Introduction
Cellulitis is a common bacterial infection of the skin and subcutaneous tissues. It often presents with poorly demarcated erythema, edema, warmth, and tenderness. Despite its prevalence, cellulitis can be a diagnostic and therapeutic challenge. This article reviews the pathophysiology, microbiology, clinical presentation, risk factors, diagnosis, and treatment of cellulitis, incorporating information from the JAMA review as well as additional insights from other recent studies.
Epidemiology
Cellulitis is a significant global health burden, particularly in the United States. Over 14 million cases occur annually in the U.S., with an estimated $3.7 billion in ambulatory care costs. Hospital admissions for cellulitis have been increasing, reflecting both a higher incidence and greater awareness of the condition. In one study, cellulitis accounted for 10.1% of infectious disease hospitalizations, with an age-adjusted rate of 156.2 hospitalizations per 100,000 persons, and a 52.2% increase in hospitalizations from 1998 to 2006 . The incidence of cellulitis has been rising, particularly among elderly populations, which underscores the importance of this condition in healthcare management .
Pathophysiology
Cellulitis involves the deep dermis and subcutaneous tissues, typically occurring when bacteria enter the skin through disruptions such as cuts, abrasions, ulcers, or insect bites. The infection is characterized by dermal edema, lymphatic dilation, and heavy neutrophil infiltration around blood vessels, evolving to include lymphocytes and granulation tissue in later stages. In the pre-antibiotic era, the mortality rate for cellulitis and erysipelas was greater than 10%, significantly reduced with the introduction of antibiotics such as sulfonamides and penicillin.
Microbiology
The majority of cellulitis cases are caused by β-hemolytic streptococci and Staphylococcus aureus, including MRSA. However, cultures often yield negative results due to low bacterial concentrations or effective immune responses. Studies have shown that only about 16% of cellulitis cases yield a positive bacterial culture. Streptococci are frequently identified in erysipelas and cellulitis cases, with serological testing often confirming streptococcal etiology in cellulitis episodes. MRSA is less frequently implicated but remains a concern, particularly in purulent infections.
Clinical Presentation
Cellulitis presents as an acute, spreading, poorly demarcated area of erythema, warmth, tenderness, and swelling. Common systemic manifestations include fever, chills, and malaise, indicating more severe infection. Cellulitis is usually unilateral and most commonly affects the lower extremities. Erysipelas, a related condition, involves infection of the superficial dermis and lymphatics, presenting as a sharply demarcated, bright-red area of raised skin.
Differential Diagnosis
Diagnosing cellulitis can be challenging due to numerous conditions that mimic its presentation. Differential diagnoses include:
- Infectious Causes: Erythema migrans (Lyme disease), herpes simplex, herpes zoster, and cutaneous abscesses.
- Inflammatory Conditions: Drug reactions, contact dermatitis, angioedema, Sweet syndrome, gout, acute bursitis, erythema nodosum, and eosinophilic cellulitis (Wells syndrome).
- Vascular Conditions: Venous stasis dermatitis, lymphedema, deep vein thrombosis, superficial thrombophlebitis, and hematoma.
- Neoplastic Causes: Carcinoma erysipeloides, Paget disease of the breast, extramammary Paget disease, inflammatory breast carcinoma, lymphoma, and leukemia.
Risk Factors
Several systemic and local factors increase the risk of developing cellulitis. Understanding these risk factors can help in both prevention and management.
Systemic Risk Factors
- Age: Elderly individuals are at higher risk due to thinner skin and potentially compromised immune function.
- Obesity: Increased body weight is associated with higher rates of cellulitis, likely due to increased skin surface area and friction.
- Homelessness: Limited access to hygiene facilities and higher exposure to skin injuries increase risk.
Local Risk Factors
- Barrier Disruption: Any break in the skin, such as wounds, ulcers, or trauma, can serve as an entry point for bacteria.
- Toe-Web Infections: Fungal infections like tinea pedis (athlete’s foot) can lead to skin breaks that predispose individuals to cellulitis.
- Edema: Conditions causing chronic edema, such as lymphedema or venous insufficiency, create an environment conducive to bacterial growth.
- History of Cellulitis: Previous episodes of cellulitis increase the likelihood of recurrence.
- Dermatitis: Inflammatory skin conditions can disrupt the skin barrier and increase susceptibility to infection.
Diagnosis
The diagnosis of cellulitis is primarily clinical, based on the patient’s history and physical examination findings. Routine laboratory tests are generally not needed for uncomplicated cases but can include white blood cell counts, C-reactive protein, or erythrocyte sedimentation rate in more complicated or unclear cases. Imaging studies like ultrasound can help differentiate cellulitis from abscesses, while MRI or CT scans can be useful in ruling out conditions like necrotizing fasciitis or osteomyelitis.
Treatment
Nonpurulent Cellulitis
Mild Cases:
Oral Antibiotics: Cephalexin, dicloxacillin, penicillin VK, amoxicillin/clavulanate, or clindamycin (for penicillin-allergic patients) for 5-10 days.
Moderate Cases:
Oral or Intravenous Antibiotics: Cefazolin, ceftriaxone, or penicillin G. Clindamycin is used for penicillin-allergic patients.
Severe Cases:
Intravenous Antibiotics: Vancomycin, clindamycin, linezolid, daptomycin, or ceftaroline. Surgical assessment for possible necrotizing fasciitis may be necessary.
Purulent Cellulitis
Mild Cases:
Oral Antibiotics: Targeting Staphylococcus aureus, such as trimethoprim-sulfamethoxazole, doxycycline, or clindamycin.
Moderate Cases:
Initial IV Antibiotics: Oxacillin, nafcillin, or cefazolin for MSSA, and vancomycin or linezolid for MRSA.
Severe Cases:
Broad-Spectrum IV Antibiotics: Vancomycin, linezolid, daptomycin, or ceftaroline, with consideration for surgical intervention in cases of suspected necrotizing fasciitis.
Duration of Therapy
The typical duration of antibiotic treatment ranges from 5 to 10 days, depending on clinical response. Severe or complicated cases may require a longer duration, typically 7 to 14 days. Early improvement should be observed within 24-48 hours; if not, the treatment plan should be reassessed.
Preventive Measures
Preventive strategies are essential to reduce the risk of recurrence. These include:
- Management of Underlying Conditions: Addressing chronic edema, fungal infections, and venous insufficiency.
- Skin Care: Regular skin inspections and maintaining hygiene can prevent skin barrier disruptions.
- Prophylactic Antibiotics: For patients with frequent recurrences, prophylactic antibiotics such as oral penicillin or erythromycin may be considered.
Complications
Appropriate and timely treatment of cellulitis is crucial to prevent complications, which can include:
- Bacteremia: A bloodstream infection that can lead to sepsis.
- Endocarditis: An infection of the heart valves.
- Osteomyelitis: A bone infection.
- Toxic Shock Syndrome: A severe, life-threatening condition.
- Elephantiasis Verrucosa Nostra: Chronic lymphedema leading to thickening of the skin.
Recurrent Cellulitis
Recurrent cellulitis is common, with recurrence rates of 14% within one year and 45% within three years. Recurrences often occur in the same location and are associated with risk factors such as edema, obesity, and venous insufficiency. Addressing these risk factors can help prevent repeated infections .
Prophylactic Therapy
For patients with multiple episodes of cellulitis per year, prophylactic antibiotics can be effective. Common regimens include:
- Oral Penicillin: 250 mg or 1 g twice daily.
- Erythromycin: 250 mg twice daily.
- Dicloxacillin: 500 mg twice daily.
- Clindamycin: 150 mg daily.
- Intramuscular Benzathine Penicillin: 1.2 million U monthly.
Conclusion
Effective management of cellulitis involves prompt and appropriate antibiotic therapy, addressing underlying conditions, and close monitoring of the patient’s response. Further research is needed to optimize diagnostic and treatment strategies for cellulitis to reduce its burden and improve patient outcomes.
References
- Raff, Adam B., and Daniela Kroshinsky. “Cellulitis: a review.” JAMA 316.3 (2016): 325-337.
- Boettler, Michelle A., Benjamin H. Kaffenberger, and Catherine G. Chung. “Cellulitis: a review of current practice guidelines and differentiation from pseudocellulitis.” American Journal of Clinical Dermatology 23.2 (2022): 153-165.
- Bystritsky, Rachel J. “Cellulitis.” Infect Dis Clin N Am 35 (2021): 49-60.
