Saturday, January 01, 2011
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis defined
by its characteristic morphology. It is a diagnosis of exclusion,
and can be simulated by various vascular and infectious
conditions.Treatment is determined by the extent and rapidity of
the cutaneous process. Treatment with granulocyte-monocyte colony
stimulating factor (GM-CSF) may cause PG-like lesions. In these
cases, lesions may respond by stopping the GM-CSF and with topical
- Systemic corticosteroids are the initial treatment of choice
for patients with established ulcerations and with multiple
lesions. Initial therapy is 1 mg/kg or higher per day. After a
response is seen, gradually taper the dose. If no response is seen
in a week, a second agent should be added.
- Local therapy is very effective for early, superficial, and
those which are not rapidly progressive. Consider these options:
- Tacrolimus ointment 0.1-0.3% (compounded) applied into the
ulcer bed twice daily, covered with a Telfa dressing. Tacrolimus
ointment mixed with Orabase may be used for peristomal PG
associated with inflammatory bowel disease.
- Intralesional triamcinolone acetonide 10 mg/mL to the edge of
- PG lesions are easily inflamed; debridement should generally be
avoided, as it will lead to exacerbation of the lesion.
- In superficial lesions and those with limited progression,
consider the following:
- Thalidomide 100-400 mg daily for 2-4 weeks, then tapered if the
- Dapsone 100-200 mg daily, monitoring for anemia.
- Colchicine 0.6-1.2 mg twice daily, to tolerance (diarrhea
limits dosing) may be added to the dapsone for additional
- Clofazamine 100 mg twice daily.
- If the response to systemic steroids is inadequate and the
process is extremely rapid, in addition to systemic steroids, treat
with cyclosporine A at an initial dose of 5-10 mg/kg/day. Response
should be dramatic and will permit rapid reduction of systemic
steroids (as long as cyclosporine complications are not
encountered). For patients in whom cyclosporine fails or is not
tolerated, oral tacrolimus may be used instead.
- In refractory cases, the following agents can be used
individually or added to treatment with systemic steroids and
- Pulse systemic steroids monthly, either with intravenous
methylprednisolone up to 1 g; or oral dexamethasone 100 mg daily
for 5 consecutive days may be added to the cyclosporine and daily
systemic steroid doses.
- Mycophenolate mofetil 1.0 g twice daily may be added to the
combination of systemic steroids and cyclosporine, and may benefit
some refractory patients.
- Anti-Tumor Necrosis Factor Antibodies: Infliximab 5 mg/kg
intravenous infusions at weeks 0, 2 and 6 or every 3 weeks in a
series until improvement is noted. Etanercept 50 mg twice weekly
may also be effective. TNF blockers have become rescue therapy for
PG and have greatly improved the prognosis of this condition.
- Azathioprine 100-300 mg daily can be an effective
steroid-sparing agent. Cyclosporine, mycophenolate, and TNF
inhibitors are associated with more rapid response, relegating
azathioprine to use as a steroid-sparing agent for long-term
management when required.
- Pulse cyclophosphamide, once used in refractory cases, is now
used only in the rare PG case in which the above agents are
- Vapor-permeable, hydrophilic membranes help control pain and
may hasten reepithelialization. Dressings can remain in place for
3-7 days. Removal must be very gentle to avoid pathergy (appearance
of disease in sites of trauma).
- Although skin grafts often will "take" in patients receiving
appropriate immunosuppressive therapy as outlined above, pathergy
at the donor site may occur. Human skin equivalents or cultured
keratinocytes may be used to avoid this potential complication.
They are very effective in reducing the pain associated with PG,
and may shorten the course of immunosuppressive treatment required
to heal the ulceration.
- Hyperbaric oxygen reportedly accelerates healing rates in some
- Workup for an associated disease is mandatory, since control of
PG often can be achieved with therapy of the underlying disease
process. Inflammatory bowel disease [i.e., both ulcerative colitis
and regional enteritis (Crohn's)] is the most common associated
- Healed lesions of PG are extremely susceptible to trauma, which
can reactivate previously quiescent lesions. Emollients should be
employed routinely, and both elevation and support stockings should
be prescribed to minimize venous pooling that can lead to leg
- PG-like lesions occur in a host of other diseases, including
carcinomas, mycobacterial and other infections, halogenoderma,
gummatous syphilis, Wegener's granulomatosis, polyarteritis nodosa,
antiphospholipid antibody syndrome, cholesterol emboli, and
factitia. At the institution of therapy, strong consideration
should be given to performing an incisional biopsy for routine
histology and cultures, and performing appropriate laboratory tests
to exclude the above conditions.
- Pathergy occurs in many patients with PG, thus all but the most
gentle debridement or other manipulations should be avoided.
- Iodides can aggravate lesions of PG.
- Dapsone can cause a host of toxic and idiosyncratic side
effects. Accelerated hemolysis owing to shortened red cell lifespan
occurs in all patients, but can be life-threatening in patients
with glucose-6-phosphate (G6PD) deficiency.
- Immunosuppressive therapy and anti-TNF treatment may be
complicated by serious infections. Baseline purified protein
derivative (PPD) and prophylaxis for pneumocystis pneumonia should
be considered when appropriate.
- Thalidomide is a potent teratogen, therefore all female
patients treated with this agent must be entered in a standardized
pregnancy prevention program.