A 74-year-old male patient with a known case of benign prostatic hyperplasia (BPH) presented on 17 October 2020 to the emergency department (ED) with fever and progressive generalized fatigability for 10 days. He had a history of dysuria for two weeks, in addition to polyuria, mild night sweating, and weight loss of 10 kg in one month. There was no history of upper respiratory tract infections, nausea, vomiting, diarrhea, or abdominal pain. He reported a history of drinking unpasteurized milk and contact with farm animals but denied any history of contact with tuberculosis (TB) patients. There was no history of diabetes mellitus (DM). There was no family history of malignancy or rheumatologic disease. Prior to this presentation, he had frequent visits to the ED due to increased fatigability and joint pain. However, no diagnosis was established, and the treatment was often conservative. On this admission, he was managed empirically with intravenous (IV) tazocin and IV paracetamol, given his history. A septic workup was also performed. Laboratory investigations revealed positive serology for Brucella abortus and Brucella melitensis, elevated erythrocyte sedimentation rate (ESR) (58 mm/hr), C-reactive protein (CRP) (165.08 mg/dl), and leukocytosis (23.32x103/muL). Chest X-ray (CXR) was unremarkable. The patient was diagnosed with brucellosis and, eventually, discharged on doxycycline and rifampin. In addition, he was scheduled for a neurological follow-up to assess his progressive fatigability.
After one month, on 17 November 2020, he was seen in the neurology clinic. The diagnosis of Guillain-Barre syndrome (GBS) was suggested as radiculoneuropathy, and axonal sensorimotor polyneuropathy was proven by electromyography (EMG) and nerve conduction study (NCS). Accordingly, the patient was admitted and received immunoglobulin (IVIG) as recommended by the neurologist. After one week of receiving IVIG, his condition was still not improving and he was referred to the outpatient rheumatology clinic to exclude possible vasculitic processes. Later on, the patient was seen in the rheumatology clinic complaining of multiple joint pain and swelling of wrists, fingers, elbows, knees, ankle, and foot, which started four weeks earlier to his visit.
The pain and swelling in the knees and elbows almost completely improved after brucellosis therapy. However, he was still complaining of pain and swelling in the other joints, which usually worsened at night and improved with movement. Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) was strongly positive (131), ESR was 53 mm/1 hr, and CRP was 132.83 mg/dL. Rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), antinuclear antibodies (ANA), cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA), and ferritin were all normal. Despite being on appropriate antibiotics treatment for brucellosis, his fever did not subside. It was recurring in episodes, with each episode lasting 20 minutes per day. The fever was not associated with sweating, shivering, or other constitutional symptoms. Furthermore, based on the constellation of several findings, which include the persisting fever despite appropriate antibiotic therapy, the EMG/NCS finding of axonal sensorimotor polyneuropathy, the persistence of elevated inflammatory markers, the positive P-ANCA, and imaging that did not show any masses or fluid collection, the likelihood of underlying systemic vasculitis was high according to the rheumatology team. Therefore, prednisolone 50 mg PO OD was started. In addition, he was continued on doxycycline and rifampin for another set of 11 days to complete six weeks of the brucellosis treatment course.
After one week of being on steroids, his fever totally subsided and other symptoms had significantly improved. Also, his CRP started to decrease, reaching 79.59 mg/dl. However, P-ANCA was still high (119.4). Therefore, the decision was made to continue on prednisolone 50 mg for another week, followed by 40 mg for two weeks and then 30 mg for two weeks. On the next visit after four weeks on 27 December 2020, he reported significant improvement in his symptoms with no more joint pain and resumed his normal activities independently. Also, lab results showed decreased P-ANCA to 57.8 and CRP to 19.36 mg/dL. Azathioprine 50 mg PO twice a day was added while he continued taking steroids with a tapering dose. After four weeks, on 26 January 2021, he reported that he was no longer experiencing fever, fatigue, joint swelling, or pain. However, he could not actively flex or extend his left index finger or right thumb, which was attributed to his peripheral neuropathy. Therefore, azathioprine dose was optimized to 50 mg three times a day. The patient was reevaluated on 7 March 2021. He was found to be asymptomatic, with no active complaints. Subsequently, azathioprine dosage was reduced to 50 mg PO BID.