In! J Gynecol Ohstet, 1991, 35: 175-178 International Federation of Gynecology and Obstetrics
Vulvar pyoderma C.S. McCalmonta,*,
gangrenosum
B. Leshina, W.L. Whiteb, F.C. Greiss Jr.C, J.L. Jorizzoa
Departments of “Dermatology, sity, 300 South Hawthorne
175
hPathology and “Obstetrics and Gynecology, The Bowman Gray School of Medicine of Wake Forest Univer-
Road,
Winston-Salem,
NC 27103
(USA)
(Received November. 27th 1989) (Revised and accepted April 10th. 1990)
Abstract Pyoderma gangrenosum is an idiopathic dermatologic disease manifested by painful cutaneous ulceration. The ulcers are characterized by their undermined, violaceous borders and necrotic tissue at the ulcer base. The lesions may have an unusual response to physical manipulation known as pathergy, a phenomenon that is manifested by rapid progression following debridement. Pyoderma gangrenosum is fiequently associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis and hematologic malignancies. Conservative wound care and systemic corticosteroids are usually effective therapy. We report the second case in the gynecologic literature of a patient with vulvar pyoderma gangrenosum.
Keywords: Pyoderma gangrenosum;
Pathergy.
Introduction
Pyoderma gangrenosum is an enigmatic skin disease characterized clinically by painful Present address: The Permanente Medical Group, 280 MacArthur Boulevard, Oakland, CA 95611, USA.
0020-7292/91/$03.50 0 1991 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
cutaneous ulcerations. Single or multiple papulopustules are present initially. These lesions then progress to ulcers with necrotic bases and violaceous undermined borders. Rapid progression and extension of these ulcers may follow debridement. This phenomenon, known as pathergy, may also be manifested at sites of trauma remote from the primary lesion(s). The lower extremities are most commonly affected, but lesions may occur anywhere on the skin or on mucous membranes. Reports of pyoderma gangrenosum involving the groin and perineum have been reported by other authors [8,20]. Only one other case of pyoderma gangrenosum involving the vulva has been reported in the gynecologic literature [23]. We report a healthy young patient with pyoderma gangrenosum involving the vulva. Case report
A 29-year-old woman was referred to the Department of Dermatology at the Bowman Gray School of Medicine of Wake Forest University in January, 1988, with a 4-month history of an enlarging exquisitely painful ulcer on the vulva. The lesion, which began as a tender pustule on her left labia, was unresponsive to multiple courses of systemic antibiotics. Debridement of necrotic tissue at the base of the ulcer, which had been performed previousCase Report
176
McCalmonf
ei al
mycobacteria and tissue cultures for such organisms were all negative. A rapid plasma reagin was nonreactive. Therapy with prednisone at a dosage of 80 mg per day was implemented. Symptomatic improvement was noted within the first week of treatment and the lesion was completely healed by 5 weeks (Fig. 2). The patient had resumed sexual activity without dyspareunia at that time. The prednisone was tapered over 6 months and the patient remains disease-free on no therapy. Fig. 1. At presentation the ulcer had a violaceous undermined border and necrotic base.
ly, was followed by extension of the lesion to the perineum and right labia. She had no other systemic symptoms. On physical examination, a 5.5 x 5.0 x 0.5 cm cutaneous ulcer was present on the labia bilaterally and the intervening perineum. Mucopurulent debris formed a pseudomembrane at the ulcer’s base. The borders of the ulcer were violaceous and undermined (Fig. 1). Hematoxylin and eosin stained sections of the lesion showed cutaneous ulceration with a dense neutrophil-rich infiltrate extending deep to the subcutaneous adipose. Intravascular fibrin deposition and thrombi were prominent. Special stains revealed no bacteria, fungi, or
Fig. 2. The lesion was completely healed 5 weeks after initiation of prednisone therapy. Inr J Gynecol Obstet 35
Discussion
The pathogenesis of pyoderrna gangrenosum remains unknown but its association with ulcerative colitis and other autoimmune diseases such as rheumatoid arthritis suggests an immunologic basis. Hickman and Lazarus have written that pyoderma gangrenosum is an expression of altered immunological reactivity [7] and Holt’s perspective is that it represents a variable tissue response to a number of immunological insults [8]. A circulating immune complex-mediated vasculopathy might be suspected based on the occasional histologic finding of vasculitis and the presence of nonspecific immunoreactants in papillary derma1 blood vessel walls [ 19,211. However, circulating immune complexes and a specific antigen have never been causative demonstrated. Early studies reported that up to half of patients with pyoderma gangrenosum have ulcerative colitis [ 181. More recent series show a less striking (6-36%) association with this disease [7,8,20]. Other diseases reported to be associated with pyoderma gangrenosum include Crohn’s disease, rheumatoid arthritis, seronegative rheumatoid-like polyarteritis, systemic lupus erythematosus, chronic active hepatitis and myeloproliferative disorders [l--3,~8,11,17,20]. Pathergy, the phenomenon of rapid disease progression secondary to manipulation, contributes to the destructiveness of pyoderma gangrenosum. This occurs locally at the site of
Vulvar pyoderma gangrenosum
a lesion and also at sites of distant trauma. When a patient with pyoderma gangrenosum has not yet been diagnosed, measures that represent the standard of care in many other types of ulcers may lead to disastrous consequences. Surgical debridement of pyoderma gangrenosum ulcers may result in exponential increase in ulcer size while simple procedures such as intravenous line placement and venipuncture, may compound the problem with multiple new lesions. Anecdotal reports describe cases in which extensive debridement resulted in limb amputation (C. Birkby, pers. commun.). The mechanism of pathergy remains unknown. Since there is no pathognomonic laboratory test or characteristic histologic change, pyoderma gangrenosum is diagnosed on clinical grounds and by exclusion of other etiologies of cutaneous ulceration. A thorough history and physical examination in conjunction with a biopsy of a lesion and supportive laboratory data rule out both necrotizing vasculitis and vasculitis associated with systemic diseases. Skin biopsy will also eliminate specific malignancies, ulcerated insect bite and ulcerated necrobiosis lipoidica diabeticorum from the differential diagnosis. Tissue cultures exclude bacterial, fungal and mycobacterial infections. Bromide and iodide levels rule out halogenodermas. Factitial ulceration may also be included in the differential diagnosis. Pyoderma gangrenosum requires aggressive therapy. The mainstay of therapy is oral corticosteroids, such as prednisone at a dosage of l-2 mg/kg per day. The prednisone taper should be performed with caution to avoid a rebound of the disease. There have been reports of small lesions resolving with intralesional corticosteroid injections and with meticulous topical care [ 15,231. Adjuvant therapies which have been used with limited success in corticosteroid-resistant pyoderma gangrenosum include pulse intravenous corticosteroids, dapsulfasalazine, sone or sulfapyridine, clofazamine, azathioprine, cyclophosphamide, cyclosporin A, minocycline and hyperbaric oxygen [4,5,8,9,12-14,16,18,24].
177
In summary, pyoderma gangrenosum is an uncommon skin disease of unknown pathogenesis. Diagnosis is based on the characteristic clinical appearance and on exclusion of other diseases. We have reported a patient with vulvar pyoderma gangrenosum. An awareness of this cutaneous disease is important for physicians who treat patients with vulvar disease. References 1
2 3
4
5 6
7
8
9
10
11
12 13 14
15
Breathnach SM, Wilkinson JD, Wilkinson DS: Pyoderma gangrenosum and chronic active hepatitis. Br J Dermatol 103. 84, 1980. Burton JL: Bullous pyoderma of leukemia. Br J Dermatol 95: 209, 1976. Callen JP, Dubin HV, Gehrke CF: Recurrent pyoderma gangrenosum and agnogenic myeloid metaplasia. Arch Dermatol lI3: 1585, 1977. Curley RK, MacFarlane AW, Vickers CFH: Pyoderma gangrenosum treated with cyclosporin A. Br J Dermatol 113: 601, 1985. Davies MG, Piper S: Pyoderma gangrenosum: successful treatment with minocycline. Clin Exp Dermatol6: 219,1981. Greenstein AJ, Janowitz HD, Sachar DB. The extraintestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine 55: 401, 1976. Hickman JG, Lazarus GS: Pyoderma gangrenosum: a reap praisal of associated systemic diseases. Br J Dermatol 102. 235, 1980. Holt PJA, Davies MG, Saunders KC, Nuki G: Pyoderma gangrenosum: clinical and laboratory findings in 15 patients with special reference to polyarthritis. Medicine 55: 114, 1980. Johnson RB, Lazarus GS: Pulse therapy: therapeutic efficacy in the treatment of pyoderma gangrenosum. Arch Dermatol 118: 76, 1982. Jorizzo JL. Neutrophilic dermatoses: Sweet’s syndrome and pyoderma gangrenosum. In: Inflammation: Basic Principles and Clinical Correlates (eds JI Gallin, IM Goldstein, R Snyderman). Raven Press, New York, 1988. Lazarus GS, Goldsmith LA, Rocklin RE, Pinals RS, deBuisseret JP, David Jr et al: Pyoderma gangrenosum, altered delayed hypersensitivity and polyarthritis. Arch Dermatol 105: 46, 1972. Lorincz AL, Pearson RW: Sulfapyridine and sulfone type drugs in dermatology. Arch Dermatol 85: 42, 1962. Lynch WS, Bergfeld WF: Pyoderma gangrenosum responsive to minocycline hydrochloride. Cutis 21: 535, 1978. Michaelsson G, Molin L, Ohman S, Gip L, Lindstrom B, Skogh M et al: Clofazimine: a new agent for the treatment of pyoderma gangrenosum. Arch DermatolIZ2: 344, 1976. Moschella SL: Pyoderma gangrenosum: a patient successfully treated with intralesional injections of steroid. Arch Dermatol 95: 121, 1967. Case Report
I78
McCalmont
et al.
I8
Newel1 LM, Malkinson FD: Pyoderma gangrenosum: response to cyclophosphamide therapy. Arch Dermatol119: 495, 1983. Olson D: Pyoderma gangrenosum with systemic LE. Acta Dermatol Vener (Stockholm) 51: 233, 1971. Perry HO: Pyoderma gangrenosum. South Med J 62: 899,
I9
1969. Powell FC, Schroeter AL, Perry HO, Su WPD: Direct im-
16
17
20
21
munofluorescence in pyoderma gangrenosum. Br J Dermatol 108: 287, 1983. Powell FC, Schroeter AL, Su WPD, Perry HO: Pyoderma gangrenosum: a review of 86 patients. Q J Med 5.5: 173, 1985. Stolman LP, Rosenthal D, Yaworsky R, Horan F: Pyoderma gangrenosum and rheumatoid arthritis. Arch Dermatol 111: 1020, 1975.
Inr J Gynecol Obstet 35
22 23 24
Tay, CH: Pyoderma gangrenosum and leukemia. Arch Dermatol 108: 580, 1973. Work BA, Jr: Pyoderma gangrenosum of the perineum. Obstet Gynecol 102: 231, 1980. Wyrick WF, Mader JT, Butler ME, Hutlet WH: Hyperbaric oxygen treatment of pyoderma gangrenosum. Arch Dermatol 114: 1232, 1978.
Address for reprints: B. L&in Department of Dermatology Bowman Gray School of Medicine 300 South Hawthorne Road Winston-Salem, NC 27103, USA
Vulvar pyoderma C.S. McCalmonta,*,
gangrenosum
B. Leshina, W.L. Whiteb, F.C. Greiss Jr.C, J.L. Jorizzoa
Departments of “Dermatology, sity, 300 South Hawthorne
175
hPathology and “Obstetrics and Gynecology, The Bowman Gray School of Medicine of Wake Forest Univer-
Road,
Winston-Salem,
NC 27103
(USA)
(Received November. 27th 1989) (Revised and accepted April 10th. 1990)
Abstract Pyoderma gangrenosum is an idiopathic dermatologic disease manifested by painful cutaneous ulceration. The ulcers are characterized by their undermined, violaceous borders and necrotic tissue at the ulcer base. The lesions may have an unusual response to physical manipulation known as pathergy, a phenomenon that is manifested by rapid progression following debridement. Pyoderma gangrenosum is fiequently associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis and hematologic malignancies. Conservative wound care and systemic corticosteroids are usually effective therapy. We report the second case in the gynecologic literature of a patient with vulvar pyoderma gangrenosum.
Keywords: Pyoderma gangrenosum;
Pathergy.
Introduction
Pyoderma gangrenosum is an enigmatic skin disease characterized clinically by painful Present address: The Permanente Medical Group, 280 MacArthur Boulevard, Oakland, CA 95611, USA.
0020-7292/91/$03.50 0 1991 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
cutaneous ulcerations. Single or multiple papulopustules are present initially. These lesions then progress to ulcers with necrotic bases and violaceous undermined borders. Rapid progression and extension of these ulcers may follow debridement. This phenomenon, known as pathergy, may also be manifested at sites of trauma remote from the primary lesion(s). The lower extremities are most commonly affected, but lesions may occur anywhere on the skin or on mucous membranes. Reports of pyoderma gangrenosum involving the groin and perineum have been reported by other authors [8,20]. Only one other case of pyoderma gangrenosum involving the vulva has been reported in the gynecologic literature [23]. We report a healthy young patient with pyoderma gangrenosum involving the vulva. Case report
A 29-year-old woman was referred to the Department of Dermatology at the Bowman Gray School of Medicine of Wake Forest University in January, 1988, with a 4-month history of an enlarging exquisitely painful ulcer on the vulva. The lesion, which began as a tender pustule on her left labia, was unresponsive to multiple courses of systemic antibiotics. Debridement of necrotic tissue at the base of the ulcer, which had been performed previousCase Report
176
McCalmonf
ei al
mycobacteria and tissue cultures for such organisms were all negative. A rapid plasma reagin was nonreactive. Therapy with prednisone at a dosage of 80 mg per day was implemented. Symptomatic improvement was noted within the first week of treatment and the lesion was completely healed by 5 weeks (Fig. 2). The patient had resumed sexual activity without dyspareunia at that time. The prednisone was tapered over 6 months and the patient remains disease-free on no therapy. Fig. 1. At presentation the ulcer had a violaceous undermined border and necrotic base.
ly, was followed by extension of the lesion to the perineum and right labia. She had no other systemic symptoms. On physical examination, a 5.5 x 5.0 x 0.5 cm cutaneous ulcer was present on the labia bilaterally and the intervening perineum. Mucopurulent debris formed a pseudomembrane at the ulcer’s base. The borders of the ulcer were violaceous and undermined (Fig. 1). Hematoxylin and eosin stained sections of the lesion showed cutaneous ulceration with a dense neutrophil-rich infiltrate extending deep to the subcutaneous adipose. Intravascular fibrin deposition and thrombi were prominent. Special stains revealed no bacteria, fungi, or
Fig. 2. The lesion was completely healed 5 weeks after initiation of prednisone therapy. Inr J Gynecol Obstet 35
Discussion
The pathogenesis of pyoderrna gangrenosum remains unknown but its association with ulcerative colitis and other autoimmune diseases such as rheumatoid arthritis suggests an immunologic basis. Hickman and Lazarus have written that pyoderma gangrenosum is an expression of altered immunological reactivity [7] and Holt’s perspective is that it represents a variable tissue response to a number of immunological insults [8]. A circulating immune complex-mediated vasculopathy might be suspected based on the occasional histologic finding of vasculitis and the presence of nonspecific immunoreactants in papillary derma1 blood vessel walls [ 19,211. However, circulating immune complexes and a specific antigen have never been causative demonstrated. Early studies reported that up to half of patients with pyoderma gangrenosum have ulcerative colitis [ 181. More recent series show a less striking (6-36%) association with this disease [7,8,20]. Other diseases reported to be associated with pyoderma gangrenosum include Crohn’s disease, rheumatoid arthritis, seronegative rheumatoid-like polyarteritis, systemic lupus erythematosus, chronic active hepatitis and myeloproliferative disorders [l--3,~8,11,17,20]. Pathergy, the phenomenon of rapid disease progression secondary to manipulation, contributes to the destructiveness of pyoderma gangrenosum. This occurs locally at the site of
Vulvar pyoderma gangrenosum
a lesion and also at sites of distant trauma. When a patient with pyoderma gangrenosum has not yet been diagnosed, measures that represent the standard of care in many other types of ulcers may lead to disastrous consequences. Surgical debridement of pyoderma gangrenosum ulcers may result in exponential increase in ulcer size while simple procedures such as intravenous line placement and venipuncture, may compound the problem with multiple new lesions. Anecdotal reports describe cases in which extensive debridement resulted in limb amputation (C. Birkby, pers. commun.). The mechanism of pathergy remains unknown. Since there is no pathognomonic laboratory test or characteristic histologic change, pyoderma gangrenosum is diagnosed on clinical grounds and by exclusion of other etiologies of cutaneous ulceration. A thorough history and physical examination in conjunction with a biopsy of a lesion and supportive laboratory data rule out both necrotizing vasculitis and vasculitis associated with systemic diseases. Skin biopsy will also eliminate specific malignancies, ulcerated insect bite and ulcerated necrobiosis lipoidica diabeticorum from the differential diagnosis. Tissue cultures exclude bacterial, fungal and mycobacterial infections. Bromide and iodide levels rule out halogenodermas. Factitial ulceration may also be included in the differential diagnosis. Pyoderma gangrenosum requires aggressive therapy. The mainstay of therapy is oral corticosteroids, such as prednisone at a dosage of l-2 mg/kg per day. The prednisone taper should be performed with caution to avoid a rebound of the disease. There have been reports of small lesions resolving with intralesional corticosteroid injections and with meticulous topical care [ 15,231. Adjuvant therapies which have been used with limited success in corticosteroid-resistant pyoderma gangrenosum include pulse intravenous corticosteroids, dapsulfasalazine, sone or sulfapyridine, clofazamine, azathioprine, cyclophosphamide, cyclosporin A, minocycline and hyperbaric oxygen [4,5,8,9,12-14,16,18,24].
177
In summary, pyoderma gangrenosum is an uncommon skin disease of unknown pathogenesis. Diagnosis is based on the characteristic clinical appearance and on exclusion of other diseases. We have reported a patient with vulvar pyoderma gangrenosum. An awareness of this cutaneous disease is important for physicians who treat patients with vulvar disease. References 1
2 3
4
5 6
7
8
9
10
11
12 13 14
15
Breathnach SM, Wilkinson JD, Wilkinson DS: Pyoderma gangrenosum and chronic active hepatitis. Br J Dermatol 103. 84, 1980. Burton JL: Bullous pyoderma of leukemia. Br J Dermatol 95: 209, 1976. Callen JP, Dubin HV, Gehrke CF: Recurrent pyoderma gangrenosum and agnogenic myeloid metaplasia. Arch Dermatol lI3: 1585, 1977. Curley RK, MacFarlane AW, Vickers CFH: Pyoderma gangrenosum treated with cyclosporin A. Br J Dermatol 113: 601, 1985. Davies MG, Piper S: Pyoderma gangrenosum: successful treatment with minocycline. Clin Exp Dermatol6: 219,1981. Greenstein AJ, Janowitz HD, Sachar DB. The extraintestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine 55: 401, 1976. Hickman JG, Lazarus GS: Pyoderma gangrenosum: a reap praisal of associated systemic diseases. Br J Dermatol 102. 235, 1980. Holt PJA, Davies MG, Saunders KC, Nuki G: Pyoderma gangrenosum: clinical and laboratory findings in 15 patients with special reference to polyarthritis. Medicine 55: 114, 1980. Johnson RB, Lazarus GS: Pulse therapy: therapeutic efficacy in the treatment of pyoderma gangrenosum. Arch Dermatol 118: 76, 1982. Jorizzo JL. Neutrophilic dermatoses: Sweet’s syndrome and pyoderma gangrenosum. In: Inflammation: Basic Principles and Clinical Correlates (eds JI Gallin, IM Goldstein, R Snyderman). Raven Press, New York, 1988. Lazarus GS, Goldsmith LA, Rocklin RE, Pinals RS, deBuisseret JP, David Jr et al: Pyoderma gangrenosum, altered delayed hypersensitivity and polyarthritis. Arch Dermatol 105: 46, 1972. Lorincz AL, Pearson RW: Sulfapyridine and sulfone type drugs in dermatology. Arch Dermatol 85: 42, 1962. Lynch WS, Bergfeld WF: Pyoderma gangrenosum responsive to minocycline hydrochloride. Cutis 21: 535, 1978. Michaelsson G, Molin L, Ohman S, Gip L, Lindstrom B, Skogh M et al: Clofazimine: a new agent for the treatment of pyoderma gangrenosum. Arch DermatolIZ2: 344, 1976. Moschella SL: Pyoderma gangrenosum: a patient successfully treated with intralesional injections of steroid. Arch Dermatol 95: 121, 1967. Case Report
I78
McCalmont
et al.
I8
Newel1 LM, Malkinson FD: Pyoderma gangrenosum: response to cyclophosphamide therapy. Arch Dermatol119: 495, 1983. Olson D: Pyoderma gangrenosum with systemic LE. Acta Dermatol Vener (Stockholm) 51: 233, 1971. Perry HO: Pyoderma gangrenosum. South Med J 62: 899,
I9
1969. Powell FC, Schroeter AL, Perry HO, Su WPD: Direct im-
16
17
20
21
munofluorescence in pyoderma gangrenosum. Br J Dermatol 108: 287, 1983. Powell FC, Schroeter AL, Su WPD, Perry HO: Pyoderma gangrenosum: a review of 86 patients. Q J Med 5.5: 173, 1985. Stolman LP, Rosenthal D, Yaworsky R, Horan F: Pyoderma gangrenosum and rheumatoid arthritis. Arch Dermatol 111: 1020, 1975.
Inr J Gynecol Obstet 35
22 23 24
Tay, CH: Pyoderma gangrenosum and leukemia. Arch Dermatol 108: 580, 1973. Work BA, Jr: Pyoderma gangrenosum of the perineum. Obstet Gynecol 102: 231, 1980. Wyrick WF, Mader JT, Butler ME, Hutlet WH: Hyperbaric oxygen treatment of pyoderma gangrenosum. Arch Dermatol 114: 1232, 1978.
Address for reprints: B. L&in Department of Dermatology Bowman Gray School of Medicine 300 South Hawthorne Road Winston-Salem, NC 27103, USA
