Gangrene overview

# Overview
Gangrene is a medical condition that involves necrosis and ischemia of a body tissue, mostly occurring in the digits or extremities. It usually appears as a black discoloration and sloughing of tissues. There are three main types of gangrene, namely wet gangrene, dry gangrene, and gas gangrene.

# Historical Perspective
Gangrene originated from a Greek word that meant mortification of a human body part. It was first used as a noun in the British Isles during the 16th century. Surgeons most often used it to refer to the cure of external human conditions.

# Classification
There are three main types of gangrene which include wet, dry, and gas gangrene. Sometimes it can be classified according to its site.

# Pathophysiology
There are three types of gangrene and they have different pathophysiology. 
A reduced arterial perfusion is observed in dry gangrene which results in the compensatory arteriolar dilation, which eventually results in distal edema, and damage of the endothelial tissue. 
Saprogenic microorganisms such as Clostridium perfringens and Bacillus fusiformis are the most common organisms observed in wet gangrene which are responsible for infecting the tissues, thereby producing a putrid smell and edema. 
Group A Steptococcus and exotoxins from Clostridium perfringens are responsible for the local and systemic infection found in gas gangrene.

# Causes
According to Hippocratic physicians, gangrene is brought about by three reasons. These include wound constriction that is followed by hemorrhage, body part compression, and necrosis due to bandages.

# Differentiating Gangrene from other Diseases
Gangrene can have several mimicking conditions despite the unique presence of necrotic tissue.

# Epidemiology and Demographics
Ischemic or dry gangrene is commonly associated with peripheral artery disease (PAD). The most advanced stage of PAD is critical limb ischemia/ chronic limb-threatening ischemia, and it has an incidence rate of 1% in the United States. Gas gangrene is a rare condition, with an annual record of 1000 cases in the United States, 50% of which are due to traumatic injuries, 30% due to post-operative complications, and the remaining part is attributed to infections.

# Risk Factors
There are several risk factors for gangrene and these include penetrating trauma, blunt trauma, recent surgery, obesity, alcoholism, mucosal breach, skin breach, and immunosuppression.

# Natural History, Complications, and Prognosis
Amputation and death are the most common consequence of critical limb ischemia/ chronic limb-threatening ischemia. Gas gangrene has higher fatality rate, ranging from 25% to 100%, if treatment is inadequate or delayed. Increased age, several comorbidities present, and involvement of trunk lead to a poor prognosis.

# Diagnosis

## History and Symptoms
Chronic limb pain is the usual chief complaint of patients who developed gangrene.

## Physical Examination
Patients with gangrene may have varying presentations depending on the type of gangrene they have.

## Laboratory Findings
Evaluation of patients with ischemic gangrene is more focused on targeting the risk factors which include hyperlipidemia, diabetes, and renal failure. Laboratory tests to deal with these risk factors are usually requested for ischemic gangrene. Wet gangrene and gas gangrene are assessed with the help of cultures.

## X-ray
X-rays are utilized in the evaluation of gas gangrene to identify any present subcutaneous gas.

## CT scan
Computed tomography (CT scan) with contrast is the best initial imaging test for gangrene.

## MRI
Magnetic resonance imaging (MRI) is not so useful in the evaluation of gas gangrene. The presence of gas is not very well detected using this imaging modality.

## Other Imaging Findings
Other recommended imaging tests to consider in the evaluation of gangrene include ultrasound, duplex ultrasound, computed tomography / (CT) angiography, digital subtraction angiography, and magnetic resonance angiography / (MRA).

## Other Diagnostic Studies
There are some useful tools that were developed to assess the possibility of gangrene. These include the recent development of the Society of Vascular Surgery which is called  WIfI which stands for wound, ischemia, foot infection, and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score.

# Treatment

## Medical Therapy
Ischemic gangrene can be medically treated with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and antiplatelet drugs such as aspirin and clopidogrel. Wet gangrene and gas gangrene are treated with antibiotics which should cover microorganisms detected in culture of the specimen with gangrene.

## Surgery
The goal of surgical treatment in gangrene is to achieve revascularization to alleviate pain and avoid limb loss.

## Primary Prevention
Gas gangrene can be prevented by always monitoring the blood glucose levels and maintaining them within the normal range, and regular foot inspection, most especially in those patients with diabetes. Post-exposure prophylaxis may be needed by immunocompromised individuals if they were in close contact with patients with necrotizing infection due to Group A streptococcus. Droplet and contact precautions are warranted to these susceptible individuals.

## Secondary Prevention
Early diagnosis and prompt medical and surgical treatment of gangrene are needed to prevent the rapid progression and worsening of the disease.

## Cost-Effectiveness of Therapy
Gangrene is a potential life-threatening condition if not given prompt treatment. Although the incidence is just low, gangrene can generate a high healthcare cost.

## Future or Investigational Therapies
A novel gene therapeutic approach is currently conducted to promote reperfusion and angiogenesis of ischemic tissues, which can help in limb salvage. Ongoing study on this approach is conducted on mice and it involves the intramuscular injection of adeno-associated virus/ (AAV) vector, and E-selectin.