Download January`s Diagnosis Pyoderma Gangrenosum

Case of the Month:
January’s Diagnosis
Pyoderma Gangrenosum
by Thomas T. Provost, MD
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January's Case of the Month correctly are:
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CENTRAL
Suzanne Hanne, MD – VA Paige Huber Tarquine, MD – KY
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Austin Moede, MD – NM
Carl Moritz, Jr., MD – CO
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Herbert Stickle, MD – WA
yoderma gangrenosum is an inflammatory disease
of unknown etiology that may be seen in association with several systemic diseases (Table 1).1 The
disease process begins with the sudden appearance of painful pustules, papules, and nodules
that rapidly spread, producing a large ulcer with a characteristic purplish undermined border (Figures 1 and 2). Pain
in the lesion is a dominant symptom. Severe tenderness
upon palpation is characteristic. The lesions, usually solitary
but may be multiple, occur on all areas of the body. They
are most prevalent, however, on the lower extremities.
In approximately 40% to 50% of cases, pyoderma gangrenosum is idiopathic. The most common underlying disease
associated with pyoderma gangrenosum is ulcerative colitis,
which has been reported in 30% to 60% of pyoderma gangrenosum cases. In most instances, the ulcerative colitis precedes the development of pyoderma gangrenosum, although it
may be the initial presentation or, rarely, may signal an exacerbation. In ulcerative colitis cases, pyoderma gangrenosum
generally has occurred in the absence of any evidence of clinical activity of the ulcerative colitis bowel disease. It should be
noted that although ulcerative colitis is most frequently associated with pyoderma gangrenosum, only 1% to 5% of ulcerative colitis patients develop pyoderma gangrenosum.
P
Dr Provost is Professor of Dermatology, Johns Hopkins University
School of Medicine, Baltimore, Maryland. He was the first faculty
member to hold the Noxell Professorship in Dermatology.
Off-Label Product Discussion: The author has disclosed that this article
references the following off-label/unapproved use of drugs or products:
cyclosporine, thalidomide, and infliximab for pyoderma gangrenosum.
116
CROHN’S DISEASE
Crohn’s disease is the second most common disease associated with pyoderma gangrenosum. Approximately 15% of
pyoderma gangrenosum patients have Crohn’s disease, whereas only 0.1% to 1.2% of Crohn’s disease patients develop
pyoderma gangrenosum. In the author’s experience, pyoderma gangrenosum adjacent to the position of an ileostomy site
on the abdomen has been frequently detected.
Pyoderma gangenosum can also be seen in patients with
an associated paraproteinemia. This is most commonly an
IgA myeloma, but other immunoglobulin classes may also
be associated.
Approximately 10% of pyoderma gangrenosum cases
may be associated with a myelodysplastic disease process
including acute or chronic myelogenous leukemia. With
leukemias, the pyoderma gangrenosum ulcers tend to be
shallow with blister formation.
Rarely, chronic active hepatitis, primary biliary cirrhosis,
systemic lupus erythematosus, and Behcet’s syndrome may
be associated.
ETIOLOGY
No etiology has been established, although a large body
of evidence suggesting a possible vasculopathy has been
accumulated. The fact that pyoderma gangrenosum has
been seen in association with leukocytoclastic angitis and
that it occurs with high frequency in Takayasu’s disease, suggests that vasculitis, possibly mediated by circulating
immune complexes, may be present.
CLINICAL FEATURES
The principal clinical features of pyoderma gangrenosum
are presented in Table 2. The disease is explosive in onset, usu-
Table 1. Pyoderma Gangrenosum: Common
Disease Associations
•
•
•
•
•
Ulcerative colitis
Crohn’s disease
Seropositive and seronegative arthritis
Myeloproliferative diseases
Paraproteinemia
– IgA myeloma
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JANUARY’S DIAGNOSIS
ally beginning as a painful pustular nodular lesion that rapidly
expands and may enlarge to 5 to10 cm within a 10-day period.
The purplish undermined border is characteristic; sinus tract
formation is also present. The base of the lesion is boggy and
necrotic and may extend to the fat and fascial layers.
There is a second uncommon variant of pyoderma gangrenosum characterized by indolent slow growth of massive
granulation tissue. Spontaneous regression and healing in
one area and progression in another occurs. Both forms of
pyoderma gangrenosum heal with thin atrophic cribriform
scar formation.
Pyoderma gangrenosum is a diagnosis of exclusion. A
recent review showed that misdiagnosis can occur frequently. Conditions that mimic pyoderma gangrenosum include
vasculitis, arterial and venous insufficiencies, cutaneous
blood vessel thrombosis secondary to the antiphospholipid
syndrome, cutaneous malignancies, and polymicrobial and
deep cutaneous fungal infections.2
PATHERGY
Pathergy, an inflammatory reaction in the skin induced by
trauma, is seen in approximately 40% of pyoderma gangrenosum patients. Clinically, this can be demonstrated by inserting
a needle into the skin at a 30-degree angle. Over the ensuing
24 to 48 hours, a sterile pustule will develop at this site.
Examples of pathergy are commonly detected at venesection
sites on patients’ arms. These sites of pathergy may on occasion produce large tender nodules. Incision and drainage of
these lesions promotes extension. These lesions are sterile.
TREATMENT
Until recently the treatment of pyoderma gangrenosum has been problematic. Isolated chronic lesions can be
successfully treated with the intralesional injection of triamcinolone (5-10 mg/cc). The slow infusion of 1 gm of
methylprednisolone over a 4-hour period for 5 consecutive days has been shown to produce an immediate
improvement in pain and to stop the spreading of the
lesion.3 However, continued use of steroids to control the
pyoderma gangrenosum is associated with many side
effects.
Recently, pyoderma gangrenosum has been successfully
treated with thalidomide. In the author’s experience, the
lesions rapidly respond to this therapy. However, peripheral
neuropathy (tingling sensations of the fingers and feet) may
occur in as many as 30% of patients, even when low doses
of 50 to 100 mg of thalidomide per day are administered.
Cyclosporine in a dosage of 4 mg per kilogram has also
been associated with a very rapid response of the pyoderma
gangrenosum lesions.4 It is important, however, to monitor
the patient for signs of hirsutism, azythemia, and hypertension, which are associated with this drug.
Most recently, evidence has appeared in the literature
indicating that infliximab (Remicade®) may be effective in
the treatment of pyoderma gangrenosum associated with
Crohn’s disease.5,6
Advanced Studies in Medicine
Figure 1. Multiple large painful lesions of pyoderma
gangrenosum on lateral lower leg and foot; note
depth of lesions extending down to fat and fascia
Figure 2. Classic lesion of pyoderma gangrenosum on
lower anterior leg; note purplish undermined border
Table 2. Common Clinical Features of Pyoderma
Gangrenosum
• Primary lesion, most commonly a pustule with an undermined purplish border, may be single or multiple
• Explosive onset generally heralded by pain; ulcers may reach
5 to 10 cm in 10 day period
• Pathergy; 40% of pyoderma gangrenosum patients develop
lesions at sites of previous trauma (ie, venesection or surgical
operative sites)
• Slow to heal; thin cribriform scar formation
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JANUARY’S DIAGNOSIS
References
1. Provost TT, Harris ML. Pyoderma gangrenosum. In:
Provost TT, Flynn JA, eds. Cutaneous Medicine: Cutaneous
Manifestations of Systemic Disease. Hamilton, Ontario: BC
Decker, Inc; 2001:464-468.
2. Weenig RH, Davis MDP, Dahl PR, Su, WPD. Skin ulcers
misdiagnosed as pyoderma gangrenosum. N Engl J Med
2002;347:1412-1418.
3. Johnson RB, Lazarus GS. Therapeutic effacies in the
treatment of pyoderma gangrenosum. Arch Dermatol.
1982;118:76-84.
118
4. Elgart G, Stover P, Larson K, et al. Treatment of pyoderma gangrenosum with cyclosporine results in 7 patients. J
Am Acad Dermatol. 1991;24:83-86.
5. Ijung T, Staun M, Grove O, Fausa O, Vita MH,
Hellstrom PM. Pyoderma gangrenosum associated with
Crohn’s disease: effect of TNF-alpha blockade with infliximab. Scand J Gastroenterol. 2002;37:1108-1110.
6. Tan M, Gordon M, Lebwohl O, George J, Lebwohl MG.
Improvement of pyoderma gangrenosum and psoriasis
associated with Crohn’s disease with anti-tumor necrosis
factor alpha monoclonal antibody. Arch Dermatol.
2001;137:930-933.
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February 2003