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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Dermatology

Diagnosis and the Immune System: How PASH Is Identified

At a Glance

PASH syndrome is diagnosed clinically by confirming pyoderma gangrenosum, acne, and suppurative hidradenitis while ruling out infections and related syndromes. Biopsy and tissue cultures can support the evaluation, but no single test proves PASH.

Because PASH syndrome is so rare, reaching a diagnosis is often a process of clinical evaluation. There is no single blood test or genetic marker that can “prove” you have PASH [1][2]. Instead, doctors rely on your clinical history and a careful evaluation to confirm the three core components: Pyoderma Gangrenosum (PG), Acne, and Suppurative Hidradenitis (SH) [3].

The “Look-Alike” Spectrum

PASH is part of a larger family of autoinflammatory syndromes. While the skin symptoms are the same across many of these, doctors look for “extra” symptoms in your joints or gut to give you the most accurate label. These “look-alikes” include:

  • PAPASH: Adds pyogenic sterile arthritis (recurrent joint swelling that does not contain bacteria) [3].
  • PASS: Adds axial spondyloarthritis (inflammation in the spine or pelvic joints) [4].
  • PsAPASH: Adds psoriatic arthritis [4][5].
  • PAC: Adds ulcerative colitis (an inflammatory bowel disease) [6].
  • PAPA: The “classic” version, which is defined by pyogenic sterile arthritis, PG, and acne (HS is not a defining component) [7].

Identifying which category you fall into is important because it helps your care team decide if you need to see other specialists, like a rheumatologist or gastroenterologist [8].

The Role of Biopsy and the Delphi Criteria

To evaluate the PG component of PASH, doctors often use the Delphi criteria, a validated classification aid for diagnosing skin ulcers [9]. (Note that these criteria are for PG, not a validated diagnostic test for PASH itself.)

  1. The Major Criterion: A biopsy (a small sample of skin) taken from the edge of the ulcer. Under a microscope, a pathologist looks for a neutrophilic infiltrate—a dense collection of white blood cells called neutrophils [9][10].
  2. The Minor Criteria: Doctors look for at least four other signs, such as pathergy (worsening after injury), a history of inflammatory bowel disease, or the specific way the ulcer heals with “wrinkled-paper” scars [9].

It is important to know that a biopsy in PG is “nonspecific.” This means the results can support PG, but they are primarily used to exclude other causes, like cancer or deep infection [11]. Furthermore, because of the risk of pathergy, your doctor will carefully weigh the need for a biopsy against the risk of the procedure causing the ulcer to grow [10].

The “Danger” of Treating Too Early vs. Treating Too Late

Before you start the strong medications (immunosuppressants) used to treat PASH, your doctor must appropriately evaluate you to ensure you do not have a primary infection mimicking PG [9][12].

  • The Hazard: If you have a deep fungal infection (like sporotrichosis) or a rare bacterial infection, taking immunosuppressants can be dangerous because it stops your body from fighting the actual germs [12][13].
  • The Process: Your doctor will likely perform “tissue cultures,” where a piece of skin is sent to a lab to see if anything grows [14][15]. However, clinicians must carefully balance the urgency of controlling destructive PG against the risk of worsening an infection; treatment may sometimes need to begin while some cultures are pending.

The Biology: Dysregulated Inflammatory Signaling

PASH is not caused by a weak immune system; it is driven by one that is highly reactive. Specifically, your innate immune system—the part that is supposed to act like a first responder to injury—is dysregulated [16].

  • Neutrophils: These white blood cells flood your skin, causing the redness, fluid, and tissue breakdown you see [16][17].
  • Cytokines: Your cells may produce high levels of inflammatory proteins called cytokines, such as TNF-alpha, IL-1, and IL-17 [16][18]. These proteins act like chemical signals that keep the inflammatory signaling sounding, leading to chronic inflammation [19][20].

While this is the proposed mechanism, the roles of these cytokines are not identical in every patient. Most modern, off-label treatments for PASH work by specifically blocking these signals to tell your immune system to stand down [21].

Common questions in this guide

How is PASH syndrome diagnosed?
PASH is diagnosed through a clinical evaluation rather than a single blood test or genetic marker. Doctors look for the combination of pyoderma gangrenosum, acne, and suppurative hidradenitis while checking for infections and related syndromes that can look similar.
What does a biopsy show in suspected PASH?
A biopsy from the edge of a pyoderma gangrenosum ulcer may show a dense collection of neutrophils, which supports the pyoderma gangrenosum diagnosis. The finding is not specific to PASH, so the biopsy is also used to rule out other causes such as cancer or deep infection.
Why are tissue cultures important before PASH treatment?
Tissue cultures help look for fungal or bacterial infections, including infections such as sporotrichosis that can resemble pyoderma gangrenosum. Starting immune-suppressing medicine during an untreated infection can make the infection worse, although doctors may need to balance culture results with the urgency of controlling a destructive ulcer.
What conditions can look like PASH?
Related autoinflammatory syndromes include PAPASH, PASS, PsAPASH, PAC, and PAPA, each defined by additional features such as sterile arthritis, spinal or pelvic joint inflammation, psoriatic arthritis, or ulcerative colitis. Persistent back pain, swollen joints, or chronic digestive symptoms may prompt screening for a different or broader diagnosis.
Does PASH mean the immune system is weak?
No. PASH is associated with a dysregulated, highly reactive first-response immune system, in which neutrophils and inflammatory signals such as TNF-alpha, IL-1, and IL-17 can contribute to ongoing skin inflammation.
Why might doctors be cautious about a skin biopsy in pyoderma gangrenosum?
A skin injury can sometimes worsen or enlarge a pyoderma gangrenosum ulcer, a reaction called pathergy. Doctors weigh the value of a biopsy against this risk and may use it when ruling out infection, cancer, or another cause is important.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my case meet the major and at least four minor Delphi criteria for pyoderma gangrenosum?
  2. 2.Have we appropriately evaluated for deep fungal infections like sporotrichosis or atypical bacterial infections through tissue cultures?
  3. 3.Should I be screened for axial spondyloarthritis or inflammatory bowel disease to see if my diagnosis fits PASS or PAC instead of PASH?
  4. 4.Given the risk of pathergy, how was the decision made to proceed with a biopsy, and what did the pathology report show regarding neutrophilic infiltrates?
  5. 5.Are there signs of joint involvement that might suggest I have PAPASH rather than PASH?

Questions For You

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References

References (21)
  1. 1

    Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa Syndrome: A Case Report and Literature Review.

    Huang J, Tsang LS, Shi W, Li J

    Frontiers in medicine 2022; (9()):856786 doi:10.3389/fmed.2022.856786.

    PMID: 35402426
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    Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: a novel whole exome sequencing approach.

    Brandao L, Moura R, Tricarico PM, et al.

    Journal of dermatological science 2020; (99(1)):17-22 doi:10.1016/j.jdermsci.2020.05.004.

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    Ancient friends, revisited: Systematic review and case report of pyoderma gangrenosum-associated autoinflammatory syndromes.

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    Journal of translational autoimmunity 2020; (3()):100071 doi:10.1016/j.jtauto.2020.100071.

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    Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia 2020; (155(5)):542-550 doi:10.23736/S0392-0488.20.06629-8.

    PMID: 32618443
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    Ultrasound-guided cooled radiofrequency ablation for sacroiliac joint pain in a patient with PsAPASH syndrome: A case report.

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    Interventional pain medicine 2026; (5(1)):100742 doi:10.1016/j.inpm.2026.100742.

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    Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in the PSTPIP1 gene.

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    Secukinumab Leading to Rapid Improvement in Pyogenic Arthritis, Acne, Pyoderma Gangrenosum, and Hidradenitis Suppurativa (PAPASH) Syndrome: A Case Report and Review of Treatment Modalities for PAPASH Patients.

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This page explains how clinicians evaluate possible PASH and pyoderma gangrenosum for informational purposes only and does not replace medical advice. Discuss biopsy, tissue cultures, infection testing, and any immune-suppressing treatment with your healthcare team.

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