An uncommon case of brucellosis with ocular presentation

We report an unusual case of brucellosis presented with headache, diminished vision, papillitis and multiple peripapillary hemorrhages accompanied by subretinal fluid extending up to macula. Diagnosis of brucellosis was made based on positive polymerase chain reaction of cerebrospinal fluid sample for Brucella species DNA, accompanied by a raised titer of anti-brucella antibodies. Patient showed remarkable improvement on triple drug therapy in form of doxycycline, rifampicin and ceftriaxone.


INTRODUCTION
Brucellosis (Malta fever) is the most common zoonosis disease that affects people at any age group. Despite the reduction in the prevalence of brucellosis, it still remains an important health problem in endemic areas such as the Middle East, Mediterranean and South America.
Brucella is an intracellular Gram-negative aerobic coccobacilli that is transmitted by consumption of uncooked meat or unpasteurized dairy products, especially involving reticuloendothelial cells. (1) Ocular involvement is a rare but serious complication of brucellosis. It can appear during the active phase of disease or later. (2) Ophthalmic signs are unusual and include red eye, ocular pain, and diminished visual acuity due to optic neuritis, retinal vasculitis and preretinal hemorrhage. (3) We hereby report a patient with bilateral optic neuropathy secondary to brucellosis.

CASE REPORT
A 66 year-old female patient presented to the ophthalmology clinic of the Shahid Sadoughi Hospital (Yazd, Iran) with a chief complaint of decreased vision in both eyes with onset one week before, associated with severe headache. Best corrected visual acuity (BCVA) in the right eye was counting finger (CF) at 50cm and in the left eye was CF at 1m. Ocular motility was in full range and painless. Pupillary reflexes were considerably reduced in both eyes. Anterior segment examination revealed no abnormality, except for early cataract in both eyes. Intraocular pressure (IOP) was in normal range in both eyes. Posterior segment examination revealed optic nerve head swelling and hyperemia with blurred margins (papillitis), and multiple peripapillary flame-shaped hemorrhages (Figures 1  and 2), accompanied by subretinal fluid extending up to macula in both eyes in optical coherence tomography imaging of macula (Figures 3 and 4).
Fluorescein angiography showed vascular leakage and staining of vessels and hyperfluorescence of the optic disc in both eyes ( Figure 5 and 6). The patient underwent brain magnetic resonance imaging, which was normal. Hematology test showed leukocytosis (10,700WBCs). Because of severe headache and diminished vision, the patient underwent lumbar puncture (LP) test. The cerebrospinal fluid (CSF) analysis revealed clear fluid, intracranial pressure (ICP) of 17cmH2O, and glucose of 58mg/ dL, LDH of 40IU/L, and 320 WBCs with 90% of lymphocytes. Polymerase chain reaction (PCR) of CSF sample for Brucella species DNA was strongly positive. ELISA test   for anti-toxoplasmosis antibody titer and PPD tests were negative.
Patient was hospitalized with diagnosis of brucellosis and treated with systemic antibiotics of ceftriaxone 2g intravenous BID, rifampin 300mg TDS and doxycycline 100mg BID for 1 month. After 1 month of systemic antibiotic therapy, the Wright tube test, Coombs Wright, and 2-mercaptoethanol (2ME) test became negative. After 1 month of treatment, LP was repeated, and the CSF analysis revealed decrease in leukocytes (79WBCs): also, PCR test of CSF sample for Brucella species DNA became negative. Peripapillary hemorrhages and subretinal fluid were completely absorbed, and optic nerve head congestion decreased after treatment. The visual acuity of patient was improved to 20/400 in the right eye and 20/200 in the left eye.
After discharge, the patient was asked for authorization to use her illness data for academic purposes and she signed an informed consent.

DISCUSSION
Brucellosis is an infectious disease that may affect any parts of the body. The four species that are pathogenic for humans are Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis. Hosts are usually cows, camels, sheep and goats. Brucella melitensis is the most common and virulent species.
Brucellosis is a chronic granulomatous disease with systemic presentations, including back pain, headache, fatigue, fever, loss of appetite, muscular pain, perspiration, weight loss, arthralgia, cough, neural signs, abdominal pain, diarrhea, and constipation. Serum agglutination, ELISA and blood culture are used to confirm the diagnosis of brucellosis. (4) Recently, Guven et al. diagnosed neurobrucellosis because of the presence of one of the following criteria: symptoms and signs suspect of neurobrucellosis, isolation of Brucella species from CSF and/or presence of anti-Brucella antibodies in the CSF, presence of lymphocytosis, increased protein, and decreased glucose levels in the CSF, or findings in magnetic resonance imaging or computed tomography. (5) Cerebrospinal fluid culture, when positive, is considered the gold standard in laboratory diagnosis of neurobrucellosis. However, serological approaches are the mainstay in the diagnosis of neurobrucellosis due to the relatively lower efficacy of bacterial culture. (6) Although ocular involvement is uncommon in brucellosis and mostly observed in patients with chronic brucellosis, any ocular structure may be involved, including keratitis, uveitis, choroiditis, episcleritis, endophthalmitis, dacryoadenitis, and optic neuropathy. (7) Optic nerve involvement, including optic neuritis and papilledema, has been described in about 10% of patients with ocular brucellosis. (8,9) It seems that optic neuropathy in brucellosis is secondary to meningeal inflammation (neurobrucellosis) and subsequent axonal degeneration. Ischemic, vasculitic, and immune-mediated mechanisms have also been suggested.
The visual prognosis of brucella-related optic neuropathy is usually good after an appropriate course of   antibiotic and steroid therapy. However, severe cases with permanent visual impairment have been described. (10) In 2005, Lashay reported a young female case of brucellosis with severe visual loss, diplopia, bilateral optic nerve swelling, subhyaloid hemorrhage, and retinal vasculitis. Clinical and ocular findings, except for optic disc atrophy, improved within 3 months after anti-brucella treatment. (3) In summary, brucellosis may cause various systemic and ocular complications, including vasculitis, optic neuritis and retinal hemorrhage. There are no specific diagnostic features that may suggest ocular involvement caused by brucellosis. Therefore, ocular brucellosis must always be considered in endemic areas. A detailed ocular examination, including fundoscopy, should be performed in all patients with a diagnosis of systemic brucellosis, particularly in endemic areas. This could minimize the risk of blindness associated with brucellosis.