Centre for Rheumatic Diseases, Ward 14/15, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 OSF, UK
SIR, We report on an unusual and unfortunately fatal cause of leg pain and septicaemia in a rheumatoid arthritis patient.
A 49-yr-old woman with rheumatoid arthritis (RA) was admitted as an emergency with a history of vomiting, diarrhoea and excruciating pain in her legs. The medical history included 11 yr of seropositive erosive RA, cervical carcinoma treated with radical hysterectomy 5 yr previously, non-steroidal enteropathy and osteoporosis. Previous disease-modifying anti-rheumatic drug therapy consisted of sulphasalazine, hydroxychloroquine, methotrexate, i.m. gold, penicillamine and minocycline. On admission, drug therapy included leflunomide 20 mg/day (started 4 months previously), prednisolone 5 mg/day, etodolac 600 mg/day, alendronate 70 mg once weekly and omeprazole 20 mg/day. Blood monitoring during leflunomide treatment had been satisfactory the week prior to admission (haemoglobin concentration 10.7 g/dl, white blood cell count 7.6x109/l, platelet count 377x109/l). On examination, she was pyrexial (38°C) and tachycardic (120 beats/min), blood pressure was 100/60 and abdominal examination revealed right upper quadrant tenderness. Musculoskeletal examination revealed no evidence of joint sepsis. Chronic lymphoedema of the lower limbs was noted (present since her hysterectomy).
Investigations revealed urea 12.4 mmol/l, creatinine 200 µmol/l, C-reactive protein 81 mg/l, haemoglobin 10.4 g/dl, white blood cell count 2.3x109/l (1.4x109/l neutrophils, 0.1x109/l lymphocytes), platelet count 294x109/l. The chest X-ray was normal. Midstream specimens of urine, stool samples and blood cultures were taken. Initial treatment consisted of intravenous fluids, intravenous hydrocortisone, analgesia and heparin for deep venous thrombosis prevention.
Twelve hours after admission there was an acute deterioration in her clinical condition. She became drowsy and had developed a new area of blistering on her right lower leg. Intravenous flucloxacillin, gentamicin and hydrocortisone were given. Within 1 h her blood pressure became unrecordable and she arrested (electromechanical dissociation). She was resuscitated and transferred to the intensive care unit, where ventilatory support, inotropes, further intravenous hydrocortisone and intravenous antibiotics were administered. Despite this, she arrested again and died 24 h after admission. Bacteriology later revealed group G streptococcus in blood culture and from swabs of her right leg. Post-mortem examination was not performed.
Group G streptococci have many bacteriological and clinical similarities to group A streptococci (GAS). These include the ability to cause a variety of skin and soft tissue infections, ranging from superficial impetigo, erysipelas and infection of pre-existing ulcers to necrotizing fasciitis and myonecrosis [1]. Streptococcal toxic shock can ensue [2]. The rapid and fatal progression of sepsis in this case was alarming. The source of sepsis was most likely her right leg. Most striking was the history of intractable leg pain, reported to be far in excess of any previous RA-related joint pain associated with the rapid development of blistering. These features have been described in necrotizing infections of the skin and fascia. Rapid progression, severe systemic toxicity and a high fatality rate are frequent [3]. By the time blister or bulla formation develops, deep soft tissue destruction and even muscle breakdown has often occurred. Diagnosis depends on clinical suspicion in the context of sepsis. Imaging techniques are of limited benefit and direct surgical exploration is required to make the definitive diagnosis. Broad-spectrum antibiotic cover initially includes penicillin G, clindamycin, gentamicin and metronidazole. Early surgical intervention is required, particularly if myonecrosis or septicaemia is present. Despite these measures, mortality rates of 3034% are reported with GAS-associated necrotizing fasciitis once the patient has developed septic shock [4].
There has been one other recent report of necrotizing fasciitis in an RA patient [5]. The 37-yr-old patient in that case was on etanercept 25 mg twice weekly and prednisolone 5 mg/day, and presented with severe left leg and hip pain, leucopenia and pneumonia. She rapidly developed leg discoloration and joint sepsis in four of her prosthetic joints. Streptococcus pneumoniae was identified in blood, synovial fluid and soft tissue and fascia from her left thigh and calf. Despite extensive surgical debridement, resection arthroplasties, antibiotics and intensive care support, this patient also died.
These cases highlight the devastating effects of sepsis in young immunosuppressed patients.
Notes
Correspondence to: A. McEntegart.
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