What is the purpose and procedure of the Pathergy test in diagnosing Behçet's disease?

Pathergy Test in Behçet's Disease

Purpose and Diagnostic Value

The pathergy test is a highly specific diagnostic tool for Behçet's disease that, when positive, has a 95.7-98.4% probability of confirming the diagnosis, making it essentially synonymous with the disease despite its declining sensitivity over time. 1

The test serves as one of the major diagnostic criteria for Behçet's disease, producing a nonspecific hyperreactive skin lesion that has been recognized since 1937. 2 While pathergy can occasionally occur in other neutrophilic dermatoses such as pyoderma gangrenosum and Sweet's syndrome, it remains most characteristic of Behçet's disease. 3, 2

Evolution of Diagnostic Performance

The pathergy test has undergone significant changes in its diagnostic characteristics over the past 35 years:

• Sensitivity has declined from 64.2% to 35.8%, meaning fewer patients with Behçet's disease now test positive 1
• Specificity has improved dramatically from 86.6% to 98.4%, meaning false positives are now extremely rare 1
• Positive predictive value increased from 82.7% to 95.7%, making a positive test highly reliable for diagnosis 1
• Positive likelihood ratio improved from 4.8 to 22.4, substantially strengthening diagnostic confidence when positive 1

This evolution means that while you are less likely to obtain a positive test today, when you do get one, it is far more diagnostically certain. 1

Test Procedure

Technique

There is no universally standardized method for performing the pathergy test, which has limited its clinical utility. 3 The test can be performed using:

• Intradermal injection (most common approach) 2
• Intravenous injection 2
• Subcutaneous injection 2

No consensus exists on which technique yields the highest positivity rate. 2

Reading and Interpretation

• Timing: The test is read at 48 hours after needle stick 2, 4
• Positive result: Development of an erythematous papule or pustule at the injection site 2
• Classic appearance: Erythematous induration with a small pustule containing sterile pus at its center 3

Clinical Correlations

Pathergy positivity is significantly associated with active folliculitis (40.7% positive with folliculitis vs 19.2% without; P=0.026), suggesting the test may be more likely to be positive during periods of active skin disease. 5 The test was also positive in all patients with active leg ulcers, though this requires further validation. 5

Histopathologic Findings

When biopsied at 48 hours, positive pathergy lesions demonstrate: 4

• Subcutaneous tissue: Mixed inflammatory cell infiltration (39.1%), lobular panniculitis without vasculitis (8.7%), neutrophil-rich infiltration (8.7%), or lymphocyte-rich infiltration (21.7%)
• Dermis: Mixed inflammatory infiltration (43.4%), leukocytoclastic vasculitis (21.7%), erythrocyte extravasation (26.0%), perivascular cell infiltration (13.0%), and endothelial swelling

Patients with dermal vasculitis on pathergy biopsy had statistically significant association with uveitis, potentially serving as a marker for disease severity. 4

Common Pitfalls

• Lack of standardization in test performance and interpretation can lead to false-positive or false-negative results 4
• Geographic variation: The test is more commonly positive in populations along the historic Silk Road, with declining frequency noted globally 1
• Timing errors: Reading the test too early or too late may miss the characteristic 48-hour response 2, 4
• Misinterpretation: The test should not be used to rule out Behçet's disease given its low sensitivity (only 35.8% of patients will test positive) 1