Pyoderma gangraenosum

Brocq, 1916; Brunsting u. Goeckermann, 1930

PG, ulcerative dermatitis, Meleney ulcer, pyodermia vegetans et ulcerans gangraenosa

• Rare, sometimes painful and destructive, sterile, inflammatory dermatosis associated with abscesses and necrosis
• It is chronically progressive and resistant to common ulcer therapy

• Rare condition
• Slight female predilection
• Mostly between the ages of 25 and 54
• Smoking can increase the risk for PG

• Ulcerative form (classic and most common type): rapidly deep- or area-progressive, purulent-serous ulceration with undermined, livid-red margins. Associated arthritides, inflammatory bowel disease, monoclonal gammopathies  
• Pustular form: 0.2-0.8 cm pustules, often associated with larger inflammatory plaque(s). Commonly associated inflammatory bowel disease
• Bullous form: Subepidermal blistering with inflammatory rim that erodes or ulcerates. 
• Vegetative superficial granulomatous form: superficial mostly solitary ulcer without undermined rim, often in surgical scars.
• Peristomal form: Ulcerating, painful  papules or plaques around stomas. Further development into the typical ulcerative form with undermined margins.
• Mucosal type = pyostomatitis vegetans: this very rare, chronic ulcerative clinical picture of the  oral mucosa is considered by some authors to be a (mucosal) variant of pyoderma gangraenosum.

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• Exact genesis unclear, discussed are abnormal function of neutrophil granulocytes, dysregulation of the immune system, genetic predisposition
• Frequent association (> 50%) with systemic diseases: e.g. chronic inflammatory bowel diseases, rheumatoid arthritis, haematological diseases or malignancies

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• Very painful focal skin lesions, often initially consisting of blisters, papules and pustules
• Pathergy: Often develops after minor trauma (insect bites, small injuries)
• During progression, deep ulcers develop across the dermis with central necrosis
• Continuous progression, centrifugal spread
• Typical: Wall-like, undermined, very painful deep red marginal zone
• Smudgy, spongy consistency.

• There are no universal diagnostic criteria, however in JAMA Derm 2018 Maverakis et al published a Delphi consensus (cited verbatim): 
  • Major criterion: Biopsy of ulcer edge demonstrating neutrophils
  • Minor critera (4 of 8): no infection; pathergy; IBD/Arthritis; papule/pustule/vesicle ulcerating within 4 days after appearance; peripheral erythema, undermined border, tenderness at ulceration site; multiple ulcerations including 1 on anterior lower leg; cribriform or wrinkles scar at healed sites; ulcer decreases size after 1 month of immunosuppressives. 
• History of present illness
• Clinical features
• Lab:
  • mildly elevated inflammatory parameters
  • mild anaemia
  • negative ANAs, cANCAs 

Predilection sites: Extensor sides of the lower extremities, even though these are also the site of most other differentials! 

• Nonspecific histology
• Dermal abscesses of polymorphonuclear neutrophils
• Later transition to a mixed cell infiltrate including plasma cells, accompanied by oedema of the papillary dermis, necrosis

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Needless debridement by surgeons when diagnosis is delayed.

Not possible before diagnosis, after diagnosis immunosuppressives should be used until the tendency to form larger ulcers has ceased. 

• Chronic, progressive course
• Frequent recurrences
• Spontaneous healing rather rare

• Therapy of the underlying primary disease
• Local therapy: General wound treatment, further externals such as glucocorticoids, tacrolimus 0.1% ointment
• Systemic therapy

• First-line therapy: combination of ciclosporine 5 mg/day/kg bw with glucocorticoids such as prednisone 100-150 mg/day (level of evidence III).

• Alternatively: glucocorticoids as pulse therapy (1 g/day i.v. day 1-5)
• If necessary, repeat after 4 weeks (level of evidence III)

• Second-line therapy:
• TNF-alpha inhibitors: infliximab, adalimumab, certolizumab (standard dosage similar to psoriasis)
• IL-17 inhibitors (standard dosage similar to psoriasis)
• IL-12/23 inhibitors (standard dosage similar to psoriasis)
• Mycophenolate mofetil: 2.0-2.5 g/day p.o. as monotherapy or in combination with ciclosporine 50 mg/day p.o. and/or prednisolone.
• Surgical therapy is contraindicated in the acute stage

1. Powell FC, Hackett BC. Pyoderma Gangrenosum. In: Wolff K, Goldsmith LA, Katz SL, Gilchrist BA, Paller AS, Leffell DJ, editors. Fitzpatrick's Dermatology in General Medicine. 7th ed. Vol. 1. New York: McGraw Hill; 2007. pp. 296–302.
2. Powell FC, Schroeter AL, Perry HO, Su WP. Direct immunofluorescence in pyoderma gangrenosum. Br J Dermatol. 1983;108:287–93
3. Hughes AP, Jackson JM, Callen JP. Clinical features and treatment of peristomal pyoderma gangrenosum. J Am Med Assoc. 2000;484:1546–8.
4. Von den Driesch P. Pyoderma gangrenosum: A report of 44 cases with follow- up. Br J Dermatol. 1997;137:1000–5
5. Jacob SE, Weisman RS, Kerdel FA. Pyoderma gangrenosum: Rebel without cure. Int J Dermatol. 2008;47:192–4.
6. Gameiro A, Pereira N, Cardoso JC, et al. Pyoderma gangrenosum: challenges and solutions. Clin Cosmet Investig Dermatol 2015;8:285–93.
7. Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol 2010;38:3–10.
8. Bellak JM, Bell MC, Durrani SR, et al. Classical pyoderma gangrenosum associated with abnormal neutrophil oxidative burst. J Allergy Clin Immunol 2012;129:AB159.doi:10.1016/j.jaci.2011.12.358.