What are the possible causes and treatments for a red, itching scrotum after total knee replacement?

Red, Itching Scrotum Post Total Knee Replacement

Primary Differential Diagnosis

This presentation most likely represents Red Scrotum Syndrome (RSS), a chronic condition characterized by well-demarcated scrotal erythema with persistent itching and burning, which may have been triggered or exacerbated by perioperative topical corticosteroid use or prolonged moisture exposure during the surgical recovery period. 1, 2

However, given the post-surgical context, you must first rule out periprosthetic joint infection (PJI) with systemic manifestations before attributing symptoms solely to a dermatologic condition. 3, 4

Initial Workup Algorithm

Step 1: Assess for Systemic Infection

• Obtain ESR, CRP, and serum interleukin-6 immediately to evaluate for occult periprosthetic joint infection, as the American Academy of Orthopaedic Surgeons strongly recommends these tests for any patient with concerning symptoms post-TKR 3, 4
• Check for knee pain, particularly night pain or pain at rest, which characteristically indicates infection rather than mechanical issues 3, 4
• Note that peripheral WBC counts are not elevated in most patients with infected prostheses, making a normal WBC meaningless for excluding infection 4
• CRP has 73-91% sensitivity and 81-86% specificity for prosthetic knee infection when using a cutoff of 13.5 mg/L 4

Step 2: If Inflammatory Markers Are Elevated

• Proceed immediately with knee joint aspiration for synovial fluid analysis to definitively rule out or confirm PJI, as recommended by the American College of Radiology 4
• Withhold antibiotics for at least 2 weeks prior to aspiration if clinically feasible to avoid false-negative cultures 4
• Obtain knee radiographs first as the initial imaging evaluation, looking for signs of loosening, osteolysis, or component migration 4, 5

Step 3: If Infection Workup Is Negative

Proceed with diagnosis and treatment of Red Scrotum Syndrome, which is the most likely primary dermatologic etiology 1, 2, 6

Red Scrotum Syndrome: Diagnosis and Management

Clinical Features Supporting RSS Diagnosis

• Well-demarcated erythema of the anterior scrotum with persistent itching and burning 1, 2
• Erythema demarcation precisely follows the scrotal hairline, suggesting hair follicles acted as scaffolding during potential biofilm formation 1
• History of prolonged topical corticosteroid use (common perioperatively for surgical site management or incidental use) 2, 6
• Condition may have begun following prolonged moisture exposure (e.g., surgical drapes, bedrest, wound drainage) that facilitated cutaneous microbial biofilm formation 1

Pathophysiology

• RSS appears to be either a manifestation of corticosteroid misuse/rebound vasodilation or cutaneous microbial biofilm formation rather than a primary disease entity 1, 2
• Histopathology reveals features resembling erythematotelangiectatic rosacea in many cases 2

Treatment Algorithm for Red Scrotum Syndrome

First-Line Treatment

Initiate oral doxycycline 100 mg twice daily combined with either amitriptyline 10-25 mg at bedtime or pregabalin 75-150 mg twice daily, along with complete cessation of any topical corticosteroids. 2, 6, 7

• All patients report significant improvement (50-80%) within 2-4 weeks of starting doxycycline 2, 6
• Complete resolution of symptoms typically occurs within 2-4 months of continuous treatment 2, 6
• The combination of doxycycline with amitriptyline or pregabalin addresses both the inflammatory/microbial component and the neuropathic pain component 2, 7

Second-Line Treatment (If Doxycycline Fails After 2 Weeks)

Switch to gabapentin 300-900 mg three times daily as monotherapy for neuropathic symptom control 7

Adjunctive Topical Therapy

• Consider twice-daily application of 0.8% menthol powder for symptomatic relief of itching and burning 1
• Avoid tacrolimus unless doxycycline provides inadequate response, as evidence is limited 7

Critical Pitfalls to Avoid

• Do not rely on the absence of fever, erythema, or warmth around the knee to exclude PJI—chronic infections frequently present with pain alone 4
• Do not dismiss scrotal symptoms as unrelated to the TKR—systemic infection can present with diverse cutaneous manifestations, and perioperative factors may trigger RSS 3, 1
• Do not prescribe topical corticosteroids for the scrotal erythema—this will perpetuate or worsen RSS 2, 6
• Recognize that 75% of RSS patients have psychiatric comorbidities (anxiety, depression), which contribute to significant psychological distress and require concurrent management 2
• Understand that even with complete symptomatic relief, the scrotal erythema may persist unchanged for years, which does not indicate treatment failure 1

Expected Outcomes

• RSS contributes to significant psychological distress and reduction in quality of life, making prompt diagnosis and treatment essential 1
• With appropriate treatment, marked improvement of erythema and complete resolution of symptoms occurs in 2-3 months 6
• Treatment must be continued for 3-4 months even after symptom improvement to prevent relapse 2