Female, age 27, presents with nine-year history of systemic lupus erythematosus and debilitating leg ulcers. Ulcers had been
unresponsive to pyoderma gangrenosum-directed therapies, including prednisone 80 mg daily, cyclophosphamide, and dapsone.
Circulating anticardiolipin antibody identified. Ulcers completely healed following two-week course of low-dose tissue plasminogen
activator followed by aspirin maintenance. Ulcers did not recur in 10 years of follow-up.
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Rochester, Minn. - The misdiagnosis of skin ulcers as pyoderma gangrenosum is not uncommon and can have serious consequences
for patients, according to a recent report in The New England Journal of Medicine (2002;347:1412-1418).
The report describes a study conducted at Mayo Clinic to determine the frequency and consequences of misdiagnosis of pyoderma
gangrenosum and to identify the causes of cutaneous ulceration in patients who presented with ulcers that resembled pyoderma
gangrenosum.
"Pyoderma gangrenosum is a diagnosis of exclusion, and many disorders may result in ulceration that resembles pyoderma gangrenosum,"
said Roger Weenig, M.D., M.P.H., dermatopathology fellow, Mayo Clinic, Rochester, Minn., and first author of the report. "No
laboratory test is specific for the disorder. After the exclusion of other diseases that may mimic pyoderma gangrenosum, the
diagnosis rests on clinical features and correlation with findings on histopathology. These points are well recognized by
most clinicians familiar with the disorder, however we have seen an increasing number of patients who present on treatment
for presumed pyoderma gangrenosum that are found to have an alternative diagnosis on further evaluation. We believed a study
was needed to increase awareness of this phenomenon."
Female, age 32, presents with 10-month history of ulcers that had been diagnosed and treated as pyoderma gangrenosum. Treatment
with prednisone 60 mg daily associated with temporary improvement.
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Dr. Weenig and co-authors reviewed charts of 240 patients who were evaluated at Mayo Clinic from 1975 through 2000 for a suspected
diagnosis of pyoderma gangrenosum. The review included 157 consecutive patients who were treated for pyoderma gangrenosum
between 1984 and 1992, and evaluated at Mayo Clinic. The doctors also reviewed the English-language medical literature and
selected cases suggesting alternative causes of the skin ulcers that resembled pyoderma gangrenosum. The study yielded 95
patients with ulcers that resembled pyoderma gangrenosum: 49 patients evaluated at Mayo Clinic and 46 cases selected from
the literature search. The 49 patients seen at Mayo Clinic included 15 patients from the group of 157 consecutive patients
who were treated for pyoderma gangrenosum, suggesting a misdiagnosis frequency of approximately 10 percent. Six disease categories
comprised the actual causes of cutaneous ulceration in the 95 patients:
- vascular occlusive or venous disease (28 patients);
- vasculitis (21 patients);
- malignancy involving the skin (16 patients);
- primary infection (14 patients);
- drug-induced or exogenous tissue injury (13 patients); and
- other inflammatory disorders (three patients).
Prednisone and other immunosuppressive drugs used to treat pyoderma gangrenosum can present serious risks for patients whose
skin ulcers are associated with other disorders. Standard treatment for pyoderma gangrenosum consists of high-dose prednisone
(1 mg or greater per kilogram body weight), often in combination with a steroid-sparing agent such as azathioprine (Imuran),
cyclosporine (Neoral), or cyclophosphamide (Neosar). In addition to expected drug-related side effects associated with treatment,
the underlying disease may be worsened by treatment with prednisone or immunosuppressive agents; furthermore, temporary improvements
seen with treatment can delay correct diagnosis.
Male, age 60, presents with one-week history of ulcer resembling pyoderma gangrenosum. Initial biopsy demonstrated dermal
abscess and subepidermal edema. (Photographs courtesy of Roger Weenig, M.D., M.P.H.)
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Treatment for pyoderma gangrenosum was given to 64 patients (67 percent of those with cutaneous ulceration resembling pyoderma
gangrenosum) before the alternative diagnosis was established. The median length of time between the initial diagnosis and
final diagnosis was 10 months (range: three months to 180 months). The skin ulcers in 23 patients were clearly refractory
to treatment for pyoderma gangrenosum. Exacerbation of the underlying condition was seen in eight patients (12 percent) with
a final diagnosis of infection or lymphoma. Temporary improvement was seen in 15 patients (23 percent) who received treatment
for presumed pyoderma gangrenosum, resulting in a delay in diagnosis of the underlying cause of the skin ulcers (vasculitis,
antiphospholipid-antibody syndrome, or lymphoma). The greatest lag time before final diagnosis was seen in patients with antiphospholipid-antibody
syndrome; skin ulcers in approximately 60 percent of these patients responded to treatment for presumed pyoderma gangrenosum.
Repeat biopsies may be needed Clinicians might be reluctant to perform initial or repeated biopsies in cases of suspected pyoderma gangrenosum for fear
of exacerbating the condition. "Pyoderma gangrenosum is a condition associated with pathergy," said Dr. Weenig, "and there
are many reports of pyoderma gangrenosum developing in surgical incision sites and in areas subjected to trauma." Of the 95
cases of misdiagnosis reviewed by Dr. Weenig and colleagues, skin biopsies had been performed in 86 cases, with histologic
findings on initial or repeat biopsy supporting alternative diagnoses in 46 cases, or 53 percent of those biopsied. In the
three cases in which another inflammatory disorder was misdiagnosed as pyoderma gangrenosum, biopsy results supported an alternative
diagnosis. Histologic findings from an initial or repeated biopsy were diagnostic in 13 (81 percent) of the 16 patients in
whom cancer was the underlying cause of cutaneous ulceration and in nine (64 percent) of the 14 patients with infection simulating
pyoderma gangrenosum. When the underlying disease was vasculitis or vascular occlusive disease, histologic findings were diagnostic
in 68 percent or 35 percent, respectively, of patients who underwent biopsy. Biopsy was not useful in diagnosis of skin ulcers
resulting from exogenous tissue injury, such as self-induced ulceration associated with Munchausen's syndrome.
Dr. Weenig recommended that clinicians entertain a broad differential diagnosis when evaluating skin ulcers clinically resembling
pyoderma gangrenosum. Patients suspected of having pyoderma gangrenosum need to be followed closely, and repeat biopsies should
be performed in patients with progressive disease and in patients refractory to standard treatment.
