A Case of Triple Arthritis: Tuberculosis, MRSA and Gout in One Knee

Aim: To report a case of concurrent tuberculous and bacterial arthritis in chronic tophaceous gout. Presentation of the Case: A 59-year old Filipino male patient consulted for sensorial changes with four-month progressive swelling of the right knee draining non-foul smelling yellowish discharge with chalky material. He eventually had arthrocentesis of right knee. Blood cultures were all negative. Acid fast bacilli were present both in the synovial fluid and endotracheal aspirate. Endotracheal aspirate grew Mycobacterium tuberculosis. Synovial fluid grew methicillin-resistant Staphylococcus aureus (MRSA). He was treated with prednisone, clindamycin, colchicine, febuxostat, tramadol, and anti-tuberculous medications. He failed to undergo surgery. Patient eventually had fatal myocardial infarction. Discussion: To our knowledge, this is the first report of concurrent tuberculous and bacterial (MRSA) arthritis in gout. Case Study Tabula et al.; BJMMR, 8(8): 732-736, 2015; Article no.BJMMR.2015.499 733 Conclusion: This case highlights the possible differential diagnoses especially infections among patients with chronic tophaceous gout. Concurrent tuberculosis and bacterial arthritis can complicate the management of these patients. Hence, microbiologic and crystal analysis of synovial fluid is a very important part of the work-up to tailor the early, specific treatment for these patients.


INTRODUCTION
Gout is a metabolic disease that leads to hyperuricemia which causes precipitation of urate crystals in joints causing severe pain and swelling. Precipitation of urate crystals may also happen in the kidneys thereby causing nephrolithiasis and worse, complicating to chronic kidney disease if left untreated. In chronically untreated or undertreated gouty patients, periarticular tophi can form causing disability and/or disfigurement. These tophi may sometimes rupture expressing chalky white discharge.
Tuberculosis is a major public health concern in the Philippines [1]. The tubercle which can be transferred through cough droplets infects the lungs. TB can also affect the lymph nodes, spine, pleura, genitourinary and gastrointestinal organs. Rarely, it affects the joints [2-4].

REPORT OF A CASE
We describe a 59-year old Filipino male with chronic tophaceous gout diagnosed twelve years prior to consult. He was previously on colchicine, diclofenac, methylprednisolone and allopurinol with gouty attacks about three times a year affecting the knees, elbows, and first metatarsophalangeal joints of feet. He had no previous arthrocentesis done nor intraarticular steroid injections prior to this admission.
He presented with a four-month history of bilateral knee pain, swelling, and warmth with the right knee being worse. He denied any history of trauma to his knees. He took diclofenac with slight relief of symptoms. Left knee improved but right knee increased in swelling and started draining non-foul-smelling yellowish fluid with chalky material. He then developed two-week history of progressive disorientation. On the day of admission, he developed dysgeusia and worsening of sensorium. He had no fever, cough, chest pain, dyspnea, vomiting, or diarrhea. He had a history of passing out stone in the urine. He had no other comorbidities except he was diagnosed with chronic kidney disease stage 5 a month ago and given sodium bicarbonate, febuxostat, colchicine, ferrous sulfate, folic acid, potassium citrate, and amlodipine. He had no known exposure to tuberculosis. He was a previous smoker and alcohol beverage drinker.
On examination, he was drowsy with a blood pressure of 90/60 mmHg, 86 beats/minute of heart rate, respiratory rate 20 cpm, temperature 36.5ºC, oxygen saturation 99% on room air. He had anicteric sclerae, no neck vein engorgement, clear breath sounds, distinct heart sounds, no murmur, apex beat at fifth intercostal space midclavicular line, normoactive bowel sounds, nontender and soft abdomen, and no bipedal edema. He had multiple tophi over extremity joints with warm and tender knees. Right knee was very swollen with draining sinus from a fistula. The hemoglobin was 82 g/L (reference range, 120 to 180), hematocrit was 29 (reference range, 40 to 54), platelet count was 420,000 (reference range, 150,000 to 450,000), white-cell count was 1256 (reference range, 4500 to 11,000), with 73% neutrophils (reference range, 50 to 70), 20% lymphocytes (reference range, 20 to 50), and 4% monocytes (reference range, 2 to 9); blood levels of blood urea nitrogen was 24.7 mmol/L (reference range, 2.9 to 9.3), and creatinine was 12 He underwent hemodialysis and blood transfusions. He was treated with clindamycin, rifampicin, pyrazinamide, and isoniazid when the synovial fluid analysis came out. Patient was also on colchicine, low-dose prednisone, febuxostat, and tramadol to control gouty attacks. Eleven days after the diagnosis of bacteriologically confirmed TB arthritis, patient demised from myocardial infarction which precipitously presented with sudden dyspnea, hypotension, acute pulmonary congestion, and decrease in sensorium.

CASE DISCUSSION
Gout is a type of inflammatory arthritis due to hyperuricemia from an increased body pool of urate. It presents usually with episodic acute and chronic arthritis from the deposition of monosodium urate crystals in joints with or without the formation of periarticular tophi. Uric acid may also deposit in the kidney interstitium causing nephrolithiasis. In the Philippines, the prevalence of gout ranges from 0.13% to 1.6% [24][25]. Progression to tophi formation usually happens in 75% of patients with untreated gout for at least 20 years [26].
Although the patient has chronic gout, he was also suspected of a concomitant septic process due to the presence of worsening sensorium, persistence of swelling of the right knee despite steroids and allopurinol, hemodynamic instability, and a draining sinus which could be an access for infections.
The patient's synovial fluid grew MRSA similar to two retrospective studies in Taiwan reporting Staphylococcus aureus as the most common causative microorganism among patients with concomitant bacterial and gout arthritis [9][10]. The knee joint was the most common site of involvement as in this patient. Possible mechanism of concomitant gouty and bacterial arthritis include the decrease in pH brought about by increased lactic acid production from neutrophilic invasion of the joint thereby decreasing the urate solubility hence the formation of its crystals [21]. Moreover, changes caused by the septic process (e.g. plasma proteins and polysaccharides) could further the precipitation of crystals [35]. The most common mechanism especially among patients with wellestablished tophaceous gout is by subcutaneous tophi rupture with secondary wound infection which must be the mechanism in our patient [9][10].
Tuberculosis (TB) is a major public health concern in the Philippines with a national incidence of 133 new smear-positive cases per 100,000 population in 2004 [1]. Pulmonary tuberculosis is the most common site of infection occasionally affecting the lymph nodes, spine, genitourinary system, pleura, meninges, and breasts. The joints are rarely affected [2]. Two percent of all cases of tuberculosis affect the bone and joint [3]. The most common peripheral joints affected are the weight-bearing joints especially the knees and the hips [3,36]. Concomitant TB and gouty arthritis is rare with a few case reports published [6][7][8]. In the Philippines, two cases were reported presenting with recurrent knee pain and swelling which has the same presentation in our patient [7].
This patient presented with concomitant TB and bacterial arthritis with chronic tophaceous gout. To our knowledge, this is the first report of these conditions concurrently in one joint.

CONCLUSION
This case highlights the need to explore other causes of joint swelling in a known case of chronic tophaceous gout. Other than the crystalinduced arthritis, concomitant septic arthritis can complicate these patients. Septic arthritis can be tuberculous, bacterial or both. Hence, the need for microbiologic and crystal analysis of synovial fluid cannot be overly emphasized to tailor the specific management for these patients.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.