This is a story that only happens in the world of chronic wounds. It illustrates why wound care practitioners need to keep asking “What is this wound a symptom OF?” It also illustrates why patients often get worse care as a result of medical specialization because the specialists put on blinders to any medical problem they consider “not in my field.”

Using Occam’s Razor on a Mathematician

This patient was a 67 year old man with well-controlled diabetes and multiple, bilateral, irregularly irregular, painful lesions located on unusual areas like the anterior shin. The wounds had all been made worse by the “serial debridements” performed at another wound center. Since he’d stopped going to that wound center, all the wounds had gotten better. Unfortunately, that part if the history is all I need to make the diagnosis of pyoderma gangrenosum (PG). “My wounds kept getting bigger as a result of the debridements at a wound center,” is a more sensitive test for PG than a biopsy. That’s because, as usual, a biopsy (which was performed at a respected academic dermatology program) was unhelpful and the dermatologist threw up her hands and told him go see a “vascular doctor.”

The day of his initial consult I performed arterial screening and he had a normal skin perfusion pressure (>40 mmHg) with a triphasic pulse volume recording. In other words, he had no peripheral arterial disease. You have only to look at these lesions to see they are NOT Venous. Here’s the most interesting part. He had a colostomy that had been performed for inflammatory bowel disease (IBD), and he had hidranitis supprativa (HS), and scars on his face from cystic acne.

The patient had a PhD in mathematics. I said, “I’m bad at math so I need you to help me do some odds calculations.”  The incidence of IBD in the USA is maybe 15:10,000; the incidence of HS is maybe 10:10,000; PG is supposed to be “rare” at 10:1,000,000. That means he had 2 relatively uncommon diseases and one “rare” one. I asked him to calculate the odds that one person had all 3 of those conditions as totally separate medical problems.

The sharpest tool I use on patients with PG is “Occam’s razor.” In other words, the simplest explanation is the best. It’s more likely that he has ONE disease with several different inflammatory manifestations. Somehow, all his problems were related.

PASH Syndrome

I sat down at the computer and did a search for, “pyoderma gangrenosum, hidradentitis and acne” and in about 5 minutes had discovered a genetic syndrome, first identified in 2012. The syndrome has been labled “PASH” for Pyoderma gangrenosum, Acne, and “Supprative Hidranenitis.” (1) In fact, there was a lot of information, (2, 3, 4) There are other PG syndromes that include inflammatory bowel disease and some that include pyogenic arthritis. Exactly where he fits in the syndrome would require genetic testing but it seemed logical and perhaps even obvious that he’s got a genetic syndrome with a name. And that meant someone in the USA was doing research on it.

I called his academic dermatologist and excitedly told her that I thought he had PASH and I intended to start prednisone. She was not at all interested, stuck to her negative biopsy, was unimpressed with my reasoning and disagreed with prednisone. I told her I’d handle it myself. Since he had diabetes, the patient and I agreed that he’d be even more strict than usual in his glucose monitoring and diet and I started 30 mg of prednisone a day for seven days only. At that point, we’d reassess. Meanwhile I checked a G-6-PD level in hopes of starting Dapsone if prednisone helped.

Then I started sending emails. All the papers I found about PASH were written in Europe. I emailed the corresponding authors and I got gracious and helpful emails from authors in 3 different countries! They pointed me to the physician at the NIH who is indeed, focused on PASH syndrome. I emailed the NIH expert, and he responded immediately. He agreed the story was convincing enough for them to want the patient to travel to the NIH for evaluation.

Good News and Bad News

His PG got dramatically better after only one week of prednisone. You can see that in the photos. Even his hidranentiis got dramatically better. There were many wounds, all of which improved, and I could post a lot of before and after photos, but that’s not really the point of this article. He was hopeful, perhaps for the first time in his life. Then, two weeks later, he died of COVID-19. His wife called to tell me the news of his death, but she wanted me to know that after a lifetime of suffering, just having a possible explanation had made a difference in his life.

Here’s the take-home message:

• If you are a wound physician and a patient’s wounds get worse with debridement, for God’s sake, stop doing it.
• Any of this man’s five specialists (and the other wound care practitioner) could have connected the dots if they’d just paid attention to the clinical picture.
• Even many dermatologists can’t make a presumptive diagnosis of PG. I do not understand why one week of prednisone is a terrifying “trial of therapy” for any physician to implement. DO NOT TRUST THE BIOPSY when it comes to PG.
• Most of the authors of published papers and certainly the folks at the NIH are incredibly responsive, so never be afraid to contact people! The correspondence I had with experts from around the world was more encouraging (and certainly more helpful) than the conversations I had with any of the patient’s specialists.
• Finally, the most important thing a wound care clinician can have is intellectual curiosity.

Caroline

1. J Am Acad Dermatol. 2012 Mar;66(3):409-15. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)–a new autoinflammatory syndrome distinct from PAPA syndrome.
2. Cugno M, Borghi A, Marzano AV. PAPA, PASH and PAPASH syndromes: pathophysiology, presentation and treatment. Am J Clin Dermatol. (2017) 18:555–62. doi: 10.1007/s40257-017-0265-1.
3. Marzano AV, Ceccherini I, Gattorno M, Fanoni D, Caroli F, Rusmini M, et al. Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases. Medicine (Baltimore). (2014) 93:e187.
4. CASE REPORT article, Front. Med., 24 March 2022 Sec. Dermatology; Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa Syndrome: A Case Report and Literature Review.

Check out the supplementary material Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa Syndrome: A Case Report and Literature Review.