Enterococcal Pyomyositis in a Patient of Rheumatoid Arthritis on Tofacitinib and Methotrexate

Dear Editor,

Pyomyositis is a purulent infection of skeletal muscles generally caused by Staphylococcus aureus in tropics. ¹ Enterococci are Gram-positive organisms observed as single cells, diplococci or short chains. They are a part of normal human microbiota of large bowel. Higher level of gastrointestinal tract colonisation is considered a critical factor in pathogenesis of enterococcal infections. ¹ Pyomyositis caused by enterococci is rare and only two cases have been reported in literature till date.^2,3 Herein we report a case of enterococcal pyomyositis in a patient of rheumatoid arthritis (RA) who was on conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and was started on tofacitinib recently for control of her disease activity.

A 50-year-old lady, a known case of RA for last six years, was receiving methotrexate 25 mg/week, sulfasalazine 1 g twice a day, hydroxychloroquine 200 mg once a day and low-dose steroids (methyl prednisolone 2 mg daily) for control of her disease. She presented in rheumatology out-patient department in June 2023 with pain and swelling in bilateral knees and shoulders for past one month despite being compliant to the treatment. She had four tender joints and two swollen joints with early morning stiffness of 1 h. Her disease activity score-28 was 3.8 and she had prediabetes with glycosylated haemoglobin of 5.9%. She was initiated on tofacitinib 5 mg twice a day after screening (radiograph chest and tuberculin skin testing) for latent tuberculosis. Sulfasalazine and hydroxychloroquine were stopped and methotrexate was continued. After three months, she presented to emergency room with high-grade fever with chills and markedly tender, erythematous and diffuse swelling along right side of neck and right supraclavicular area. She also complained of chest pain on right side posteriorly on deep inspiration. At admission, her pulse rate was 96 min⁻¹, blood pressure 126/80 mmHg in right-arm supine position and temperature was 101°F. Blood investigations were suggestive of anaemia (Hb 9.9 g/dL), leukocytosis (Total Leukocyte Count [TLC] 57,130 cells/µL), thrombocytosis (platelet count 454,000 µL⁻¹) and erythrocyte sedimentation rate (ESR) of 55 mm at the end of 1 h. Her liver function test (LFT) was mildly deranged, aspartate transaminase was 73 U/L, alanine transaminase was 58 U/L and kidney function test (KFT) was normal; blood urea nitrogen was 10 mg/dL and serum creatinine was 0.8 mg/dL. Her blood and urine cultures were sterile. Her computed tomography of neck and chest (Figure 1) revealed pyomyositis involving muscles of right side of the neck and thoracic cage. Her 2D echocardiogram and serum immunoglobulin (IgG, IgA, IgM) levels were normal. Under ultrasound (USG) guidance, 400 mL of pus was aspirated and a malecot’s catheter drain was left in the pus cavity. Her pus culture showed heavy growth of Enterococcus fecalis and antibiotics were tailored according to the sensitivity. She improved completely over 14 days’ time and drain was removed after reassessing the resolution of pus collection through USG and negative drain for three consecutive days.

Figure 1.

Note: The image is from patient’s original CT scan and has been obtained after taking due consent.

This is the first case of enterococcal pyomyositis being reported in a patient of RA who was on combination therapy of methotrexate and tofacitinib along with low-dose steroids. The only possible predisposing factor we could identify was the ongoing DMARD therapy. However, none of the DMARDs have previously been reported to cause such an infection. E. fecalis causing pyomyositis per se is rarely reported in literature. We could come across only two such cases and both had known predisposing risk factors for enterococcal infection.^2,3

In an integrated safety analysis of tofacitinib, including all the healthy RA patients who participated in randomised controlled trials, 7,061 patients treated with tofacitinib for up to 9.5 years; with a total of 22,875 patient-years of exposure, the frequency of serious infections was comparable to biologic DMARD. ⁴ However, there were no reported cases of enterococcal pyomyositis. Similarly, in ORAL (Oral Rheumatoid Arthritis Trial) surveillance trial also, which included patients who had active RA and who were at least 50 years old and had at least one additional cardiovascular risk factor, no such case was reported. ⁵

Tofacitinib improves overall mucosal immunity and promotes favourable microbiota diversity. These classes of drugs are being tried in inflammatory bowel disease with tofacitinib gaining FDA approval for use in Crohn’s disease. ⁶ There is no suggestion of enhanced colonisation by pathogenic Enterobacteriaceae in patients treated with tofacitinib.

The objective of reporting the present case is to make clinicians aware about the possible complications of tofacitinib therapy. Plausible cause for such an infection in our patient could not be ascertained beyond reasonable doubt as there are no data to support such occurrence in patients who are already on Janus kinase (JAK) inhibitors, neither is there any evidence of gut microbiota alteration leading to colonisation by pathogenic Enterobacteriaceae. Exercising care, not only in choosing right drug for the right patient but also regular monitoring and vigilance for uncommon infections, is of utmost importance in current context where highly effective newer therapies are becoming popular but at the same time warrant a caution regarding the risks associated with their use.