 |
|
Acute Pyoderma Gangrenosum Does Not Require Surgical Therapy
Yong-Kwang Tay, MD;
Marti Friednash, MD;
John L. Aeling, MD
Arch Fam Med. 1998;7:377-380.
ABSTRACT
Pyoderma gangrenosum is an uncommon ulcerative skin disorder that is often associated with underlying systemic diseases, the most common of which is inflammatory bowel disease. We report an illustrative case of a 36-year-old woman with pyoderma gangrenosum occurring at surgical sites and at sites of trauma. She had associated Crohn disease. Multiple surgical procedures were performed on this patient, without improvement. Pyoderma gangrenosum can mimic a necrotizing soft tissue infection. Early recognition of the characteristic lesion may prevent unnecessary operations and facilitate effective control with appropriate medical therapy.
REPORT OF A CASE
In April 1994, a 38-year-old white woman noted erythematous, painful plaques of the left palm and the proximal phalanx of the left middle finger (Figure 1). This was thought to be cellulitis, and a regimen of broad-spectrum antibiotics was started. The lesions were subsequently débrided. A similar lesion appeared on the distal phalanx of the same finger. She was transferred to the University of Colorado Health Sciences Center, Denver, for further evaluation.
|
|
|
|
Figure 1. Erythematous plaque with hemorrhagic bullae surrounded by violaceous margins.
|
|
|
The patient had similar symptoms of her right third finger in September 1992 after blunt trauma to the same finger. New lesions developed on her right second and fourth fingers despite broad-spectrum antibiotic therapy. Surgical débridement was performed for suspected necrotizing soft tissue infection. Five days later, lesions recurred at the surgical margins despite cultures being negative for pathogens. Further surgical treatment was undertaken, resulting in amputations of the right second, third, and fourth digits (Figure 2). The wound healed uneventfully.
|
|
|
|
Figure 2. Right hand showing the amputated right index, middle, and ring fingers.
|
|
|
Her medical history was notable for Crohn disease that was diagnosed in 1991 and treated with prednisolone. In March 1992, a rectovaginal fistula developed, requiring a diverting colostomy. Parenteral steroid therapy was discontinued in the fall of 1992. One year later, a regimen of prednisolone and azathioprine was started for a flare of her intestinal disease. Prednisolone was subsequently discontinued. Thus, the patient's lesions corresponded to periods when she was not taking prednisolone.
Social and family histories were noncontributory.
On examination, the patient was afebrile. The left middle finger was swollen and tender with erythematous, dusky plaques on the left palm and the distal phalanx of the left middle finger. An open wound with purple margins was seen of the proximal phalanx at the site of the surgical débridement (Figure 3). Erythematous, violaceous plaques were present on the left thigh and the dorsum of the right foot, which was the site of an intravenous line. Laboratory investigations revealed an elevated white blood cell count of 11.6x109/L (11600/µL) with a differential count of 0.80 (80%) polymorphonuclear leukocytes. The erythrocyte sedimentation rate was 92 mm/h. Histological examination of a biopsy specimen taken from the edge of the ulcer on the left middle finger showed a nonspecific, diffuse, neutrophilic dermal infiltrate with scattered chronic inflammatory cells and areas of focal necrosis. Cultures of the biopsy material were negative for acid-fast bacilli, bacteria, and fungi. The results of the following investigations were either normal or negative: blood biochemistry tests, liver function tests, hepatitis B and C serologic tests, complement levels, antinuclear antibody test, and serum and urinary protein electrophoresis.
|
|
|
|
Figure 3. Open débrided wound with violaceous margins of the left proximal phalanx of the middle finger. Erythematous dusky plaques are seen on the left palm and the left distal phalanx of the middle finger.
|
|
|
A diagnosis of the pyoderma gangrenosum associated with Crohn disease was made. Pulse therapy with methylprednisolone sodium succinate, 1 g/d for 3 days, was given. A dramatic response occurred within 12 hours with a reduction of pain and erythema. Her lesions started to heal within a week, and she was discharged with a regimen of prednisone, 60 mg twice a day, and sulfasalazine, 1 g twice a day.
COMMENT
Pyoderma gangrenosum is an uncommon necrotizing and ulcerating skin disease that was first described by Brunsting et al1 in 1930. The diagnosis is made clinically because no specific histopathologic or immunofluorescent patterns are present.2 The earliest symptom may be pain in the area, followed by small erythematous papules. The lesions rapidly evolve into tender pustules surrounded by indurated erythematous skin that breaks down to form an ulcer. The rapidity of the development of the lesions and the appearance of the ulcers, with their pus-covered centers and the ragged, undermined, violaceous borders, are hallmarks of the disease and distinguish it from soft tissue infection.3 Vesicles and bullae may be present,4 as in our patient. Lesions are most commonly found on the lower extremities2 but have been reported on the scalp, face, trunk, and arms. Lesions may be single or multiple and may be precipitated by trauma (pathergy), as in our patient. Pathergy is a condition in which the application of a stimulus makes the organism unduly susceptible to a subsequent stimulus of a different kind. The Behçet and the Sweet syndromes also involve this type of pathergy. A history of pathergy is reported in 25% of patients.5 Ulcers heal with cribriform, atrophic scars.1 All age groups are involved, with the youngest documented patient being a 3-week-old infant.6 Peak incidences occur in the third and fourth decades of life for female patients, as in our patient, and in the fifth decade of life for male patients.3
Pyoderma gangrenosum is a marker of various systemic diseases (Table 1). It is most often associated with inflammatory bowel disease.25 It occurs in 0.5% to 5% of patients with ulcerative colitis and in 0.8% to 1.5% of patients with Crohn disease.26 The appearance of pyoderma gangrenosum is nearly always preceded by the inflammatory bowel disease,2 as in our patient. Exacerbations of skin lesions tend to parallel recurrences of the intestinal inflammation.27
|
|
|
|
Pyoderma Gangrenosum and Associated Systemic Disease*
|
|
|
Pyoderma gangrenosum has been reported to occur during granulocyte colony-stimulating factor therapy.7-8 The up-regulation of neutrophilic function and secondary release of cytokines may induce this complication.28 In 40% of patients with pyoderma gangrenosum, no associated disease can be identified.2
The cause of pyoderma gangrenosum remains obscure. Brunsting et al1 initially called it a pyoderma because it was thought to be a bacterial infection caused by streptococci or staphylococci. The cause is now recognized to be noninfectious, although secondary bacterial colonization may occur. Recent investigations emphasize an altered immune system with impaired cellular immunity and defective function of polymorphonuclear leukocytes.9
The histopathologic appearance of pyoderma gangrenosum is not diagnostic (Figure 4). Early lesions show a deep folliculitis with numerous neutrophils surrounding the pilosebaceous unit.29 Vascular changes may be noted. Later, changes of suppurative granulomatous dermatitis supervene, with collections of histiocytes, macrophages, and giant cells. Massive papillary dermal edema may occur. Finally, lesions regress with marked fibroplasia.30 Although the histopathologic features are not diagnostic, a skin biopsy is necessary to rule out other causes of acute skin ulcerations, particularly infections and necrotizing vasculitis.
|
|
|
|
Figure 4. Photomicrograph of lesional skin biopsy showing epidermal necrosis and a massive dermal infiltrate of neutrophils (hematoxylin-eosin, original magnificationx40).
|
|
|
The differential diagnoses for pyoderma gangrenosum include bacterial infection, synergistic gangrene, deep fungal infection, necrotizing vasculitis, bullous erythema multiforme, Sweet syndrome, Behçet syndrome, halogen dermatitis, brown recluse spider bites, amebiasis, purpura fulminans, and factitial ulcer.3 The diagnosis of pyoderma gangrenosum is based on the clinical appearance of the lesion, its association with systemic disease, the exclusion of other causes of dermatitis, and a poor response to antibiotics.10 In the absence of associated systemic disease, the diagnosis is more difficult but is based on the same variables.
The management of pyoderma gangrenosum is directed at the systemic disease, with high-dose corticosteroid therapy and local wound care. Corticosteroid therapy has been the main method of treating pyoderma gangrenosum.2 Initial doses of prednisone of up to 80 to 120 mg/d may be given, with subsequent tapering of dosages to maintenance levels.2 Johnson and Lazarus11 used pulsed therapy of methylprednisolone sodium succinate, 1 g intravenously, in 150 mL of 5% dextrose solution for 5 days to treat refractory pyoderma gangrenosum. They observed a dramatic response with minimal adverse effects. Our patient had a rapid response to pulsed methylprednisolone therapy with a reduction of pain and erythema within 12 hours. Intralesional steroids, in the form of triamcinolone acetonide suspension, have been used to treat early lesions of pyoderma gangrenosum, with good results.12 Other drugs that have been used to treat pyoderma gangrenosum, either alone or in conjunction with steroids, with variable success include sulfones such as dapsone13 and sulfasalazine,3 clofazimine,14-15 minocycline hydrochloride,16 potassium iodide,17 colchicine,18 human intravenous immune globulin,19 and immunosuppressive agents such as azathioprine,2 cyclophosphamide,20, 31 chlorambucil,21 cyclosporine,22-23 and tacrolimus.24, 32 Any of these agents can be used without associated systemic disease. Reported topical agents that have been used successfully include topical cromolyn sodium28, 31 and topical mechlorethamine hydrochloride.30 Hyperbaric oxygen also has been used successfully to treat pyoderma gangrenosum.33-34 Surgical procedures such as débridement and skin grafting are not recommended during the acute stage of pyoderma gangrenosum, especially in patients who exhibit pathergy, because this could lead to further tissue destruction and progression.35
CONCLUSIONS
We have presented a case of pyoderma gangrenosum associated with Crohn disease that mimicked a soft tissue infection. Besides inflammatory bowel disease, other important associated systemic diseases include hematologic and rheumatologic conditions. Although acute pyoderma gangrenosum may simulate an infection, the characteristic morphologic appearance of the lesions, the association of systemic disease, cultures that are negative for pathogens, results of a skin biopsy that are consistent with the diagnosis, and a failure to respond to antibiotic therapy should point strongly to a diagnosis of pyoderma gangrenosum. High-dose parenteral corticosteroids are the treatment of choice for acute pyoderma gangrenosum. Often a steroid-sparing drug is needed for chronic or recurrent disease. The use of cyclosporine has been reported to be effective in problem or refractory cases. Finally, surgical débridement or grafting should be undertaken with great caution and only in patients who have no clinical evidence of active disease and are receiving appropriate immunosuppressive therapy.
AUTHOR INFORMATION
Accepted for publication August 6, 1997.
Reprints: John L. Aeling, MD, Department of Dermatology, University of Colorado Health Sciences Center, Campus Box E-153, 4200 E Ninth Ave, Denver, CO 80262.
From the Division of Pediatric Dermatology (Dr Tay), the Department of Dermatology (Drs Friednash and Aeling), University of Colorado Health Sciences Center, Denver.
REFERENCES
1. Brunsting LA, Goeckerman WH, O'Leary PA. Pyoderma (ecthyma) gangrenosum: clinical and experimental observations in five cases occurring in adults. Arch Dermatol Syph. 1930;22:655-680.
2. Schwaegerle SM, Bergfeld WF, Senitzer D, Tidrick RT. Pyoderma gangrenosum: a review. J Am Acad Dermatol. 1988;18:559-568.
WEB OF SCIENCE
| PUBMED
3. Perry HO. Pyoderma gangrenosum. South Med J. 1969;62:899-908.
WEB OF SCIENCE
| PUBMED
4. Perry HO, Winkelmann RK. Bullous pyoderma gangrenosum and leukemia. Arch Dermatol. 1972;106:901-905.
FREE FULL TEXT
5. Powell FC, Schroeter AL, Su WPD, Perry HO. Pyoderma gangrenosum: a review of 86 patients. Q J Med. 1985;55:173-186.
6. Graham JA, Hansen KK, Rabinowitz LG, Esterly NB. Pyoderma gangrenosum in infants and children. Pediatr Dermatol. 1994;11:10-17.
PUBMED
7. Ross HJ, Moy LA, Kaplan R, Figlin RA. Bullous pyoderma gangrenosum after granulocyte colony-stimulating factor treatment. Cancer. 1991;68:441-443.
PUBMED
8. Johnson ML, Grimwood RE. Leukocyte colony-stimulating factors: a review of associated neutrophilic dermatoses and vasculitides. Arch Dermatol. 1994;130:77-81.
FREE FULL TEXT
9. Zonana-Nacach A, Jimenez-Balderas FJ, Martinez-Osuna P, Mintz G. Intravenous cyclophosphamide pulses in the treatment of pyoderma gangrenosum associated with rheumatoid arthritis: report of 2 cases and review of the literature. J Rheumatol. 1994;21:1352-1356.
WEB OF SCIENCE
| PUBMED
10. Rand R, Brown G, Bostwick J. Pyoderma gangrenosum and progressive cutaneous ulceration. Ann Plast Surg. 1988;20:280-284.
FULL TEXT
| PUBMED
11. Johnson RB, Lazarus GS. Pulse therapy: therapeutic efficacy in the treatment of pyoderma gangrenosum. Arch Dermatol. 1982;118:76-84.
FREE FULL TEXT
12. Jennings JL. Pyoderma gangrenosum: successful treatment with intralesional steroids. J Am Acad Dermatol. 1983;9:575-580.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
13. Soto LD. Diaminodiphenylsulfone and steroids in the treatment of pyoderma gangrenosum. Int J Dermatol. 1970;9:293-300.
PUBMED
14. Michaelsson G, Molin L, Ohman S, et al. Clofazimine: a new agent for the treatment of pyoderma gangrenosum. Arch Dermatol. 1976;112:344-349.
FREE FULL TEXT
15. Kaplan B, Trau H. Treatment of pyoderma gangrenosum with clofazimine. Int J Dermatol. 1992;31:591-593.
PUBMED
16. Lynch WS, Bergfeld WF. Pyoderma gangrenosum responsive to minocycline hydrochloride. Cutis. 1978;21:535-538.
WEB OF SCIENCE
| PUBMED
17. Richardson JB, Callen JP. Pyoderma gangrenosum treated successfully with potassium iodide. J Am Acad Dermatol. 1993;28:1005-1007.
PUBMED
18. Paolini O, Hebuterne X, Flory P, Charles F, Rampal P. Treatment of pyoderma gangrenosum with colchicine. Lancet. 1995;345:1057-1058.
FULL TEXT
19. Gupta AK, Shear NH, Sauder DN. Efficacy of human intravenous immune globulin in pyoderma gangrenosum. J Am Acad Dermatol. 1995;32:140-142.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
20. Newell LM, Malkinson FD. Pyoderma gangrenosum: response to cyclophosphamide therapy. Arch Dermatol. 1983;119:495-497.
FREE FULL TEXT
21. Callen JP, Case JD, Sager D. Chlorambucil: an effective corticosteroid-sparing therapy for pyoderma gangrenosum. J Am Acad Dermatol. 1989;21:515-519.
PUBMED
22. Elgart G, Stover P, Larson K, et al. Treatment of pyoderma gangrenosum with cyclosporine: results in seven patients. J Am Acad Dermatol. 1991;24:83-86.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
23. Matis WL, Ellis CN, Griffiths CEM, Lazarus GS. Treatment of pyoderma gangrenosum with cyclosporine. Arch Dermatol. 1992;128:1060-1064.
FREE FULL TEXT
24. Abu-Elmagd K, Jegasothy BV, Ackerman CD, et al. Efficacy of FK 506 in the treatment of recalcitrant pyoderma gangrenosum. Transplant Proc. 1991;23:3328-3329.
WEB OF SCIENCE
| PUBMED
25. Cairns BA, Herbst CA, Sartor BR, Briggaman RA, Koruda MJ. Peristomal pyoderma gangrenosum and inflammatory bowel disease. Arch Surg. 1994;129:769-772.
FREE FULL TEXT
26. Keltz M, Lebwohl M, Bishop S. Peristomal pyoderma gangrenosum. J Am Acad Dermatol. 1992;27:360-364.
WEB OF SCIENCE
| PUBMED
27. Schoetz D Jr, Coller JA, Veidenheimer MC. Pyoderma gangrenosum and Crohn's disease: eight cases and a review of the literature. Dis Colon Rectum. 1983;26:155-158.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
28. DeCock KM, Thorne MG. The treatment of pyoderma gangrenosum with sodium cromoglycolate. Br J Dermatol. 1980;102:231-233.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
29. Hurwitz RM, Haseman JH. The evolution of pyoderma gangrenosum: a clinicopathologic correlation. Am J Dermatopathol. 1993;15:28-33.
WEB OF SCIENCE
| PUBMED
30. Tsele E, Yu RCH, Chu AC. Pyoderma gangrenosum: response to topical nitrogen mustard. Clin Exp Dermatol. 1992;17:437-440.
PUBMED
31. Anderson LL, Samlaska CP, Cardone JS, Holtzmuller KC. Treatment of pyoderma gangrenosum with 4% cromolyn. Arch Dermatol. 1994;130:1117-1120.
FREE FULL TEXT
32. Abu-Elmagd K, Van Thiel DH, Jegasothy BV, et al. Resolution of severe pyoderma gangrenosum in a patient with streaking leukocyte factor disease after treatment with tacrolimus (FK 506). Ann Intern Med. 1993;119:595-598.
33. Thomas CY Jr, Crouch JA, Guastello J. Hyperbaric oxygen therapy for pyoderma gangrenosum. Arch Dermatol. 1974;110:445-446.
FREE FULL TEXT
34. Wasserteil V, Bruce S, Sessoms SL, Guntupalli KK. Pyoderma gangrenosum treated with hyperbaric oxygen therapy. Int J Dermatol. 1992;31:594-596.
PUBMED
35. Fulbright RK, Wolf JE, Tschen JA. Pyoderma gangrenosum at surgery sites. J Dermatol Surg Oncol. 1985;11:883-886.
PUBMED
|
