JAMA Clinical Challenge March 21, 2022
Fever, Hypotension, and a Worsening Necrotic Wound
Danielle M. Peterson, William E. Damsky, Matthew D. Vesely
JAMA. Published online March 21, 2022. doi:10.1001/jama.2022.2806
On the day of giving birth via a normal vaginal delivery, a healthy woman in her 20s developed painful swelling on her right thigh, at the site of a methergine injection administered 1 day prior. Despite 3 days of treatment with an oral antibiotic (cefalexin), her thigh pain and swelling did not improve, and she was readmitted to the hospital and intravenous clindamycin was started. Wound cultures and blood cultures obtained during incision and drainage performed on hospital day 1 were negative for bacterial, mycobacterial, and fungal organisms. The following day, her temperature was 39.4 °C (102.9 °F), blood pressure was 86/42 mm Hg, and heart rate was 131/min. She was transferred to the intensive care unit for presumed septic shock, and her antibiotics were changed to vancomycin and meropenem. Surgical debridement of the right thigh was performed on hospital day 3.
On hospital day 4, a new purple dusky border developed along the wound edge, and the patent underwent a second surgical debridement. After debridement on hospital day 5, her temperature was 39.8 °C (103.6 °F), and she required vasopressor infusion with norepinephrine for shock. Her right thigh had a deep 9 × 8–cm ulcer with a dusky violaceous border extending 2 to 5 cm from the wound edge (Figure, left), with many 1- to 2-mm pustules (not visible in Figure). Laboratory testing showed a white blood cell count of 30 000/μL (88% neutrophils); lactate level, 77.5 mg/dL (8.6 mmol/L); and procalcitonin level, 16.1 ng/mL (reference, <0.1 ng/mL). Histologic examination of the tissue obtained during the second surgical debridement revealed ulceration with extensive neutrophilic inflammation (Figure, right). Stains for microorganisms, and tissue and blood cultures, remained negative.
What Would You Do Next?
- Add intravenous amphotericin B
- Further surgical debridement
- Start hyperbaric oxygen therapy
- Start intravenous glucocorticoids
Discussion
Necrotizing pyoderma gangrenosum
D. Start intravenous glucocorticoids
The key to the correct diagnosis of necrotizing pyoderma gangrenosum in this case was the presence of a dusky ulcer with a violaceous border, histopathologic findings of a dense pan-dermal neutrophilic infiltrate (Figure, right), and absence of an infectious organism on multiple blood and tissue cultures. Because pyoderma gangrenosum is an inflammatory condition, additional antifungal therapy (choice A) is not effective, and additional surgical debridement (choice B) could worsen the condition because of pathergy. Hyperbaric oxygen therapy (choice C) may be used for wound healing but would not resolve the inflammation associated with pyoderma gangrenosum.
Neutrophilic dermatoses are a heterogenous group of inflammatory, noninfectious skin disorders that present with a sterile, neutrophilic infiltrate on histopathology.1,2 Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis with an estimated worldwide incidence of 3 to 10 cases per million people per year, with a female to male ratio of 1.8:1 across all ages.3 Pyoderma gangrenosum typically presents with ulcerative (classic), bullous, pustular, or vegetative lesions. Early lesions of ulcerative pyoderma gangrenosum appear as tender erythematous nodules or papulopustules that can erode to create ulcers with a purulent base and inflammatory, violaceous, and overhanging borders. More than half of patients develop pyoderma gangrenosum in association with an underlying systemic disease, such as inflammatory bowel disease, rheumatoid arthritis, or hematologic malignancy. Pyoderma gangrenosum is also associated with pathergy, a condition in which trauma to the skin (such as surgical debridement) results in skin lesions or ulcers that may be resistant to healing.4-6 In this patient, the methergine injection likely served as the source of pathergy.
Pyoderma gangrenosum and Sweet syndrome, a neutrophilic dermatosis typically characterized by painful nodules or plaques, may present with systemic symptoms that can mimic necrotizing fasciitis or severe infection, including fever, shock, and leukocytosis.4,7 Necrotizing neutrophilic dermatosis has been recently proposed as a unifying term for necrotizing pyoderma gangrenosum and necrotizing Sweet syndrome4 and is characterized by histopathologic findings of diffuse dermal and subcutaneous neutrophilic infiltration with necrosis, negative blood and tissue cultures, and prominent clinical signs or symptoms of systemic inflammation (such as leukocytosis and shock).1
Pyoderma gangrenosum is frequently misdiagnosed, which can lead to a delay in appropriate treatment as well as unnecessary and ineffective treatment with antibiotics. Moreover, surgical debridement may worsen pyoderma gangrenosum through pathergy. Key diagnostic criteria for pyoderma gangrenosum recently proposed by international expert panels include development of a progressive ulcer with a neutrophilic infiltrate seen on histologic examination, no evidence of an infectious cause (negative tissue culture and special stains for bacteria, fungi, and mycobacteria), and a therapeutic response to immunosuppressants.8,9 In addition, workup for hematologic malignancy, inflammatory bowel disease, and rheumatoid arthritis should be performed for individuals diagnosed with pyoderma gangrenosum.
First-line treatment of pyoderma gangrenosum involves use of systemic glucocorticoids over the course of days to weeks.1,2,4 Glucocorticoid-sparing treatments, including infliximab and cyclosporine, can also be used.1,10
On hospital day 6, intravenous methylprednisolone (25 mg every 8 hours) was started; within 24 hours, the patient’s vital signs normalized and vasopressors were discontinued. Glucocorticoids were stopped after 3 days, and she remained in the hospital for wound care until postoperative day 14, when she was discharged home with a vacuum-assisted closure of her wound. The wound closure device was removed 8 weeks later, at which point her wound had healed. The patient has not had a recurrence of pyoderma gangrenosum in more than 3 years.
