Nodular Scleritis and Pyoderma Gangrenosum Associated with Active Ulcerative Colitis: A Case Report Open Access

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) and is characterized by chronic inflammation of the colon. This inflammation can be refractory to treatment, and UC is well known to cause several extraintestinal complications, including ocular symptoms, which occur in 1.6%–5.4% of cases [1]. IBD can cause ocular manifestations, notably episcleritis (2%–5%) and anterior uveitis (0.5%–3.5%), with scleritis being a rare symptom occurring in <1% of cases [1].

Pyoderma gangrenosum is a rare type of neutrophilic dermatosis, with an incidence of 3–10 cases per million people per year globally [2]. Although this condition is sometimes associated with systemic diseases, such as IBD [3], rheumatoid arthritis, and myeloproliferative disorders [2], ocular involvement is rare. Here, we report a rare case of UC in which nodular scleritis and pyoderma gangrenosum developed almost simultaneously, providing insights into the mechanisms underlying the development of nodular scleritis.

A 55-year-old man had been diagnosed with UC 15 years earlier and was undergoing maintenance treatment with oral 5-aminosalicylic acid (5-ASA). Recently, he developed diarrhea and bloody stools, which were additionally treated with a 5-ASA enema. The gastroenterologist was also considering initiating oral steroid therapy. Approximately 2 weeks after the exacerbation of intestinal symptoms, he also developed a painful red eye and experienced decreased visual acuity in his left eye. He was referred to our ophthalmology department for further evaluation and treatment 10 days after the onset of these ocular symptoms.

The patient’s best corrected visual acuity at his initial visit was 20/20 in the right eye and 20/50 in the left eye, with normal intraocular pressure in both eyes. Slit-lamp examination of the left eye revealed scleral hyperemia, peripheral corneal ulcer, anterior chamber cells (2+), and fine keratic precipitates (shown in Fig. 1a). The right eye was unremarkable, and the fundus examination revealed normal findings in both eyes. Based on these findings, a diagnosis of anterior diffuse scleritis with a peripheral corneal ulcer in the left eye was made, and treatment with 0.1% betamethasone eye drops and prednisolone ophthalmic ointment was initiated.

Laboratory tests revealed an elevated C-reactive protein level of 9.9 mg/dL (reference range, 0–0.3) and an erythrocyte sedimentation rate of 64 mm/1 h (reference range, 2–10). The proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA) level was 15.2 IU/mL (reference range, 0–2). Tests for rheumatoid factor, anti-cyclic citrullinated peptide antibodies, myeloperoxidase-ANCA, interferon-gamma release assay, and syphilis were negative. Blood urea nitrogen and serum creatinine levels showed no elevation, and urinalysis findings were unremarkable.

Despite treatment with 0.1% betamethasone eye drops and prednisolone ophthalmic ointment, the patient developed nodular scleritis in the left eye 4 days after initiation of treatment (Fig. 1b). Nodular scleritis developed in the right eye 2 weeks later (shown in Fig. 1c), and multiple painful abscesses appeared on his trunk and head simultaneously (shown in Fig. 2a, b). Skin biopsy revealed diffuse neutrophil infiltration, primarily in the dermis (shown in Fig. 2c, d). Based on the clinical course and histopathological findings, a diagnosis of pyoderma gangrenosum was made by a dermatologist. Lower gastrointestinal endoscopy confirmed active UC (shown in Fig. 3).

Contrast-enhanced computed tomography from the head to the pelvis revealed no signs of vasculitis. Although UC is a common underlying condition associated with pyoderma gangrenosum, ANCA-associated vasculitis is rare. Moreover, elevated PR3-ANCA levels are frequently observed in patients with UC [4]. Based on these findings – and the fact that the patient did not meet the diagnostic criteria for ANCA-associated vasculitis – the rheumatologist concluded that the elevated PR3-ANCA level in this case was associated with active UC. A diagnosis of simultaneous onset of bilateral nodular scleritis and pyoderma gangrenosum during an active phase of UC was made after ruling out other potential causes of scleritis and systemic disease.

Oral steroid therapy (35 mg/day of prednisolone) was initiated 20 days after the initial visit, as the nodular scleritis did not respond to steroid eye drops. This resulted in improvement of both scleritis and pyoderma gangrenosum, and clinical remission of UC was achieved. Oral steroids were tapered and discontinued over a period of 9 months, followed by an additional 18 months of observation, during which no recurrence of skin or ocular symptoms (shown in Fig. 4) was observed. After initiating oral steroid therapy, topical steroid eye drops were continued but gradually tapered as the scleritis improved. Betamethasone 0.1% eye drops were maintained at a low frequency to prevent recurrence and were discontinued 9 months after cessation of oral steroids. Clobetasol propionate 0.05% ointment was used as adjunctive therapy for pyoderma gangrenosum and was stopped 2 months after discontinuing oral steroids. During the follow-up period, oral 5-ASA therapy was continued for UC. One week after starting oral steroids, the visual acuity in the left eye improved from 20/50 at presentation to 20/17 and remained stable thereafter. The visual acuity in the right eye was good from the initial visit and measured 20/17 at the final follow-up.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546828).

The most common systemic diseases associated with scleritis include rheumatoid arthritis, ANCA-associated vasculitis, and relapsing polychondritis [5]. Although the present case exhibited elevated PR3-ANCA, ANCA-associated vasculitis was ruled out through systemic evaluation. Elevated PR3-ANCA is reportedly a feature of UC in 31.1% of cases, particularly affecting patients with extraintestinal complications [4]. Thus, elevated PR3-ANCA observed here was concluded to be associated with the active phase of UC. ANCA testing is commonly performed during the evaluation of uveitis and scleritis; however, in patients with coexisting UC, elevated PR3-ANCA levels should be interpreted with caution.

Scleritis is rare in both UC and pyoderma gangrenosum. The incidence of scleritis in patients with IBD is <1% [1], and scleritis associated with pyoderma gangrenosum has been reported only in a few case studies [6‒9], with its incidence remaining unknown. Although pyoderma gangrenosum occurs in 0.75%–1.5% of patients with IBD [3], it is a rare disease in the general population, which may partly explain the limited number of reported scleritis cases. In UC, a case of pyoderma gangrenosum associated with necrotizing scleritis has been described [8]; however, to the best of our knowledge, no case of pyoderma gangrenosum with nodular scleritis in a patient with UC has been reported. Thus, the coexistence of UC, pyoderma gangrenosum, and scleritis is rare, and the frequency of their simultaneous occurrence remains unknown.

Peripheral corneal ulceration, which was also observed in the present case, has been reported as the most common ocular manifestation of pyoderma gangrenosum [2]. Additionally, Hida et al. [8] described a patient with UC in whom pyoderma gangrenosum and necrotizing scleritis developed simultaneously [8]; similarly, in our case, pyoderma gangrenosum and nodular scleritis occurred concurrently. Braun et al. [6] reported that histopathological analysis of a scleral nodule in a patient with pyoderma gangrenosum revealed inflammatory cell infiltration, with or without abscess formation – findings consistent with pyoderma gangrenosum. Based on these reports, we believe that our case represents nodular scleritis associated with pyoderma gangrenosum.

Five-ASA is the first-line therapy for inducing and maintaining remission in mild-to-moderate UC, whereas moderate to severe cases may require advanced therapies targeting specific inflammatory pathways, including anti-TNF agents [10]. Corticosteroids (topical and/or systemic) are the first-line treatment for pyoderma gangrenosum associated with UC, and anti-TNF agents should be considered if a rapid response to corticosteroids is not achieved [11]. Ocular inflammation related to UC is typically treated with topical or systemic corticosteroids or nonsteroidal anti-inflammatory drugs, with immunosuppressive or anti-TNF agents reserved for refractory cases [11]. In the present case, the patient developed scleritis and pyoderma gangrenosum associated with underlying UC, and the disease activity of UC was initially considered to be poorly controlled. Following induction therapy with systemic corticosteroids, the use of biologic agents was considered in case the UC or extraintestinal manifestations became unmanageable. However, as both intestinal and extraintestinal symptoms achieved remission with systemic corticosteroids, maintenance therapy with oral 5-ASA was continued. Biologic agents will be considered in the future if extraintestinal manifestations recur or if UC disease activity worsens despite ongoing oral 5-ASA therapy.

In conclusion, this rare case of UC complicated by nodular scleritis and pyoderma gangrenosum highlights the importance of examining the history of systemic disease and confirming systemic symptoms, including skin manifestations, to identify the causative disease in cases of scleritis.

This study was approved by the Research Ethics Committee of the Graduate School of Medicine and Faculty of Medicine at the University of Tokyo, Approval No. 2217. Written informed consent was obtained from the patient for publication of the details of this medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Kazuki Yashiro: writing – original draft. Sozaburo Ihara and Hikari Boki: investigation, writing – review and editing. Amane Yamamoto: investigation and writing – review and editing. Rie Tanaka: conceptualization, investigation, and writing – review and editing, and supervision.

All data analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.