Pyoderma Gangrenosum

Definition

Dermatosis characterized by development of necrotic ulcers from acneiform pustules or erythematous nodules and is associated with a wide variety of systemic disorders such as inflammatory bowel disease, hepatitis C, lymphomas and leukemias to name a few.

Clinical Features

Pustule or nodule:
- erythematous
- single or multiple1
- rapid progression to necrotic ulcer with ragged, undermined, violaceous edge:2–4
  - may coalescence to form large lesions ≥20cm diameter 1
  - heals leaving parchment or cribriform scar
Onset:
- not infrequently initiated by minor trauma5,6
- usually mid-adult life 7–14
Location:
- predilection for:
  - lower extremities 3
- sometimes:
  - trunk
- rarely:
  - head and neck7,15
  - penis 16,17
Extracutaneous manifestations:
- sterile pyoarthrosis 18
- oropharyngeal involvement19
- neutrophilic myositis20
- pulmonary inflammatory infiltrates21
Course:
- may be:
  - acute progressive with rapidly expanding lesions22,23
  - more chronic with slow extension and sometimes spontaneous regression after weeks or months 22

Associations

Chronic multifocal osteomyelitis24
Systemic illness >50% of cases such as:
- ulcerative colitis24
- Crohn's disease25–27
- rheumatoid arthritis 3
- seronegative polyarthritis
- monoclonal gammopathy, particularly IgA type28
Parastomal lesions important complication of inflammatory bowel disease29,30
Many rare clinical associations 3,19,31–58

Variants

PAPA Syndrome

Autosomal dominant
Pyogenic sterile arthritis, pyoderma gangrenosum and acne74

Pathogenesis

Multiple abnormalities of humoral immunity, cell-mediated immunity and neutrophil function:
- pathogenetic significance an enigma:2,75–78
- role, if any, of vasculitis debatable

Histopathology 79–81

Findings:
- variable
- depend on:
  - age of lesion
  - site biopsied
Presence (or absence) of vasculitis:33
- most controversial aspect
- lymphocytic and/or leukocytoclastic vasculitis at advancing erythematous edge in 73% of cases4
Earliest lesion:
- follicular and perifollicular inflammation with intradermal abscess formation9,82,83
Later lesions:
- necrosis of superficial dermis and epidermis:
  - forms ulcer:
    - base shows mixed inflammatory cell infiltrate with abscess formation 81
  - may extend into underlying subcutis (Fig. 1
    Fig. 1: Pyoderma gangrenosum. A deep ulcer is present, as is tight lymphocytic cuffing of vessels in the margin of the ulcer. (H&E)
    )
- sometimes giant cells:
  - particularly if associated Crohn's disease84
Advancing edge:
- lymphocytic vasculitis:8
  - tight perivascular infiltrate of:
    - lymphocytes
    - plasma cells
  - endothelial swelling
  - disputed by some authors23
- sometimes leukocytoclastic vasculitis83,85,86
- often subepidermal edema:
  - prominent
  - associated with intraepidermal bullae with pustulation in variants with bullous changes
Acanthosis:
- prominent in perilesional erythematous zone

Variants

Superficial Granulomatous Pyoderma

Superficial dermal abscesses surrounded by:
- then mixed inflammatory cell infiltrate:
  - usually includes:
    - some giant cells of foreign body type:67,68,70,87
      - necrotizing granulomas:
        rarely seen in other forms 88
Often pseudoepitheliomatous hyperplasia
Follicular infundibula:
- may be enlarged:
  - possibly in association with transepidermal elimination of inflammatory debris

Clinical And Histological Variants

Four distinctive variants suggested:
- ulcerative:
  - central neutrophilic abscesses
  - ‘peripheral lymphocytic angiocentric’ infiltrates
- pustular:
  - subcorneal pustules
  - subepidermal edema
  - dense dermal neutrophilia
- bullous:
  - subepidermal bullae
  - dermal neutrophilia
- vegetative:89
  - pseudoepitheliomatous hyperplasia
  - dermal abscesses
  - sinus tracts (Fig. 2
    Fig. 2: Pyoderma gangrenosum, superficial granulomatous type. There is a dermal abscess, which drains into an overlying follicle. (H&E)
    )
  - palisading granulomatous reaction89

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Pyoderma Gangrenosum

May mimic cutaneous tuberculosis90
Blastomycosis-like pyoderma:
- some resemblance to superficial granulomatous pyoderma, but:
  - inflammatory process usually much deeper in dermis
  - palisading histiocytes not usually prominent
- usually at different site

Management

Responses reported to:
- thalidomide91,92
- clofazimine 93
- mycophenolate mofetil94,95
- immunosuppression combined with bioengineered-skin grafting 96

References

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Last updated: 30 Dec 2006