Correspondence

Skin Ulcers Misdiagnosed as Pyoderma Gangrenosum

N Engl J Med 2003; 348:1064-1066March 13, 2003

Article

To the Editor:

Weenig et al. (Oct. 31 issue)1 stress the need for extensive investigations in cases of skin ulcers that are suggestive of pyoderma gangrenosum. However, their recommendation of colonoscopy in Table 3 of their article is unclear. We believe that the decision to perform colonoscopy should be tailored to individual patients according to the expected effect on the management of their condition.

In a series of 86 patients with pyoderma gangrenosum from the Mayo Clinic,2 31 had inflammatory bowel disease. Pyoderma gangrenosum coincided with a flare of known inflammatory bowel disease in six patients and antedated the onset of inflammatory bowel disease in one patient. Even if it is assumed that clinically silent inflammatory bowel disease could be detected in some patients with pyoderma gangrenosum at the time of initial skin manifestations with the systematic use of colonoscopy, the therapeutic relevance of such a diagnosis is questionable. Indeed, no particular clinical2,3 or prognostic3 profile seems to differentiate pyoderma gangrenosum with associated inflammatory conditions from idiopathic pyoderma gangrenosum. Furthermore, given that the relation between pyoderma gangrenosum and inflammatory bowel disease is loose,2-4 systematic colonoscopy in patients with known inflammatory bowel disease at the time of a flare of pyoderma gangrenosum is not justified.

In addition, screening for inactive inflammatory bowel disease in patients with lesions suggestive of pyoderma gangrenosum would not help to differentiate genuine pyoderma gangrenosum from conditions mimicking pyoderma gangrenosum. Indeed, in the study by Weenig et al., inflammatory bowel disease was also observed in patients with the latter conditions. Finally, attention should be drawn to the possibly misleading active focal colitis and aphthoid ulcers induced by the oral purgative agents sodium phosphate5 and polyethylene glycol that are used before colonoscopy. Given these considerations and the increasing cost of health care, we believe that colonoscopy should be restricted to the few patients whose clinical presentation is suggestive of active inflammatory bowel disease, irrespective of the presence or absence of pyoderma gangrenosum.

Nadine G. Rouphael, M.D.
Emory Hospital, Atlanta, GA 30329

Nakhle M. Ayoub, M.D.
Roland R. Tomb, M.D., Ph.D.
Hôtel-Dieu de France Hospital, 16-6830 Beirut, Lebanon
roltomb@dm.net.lb

5 References

1. 1

   Weenig RH, Davis MDP, Dahl PR, Su WPD. Skin ulcers misdiagnosed as pyoderma gangrenosum. N Engl J Med 2002;347:1412-1418
   Full Text | Web of Science | Medline

2. 2

   Powell FC, Schroeter AL, Su WP, Perry HO. Pyoderma gangrenosum: a review of 86 patients. Q J Med 1985;55:173-186
   Web of Science | Medline

3. 3

   von den Driesch P. Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol 1997;137:1000-1005
   CrossRef | Web of Science | Medline

4. 4

   Paller AS. Cutaneous changes associated with inflammatory bowel disease. Pediatr Dermatol 1986;3:439-445
   CrossRef | Medline

5. 5

   Driman DK, Preiksaitis HG. Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution. Hum Pathol 1998;29:972-978
   CrossRef | Web of Science | Medline

To the Editor:

Weenig et al. mention primary infections, including cutaneous tuberculosis, as part of the differential diagnosis of pyoderma gangrenosum. In certain parts of the world, particularly in West African countries, skin ulceration is commonly caused by Mycobacterium ulcerans, also known as Buruli ulcer.1 Like pyoderma gangrenosum, Buruli ulcer often affects the legs (Figure 1Figure 1Buruli Ulcer at the Knee of a 12-Year-Old West African Boy.). Although Buruli ulcer is usually painless, we think it should be added to the differential diagnosis of pyoderma gangrenosum. In European and U.S. hospitals, patients occasionally present with this condition.2

It may be difficult to diagnose Buruli ulcer; the culture requires a low ambient temperature (32°C), and growth is very slow. Acid-fast bacilli can be found in biopsy specimens in actively ulcerating cases, but otherwise the diagnostic yield is fairly low. Nested polymerase chain reaction with the use of insertion fragment 2404 appears to be a promising diagnostic tool.3 Animal models suggest that antimycobacterial drugs are beneficial. No clinical data are available to suggest that these drugs can cure Buruli ulcer. The standard of care is still surgical excision and skin grafting if primary closure is not feasible.

Disseminated forms of M. ulcerans infection have been reported in patients with human immunodeficiency virus infection or AIDS.4 Mistaken treatment of Buruli ulcer as pyoderma gangrenosum with high-dose corticosteroids that impair cellular immune defense may cause harm.

Tjip S. van der Werf, M.D., Ph.D.
Ymkje Stienstra, M.D.
Winette T. van der Graaf, M.D., Ph.D.
Groningen University Hospital, 9700 RB Groningen, the Netherlands
t.s.van.der.werf@int.azg.nl

4 References

1. 1

   van der Werf TS, van der Graaf WT, Tappero JW, Asiedu K. Mycobacterium ulcerans infection. Lancet 1999;354:1013-1018
   CrossRef | Web of Science | Medline

2. 2

   Hofer M, Hirschel B, Kirschner P, et al. Disseminated osteomyelitis from Mycobacterium ulcerans after a snakebite. N Engl J Med 1993;328:1007-1009
   Full Text | Web of Science | Medline

3. 3

   Stienstra Y, van der Werf TS, Guarner J, et al. Analysis of the IS2404-based nested PCR for diagnosis of Buruli ulcer disease in regions of Ghana where the disease is endemic. J Clin Microbiol 2003;41:794-797
   CrossRef | Web of Science | Medline

4. 4

   Johnson RC, Ifebe D, Hans-Moevi A, et al. Disseminated Mycobacterium ulcerans disease in an HIV-positive patient: a case study. AIDS 2002;16:1704-1705
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Dr. Rouphael and colleagues that colonoscopy is not mandatory in the workup of pyoderma gangrenosum. However, it should be considered, as described in Table 3 of our article. The prevalence of inflammatory bowel disease in patients with bona fide pyoderma gangrenosum ranges from 27 to 36 percent, but the activity of the bowel disease may not correlate with a flare of or recovery from pyoderma gangrenosum.1,2 We recognize that the identification or ruling out of inflammatory bowel disease does not confirm or refute a diagnosis of pyoderma gangrenosum. As with all laboratory tests, the decision to perform a colonoscopy should be considered on a patient-by-patient basis, and it should be performed only if clinically indicated.

We thank Dr. van der Werf and colleagues for identifying another entity that may produce pyoderma gangrenosum–like ulceration — the Buruli ulcer. As they mention, our study was a retrospective review of cases from one institution and a review of the English-language literature. Had we known of their unreported case, we would have included it in our review. We are certain that there are additional conditions, yet to be described, that can result in severe cutaneous ulceration that mimics pyoderma gangrenosum.

Roger H. Weenig, M.D., M.P.H.
Mark D.P. Davis, M.D.
Mayo Clinic, Rochester, MN 55905

2 References

1. 1

   Bennett ML, Jackson JM, Jorizzo JL, Fleischer AB Jr, White WL, Callen JP. Pyoderma gangrenosum: a comparison of typical and atypical forms with an emphasis on time to remission: case review of 86 patients from 2 institutions. Medicine (Baltimore) 2000;79:37-46
   CrossRef | Web of Science | Medline

2. 2

   Powell FC, Schroeter AL, Su WP, Perry HO. Pyoderma gangrenosum: a review of 86 patients. Q J Med 1985;55:173-186
   Web of Science | Medline