Pathogenesis and diagnosis
Historically, myonecrosis (better known as gas gangrene) was a common wound infection due to poor hygiene, with an incidence as high as 5% (currently estimated at 0.1%).
Two distinct types of clostridial myonecrosis are known. One type occurs in traumatized tissue and is associated with Clostridium perfringens and Clostridium histolyticum. The other type arises spontaneously and is caused by Clostridium septicum, presenting with hematogenous seeding from the gastrointestinal tract to the muscles. The incidence of spontaneous clostridium myonecrosis (SCM) is not known, probably due to difficult diagnosis. C. septicum is estimated to cause 20% of all (traumatic and spontaneous) cases . Clostridium species are anaerobic, large, gram-positive, gas-producing rod-like bacteria with the ability to produce environmentally resistant endospores that are widespread in nature and can be found in soil and the intestinal tracts of humans and animals . Still, C. septicum is considered a rare component of the gastrointestinal flora, only present in 2% of the population, preferably localized in the cecum and ileocecal junction . Its capacity to cause disease likely originates from coincidental occurrence of transient carriage and enhanced host susceptibility .
C. septicum produces multiple toxins, of which the alpha toxin, a necrotizing pore-forming cytolysin, is the most lethal, causing the extensive myonecrosis associated with fulminant SCM . The capability to infect normal healthy tissue, due to its aerotolerant characteristics, distinguishes C. septicum from other strains such as C. perfringens and C. difficile, which are obligate anaerobes .
The pathogenesis of SCM remains largely unclear, yet three possible patterns have been described: (i) visceral anaerobic cellulitis, (ii) visceral anaerobic cellulitis with contiguous spread to adjacent muscle, and (iii) myonecrosis arising at a site distant from the initial visceral lesion (less common) . The present case entails myonecrosis at multiple distant sites. It is suspected that the infection descends along the iliopsoas sheath from (most often) a gastrointestinal mucosal origin lesion, with ensuing hematogenous spreading . It is well described in literature that such gastrointestinal lesions are frequently undiagnosed adenocarcinoma of the colon, as is the case in our casus . Other predisposing factors such as leukemia, inflammatory bowel disease, diverticulitis, gastrointestinal surgery, lymphoproliferative disorders, chemotherapy, neutropenia, radiation therapy, AIDS, diabetes mellitus, necrotizing enterocolitis or distal ileitis, and the use of NSAID were not applicable to the current case .
While it has been established that C. difficile infections disproportionately affect older patients (≥ 65 years of age), such a correlation has not yet been described for C. septicum infections. Therefore, we performed a retrospective literature search of C. septicum case reports in the PubMed database over the last 10 years to gauge the prevalence of SCM in the elderly population. From a total of 160 case reports, we found 89 reports of adult patients with C. septicum infection (graph 1). The prevalence of SCM remains at a low steady level throughout the 4 youngest age groups spanning 18–54 years. Noteworthy, we observed a sudden increase in cases within the age group of 55–66 years, persisting up to the group of 74–85 years. In contrast, SCM prevalence in the age group ≥ 85 years dropped significantly, almost to the level found for the youngest age groups. Based on these findings, we hypothesize that SCM is underdiagnosed in the oldest age group.
Early recognition and treatment of SCM are critical for a desired outcome, but diagnosis is not straightforward and is usually delayed . The clinical presentation of SCM often starts with a sudden onset of severe localized muscle pain, in the absence of manifest injury, or other explanatory causes. Sometimes, heaviness or numbness is mentioned as early signs . The skin over the affected area may appear pale at first and then progress rapidly to a bronze appearance and finally to a purple or red hue . Typically, such colorations are combined with the development of edema and bullae filled with cloudy hemorrhagic or purplish fluid. Very often, crepitations are present, which differentiates SCM from streptococcal myositis [1, 14]. Other differential diagnosis can be (i) viral myositis, where injury is also absent but where pain perception is mostly diffuse, rather than localized, or (ii) rhabdomyolysis caused by trauma, intoxication, or metabolic disorders.
Initial systemic manifestations vary from the presence of fever and tachycardia to the development of signs of systemic shock. Illness progresses with thrombocytopenia, anemia, diffuse intravascular coagulation, kidney failure, and acute respiratory distress syndrome, ultimately leading to multiple organ failure . Sometimes, the disease can be obscure and only present with initial tachycardia, whereas severe pain, hypotension, and fever occur later in time . Routine laboratory analyses should be performed, since the levels of creatine phosphokinase, myoglobin, and potassium can be elevated after release from tissue and muscle breakdown. Additionally, knowledge of ABG, lactate, and pre-calcitonin levels can be useful when evaluating sepsis. Imaging such as radiography (echography), CT scan, or MRI may visualize gas bubbles present in soft tissue . Visualized gas offers a differential diagnosis from pyomyositis, where there is usually no systemic toxicity or gas present. On the short term, the involvement of a bacterial pathogen can be proven by gram staining of the affected tissue (e.g., bullous fluid) . If muscle necrosis is present, with spreading to skin, fat, subcutaneous tissue, and fascia, large gram-positive bacilli can be microscopically visible in between the degenerating muscle bundles without the characteristic lack of inflammatory cells (leukocytes) . A final diagnosis can only be obtained from a blood culture that can identify C. septicum.
Treatment and prognosis
There are two options for SCM treatment: (i) early and aggressive, often multiple, surgical debridement and (ii) antibiotic therapy . In want of the identification of the causative pathogen, a broad-spectrum empiric antibiotic treatment should be started promptly. Mostly, piperacillin-tazobactam 4.5 g plus clindamycin 900 mg are administered intravenously every 8 h .
Thorough surgical debridement is believed to be the single best predictor of outcome , but is not feasible with a widespread infection. In case of elevated compartment pressures, a fasciotomy may be necessary .
Once the definitive causative species C. septicum is known, the antibiotic therapy can be switched to penicillin 3–4 million units plus clindamycin 900 mg both intravenously every 8 h or tetracycline 500 mg intravenously every 6 h. In case of penicillin allergy, only clindamycin can be used.
Despite the fact that C. septicum is aerotolerant, one study did show promising results combining the above treatment with hyperbaric chamber therapy, showing a decrease in mortality from 70 to 25% . However, choosing for hyperbaric oxygen therapy should never delay antibiotics admission or surgical debridement.
Every patient that survives the treatment should undergo a colonoscopy to rule out gastrointestinal tract lesions , since a spontaneous systemic infection with C. septicum likely originates from infiltration of the pathogen from the gut. If applicable, a colectomy or lesion resection could prevent reinfections from occurring.
Overall prognosis is poor, and mortality rates reach levels of 67–100%. In most cases, death occurs within 24 h . More specifically, risk factors for a fatal outcome are underlying malignancy and an immunocompromised state. The prognosis of SCM is worse compared to the traumatic type, with survival rates as low as 19% .