Pyoderma Gangrenosum Secondary to Chimeric Antigen Receptor T-Cell Therapy for Diffuse Large B-Cell Lymphoma

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PG is a rare neutrophilic dermatosis that presents as rapidly progressive, painful skin ulcers. It is characterized by undetermined violaceous borders, and it most commonly affects the lower extremities.¹ PG is a clinical diagnosis of exclusion and often is associated with underlying conditions, including inflammatory bowel disease, malignancy, and rheumatologic diseases. PG is characterized by pathergy, or an exaggerated response to minor trauma.²

The current report describes a novel case of PG after successful treatment of DLBCL with skin involvement with chemotherapy, site irradiation, and CAR T-cell therapy. 

A female in her 60s with a medical history significant for DLBCL diagnosed 2 years prior, presented to the authors’ institution for a chest wound. The patient had previously undergone several cycles of salvage chemotherapy with rituximab plus gemcitabine, dexamethasone, and cisplatin with clinical response but kinetic failure. She was treated with subsequent radiation therapy targeted at the left breast DLBCL tumor, followed by CAR T-cell therapy with axicabtagene ciloleucel. Subsequently, a wound developed that worsened with surgical debridement and progressed over the next 2 months despite the care of standard wound specialty services. An 8-cm × 9.7-cm round ulceration with a yellow fibrinous base on the left chest wall was noted on physical examination (Figure 1).

Laboratory findings were negative for rheumatoid factor, antinuclear antibodies, hepatitis panel, HIV, antineutrophil cytoplasmic autoantibody, immunofluorescence, antiphospholipid antibodies, and stool calprotectin. A skin biopsy demonstrated diffuse neutrophilic infiltrate consistent with a diagnosis of PG (Figures 2, 3).

Microbial special stains were negative for bacterial organisms. Notably, the wound also enlarged after the biopsy was performed. The patient was assigned a PARACELSUS score of 17. A PARACELSUS score of 10 or greater, out of a total of 20 points, represents a high likelihood of PG. The patient was diagnosed with PG and started on prednisone 60 mg daily with a 6-week taper and wound vacuum. 

At 3 months, 90% wound reepithelialization was noted, and the wound completely closed by 4 months (Figure 4). As of this writing, the patient’s DLBCL is in remission, and PG has not recurred in 3 years.

To the authors’ knowledge, this is a unique presentation of PG on the chest wall in a patient with DLBCL after treatment with CAR T-cell therapy. A case of PG secondary to cutaneous T-cell lymphoma treated with chemotherapy, radiation, and stem cell transplantation has been reported.³ No cases of PG secondary to CAR T-cell therapy for lymphoma with cutaneous involvement have been reported. While PG can be associated with malignancies, including lymphoma, the temporal relationship between the administration of CAR T-cell therapy and the onset of PG in the patient in the current report suggests a potential link. The absence of PG during the patient’s initial diagnosis of follicular lymphoma and subsequent years of chemotherapy and radiation therapy further supports this distinction. Additionally, the location of the PG in the same region as the radiation site could reflect the immune-modulating effects of CAR T-cell; skin-related immune reactions have been documented months to years following immunotherapy.⁴ 

This case report has several limitations. The main limitations include the lack of generalizability, the inclusion of only 1 patient, and the retrospective nature of the study. 

It is important for dermatologists to be aware of the possible skin reactions associated with CAR T-cell therapy and the particular intersection with cutaneous lymphomas. Continued reporting of cutaneous adverse effects in patients treated with CAR T-cell therapy, as in this case of secondary PG, is essential for monitoring treatment outcomes and follow-up recommendations. In this case, the complication was adequately managed with immunosuppression, and the patient achieved and, as of this writing, has maintained, remission of her lymphoma.