What causes cellulitis of the leg, particularly in individuals with compromised skin integrity or underlying conditions such as diabetes or poor circulation?

How Cellulitis of the Leg Develops

Cellulitis occurs when bacteria penetrate through breaks in the skin barrier and invade the dermis and subcutaneous tissues, triggering an inflammatory response. 1, 2

Primary Entry Mechanisms

The infection arises through several pathways:

• Disrupted skin integrity from trauma, preexisting skin infections (impetigo, ecthyma), ulceration, fissured toe webs from maceration or fungal infection, and inflammatory dermatoses like eczema 1
• Macerated interdigital toe spaces serve as the most common reservoir for streptococci in lower extremity infections, with organisms residing in fissured or fungal-infected toe webs 1, 2
• Clinically inapparent breaks in the skin often serve as entry points, even when no obvious wound is visible 1

Major Predisposing Factors

Conditions That Compromise Skin Integrity

• Venous insufficiency causes increased venous hypertension and capillary permeability, leading to protein-rich fluid accumulation that weakens tissue defenses 1, 2
• Lymphatic obstruction from any cause creates local edema that impairs immune surveillance 1
• Obesity makes skin more fragile and reduces local host defenses 1
• Previous cutaneous damage from any source increases susceptibility 1

Diabetes-Specific Risk Factors

In diabetic patients, multiple mechanisms converge:

• Peripheral sensory neuropathy eliminates protective sensation, leading to unattended minor injuries from excess pressure or mechanical/thermal trauma 1
• Peripheral motor neuropathy causes abnormal foot anatomy with clawing of toes, high arch, and subluxed metatarsophalangeal joints, creating excess pressure points 1
• Peripheral autonomic neuropathy produces deficient sweating that leads to dry, cracking skin 1
• Hyperglycemia and metabolic derangements impair neutrophil function and wound healing 1
• Vascular insufficiency compromises tissue viability, wound healing, and neutrophil delivery 1

Surgical Disruption of Lymphatic Drainage

Specific procedures dramatically increase cellulitis risk:

• Saphenous venectomy disrupts lymphatic drainage in the lower extremity 1
• Axillary node dissection for breast cancer predisposes to upper extremity cellulitis 1
• Radical vulvectomy and radical hysterectomy with lymph node dissection, especially when followed by radiation therapy 1

Common Bacterial Pathogens

Streptococci (groups A, B, C, or G) cause the majority of cellulitis cases, with the source frequently being macerated or fissured interdigital toe spaces 1, 2

• Staphylococcus aureus less frequently causes cellulitis, typically associated with penetrating trauma or injection drug use sites 1
• Group B streptococci may originate from the vagina in patients with previous gynecologic cancer treated with surgery and radiation 1
• Unusual organisms like Proteus mirabilis, E. coli, or other gram-negative rods occasionally cause cellulitis in immunocompromised patients or those with underlying chronic diseases 3, 4, 5

Critical Clinical Sequence

The infection develops through this progression:

1. Bacteria colonize a reservoir site (commonly toe web spaces with tinea pedis) 1, 2
2. Skin barrier breach occurs through trauma, maceration, or chronic skin conditions 1
3. Organisms invade the dermis and subcutaneous fat 1
4. Inflammatory cascade produces rapidly spreading edema, erythema, warmth, and tenderness 1, 2
5. Systemic manifestations (fever, tachycardia, confusion) may occur hours before skin changes appear 1, 2

Prevention Implications

Understanding these mechanisms reveals prevention targets:

• Aggressively treat tinea pedis and interdigital maceration to eliminate streptococcal reservoirs 2
• Manage venous insufficiency with compression therapy once acute infection resolves 2
• Keep skin hydrated to prevent cracking in patients with autonomic neuropathy 1
• Reduce underlying edema from any cause to restore local immune function 2
• Inspect feet daily in patients with sensory neuropathy who cannot feel minor injuries 1