Pathergy phenomenon is a state of non-specific hypersensitive tissue response to minor trauma. The pathergy test has a high diagnostic value that helps clinicians to choose the right therapy and also helps inform of complications if any.

Introduction

Pathergy phenomenon is not restricted to skin or mucosa, it can be evident in other tissues as well. For example development of uveitis after intraocular injection or synovitis exacerbation after arthrocentesis or vascular aneurysm formation after vascular surgery etc.

It is characteristically seen in Behcet's disease and is a part of the classification criteria for Behcet's. In India, Behcet's disease is not an uncommon condition commonly encountered in ophthalmology clinics with uveitis as presentation or dermatology or rheumatology clinic with recurrent oral and genital ulceration, unspecified spondyloarthritides, variable vasculitis and other systemic manifestations. Behcet's disease is strongly associated with HLA B5 and one of the studies showed high prevalence in north Indians. This phenomenon can also be seen in conditions like neutrophilic dermatoses - pyoderma gangrenosum and sweet syndrome. Others are inflammatory bowel disease or eosinophilic pustular folliculitis.

A test demonstrating a pathergy phenomenon is called a pathergy test. First described by Blobner in 1937, a pathergy test is performed in two ways - Skin Pathergy Reaction (SPR) and Oral Pathergy Reaction (OPR).

Pathogenesis

Exact pathogenesis is not clear. It is thought to be a cutaneous inflammatory response that is seen due to aberrant production of cytokines by keratinocytes or cells of dermis or epidermis in response to tissue injury. It leads to perivascular infiltration of inflammatory cells as demonstrable in skin biopsy.

Factors affecting pathergy test 

• Race/ethnicity - Positivity rate is higher in highly prevalent countries like Turkey, China, Iran, Iraq, Egypt, Japan, and lower in low prevalence countries like Denmark, Norway. The pathergy positivity rate in India is 31%
• Disease activity - Pathergy phenomenon follows remitting relapsing course. Higher positivity is seen with higher disease activity
• Male sex
• Higher positivity rate in those having concomitant recurrent oral ulcers, pseudofolliculitis or uveitis
• Technique - High yield with the usage of blunt needle 20G, multiple prick or puncture (at least 2 or more), preferred site - flexor aspect of the forearm; increased use of disposable needles has decreased sensitivity over non-disposable needles
• Patients already on glucocorticoids decrease the positivity rate

Indication and interpretation of positive pathergy test

1. In an appropriate clinical context (i.e presence of recurrent oral ulcer and one of the following - genital ulcer or eye or skin lesion or neurological manifestation or thrombophlebitis), it can help in diagnosis.
2. It indicates active disease.
3. It is an independent risk factor for postoperative complications.

The technique of skin pathergy test

1. Site: Hairless aspect of flexor area of forearm is preferred because of higher positivity rate compared to other sites. The abdomen has the least positivity rate. It might be explained because of variation in the structure, thickness and vasculature of skin.
2. Route: Various routes have been tried i.e Intradermal, intravenous, subcutaneous. Yield with intradermal route has been higher than others; therefore, the intradermal route is preferred.
3. Needle - Blunt needle of 20 G is preferred over a sharp needle of 26 G because of the higher extent of the injury with the blunt needle.
4. Agent: Various agents that have been tried to increase positivity rate are - normal saline, monosodium urate crystals, pneumococcal antigens etc. Some doesn't use an agent and conduct direct prick with a sterile needle.
5. Number of pricks: More the number, the better is the sensitivity. The commonly used protocol is 4 to 6 pricks.
6. Procedure: There is no standardised protocol. The skin of both forearms is cleansed with an antiseptic, commonly alcohol. Blunt sterile 20 G needles should be inserted either perpendicular or oblique at an angle of 45 degrees or less through the skin to a depth of 3-5 mm. The bevelled end of a needle to be kept up and the needle should reach the dermis for proper response. At Least 2 to 3 pricks in each forearm to be performed.

Test result interpretation

Time - Although results can be read within 24 or 48 hours of a prick, a 48-hour reading has higher sensitivity and hence is preferred.

Clinical assessment 

1. Skin reaction: Papular or pustular lesion surrounded by erythematous halo and induration at the site of needle prick. Interpretation to be done with the naked eye.
2. Positive test - An erythematous papule ≥2 mm or a pustule at the site of prick.
3. Negative test - No changes at the site of needle prick or erythema without induration
4. Histological assessment: sensitivity of histological assessment is similar to clinical assessment; hence clinical assessment is recommended for interpretation.

Oral pathergy test 

1. Site: Lower lip
2. Procedure: prick the mucous membrane of the lower lip to the submucosa using a 20 gauge blunt disposable needle.
3. Assessment: Readings are taken after 48 hours, and the test is considered positive if a pustule or ulcer is seen.
4. Advantage: Easier to assess - no need for size measurement.
5. Disadvantage: Sensitivity of oral pathergy is lower than skin pathergy.

Conclusion

Diagnosis of Bechet's requires a high index of suspicion and in certain relevant clinical conditions, pathergy tests can help in making a diagnosis. It is simple and easy to perform outpatient/bedside tests by clinicians. Skin pathergy test is preferred over oral pathergy because of its higher sensitivity. If appropriately conducted, it can provide a high diagnostic adjunct. Positive tests also indicate active disease which helps clinicians in making decisions on therapeutic intervention and also warns surgeons of surgical complications. But we should always consider other conditions where the pathergy test can be positive and should always be ruled out.

This article was originally published on 16 July 2021.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising Rheumatologist from Bangalore.