Lessons from practice
Volume 204 - Issue 4
Necrotising myositis presenting as multiple limb myalgia
Authors: Henrique Nicola and David JR Morgan
Med J Aust 2016; 204 (4): 157-158. || doi: 10.5694/mja15.00815
Published online: 7 March 2016
Published online: 7 March 2016
This rare but potentially fatal condition is a diagnostic conundrum, often presenting as systemic toxicity and widespread myalgia without focal features
Clinical record
A previously healthy 40-year-old man was referred by his general practitioner to our hospital after a short prodromal period of a sore throat and rapidly deteriorating constitutional symptoms. Most pertinent to his diagnosis was the development of non-traumatic, localised, right calf pain 48 hours before admission that progressed to an inability to bear weight by the time of hospital presentation. On initial physical examination, he had a temperature of 37.8°C, diffuse muscle tenderness in all four limbs and an exquisitely hyperalgesic localised area on the right mid-calf. Examination of his throat showed a diffuse pharyngitis. There was no rash or arthritis, and his cardiovascular, respiratory and gastrointestinal systems were all unremarkable at admission.
A blood sample and throat swab were taken and, after an initial blood and microbiological culture work-up, empirical treatment with intravenous flucloxacillin and vancomycin was commenced. Early pathology test results showed a creatine kinase (CK) level of 380 U/L (reference interval [RI], < 171 U/L), serum creatinine level of 158 μmol/L (RI, 55–105 μmol/L), white cell count of 3.1 × 109/L (RI, 4.0–11.0 × 109/L) with increased band forms, and deranged liver function test results, with a bilirubin level of 60 μmol/L (RI, < 20 μmol/L) and alanine transaminase level of 242 U/L (RI, 0–45 U/L).
Over the next 24 hours, the patient’s condition deteriorated, prompting consultation with an infectious diseases specialist. This resulted in a change of antibiotic therapy to ceftriaxone to broaden the coverage of respiratory pathogens, given his acute pharyngitis, and clindamycin to restrict any potential toxin production. By the evening of the second hospital day, the patient was referred to the intensive care unit (ICU) with evolving multiple organ failure. He was now febrile to a temperature of 40°C, with evolving septic shock, pulmonary infiltrates, worsening acute kidney injury (serum creatinine level, 201 μmol/L, and oliguria) and mild delirium. His right calf remained a focal point of concern, with an accompanying tenfold rise in CK level to 3656 U/L.
The patient’s condition further deteriorated during his first night in the ICU, necessitating aggressive fluid resuscitation, vasopressor support and haemodialysis. By the morning of the third day in hospital, 12 hours after ICU admission, an isolated, small, tender area of discolouration was noted over the distal posteromedial aspect of the right leg, with no other clinically apparent lesions, but persisting myalgia in all four limbs. This, in conjunction with the confirmation of gram-positive cocci grown from the admission blood and throat swab cultures, prompted the initial consideration of necrotising fasciitis. Subsequent imaging of the lower limbs with ultrasound and non-contrast computed tomography (CT) scans excluded venous thrombosis and fascial thickening, but both tests showed subtle swelling of the calf muscles, suggesting myositis (Figure, A). An urgent plastic surgery consultation mandated surgical exploration of the right calf, and the diagnosis of necrotising myositis (NM) (Figure, B) was subsequently obtained.
Due to the ongoing requirement for frequent soft tissue debridement, the patient was ventilated and transferred to the nearest quaternary hospital. Here, he underwent further imaging of all four limbs and successive debridement of his right leg and both arms for NM on Days 4, 5, 7, 9 and 18 of admission. After receiving confirmation of susceptibility, the ceftriaxone was changed to benzylpenicillin, while clindamycin was retained and intravenous immunoglobulin (IVIG) commenced. Microbiological serotyping confirmed Streptococcus pyogenes with type emm 89.0 strain; exotoxin assays were not conducted. The patient’s total ICU stay lasted 17 days, with liberation from haemodialysis after 7 days and the ventilator after 9 days, resolution of his multiple organ failure, and all four limbs preserved without amputation. After 33 days in hospital, he was discharged to a rehabilitation centre.
Necrotising myositis is a rare but potentially fatal form of infection, predominantly characterised by muscle necrosis capable of rapidly progressing to multiple organ failure in healthy young adults. Published literature attributes group A streptococcus as the most commonly implicated pathogen, but NM has also been associated with groups C and G streptococci, Bacteroides subtilis, Staphylococcus aureus and Peptostreptococcus.1,2
Our case highlights three important clinical lessons. First, NM typically involves a single limb or area. Multiple limb involvement in the initial presentation has only been reported in two previous cases.3,4 Second, despite the widespread limb involvement in our patient, skin discolouration was a subtle, late sign. It presented in only one limb 72 hours after symptom onset, at a stage when the toxic shock syndrome was already apparent. Of 14 previously reported cases, only five describe skin discolouration and two describe local erythema.1,3-8 Third, and most crucially, NM, like necrotising fasciitis, remains a clinical diagnosis, with most investigations being indeterminate.
Increased serum CK level has previously been lauded as a potential early warning sign,4-6 but the initial CK result at our patient’s hospital admission (already more than 48 hours after the onset of symptoms) was only marginally raised (380 U/L). We found two other previously reported cases of NM where the CK level remained below 500 U/L at 48–72 hours after symptom onset.6,7 These findings suggest that excluding NM on the basis of small rises in serum CK level (< 500 U/L) is unreliable. Similarly, a reliance on imaging to provide a diagnosis can result in non-specific or negative findings, delaying a definitive surgical diagnosis and treatment.8 While modern imaging can be performed rapidly, the CT and ultrasound scan findings in our patient were subtle, non-specific and ultimately delayed surgery by 3–4 hours.
Once a diagnosis of NM is suspected, aggressive surgical debridement, appropriate antibiotic therapy and supportive care are mandated for survival. Early surgical intervention has reduced mortality from 100% to 37%,1 but with the consequence of significant long-term morbidity for many survivors. Aggressive group A streptococcal infections respond less well to penicillin and continue to be associated with high mortality and extensive morbidity, leading to the use of adjunctive therapies.9 In a recent observational Australian study of 84 patients with severe invasive group A streptococcal infection, the addition of clindamycin resulted in a significant reduction in mortality, which was further enhanced by the inclusion of IVIG.10 Clindamycin inhibits bacterial protein synthesis at the level of the 50S ribosome, resulting in decreased exotoxin production and increased microbial opsonisation and phagocytosis, while IVIG increases the ability of plasma to neutralise superantigens.9,10 Finally, conclusive evidence is lacking for the use of hyperbaric oxygenation, aimed at reducing hypoxic leucocyte dysfunction, and it was not used for this patient.Lessons from practice
Necrotising myositis is a rare but potentially fatal condition. It is a diagnostic conundrum, often presenting as systemic toxicity and widespread myalgia without focal features.
Improved survival is underpinned by early clinical diagnosis, appropriate antibiotic therapy including clindamycin to reduce exotoxin load, and urgent surgical referral. Adjunctive therapies such as intravenous immunoglobulin and hyperbaric oxygenation should be considered based on individual circumstances.
Previously suggested diagnostic investigations such as serum creatine kinase levels, ultrasound and computed tomography scans are unreliable, mandating a high index of clinical suspicion to make a diagnosis.
Figure
A: Computed tomography scan (transverse plane) of the right leg, showing subtle hypointense and mildly expanded gastrocnemius and soleus muscles with intact fascia, suggestive of myositis. B: Haematoxylin and eosin stained paraffin section of the right gastrocnemius muscle, showing necrotic skeletal muscle, inflammatory infiltrate with disintegrating neutrophils and colonies of streptococcal bacteria.
Competing interests
No relevant disclosures.
Acknowledgements
We thank Clayton Golledge, infectious diseases physician at Sir Charles Gairdner Hospital, and Heinrich Sonnendecker and Bridget Cooke, histopathologists at St John of God Subiaco Hospital, for providing valuable additional insights and contributions to this case report.
References
- Baevsky R, Ishida JT, Lieberman SA. Group A beta-hemolytic streptococcal glossal necrotizing myositis - case report and review. Med Gen Med 2005; 7: 8.
- Nordal HH, Kittang BR, Bindoff LA. Rhabdomyolysis after group C streptococcal infection. Infect Dis Rep 2010; 2: e15.
- Wagner JG, Schlievert PM, Assimacopoulos AP, et al. Acute group G streptococcal myositis associates with streptococcal toxic shock syndrome: case report and review. Clin Infect Dis 1996; 23: 1159-1161.
- Kang N, Antonopoulos D, Khanna A. A case of streptococcal myositis (misdiagnosed as hamstring injury). J Accid Emerg Med 1998; 15: 425-426.
- Subramanian KN, Lam KS. Malignant necrotising streptococcal myositis: a rare and fatal condition. J Bone Joint Surg Br 2003; 85: 277-278.
- Madhusudhan TR, Sambamurthy S, Williams E, Smith IC. Surviving streptococcal toxic shock syndrome: a case report. J Med Case Rep 2007; 1: 118.
- Hourmozdi JJ, Hawley DA, Hadi CM, et al. Streptococcal necrotizing myositis: a case report and clinical review. J Emerg Med 2014; 46: 436-442.
- Chaudhry AA, Baker KS, Gould ES, Gupta R. Necrotizing fasciitis and its mimics: what radiologists need to know. AJR Am J Roentgenol 2015; 204: 128-139.
- Stevens DL. Streptococcal toxic-shock syndrome: spectrum of disease, pathogenesis, and new concepts in treatment. Emerg Infect Dis 1995; 1: 69-78.
- Carapetis JR, Jacoby P, Carville K, et al. Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group a streptococcal infections. Clin Infect Dis 2014; 59: 358-365.