A 50-year-old male with no past medical history presented to the hospital with one week of painless blurry vision of the right eye. He had also been having intermittent fevers, headache, body aches, and a nonpruritic maculopapular rash on the bilateral lower extremities for 6 months. On further review of systems, the patient noted one isolated episode of left knee swelling as well as testicular swelling in the past. The patient otherwise denied any neck stiffness, nausea, vomiting, Raynaud's phenomenon, oral ulcerations, chest pain, shortness of breath, abdominal pain, or photosensitivity. He worked as a flooring installer, and he did not have any toxic habits such as smoking, drinking, or illicit drug use.
The patient's vital signs were normal. On physical exam, the patient was found to have bilateral papilledema and optic nerve erythema, right greater than left, right inferior nasal quadrant visual field defect, and a right afferent pupillary defect. Muscle strength was 5/5 throughout, and reflexes were 2+ throughout. Sensation to light touch, pinprick, vibration, and proprioception was intact. The bilateral lower extremities demonstrated a maculopapular rash (Figure 1).
The admitting labs were notable for a microcytic anemia (Hb 11.6 gm/dL (ref 13.6-17.3); Hct 35.3% (ref 39.8-50.7); MCV 76.9 fL (ref 80.3-98.1)), hyponatremia (133 mmol/L (ref 136-144)), elevated ESR (33 mm/hr (ref 0-15)), and elevated CRP (13.3 mg/L (ref 0.0-7.0)). Urinalysis did not show protein or blood. Lumbar puncture was colorless/clear with 2/cumm RBC (ref 0), 56/cumm WBC (ref 0-9), 39% segmented neutrophils (ref 0-2), 53% lymphocytes (ref 40-80%), 30 glucose (ref 40-70), 69 protein (ref 15-45), with presence of oligoclonal bands, an elevated IgG index (+19.8 mg/24 hr (ref -9.9 to +3.3)), and normal opening pressure (16 cm H20 (ref 10-25 cm H20)). The initial CT scan of brain and orbits demonstrated no acute intracranial process, and the MRI of the orbits was also unremarkable.
Given the patient's history of fever, myalgia, rash, and joint pain with CSF studies showing both a neutrophilic and lymphocytic pleocytosis, there was concern for infectious etiologies, including both bacterial and viral infections, as well as autoimmune etiologies. The differential diagnoses included neuromyelitis optica, multiple sclerosis, neuropsychiatric SLE, HIV, syphilis, tuberculosis, coccidioidomycosis, cryptococcus, Lyme, and West Nile virus.
Further investigation was pursued to work up the aforementioned etiologies, and the patient was found to have a positive double-stranded DNA (>1 : 640), low C4 (10 mg/dL (ref 16-47)), low CH50 (13 U/mL (ref 31-60)), normal C3, negative ANA by immunofluorescence assay (repeated twice) and negative anti-Sm/RNP, anti-SSA/B, Coombs antibody, anti-beta2 glycoprotein, anticardiolipin, and lupus anticoagulant. ANCA, ACE, and cryoglobulin were negative. Rheumatoid factor was positive (38 IU/mL (ref < 14)). The infectious disease service was consulted, and the infectious workup including HIV, hepatitis antibodies, cocci antibodies, RPR, cryptococcus antibodies, Lyme antibodies, West Nile virus antibodies, and Quantiferon Gold were all negative. CSF cultures showed no growth. Skin biopsy of the lower extremity rash was done, pending results.
The presence of a high-titer positive double-stranded DNA antibody raised concern for an autoimmune etiology, although in the setting of a negative ANA the validity of the dsDNA titer was questioned with a high concern for a false-positive test. Given the lack of other findings to suggest autoimmune disease, the rheumatology service requested additional studies. Given the negative infectious workup to date, the neurology service recommended initiation of pulse corticosteroids with methylprednisolone 1,000 mg intravenous daily for which the patient received 2 doses, with improvement in his symptoms, which was then followed by oral prednisone taper.
Approximately one week later, the patient returned to the hospital with acute onset right arm weakness and numbness. On physical exam, the patient was found to have 4/5 muscle strength in the right upper extremity with decreased sensation to light touch over the fourth and fifth digits of the right hand. MRI of the brain showed multiple subacute infarcts in the left parietal lobe (Figure 2). CT angiogram of the brain was negative. Furthermore, the results of skin biopsy had returned demonstrating leukocytoclastic vasculitis (Figure 3). With these new clinical, radiographic, and pathologic findings, there was concern for a CNS small vessel vasculitis possibly secondary to SLE given satisfaction of SLICC criteria which included low C4 and low CH50, high-titer double-stranded DNA, maculopapular rash of the lower extremities, and bilateral papilledema and erythema resulting from cranial neuropathy of the optic nerves. SLICC criteria require that there be greater than or equal to 4 criteria met including at least 1 clinical and 1 laboratory criteria. The patient's history of knee swelling also raised concern for synovitis, although this did not meet the SLICC criteria explanation for synovitis as our patient demonstrated swelling in only one joint, and SLICC criteria require synovitis in two or more joints. Other etiologies such as embolic phenomenon from endocarditis or paraneoplastic syndrome were considered; as a result, blood cultures were sent, and ECHO was done showing no valvular vegetations. Blood cultures had shown no growth x 5 days. As a result of the above workup, the patient was given a working diagnosis of neuropsychiatric SLE (NPSLE) with new onset neurologic changes, and he was treated with pulse dose methylprednisolone 1 gram for a total of five days with prednisone taper as well as one induction dose of intravenous cyclophosphamide 1,000 mg.
After the patient was discharged, the blood cultures that had been initially reported as no growth, were later found to have 2/4 bottles positive for Gram-variable bacteria. The cultures were sent to Public Health for confirmation, and the organism was speciated as Brucella melitensis by PCR. Subsequently, the patient was readmitted to the hospital and confirmed to have positive Brucella serologies including total antibody titer (1 : 320 (ref < 1 : 80)), IgG (6.99 (ref < 0.80)), and IgM (1.42 (ref < 0.80)). Brucella bacteremia, positive Brucella serum serologies, and clinical presentation with subacute stroke were all consistent with a diagnosis of neurobrucellosis. On further history, the patient noted to have eaten unpasteurized cheese in Mexico 6 months prior which was thought to be the source of infection. The corticosteroids were tapered off, no further doses of cyclophosphamide were given, and the patient was given four weeks of intravenous ceftriaxone as well as three months of oral doxycycline and rifampin.
On follow-up, the patient's serum Brucella IgM became negative, repeat blood cultures showed no growth, and repeat lumbar puncture demonstrated resolution of pleocytosis. The patient's symptoms of weakness, blurry vision, headaches, intermittent fevers, and body aches resolved. The patient's visual acuity returned to normal, and the papilledema resolved, but the patient was noted to have some residual optic nerve atrophy.