At the 2025 ODAC Dermatology conference, Dr. Anthony Fernandez, MD, PhD gave an informative presentation titled, No-Brainer Approaches to Neutrophilic Dermatoses. His presentation focused on discussing the clinical presentation, differential diagnosis considerations, and treatment options of pyoderma gangrenosum and Sweet syndrome.
Pyoderma Gangrenosum (PG)
Pyoderma gangrenosum typically presents as an erythematous papule or pustule that rapidly evolves into a painful ulcer with undermined borders with gunmetal gray hue. Pathergy (occurrence at areas of trauma) is a hallmark feature. The most common locations for PG are the lower extremities and peristomal areas. The most common diseases associated with PG are inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies. However, studies suggest only approximately 30% of patients with PG will have one of these diagnoses.
Diagnosis
The differential diagnosis of a PG ulcer includes ulcers caused by any other etiology. Thus, PG has traditionally been a diagnosis of exclusion that requires a thorough evaluation to search for other potential etiologies. However, in recent years several groups have developed diagnostic criteria tools aimed at helping physicians more actively make a diagnosis of PG. One of the most commonly utilized diagnostic scoring tools is calculation of a PARACELSUS score. Each letter in PARACELSUS stands for a diagnostic characteristic of pyoderma gangrenosum: progressive disease, assessment of relevant differential diagnoses, reddish-violaceous wound border, characteristically irregular ulcer shape, extreme pain of >4/10 on the visual analogue scale (VAS), localization of lesion at site of trauma (pathergy), suppurative inflammation in histopathology, and undermined wound border. Each characteristic that is present assigned a number of points based on the characteristic’s classification as a major, minor, or additional criterion. When a patient has a total PARACELSUS score of ten or more points, a diagnosis of PG is likely. Alternatively, if the score is < 10, a diagnosis of PG is unlikely.
Treatment
Topical steroids and intralesional corticosteroids may be used for small ulcers and stomal ulcers. However, most patients with PG are going to require systemic treatment, with systemic corticosteroids being first-line. Dr. Fernandez highlighted the second-line medications he typically uses for treatment of PG in his patients: cyclosporine, dapsone, IVIG, and TNF inhibitors (especially for PG associated with inflammatory bowel disease or rheumatoid arthritis). These treatments can often control and resolve the active inflammation of PG; however, patients are still typically left with a large ulcer that needs to heal. Importantly, Dr. Fernandez stressed that this implies knowledge and application of basic and advanced wound care strategies is imperative in order to achieve healing of PG ulcers.
Dr. Fernandez described several cases of PG he has seen and the various treatment regimens that led to ulcer healing. He also reminded audience members that it is important to consider the possibility that PG-like ulcers are a manifestation of other diseases. He shared the case of a patient with a PG-like ulcer who was eventually found to have granulomatosis with polyangiitis (GPA). GPA should especially be considered when PG occurs in atypical locations of the body, especially the face.
Sweet Syndrome
Clinical and Histological Presentation
Sweet syndrome typically presents with tender erythematous papules and plaques, usually on the upper body. Patients often have constitutional symptoms of fevers and arthralgias. Serologic studies may reveal an elevated white blood cell count with neutrophilia and elevated sedimentation rate. On histopathologic examination, there is a dense neutrophilic infiltrate with prominent papillary dermal edema.
Treatment
Most patients with Sweet syndrome have episodes for only several weeks, in comparison to a course of several months for PG. Given the often-shorter duration of the disease, most patients can be managed with a short course of oral glucocorticoids. Dapsone, colchicine, and cyclosporine may be needed for recurrent or refractory cases. Sweet syndrome often occurs in association with underlying disorders, so a full evaluation and workup for underlying diagnoses should be performed. In the setting of inflammatory bowel disease (IBD), Sweet syndrome activity often parallels the IBD activity. In such cases, treating the IBD effectively will also often lead to control of Sweet Syndrome lesions.
Consider VEXAS Syndrome in differential diagnosis
VEXAS syndrome is a relatively recently described auto-inflammatory syndrome affecting older men. On bone marrow biopsy, there are characteristic vacuoles in myeloid precursor cells from bone marrow. Up to 90% of patients with VEXAS syndrome will have a rash that is typically consistent with a neutrophilic dermatosis, especially Sweet syndrome or small-to-medium vessel vasculitis. Patients with VEXAS syndrome usually only respond to high-dose glucocorticoids, while traditional steroid-sparing agents having little effect. In a study of twenty-two patients with VEXAS syndrome, 40% of patients died either secondary to manifestations of the disease or from adverse effects related to long-term, high-dose glucocorticoid use. VEXAS patients have somatic mutations in the ubiquitin activating enzyme gene 1 (UBA1) gene. This is found on the X chromosome, which explains why this disease only affects male patients. UBA1 functions in the ubiquitin-proteosome system, which targets damaged proteins within cells for degradation. When this gene is mutated, damaged cells build up within cells and eventually trigger production of inflammatory cytokines that lead to the manifestations of VEXAS syndrome. Several studies suggest the most common differential diagnosis of the rash seen in VEXAS syndrome is Sweet syndrome. Thus, it is important to consider the possibility of VEXAS syndrome when evaluating older men with rashes suggestive of Sweet syndrome. JAK inhibitors, particularly ruxolitinib, has been shown to be efficacious in management of VEXAS syndrome.
Conclusion
In conclusion, PG can be difficult to diagnose and treat. However, use of new diagnostic criteria tools may be useful for clinicians to use in order to increase their confidence in a PG diagnosis. Corticosteroids are first-line treatment, but there is an important role for use of steroid-sparing agents, such as cyclosporine, dapsone, IVIG, and TNF inhibitors. PG-like ulcerations can be a sign of ANCA-associated vasculitis, especially granulomatosis with polyangiitis. In patients with new or refractory Sweet syndrome, workups to rule out underlying diseases, especially VEXAS syndrome when occurring in older men, can truly be lifesaving for these patients.
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