What is the current evidence on the pathergy test (pathergy test) for diagnosing conditions like Behçet's disease?

Pathergy Test: Current Evidence and Clinical Utility

The pathergy test remains a highly specific diagnostic tool for Behçet's disease, with specificity reaching 98.4% in recent data, though its sensitivity has declined significantly from 64.2% to 35.8% over the past 35 years. 1

What is the Pathergy Test?

The pathergy test evaluates skin hyper-reactivity to minimal trauma by inserting a sterile needle into the forearm skin. 2 A positive result consists of an erythematous papule or pustule (≥2mm) developing at the needle stick site 24-48 hours after the procedure. 1, 2

Diagnostic Performance in Behçet's Disease

Current Test Characteristics

• Specificity: 98.4% (improved from 86.6% in earlier decades) 1
• Sensitivity: 35.8% (declined from 64.2% over 35 years) 1
• Positive Predictive Value: 95.7% (improved from 82.7%) 1
• Positive Likelihood Ratio: 22.4 (improved from 4.8) 1
• Diagnostic Odds Ratio: 34.3 (improved from 11.6) 1

The declining sensitivity represents a geographic and temporal phenomenon, with highest rates historically reported along the Silk Road countries. 1

Clinical Interpretation

When the pathergy test is positive, it is virtually synonymous with Behçet's disease, with a 98.4% probability of the diagnosis. 1 However, the negative predictive value has deteriorated to 60.5%, meaning a negative test does not exclude Behçet's disease. 1

Role in Diagnostic Criteria

The pathergy test is incorporated into multiple classification/diagnosis criteria for Behçet's disease. 3 When pathergy testing is removed from these criteria sets:

• Sensitivity decreases across all criteria (largest loss: 35% for Hubault-Hamza criteria) 3
• Specificity increases modestly (largest gain: 4.7% for Dilsen criteria) 3
• Overall accuracy decreases (greatest loss: 20.4% for Hubault-Hamza criteria) 3

The International Criteria for Behçet's Disease (ICBD) shows the least dependence on pathergy results, losing only 6.5% sensitivity and 3.6% accuracy when pathergy is excluded. 3

Histopathologic Findings

Histopathologic examination of positive pathergy lesions can enhance diagnostic confidence and correlate with disease activity. 4, 5

Dermal Findings

• Mixed inflammatory cell infiltration (43.4% of cases) 5
• Leukocytoclastic vasculitis (21.7%) 5
• Endothelial swelling and thickening (17.3%) 5
• Lymphocytic vasculitis (13.0%) 5

Subcutaneous Findings

• Mixed inflammatory infiltration (39.1%) 5
• Lymphocyte-rich infiltration (21.7%) 5
• Neutrophil-rich infiltration (8.7%) 5

Patients with vasculitis on dermis histopathology have statistically significant association with uveitis, potentially indicating more severe disease. 5

Pathergy in Other Conditions

Pathergy is not pathognomonic for Behçet's disease. 2 The phenomenon also occurs in:

• Pyoderma gangrenosum (lesions often preceded by trauma) 6, 7
• Sweet's syndrome 2
• Other neutrophilic dermatoses 2

In pyoderma gangrenosum, pathergy is a well-recognized phenomenon where trauma triggers new lesion development, and surgical debridement should be avoided during active disease. 6, 7

Standardization Challenges

The lack of internationally standardized methodology for performing and interpreting the pathergy test limits its clinical utility. 2 Variations include:

• Needle gauge and type
• Depth of insertion
• Number of puncture sites
• Timing of assessment (24 vs 48 hours)
• Criteria for positive result (size threshold, presence of pustule)

Clinical Recommendations

When to Use the Pathergy Test

• Suspected Behçet's disease with compatible clinical features (recurrent oral ulcers, genital ulcers, uveitis, skin lesions) 1
• Populations with higher pretest probability (Mediterranean, Middle Eastern, Asian ancestry) 1

Interpretation Algorithm

1. Positive test (≥2mm papule/pustule at 24-48 hours): Strongly supports Behçet's disease diagnosis with 95.7% positive predictive value 1
2. Negative test: Does NOT exclude Behçet's disease; proceed with clinical diagnosis based on other criteria 1, 3
3. Equivocal results: Consider histopathologic examination of the test site 4, 5

Common Pitfalls

• Over-reliance on negative results: With only 35.8% sensitivity, most Behçet's patients will have negative pathergy tests 1
• False positives: Can occur in pyoderma gangrenosum and other neutrophilic dermatoses 6, 2
• Technical variability: Non-standardized technique may produce inconsistent results 2
• Geographic variation: Test performance varies significantly by population 1

Practical Value

Despite declining sensitivity, the pathergy test has not lost its diagnostic value due to markedly improved specificity and positive predictive value. 1 A positive test result provides strong confirmatory evidence for Behçet's disease, while a negative result should not deter diagnosis in patients with compatible clinical features.