Pathophysiology paper: Necrotizing fasciitis

Pathophysiology paper: Necrotizing fasciitis
Anatomical and Physiological Background
The major system affected by necrotizing fasciitis is the integumentary system which consists of the skin and its appendages. The subcutaneous fascia is made up of sheets of connective tissue located beneath the skin. The primary function of this tissue is to stabilize, impart strength, separate muscles, and maintain vessel patency. There are various classifications of fascia to include superficial, deep, visceral, and classification according to anatomical location (Tobin, 2011). The superficial fascial is located directly below the skin and superficial adipose tissue. The composition of this fascial is loosely packed with interwoven collagen and elastic fibers. On the other hand, deep fascia surrounds the bones, muscles, nerves, and blood vessels. The deep fascia is further divided into the aponeurotic fascia and epimysial fascia which surrounds skeletal muscles.

Fascia provides support to surrounding tissues and transmits mechanical tension generated by external forces. A healthy fascia is relaxed, wavy, and flexible and these properties become lost when damaged through injury or inflammation. During these activities, the fascial layers tighten and restrict the movement of underlying layers causing pain and decreased blood flow. Within the fascia are sensory nerves including the nociceptors, proprioceptors, mechanoreceptors, thermoreceptors, and chemoreceptors (Tobin, 2011). A complex subcutaneous vascular network located between the dense and loose adipose tissue supplies blood to the skin. Necrotizing fasciitis is a rare disease that causes inflammation and necrosis of multiple layers including the muscles, subcutaneous fat, and vessels that form the fascia. The disease interferes with the integrity of the subcutaneous and deep fascia including surrounding blood vessels leading to ischemia. Emergency debridement of the necrotic tissue is the standard therapy for the management of the disease.

Introduction to the Disease

Skin diseases are common in healthcare today and they are found in more than half of the adult population. Although most of these diseases occur commonly and are easily treated, some rare and potentially fatal skin diseases are observed. Necrotizing fasciitis (NF) is an uncommon skin disease that results in gross mortality and morbidity if left untreated. The disease affects soft tissues and destroys the skin as well as the subcutaneous tissue beneath the skin. Necrotizing fasciitis is commonly known as a flesh-eating disease and is believed to be caused by group A Streptococcus. The disease can be easily confused with cellulitis and other superficial infections with studies indicating that only 15% to 34% of the cases are accurately diagnosed (Tessier et al., 2019). The disease was first described in 1883 by a confederate army surgeon, Joseph Jones. The disease rarely occurs in children and adults between the age of 38 to 44 are commonly affected. Understanding the manifestation of the disease and its pathophysiology is critical because only early diagnosis and aggressive surgical treatment can reduce mortality and morbidity.

Pathophysiology of the Disease

Necrotizing fasciitis is a progressive skin disease that rapidly spreads through the fascial planes causing extensive tissue destruction. Generally, necrotizing fasciitis begins as other skin diseases with signs of erythema, reddish-purple, or bluish-gray skin. At this stage, the skin becomes tender and is painful on palpation. After a few days of infection, bullae appear, and gangrene is observed. The death of tissues and destruction of blood vessels around the affected area makes the surface less painful in subsequent infections. However, the infection can rapidly spread systemically whereby the individual will present with symptoms such as fever, tachycardia, and sepsis (Tessier et al., 2019). The occurrence of these processes can be described at the cellular level using the approach below.

Microbial invasion of the subcutaneous tissue occurs either through trauma or through penetration of perforated viscus or urogenital organs. These bacteria then track the subcutaneous tissue releasing endotoxins that are observed to cause tissue death, and systemic illnesses. Depending on the type of microbial invasion, the skin infections can spread very fast within hours. Apart from endotoxins, these microbes release exotoxins that accelerate the process of infection. For instance, the clostridium species produces alpha toxins which result in extensive tissue damage or necrosis and cardiovascular collapse. Another example is the staphylococcus aureus and the streptococcus species which release M1 and M3 exotoxins (Tessier et al., 2019). Upon the release of the toxins, different mechanisms apply to lead to tissue death and cardiovascular breakdown. The M proteins are observed to increase the ability of the microbes to adhere to the affected tissue escaping phagocytosis. Other toxins like A and B damage the endothelium leading to loss of vascular integrity resulting in tissue edema and impaired blood flow to the capillaries.

The invasion of the tissues with toxins stimulates the CD4 cells and macrophages to produce tumor necrosis factor (TNF) and interleukins 1 and 6. These cytokines are responsible for the initiation of the inflammatory process which is fatal to the affected individual. Mostly observed is progression to shock, multisystem organ dysfunction, and death. Specifically, the alpha tumor necrosis factor causes injury to the vascular endothelium while the T cells activate the complement system leading to coagulation and thrombosis that result in tissue ischemia. Studies indicate that the complex activation of the immune system impairs oxidative destruction of bacteria by the polymorphonuclear cells rendering antibiotics ineffective in the management of the disease (Sarani et al., 2009). The only available remedy for the disease is surgical debridement because the use of antibiotics has little value in preventing the spread of the bacteria.

The key feature in the pathology of necrotizing fasciitis is the thrombosis of penetrating vessels to the skin. It is established that thrombosis of the small blood vessels beneath the skin must occur before skin changes are observed. Therefore, the extent of infection is usually larger than expected during initial diagnosis because of the infected dermal capillaries beneath the skin. Thrombosis is caused by increased interstitial pressure, platelet-neutrophil plugging, and hypercoagulation resulting in decreased blood flow to the surrounding tissues (Sarani et al., 2009). The superficial skin and deeper muscles are typically spared until the late stages where lesions develop liquefactive necrosis at all tissue levels.

Diagnosis and Treatment of the Disease

Clinical Manifestation

Decreasing the mortality and morbidity associated with necrotizing fasciitis is dependent on early diagnosis and instituting proper therapy. The nonspecific findings and variable time course of the disease make it difficult to diagnose NF. However, classical symptoms and the use of approved diagnostic measures can greatly improve the diagnosis and management of the disease. The first part towards the establishment of proper diagnosis is history taking and performance of physical examination. The classical symptoms of necrotizing soft tissue injuries include pain, anxiety, and diaphoresis which worsen rapidly (Sun & Xie, 2015). During history taking, the patient might relate a history of trauma or skin breakdown hours or a few days before the onset of the symptoms.

Similarities are observed during the diagnosis of NF and other necrotizing soft tissue injuries like cellulitis. For example, pain and swelling are observed in both conditions. However, NF manifests with a disproportionate level of pain compared with physical findings. A patient with a small blister or bullae can manifest with more severe pain than normal due to the spread of the infection beneath the skin. Findings suggest that unlike cellulitis where the infection begins at the junction between the dermis and superficial fascia, NF begins at the level of subcutaneous fat and deep fascia. The epidermal and dermal layers of the skin are spared initially and the absence of erythema or edema can lead to misdiagnosis by inexperienced physicians.

Skin changes in NF are rarely observed unless the disease is in advanced stages. There is always normal skin appearance in the early stages due to the spread of the disease subcutaneously. The rate of disease progression can vary from presentation to a rapid decline and death within hours of presentation. Bullae or blister formation can be a sign of NF but usually occur after tissue ischemia or extensive thrombosis of underlying blood vessels. Additionally, patients with NF in the late stages will present with signs of shock, multi-organ system failure, and toxic shock syndrome. Among the common features of these patients include tachypnea, tachycardia, confusion, coagulopathy, and thrombocytopenia.

The manifestation of NF is also dependent on the causal organism. For example, fulminant NF caused by vibrio fulfinicus bacteria is associated with cardiovascular collapse before the manifestation of tissue damage. It is observed that the bacteria causes rapid systemic inflammation that causes cardiovascular collapse even before skin changes occur. Cardiovascular collapse is attributed to the release of bacteria-derived toxins and endogenous cytokines. It is recommended that surgical debridement should be done once the patient is resuscitated and stabilized. Due to difficulties in diagnosing NF and the need for effective treatment, the manifestation of the disease is divided into three stages. The first stage manifests with signs of erythema, tenderness, swelling, and hot skin. The second stage involves signs like the formation of skin bullae, blisters, and skin fluctuation. Stage three NF manifests with hemorrhagic bullae, crepitus, skin necrosis, and gangrene.

Diagnostic Measures

The diagnosis of necrotizing fasciitis is essentially clinical with an exploration of the tissue being the gold standard. However, the clinical diagnosis of NF is accompanied by a series of tests. Radiographic imagery tests can be used to determine the existence of necrotizing soft tissue injuries. A plain X-ray can reveal subcutaneous gas or soft tissue swelling although it is insensitive. A CT scan can be used to indicate inflammation including signs such as edema, thickening, and gas formation. These imagery tests usually identify fluid and gas collection in subcutaneous tissues and therefore cannot be conclusive. An MRI can be more specific than a CT scan because it displays hyperintense signals in the deep fascia and peripherals with the use of contrast.

The second approach to the diagnosis of NF is the use of laboratory investigations and grading of the findings using a scoring system. Hematological changes like leukocytosis, coagulopathy, thrombocytopenia, and anemia are consistent with septic processes. Biochemistry results can indicate raised serum creatinine kinase which is suggestive of myonecrosis. Secondly, hypocalcemia is present due to fat necrosis and the deposition of calcium in the necrotic tissues. The presence of inflammation and necrosis potentially leads to a rise in C-reactive proteins (CRP).  Blood cultures are positive for bacteria in approximately 60% of the patients (Tessier et al., 2019). Tissue biopsy is the recommended investigation but sometimes percutaneous needle aspiration is used.

Any rapidly progressing soft tissue infection should be managed rapidly due to the fatality of necrotizing fasciitis. In 2004, the Laboratory Risk Indicator Infection Score (LRINEC) was developed to guide the diagnosis of NF and other soft tissue injuries. The most significant indicators to differentiate necrotizing from non-necrotizing soft-tissue infections include CRP, creatinine, hemoglobin, white cell count, sodium, and serum glucose. Each of the six predictive factors contains different scores and the LRINEC score is based on individual scores from the identified factors. A cumulative score of >6 has a positive predictive value of 92% and a negative predictive value of 96%. A score of ≥8 is strongly predictive of NF, with a positive predictive value of 93.4% (Tessier et al., 2019).


The effective management of NF involves early diagnosis, aggressive resuscitation, surgical debridement, the use of antibiotics, and supportive management. The resuscitative process aims at restoring the normal hemodynamic process especially in patients with septic shock. While caring for these patients, adequate nutrition is required to prevent nosocomial infections. The cornerstone therapy for NF is surgical debridement because it removes the source of infection and toxins (Sun & Xie, 2015). Debridement also ensures that subsequent management with antibiotics is effective. Serial debridements can be required when the infection is widespread to ensure total control of gross infection. Empirical management of NF requires the use of antibiotics targeting specific microorganisms. Commonly used drugs include tazocin, piperacillin, clindamycin, and carbapenems (Sun & Xie, 2015). Other recommended treatment options include IV immunoglobulin therapy and the use of hyperbaric oxygen.



Sarani, B., Strong, M., Pascual, J., & Schwab, C. W. (2009). Necrotizing fasciitis: Current concepts and review of the literature. Journal of the American College of Surgeons208(2), 279-288. DOI: 10.1016/j.jamcollsurg.2008.10.032

Sun, X., & Xie, T. (2015). Management of necrotizing fasciitis and its surgical aspects. The International Journal of Lower Extremity Wounds14(4), 328-334.

Tessier, J. M., Sanders, J., Sartelli, M., Ulrych, J., De Simone, B., Grabowski, J., … & Duane, T. M. (2019). Necrotizing soft tissue infections: A focused review of pathophysiology, diagnosis, operative management, antimicrobial therapy, and pediatrics. Surgical Infections21(2), 81-93.

Tobin, D. J. (2011). The anatomy and physiology of the skin. Springer Publishing Company, New York, New York, USA.

Clinical Case Study

A 35-year old male patient presented to the emergency room with complaints of swollen right lower limb. The patient reported a history of trauma to knee two weeks before admission. On examination, slight tenderness was observed, and the limb was swollen and warm on touch. A preliminary diagnosis of cellulitis was made by the primary care physician and was discharged home on antibiotics. A day later, the patient was brought back to the facility unable to walk and progressive limb swelling was observed. Further examination revealed constipation, crepitations on both lungs,multiple developing superficial wounds and anesthesia on some part of the lower limb. Prompt clinical diagnosis using MRI was made but before any further management the patient died.

  1. Based on the information above, which stage of NF was the patient in?
  2. Stage 1
  3. Stage 2
  4. Stage 3
  5. Stage 4

Answer: The correct answer is stage 3: Stage 3 NF presents with symptoms such as crepitus, skin necrosis, and gangrene.

  1. Which is the most preferred technique to detect necrotizing soft tissue infections?
  2. Computerized tomography
  3. Magnetic resonance imaging
  4. Laboratory examination
  5. Ultrasonography

Answer: Magnetic resonance imaging (MRI)is prefered because of its unsurpassed soft tissue contrast and sensitivity in detecting soft tissue fluid, its spatial resolution, and its multiplanar capabilities.

  1. The most appropriate statement concerning the diagnosis of NF include:
  2. The diagnostic method of choice is fine needle aspiration
  3. The diagnostic method of choice is tissue biopsy
  4. The LRINEC scoring system and MRI are recommended for diagnosis of NF.
  5. CT imaging has a role when there is strong clinical suspicion of NF
  6. All the above

Answer: The diagnostic method of choice is tissue biopsy. The gold standard for NF diagnosis is tissue biopsy following operative exploration. The biopsy will indicate lack of normal resistance of the fascia, dermal edema and polymorphonuclear infiltration into the dermis.

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