1

Introduction

Histoplasma capsulatum is a ubiquitous dimorphic fungus found in soil and is endemic to the Midwest United States along the Ohio and Mississippi River valleys. Approximately 90% of systemic infections by H. capsulatum are subclinical and self-limited. Rarely, severe infections may present with acute pulmonary disease or hematogenous dissemination into multiple organ systems, most commonly the liver, spleen, gastrointestinal tract, and bone marrow. Ocular infections are a rare complication of systemic H. capsulatum infection.

H. capsulatum is the alleged causative agent in the presumed ocular histoplasmosis syndrome (POHS) which is on the spectrum of inflammatory choroidopathies. Other less common ocular presentations of histoplasmosis include endophthalmitis, conjunctival granulomas, and chorioretinitis. Infectious scleritis from H. capsulatum is exceedingly rare, with only two unilateral cases documented in the literature. ^, We report a case of bilateral infectious necrotizing scleritis secondary to H. capsulatum after cataract surgery in a patient who is both locally and systemically immunosuppressed.

2

Case report

A 45-year-old Caucasian male with a history of HLA-B27 associated ankylosing spondylitis and anterior uveitis on secukinumab initially presented with progressively worsening vision in both eyes. He is a resident of rural Ohio and works as commercial truck driver. He underwent sequential cataract surgery in both eyes one month apart and was placed on extensive perioperative steroids, including intravitreal triamcinolone, topical prednisolone, and oral prednisone to control his robust inflammatory response. Post-operatively the patient was successfully tapered off of all steroids and remained inactive on secukinumab.

Six weeks after his second cataract surgery the patient presented with mild irritation in both eyes. Ocular examination revealed a visual acuity of 20/30 in his right eye (OD) and 20/50 in his left eye (OS). Examination of the right eye revealed diffuse temporal scleral injection with central whitening, sub-conjunctival purulence, and scleral necrosis ( Fig. 1 A). The left eye revealed similar, but more severe findings ( Fig. 1 B). There was no evidence of intraocular inflammation. Residual triamcinolone could be visualized in the left anterior vitreous. Anterior segment optical coherence tomography of these lesions demonstrated thickening of the temporal sclera with hypoechoic cysts within the sclera ( Fig. 1 C–D).

External photos of the A) right and B) left eye at initial presentation demonstrating temporal sub-conjunctival abscesses and surrounding injection. OCT b-scans through the purulent abscesses of C) right and D) left eye with scleral thickening and hypoechoic cysts. External photos at week 3 (E–F), week 5 (G–H), and month 9 (I–J) after initial presentation of right and left eyes demonstrate resolution of scleritis of both eyes.

The conjunctiva was punctured, and the subconjunctival purulence was cultured from both eyes. He was initially started on oral and topical moxifloxacin. After 3 days there was no growth of the cultures and the patient’s exam remained unchanged. He was started on 50mg oral prednisone. One week later, fungal culture with staining by lactophenol cotton blue of the left eyes revealed tuberculate macroconidium consistent with H. capsulatum , which was confirmed by DNA accuprobe (Hologic, Marlborough, MA). He was initiated on oral itraconazole 200 mg twice daily and fortified topical amphotericin B 0.15% four times daily with a rapid taper of oral prednisone. Chest X-ray was negative for intra-pulmonary nodules suggestive of active pulmonary histoplasmosis. Complete evaluation by an infectious disease specialist was unconcerning for associated disseminated systemic disease. Three days later his right eye grew H. capsulatum . The patient was treated with topical amphotericin for two months until the subconjunctival purulence resolved ( Fig. 1 E–H). The patient is maintained on a six-month course of itraconazole guided by an infectious disease specialist. On most recent follow-up, nine months after presenting with subconjunctival purulence, the patient had a BCVA of 20/30 OD and 20/80 OS without evidence of active scleritis ( Fig. 1 I–J). Visual acuity of the left eye was limited by cystoid macular edema secondary to HLA-B27 iritis.

3

Discussion

Infection is an uncommon cause of scleritis, accounting for only 5–10% of cases. Among the infectious etiologies, the most common cause is Pseudomonas aeruginosa, with mycotic etiologies ranging from 5 to 38% of infectious cases. If a fungal organisms are suspected, cultures should be kept for longer regardless of persistently negative bacterial cultures. Fungal cultures at our institution are kept for 28 days minimum. A review of the literature reveals that there are only two case reports of H.capsulatum scleritis. ^, In both reported cases, unilateral scleritis was described.

In one case, a 47-year-old woman on methotrexate, azathioprine, and oral prednisone for rheumatoid arthritis and dermatomyositis presented with red eye and decreased visual acuity. Exam revealed a purulent and necrotic scleral lesion and she was diagnosed with H. capsulatum scleritis via fungal cultures and PCR. The patient demonstrated marked improvement after 8 days of oral itraconazole. The second case described a 77-year-old man who developed a painless yellow scleral lesion one month after uncomplicated cataract surgery. Notably, he had received a periocular triamcinolone injection for idiopathic vitritis eight months prior to developing scleritis. Similar to the present case, this patient was treated with oral itraconazole and topical amphotericin B 0.15%, but ultimately required surgical debridement due to non-response with extension of the necrosis through Tenon’s capsule and the lateral rectus muscle.

Our case is unique given the bilateral presentation in a patient who underwent cataract surgery months earlier. Our patient was chronically immunosuppressed on secukinumab, a human monoclonal antibody which inhibits IL-17A and is FDA approved for the treatment of alkylosing spondylitis. He also received peri-operative intravitreal triamcinolone in both eyes, as well as post-operative topical and oral steroids to treat his exuberant post-operative inflammation. We hypothesize that the combination of systemic immunosuppression in combination with long-acting local steroids allowed the opportunistic H. capsulatum to thrive in the locally immunosuppressed sclera. The patient has no prior history of H. capsulatum infection, and as such, it is difficult to know if this represents de novo infection versus latent reactivation. Beyond a chest x-ray, no further systemic work-up was pursued as guided by our infectious disease specialist as the patient did not exhibit signs or symptom of disseminated disease. Nonetheless, systemic histoplasmosis has been associated with immunomodulatory therapy in the uveitic population. Starr et al. examined patients on systemic immunosuppression for noninfectious uveitis and the development of disseminated or pulmonary histoplasmosis. They found this population to be at higher risk of developing Histoplasma infections, with nine reported cases of disseminated or pulmonary disease that recovered after systemic antifungals.

Ophthalmologists must be aware that scleritis is a rare manifestation of systemic Histoplasma capsulatum infection and that immunomodulatory therapy appears to be a risk factor for H. capsulatum infection. Additionally, cataract surgery in uveitic patients brings with it a set of unique challenges. The high rates of postoperative inflammation mandates aggressive peri-operative control of inflammation, often achieved with a combination of systemic immune suppression and local steroid therapy. The use of aggressive immunosuppression increases the risk of local infection with both typical and atypical microbes. This report emphasizes the need for careful monitoring of post-operative uveitis patients especially those who are actively managed with systemic and local immunosuppressive therapy.

Patient consent

Consent to publish the case report was not obtained. This report does not contain any personal information that could lead to the identification of the patient.

Financial support

Dr. Deaner is a 2020–2021 Heed Fellow supported by the Heed Ophthalmic Foundation.

Disclosures

None of the authors have disclosures related to the submitted work.

Dr. Deaner has the following disclosures outside of the submitted work: Alimera Sciences, Inc: Honoraria. Dr. Srivastava has the following disclosures outside of the submitted work: Consultant/Advisory Board: Bausch and Lomb, Allergan, Clearside, Regeneron, Santen, Sanofi, Zeiss, Optos; Research Grants: Bausch and Lomb, Allergan, Novartis, Clearside, Zeiss, Sanofi, Santen; Licensing Royalty: Bioptigen, Synergetics; Grant Funding: Oho Department of Development TECH-13-059.

Authorship

All authors attest that they meet the current ICMJE criteria for Authorship.

Funding

All of the sources of funding for the work described in this publication are acknowledged below.