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Pyoderma Gangrenosum

Key Points

  • Pyoderma gangrenosum is a type of ulcerating neutrophilic dermatosis.
  • The classic morphology of pyoderma gangrenosum is an ulcer with a violaceous rim and undermined border.
  • PG lesions may develop very rapidly (in days) and may be triggered or exacerbated by minimal trauma.
  • PG is a diagnosis of exclusion; inflammatory and infectious conditions may mimic PG-like ulcers. PG may occur in association with an underlying systemic disorder.
  • Treatment of PG requires both management of inflammation and optimized wound care. Advanced lesions may often require systemic immunosuppression.

Introduction

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis defined by its characteristic morphology. Ulcerating lesions marked by a violaceous rim and undermined border may develop rapidly (in days) and may be triggered or exacerbated even by minimal trauma (pathergy). It is a diagnosis of exclusion and can be simulated by various inflammatory, vascular and infectious conditions. PG lesions may occur in isolation or occur in association with an underlying systemic disorder, such as a rheumatologic disease, inflammatory bowel disease, malignancy (especially hematologic malignancy), immunodeficiency, or infection. Lesions may also be induced by medications; for example, exogenous granulocyte-monocyte colony stimulating factor (GM-CSF) may cause PG-like lesions. In these cases, lesions may respond by stopping the inciting medication and topical treatment. The diagnostic evaluation of PG thus requires formal exclusion of conditions that may mimic this disorder in addition to diagnostic work-up for associated systemic diseases.

Treatment is determined by the extent and rapidity of the cutaneous process and requires both aggressive management of inflammation and optimal wound care. Though treatment of early lesions can often be managed through topical medications and good wound care, advanced or rapidly expanding lesions may require systemic immunosuppression to halt progression and promote healing. PG lesions may be exquisitely painful, sometimes out of proportion to their clinical appearance or size; reduction in pain associated with a lesion represents an important early sign of effective treatment. Lesions often heal with a very characteristic cribiform, atrophic scar pattern.

Initial Evaluation

Differential diagnosis

Venous stasis ulcer

Leishmania ulcer

Sweet’s syndrome

Treatment

First-line therapy: The first-line therapy for pyoderma gangrenosum is comprised of two key elements: controlling inflammation and optimizing wound care. Inflammatory control may require systemic immunosuppression and/or the use of multiple therapeutic agents in combination.

First steps

  • Systemic corticosteroids are the initial treatment of choice for patients with established or multiple ulcerations, rapidly expanding 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 immunosuppressive agent should be added.
  • Local therapy is very effective for early, superficial, and those lesions that are not rapidly progressive. Consider these options in addition to optimal wound care:
  • PG lesions are easily inflamed; surgical debridement or grafting should generally be avoided, as it will lead to exacerbation of the lesion.

Ancillary steps

  • Vapor-permeable, moisture-retentive, hydrophilic membranes help control pain and may hasten re-epithelialization. Dressings can remain in place for 3-7 days. Dressings on exudative ulcers should be changed frequently to avoid maceration; alternatively, ulcers should be covered by a non-adherent dressing with absorptive features (such as foam or alginate). Removal must be very gentle to avoid pathergy (appearance of disease in sites of trauma).
  • Work-up 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 illness. Other systemic disorders associated with PG include rheumatologic disease, malignancy (especially hematologic), infection, immunodeficiency, and medications. The diagnostic work-up, especially for an underlying malignancy, is also required as treatment of patients with PG may necessitate systemic immunosuppression, which may be relatively contraindicated in the setting of malignancy.
  • 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 ulcers.

Subsequent steps

  • If the response to systemic steroids is inadequate and the process is extremely rapid, treat with cyclosporine A at an initial dose of 5-10 mg/kg/day (in addition to systemic steroids) with close monitoring for side effects. Response should be dramatic and will permit rapid reduction of systemic steroids (as long as cyclosporine complications are not encountered).
  • In superficial lesions and those with limited progression, addition of minocycline, dapsone, colchicine, clofazamine, thalidomide may improve the PG lesion.
  • In refractory cases, pulsed systemic steroids, or addition of mycophenolate mofetil, anti-tumor necrosis factor blockade, or azathioprine to systemic steroids may halt the progression of disease.

Pitfalls

  • Pyoderma gangrenosum-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 can be mimicked by factitial ulcers. 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.

When to refer to a dermatologist

  • When the diagnosis of pyoderma gangrenosum is not clear.
  • For biopsy of the ulcerating lesion to exclude an infectious or inflammatory condition mimicking PG.
  • For co-management of systemic immunosuppression and wound healing.

Clinical Cases

Case 1

  • 67-year-old male
  • No significant past medical history
  • Review of systems is notable for six-month history of unexplained weight loss, night sweats, fatigue
  • Presents for management of an extremely painful leg ulcer that rapidly developed over the past four days without inciting trauma
  • Currently using antibiotic ointment daily covered by a bandage
  • Reports rapid progression of the ulcer

Initial evaluation

  • Thin, tired-appearing male
  • Left leg ulcer that is approximately 2×2 cm in size with a violaceous, undermined border
  • Diagnosis: pyoderma gangrenosum
  • A skin biopsy to exclude infectious or other inflammatory etiology is declined by the patient
  • Clobetasol ointment 0.05% applied daily under an occlusive hydrocolloid dressing is recommended
  • Concern for an underlying inflammatory condition or malignancy triggers a diagnostic evaluation including age-appropriate cancer screening, chest X-ray, and blood tests including complete blood count with differential, erythrocyte sedimentation rate, and rheumatologic serologies
  • Follow-up in 1 week

Follow-up evaluation

  • The ulcer has not progressed in size but also shows no improvement in healing
  • The patient reports that he has mild reduction in ulcer pain
  • Blood tests indicate a pancytopenia with atypical granulocytes noted on peripheral smear, and widespread mediastinal lymphadenopathy is noted on chest X-ray
  • The patient is referred to hematology/oncology for a bone marrow biopsy
  • Ongoing wound care with clobetasol ointment under occlusion is recommended
  • Minocycline 100 mg twice daily is added
  • Follow-up in 1 week

One-week follow-up evaluation

  • Minimal interval improvement
  • The patient’s bone marrow biopsy reveals acute myeloid leukemia; he is admitted to the hospital and started on induction chemotherapy; in the hospital, his wound care is continued
  • As his leukemia goes into remission, his PG lesion heals with characteristic atrophic, cribiform scarring

Case 2

  • 37-year-old male
  • Past medical history notable for inflammatory bowel disease (IBD) for which he takes 6-mercaptopurine
  • Review of systems is notable for one-month history of weight loss, fatigue, blood diarrhea typical of his IBD flares
  • Presents for management of extremely painful leg ulcers present on bilateral ankles that rapidly developed over the past two weeks without inciting trauma
  • Currently covering the ulcers with bandages only
  • Reports rapid progression of the ulcers over the past two days

Initial evaluation

  • Thin, ill-appearing male
  • Bilateral leg ulcers approximately 4x6cm in size with a violaceous, undermined border and sieve-like ulceration within
  • Diagnosis: pyoderma gangrenosum
  • A skin biopsy to exclude infectious or other inflammatory etiology is performed
  • Tacrolimus ointment 0.1% applied daily under an occlusive hydrocolloid dressing is recommended
  • Concern for an underlying inflammatory condition or malignancy triggers a diagnostic evaluation including age-appropriate cancer screening, chest X-ray, and blood tests including complete blood count with differential, erythrocyte sedimentation rate, and rheumatologic serologies
  • The patient is urgently referred to gastroenterology for colonoscopy to confirm a suspected IBD flare
  • Follow-up in 1 week

Follow-up evaluation

  • The patient was seen by gastroenterology and given the high suspicion for recurrent IBD flare, he was started on prednisone 1 mg/kg daily; the ulcers have improved significantly and the patient reports that he has marked reduction in ulcer pain
  • Blood tests indicate evidence of systemic inflammation and mild anemia; age-appropriate malignancy screening does not reveal an underlying malignancy
  • Ongoing wound care with tacrolimus ointment under occlusion is recommended
  • Follow-up in 1 week

One-week follow-up evaluation

  • Ongoing interval improvement
  • The patient’s diarrhea and skin ulcerations are greatly improved; his prednisone is tapered and he is started on a TNF cytokine blockade for management of both IBD and PG (with subsequent clinical improvement)

References

Ahronowitz I, Harp J, Shinkai K (2012) Etiology and management of pyoderma gangrenosum: a comprehensive review, Am J Clin Derm, 13(3): 191-211.