Moraxella nonliquefaciens-associated infectious scleritis

Abstract

Infectious scleritis is a rare disease entity with potentially devastating visual sequelae. Here we present the clinical history, work-up and aetiology of an unusual case of infectious scleritis.

Background

This case highlights the importance of considering an infectious diagnosis in a patient with a known inflammatory condition. Infectious scleritis often mimics immune-mediated disease, and it is a pitfall not to rule out infection in these patients. We performed an extensive literature review and, to the best of our knowledge, this is the first reported case of Moraxella-associated infectious scleritis.

Case presentation

A man in his 50s presented to the eye emergency department with a red painful left eye associated with foreign body sensation and marked photophobia. His general practitioner diagnosed conjunctivitis and prescribed topical dexamethasone, neomycin and polymyxin B (maxitrol) four times a day. His medical history was significant for HLA-B27-associated ankylosing spondylitis (AS) diagnosed in 2009 and chronic lymphocytic leukaemia (CLL) diagnosed in 2020. His ocular history was relevant for HLA-B27-associated acute anterior uveitis (AAU), which first presented in 2009. There had been no recurrence of his uveitis since 2017 and he was on no treatment.

On presentation to the eye emergency department, visual acuity in his right eye was 6/5 and left eye 6/24 (pinhole 6/10) best corrected. Slit-lamp examination of his right eye was unremarkable. Examination of the left eye demonstrated upper lid oedema, conjunctival chemosis, fine keratic precipitates, and 3+ cells and 3+ flare in the anterior chamber, as well as posterior synechiae. Intraocular pressure (IOP) of the left eye with Goldmann applanation tonometry was 27 mm Hg. IOP in his right eye was normal. The patient was diagnosed with left eye AAU and was prescribed: guttate (g) prednisolone acetate 1% 1 hourly, g cyclopentolate 1% three times a day, g brinzolamide/timolol two times per day and g chloramphenicol four times a day for his left eye.

Over the next 4 weeks, he visited the emergency department six times, reporting worsening symptoms despite topical therapy and reduced visual acuity (counting fingers left eye). IOP remained elevated and inflammatory activity in the anterior chamber varied but never settled completely. The patient was treated with oral and topical pressure-lowering medication as well as two subconjunctival injections of mydricaine (atropine, epinephrine and procaine hydrochloride) and dexamethasone with the intention of breaking posterior synechiae and reducing inflammation. He continued to use steroids topically, varying in frequency from four times a day to hourly.

He was referred to the outpatient uveitis clinic for consideration of systemic immunosuppressive therapy. On presentation to clinic, his visual acuity was still counting fingers, although he did not report any subjective pain. Slit-lamp examination revealed a diffusely hyperaemic left eye with an infiltrate of 3 mm in diameter and an associated scleral melt on the nasal sclera. He also had active scleritis on the temporal sclera but without ulceration or melting. There was a fibrinous membrane across the pupil and dilatation of the deep scleral vessels (figure 1A, B). Our working diagnosis was infectious scleritis with an associated scleral melt.

Figure 1.

(A, B) Anterior segment photographs of the left eye demonstrating a 3 mm area of scleral melt and infiltrate nasally (A) and a 1.5×1.5 mm infiltrate temporally (B), both associated with marked scleral injection and avascularity.

Investigations

Microbiological scrapes were taken, and serum was tested for infectious and autoimmune causes of scleritis (full blood count, kidney function test, liver function tests, C reactive protein, Quantiferon, venereal disease research laboratory test, antinuclear antibody, antineutrophil cytoplasmic antibody, serum protein electrophoresis, complement). Blood results revealed severe neutropenia (0.2×10⁹/L), high white cell count (47.7×10⁹/L) and lymphocytosis (46.5×10⁹/L), for which he was reviewed by haematology. The scleral scrapes grew Moraxella nonliquefaciens, which was sensitive to ceftazidime and ofloxacin.

Treatment

The patient was commenced on oral ciprofloxacin 500 mg two times per day and topical ofloxacin eye drops hourly while the microbiology results were pending. Following microbiology sensitivity results, the patient remained on ofloxacin and topical ceftazidime drops were added. Topical steroid drops and IOP-lowering medications were discontinued.

Outcome and follow-up

On examination at his next outpatient appointment 1 week later, the infection was clinically improving. However, hypotony was noted with an IOP of 3 mm Hg. We hypothesised that this might be due to inflammation and considered intravenous methylprednisolone, but due to his extremely low neutrophil count (0.1×10⁹/L), this was deemed unsafe owing to risk of sepsis. One week later, the patient continued to improve. IOP increased to 12 mm Hg and a YAG peripheral iridotomy was performed, due to the development of iris bombe secondary to posterior synechiae.

The patient continued to improve with antibiotic treatment alone, and the size of the scleral infiltrate decreased (figure 2A). Two weeks after commencing antibiotic therapy, a 1.2 mm hyphaema was noted in the anterior chamber, as well as fibrin and blood on the pupillary margin. The scleral infiltrate had further reduced in size but the scleral thinning had worsened. Seidel test was negative. Inferior stellate keratic precipitates were present and corneal thinning was evident in the nasal peripheral cornea. The topical antibiotics were reduced to every 2 hours and oral ciprofloxacin 500 mg two times per day was continued.

Figure 2.

(A, B) Anterior segment photographs of the left eye showing resolution of the scleral infiltrate (A), the cataractous lens as well as posterior synechiae covering 360° of the pupil margin resulting in iris bombe (B) and later in the clinical course, the presence of scleromalacia superiorly (C, D).

Six weeks after the start of antibiotic therapy, the infection had resolved and the anterior chamber was quiet. The visual acuity remained counting fingers left eye due to cataract formation and posterior synechiae (figure 2B). IOP was 12 mm Hg. Slit-lamp examination revealed a bluish sheen secondary to significant scleral thinning in the area that was previously ulcerated but also extending beyond to include the entire circumference of the eye, indicative of scleromalacia (figure 2B and D). The patient had also developed a deprivation exotropia.

Discussion

To our knowledge, we present the first reported case of infectious scleritis caused by the gram-negative organism M. nonliquefaciens, a rare subtype of the Moraxella spp. Infectious scleritis is a rare disease entity, and it is a diagnosis often initially overlooked. We present this case to highlight patient-specific aspects that can delay the diagnosis of infectious scleritis and attribute to a more severe course of the disease and worse final visual outcome.

Scleritis, a potentially sight-threatening ocular inflammatory condition, is clinically characterised by inflammation of both the episcleral and scleral tissues and vessels. Other ocular structures, including the cornea and uveal tract, can be involved.¹ The pathogenesis of scleritis has not yet been fully elucidated, although a final common pathway appears to be production of matrix metalloproteinases that propagate scleral tissue destruction.¹ Anatomically, scleritis may be subclassified into anterior scleritis, occurring anterior to the insertion of the rectus muscles and posterior scleritis, involving structures posterior to the rectus muscle insertions. Scleritis may be classified aetiologically as idiopathic, autoimmune or infectious.² While 50% of patients with scleritis have a concurrent systemic autoimmune disease pathology, most commonly rheumatoid arthritis,¹ it is estimated that only 5%–10% of all anterior scleritis cases are infectious. The most common exogenous risk factors for the development of infectious scleritis are ocular surgery (encompassing cataract, vitreoretinal, pterygium, conjunctival lesion excision surgeries and intravitreal injections) and ocular trauma.^2–4

The prognosis of infectious scleritis is poor. Hodson et al reported on 56 patients with a diagnosis of infectious scleritis. They noted that 50% of patients lost functional vision and 15 eyes underwent either evisceration or enucleation.⁴ There are a number of risk factors for poor prognosis, including presenting visual acuity of less than 20/200, scleritis associated with concurrent infection in other ocular structures such as keratitis or endophthalmitis as well as fungal aetiologies.⁵ Pseudomonas aeruginosa is the most common cause of infectious scleritis in Western countries, accounting for approximately 85% of such cases. Other rare microbial causative pathogens of scleritis reported in the literature include Nocardia asteroides⁶ and Stenotrophomonas maltophilia.⁷ Less than five cases of corneal infections secondary to M. nonliquefaciens have been reported in the literature, whereas other subspecies of Moraxella are more common.^8–10 Other than the cornea and conjunctiva, the sclera is covered in two membranes, tenons and the conjunctiva, which attributes to the rarity of infectious scleritis. The Moraxella genus is known to cause a conjunctivitis and keratitis, both with a more persistent course and slower recovery time than other bacterial pathogens. Using DNA sequencing and vancomycin susceptibility, LaCroce et al established both M. nonliquefaciens and M. osloensis as ocular pathogenic organisms.¹⁰ Moraxella spp are commonly present in mucous membranes and normally low virulence. Risk factors for opportunistic infections with Moraxella include an immunocompromised state, alcohol dependency, older age, thyroid disease and diabetes mellitus. Local risk factors include contact lenses, blepharitis, previous eye surgery, ocular trauma and a history of herpetic keratitis.⁸

There are two pertinent patient-specific aspects to this case worth emphasising and discussing further. First, the patient had a diagnosis of CLL and at the time of diagnosis was severely neutropenic. Second, the treatment choices employed were influenced by the fact that the patient had HLA-B27⁺ AS.

The patient initially presented to his general practitioner with symptoms suggestive of conjunctivitis (red eye, lid oedema and foreign body sensation) but also had pain and photophobia, which are atypical of conjunctivitis and more consistent with a diagnosis of AAU. The diagnosis of AAU was confirmed at the eye emergency department following slit-lamp examination. This patient was HLA-B27⁺ and reported several previous flares of AAU, as well as demonstrating objective clinical signs suggestive of AAU, including anterior chamber cells and flare. We believe that the initial diagnosis of AAU was probably correct. We hypothesise that the onset of the infectious scleritis was later than the initial presentation. After a promising initial response to steroid treatment, the patient deteriorated markedly following the subconjunctival steroid injections. There are several reports of infectious scleritis following periocular or intraocular injection, either subtenon or intravitreal^{11 12} and, as mentioned above, one of the major risk factors for infectious scleritis is ocular surgery.¹ The patient’s susceptibility to infection was markedly increased by both local immunosuppression (topical and periocular steroids) but, perhaps more importantly, systemic immunosuppression due to CLL. M. nonliquefaciens is a commensal bacterium to the upper respiratory tract. The source of the infection could therefore be the patient’s own microflora or a nosocomial transfer.⁸

Scleritis in patients with leukaemia has been rarely reported. However, studies by Patel et al and Nachbor and Minkus describe patients with non-infectious scleritis that occurred secondary to leukaemia or as part of a paraneoplastic phenomenon.^{13 14} These reports suggest that these entities should be included in the differential diagnosis of a patient with known leukaemia and scleritis. There is one documented case report in the literature describing scleritis in a patient with CLL.¹⁵ The case presented here demonstrates the importance of microbiological tests in an infectious scleritis work-up.

While HLA-B27 is associated with different types of uveitis, a recent survey presented by Hossain et al shows that only 0.4% of patients with HLA-B27⁺ uveitis had a history of scleritis.¹⁶ Thus, it was highly unlikely that the scleritis was associated with the HLA-B27⁺ status of the patient. We believe that it is more likely that the subsequent treatment with subconjunctival dexamethasone was the inciting event ultimately resulting in the development of infectious scleritis. It is important to evaluate the response to topical steroids during the treatment course and to re-evaluate the differential diagnosis if needed.

The diagnosis of infectious scleritis may pose diagnostic and treatment challenges, often masquerading as an immune-mediated disease. It is important that a prompt diagnosis of infectious scleritis is made, and the causative organism identified, in order to commence timely treatment and negate potentially devastating sight-threatening complications. This case identified M. nonliquefaciens as a cause of infectious scleritis, and in future should be considered in the differential diagnosis of scleritis.

Learning points.

• Infectious scleritis is rare but can lead to devastating visual consequences if missed.

• Re-evaluation of differential diagnoses is required when patients do not improve on steroids.

• A known background of inflammatory disease can obscure infectious conditions.

• It is important to obtain a culture in cases of scleritis that are not responding to corticosteroids and/or antibiotics.

• Ulceration and infiltration of the sclera were highly suggestive of infection. Dual pathology should be considered in patients who demonstrate a suboptimal response to treatment, and do not respond adequately to topical steroids.

Ethics statements

Patient consent for publication

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