Amputations in Pyoderma Gangrenosum Patients: Underreported or Very Rare?

There is limited literature on the topic of amputation in pyoderma gangrenosum (PG). For example, a PubMed search of the terms “amputation” and “pyoderma gangrenosum” yields only 38 results. For a search of “pyoderma gangrenosum” there are 4,021 results meaning that less than 1% of these articles discuss amputation.

As the diagnosis of PG can be challenging and misdiagnosis is common (there is no definitive test and many mimickers exist), it follows that amputation prior to diagnosis would not be an exceedingly rare occurrence. In our experience, some providers will not diagnose patients with PG (or other inflammatory ulcers) unless biopsy is “positive” though biopsy findings in PG are often nonspecific.¹ Furthermore, in a retrospective review of 103 PG patients at Brigham and Women’s Hospital and Massachusetts General Hospital, only 7% of patients had characteristic features of PG on biopsy.²

Are providers missing the diagnosis of PG because they are anchoring on “positive” biopsy findings? Could we be missing cases in which PG patients underwent amputation, didn’t have a recurrence, and were never diagnosed? Or are we just not talking about amputation in pyoderma gangrenosum?

Our research group at Oregon Health and Science University has published two studies on amputation in pyoderma gangrenosum. The first study consisted of a systematic review on cases in which amputation was considered prior to the diagnosis of PG and a case series of patients with known PG who underwent amputation.³ Reviewing the prior to diagnosis cases led to the observations that necrotizing soft tissue infections (eg, necrotizing fasciitis) was the most common clinical mimicker of PG and the location of the ulcers did not aid in differentiating the two conditions. Furthermore, in the cases that resulted in amputation, dermatology was not consulted until the patient’s condition necessitated amputation.

In the second study, a multi-institutional case series amputation after a diagnosis of PG, we identified factors that may predispose patients to complications requiring amputation.⁴ These factors included non-healed ulcers for > 2 years in elderly patients as well as the presence of classic comorbidities such as diabetes mellitus, heart disease, and kidney disease. In both studies, cases of recurrence after amputations were described that can also aid in diagnosing pyoderma gangrenosum if PG has not been considered.

PG is a non-infectious inflammatory disease that can recur, have extracutaneous organ involvement, or even mimic a sepsis-like presentation^5,6 (eg, PG with systemic manifestations is included within the broad category of necrotizing neutrophilic dermatoses). Therefore, it is understood that amputation does not guarantee that a patient will not have new PG ulcers in the future.

Multifaceted treatment through the use of medical immunosuppressive therapy, wound management, and pain control for PG⁷ is certainly preferable to amputation, though a few clinical scenarios may necessitate amputation. For example, if a digit or limb becomes necrotic or the patient develops a life-threatening polymicrobial infection, amputation of the affected anatomic area may become the only option for source control. And while amputation may buy the patient and provider more time, the patient remains at risk for new ulcerations, further amputation and further complications.

Undoubtedly, we would prefer to only have tales of success to regale the wound care world with, but we find that reviewing the challenges and unfavorable outcomes are of equal importance, and we have seen that studying this undesirable outcome can lead to important conclusions and give us clues on how to do better for our PG patients.

So we ask: what is the reason for the lack of literature on amputation in PG? Is it that authors don’t want to write about negative outcomes? (We can recall at least one case last year discussed with us but it was never published) Or that PG remains underrecognized? Or are we overestimating the frequency of this outcome?

We invite you to take this four-question survey and comment with your experiences with PG.
 
Shannon Kody, MD, is affiliated with the Department of Dermatology at Oregon Health and Science University.

Alex G. Ortega-Loayza, MD, MCR, is affiliated with the Department of Dermatology at Oregon Health and Science University. Contact information: Ortegalo@ohsu.edu; Twitter handle: @ThePGguy

Click here to download a PDF of this article.

References
1.    Hammer P, Latour E, Bohnett MC, et al. The utility and challenges of histopathologic evaluation in the diagnosis of nonmalignant skin ulcers. Wound Repair Regen. 2020; 28(2): 219–223. 
2.    Binus AM, Qureshi AA, Li VW, Winterfield LS. Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients. Br J Dermatol. 2011;165(6):1244–1250.  
3.    Shakshouk H, Lehman JS, Wu B, et al. Limb amputation in patients with pyoderma gangrenosum: a multi-institutional case series [published online ahead of print, 2022 Nov 29]. Arch Dermatol Res. 2022;10.1007/s00403-022-02484-3. doi:10.1007/s00403-022-02484-3
4.    Haag CK, Nutan F, Cyrus JW, et al. Pyoderma gangrenosum misdiagnosis resulting in amputation: A review. J Trauma Acute Care Surg. 2019;86(2):307–313.
5.    Sanchez IM, Lowenstein S, Johnson KA, et al. Clinical features of neutrophilic dermatosis variants resembling necrotizing fasciitis. JAMA Dermatol. 2019 Jan 1;155(1):79–84.
6.    Morse DC, Patel PM, Haag C, Ortega-Loayza AG. Successful mastectomy and chemotherapy in a patient with breast cancer and active generalized pyoderma gangrenosum. Wounds. 2020 Apr; 32 (4):E19–E22
7.    Orfaly VE, Reese AM, Friedman M, et al. Pyoderma gangrenosum study pilot registry: The first step to a better understanding. Wound Repair Regen. 2022 May;30(3):334–337.