Dermatology Online Journal

Pustular pyoderma gangrenosum: An uncommon variant which is easily misdiagnosed
MW Chia, L Teo, YK Tay, WT Poh
Dermatology Online Journal 14 (2): 21

Division of Dermatology, Changi General Hospital, Singapore, Division of Pathology, Changi General Hospital, Singapore

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Abstract

Pustular pyoderma gangrenosum is a relatively uncommon clinical form of pyoderma gangrenosum; it presents with vesiculo-pustular lesions that do not develop into frank ulceration. We report a case of a 44-year-old man with associated ulcerative colitis, who was misdiagnosed as having necrotizing fasciitis. He underwent multiple debridements and a subsequent skin grafting procedure, but without improvement. The diagnosis of pyoderma gangrenosum is often challenging because there is no defining diagnostic clinical, laboratory, or histopathological feature. A high index of suspicion is, therefore, essential to diagnose pyoderma gangrenosum clinically because failure to do so in the early stages of the disease can lead to disfigurement and even unnecessary and detrimental surgery.

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Clinical synopsis

A 44-year-old man was referred to the dermatology department following a breakdown of a split-thickness skin graft (SSG) site. He first presented to his orthopedic surgeon 7 months prior with 3 small ulcers (about 5mm wide) over the left ankle region with surrounding inflammation and erythema. This was diagnosed as an abscess for which the patient underwent wound debridement and saucerization. The patient was started on a course of intravenous cloxacillin and penicillin V. The antibiotics were continued for 1 week because the patient remained pyrexial but a full septic work-up did not reveal any infection and no pathogens were isolated from the tissue specimen. His wound improved and he was discharged from the hospital.

The patient was re-admitted soon after because the wound had progressed. This time, a diagnosis of necrotizing fasciitis was made based on the relentless progression of necrosis in association with pyrexia and constitutional upset. Multiple and extensive debridement and saucerization of the wound followed, and antibiotics re-started. He was given intravenous clindamycin and then vancomycin because he reported to have developed an exanthematous skin rash to penicillin earlier.

Although wound culture isolated Staphylococcus aureus with mixed growth of skin flora, the infectious disease physician's opinion was that of colonization rather than true infection. This was because the wound swab microscopy showed no polymorphs, and the wound appeared clean.

Subsequently, when the left ankle wound was stable, he underwent a split-thickness skin graft involving harvest from the left thigh to the left ankle wound. Although the skin graft site had taken well, the donor site developed areas of necrosis 3-4 weeks post-SSG. Again, wound cultures were negative for bacterial growth. Despite systemic antibiotics with ciprofloxacin for 6 weeks and meticulous wound dressing, the lesion did not improve. The patient was then admitted for a planned surgical debridement. On this occasion, he was referred to the dermatology department.

The patient reported a history of ulcerative colitis which was diagnosed 8 years prior. Since then, he had defaulted treatment and follow-up. His ulcerative colitis was in remission; he had no symptoms of abdominal pain, diarrhea, mucoid or bloody stools. The stool consistency was normal.

On examination, there was crusting and pustules with surrounding violaceous erythema on the donor SSG area (Fig. 1). The recipient site showed a scaly, hyperpigmented plaque with a violaceous border.

Bacterial swabs from these inflammatory pustules revealed neutrophilic pus. The wound culture had mixed growth of skin commensals, and there was no evidence of bacterial infection. Although his inflammatory markers were elevated [his erythrocyte sedimentation rate was 60 mm/h (normal range, 2-10 mm/h) and C-reactive protein was 14.5mg/L (0-6 mg/L)], his full blood count showed normal white cell count with no neutrophilia.

Figure 1	Figure 2
Figure 1. Crusting and pustules with surrounding violaceous erythema on the donor SSG area Figure 2. Photomicrograph of biopsy over the pustular lesion on the left thigh showing a non-specific diffuse, neutrophilic infiltration in the superficial dermis, accompanied by inflammatory cells (hematoxylin-eosin, original magnification x 10).

Figure 3
Figure 3. Marked improvement after systemic steroids was started. This picture was taken 3 days after systemic steroids was started. The pustules have resolved and the crusting and inflammation have significantly reduced.

Histological examination of a biopsy over the pustular lesion on the left thigh (Fig. 2) showed a non-specific diffuse, neutrophilic infiltration in the superficial dermis, accompanied by edema, interspersed lymphocytes, and other inflammatory cells. Mild to moderate perivascular infiltrate of plasma cells and lymphocytes were present throughout the dermis up to the dermo-cutaneous junction. These features were consistent with a neutrophilic dermatosis.

Based on his clinical presentation and the skin biopsy histopathology, a diagnosis of pustular pyoderma gangrenosum (PG) was made. The patient was commenced on prednisolone at a dose of 60mg daily (1mg/kg/day).

There was rapid improvement of the pustular lesion after 3 days (Fig. 3). His inflammatory markers also normalized as his skin improved. He was referred to the gastroenterologist who commenced him on sulfasalazine for treatment of his inflammatory bowel disease. He was subsequently discharged and followed up in the outpatient clinic.

Discussion

We have presented a case of pustular pyoderma gangrenosum associated with ulcerative colitis. This is a rare form of PG. There are four described clinical variants of PG as follows: ulcerative, pustular, bullous, and vegetative. Each variant has distinctive clinical and histopathological features (Table 1), characteristic rates of progression, different disease associations, and often responses to different types of treatment. Usually only one specific type of PG occurs in an individual, but occasionally combinations of different clinical types may occur [1].

The pustular form of PG was first recognized by O'Loughlin and Perry [2] in two patients with acute ulcerative colitis in whom a diffuse pustular eruption developed, but did not progress to ulceration. The pustules were described as being painful and occurred mainly on the extensor extremities and upper trunk during severe exacerbation of colitis and were associated with fever and arthralgia.

Categorizing PG according to its predominant morphologic features is helpful as a guide to the likelihood and type of underlying systemic disease (Table 2). Overall, approximately 50 percent of patients with PG have an associated systemic disease [3]. It has been shown that the majority of patients (>70%) with ulcerative PG will have an associated disease [3] such as inflammatory bowel disease (IBD), rheumatoid arthritis, monoclonal gammopathy, and internal malignancy (particularly myeloproliferative disorders). Pustular PG is most commonly encountered in patients with active IBD, whereas bullous PG has a strong association with underlying myelodysplastic disease and vegetative PG tends not to be associated with systemic diseases [1].

Pustular PG is frequently associated with ulcerative colitis [3], occurring with a frequency of 1-6 percent [4]. The course of pustular PG often parallels the severity of the bowel symptoms [5], occurring especially during exacerbation of colitis. It may be used as a marker of bowel-disease activity, and often improves with treatment of the underlying inflammatory bowel disease [6]. However PG may manifest itself during periods when symptoms of colitis are absent or minimal [7]. Although our patient had ulcerative colitis, his PG developed while he had no bowel symptoms. However, he had defaulted treatment for a long time. A review of his case showed that his stool tested positive for occult blood on a prior admission even though he denied any bowel symptoms. Thus, the patient's lesions corresponded to a period when he was not treated for his inflammatory bowel disease.

The diagnosis of PG is made clinically because no specific histopathologic or immunofluorescent patterns are present [9]. It can be challenging and depends on the recognition of the wide spectrum of clinical features, the presence of systemic disease associations and the exclusion of differentials.

Although the histopathologic features are not diagnostic, a skin biopsy is necessary to exclude other causes of acute skin ulcerations, particularly infections and necrotizing fasciitis [9]. In pustular PG, there are subcorneal neutrophilic accumulation [10], perifollicular neutrophilic infiltration [11], and subepidermal edema with dense dermal neutrophilic infiltrate, indicating a range of changes within the same disease that probably reflect the timing of the biopsy in relation to the evolution of the disease [1].

There are reports where PG is misdiagnosed and treated as necrotizing fasciitis [9, 12]. Although the early lesions of PG often present as pustules or nodules, the initial clinical picture of necrotizing fasciitis resembles cellulitis. The borders of necrotizing fasciitis are usually poorly defined and rapidly progressive over hours (as opposed to PG, which has well-defined violaceous ulcer edge and progresses more slowly over days). Moreover, cultures in PG are often negative with poor response to systemic antibiotics [19]. The most distinctive feature of PG is its rapid and dramatic response to corticosteroids [6]. A high index of suspicion is, therefore, essential to diagnose PG clinically because failure to do so in the early stages of the disease can lead to disfigurement [13] or amputation [9], and even unnecessary and detrimental surgery, as in our case. A case of necrotizing fasciitis that is progressing despite adequate surgical debridement and antibiotic cover should arouse the clinician's suspicion of the possibility of PG.

Up to 25 percent of patients with PG give a history of new lesions developing at the site of trauma (the pathergic phenomenon) [1], as in our patient who developed pustular PG over the donor graft site. The potential for these lesions to arise at sites of surgical trauma, wound debridement and skin grafting may lead to further progression of lesions and even to new lesions at donor sites [14, 15]. Pyoderma gangrenosum after surgery has been previously reported in post-caesarean section wound site [16], as a complication of percutaneous endoscopic gastrectomy tube insertion [17], and after coronary artery bypass grafting [18].

Conclusion

Pustular PG is a relatively uncommon clinical form of PG, presenting with vesiculo-pustular lesions that do not develop into frank ulceration. We have presented one such patient who was misdiagnosed as having necrotizing fasciitis. This resulted in multiple debridements and a subsequent skin grafting procedure for the patient.

Pustular PG should be considered in the differential diagnosis of pustular skin eruption, particularly in the presence of underlying systemic condition such as inflammatory bowel disease. The diagnosis of PG is often challenging as there is no defining diagnostic clinical, laboratory or histopathological feature. We should strongly consider a diagnosis of pyoderma gangrenosum when the morphologic appearance of the lesion is characteristic, there is association with a systemic disease, cultures are negative, results of a skin biopsy is consistent , and the patient fails to respond to antibiotics.

Surgical debridement or grafting are not recommended in the acute stages because this could lead to further tissue destruction and disease progression [16, 10].

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