Early diagnosis, debridement improves necrotizing soft tissue infection results

Early diagnosis of necrotizing soft tissue infection — often referred to as necrotizing fasciitis — is essential, but according to experts who are familiar with these conditions, they can be challenging to diagnose because they lack distinct clinical features. However, early surgery and choosing the right course of antibiotic treatment may help prevent mortality, particularly with necrotizing fasciitis.

A variety of tools have been described for the diagnosis of necrotizing fasciitis. “But, no one tool is sensitive and specific enough,” Carlo L. Romanò, MD, of Istituto Ortopedico Galeazzi, in Milan, told Orthopaedics Today Europe. Therefore, an orthopaedic surgeon who suspects the patient has this infection is one of the most important diagnostic tools there is, he said.

Romanò discussed the three types of necrotizing fasciitis (NF). Type 1 NF is a polymicrobial infection with one or more facultative anaerobic species. He said they may include various fungi, as well as A-hemolytic streptococci, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.

Image: Calamita M

“The infecting organisms are often introduced at sites of surgery or trauma and are typically located at the trunk, abdominal wall, perianal and groin areas,” Romanò said.

Type 2 NF is monomicrobial and encompasses invasive group-A hemolytic streptococci and, less frequently, other types of streptococci or staphylococci. It can occur in healthy immunocompetent patients with “minor cutaneous/muscular injuries,” according to Romanò.

The type 3 NF is caused by marine gram-negative vibrio bacteria, such as Vibrio vulnificus. They are present after minor injuries that occur in salt water, such as fish stings or shellfish injuries.

“This third type is associated with a fulminant course with development of multiorgan failure within 24 hours, if not treated,” Romanò said.

Incidence, mortality rates

Necrotizing fasciitis rarely occurs and it develops mainly in adults. Per year, the illness affects 0.08 children in 100,000 and 0.4 adults in 100,000, Romanò said. Its incidence increases in adults older than 50 years and reaches an incidence of 12 cases per 100,000 people in individuals older than 80 years.

Mortality rates range from 25% to 30%, with 30% of all mortality due to sepsis, according to Romanò, who noted children may have a higher risk of mortality from a fulminant course.

People with pre-existing conditions are also at higher risk for NF, especially anyone with diabetes mellitus, immunosuppression, end-stage renal failure, liver cirrhosis, pulmonary disease or malignancy.

“I would like all surgeons to be aware of the disease, because you do not diagnose a condition that you do not think about, and always have this diagnosis in mind, especially for the elderly and the very young, the people who are intravenous drug abusers or people with hepatitis C infection,” Amr Abdelgawad, MD, an orthopaedist in the Department of Orthopaedic Surgery & Rehabilitation, Paul L. Foster School of Medicine, Texas Tech University Sciences Center, in El Paso, Texas, USA, told Orthopaedics Today Europe.

“Have the diagnosis in mind always, and be aggressive,” he said.

Early recognition and diagnosis

Early diagnosis of NF may save a patient or increase their chance of survival, yet, according to Lancerotto and colleagues, the diagnosis was missed or delayed in 85% to 100% of cases in large studies published in the literature, Romanò noted.

By comparison, a missed diagnosis could result in death or amputation for the patient. Russell R. Russo, MD, an orthopaedist in the Department of Orthopaedics at Louisiana State University Health Sciences Center, in New Orleans, USA, said.

Russo noted the infection can rapidly spread at a rate of 1 cm per hour.

Because it lacks specific clinical features in the initial stage of the disease, necrotizing fasciitis is in fact often underestimated or confused with various conditions, including cellulitis or abscess, erysipelas, phlebitis, arthritis, deep vein thrombosis, sciatica, viral illness, traumatic knee effusion, or bursitis, etc.,” Romanò said. “A patient complaint of severe pain out of proportion to the apparent severity of the lesion should alert the physician to the possibility of necrotizing fasciitis.”

Manjunath noted in his research that physicians should look for flu-like symptoms, such as diarrhea, thirst or gastric symptoms, red, shiny, tense and edematous lesions that lack borders, blistering, which are seen in half of all patients, and such late signs as crepitus and necrosis.

Blood test and cultures

According to Lancerotto and colleagues, necrotizing fasciitis is characterized by subtle, rapid onset of spreading inflammation. The necrosis starts from the fascia, muscles and subcutaneous fat, with subsequent necrosis of the overlying skin.

Diagnostic testing may not detect NF early, according to Romanò, because it is neither sensitive nor specific enough, he said. However, blood cultures may be used to check elevated C-reactive protein levels, white blood cell counts, creatinine phosphokinase levels, reduced amounts of albumin and sodium, and increased prothrombin time or activated partial thromboplastin.

None of these parameters are specific, according to Romanò.

Treatment options

If an orthopaedic surgeon suspects NF, then immediate and extensive radical debridement of necrotic tissues is mandatory, Romanò said. He explained there is a nine-fold increase in mortality that was reported in the literature when debridement was delayed more than 24 hours after hospital admission or if the surgeon does not perform a complete debridement.

Follow-up with appropriate antibiotics, amputation and reconstructive surgery, if necessary, is also something that Romanò mentioned.

Russo told Orthopaedics Today Europe, “People who have their surgery and debridement within 10 [hours] to 24 hours once they hit the door, do much better than the patients for whom the diagnosis is not made for days” after they are hospitalized.

When patients seem sicker than they appear, orthopaedists should have a high index of suspicion, orthopaedic surgeon William T. Obremskey, MD, MPH, of Vanderbilt Orthopaedic Institute, in Nashville, Tenn., USA, told Orthopedics Today Europe.

A hands-on physical examination is necessary to recognize the condition early, according to Russo, because X-rays, CT scans and other imaging may not detect the disease and are time-consuming.

Excise, then use hyperbaric oxygen

Clinical diagnosis, excision of infected tissue, and prescribing the correct antibiotic help eliminate the disease, according to Klaus Kirketerp-Møller, MD, of the Department of Orthopaedic Surgery at Hvidovre Hospital, in Hvidovre, Denmark.

“I think most surgeons might see one or two [cases of NF] in their whole career, so to know that it is there is very important,” Kirketerp-Møller told Orthopaedics Today Europe. “If you suspect it, and your suspicion is more than fair, then you should go for surgery and then treat with antibiotics. And then, [once] you have control of the patient, the patient is revived, and they do not have rapid development of the infection, [then] you should consider hyperbaric oxygen, unless you have it available in the hospital and you could use it right away” he said.

The high mortality rates with this condition are increased in individuals with comorbidities based on a study by Das and colleagues published in 2012, Kirketerp-Møller said. He noted, however, that even healthy patients may develop NF and related soft tissue infections.

Diagnosis of NF requires a clinical examination to recognize the symptoms early, which include redness, warmth, swelling and pain, Kirketerp-Møller said. But, the symptoms then rapidly progress into worsening pain and increased deterioration, at which time the physician may notice crepitus in the skin on palpation, which he described as feeling like cold snow in the hands.

Physical exam critical

“Nowadays, people tend to rely on X-rays, CT scans and labs,” Abdelgawad said. “We are getting farther away from going to see patients and putting hands on them — the human touch, the human effect. With [recognizing] necrotizing fasciitis, it is all physical examination.”

During surgery to debride or excise tissue and diagnose NF, the orthopaedist may see fluid in the patient’s tissues of that looks like dirty dishwater, Kirketerp-Møller said. He recommended a combination of surgery, hyperbaric oxygen and broad-spectrum antibiotics to eliminate the infection since antibiotics alone would not reach the infection.

The act of debridement rids the tissues of the anaerobic environment in which the bacteria thrive. Hyperbaric oxygen also would diminish those areas, Kirketerp-Møller said, but not all European hospitals have access to that technology.

“It has been proven that the neutrophils are activated by hyperbaric oxygen,” Kirketerp-Møller told Orthopaedics Today Europe. “Hyperbaric oxygen reactivates the immune system.”

The surgery may also require excision down to the fascia, removal of the fascia itself, and sometimes excision of “the entire skin of an extremity or the trunk,” he said.

Causative pathogens, antibiotics

If the surgeon has access to immediate microscopy, then he or she should send a tissue sample in order to identify the pathogen(s) and prescribe the correct antibiotic, according to Kirketerp-Møller.

“The antibiotic treatment in the beginning needs to be very broad spectrum antibiotics,” he said. “Giving the wrong antibiotic or too narrow spectrum in the beginning could be bad.”

The necessary antibiotics depend not only on the pathogen present but also on the resistance of the bacteria to antibiotics in different geographic areas, he said.

“In Scandinavia and Holland, we rarely see resistance to the most common antibiotics,” Kirketerp-Møller said, although “in the United States and in southern Europe, you have to treat with more aggressive antibiotics.”

According to Romanò, “Further investigation on the pathogenesis and the development of new diagnostic tools for early and differential diagnosis of the disease may reduce the impact of this challenging disease.”

Experts agreed that greater awareness of necrotizing soft tissue infections and their treatment may improve the rates of early diagnosis and recovery. – by Renee Blisard Buddle

• References:
• Das DP. BMC Infectious Diseases. 2012; doi: 10.1186/1471-2334-12-348.
• Lancerotto L. J Trauma Acute Care Surg. 2012. doi: 10.1097/TA.0b013e318232a6b3.
• Majunath K. A clinico pathological study and management of necrotising fasciitis [dissertation]. Bangalore, India. Rajiv Gandhi University of Health Sciences; 2010. http://119.82.96.198:8080/jspui/handle/123456789/4752. Accessed February 12, 2013.
• Naqvi GA. Scand J Trauma Resusc Emerg Med. 2009; doi: 10.1186/1757-7241-17-28.

• For more information:
• Amr Abdelgawad, MD, can be reached at 4801 Alberta Ave., El Paso, TX 79905, USA; email: amr.abdelgawad@ttuhsc.edu.
• Klaus Kirketerp-Møller, MD, can be reached at Kettegaards Alle 30, 2650 Hvidovre, Denmark; email: kkm@dadlnet.dk.
• William T. Obremskey, MD, MPH, can be reached at 1215 21st Ave. South, Suite 4200, Nashville, TN 37232, USA; email: william.obremskey@vanderbilt.edu.
• Carlo L. Romanò, MD, can be reached at Via Riccardo Galeazzi, 4 20161 Milan, Italy; email: carlo.romano@grupposandonato.it.
• Russell R. Russo, MD, can be reached at 1542 Tulane Ave., 6th Floor, New Orleans, LA 70112, USA; email: rrusso@lsuhsc.edu.

Disclosures: Abdelgawad, Kirketerp-Møller, Obremskey, Romanò and Russo have no relevant financial disclosures.

 

What non-invasive methods can surgeons use to differentiate between cellulitis and necrotizing fasciitis? What is the role of diagnostic imaging?

No reliable diagnostics help differentiate

There are no reliable non-invasive diagnostics to differentiate between cellulitis and necrotizing fasciitis. The gold standard is still surgical exploration and gram stain.

Wong and colleagues published a scoring system, the Laboratory Risk Indicator for Necrotizing Fasciitis, to differentiate between a necrotizing fasciitis (NF) and non-necrotizing soft tissue infection. This scoring system has a relatively good positive and negative predictive value. However, this cohort is a retrospective study and up to now has not been prospectively validated.

The role of diagnostic imaging is still limited. Sensitivity of a plain X-ray is 39% to 57%, according to Elliott and colleagues and Wall and colleagues. MRI is a much better tool to image soft tissue infection. Unfortunately, the sensitivity is still only 80% to 90% and the specificity is 50% to 55%. Another difficulty is the lack of 24/7 availability of MRI. CT could probably make a better differentiation. Zacharias and colleagues state that a negative CT (absence of abnormal soft tissue swelling, absence of gas and absence of infection of the fascia, abscess or necrosis) rules out NF, and with a positive CT, the diagnosis is plausible (sensitivity 100% and specificity of 81%). However, given that, NF is an aggressive and progressing disease. Imaging should not delay treatment (antibiotics, diagnostic incision, skin sparing necrotectomy and resuscitation).

• References:
• Elliott DC. Ann Surg. 1996;224:672-683.
• Wall DB. Objective criteria may assist in distinguishing necrotizing fasciitis from non-necrotizing soft tissue infection. Am J Surg. 2000;179:17-21.
• Wong CH. Crit Care Med. 2004;32:1535-1541.
• Zacharias N. Arch Surg. 2010; doi: 10.1001/archsurg.2010.50.

Vincent de Jong, MD, is a trauma surgeon at the Academic Medical Centre in Amsterdam.
Disclosure: de Jong has no relevant financial disclosures.

Differentiate with surgical intervention

In necrotizing fasciitis, cellulitis only involves the subcutaneous layer, however in the initial setting it may be difficult to differentiate between these two conditions (Schmid MR). Necrotizing fasciitis is a rare, rapidly progressing disorder characterized by necrosis of the subcutaneous tissue and fascia. It is usually associated with systemic toxicity. Cellulitis only involves the subcutaneous layer, however, in the initial setting it may be difficult to differentiate between these two conditions (Schmid MR). The most reliable method of differentiating the two is through surgery. Clinical suspicion is important and in a moribund patient, necrotizing fasciitis (NF) should be kept in mind. Non-invasive methods can be divided into clinical examination and investigations, such as ultrasounds, radiographs, CTs and MRIs. Clinical examination of a patient with NF may reveal evidence of systemic toxicity. The ideal non-invasive screening test should be accessible, acceptable, sensitive, specific and cost-effective. It should recognize the disease at an early stage in order to guide treatment (Wilson JMG).

Ultrasound is accessible and acceptable to most patients. Studies have found high specificity and sensitivity in the hands of highly skilled technicians (Yen ZS). Plain radiography is often the first radiographic assessment and subcutaneous gas is said to be pathognomonic of NF. Unfortunately, this is not always present on the radiograph in the early stages of the disease and can often provide false reassurance (Saldana M). Like plain radiographs, a negative CT should not provide reassurance. CT has a higher sensitivity and specificity than plain radiographs, but MRI is preferable due to the reduced amount of ionizing radiation in comparison. MRI may be the ideal tool to differentiate between NF and cellulitis because MR imaging does a good job of revealing contrast enhancement of soft tissues and is highly sensitive in the detection of fluid collections (Rahmouni A, Schmid MR). Accessibility to MRI may also be an issue acutely.

In conclusion, the ideal non-invasive modality does not exist. There are merits of each technique, but ultimately surgical intervention provides definitive diagnosis and treatment for this severe disease.

• References:
• Rahmouni A. Radiology. 1994;192(2):493-496.
• Saldana M. Eur J Ophthalmol. 2010; 20:209-214.
• Schmid MR. AJR Am J Roentgenol. 1998;170(3):615-620.
• Wilson JMG. WHO Chronicle Geneva: World Health Organization. Public Health Paper #34. 1968;22(11):473. http://whqlibdoc.who.int/php/WHO_PHP_34.pdf
• Yen ZS. Acad Emerg Med. 2002;9(12):1448-1451.

Harry Benjamin-Laing, BSc, MBChB, MRCSEd, is a clinical research fellow in the Department of Trauma & Orthopaedic Surgery at University College London.
Disclosure: Benjamin-Laing has no relevant financial disclosures.