Fulminant Clostridium Septicum myonecrosis in well controlled diabetes: a case report
© Tran and Myint; licensee BioMed Central Ltd. 2007
Received: 19 April 2007
Accepted: 30 October 2007
Published: 30 October 2007
Diabetic myonecrosis with Clostridium Septicum is uncommon but carries a high mortality rate. This commensal organism is part of the gastrointestinal tract flora and can become extremely virulent, often in the setting of immuno-suppression such as neutropenia, occult malignancy (commonly caecal) and poorly controlled diabetes. The case report is unusual in that there are few risk factors other than very mild neutropenia. This highlights the opportunistic character of the organism and recommends that a high index of suspicion and vigilance be carried out in the presence of fevers and sepsis, even in the well-controlled diabetic population.
The case reports a unique and peculiar condition of extensive and fatal Clostridium Septicum myonecrosis in a diabetic patient undergoing chemotherapy for her breast cancer. Contrary to previous reports where the common risk factors are poorly controlled diabetes, severe neutropenia and classically caecal carcinoma, a sanctuary for the bacillus, our patient had only mild and asymptomatic neutropenia. Another notable risk factor was morbid obesity in the patient which confers a general increase in all-risk mortality. Hyperinsulinaemia in the setting of insulin resistance and obesity is another critical factor, thought to differentially inhibit neutrophil function. Whilst each factor is modest on its own, the combination delivers a fatal outcome in this case once the organism has disseminated.
A 68 year-old woman with type 2 diabetes mellitus and intraductal breast carcinoma presented with a 2-day history of rapidly onset left groin pain and leg weakness. There were some discoloration and blisters on the medial aspect of the same thigh and she had felt warm but denied any rigors. She became unable to weight bear and began to vomit on the day of presentation. No history of trauma was noted to the area. Her past medical history included type 2 diabetes of eight years with reasonable control, requiring Metformin 1 gm twice daily. Her home daily glucose readings oscillated between ~5–7 mmol/L in the previous 6–8 weeks, with a HbAc1 of 6.5% two weeks prior. Serial levels had been between 6.2 and 7.1% in the previous 2 years. The only diabetes complication included mild background non-proliferative retinopathy which has been observed. Her breast cancer was diagnosed 6 months prior with grade 3 intraductal carcinoma with axillary metastasis requiring mastectomy with axillary clearance followed by systemic adjuvant chemotherapy with Adriamycin and Cyclophosphamide. Her last course of chemotherapy was 10 days prior with no mucositis or any other adverse effects. Past medical problems included hypertension and diverticular disease requiring partial sigmoid bowel resection 6 years ago.
Necrotising fasciitis is a critical condition involving the Clostridial species. Cl. Septicum is part of the normal gastrointestinal tract flora but when infection occurs, it is often fatal, especially in the diabetic population. The infection is well documented in other immunocompromised states such as leukaemia, post-chemotherapy neutropenia and occult malignancies, often colonic [1, 2]. Contrary to its close cousin, Cl. Perfringens which is strictly anaerobic, Cl. Septicum is relatively more aerotolerant and thus can survive much longer as spores in normal and consequently can infect healthy tissues. It is also more virulent because the inoculum required for Cl. Septicum to cause an infection is ~300 times lower in mice compared with Cl. Perfringens . It flourishes in tumor tissue because there is often marked anaerobic glycolysis occurring. Focal area of necrosis present in such tissue may also be hypoxic, accelerating the spread of the organism. The presence of poorly controlled diabetes can aggravate the risk by the poor vascular supply with relative ischaemia of the muscle. Where there is persistent hyperglycaemia, leucocytes do not function optimally, further aggravating the risk of systemic sepsis. In neutropenic sepsis and haematologic malignancies, there are often abrasions and ulcerations of bowel mucosa allowing the organism a port of entry into the circulation. This species is made more virulent by producing large amount of toxins and proteolytic enzymes, further accelerating its spread . The DNases β-toxin is thought to assist in spreading through the tissue planes and hyaluronidase δ-toxin in the muscular tissue destruction respectively.
Another important factor is the patient's morbid obesity, which contributes to her both primary diagnoses of breast cancer and well controlled type 2 diabetes . Although not directly responsible for the fasciitis, the obesity also markedly amplifies her risk of all cause mortality . Furthermore, obese patients appear to under-report their own health status, even in the absence of chronic disease, which may have delayed the patient's presentation with a subsequent fatal outcome .
The case is unusual in two aspects. The first is the complete absence of trauma or the presence of a colonic malignancy. Secondly, her diabetes control had been satisfactory as reflected by the biochemical parameters. This is thought to be due to the differential effect of hyperinsulinaemia in the setting of insulin resistance on neutrophil function, irrespectively of glycaemic status [8, 9]. Thus, it is postulated that in the presence of mild neutropenia, whose function is inhibited by effect of insulin excess, the bacillus was able to find a port of entry, probably via micro-abrasions of the bowel mucosal lining. It then is able to systemically and overwhelmingly disseminate by the mechanisms previously described.
Because of this accelerated spread of infection, most cases invariably succumb to overwhelming sepsis with a mortality exceeding 80%. Outcome therefore critically depends upon early recognition and diagnosis of the condition. Treatments should include aggressive resuscitation, prompt institution of the appropriate combination antibiotics and radical surgical debridement. Hyperbaric therapy should also be considered where available. In paediatric patients where there are often fewer co-morbidities, the situation can sometime be salvaged with extensive surgery .
The case highlights the grave prognosis of Clostridial sepsis, especially where there are associated co-morbidities. It is critically important that this highly fatal condition is considered early and frequently in septic patients, even in the presence of well controlled diabetes so that early and appropriate therapy can be implemented. With the increasing immunocompromised population, compounded by the exploding epidemic of type 2 diabetes, obesity and breast tumor being the commonest cancer in females, the incidence of this peculiar infection can only be expected to escalate.
Written informed consent was obtained from the patient's next of kin.
We are very much indebted to Geoffrey M Kellerman for his constructive and analytical comments of this manuscript (sighted and approved by GMK).
- Chew SSB, Lubowski DZ: Clostridium Septicum and malignancy. ANZ J Surg. 2001, 71: 647-649. 10.1046/j.1445-1433.2001.02231.x.View ArticlePubMedGoogle Scholar
- Katlic MR, Derkac WM, Coleman WS: Clostridium septicum infection and malignancy. Ann Surg. 1981, 193: 361-4. 10.1097/00000658-198103000-00020.View ArticlePubMedPubMed CentralGoogle Scholar
- Stevens DL, Musher DM, Watson DA, Eddy H, Hamill RJ, Gyorkey F, Rosen H, Mader J: Spontaneous nontraumatic gangrene due to Clostridium septicum. Rev Infect Dis. 1990, 12: 286-296.View ArticlePubMedGoogle Scholar
- MacFarlane S, Hopkins MJ, MacFarlane GT: Toxin synthesis and mucin breadkdown are related to swarming phenomenon in Clostridium septicum. Infect Immun. 2001, 69: 1120-1126. 10.1128/IAI.69.2.1120-1126.2001.View ArticlePubMedPubMed CentralGoogle Scholar
- Bray GA: Medical consequences of obesity. J Clin Endocrinol Metab. 2004, 89: 2583-2589. 10.1210/jc.2004-0535.View ArticlePubMedGoogle Scholar
- Australian National Health Medical Research Council – Clinical practice guidelines for the management of overweight and obesity in adults. 2003, last accessed 12-November-2007,http://www.health.gov.au/internet/wcms/publishing.nsf/Content/obesityguidelines-guidelines-adults.htm/
- Okosu I, Choi S, Matamoros T, Dever G: Obesity is associated with reduced self-rated general health status: evidence from a representative sample of white, black, and Hispanic Americans. Prev Med. 2001, 32: 429-36. 10.1006/pmed.2001.0840.View ArticleGoogle Scholar
- Alba-Loureiro TC, Hirabara SM, Mendonca JR, Curi R, Pinthon-Curi TC: Diabetes causes marked changes in function and metabolism of rat neutrophils. J Endocrinol. 2006, 188: 295-303. 10.1677/joe.1.06438.View ArticlePubMedGoogle Scholar
- Fejfarova V, Jirkovska A, Lupinkova J, Kovar J, Kalanin J, Striz I, Skibova J, Boucek P, Pelikanova T: Effect of acute hyperglycemia and/or hyperinsulinemia on polymorphonuclear functions in healthy subjects. Metabolism. 2006, 55: 811-8. 10.1016/j.metabol.2006.02.007.View ArticlePubMedGoogle Scholar
- Barnes C, Gerstle JT, Freedman MH, Carcao MD: Clostridium septicum myonecrosis in congenital neutropenia. Paediatrics. 2004, 114: 757-760. 10.1542/peds.2004-0124.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.