By Gary M. White, MD
Pyoderma gangrenosum (PG) is an ulcerative disease that classically is associated with chronic inflammatory conditions such as ulcerative colitis, Crohn's disease, arthritis, chronic active hepatitis, and Takayasu's arteritis. An IgA paraprotein has been associated in approximately 10% of patients. PG affects slightly more women than men and is most common in patients 10-50 years of age.
PG may be separated into several clinical variants. The classic ulcerative type begins as a papule or pustule which breaks down to form an ulcer with an undermined, violaceous, jagged border. In pustular PG, painful, sterile pustules with a surrounding halo of erythema occur. They may or may not ulcerate. Fever, arthralgias, and the finding of IBD are typical in pustular PG. In bullous PG, pseudovesicular lesions occur. In superficial granulomatous pyoderma, the lesions are more superficial, less aggressive, and more chronic. The edges are less violaceous. There is a predilection for the trunk and many patients do not have any associated diseases. PG lesions of any sort may occur at sites of trauma (pathergy).
An ulcer or ulcers about an ostomy site may represent pyoderma gangrenosum. If Crohn's disease is the reason for the ostomy, involvement of the GIT adjacent to the ostomy site should be considered. Often, there are multiple holes and fistulous tracts that characterize PG as opposed to a periostomal ulcer caused by a poorly fitting ostomy apparatus.
One female patient was noted to have a premenstrual flare of her PG and benefited from a combined oral contraceptive (Ethinyl Estradiol/Drospirenone--Yasmin) [BJD 2015 Dec online].
Postoperative PG is rare. When it does occur, it has a predilection for women on the breasts and abdomen. There is less an association with systemic disease. In one study of 18 patients, the average time to symptoms was 11 days [JAAD 2015;73;615].
A review of 13 children with PG found that the skin lesions have a more varied anatomic distribution (i.e., legs, trunk, arms, head and neck), a greater predominance of pustular lesions and a strong association with inflammatory bowel disease--Crohn's disease being the most common [PD 2017;34;39].
Drug-induced PG is rare but does occur. Most are colony-stimulatings factor (e.g., granulocyte colony-stimulating factor) or small-molecule tyrosine kinase inhibitors (e.g., gefitinib, imatinib, simitinib and pazopanib) [Br J Dermatol 2017;177;72].
Pyoderma gangrenosum is a diagnosis of exclusion. One should consider systemic vasculitis (e.g., granulomatosis with polyangiitis), halogenodermas, gummatous syphilis, factitial disease, mycobacterial infection, atypical mycobacterial infection, deep fungal infections, synergistic gangrene, and antiphospholipid syndrome.
Extra-cutaneous PG (lung, intestine, cornea, spleen, etc.) involvement is rare. Pulmonary involvement is the most common, although there are only few reported cases [JEADV 2017;31;e214].
Workup is focused on excluding other disease as PG is a diagnosis of exclusion. It may include ANA, RF, hepatic and renal enzymes, antiphospholipid syndrome, CBC, RPR, SPEP, GI evaluation, serum iodide and bromide levels, and biopsy of the margin of the ulcer for histopathology and culture (e.g., bacterial, viral, fungal, AFB). The patient should be asked about cocaine use as levamisole-adulterated cocaine can precipitate PG [JAAD 74;892]. In recalcitrant cases, rarer associations with syndromes should be considered [BJD 2015;172;1487]. This may also influence therapy. For example, in cases of PAPA syndrome, PG responds best to IL-1 blockade. Treatment with B vitamins has been shown to improve PG in cases of methylenetetrahydrofolate reductase mutations, whereas patients with myelodysplastic syndrome may improve with thalidomide treatment.
Either systemic steroids or cyclosporin (CsA) are usually prescribed initially. Both of these may be combined with a potent topical steroid daily (e.g., clobetasol). Alternatively, tacrolimus ointment may be employed. Prednisone 1 mg/kg or higher (e.g., 40 to 120 mg/day) is common but pulse methylprednisolone has been used. This high-dose therapy should be continued until the ulcers are healed. Tapering too quickly can cause a flare. Low-dose therapy may be needed to prevent recurrence.
Patients with solitary PG or smaller lesions may be candidates for potent topical steroid therapy alone. In one study of such patients, 44% healed within 6 months [JAAD 2016;75;940]. Patients may also keep the topical steroid around to use as early as possible if their lesions recur.
Cyclosporin (orally e.g., 5 mg/kg/day) is dramatically effective and many consider it the drug of choice. It is an excellent alternative to prednisone. CsA at lower doses (e.g., 3 mg/kg/d) has also been used [Ht 1995;46;697] but required 3-6 months for healing. Cyclosporin can be very effective alone, but if the patient is already on prednisone, the CsA may be added without stopping the steroid.
Mycophenolate mofetil appears quite effective and is often given with prednisone [JAAD 2013;69:565-9]. Dapsone 100-200 mg/day can be of considerable benefit.
Intralesional steroids may be tried if feasible (e.g., 10 mg/cc) as well as IL CsA although the patient must accept that it may worsen the ulcer through pathergy.
Infliximab (Remicade) has been very helpful in treating pyoderma gangrenosum including in children as young as 17 months of age [Dermatology Online Journal 22(4)]. It may be used in combination with topical tacrolimus and/or prednisone. One protocol suggested is infusions of infliximab at zero, two, and eight weeks using a dose of 4-5 mg/kg. Often the prednisone may be tapered once the Remicade is started and then maintenance of infliximab may be given. In some cases, topical tacrolimus is sufficient to maintain control.
Canakinumab is a human monoclonal antibody that selectively blocks IL-1β. It has been studied in 5 patients with PG [BJD 2015 173;1216–1223]. Canakinumab 150 mg was administered subcutaneously to all patients at week 0 with more doses administered depending upon clinical response. Four of five patients showed a decrease in target-lesion size, and three of five achieved complete remission.
In severe, recalcitrant cases, combination therapy may be needed. For example, a 13-year-old girl was treated with prednisone and cyclosporine but remission was not achieved until the addition of adalimumab [Dermatology Online Journal 2014].
Once a medical regimen has controlled the pain and stopped progression, gentle wound debridement may be helpful along with attention to dressings and controlling any wound infection. (Without control of the PG, pathergy may occur.)
Topical cromolyn sodium (e.g., 4% stock solution sprayed or poured and occluded with a hydrocolloid dressing changed Q 2-3 days) has been reported effective within 2 weeks. Local wound care and oral antibiotics should be given if bacterial superinfection occurs. Other drugs that have been used include supersaturated potassium iodide (SSKI), minocycline, clofazimine, azathioprine, cyclophosphamide, IV Cytoxan, and pulse steroids with chlorambucil. Healing may leave a cribriform scar.
Anemia is very common in patients with PG [Orphanet J Rare Dis. 2013;8:136]. A 30-year-old man with Crohn's disease, anemia, and recalcitrant PG cleared completely after iron sucrose infusion [JAAD Case Reports March 2015 Volume 1, Issue 2, Pages 54–55].
PG before and after cyclosporin. Note the dramatic reduction in the inflammation at the edges.
Multiple lesions after surgery.
An early hemorrhagic pustular lesion on the shin.
A larger, vegetating lesion. Courtesy Michael O. Murphy, MD
Pustular PG. Dermatology Online Journal 17(10)
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