Infectious arthritis due to Candida species is a rare disease. We report a case of infectious arthritis due to Candida tropicalis in a 27-year-old β thalassemic female patient who presented with pain and swelling in the left knee joint since the last three months. The diagnosis was established by culture of the aspirated synovial fluid, which showed the growth of Candida tropicalis. The patient was started on intravenous amphotericin B, to which the patient responded well with the subsidence of the pain and swelling of the left knee joint. The patient was discharged after a period of two weeks on oral fluconazole and was asymptomatic on last follow-up. The patient had no other predisposing factor like trauma or aspiration of the joint, except for the severe anemia, associated grade III malnutrition, and diabetes.
Keywords: Arthritis, Candida tropicalis, thalassemia
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Kumar S, Bandopadhyay M, Bandopadhyay M, Mondal S, Pal N, Banerjee P. A rare case of Candida tropicalis arthritis in a patient of β thalassemia. Ann Trop Med Public Health 2012;5:362-4
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Kumar S, Bandopadhyay M, Bandopadhyay M, Mondal S, Pal N, Banerjee P. A rare case of Candida tropicalis arthritis in a patient of β thalassemia. Ann Trop Med Public Health [serial online] 2012 [cited 2020 Aug 15];5:362-4. Available from: https://www.atmph.org/text.asp?2012/5/4/362/102059
Infectious arthritis due to Candida species is a rare disease. Candida albicans is the most commonly isolated species, but septic arthritis due to Candida tropicalis, Candida guilliermondi, and Candida parapsilosis has also been reported.  There have been rare reports of infectious arthritis due to Candida zeylanoides as well.  We report a case of arthritis due to Candida tropicalis in a 27-year-old female who was a known case of β thalassemia major and was suffering from grade III malnutrition and was negative for HIV, hepatitis B, and hepatitis C infections. The diagnosis was confirmed by culture of aspirated pus from the knee joint, which showed growth of Candida tropicalis. The patient was successfully treated with intravenous amphotericin B therapy, to which the patient responded well with the subsidence of the pain and swelling. The patient was later discharged on oral flucanozole and was symptomless at the last follow-up.
A 27-year-old female was admitted to the hospital with a complaint of pain and swelling in the left knee since the last three months. There was neither past history of trauma to the joint nor was there any history of joint aspiration done in the past. She was diagnosed as a case of β thalassemia major at the age of 11 years. From the time of diagnosis, she had been receiving blood transfusions at eight monthly intervals, but for the last three years, she was requiring the transfusions at two to three months interval. On general examination, the patient had pallor with grade III malnutrition, chronic hemolytic anemia facies, heart rate of 92/ minute, and blood pressure 120/70 mm of Hg. The cardiothoracic examination revealed mild bilateral crepitations in the chest, the abdomen was soft on palpation, and moderate hepatosplenomegaly was observed. The left knee was swollen and tender with signs of inflammation. There was no associated fever in the patient.
The complete blood parameters were as follows: Hemoglobin 4.19 gm/dl, white blood cell count was 3900/ml (polymorphs 51%, lymphocyte 46%, eosinophils 2%, monocyte 1%). The biochemical investigations were as follows: Fasting sugar- 161 mg/ dl, urea 27 mg%, creatinine 0.84 mg%, bilirubin 1.3 mg/dL, conjugated bilirubin 0.8 mg/dL, alkaline phosphatase 541, SGPT 58 IU/mL, SGOT 78 IU/ mL, total protein 6.7 g/dL, albumin 3.5 g/dL, sodium 128 nmol/l, and potassium 4.7 nmol/l. The patient was non-reactive for HIV and anti-HCV antibodies and was hepatitis B surface antigen-negative. The chest X-ray showed mild hilar fullness, and the X-ray of the affected left knee showed mild tissue swelling with osteoporotic changes [Figure 1].
|Figure 1: X-ray of the left knee joint, suggestive of tissue swelling and osteoporotic changes|
The patient was started empirically on intravenous ceftriaxone, cloxacillin, and gentamycin. The synovial fluid was aspirated under aseptic precautions and sent for pathological and microbiological investigations. The aspirated synovial fluid was purulent with some amount of hemorrhage. The microscopic investigation revealed plenty of red blood cells and white blood cells with polymorphs 99% and lymphocyte 1%. The Zeihl Neelsen stain showed no acid fast bacilli. The synovial fluid was cultured on Blood agar and MacConkey agar for aerobic culture, thioglycollate medium, Sabouraud’s Dextrose agar, and Lowenstein Jenssen media. After overnight incubation, the blood agar and Sabouraud’s agar revealed growth of yeast-like colonies. The yeast was later identified to be Candida tropicalis by colony morphology on cornmeal agar [Figure 2] and carbohydrate fermentation – assimilation tests. The organism was also found to be sensitive to amphotericin B. The thioglycollate medium did not show any anaerobic growth, and the Lowenstein Jensen medium did not show any growth after eight weeks of incubation.
|Figure 2: Lactophenol cotton blue mount preparation from cornmeal agar showing blastoconidia singly or in very small groups along the pseudohyphae|
Meanwhile, based on the preliminary reports, the patient was started on intravenous amphotericin B and was transfused two units of blood, to which the patient responded well with the subsidence of the pain and swelling of the left knee joint and improvement in the pallor. No evidence of disseminated candidiasis was present in this patient as shown by no growth in the blood cultures. The oral, vaginal, and perianal swabs collected for fungal cultures did not show any growth of Candida species. The patient was discharged after a period of two weeks on oral fluconazole, and on follow-up after one month, the patient was asymptomatic.
Risk factors known to predispose to Candida infection are parenteral nutrition, corticosteroids or immunosuppressive agents, drug abuse, extensive surgery, use of broad-spectrum antibiotics and compromised host state, trauma of the skin, and intravascular catheters. , Arthritis due to Candida results from hematogenous spread of the organism to the synovium, the knee being the most commonly affected joint. , The arthritis arises by either direct inoculation or hematogenously disseminated candidiasis. The former occurs mostly in immunocompromised patients who have previously undergone an intra-articular injection and surgical procedures, while the latter is found in patients with leukopenia, cancer, sepsis, and autoimmune diseases with multiple antibiotics use.  In our case, the patient was suffering from grade III malnutrition, which was a predisposing factor along with the severe anemia and associated diabetes. The patient had no previous history of any trauma or aspiration done on the joint. The predisposing factors for developing fungal arthritis in patients with hematologic malignancies are intensive chemotherapy, neutropenia, immunosuppressive drug usage, long-term use of broad-spectrum antibiotics. In our case, gross malnutrition seemed to play an important role in developing C. tropicalis arthritis. It is difficult to identify the fungus via a smear of synovial fluid while the culture has the major role for diagnosis. 
The treatment of fungal arthritis must include joint aspiration and intravenous or possibly intra-articular anti-fungal drugs, and synovectomy may also be considered. , Amphotericin B remains the drug of choice for treatment of this disease because it penetrates into the synovial fluid. Drugs like miconazole and ketoconazole are less toxic than amphotericin B and deserve further investigation since they are also able to penetrate into the joint. The evolution of Candida arthritis may be slow, and the correct diagnosis may be delayed for months or even years. 
Many anti-fungal drugs including fluconazole, ketoconazole, miconazole, amphotericin B, 5-flucytosine, and caspofungin have been used to treat fungal arthritis successfully, but relapse rate was unknown. ,,,, The most reliable treatment is amphotericin B,  which was not widely used because of the notorious side effects. Fluconazole is effective for treating C. tropicalis arthritis and can achieve a drug level in the synovium nearly equal to the serum. 
In conclusion, Candida infection should be considered as a possibility when arthritis arises in patients with hematological malignancies, especially when broad-spectrum antibiotics have been used during the neutropenic period.
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