Genital Ulcerative Pyoderma Gangrenosum in Behçet's Disease: A Case Report and Review of the Literature.

Behçet's disease (BD), first described by Hulusi Behcet, is a multisystemic disease characterized by recurrent oral and genital ulcerations, ocular and cutaneous lesions, arthritis and vascular disease. Pyoderma gangrenosum (PG) is a rare, chronic, sterile pustular and progressive ulcerative process of unknown cause; sometimes can participate in the differential diagnosis of Behcet's ulceration. A 33-year-old woman complained a severe genital ulcer. She had a purulent oozing and stinky ulceration on the right side of labium minor measuring 5-8 cm. A punch biopsy at ulcer margin showed that the lymphocytic panniculitis was extending to the subcutaneous fat tissue without fibrin deposition or necrotic changes in the vessel wall. Based on the clinical and histological findings, she was diagnosed as genital ulcerative PG, which occurred during the exacerbation of BD.

What was known?

50% of pyoderma gangrenosum cases are associated with an underlying systemic illness, in particular inflammatory bowel disease such as ulcerative colitis or Crohn disease, arthritis, monoclonal gammopathy, malignancy, myeloproliferative disorder.

Introduction

Behcet's disease (BD) was described by Hulusi Behçet as a complex of multisystem disease characterized. Although oral ulceration, genital ulceration and eye disease are the classic triad of manifestations, the cardiovascular, gastrointestinal, musculoskeletal and central nervous systems can also be affected. The presence of skin reactivity to needle trauma and erythema nodosum are particularly helpful findings.[1] On the other hand, pyoderma gangrenosum (PG) is a rare, chronic, sterile, pustular and progressive ulcerative process with unknown cause.[2] Its clinical appearance is a characteristic burrowing ulcer. Approximately, 50% of the cases are associated with an underlying systemic illness, in particular inflammatory bowel disease such as ulcerative colitis or Crohn disease, arthritis, monoclonal gammopathy, malignancy, myeloproliferative disorder[3] and rarely Behçet's disease.[4] Four clinical and histological variants have been recognized: Ulcerative, pustular, bullous and vegetative. There are confusing cases involving the diagnosis of BD and PG in the literature. We report here a case of BD who had genital ulcerative PG afterwards.

Case Report

A 33-year-old woman complained of severe genital ulcer in January 2012. On admission, the patient had painful ulcer on the genital area for the past 10 days with purulent discharge [Figure 1]. She was diagnosed as BD based on criteria of International study group[1] by the presence of pathergy together with oral and genital ulcers in 2004 and treated with colchicine 0.5 mg orally 3 times/day. In 2009, she had diplopia as a result of neurological manifestations of BD and was successfully treated with systemic steroids. There was no evidence for a systemic disease or malignancy. Her family history was positive for BD.

Figure 1

The purulent oozing and stinky ulceration on the right side of labium minor measuring 5-8 cm

On dermatological examination; she had a purulent oozing and stinky ulceration on the right side of labium minor measuring 5-8 cm. There was no lymphadenopathy. Repeated smears and cultures for bacteria and fungi were negative. Physical examination revealed no systemic involvement. On laboratory examination increased erythrocyte sedimentation rate, white blood cell count and C-reactive protein (CRP); with anemia were detected. The X-ray imaging of the chest was normal. The punch biopsy of ulcer margin showed the lymphocytic panniculitis, which was extending to the subcutaneous fat tissue without fibrin deposition or necrotic changes in the vessel wall [Figures 2 and 3]. The patient of erythrocyte sedimentation rate and CRP levels were higher and she had three oral ulcers. Although the histological findings are not very typical for PG, based on the clinical and histological findings, our case was diagnosed as genital ulcerative PG, which occurred during the exacerbation of BD. Ulcer markedly improved and healed with scarring after oral prednisolone therapy with 20 mg/day for 8 weeks together with topical sucralfate and mometasone furoate therapy [Figure 4].

Figure 2

The histopathological image stained with hematoxylin eosin X10 magnification

Figure 3

The histopathological image stained with hematoxylin eosin X400 magnification

Figure 4

The patients lesion healed with scar

Discussion

Since, the first report by Munro and Cox in 1988[5] 13 cases of PG associated with BD have been reported in the literature[67891011121314151617] [Table 1]. Both BD and PG belong to the category of the neutrophilic dermatoses, in which primary pustular lesions occur and neither of them has a characteristic histological appearance. Oral and genital ulcerative lesions can be observed in both diseases.[4] On the other hand, the frequency of the mucosal ulcers is absolutely different between two diseases. Orogenital ulcers are commonly seen in BD, whereas rarely seen in PG.[5] In BD, oral ulcers tend to be small and round, with well-circumscribed margins, erythematous halo and yellow-grey floor. The lesions resemble those seen with a recurrent aphthous stomatitis. Genital ulcers are similar in appearance to oral ulcers and can sometimes cause scar formation.[6] Pustular lesions can be the initial skin manifestation and skin hyperreactivity or pathergy is often found in both diseases. In PG, the ulcers of the genital mucosa appear similar to those skin, which are comprised of a shallow burrowing ulcers with irregular margins and a ragged purple overhanging edges.[2] Rapid local destruction may occur in PG.[7] Thus, the clinical features of mucosal ulcers are different to some degree between the two diseases. However, there is a histopathological distinction between PG and BD.[18] In PG, vascular involvement ranges from none to fibroid necrosis, and in most cases a neutrophilic infiltrate is present with limited vascular damage. Conversely, in BD, mononuclear cell vasculitis with variable fibrin deposition or leukocytoclastic vasculitis is usually found.

Table 1

The reported cases of Behçet's disease with pyoderma gangrenosum

According to the clinical appearance, the rate of progression, the associated systemic disease and the histopathological changes, PG has been classified into four clinical variants: As ulcerative, pustular, bullous and vegetative.[3] Our case had vegetative types of PG. Vegetative form of PG is a limited, non-aggressive, chronic and superficial variant, which is also termed superficial granulomatous pyoderma. Unlike classic PG, many patients with vegetative PG do not have an associated systemic disease. However, Langan and Powell reported that 18% of patients had other medical conditions, including diabetes mellitus, rheumatoid arthritis, chronic lymphocytic leukemia, polycythemia rubra vera, paraproteinemia and pulmonary sarcoidosis.[19] There is a clinical and histological overlap between PG and BD.[45] Skin lesions of PG and BD may show similar range of histological appearances, including a neutrophilic vascular reaction. In our case, there were not any necrotic changes with fibrinoid material in the vessel wall in favor of PG.

Glucocorticoids, sulfa-drugs, dapsone and immunosuppressive agents, such as cyclosporine, azathioprine or cyclophosphamide are therapeutic agents used to treat both PG and BD.

In the present case, genital ulcerative PG developed concurrently with an exacerbation of BD. Therefore, this clinical course accepted as the overlap of PG and BD. In this report, our patient had been diagnosed with BD before and she had ulceration of the labia minora and major afterwards. The genital ulcers appeared as large burrowing ulcers, which were characteristic of PG. This finding suggested that our case might be PG. We reported the second case of PG in the literature, showing mucosal ulcers, which were difficult to distinguish from BD at the first medical examination.

What is new?

Pyoderma gangrenosum(PG) is rarely associated with Behçet's disease (BD). PG and BD may overlap.