What is the pathophysiology of cellulitis in a general adult population?

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Pathophysiology of Cellulitis

Cellulitis develops when bacteria penetrate breaches in the skin barrier and invade the dermis and subcutaneous tissue, triggering a robust inflammatory response that produces the characteristic signs of erythema, edema, warmth, and tenderness. 1

Mechanism of Bacterial Entry and Invasion

  • Bacteria enter through disruptions in the cutaneous barrier, which may result from trauma (often minor and clinically inapparent), preexisting skin infections (impetigo, ecthyma), ulceration, fissured toe webs from maceration or fungal infection, or inflammatory dermatoses such as eczema 2, 1
  • The infection spreads through tissue planes, causing rapidly expanding areas of inflammation as organisms proliferate in the dermis and subcutaneous fat 1
  • Streptococci (particularly group A, but also groups B, C, and G) are the predominant causative organisms, accounting for the majority of cases based on culture data, serologic studies, and immunofluorescent antibody techniques 2, 1
  • Staphylococcus aureus less frequently causes cellulitis, typically only in cases with prior penetrating trauma or injection sites from illicit drug use 2, 1

Predisposing Factors That Compromise Skin Defenses

  • Conditions that make the skin more fragile or local host defenses less effective include obesity, previous cutaneous damage, and edema from venous insufficiency or lymphatic obstruction 2
  • Surgical procedures that disrupt lymphatic drainage significantly increase cellulitis risk, including saphenous venectomy, axillary node dissection for breast cancer, and operations for gynecologic malignancies involving lymph node dissection, especially when followed by radiation therapy 2, 1
  • The source of streptococci in lower extremity infections is frequently the macerated or fissured interdigital toe spaces, emphasizing the importance of detecting and treating tinea pedis 2, 1
  • Other bacterial reservoirs may include the anal canal or vagina, particularly for group B streptococci causing cellulitis in patients with previous gynecologic cancer treated with surgery and radiation 2, 1

Inflammatory Response and Clinical Manifestations

  • The infection triggers a robust inflammatory response in the affected tissues, resulting in the classic signs of inflammation: erythema, edema, warmth, and tenderness 1
  • Superficial cutaneous edema surrounds hair follicles, causing the skin surface to resemble an orange peel (peau d'orange) because the follicles remain tethered to the underlying dermis, creating dimpling 2
  • Vesicles, bullae, and cutaneous hemorrhage in the form of petechiae or ecchymoses may develop on the inflamed skin 2
  • Systemic manifestations including fever, tachycardia, confusion, hypotension, and leukocytosis can occur, sometimes hours before the skin abnormalities appear 2, 1

Role of Host Immune Response

  • The warmth and erythema associated with cellulitis are produced both by a small number of residual bacteria and by fragmented bacterial remnants, amplified by lymphokines secreted in response to antigenic challenge 3
  • The skin's unique lymphoid and reticular cells secrete lymphokines and cytokines that rapidly reduce the number of viable bacteria by enhancing infiltration of macrophages and neutrophils 3
  • Cutaneous inflammation may worsen after initiating antibiotic therapy because sudden destruction of pathogens releases potent enzymes that increase local inflammation 2, 1

Tissue Damage and Long-Term Consequences

  • Each episode of cellulitis causes lymphatic inflammation and potentially permanent damage, with severe or repeated episodes leading to lymphedema, sometimes substantial enough to cause elephantiasis 1
  • The low bacterial concentration in cellulitic tissue (typically 20-30% culture yield from punch biopsies) reflects the role of bacterial antigens and host inflammatory mediators rather than massive bacterial proliferation 2

Distinguishing Anatomic Features

  • Cellulitis involves the deeper dermis and subcutaneous fat, whereas erysipelas affects the upper dermis and superficial lymphatics 2, 1
  • Unlike necrotizing fasciitis, which tracks along fascial planes with a wooden-hard feel of subcutaneous tissues, cellulitis maintains yielding tissues 1

References

Guideline

Pathophysiology of Cellulitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cutaneous cellulitis.

Archives of dermatology, 1991

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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