A 69-year-old man was transferred to our hospital in Indiana, United States, from an outside facility with multiple brain lesions. Since 6 months prior to his admission, he had developed progressive right knee arthritis and underwent a redo knee arthroplasty with total knee replacement. The joint was inflamed and thought to be possibly infected, and the patient was placed on antibiotics. A few months later, he presented with polyarticular joint swelling and warmth, especially of the left wrist. He was seen by a variety of specialists and was diagnosed with rheumatoid arthritis (RA). He was placed on prednisone 40 mg daily without much improvement. Intra-venous methotrexate initiated and after the second dose, he started depicting odd behavior, forgetfulness, intermittent fevers, left wrist electric shock sensation and weakness of hands. He was admitted to outside hospital for syncope. CT scan of head demonstrated occipital hypodensity and 4 cm lesion in left parietal lobe. Brain MRI revealed many enhancing brain lesions most prominent on the left parietal lobe concerning for septic emboli versus metastatic diseases. Blood cultures were negative, and patient was placed on vancomycin plus piperacillin/tazobactam and transferred to our hospital.
His past medical history was significant for hypertension, osteoarthritis, and rheumatic arthritis. He was diagnosed with latent tuberculosis infection (LTBI) 2 years prior to the admission. Patient was initially started on isoniazid and rifapentine weekly but rifapentine was discontinued due to a rash. He then completed treatment with isoniazid for 9 months.
On admission, review of systems was positive for weakness, fever, recent unintentional weight loss of 25 pounds, occasional dyspnea with exertion, arthralgias, myalgia, left wrist and right knee pain and swelling, impaired grip, numbness and tingling all over the body especially hands and hypersomnolence. Physical examination demonstrated tachycardia and tachypnea, and lethargy. He was oriented to time, place and person, had 5/5 strength in lower and 4/5 strength in upper extremities, had intact reflexes and sensation, and had tender joints all over the body with swollen left wrist.
Initial laboratory investigations demonstrated WBC count of 5.7 x 109cells per liter (85% polymorphonuclear leukocytes, 7% lymphocytes, 7% monocytes), hemoglobin of 11.2 g/dL, hematocrit of 33.3%, mean corpuscular volume of 87 and platelet of 139 billion/L. Fibrinogen of 563 mg/dL with normal ranges of PT and INR. Liver enzymes, lactate, troponin, urine analysis and metabolic panel were within normal ranges except for sodium of 126 mEq/L. Antinuclear antibody titer and rheumatoid factor were both negative. Second brain MRI revealed numerous enhancing intra-parenchymal lesions in cerebral and cerebellar hemispheres with surrounding vasogenic edema (Fig. 1). Some lesions had central diffusion restrictions which suggested abscesses. Electroencephalogram (EEG) demonstrated diffuse slowing with no ictal or inter-ictal epileptiform waves. Lumbar puncture results showed WBC count 1 cell/micro L, protein 40 g/dL, glucose 74 mg/dL and negative cerebrospinal fluid (CSF) culture including cryptococcus, herpes and lyme disease. Negative testing included bacterial cultures, TB polymerase chain reaction (PCR), CSF TB PCR, mycobacterial cultures, toxoplasmosis PCR, venereal disease research laboratory (VDRL) test, human immunodeficiency virus (HIV) antibodies, acid-fast bacilli (AFB) and fungal blood cultures and serologies of histoplasmosis, cryptococcus, bartonella, coxiella, rickettsia, legionella. Transthoracic and transesophageal echocardiogram were negative for vegetations. CT scan of chest showed diffuse tiny upper lung nodularity likely due to infectious bronchiolitis or hypersensitivity pneumonitis. Left wrist X-ray revealed osteonecrosis of scaphoid and diffuse osteoarthritis of the left hand.
Brain biopsy of brain lesions was planned but held as the patient developed gastrointestinal bleeding. He also had developed acute kidney injury during his hospital course. Esophagogastroduodenoscopy and colonoscopy were performed. Colonoscopy showed a 3 cm ulcer in the ascending colon and random biopsies were taken and sent for fungal, periodic acid-Schiff stain (PAS) and AFB stains. AFB stain on the colon biopsy turned positive. Sputum, urine and stool samples were collected and had positive ABF stains and confirmed with positive MTB PCR. Diagnosis of disseminated MTB infection (pulmonary and extrapulmonary) was established and extrapulmonary involvements included CNS, intestine, kidney and likely prosthetic and native joints.
The patient was successfully treated with isoniazid (plus pyridoxine), pyrazinamide, moxifloxacin and ethambutol for 18 months, followed by isoniazid and pyrazinamide for additional 2 months. Prednisone 60 mg daily was administrated for the first 2 months of induction. Rifampin was added under pharmacist supervision but was discontinued after the development of rash. The reason for prolonged therapy was brain tuberculomas and rifampin free regimen. Post induction phase, MRI of the head showed resolution of brain lesions.
On his follow up in the 20th month of therapy, he had some residual memory loss, but his mental status had improved dramatically, and all the joint symptoms were resolved as well. During the treatment course, patient developed transient drug induced leukopenia which resolved after granulocyte-colony stimulating factor (G-CSF) administration, neuropathy which was likely due to isoniazid and controlled with gabapentin, vision impairment due to cataract which was probably an adverse effect of steroids and potential tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). Overall, patient was clinically better and on multiple clinic follow-ups, he continued to improve and returned to his baseline health.