What are the causes of a vesiculonodular lesion on the knuckle?

Causes of Vesiculonodular Lesions on the Knuckle

A vesiculonodular lesion on the knuckle should prompt immediate consideration of fungal infection (particularly Aspergillus species), nontuberculous mycobacteria, or traumatic inoculation, with tissue biopsy and culture being mandatory for definitive diagnosis.

Primary Infectious Etiologies

Fungal Infections

Aspergillus species are the most critical consideration for vesiculopapular lesions on extremities, particularly the knuckles:

• Aspergillus chevalieri specifically causes morphologically distinct skin lesions that appear erythematous, hyperkeratotic, and vesiculopapular in nature, distinguishing it from other Aspergillus species 1
• Primary invasive skin infections occur through direct cutaneous inoculation of delicate or macerated skin, with traumatic injury being a key mechanism 1
• These lesions commonly occur on extremities and may be single or multiple, often non-tender initially 1
• The lesions first appear as erythematous papules, then become pustular, and subsequently develop central ulceration with an elevated border covered by black eschar 1

Other mold infections to consider:

• Fusarium species cause vesiculopapular lesions that begin as erythematous macules with central pallor, evolving to papules and necrotic nodules, with preferential localization to extremities, especially feet and hands 1
• Mucor and Rhizopus species cause painful erythematous skin nodules that become necrotic, typically following contaminated bandages or skin trauma 1

Nontuberculous Mycobacteria (NTM)

Direct inoculation injuries are the primary mechanism:

• M. marinum, M. fortuitum, M. abscessus, and M. chelonae cause localized infections after puncture wounds or traumatic injuries 1
• These organisms particularly affect tendon sheaths, bursae, and joints of the hand through accidental trauma or surgical incisions 1
• Chronic granulomatous infection develops in tendon sheaths and joints after direct inoculation, with M. marinum and MAC being particularly prone to causing hand tenosynovitis 1
• The presentation is typically indolent and chronic, with nodular or vesicular characteristics 1

Candida Species

• Disseminated candidiasis causes discrete pink to red papules (0.5-1.0 cm) on trunk and extremities, though knuckle involvement is less common 1
• Lesions may be non-tender but can develop central pallor 1

Traumatic and Iatrogenic Causes

Direct inoculation mechanisms include:

• Contaminated adhesive dressings or venous access devices contaminated with Aspergillus spores cause erythematous indurated plaque-like lesions that progress to necrotic ulcerative lesions 1
• Burn wounds or macerated skin in newborns may become secondarily infected 1
• Post-surgical or post-injection sites, particularly after intra-articular or bursal steroid injections 1

High-Risk Patient Populations

Immunocompromised patients are at dramatically increased risk:

• Patients with chronic granulomatous disease are particularly susceptible to Aspergillus bone and soft tissue infections 1
• Injection drug abusers have increased risk through hematogenous spread or direct inoculation 1
• Neutropenic patients (particularly those with profound neutropenia <100 cells/mL for >7-10 days) are at risk for disseminated fungal infections with cutaneous manifestations 1
• Transplant recipients and patients on immunosuppressive therapy (anti-TNF agents, monoclonal antibodies) require broader differential consideration 1

Critical Diagnostic Approach

Immediate biopsy is mandatory for any vesiculonodular knuckle lesion:

• Skin biopsy with fungal culture is indicated to rule out infections that may manifest similarly 1
• The Infectious Diseases Society of America emphasizes that skin lesions should be aggressively evaluated by culture aspiration, biopsy, or surgical excision as they may be caused by resistant microbes, yeast, or molds 1
• Tissue biopsy is the most sensitive means of obtaining specimens for culture in suspected NTM infections 1
• Both bacterial and fungal cultures should be obtained, along with histopathology with special fungal stains (periodic acid-Schiff, Grocott's methenamine silver) 2

Key distinguishing clinical features to assess:

• Immune status (dramatically changes differential and management) 3
• History of trauma, puncture wounds, or surgical procedures 1
• Presence of systemic symptoms (fever, malaise) suggesting disseminated infection 3
• Rate of lesion progression (rapidly enlarging lesions >1 cm in <24 hours suggest aggressive infection like ecthyma gangrenosum) 3
• Single versus multiple lesions (multiple suggests hematogenous dissemination) 1

Common Pitfalls to Avoid

• Never assume all vesiculonodular lesions are benign, especially in immunocompromised patients where opportunistic infections like cryptococcosis and disseminated fungal infections must be considered 3
• Do not perform incision and drainage or fine needle aspiration alone for suspected NTM lymphadenitis or soft tissue infection, as this may lead to chronic fistula formation; complete surgical excision is preferred 1
• Avoid delaying biopsy in favor of empiric treatment, as the appearance of fungal skin lesions is not pathognomonic and requires definitive diagnosis 1
• Blood cultures are rarely positive in Aspergillus infections, so negative blood cultures should not exclude the diagnosis 1