Understanding the Zebras of Wound Care: An Overview of Atypical Wounds

Elizabeth Ansert, DPM, MBA, MA; Anthony Tickner, DPM, FACCWS, FAPWCA, FAPWH; Donald Cohen, DPM; Weldon Murry, DPM; Samuel Gorelik, DPM


Wounds. 2022;34(5):124-134. 

In This Article

Abstract and Introduction


Atypical wounds account for approximately 5% to 20% of chronic ulcerations. Typically, clinical suspicion of an uncommon etiology is warranted for wounds that do not show signs of healing with conventional care, that are associated with pain out of proportion to the clinical presentation, or that are atypical in appearance. This review provides a general overview of various atypical wound etiologies, clinical presentations and appearance, and current treatment protocols. The clinical presentation, pathophysiologic etiology, and current literature on each etiology are presented. The etiologies discussed are pyoderma gangrenosum, calciphylaxis, lichen planus, necrobiosis lipoidica, infectious ulcers, hidradenitis suppurativa, artefactual ulcers, hydroxyurea-induced ulcers, vasculopathies, and neoplastic ulcers. Patients with atypical wounds experience a poorer prognosis and slower healing rate compared with patients with typical wound etiologies (eg, vascular and diabetic wounds). Biopsy is often vital in wound care to identify and differentiate wound etiologies. It is important to note that multiple characteristics or histologic features can overlap in a biopsy with atypical wounds. Therefore, a biopsy will still require an understanding of the presentation of these different wounds and should only be used when appropriate. The proper diagnosis for an atypical wound can greatly hasten wound closure, decrease the cost for the patient and the health care system, and improve the patient's quality of life. Because of the limited availability of patient populations with atypical wound etiologies, literature concerning specific pathologies is limited. More research on each pathology is needed, as is a universally accepted treatment protocol for atypical wounds.


Atypical etiologies account for approximately 5% to 20% of chronic ulcerations,[1] whereas 43% of chronic ulcerations are infected ulcerations, 22% are diabetic ulcerations, and 19% are vascular ulcerations.[2–5] Because of the lower proportion of atypical etiologies, research and industry interest in these ulcerations is lower than in the more common ulceration etiologies. The ability to recognize these so-called zebras, or wounds that are epidemiologically rare, can be critical to the treatment course and the patient's overall well-being.[6] An uncommon etiology should be suspected clinically when a wound does not show signs of healing with conventional care, when pain is out of proportion to the clinical presentation, or for the wound with an atypical clinical appearance.[6–8] Additionally, an etiology may be uncommon in the United States but typical in other countries.

Atypical wounds may be categorized into different groups, including inflammatory ulcers, vasculopathies, neoplastic ulcers, hematologic ulcers, infectious ulcers, hydroxyurea-induced ulcers, and heroin-induced ulcers.[5] Ulcer categorization also may vary by the clinician evaluating the wound. In addition, many patients with diabetes may have components of vasculopathic, inflammatory, and infectious processes that contribute to the wound.[3] A complete patient history should be obtained, and the pathophysiology of various comorbidities should be considered. This article provides a general overview of various atypical wound etiologies, presentations, and clinical appearances, as well as current treatment protocols.