Pyoderma Gangrenosum

Table II.

Treatment Options

Wound management and topical care are important, but a systemic antiinflammatory / immunosuppressive drug is the main focus of PG management.

Corticosteroids are the initial treatment of choice. It is reasonable to begin with 1-2mg/kg prednisone daily in divided doses to halt the progression of the disease and induce healing. A rapid improvement of pain and other discomfort is often recorded early, but high-dose steroids must be continued until lesions show evidence of healing, after which gradual tapering is possible. Measures to prevent and control steroids side effects (bone demineralisation) must be started early. Some authors advocate the use of intravenous steroids.

In chronic, paucilesional PG, steroid-sparing antiinflammatory drugs can be useful. These are dapsone, clofazimine, minocycline. In recurrrent cases, prompt treatment with intra-lesional injections of triamcinolone acetonide (10-40mg/ml) can be effective in aborting development of large ulcerated lesions.

In severe, recalcitrant PG, or in cases with contraindications or intolerance to steroids, cyclosporine (3-5mg/kg/day) is probably the best option. Other immunosuppressive drugs such as methotrexate, mycophenolate mofetil, and azathioprine have given good results, usually in association with oral steroids.

Anti-tumor necrosis factor (TNF)-alpha agents have recently been used with success, in PG associated with inflammatory bowel disease (IBD) and also in PG itself. Whether anti-TNF agents or anti-IL-1 agents, such as anakinra, become standard therapy for all PG patients awaits additional clinical research.

Optimal Therapeutic Approach for this Disease

A patient with PG must be evaluated for the following:

• diagnosis confirmation

• search for extracutaneous disease

• evaluation of associated diseases (co-morbidities)

• general workup, including drug safety issues

• initiation of professional topical care

Topical wound care requires experienced health professionals. Treatments must reduce pain and avoid superinfection. It is also important to minimize any physical trauma, including physical wound debridement, as pathergy is a cause of initiation or aggravation of PG lesions.

Antiseptic solutions must be used for cleansing. Nonadhesive dressings should be applied over the lesions and held in place with elasticized bandages. Hydrocolloid dressings are useful.

Potent topical corticosteroids (clobetasol), and/or topical tacrolimus may be useful to heal small, superficial PG ulcers.

Systemic antiimmflamatory/immunosuppressive therapy should be intiated promptly after diagnosis confirmation. As mentioned in treatment options, corticosteroids are the treatment of choice for inital therapy to suppress the inflammatory process. After an initial suppression period of at least 6 weeks (depending on the size and number of lesions), a steroid-sparing agent is typically added and steroid/steroid-sparing therapies are consolidated so that corticosteroids can be weaned and the patient can be maintained on a steroid-sparing agent. After a peroid of stability without active and ulcerated leasions (3-6 months), maintenance therapy can be tapered to the lowest effective suppressive dose. The use of inhibitors of IL-1, anti-TNF inhibitors, and other important mediators is under investigation.

Patient Management

Patients with PG must be managed by dermatologists with experience treating internal medicine patients, or in cooperation with an internist. Patients must be informed of the expected healing time of the ulcers, the importance of topical care, and the careful monitoring of the efficacy and side effects of the drugs used.

Nurses and other health professionals must work in close contact with the physicians. It is important to emphasize to the patient the fact that the ulcerations, even the most dramatic ones, will heal, usually only leaving a slightly atrophic, depressed scar. In patients with recurrent PG, maintenance therapy with low-dose steroids and/or immunosuppressives will help prevent new lesions.

Unusual Clinical Scenarios to Consider in Patient Management

Pyoderma gangrenosum

PG variants are usually less severe, and more often associated with multisystemic diseases.

Bullous PG (a form which overlaps with Sweet syndrome and is commonly associated with hematologic disease) presents as rapidly expanding blister or erosion, which do not end as deep ulcerations (Figure 3).

Figure 3.

Pustular PG (often associated with IBD) consists of multiple, large painful pustules (Figure 4).

Figure 4.

Vegetative PG (or superficial granulomatous PG) usually presents as a single nodule or plaque. It evolves slowly and may be responsive to topical therapy (Figure 5).

Figure 5.

Pyoderma gangrenosum overlapping with or existing with other neutrophilic dermatoses

In recent years, numerous case reports and clinical publications suggested that some neutrophilic dermatoses (NDs) must be considered as a single group. This group includes PG, Sweet syndrome, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), erythema elevatum diutinum, and other conditions. In this continuous spectrum of inflammatory conditions, overlapping symptoms are common. Patients with overlapping ND may have a blood disorder, a gammopathy, an inflammatory bowel disease, a chronic rheumatic disease, or no associated disease.

Postoperative pyoderma gangrenosum

Postoperative PG (Figure 6) may be considered as a consequence of pathergy. It is often unrecognized by surgeons because this enlarging purulent ulceration of a surgical scar is usually attributed to superinfection, leading to inefficient antibiotic therapy and aggressive surgical debridement. The initial surgery may have been motivated by an internal manifestation of pyoderma gangrenosum, misdiagnosed as an infection or malignancy. Peristomal PG is another manifestation of cutaneous pathergy in patients with inflammatory bowel disease who have an ileostomy or colostomy.

Figure 6.

PAPA syndrome

PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome is a rare autosomal dominant disease described in 1997. It belongs to the group of the monogenic autoinflammatory diseases. Successful treatment of PG in PAPA syndrome by anakinra has recently been reported. Such exceptional patients may give insights to pathophysiological considerations and therapeutic progress in non genetic PG.

What is the Evidence?

Brocq, L. “Nouvelle contribution à l’étude du phagédénisme géométrique”. Ann Dermatol Syph. vol. 9. 1908. pp. 1-39. (For French-reading lovers of beautiful texts of clinical dermatology, the description of the typical PG ulcer.)

Brooklyn, TN, Dunnill, GS, Shetty, A. “Infliximab for the treatment of pyoderma gangrenosum: a randomised, double-blind placebo-controlled trial”. Gut. vol. 55. 2006. pp. 505-9. (First clinical trial of infliximab in PG.)

Brunsting, LA, Goeckerman, WH, O’ Leary, PH. “Pyoderma (ecthyma) gangrenosum : clinical and experimental observations in five cases occurring in adults”. Arch Dermatol. vol. 22. 1930. pp. 655-80. (The initial description of PG by the Mayo Clinic Team. Four of these five patients had ulcerative colitis.)

Butler, D, Shinkai, K. “What do autoinflammatory syndromes teach about common cutaneous diseases such as phoderma gangrenosum? A commentary”. Dermatol Clin. vol. 31. 2013. pp. 427-35. (The current view of the pathophysiology of PG and other ND.)

Caughman, W, Stern, R, Haynes, H. “Neutrophilic dermatosis of myeloproliferative disorders”. J Am Acad Dermatol. vol. 9. 1983. pp. 751-8. (First description of a condition overlapping PG and Sweet syndrome, in patients with hematologic disorders.)

Field, S, Powell, FC, Young, V, Barnes, L. “Pyoderma gangrenosum manifesting as a cavitating lung lesion”. Clin Exp Dermatol. vol. 33. 2008. pp. 418-21. (This patient’s PG started in the lung, and involved the skin secondarily.)

Lindor, NM, Arsenault, TM, Solomon, H, Seidman, CE, McEvoy, MT. “A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome”. Mayo Clin Proc. vol. 72. 1997. pp. 611-5. (First description of this monogenic autoinflammatory disorder, which could be an example for future research on pathophysiology and treatment of PG.)

Powell, FC, Collins, S. “Pyoderma gangrenosum”. Clin Dermatol. vol. 18. 2000. pp. 283-93. (An excellent review of PG including classification, associated conditions, and management. The whole issue of this journal is about the neutrophilic dermatoses.)

Vignon-Pennamen, MD, Wallach, D. “The cutaneous manifestations of neutrophilic disease”. Dermatologica. vol. 183. 1991. pp. 255-64. (First indication that the neutrophilic dermatoses are not limited to the skin.)

Vignon-Pennamen, MD. “The extracutaneous involvement in the neutrophilic dermatoses”. Clin Dermatol. vol. 18. 2000. pp. 339-47. (Describes all the noncutaneous neutrophilic lesions.)

von den Driesch, P. “Pyoderma gangrenosum: a report of 44 cases with follow-up”. Br J Dermatol. vol. 137. 1997. pp. 1000-5. (Good clinical review, including the proposal of diagnostic criteria.)

Weenig, RH, Davis, MD, Dahl, PR, Su, WP. “Skin ulcers misdiagnosed as pyoderma gangrenosum”. N Engl J Med. vol. 347. 2002. pp. 1412-18. (Important clinical study focusing on ulcers that mimic PG. Insists on the necessary evaluation of al patients with suspected PG.)