Pyoderma Gangrenosum of the Eyelid: A Challenging Case

Introduction

Pyoderma gangrenosum (PG) is a rare inflammatory skin disease with an incidence of approximately 6 cases per 1 million people annually in the United Kingdom [1]. It is characterized by the formation of nodules or papules that progress into ulcers with ill-defined borders [2]. The exact etiology of the condition remains unclear, although it is believed to involve immune dysregulation and neutrophilic infiltration of the dermis, leading to tissue destruction [2]. Although PG can occur anywhere on the body, it more frequently affects the lower extremities and trunk [3,4]. It may arise spontaneously or in association with systemic diseases such as inflammatory bowel disease and Behçet’s disease [2]. Ocular PG is extremely rare, and eyelid involvement is even more uncommon. Eyelid involvement in ocular PG presents substantial challenges because it is often misidentified as other conditions, including chalazion, infections, or tumors [5]. Its rarity frequently delays diagnosis and complicates management, which may ultimately result in worse outcomes. Early detection is essential to prevent such complications. Only a few cases of eyelid PG have been reported. Available data regarding its clinical features, diagnostic criteria, and management remain limited. This case underscores the importance of early recognition and prompt treatment to optimize both functional and aesthetic outcomes. Further research is warranted to evaluate different treatment approaches and their effectiveness in eyelid PG.

Case Report

A 29-year-old man who had a known history of ulcerative colitis (UC) presented to the emergency department with a 6-month history of a slowly progressive, painless lesion on his left upper eyelid. The patient had previously been evaluated at another hospital, where the lesion was treated as a chalazion but failed to respond to conventional chalazion therapy. He reported no constitutional symptoms.

On examination, a pinkish-yellow ulcerative lesion with ill-defined borders and central necrosis was noted, distorting the contour of the lid margin. The lesion was soft in consistency and involved most of the upper eyelid while sparing the punctum. It was large enough (approximately 20 mm [horizontal] × 20 mm [vertical]) to cause mechanical ptosis (Figure 1). Systemic examination revealed no palpable lymphadenopathy. A comprehensive ophthalmological evaluation showed no abnormal findings and no signs of orbital involvement. However, the left upper-eyelid mass appeared suspicious, prompting an incisional biopsy to exclude malignant causes.

The patient underwent an extensive systemic evaluation to exclude infectious, vasculitic, and rheumatologic etiologies, all of which yielded negative results. Histopathological examination revealed focal ulceration, acute inflammatory infiltration with neutrophils and eosinophils, and microabscesses, consistent with a diagnosis of PG (Figure 2). Periodic acid-Schiff, Grocott’s methenamine silver, and Gram stain results were negative, excluding bacterial and fungal causes. Histopathological findings also ruled out necrotizing fasciitis, given that the inflammation did not extend into deeper subcutaneous tissues and no microorganisms were identified. Immunohistochemical staining results for CD68 and CD163 were positive, highlighting foamy histiocytes and macrophages. No malignant cells were detected on hematoxylin and eosin staining, ruling out neoplastic causes.

Considering the biopsy results, an intralesional triamcinolone injection was administered 1 week after the initial presentation. At the 1-month follow-up, the lesion showed only minimal reduction in size, without significant clinical improvement. A second intralesional dose of triamcinolone was administered. One month later, inflammatory signs had diminished; however, the response remained suboptimal. Consequently, initiation of biologic immunomodulatory therapy was recommended in collaboration with a gastroenterologist. The patient experienced a concurrent UC flare. The biologic immunomodulator ustekinumab, a humanized monoclonal antibody targeting IL-12- and IL-23-mediated pathways, was selected due to its efficacy in moderate to severe UC. The patient received the first injection of ustekinumab after which a gradual reduction in the eyelid lesion was observed. The lesion then flattened and decreased to approximately 10 mm (horizontal)×3 mm (vertical); it became confined to the medial aspect. At the 3-month follow-up, clinically significant improvement in lesion appearance was noted; only mild hyperkeratosis and tylosis persisted (Figure 3). The patient remained stable without relapses during 1 year of follow-up.

Discussion

PG of the eyelid is an uncommon manifestation compared with PG affecting other body sites. In the available literature, the demographics of patients with ocular PG slightly differ from those of patients with more typical forms of PG. Although PG typically occurs in individuals aged between 27 and 90 years, most reported cases of ocular PG have involved patients older than 60 years [6]. In contrast, the present case involved eyelid PG in a young man.

Only 15 cases (11 articles) have been reported in the literature; they have shown a wide range of clinical presentations and anatomical sites of involvement [7–17]. Our case is similar to previously reported cases in that it was limited to the eyelid. Some other reports have described scleral, corneal, and orbital involvement. Two cases of scleritis have been documented: 1 responded to oral corticosteroids, whereas the other required a combination of oral corticosteroids, cryotherapy, and azathioprine. Peripheral ulcerative keratitis has also been reported in association with PG. Notably, 2 cases resulted in ocular perforation – 1 involving bilateral corneal perforations and another comprising scleromalacia perforans associated with acute myeloid leukemia [8,17–20].

The etiology of eyelid PG remains unclear. Several case reports have linked PG to systemic diseases such as UC, Behçet’s disease, and rheumatologic disorders. A recent large systematic review and meta-analysis by Kilic and colleagues showed that ocular manifestations, including episcleritis, scleritis, and anterior uveitis, are more common in Crohn’s disease than in UC [21]. According to published case reports, eyelid PG appears to occur more frequently in patients with UC than in those with Crohn’s disease. PG-related eyelid involvement has been described only once in a 63-year-old man with recurrent lower-extremity ulcerations and coexisting right upper-eyelid ulceration [22].

Eyelid PG in patients with UC has been described only twice in the literature prior to the present report. The first case involved an 80-year-old woman who developed bilateral eyelid swelling coinciding with a UC flare [10], closely resembling our patient’s clinical course. The second case concerned a 66-year-old man with UC and ankylosing spondylitis who developed a full-thickness eyelid defect after biopsy-induced pathergy [22]. In contrast, our patient did not develop pathergy after the incisional biopsy.

Most eyelid PG lesions are initially misdiagnosed as chalazion, preseptal cellulitis, or eyelid tumors [5]. Saito et al [15] described a 65-year-old Japanese man with a 9-month history of an ulcerative lesion in the right upper eyelid that was initially treated as a chalazion; repeated incision, drainage, and topical antibiotics did not result in improvement. This course parallels that of our patient, who was treated for a presumed chalazion for 6 months without response. We speculate that the incision and drainage procedure contributed to lesion recurrence and persistence.

The diagnosis of eyelid PG lesions is primarily clinical; it is supported by histopathology findings and immunosuppressive therapy response observations [3]. Infectious – bacterial and fungal – and neoplastic causes must be excluded in cases of ulcerative eyelid lesions [5]. This exclusion was achieved in the present case through laboratory testing and histopathologic evaluation.

Management of PG is challenging and usually follows a stepwise approach. Minor lesions may initially be managed with external dressings, followed by intralesional triamcinolone injections, which can provide favorable outcomes when administered promptly. Corticosteroids – either alone or in combination with immunosuppressive agents – represent the mainstay of treatment [9]. In the present case, we administered intralesional triamcinolone as first-line therapy, consistent with previous reports; however, the response was suboptimal.

Habieb et al described a 66-year-old man with UC who exhibited edema and erythema of the right upper eyelid. He was initially treated with systemic corticosteroids and later transitioned to weekly adalimumab to maintain remission [22]. Although management of comorbid conditions can influence PG activity, the severity of PG is not always linked to underlying disease activity [23]. In our patient, ustekinumab was initiated for UC management; this was followed by rapid improvement in the eyelid lesion.

Other immunosuppressants reported for eyelid PG include cyclosporine A, azathioprine, chlorambucil, adalimumab, cyclophosphamide, mycophenolate mofetil, sulfasalazine, and dapsone. In the present case, ustekinumab was selected to induce remission of both UC and eyelid PG, resulting in notable clinical improvement. This therapy has previously been reported to achieve remission in UC-associated PG [24]. To our knowledge, this is the first case to demonstrate the use of ustekinumab for eyelid PG, highlighting its efficacy in patients with concurrent eyelid PG and UC flares.

Regarding treatment outcomes in patients with ocular PG, a notable association has been observed between the anatomical site of involvement and the risk of relapse. Lesions confined to the globe or orbit carry a higher likelihood of recurrence compared with involvement limited to the periorbital region [5]. Consistent with these findings, our patient remained relapse-free during 1 year of follow-up. Accordingly, patients with ocular PG should be promptly referred to ophthalmology, aggressively treated, and closely monitored.

Conclusions

PG is a severe ulcerative condition that can involve the eyelid. Identification of eyelid lesions associated with PG represents a diagnostic challenge for clinicians. A comprehensive assessment – including clinical features, histopathological findings, and lesion response to immunosuppressive therapy – can help establish the diagnosis. Treatment should focus on management of the underlying disease to prevent complications and reduce the need for complex eyelid reconstruction.