Cellulitis: symptoms, causes, clinical features, diagnostics and treatment

Medically reviewed: 9, December 2023

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Cellulitis: A Review of Diagnosis and Management

Cellulitis is a common and potentially serious bacterial infection of the skin and subcutaneous tissue, usually caused by streptococci or staphylococci. It typically presents with erythema, edema, warmth, tenderness, and fever, and may be complicated by abscess formation, necrotizing fasciitis, septicemia, or chronic lymphedema.

Diagnosis is mainly clinical, but blood cultures, wound cultures, imaging, and laboratory tests may be helpful in some cases. Treatment consists of empiric antibiotic therapy, usually with a beta-lactam or a beta-lactamase inhibitor, and supportive measures such as analgesia, elevation, and compression. Prevention strategies include avoiding skin injuries, treating skin conditions, maintaining good hygiene, and managing underlying medical conditions.

This article reviews the epidemiology, pathophysiology, clinical features, diagnosis, treatment, prevention, and prognosis of cellulitis, with an emphasis on the latest evidence and guidelines.

What is Cellulitis?

Cellulitis is a common and potentially serious bacterial infection of the skin and subcutaneous tissue, affecting about 14.5 million people per year in the United States¹. It accounts for about 3% of all emergency department visits and 10% of all hospital admissions for skin and soft tissue infections. Cellulitis can affect any part of the body, but the lower extremities are the most frequently involved, followed by the face, trunk, and upper extremities. Cellulitis can occur at any age, but it is more common in older adults, males, and people with comorbidities such as diabetes, obesity, peripheral vascular disease, or immunosuppression.

Cellulitis is usually caused by gram-positive bacteria, mainly streptococci (group A, B, C, G, or F) or staphylococci (including methicillin-resistant Staphylococcus aureus, or MRSA). Other less common causes include gram-negative bacteria (such as Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa), anaerobes (such as Bacteroides fragilis or Peptostreptococcus spp.), or mixed infections [^10^]. The bacteria enter the skin through a breach in the epidermal barrier, such as a cut, abrasion, ulcer, insect bite, or surgical wound, and then spread along the lymphatic vessels and the subcutaneous tissue, causing inflammation and tissue damage .

Cellulitis typically presents with erythema, edema, warmth, tenderness, and fever, and may be associated with lymphangitis, lymphadenitis, or systemic symptoms such as malaise, chills, or rigors . The affected area is usually well-demarcated, but the borders may be indistinct or irregular in some cases. Cellulitis may be complicated by abscess formation, necrotizing fasciitis, septicemia, or chronic lymphedema, which can lead to significant morbidity and mortality .

Diagnosis of cellulitis is mainly clinical, based on the history and physical examination. However, blood cultures, wound cultures, imaging, and laboratory tests may be helpful in some cases, especially when the diagnosis is uncertain, the infection is severe or recurrent, or the patient has risk factors for atypical or resistant organisms . Treatment of cellulitis consists of empiric antibiotic therapy, usually with a beta-lactam or a beta-lactamase inhibitor, and supportive measures such as analgesia, elevation, and compression . Prevention strategies include avoiding skin injuries, treating skin conditions, maintaining good hygiene, and managing underlying medical conditions .

Epidemiology of Cellulitis

Cellulitis is a common and potentially serious bacterial infection of the skin and subcutaneous tissue, affecting about 14.5 million people per year in the United States. The incidence of cellulitis has been increasing over the past decades, partly due to the emergence of MRSA and the aging of the population .

The annual incidence of cellulitis in the United States is estimated to be 24.6 cases per 10,000 person-years, with a peak in the summer months. The incidence of cellulitis varies by age, sex, and geographic region. Cellulitis is more common in older adults, with an incidence of 64.4 cases per 10,000 person-years in people aged 65 years or older, compared with 12.8 cases per 10,000 person-years in people aged 18 to 44 years. Cellulitis is also more common in males, with an incidence of 29.2 cases per 10,000 person-years in males, compared with 20.1 cases per 10,000 person-years in females. Cellulitis is more prevalent in certain geographic regions, such as the Northeast and Midwest of the United States, and less prevalent in the West and South.

Cellulitis accounts for about 3% of all emergency department visits and 10% of all hospital admissions for skin and soft tissue infections. The average length of hospital stay for cellulitis is 4.5 days, and the average cost of hospitalization is $10,500 per case. Cellulitis is associated with significant morbidity and mortality, especially in patients with comorbidities or complications. The mortality rate of cellulitis is estimated to be 0.5% to 1%, but it can be as high as 6% in patients with septic shock or necrotizing fasciitis . The recurrence rate of cellulitis is estimated to be 8% to 28%, and it is higher in patients with lymphedema, venous insufficiency, or previous episodes of cellulitis .

Pathophysiology of Cellulitis

Cellulitis is usually caused by gram-positive bacteria, mainly streptococci or staphylococci, that enter the skin through a breach in the epidermal barrier, such as a cut, abrasion, ulcer, insect bite, or surgical wound. The most common causative organisms are group A streptococcus (GAS), which accounts for 60% to 80% of cases, and Staphylococcus aureus, which accounts for 20% to 30% of cases . Other less common causes include group B, C, G, or following pathogens:

F streptococci, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus, Streptococcus dysgalactiae, Streptococcus intermedius, Streptococcus milleri, Streptococcus mitis, Streptococcus oralis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus viridans, Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus saprophyticus, Staphylococcus haemolyticus, Staphylococcus simulans, Staphylococcus warneri, Staphylococcus capitis, Staphylococcus hominis, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus sciuri, Staphylococcus auricularis, Staphylococcus pasteuri, Staphylococcus schleiferi, Staphylococcus saccharolyticus, or Staphylococcus equorum.

The incidence of MRSA as a cause of cellulitis has been increasing over the past decades, especially in the community setting . MRSA is a type of staphylococcus that is resistant to methicillin and other beta-lactam antibiotics, and it can cause more severe and complicated infections than methicillin-sensitive Staphylococcus aureus (MSSA) .

  • MRSA can be classified into two types: hospital-acquired MRSA (HA-MRSA) and community-acquired MRSA (CA-MRSA).
  • HA-MRSA is usually acquired in health care settings, such as hospitals, nursing homes, or dialysis centers, and it is associated with invasive procedures, indwelling devices, or previous antibiotic use.
  • CA-MRSA is usually acquired in the community, such as schools, gyms, or prisons, and it is associated with young age, poor hygiene, crowded living conditions, or contact sports . CA-MRSA is more likely to cause skin and soft tissue infections than HA-MRSA, and it often produces a toxin called Panton-Valentine leukocidin (PVL), which can cause tissue necrosis and leukocyte destruction.
  • PVL is a cytotoxin that forms pores in the membranes of neutrophils, monocytes, and macrophages, leading to their lysis and release of inflammatory mediators.

PVL can also activate the complement system and the coagulation cascade, resulting in tissue damage and thrombosis. PVL can cause severe and necrotizing skin and soft tissue infections, such as furuncles, carbuncles, abscesses, cellulitis, impetigo, or necrotizing fasciitis. PVL can also cause systemic infections, such as pneumonia, septic arthritis, osteomyelitis, endocarditis, or septic shock. PVL is more common in CA-MRSA than in HA-MRSA, and it is associated with a higher risk of morbidity and mortality .

Once the bacteria enter the skin and subcutaneous tissue, they multiply and secrete various virulence factors that facilitate their invasion and survival. These factors include enzymes, such as hyaluronidase, collagenase, elastase, or lipase, that degrade the extracellular matrix and the connective tissue; toxins, such as hemolysins, leukocidins, or exfoliative toxins, that damage the host cells and tissues; adhesins, such as fibronectin-binding proteins, clumping factors, or protein A, that bind to the host receptors and evade the immune system; and biofilm, which is a complex structure of polysaccharides, proteins, and DNA, that protects the bacteria from the host defenses and the antibiotics .

The host response to the bacterial infection involves the activation of the innate and adaptive immune systems, which attempt to eliminate the bacteria and limit the tissue damage. The innate immune system consists of the physical and chemical barriers of the skin, the complement system, the phagocytic cells, such as neutrophils, monocytes, and macrophages, and the inflammatory mediators, such as cytokines, chemokines, and prostaglandins.

The adaptive immune system consists of the lymphocytes, such as B cells and T cells, and the antibodies, which recognize and target the specific antigens of the bacteria. The immune response can be effective in controlling the infection, but it can also cause collateral damage to the host tissues, resulting in inflammation, edema, necrosis, and scarring.

Symptoms of Cellulitis

The clinical features of cellulitis vary depending on the location and severity of the infection, but they generally include the following:

Erythema

This is the redness of the skin, which may be diffuse or well-defined, and may have a raised or indurated border. The erythema may expand rapidly, especially in the lower legs, and may be accompanied by streaks of lymphangitis or satellite lesions. The erythema may be less visible on dark skin, and may be masked by chronic venous insufficiency or stasis dermatitis.

Edema

This is the swelling of the skin and subcutaneous tissue, which may be soft or firm, and may cause pitting or nonpitting indentation. The edema may be localized or generalized, and may impair the function or mobility of the affected area. The edema may also cause blisters, bullae, or skin breakdown.

Warmth

This is the increased temperature of the skin, which may be detected by palpation or thermography. The warmth may indicate increased blood flow or inflammation, and may be associated with fever or chills.

Tenderness

This is the pain or discomfort of the skin, which may be elicited by pressure or movement. The tenderness may be mild or severe, and may limit the use or range of motion of the affected area. The tenderness may also radiate to adjacent areas or structures, such as the joints or bones.

Fever

This is the elevation of the body temperature above the normal range, usually above 38°C (100.4°F). Fever may be accompanied by systemic symptoms, such as malaise, fatigue, headache, or muscle ache. Fever may indicate a severe or complicated infection, or a concomitant infection, such as bacteremia, endocarditis, or osteomyelitis.

The clinical features of cellulitis may be modified by the presence of comorbidities, such as diabetes, peripheral vascular disease, or immunosuppression, which may impair the host defense, delay the healing, or increase the risk of complications. The clinical features of cellulitis may also be influenced by the causative organism, which may have specific characteristics, such as toxin production, biofilm formation, or antibiotic resistance, that may affect the presentation, course, or outcome of the infection.

Diagnosis of Cellulitis

The diagnosis of cellulitis is mainly based on the clinical features, but it may be supported by laboratory tests, microbiological cultures, or imaging studies, especially in cases of uncertainty, severity, recurrence, or failure to respond to treatment.

Laboratory tests

These include blood tests, such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood urea nitrogen (BUN), creatinine, glucose, and electrolytes, which may indicate the presence and extent of inflammation, infection, or organ dysfunction.

Blood cultures may be performed in patients with fever, leukocytosis, or suspected bacteremia, but they have a low yield, ranging from 2% to 10%, and they may not reflect the etiology of the skin infection. Wound cultures may be obtained from purulent or exudative lesions, such as abscesses, ulcers, or bullae, but they may be contaminated by the skin flora, and they may not reflect the causative organism of the cellulitis. Needle aspiration or punch biopsy may be performed in selected cases, such as when there is a suspicion of an underlying abscess, foreign body, or malignancy, or when there is a need for histopathological examination or culture of the deep tissue.

Imaging studies

These include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide scanning, which may help to identify or exclude the presence of complications, such as abscess, necrotizing fasciitis, osteomyelitis, or septic arthritis.

Ultrasound is the most widely available and cost-effective modality, and it can detect subcutaneous fluid collections, gas, or foreign bodies, as well as assess the blood flow and the lymphatic drainage of the affected area. CT and MRI can provide more detailed information about the extent and depth of the infection, as well as the involvement of the adjacent structures, such as the muscles, bones, or joints.

Radionuclide scanning, such as gallium, indium, or technetium, can provide functional information about the metabolic activity and the inflammatory response of the infected tissue, but it has a low specificity and a high cost.

The diagnosis of cellulitis may be challenging in some situations, such as when the clinical features are atypical, nonspecific, or mimicked by other conditions, such as allergic reactions, contact dermatitis, drug eruptions, erythema multiforme, gout, herpes zoster, insect bites, lymphedema, or thrombophlebitis. The diagnosis of cellulitis may also be difficult in patients with chronic or recurrent infections, which may be caused by resistant or unusual organisms, or by underlying predisposing factors, such as foreign bodies, fistulas, or immunodeficiencies.

In these cases, a careful history, a thorough physical examination, and a judicious use of ancillary tests may help to establish the correct diagnosis and to guide the appropriate treatment.

Treatment of Cellulitis

The treatment of cellulitis is mainly based on the empirical antibiotic therapy, which aims to cover the most likely causative organisms, and the supportive measures, which aim to relieve the symptoms and prevent the complications. The choice, route, dose, and duration of the antibiotic therapy depend on the severity and location of the infection, the presence of comorbidities or risk factors, the history of previous infections or treatments, and the local patterns of antibiotic resistance .

Antibiotic therapy

The most common empiric antibiotic therapy for cellulitis is a beta-lactam or a beta-lactamase inhibitor, such as penicillin, amoxicillin, ampicillin, cephalexin, cefazolin, or amoxicillin-clavulanate, which are effective against streptococci and MSSA.

However, if there is a suspicion or confirmation of MRSA, or if there is a history of allergy or intolerance to beta-lactams, alternative antibiotics may be used, such as clindamycin, doxycycline, minocycline, trimethoprim-sulfamethoxazole, or linezolid, which are effective against MRSA and some streptococci. If there is a suspicion or confirmation of gram-negative or anaerobic bacteria, or if there is a history of animal or human bites, additional antibiotics may be added, such as metronidazole, ciprofloxacin, levofloxacin, or moxifloxacin, which are effective against gram-negative and anaerobic bacteria. The antibiotic therapy may be initiated orally or intravenously, depending on the severity of the infection and the availability of the service.

The oral route is preferred for mild to moderate infections, as it is more convenient, less invasive, and less costly. The intravenous route is reserved for severe or complicated infections, or when the oral route is not feasible or effective. The duration of the antibiotic therapy may vary from 5 to 14 days, depending on the clinical response and the resolution of the infection. The antibiotic therapy may be switched from intravenous to oral, or from one agent to another, based on the culture results, the clinical improvement, or the adverse effects.

Supportive measures

These include analgesia, elevation, and compression, which aim to relieve the pain, swelling, and inflammation of the affected area. Analgesia may be provided by nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, or diclofenac, or by opioids, such as codeine, tramadol, or morphine, depending on the intensity and type of the pain.

Elevation may be achieved by raising the affected limb above the level of the heart, using pillows, cushions, or slings, which may help to reduce the edema and improve the blood flow and the lymphatic drainage.

Compression may be applied by using elastic bandages, stockings, or sleeves, which may help to reduce the edema and prevent the recurrence of the infection. Supportive measures may be continued until the infection is resolved, and may be combined with physical therapy, massage, or exercise, to improve the function and mobility of the affected area.

The treatment of cellulitis may be modified by the presence of comorbidities, such as diabetes, peripheral vascular disease, or immunosuppression, which may impair the host defense, delay the healing, or increase the risk of complications. The treatment of cellulitis may also be influenced by the causative organism, which may have specific characteristics, such as toxin production, biofilm formation, or antibiotic resistance, that may affect the presentation, course, or outcome of the infection.

Prevention of Cellulitis

The prevention of cellulitis is based on the avoidance of skin injuries, the treatment of skin conditions, the maintenance of good hygiene, and the management of underlying medical conditions, which may reduce the risk of exposure, colonization, or invasion of the bacteria .

Avoidance of skin injuries

This includes avoiding or minimizing the trauma, friction, or irritation of the skin, such as by wearing protective clothing, footwear, or gloves, by using lubricants or moisturizers, by trimming the nails and shaving carefully, by applying insect repellents or sunscreen, and by avoiding contact with animals or plants that may cause bites, scratches, or stings.

This also includes cleaning and covering any wounds, such as cuts, abrasions, ulcers, or burns, with sterile dressings, antiseptics, or antibiotics, and changing them regularly, to prevent the entry or growth of the bacteria. This also includes seeking medical attention for any signs of infection, such as redness, swelling, warmth, tenderness, or pus, and following the prescribed treatment, to prevent the spread or worsening of the infection.

Treatment of skin conditions

This includes treating any skin conditions that may predispose to or complicate the cellulitis, such as eczema, psoriasis, dermatitis, acne, or fungal infections, with appropriate medications, such as corticosteroids, antihistamines, antibiotics, or antifungals, and following the recommended skin care, such as washing, moisturizing, or exfoliating, to prevent the breakdown or inflammation of the skin.

This also includes treating any conditions that may affect the blood flow or the lymphatic drainage of the skin, such as varicose veins, venous ulcers, or lymphedema, with appropriate interventions, such as surgery, sclerotherapy, or compression, to prevent the stasis or accumulation of the fluid.

Maintenance of good hygiene

This includes maintaining good hygiene of the skin and the body, such as by washing regularly with soap and water, by drying thoroughly, by using clean towels and clothes, by avoiding sharing personal items, such as razors, toothbrushes, or cosmetics, and by disinfecting any equipment or surfaces that may come in contact with the skin, such as scissors, tweezers, or needles, to prevent the colonization or transmission of the bacteria.

This also includes maintaining good hygiene of the oral cavity, such as by brushing, flossing, and rinsing, by visiting the dentist regularly, and by treating any dental problems, such as caries, gingivitis, or periodontitis, to prevent the spread of the bacteria from the mouth to the skin.

Management of underlying medical conditions: This includes managing any medical conditions that may impair the immune system or increase the susceptibility to the infection, such as diabetes, obesity, peripheral vascular disease, or immunosuppression, with appropriate medications, such as insulin, antidiabetics, statins, or immunosuppressants, and following the recommended lifestyle, such as diet, exercise, or smoking cessation, to prevent the impairment or deterioration of the host defense.

This also includes receiving any vaccinations that may prevent or reduce the severity of the infection, such as the pneumococcal, meningococcal, or tetanus vaccines, and following the recommended schedule and dosage, to prevent the exposure or invasion of the bacteria.

Prognosis of Cellulitis

The prognosis of cellulitis depends on many factors, such as the location and severity of the infection, the presence of comorbidities or complications, and the response to treatment. The prognosis of cellulitis is typically favorable, as most cases respond well to the antibiotic therapy and the supportive measures, and resolve without sequelae.

However, some cases may have a poor prognosis, due to the delay or failure of the diagnosis or treatment, the recurrence or persistence of the infection, or the development of complications, such as abscess, necrotizing fasciitis, septicemia, or chronic lymphedema, which can lead to significant morbidity and mortality .

The prognosis of cellulitis can be assessed by using various indicators, such as the clinical improvement, the resolution of the infection, the recurrence rate, the complication rate, the hospitalization rate, the mortality rate, or the quality of life. The prognosis of cellulitis can be improved by using various strategies, such as the early and accurate diagnosis, the appropriate and timely treatment, the prevention and management of the risk factors, the education and empowerment of the patients and the families, and the collaboration and communication of the health care providers.

Conclusion

Cellulitis is a common and potentially serious bacterial infection of the skin and subcutaneous tissue, usually caused by streptococci or staphylococci. It typically presents with erythema, edema, warmth, tenderness, and fever, and may be complicated by abscess formation, necrotizing fasciitis, septicemia, or chronic lymphedema.

Diagnosis is mainly clinical, but blood cultures, wound cultures, imaging, and laboratory tests may be helpful in some cases.

Treatment consists of empiric antibiotic therapy, usually with a beta-lactam or a beta-lactamase inhibitor, and supportive measures such as analgesia, elevation, and compression. Prevention strategies include avoiding skin injuries, treating skin conditions, maintaining good hygiene, and managing underlying medical conditions.

The prognosis of cellulitis depends on many factors, such as the location and severity of the infection, the presence of comorbidities or complications, and the response to treatment. The prognosis of cellulitis is typically favorable, but some cases may have a poor prognosis, due to the delay or failure of the diagnosis or treatment, the recurrence or persistence of the infection, or the development of complications, which can lead to significant morbidity and mortality.

Cellulitis is a common and important condition that requires prompt and appropriate diagnosis and management, to improve the outcome and quality of life of the patients and the families.

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