A 40-year-old Hispanic man from Mexico presented with pain and swelling of the right foot for 1 year. His medical history was only remarkable for latent TB diagnosed 9 months prior to presentation and was prescribed isoniazid for 9 months, but only 2 months was completed by the patient for unknown reasons. The pain in his right foot had been increasing in intensity and began to hinder his ambulation, thus leading to a visit to the emergency room. The pain was throbbing in nature, localized to the right foot, and was exacerbated by walking and movement of the ankle. The patient was unable to bear weight on his ankle. He denied any trauma, insect bites, or recent travels. Review of systems was negative for dyspnea, cough, sputum production, chest pain, pleurisy, fevers, chills, or night sweats. He did, however, report a 20-pound weight loss over the past 6 months.
On physical examination, inspection of the right foot showed no erythema, pallor, lesions, or discharge. The right foot was warm to touch and tender, especially along the lateral portion of the dorsum of foot. There was decreased range of motion secondary to pain and edema that extended from the mid-foot up to the ankle. Pedal pulses were intact, and there were no signs of trauma or infection. The remainder of his physical examination, including the lungs, was unremarkable. Initial laboratory studies revealed the following values: white blood cell (WBC) count 10.8 (normal 4.8-10.8 thousands/mL); hemoglobin 10.5 (normal 14-18 g/dL); hematocrit 31 (normal 42-52%); platelets 172,000 (normal 130,000-400,000); serum sodium 130 (normal 135-145 mmol/L); serum potassium 4.6 (normal 3.5-5.1 mmol/L); serum chloride 94 (normal 98-107 mmol/L); serum bicarbonate 25 (normal 22-29 mmol/L); Blood Urea Nitrogen (BUN) 17 (normal 6-20 mg/dL); serum creatinine 0.96 (normal 0.7-1.2 mg/dL). Liver function tests were all within normal limits, except for elevated alkaline phosphatase of 584 (normal 40-129 u/L). On admission, HIV screening was positive which was confirmed with western blot assay. HIV viral load was found to be 76,168 copies (normal <175) and CD4 count was 89 (normal 490-1,740 cells/microL). Admission chest x-ray was suggestive of miliary TB (Fig. 1a).
The patient was admitted and placed in respiratory isolation. CT demonstrated a diffuse pattern of nodules throughout both lungs, also suggestive of military TB (Fig. 1b). Radiography and magnetic resonance imaging (MRI) of the right foot and ankle revealed significant destruction of the navicular cuneiform joints with associated osteomyelitis compared to initial imaging 1 year prior (Fig. 2a and b). Differential diagnosis at the time of admission included septic arthritis, inflammatory arthritis, aseptic necrosis, and TB osteomyelitis. Serological investigations revealed the following: C Reactive Protein (CRP) 5.24 (normal <0.5 mg/dL); Erythrocyte Sedimentation Rate (ESR) 100 (normal 20 mm/h); uric acid 6.4 (normal 3.4-7.0 mg/dL); Lactate Dehydrogenase (LDH) 248 (normal 135-225 units/L); Anti-Nuclear Antibodies (ANA) negative; anti-Cyclic Citrullinated Peptide (CCP) <16 (normal <20); Rheumatoid Factor negative; and Quantiferon-TB Gold positive. Acid-fast bacilli (AFB) sputum smears and cultures were negative. On discussion with an infectious disease consultant regarding initiation of anti-TB chemotherapy, it was recommended that treatment be started after a tissue diagnosis has been obtained. A fluoroscopy guided bone biopsy of the right first cuneiform was performed which revealed severe acute and chronic mycobacterial osteomyelitis with numerous AFB (Fig. 3). Furthermore, cultures were positive for mycobacterium TB and it was sensitive to all anti-TB drugs. Anti-tubercular chemotherapy was initiated after tissue diagnosis was obtained. Highly active anti-retroviral therapy (HAART) was started 2 weeks later due to the increased risk of immune reconstitution syndrome (IRIS). The patient was found to have iron deficiency anemia and subsequently started on iron supplementation. During the course of the hospital stay, he started having fevers with a T-max of 102.7 F along with watery diarrhea associated with non-specific abdominal pain and oral thrush. He was empirically started on vancomycin, cefepime, bactrim, and fluconazole for possible septic arthritis, pneumonia, Pneumocystis pneumonia infection, and oral candidiasis. CT of the abdomen and pelvis with oral contrast revealed diffuse colitis and metronidazole was added to therapy. All blood, sputum, and urine cultures were negative, including toxins for Clostridium difficile. Eventually the fevers and diarrhea resolved; however, his renal function began to deteriorate. Vancomycin was discontinued and trimethoprim-sulfamethoxazole was switched to atovaquone. Renal function quickly improved with hydration and the change in drug regimen.
Our patient had a positive clinical response to medical therapy with a decrease in the pain and swelling of his right foot and ankle in 2 weeks time. Upon discharge, his ambulatory dysfunction resolved and he was walking with the assistance of a cane. Follow-up with 3 months of anti-TB treatment, repeat chest x-ray showed significant improvement from the previously seen miliary TB pattern (Fig. 4). His viral load was undetectable and CD4 trended up. One year after discharge the patient was ambulating without any assistance. Follow-up chest x-ray and MRI of his right foot showed no pulmonary abnormalities and significant improvement of the navicular and first and second cuneiforms of the right foot, with the bones appearing relatively normal (Fig. 5). His total anti-TB therapy duration was 9 months of rifabutin, which was used instead of rifamycin during his therapy. After HRZE therapy (isoniazid, rifabutin, pyrazinamide, and ethambutol) for 2 months, patient received 7 months of isoniazid (INH)/rifabutin treatment. His HAART treatment consisted of protease inhibitor (PI)-based therapy.