| Abstract|| |
Pyoderma gangrenosum (PG) is an ulcerative disease of the skin of unknown etiology. Its association with infection, autoimmune disease, inflammatory bowel disease, malignancy, and certain drugs suggests a hypersensitivity reaction. We herewith present a renal transplant recipient who developed PG. The patient presented with multiple necrotizing skin ulcers on both the upper and lower extremities associated with malaise, myalgia, arthralgia, weight loss and low-grade fever. To our knowledge, the association between PG and renal transplant has not been reported previously.
Keywords: Renal transplant, Pyoderma gangrenosum, Multiple necrotizing skin ulcer, Subcutaneous nodule, Cytomegalovirus.
|How to cite this article:|
Al-Hwiesh AK. Pyoderma Gangrenosum in a Renal Transplant Recipient: A Case Report. Saudi J Kidney Dis Transpl 2006;17:559-63
| Introduction|| |
Pyoderma gangrenosum (PG) is an ulcerative disease of the skin of unknown etiology. The association of PG with infection, autoimmune disease, inflammatory bowel disease, malignancy, and drugs suggests a hypersensitivity reaction. The initial hypothesis, which has not been supported by experimental data, includes an immune-complex vasculitis, Tcell activation, and altered neutrophil function. It is currently thought that cytokine dysregulation accounts for most of the clinicopathological changes seen in PG.
Among the cytokines involved are interleukin (IL)- 1, IL-3, IL-6, IL-8, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor GMCSF and interferon gamma. ,
The skin lesions of PG may be single or multiple and chronic or recurrent. The lesions occur most commonly on the leg, especially the peritibial area, but can develop in any part of the body. The initial lesion usually begins as follicular erythematous papules or pustules, or inflammatory nodules [Figure - 1]. The lesion then forms an ulcer with a purulent base and a ragged undermined, violaceous gunmetal color border, which spreads peripherally [Figure - 2].
Approximately one-half of cases of PG are associated with underlying systemic disease such as inflammatory bowel disease, arthritis, or lymphoproliferative disorders. ,,, The disease occurs in up to 5% of patients with ulcerative colitis and 2% of those with Crohn's disease.  PG has been described in patients with Sweet's syndrome, Behcet's disease, subcorneal pustulosis, and as a complication of therapy with G-CSF. ,
The occurrence of PG in a renal transplant recipient has not been reported previously. We herewith describe a middle-aged male renal transplant recipient, who developed lesions typical of PG. To our knowledge, this is the first report in the literature of such an association.
| Case History|| |
A 57-year-old Saudi gentleman, a known case of chronic renal failure (CRF) of unknown etiology, underwent a living unrelated donor kidney transplant in India in 1992. His transplanted kidney functioned for six years after which he developed chronic rejection and returned to hemodialysis (HD), performed three times per week, through a left arteriovenous (AVF).
He remained on dialysis for six years after which, in July 2004, he went to Pakistan for a second living unrelated donor kidney transplantation. After transplantation, he experienced multiple rejection episodes. He was treated with pulse steroids and maintained on immunosuppression with cyclosporine A (CyA), mycophenolate mofetil (MMF), oral steroids, along with amlodipine for hypertension. Four weeks prior to presentation at our institution, he developed easy fatigability, low-grade fever, myalgia, arthralgia and active arthritis of the right ankle. He also had multiple painful necrotic skin ulcers on the extensor surfaces of the upper and lower extremities, especially at the peritibial area with subcutaneous nodules. There was sparing of the palms, soles, and mucous membranes. These symptoms were associated with weight loss and loss of appetite. No history of nausea, vomiting, diarrhea, cough, hemoptysis, orthropnea, alopecia, Raynaud's phenomenon, or dryness of the eyes and mouth was elicited. There was no history of recent treatment with antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs).
| Clinical Examination|| |
At presentation, the patient had a blood pressure of 110/70 mm Hg, pulse rate of 90/ min, temperature of 38.5 o C and a respiratory rate of 20/minute. His body weight was 50 kg and height was 165 cm. There were multiple necrotic skin ulcers [Figure - 3] and subcutaneous nodules. Examination of the cardiovascular, nervous and respiratory systems as well as abdominal examination did not reveal any abnormality. The transplanted kidney was palpable and non-tender. The lower limbs showed multiple necrotic skin ulcers. The initial differential diagnosis included Kaposi's sarcoma, PG, paniculitis, T-cell lymphoma, bacillary angiomatosis, and fungoid mycosis.
Laboratory investigations revealed the following: white blood cell count (WBC) of 6x10 9 /L with normal differential, hemoglobin of 70 g/L with a microcytic hypochromic picture, serum sodium of 140 mmol/L, potassium of 4.5 mmol/L, chloride of 111 mmol/L, bicarbonate of 22 mmol/L, blood urea nitrogen of 35 mg/dl, serum creatinine of 3 mg/dl, phosphate of 3 mg/dl, glucose of 110 mg/dl, calcium of 8.1 mg/dl, alkaline phosphatase of 200 U/L, total protein of 7.2 g/dl, serum albumin of 3.3 g/dl and liver enzymes which were within normal limits.
Urinalysis was unremarkable except for mild proteinuria. The thyroid function tests as well as serum and urine protein electrophoresis were within normal limits. The ESR was 120 mm/hour. Bone marrow biopsy and aspiration were normal.
A dermatology opinion was sought and skin biopsy was performed. Histology showed spindle cells and small vessel proliferation with lymphocytic infiltration consistent with PG [Figure - 4]. Due to the active arthritis in the right ankle, an orthopedic opinion was taken and a diagnosis of chronic osteomyelitis was made. Debridement and drainage of the fluid from the right ankle was performed and analysis of the fluid did not show any organisms. Computerized tomographic scans of the chest and pelvis were normal. Endoscopy of the upper and lower gastrointestinal tract was normal. Connective tissue studies that included anti-nuclear antibody (ANA), AntiDNA, C3, C4, CH50, cryoglobulin, anti-Smith antibodies, and Brucella More Details and amoeba antibody titers were normal. Multiple blood and skin cultures were negative. Virology studies for hepatitis B, cytomegalovirus (CMV), and human immunodeficiency virus (HIV) were negative except for positive CMV IgG antibodies.
The patient was started on pulse steroid therapy, which resulted in the dramatic improvement of skin lesions. The serum creatinine decreased to 1.5 mg/dl. The steroid dose was gradually tapered but was followed by a recurrence of the fever, skin ulcers and a subcutaneous nodule several days later. The subcutaneous nodule was re-biopsied and showed small blood vessel proliferation with plump endothelial cells showing intra-cytoplasmic, inter-nuclear inclusions and lymphocytic infiltration [Figure - 5].
The patient's immunochemistry was negative for Kaposi's sarcoma and T-cell lymphoma. Although his CMV blood test was negative for IgM antibodies, the clinical features were suggestive of CMV infection. Meanwhile, tissue culture of the right ankle came was positive for acid-fast bacilli (AFB). Thus, the patient was treated with anti-tuberculous medications as well as with a short course of ganciclovir and showed dramatic improvement.
| Discussion|| |
There are six identified broad disease categories that can cause PG. Vascular occlusive or venous disease, vasculitis, cancer, infection, exogenous tissue injury and other inflammatory disorders should be specifically ruled out before a diagnosis of PG is made. In 1930, Birunstinay et al  of Mayo Clinic described five patients with rapidly progressive, painful, suppurative, cutaneous ulcers with edematous baggy blue undermined and necrotic borders, which they called PG. This condition falls in the spectrum of neutrophilic dermatosis, a group of inflammatory disorders that commonly display a tendency for pathergy (induction of the inflammatory process after skin trauma) and the presence of non-infectious neutrophilic infiltration of the skin.
PG is associated with a number of specific diseases including inflammatory bowel disease, paraproteinemia, arthritis, and myeloproliferative disorders. The pathogenesis of PG is poorly understood. However, neutrophil dysfunction (defect in chemotaxis with hyperreactivity) and over expression of IL-8 2 and IL-16[ 11], have been reported. These observations suggest that PG represents an over reactive inflammatory response to trauma, inflammatory or neoplastic process in susceptible patients.
There may be one or multiple lesions. They commonly occur on the legs, especially in the pretibial area, but can develop in any area of the body including the abdominal wall adjacent to stoma after colectomy. The initial lesion usually begins as a follicular erythematous papule or pustule, an inflammatory nodule or a hemorrhagic bulla with an erythematous base [Figure - 1]. The lesion breaks down to form an ulcer with a purulent base and a ragged, undermined violaceous gunmetal color border, which spreads peripherally. If there are several ulcers, they may coalesce to form a larger ulcer, and heal with an atrophic, pigmented, cribriform scar.
Biopsy of an early lesion of PG demonstrates a dermal neutrophilic abscess. Later stage lesions show epidermal necrosis and ulceration, superficial dermal edema and a dense mixed dermal infiltration that may extend to panniculitis. Histological examination of the advancing, inflamed border reveals dense perivascular lymphatic inflammation, which may at times be associated with vascular destruction. None of these histological features is pathognomonic for PG. No laboratory finding is diagnostic of PG and investigations should focus on identifying associated diseases, if any, and excluding lesions that may simulate PG. The frequency of misdiagnosing PG is approximately 10%.
Treatment directed at PG can itself produce complications or may adversely affect other causes of ulceration. For example, it may promote the progression of infection or lymphoma. It may also result in temporary improvement of disorders such as vasculitis, anti-phospholipid antibody syndrome and lymphoma, and thereby delay the diagnosis of these disorders.
The initial improvement shown by our patient to pulse steroid therapy and the reappearance of the skin lesion and subcutaneous nodule after tapering the steroids, along with the classical histopathologic features, are highly suggestive of PG. Biopsy of the subcutaneous nodule showed inclusion bodies consistent with CMV suggesting that PG can be precipitated by CMV infection, especially in patients who are carriers of CMV and do not receive prophylaxis.
The fact that culture from the right ankle was positive for AFB while those from the other skin ulcers and subcutaneous nodules were negative suggests a super-imposed infection. A Medline literature search by the author did not disclose any report of an association between CMV and PG in renal transplant patients.
In conclusion, we present a middle-aged Saudi male renal transplant recipient who developed multiple necrotic skin ulcers consistent with PG, probably precipitated by CMV infection. To our knowledge, such an association has not been reported previously.
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Abdullah K Al-Hwiesh
Consultant Internist/Nephrologist, Department of Internal Medicine, P.O. Box 40246, Al-Khobar 31952
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]