What is the cause and treatment of multiple subcutaneous knots on the arm and face in a patient of unknown age and sex with no provided past medical history?

Multiple Subcutaneous Nodules on Arm and Face

The most critical first step is to obtain a biopsy of at least one representative lesion to establish a definitive diagnosis, as multiple subcutaneous nodules have a broad differential diagnosis ranging from benign conditions to serious infections and malignancies that require vastly different management approaches. 1

Immediate Diagnostic Approach

Clinical Assessment Priority

• Examine for signs of infection or systemic illness: fever, pain, erythema, warmth, fluctuance, or constitutional symptoms 1
• Assess immune status: history of immunosuppression, organ transplantation, chemotherapy, or immunomodulating medications (anti-TNF agents, monoclonal antibodies) 1
• Document lesion characteristics: size, depth (superficial vs deep), tenderness, color, texture, distribution pattern, and whether lesions are mobile or fixed 2
• Evaluate for trauma history: prior injections, insect bites, or foreign body exposure 1

When to Pursue Urgent Evaluation

Immediate dermatology or infectious disease consultation is warranted if the patient has cellular immune defects (lymphoma, organ transplant, immunosuppressive drugs) because cutaneous manifestations may represent life-threatening disseminated fungal, mycobacterial, or bacterial infections. 1

Differential Diagnosis Framework

Infectious Etiologies (Require Urgent Consideration)

• Fungal infections: Aspergillus, Mucor, Fusarium, or Candida species present as painful erythematous nodules that may become necrotic, particularly in immunocompromised patients 1
• Mycobacterial infections: Nontuberculous mycobacteria cause painless 1-2 cm nodules, poorly resolving cellulitis, or subcutaneous abscesses 1
• Nocardia: Subcutaneous nodules or abscesses that are frequently painless and described as "cold to the touch" 1
• Cutaneous abscesses: Painful, tender, fluctuant red nodules with surrounding erythema, typically polymicrobial 1

Non-Infectious Etiologies

• Epidermoid cysts: Often multiple, contain cheesy keratinous material, may become inflamed without true infection 1
• Cutaneous mastocytosis: Red to brown to yellow nodules or plaques, positive Darier's sign (wheal and flare after stroking), more common in children 1
• Osteoma cutis: Hard papular lesions, can occur as complication of chronic inflammatory acne on face 3
• Dermatitis artefacta: Self-inflicted lesions, often multiple, patient typically denies self-infliction initially 4

Diagnostic Workup

Biopsy is Essential

Perform incisional or excisional biopsy with tissue sent for both histopathology and culture (bacterial, fungal, mycobacterial) to definitively establish diagnosis. 1

• For suspected infection in immunocompromised patients: Consider early surgical debridement in addition to biopsy 1
• Culture requirements: Request aerobic, anaerobic, fungal, and mycobacterial cultures when infection is suspected 1
• Histopathology guides treatment: Distinguishes inflammatory, infectious, and neoplastic processes 1

Additional Testing Based on Clinical Context

• Imaging (ultrasound or CT): May help characterize depth and extent of lesions, particularly useful for suspected osteoma cutis 3
• Blood cultures: If systemic signs present, especially in immunocompromised patients with suspected disseminated fungal infection 1

Treatment Algorithm

If Infectious Etiology Confirmed or Suspected

For immunocompromised patients with life-threatening presentations, initiate empiric broad-spectrum antibiotics, antifungals, and/or antivirals immediately while awaiting culture results, with input from infectious disease specialists. 1

• Fungal infections (Aspergillus, Fusarium, Scedosporium): Voriconazole is first-line; amphotericin B is alternative; consider surgical debridement 1
• Mucormycosis: Amphotericin B plus surgical debridement 1
• Nontuberculous mycobacteria: Prolonged combination therapy (6-12 weeks) with macrolide (clarithromycin) plus second agent based on susceptibilities; surgical debridement crucial 1
• Nocardia: Trimethoprim-sulfamethoxazole for 6-24 months; consider combination therapy for severe disease; surgical debridement for large abscesses 1
• Simple cutaneous abscesses: Incision and drainage with thorough evacuation; antibiotics rarely necessary unless extensive cellulitis or systemic symptoms 1

If Non-Infectious Etiology Confirmed

• Epidermoid cysts: Incision, evacuation, and probing to break up loculations; antibiotics rarely needed 1
• Osteoma cutis: Needle microincisions with mechanical extirpation or curettage of bony formations 3
• Cutaneous mastocytosis: Symptomatic management with antihistamines; avoid triggers; most pediatric cases resolve by puberty 1

Critical Pitfalls to Avoid

• Never assume benign etiology without biopsy: Multiple nodules in immunocompromised patients may represent disseminated life-threatening infection 1
• Do not delay biopsy in immunosuppressed patients: Early tissue diagnosis is critical as empiric therapy may be inadequate 1
• Avoid empiric antibiotics for simple abscesses: Incision and drainage alone is usually sufficient; cultures are rarely helpful 1
• Do not miss PHACE syndrome: Segmental facial lesions in infants may indicate underlying structural anomalies requiring imaging 1
• Consider dermatitis artefacta: Patients typically deny self-infliction; psychological support is needed, though often refused 4