Lesson of the month 2: Toxic shock syndrome

Presentation

A 45-year-old female patient presented to the accident and emergency department (A&E) having been generally unwell for the past 12 hours. She had begun to develop rigors. Her past medical history was of birdshot chorioretinopathy, an autoimmune disease causing posterior uveitis, for which she was taking prednisolone and mycophenolate mofetil. She denied any preceding flu-like illness or respiratory, urinary or gastrointestinal symptoms. She had neither headaches nor neck stiffness. She worked as a teaching assistant and was a mother to two children who were well. She did not consume alcohol, had never smoked and had no recent travel history.

On examination she had a temperature of 39.7°C and tachycardia at 110 beats per minute. However, her blood pressure (BP), oxygen saturations and respiratory rate were within normal limits and she was fully alert and orientated. Cardiorespiratory and abdominal examination was normal. There were no signs of skin rash, joint swelling or stigmata of infective endocarditis. An oral examination revealed good oral hygiene, but mild pharyngitis was noted. Electrocardiography (ECG) showed sinus tachycardia and chest X-ray was unremarkable. A urine dipstick test only revealed a trace of blood and was negative for nitrites and leucocytes. Bloods on admission showed venous lactate of 1 mmol/l (blood results are shown in Table 1). Initially this gave an impression of sepsis with unknown origin (in view of fever on a background of an immunosuppressed status). The treatment plan included intravenous (IV) crystalloid fluids, Tazocin (broad spectrum antibiotic) after blood cultures were taken, doubling the dose of prednisolone and omitting the mycophenolate mofetil, pending the results of the septic screen.

However, 2 hours later it was noted the patient appeared to be drowsy, but responsive and obeying commands. Another hour later the patient was given a computed tomography (CT) scan of the head following further concerns about her progressive drowsiness. This was reported as normal and a lumbar puncture was planned to rule out meningoencephalitis. Following the CT scan, she became profoundly hypotensive with a systolic BP of 60–70 mmHg. Given the amount of fluid resuscitation needed, a catheter was inserted by nursing staff who reported that there was a tampon present with some green discharge. This was removed and sent for culture and sensitivity (C+S) testing. The patient reported that the tampon had been inserted less than 12 hours prior to admission. A diagnosis of toxic shock syndrome was made and the patient was transferred to the intensive care unit (ICU).

Following advice from the microbiology department the patient was started on clindamycin and meropenem treatment on arrival at ICU, and Tazocin was discontinued. Noradrenaline was commenced; however, it soon became clear that the patient had developed vasoplegia secondary to severe sepsis. Adrenaline and vasopressin were subsequently commenced with good effect. Intravenous immunoglobulin (IVIG) was also started. Despite vasopressors and aggressive fluid resuscitation the patient remained oliguric and became progressively more acidotic. Continuous veno-venous haemofiltration (CVVHF) was initiated. After 3 days on intensive care she was weaned off the CVVHF and vasopressor support, and transferred to ward care. Four days later she was discharged home from the ward, with advice from the gynaecologist to not use tampons again. A high vaginal swab subsequently grew Staphylococcus aureus, while two sets of blood C+S tests were negative.

Investigations

Clinical suspicion is the most important step, as there may be no clues. Common laboratory findings include abnormal liver function tests with hypoalbuminemia, acute renal failure, low platelet count and raised creatinine kinase.¹⁴

Skin, vaginal and pharyngeal swabs (according to the focus of infection) can confirm the source of infection. Blood C+S may be positive and, in cases of GABHS TSS, antistreptolysin O titre (ASOT) may be detected.^14,15

Failure to treat the infection with penicillin is common. Clindamycin is superior to penicillin because of its potency in suppressing bacterial toxin synthesis as well as facilitating phagocytosis. Clindamycin also suppresses lipopolysaccharide-induced monocyte synthesis of TNF-α.¹⁶

Intravenous immunoglobulin (IVIG) therapy reduces T cell production of pro-inflammatory cytokines, and significantly increases the plasma neutralising activity against super-antigens, thereby resulting in improved survival in many TSS studies.^16,17 IVIG therapy has also demonstrated an anti-TSST-1 effect and significantly improved survival in cases of S aureus TSS.¹⁸

Identification of potentially implicated foreign bodies – especially tampons, surgical drainage and irrigation or excision of infected sites such as implants or necrotizing fasciitis – is of high priority, and input from surgical teams can be essential.

Our case emphasises the importance of maintaining a high level of suspicion for TSS in patients who are at high risk of the condition (eg menstruating ladies using tampons, patients who are immunosuppressed, and patients who have trauma, burns, cellulitis, pharyngitis or implants) and who are presenting with a febrile illness and signs of shock or hypoperfusion. It is important to take a formal and accurate menstrual and sexual history in selected cases.

Fluid resuscitation and intravenous antibiotics after blood C+S is essential and early ICU involvement for possible vasopressors, haemofiltration and IVIG use is required. Surgical excision of any focus of infection may result in a significant decrease in morbidity and mortality.