A case of disseminated nocardiosis with orbital apex involvement and endophthalmitis

ABSTRACT

Nocardia is a rare cause of ocular infections and most commonly occurs secondary to trauma. Systemic Nocardiosis may have ocular involvement in rare cases. We report a case of disseminated nocardiosis with orbital apex involvement and endophthalmitis in an immunocompromised patient. The patient presented with respiratory sepsis, and later developed complete ptosis and ophthalmoplegia in the left eye. This was on the background of treatment with high-dose prednisolone. Magnetic resonance imaging showed enhancement of the entire clivus, extending into the left orbital apex and cavernous sinus. The patient was initially treated empirically for CNS tuberculosis. Bronchoscopic cultures returned positive for Nocardia farcinica, and the patient was treated with trimethoprim/sulfamethoxazole and weaned off previous corticosteroids.

KEYWORDS:

• Nocardia
• orbital apex
• case report
• disseminated Nocardia
• ophthalmology

Nocardia, an aerobic, gram-positive filamentous bacteria,¹ is a rare cause of ocular infections. Reported ocular manifestations include keratitis and rarely scleritis, conjunctivitis, orbital cellulitis and endophthalmitis, often secondary to eye trauma.^2,3 Orbital apex involvement secondary to systemic nocardiosis has not been previously described. We present a case of orbital apex syndrome and endophthalmitis secondary to disseminated Nocardia. The collection and evaluation of protected patient health information were HIPAA compliant and this report adhered to the ethical principles outlined in the Declaration of Helsinki as amended in 2013.

Case presentation

A man in his 60s visiting from India presented to hospital with respiratory sepsis. During hospitalisation, he developed left eye symptoms with complete ptosis in the left eye and total ophthalmoplegia. Best corrected visual acuity was initially 6/60 in the left eye and progressed to HM in 1 week, compared to 6/18 in the right eye. Fundus examination was consistent with bilateral vitritis (L>R), bilateral chorioretinitis and progressive outer retinal necrosis (Figure 1). Corneal sensation was absent in the left eye. The patient underwent a vitreous tap with subsequent cultures showing no growth. MRI demonstrated multiple intraparenchymal abscesses and bilateral dural enhancement of the entire clivus and sphenoid bone, extending into the left orbital apex and left cavernous sinus (Figure 2). The dural enhancement is likely secondary to clivus osteomyelitis with secondary involvement of the orbital apex and cavernous sinus. In addition, in his most recent scan, there was evidence of abnormal thickening and enhancement of the left optic nerve sheath with adjacent intraconal inflammatory fat stranding and hazy enhancement. There was also evidence of enhancement in the interpeduncular cistern. This is consistent with spread of infection along the pachymeninges of the left optic nerve and cisternal portion of the oculomotor nerve.

Figure 1. Fundus photograph showing bilateral chorioretinitis and progressive outer retinal necrosis.

Figure 2. Magnetic resonance imaging of the brain showing (A) optic perineuritis, (B) skull base osteomyelitis, (C) tuberculum and sphenoid planum and (D) cerebral lesions.

This was on the background of presenting to the hospital five months prior with a one-month history of diplopia and right eye ptosis. In his first presentation, examination was consistent with right trochlear and abducens palsy. The left eye had a normal examination and visual acuity was 6/9 + 2. The anterior and posterior segment exam were normal bilaterally with no evidence of chorioretinitis or retinal necrosis. Magnetic resonance imaging (MRI) brain showed dural enhancement and subtle marrow signal abnormality about the central skull base. There was a right orbital apex/cavernous sinus lesion and left zygomatic arch lesion. This was performed prior to a lumbar puncture. Screening computed tomography (CT) scan of the chest showed multiple pulmonary nodules, of which some had calcification. Lumbar puncture and bronchoscopy were performed and showed no growth of mycobacteria, Nocardia or fungi after 14 days. The patient subsequently returned to India where he had a brain MRI which again showed right orbital apex lesion and left zygomatic arch lesion. The lumbar puncture in India showed no growth on culture and the patient was therefore given a presumptive diagnosis of neurosarcoidosis and commenced on high dose prednisolone.

Given his recent travel history and immunosuppression, he was initially treated empirically for CNS tuberculosis with levofloxacin 750 mg daily, rifampicin 900 mg daily, isoniazid 300 mg daily, ethambutol 800 mg daily, pyrazinamide 1250 mg daily and pyridoxine supplement. Quantiferon Gold was negative. Lumbar puncture was also negative for Acid-Fast Bacillus or Ziehl-Neeson staining, and cultures demonstrated no growth, therefore decreasing the likelihood of this presentation being due to disseminated tuberculosis. Subsequent repeat bronchoalveolar lavage was positive for Nocardia farcinica and the treatment regime was adjusted accordingly. He was initially treated with trimethoprim/sulfamethoxazole 320 mg/1600 mg TDS, linezolid 600 mg BD and meropenem IV 2 g TDS pending sensitivities, followed by trimethoprim/sulfamethoxazole 320 mg/1600 mg BD and meropenem IV 2 g TDS from for 6 weeks total as induction phase therapy. He was then subsequently switched to trimethoprim/sulfamethoxazole 320 mg/1600 mg BD for a minimum of 18 months and weaned off the previous corticosteroids.

On three-month follow up, the visual acuity in his right eye improved to 6/7.5 and was hand movements in the left eye. The patient had no new symptoms and did not complain of any ocular pain. Fundus examination revealed improvement of the chorioretinitis, and a pale left optic disc (Figure 3). There was no evidence of new chorioretinal lesions. MRI showed tiny enhancing foci throughout, however they were significantly fewer and smaller than previous. CT chest showed stable lung changes from the previous diagnostic CT.

Figure 3. Fundus photograph showing improvement of the chorioretinitis and a pale left optic disc following treatment of Nocardia.

Discussion

Ocular infection from Nocardia is usually secondary to trauma. Ocular manifestations of Nocardia secondary to trauma include endophthalmitis, ophthalmoplegia and orbital cellulitis.^4–7 Other rarer predisposing factors include surgery, topical corticosteroid use and contact lens wear.³ Steroid use alone or in combination with other immunosuppressants has been reported in over 70% of patients. Rarely, ocular infection can occur due to systemic Nocardiosis. There are some previous case reports on ocular involvement from disseminated Nocardiosis.^8–10 There are also two previous case reports presenting clivus osteomyelitis from a nocardia infection.^11,12 To the best for our knowledge, our case is the first case of clivus/sphenoid osteomyelitis from systemic disseminated Nocardiosis with secondary involvement of the orbital apex.

Disseminated Nocardiosis typically occurs in patients who are deficient in T-cell mediated immunity. Patients at greatest risk are those with impaired local pulmonary defence mechanisms or systemic immunosuppression. These include patients on long-term corticosteroids, those with cancer, organ, or bone marrow transplantation or patients with chronic infections such as HIV or tuberculosis.¹³ In our case, a predisposing factor for the nocardiosis was the immunosuppression from the use of high dose of prednisolone due to the patient’s provisional diagnosis of neurosarcoidosis five months prior to presentation. This is thought to have accounted for extension of infection from the central skull base to the orbital apex. An observational study found that the most common underlying immunocompromising condition for the development of nocardiosis was the use of high-dose corticosteroids for at least three weeks prior to the presentation.¹⁴ Corticosteroids are known to suppress T-cell function, which is a risk factor of nocardiosis. In addition, the patient also had a history of insulin dependent diabetes which may also be associated with impaired immune response.

Ocular Nocardia patients are often misdiagnosed on initial presentation as Nocardia is a slow growing microorganism and may require prolonged incubation of up to three weeks to isolate the organism.¹⁵ Diagnosis of Nocardiosis occurs through identification of Nocardia species in the tissue or in culture of samples from the localised lesions identified through examination or imaging.¹⁶ In our case, diagnosis occurred through a bronchoalveolar lavage. The Centers for Disease Control and Prevention recommends holding routine cultures for at least 14 days if a Nocardia infection is suspected.¹⁷ This is especially necessary if a patient presents with evidence of systemic infection, as in our case. Approximately 50% of patients with endogenous Nocardia present due to ocular involvement.⁸

Appropriate antibiotic therapy is important to treat Nocardia infections. In our case, triple therapy of trimethoprim-sulfamethoxazole, linezolid and meropenem was initially started for the systemic infection. Intravitreal moxifloxacin injections were used for both eyes. The patient was also weaned off previous corticosteroids. There was a good response to treatment in the right eye with an improvement in visual acuity. The left eye chorioretinal lesions appearance remained unchanged, however the visual acuity remained at hand movements likely due to optic neuropathy from the orbital apex lesions. Visual prognosis is often poor in Nocardia patients presenting with ocular symptoms, and approximately 30% of patients undergo ophthalmectomy.^8–10 Early diagnosis of ocular nocardiosis and prompt treatment may improve visual outcomes.

In conclusion, we present a case of orbital apex involvement from disseminated nocardiosis in an immunocompromised patient. Immunocompromised patients are at an increased risk of presenting with atypical infections such as Nocardia, which need to be specifically cultured for. Patients who are suspected to have disseminated nocardiosis should undergo early ophthalmic screening.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.