Atypical Ulcers: A Stepwise Approach for Clinicians

Melissa A. Nickles, MD; Maria M. Tsoukas, MD, PhD; Nadera Sweiss, MD; William Ennis, DO, MBA; Igor A. Altman, DO, MBA


Wounds. 2022;34(10):236-244. 

In This Article

Abstract and Introduction


Chronic ulcers are associated with significant morbidity and mortality. Typical ulcers are due to venous insufficiency, diabetes, ischemia, pressure, and lymphedema. A chronic ulcer that does not respond to standard therapies should be reevaluated for potential atypical etiologies. Atypical ulcers are less common and more difficult to diagnose due to a wide range of possible etiologies, including inflammatory (autoimmune), neoplastic, vasculopathy, hematologic, infectious, drug-induced, or external. No standardized approach to the management of complex atypical ulcers exists. In this review, a stepwise approach to atypical ulcers is proposed with the aim of assisting physicians in their identification and diagnosis. If perfusion is adequate and there are no signs of infection, then the authors recommend obtaining an ulcer biopsy for microbiologic, DIF, and histopathologic evaluation as the criterion standard for diagnosis. Laboratory testing, including an autoimmune panel, a hypercoagulable panel, and an infectious diseases panel, can further aid in diagnosis. Atypical ulcers often require multidisciplinary care, with input from specialists in rheumatology, dermatology, infectious diseases, wound care, vascular surgery, hematology, and oncology. Effective communication within the health care team is essential for accurate diagnosis and management of atypical ulcers. Active dialogue between providers can improve consult efficiency and ultimately lower the cost of care.


Chronic ulcers commonly present on the lower extremities and greatly affect quality of life.[1,2] Chronic leg ulcers are those that persist for more than 6 weeks and show no tendency to heal after 3 or more months of appropriate treatment.[2] While common causes of chronic ulcers include venous leg ulcers, diabetic foot ulcers, PIs and PUs, and arterial ulcers,[3] it is estimated that autoimmune diseases may play a role in 20% to 23% of patients with a chronic leg ulcer.[4,5] The potential etiologies and workup of an atypical ulcer are reviewed herein.