallum and Kinmon07 reported a 43 per cent incidence of skin complications in 138 patients with Crohn's disease; one patient had pyoderma gangrenosum. Farmer et al. TM reported nine cases of pyoderma in 615 cases of Crohn's disease at the Cleveland Clinic (an incidence of 1.5 per cent). Greenstein et al.,19 in a series from Mr. Sinai Hospital in New York, described six cases in 498 patients (an incidence of 1.2 per cent). Samitz e~ reported a 1 per cent incidence in 200 patients. The current study, with an incidence of pyoderma of 0.8 per cent in 961 patients, concurs with these previously reported series.

Farmer et al. TM and Greenstein et al. 19 concluded that pyoderma is associated more often with either colitis or ileocolitis than with Crohn's disease confined to the small bowel. The present study confirms these observations, with seven of eight patients exhibit ing colonic involvement with Crohn 's disease. Unlike these two studies, however, we found that pyoderma is associated more often with ileocolitis than with colitis alone.

Clinical characteristics of pyoderma gangrenosum associated with Crohn's disease, other than the distribution of Crohn's disease, have not been detailed in previous series. Case reports 4-7 have suggested that the pyoderma in patients with Crohn's disease may present coincident with, or subsequent to, the onset of bowel symptoms. In our series, two of the eight patients presented coinciden- tally, whereas in the remainder pyoderma developed an average of 7.3 years after the onset of Crohn 's disease. As in most other reports, the lower legs of all patients were affected; however, other sites of involvement were present in two of our eight patients.

Reactivation of pyoderma was seen most frequently in patients with recurrent Crohn's disease; in five of the

eight patients, a close correlation between the activity of the two disease processes was noted. In two patients, the pyoderma prompted radiologic investigation of the gastrointestinal tract and revealed recurrent Crohn 's disease in patients who were otherwise asymptomatic. As in ulcerative colitis, however, pyoderma may occur inde- pendently of Crohn 's disease; this was seen in three of eight patients.

Other extraintestinal manifestations of Crohn's disease occurred in five of eight patients. The National Coopera- tive Crohn 's Disease Study (NCCDS) 21 found that more than one extraintestinal manifestation developed in 5.3 per cent of 569 patients; our data indicate a rate of multi- ple extraintestinal complications in patients with pyoderma gangrenosum that is much higher than that found by the NCCDS.

Treatment of pyoderma is directed at the underlying Crohn's disease. Control of bowel disease with systemic corticosteroids, Azulfidine~, and immunosuppress ive agents resulted in improvement of the pyoderma in many patients. Resection of involved bowel, while not performed in the present series specifically to control pyoderma, will also result in improvement of the skin lesions. Local measures, including judicious debridement, compresses of Burow's solution, and topical antibiotics, should be used in all patients to prevent secondary local septic complications. Moschella 22 has described the intralesional injection of steroids as an adjunctive method of treatment of pyoderma; this part icular technique was used with success in four of our patients. Most recently, systemic administrat ion of dapsone ~3 or clofazimine 24 has been advocated as an ancillary mode of therapy for pyoderma; the mechanism of action of these antileprosy drugs remains unknown. These latter methods of therapy may be particularly beneficial for patients without active bowel disease or for those in whom the complications of high-dose systemic corticosteroids preclude their use in doses sufficient to control the pyoderma.

In summary, pyoderma gangrenosum is a rare cutaneous complicat ion of Crohn's disease occurring in less than 1 per cent of the patients who were treated at the Lahey Clinic for Crohn 's disease between 1957 and 1980. Ileocolitis and colitis are much more frequently associated with the development of all:skin lesions, and pyoderma is no exception. Activi ty of the pyoderma frequently paral- lels the activity of the bowel disease and may herald reactivation of previously quiescent Crohn 's disease. The diagnosis of pyoderma is clinical; biopsy is used primari ly to exclude the presence of vasculitis. Treatment of the pyoderma is directed at the underlying Crohn 's disease supplemented with intralesional corticosteroids and local wound care. Resection of the bowel should be considered only in those patients whose disease is refractory to medi- ca• management; this was not necessary in any of our

I)b,. Cal . ,~ Rv~L. 1 5 8 SCHOE'FZ, E'I" AL. xt~,,h m~3

p a t i e n t s . A n a g g r e s s i v e a p p r o a c h to these p a t i e n t s w i l l

r e s u l t i n the c o n t r o l of th i s f r e q u e n t l y d e b i l i t a t i n g s k i n

disease .

References

1. Brunsting I.A, Goeckerman WH, O'Leary PA. Pyoderma (ecthyma) gangrenosum: clinical and experimental observations in five cases occurring in adults. Arch Dermatol 1930; 22:655-80.

2. PerryHO. Pyodermagangrenosum. SouthMedJ 1969;62:899-908. 3. Sparberg M, Fennessy ], Kirsner JB. Ulcerative proctitis and mild

ulcerative colitis: a study of 220 patients. Medicine 1966; 45:391 - 412.

4. Stathers GM, Abbott LG, McGuinness AE. Pyoderma gan~elmsum in association with regional enteritis. Arch Dermatol 1967; 95:375-80.

5. McGarity WC, Barnett SM. Py(xterma gangrenosum in Crohn's disease: report of a case. Dis Colon Rectum 1977; 20:49-52.

6. Bmndt I., Gfirmer I, Nilss(rn PC. Olo[sson "1". Pyoderma gangrenosum associated with regional enteritis: improvemenr in defective granulocyte function and healing of skin lesions during adminis- tration of clo[azimine. Acta Med Stand 1977; 201:141-4.

7. Korelitz BI. Sommers SC. Pyoderma gangrenosum complicating Crohn's disease. Am J Gastroenterol 1977; 68:171-6.

8. Holt PJA, Davies MG, Saunders KC, Nuki G. Pyoderma gangrenosum: clinical and laboratory findings in 15 patients with special reference to polyarthritis. Medicine 1980; 59:114-33.

9. Percival GIL Pyoderma gangrenosum: the histology of the primary lesion. Br J Dermatol 1957; 69:130-6.

10. Dantzig PI. Pycxterma gangrenosum (letter). N Engl J Med 1975; 292:47-8.

11. Basler RSW. Ulcerative colitis and the skin. Med Clin North Am 1980; 64:941-54.

12. Callen JP, Taylor WB. Py(xterma gangrenosum~a literature review. Curls 1978; 21:61-4.

13. Rostenberg A Jr. The Shwartzman phenomenon: a review with a consideration of some Imssible dermatological manifestations. Br J Dermatol 1953; 65:389-405.

14. Perry I-{O, Brunsting I,A. Pyoderma gangrenosum: a clinical study of nineteen cases. Arch Dermatol 1957; 75:380-6.

15. l,ockhart-Mummery HE, Morson BC. Crohn's disease of the large intestine. Gut 1964; 5:493-509.

16. Lindner AE, Marshak RH, Wol f BS, Janowitz HD. Granulomatous colitis: a clink:al study. N Engl J Med 1963; 269:379-85.

17. McCallum DI, Kinmont PDC. Dermatological manifestations of Crohn's disease. Br J Dermatol 1968; 80:1-8.

18. Farmer RG, Hawk WA, Turnbull RB Jr. Clinical patterns in Crohn's disease: a statistical study of 615 cases. Gastroenterology 1975; 68:62%35.

19. Greenstein A J, Janowitz HI), Sachar DB. The extraintestinal complications of Crohn's disease and ulcerative colitis: a s~ udy of 700 patients. Medicine 1976; 55:401-12.

20. Samitz MH. Skin complications of ulcerative colitis and Crohn's disease (with special reference to pyoderma gangrenosum). Cutis 1973; 12:533-7.

21. Rankin GB, Watts HD, Melnyk CS, Kelley MI, Jr. National Cooperative Crohn's Disease Study: exnaintestinal manifestations and perianal complications. Gasm~enterology 1979; 77:91't-20.

22. Moschella SL. Pyoderma gangrenosum: a patient successfully treated with intralesional injections ol steroid. Arch Dermatol 1967; 95:121-3.

23. Soto I.D. Diaminodiphenylsulfone and steroids in the treamwnt of pyoderma gangrenosum, lnt J Dermatol 1970; 9:293-300.

24. Michablsson G, Molin L, Ohman S, et al. Clofazimine: a new agent for the treatment of pyoderma gangrenosuln. Arch Dermatol 1976; 112:344-9.

Announcement

I N T E R N A ' F I O N A L C O N G R E S S O N C O I . O N C A N C E R

CLINICAI_. AND EXPERIMENFAI. SFI'I)IES

May 26-28, 1983

T h e Depar t lnen t of Surgery, Univers i ty t Iospilal "Dijkzigt ," Rot te rdam, is sponso r ing this congress wh ich will be open to all c l in ic ians and scient- ists interested in colorectal cancer. T h e p r o g , a m will include review lec- tures, panel discussions, and l)rofiel-ed paper sessions on p reven t ion and early d iagnosis of colorectal cancer, carcinogenesis in a t t imal and man. advances in surgical m a n a g e m e n t , prognost ic factors in colorectal (an(er , methods of ad juvan t therapy, nu t r i t ion , and the cancer patient . Invited speakers are Allgower (Basel), B rennan ( New York ), Cope land ( I tous ton) , Day (Liverpool) , DeCosse (New York), van Slooten (Amsterdam), Sugar- baker (Bethesda). Tay lo r (Sou thampton) , Welch (Boston), Wi l l i amson (Bristol), Zwavel ing (Leiden). D u n c a n (Ed inburgh) . Malt (Boston) attd P ich lmayr (Hannover ) . For more in fo rma t ion contact: Congress Secreta- riat, c / o Comprehens ive Cancer Center (IKR), p . o . Box 1738 3000 DR Rot terdam, T h e Netherlands. Te lephone : 10-634130.