LAUSR

Necrotizing fasciitis (NF) is a rapidly progressive, lifethreatening infection involving the skin, soft tissue and deep fascia [1]. The pathogenesis of NF with group A Streptococcus pyogenes (GAS) infection is thought to involve interleukin-6 (IL-6), tissue-damaging enzymes released by activated host neutrophils, and uncontrolled T-cell responses to superantigens [2]. Tocilizumab, an anti-IL-6 receptor monoclonal antibody, reduces the disease activity of rheumatoid arthritis (RA) by the blockade of IL-6 [3]. In RA patients, tocilizumab treatment increases the risk of severe infection and masks its symptoms by suppressing C-reactive protein (CRP) production [4]. Herein, we report a case of NF with slow progression in a patient receiving tocilizumab to treat RA. A 68-year-old woman noticed acute development of pain, swelling, erythema, and purpura over the right lower leg without fever, and visited our emergency department three days later (figure 1A). The patient had been treated with methotrexate (4 mg/week) and tocilizumab (8 mg/kg once every four weeks) for RA. The last administration of tocilizumab was given 25 days before the first visit. Physical examination revealed swelling, erythema, and purpura from the right lower leg to the dorsum of the foot without septic shock. Laboratory tests showed leukocytosis (19,300/ L [normal range: 3,200–9,400/ L]) and an elevated CRP level (2.4 mg/dL [normal range: 0–0.2 mg/dL]) with otherwise normal findings. Blood culture test results were negative. Computed tomography showed no abscesses or gas spaces. Hence, she was diagnosed with cellulitis of the right leg. The patient was hospitalized and treated with cefazolin intravenously. Her condition did not improve, and the cefazolin was switched to piperacillin-tazobactam on Day 4. Clinical findings revealed no recovery despite four days of treatment, therefore the patient was transferred to our dermatology department and vancomycin was added on Day 5. A blood blister larger than 10 cm in diameter developed in the lesion on Day 6, suggesting epidermal necrosis (figure 1B). Laboratory tests showed a white blood cell count of 9,890/ L, and a CRP level of 2.4 mg/dL. The creatine kinase level was not elevated (20 U/L [normal range: 43–157 U/L]). A surgical incision and a finger test in the lesion led to the diagnosis of NF. Radical debridement was subsequently performed with additional clindamycin administration. GAS was detected from the microbial culture of the excised tissues and was susceptible to antibiotics including penicillin and cephem. Thus, we switched piperacillin-tazobactam to ceftriaxone on Day 11. Skin grafting using negative pressure wound therapy was applied to the wound, and she was discharged on Day 82 when most of the lesion was epithelialized. In this case, the patient was diagnosed with NF 10 days after onset, due to slow progression without severe symptoms. Similar RA cases treated with tocilizumab were reported to exhibit the delayed manifestations of NF [5-7]. Only one (14%) out of seven reported cases, including our current case, died of NF, whereas the mortality rate in general NF cases is about 33% [1]. The precise mechanism of NF with GAS remains elusive, although superantigens are assumed A B