Introduction
Aplastic anemia is a rare bone marrow failure syndrome with a spectrum of severity that dictates therapy ranging from immunosuppression to hematopoietic stem cell transplantation (HSCT).1
A significant complication of HSCT is chronic graft-versus-host disease (cGVHD), which occurs in 30% to 70% of patients.2 cGVHD can affect any organ system, with cutaneous involvement in up to nearly 80% of cases, and presents with a wide range of severity.3 The cornerstone of treatment remains corticosteroids. For steroid-refractory disease, therapeutic options include ibrutinib, ruxolitinib, extracorporeal photopheresis (ECP), and belumosudil.4
Cannabidiol (CBD) is a naturally occurring compound with established anti-inflammatory properties. CBD has demonstrated anti-inflammatory and anti-fibrotic effects in preclinical GVHD models and skin models, including inhibition of collagen synthesis and fibroblast activity; however, clinical evidence in keloid disease remains extremely limited.5 We report a patient with relapsed severe aplastic anemia (SAA) who underwent a matched unrelated donor (MUD) HSCT who developed severe cutaneous and myofascial cGVHD, associated with multiple severe keloids of the feet causing functional impairment (Fig 1). Following CBD oil application, his keloids improved dramatically, resulting in full restoration of function and marked improvement in quality of life (Fig 2).
Fig 1.
Bilateral keloids on the ankles and dorsal feet, resulting in significant functional impairment.
Fig 2.
After treatment with topical CBD oil, the keloids (arrows) rapidly and significantly flattened, with full resolution of symptoms.
Case report
A 37-year-old white male with relapsed SAA underwent a MUD HSCT complicated by biopsy-confirmed sclerotic cutaneous and myofascial cGVHD after presenting with large pink papules and plaques on his ankles and dorsal feet along with joint stiffness. Of note, he had no prior history of skin lesions. The patient was steroid-refractory and had failed multiple lines of therapy, including topical medications, ibrutinib, ruxolitinib, ECP, mycophenolate mofetil (MMF), and rituximab. Given the growth of his scars now with a hypertrophic appearance and use of abrasive work boots, he underwent repeat evaluation by dermatology, underwent repeat skin biopsies and was given the diagnosis of keloids of the feet (Fig 1). Belumosudil was subsequently initiated, with improvement in myofascial manifestations but no meaningful improvement in the cutaneous lesions. Standard local therapies, including intralesional triamcinolone acetate injections and laser therapy, provided minimal additional benefit.
Given the refractory nature of the keloids and persistent occupational limitations, a therapeutic trial of topical cannabidiol oil was initiated. The patient applied a cannabidiol product (“Osteo Flow,” Noco CBD Co) to the affected areas of the feet 3 times a day for the first 6 months then 1 to 2 times daily thereafter. The patient used it for a fixed duration of 24 months. He denied experiencing any side effects. Following initiation, the keloids demonstrated near complete flattening after about 12 months, with restoration of function and marked improvement in quality of life soon after initiation (Fig 2). This case suggests a potential adjunctive role for topical CBD in the management of keloids and possibly refractory cutaneous and myofascial cGVHD.
Discussion
cGVHD is a significant complication of HSCT, imposing substantial burdens on quality of life due to prolonged, often toxic treatment regimens. While keloids are often a clinical diagnosis, biopsy should be performed to differentiate it from cGVHD to guide management.
Keloids can be treated with a range of modalities, including intralesional corticosteroids, 5-fluorouracil, surgery, and radiation, with variable outcomes.6 Although many patients experience some degree of improvement, a subset, such as the patient described here, remain refractory to these therapies, and recurrence rates are high. These therapies are also associated with adverse effects, including bleeding, pain, and, in some cases, systemic absorption of corticosteroids. Additionally, most modalities require repeated treatments over time, placing demands on both patients and healthcare resources, with intralesional therapies often administered every 4 weeks for extended periods of time.6
CBD is a naturally occurring substance with known anti-inflammatory properties. The pathophysiology of cGVHD involves initial tissue damage leading to innate immune activation and subsequent fibrosis from macrophage-derived growth factors.3 The benefit observed in this case may be attributed to CBD's anti-inflammatory action, which potentially interrupted the pathological cascade, and/or potentially possessed or resulted in anti-fibrotic properties that target keloids as well as other pathophysiologic drivers of myofascial cGVHD.7
Remarkably, our patient experienced a significant flattening of his keloids following the introduction of CBD oil, with improvements that were temporally associated with its initiation and were dramatic in nature. The overall contribution of CBD to his cGVHD is not totally clear given concomitant therapies. This improvement was objectively documented by medical photography. Following regression of the keloids with CBD oil, the patient was able to successfully taper MMF and corticosteroids, reducing his risk of opportunistic infection.
Coupled with existing preclinical data suggesting potential benefit in GVHD, this dramatic clinical response, facilitating de-escalation of costly and toxic therapies, supports the need for prospective, controlled clinical studies to more rigorously evaluate the efficacy and mechanisms of CBD in the treatment of keloids.
Declaration of generative AI and AI-assisted technologies in the writing process
AI was not used for the preparation of this manuscript.
Conflicts of interest
None disclosed.
Acknowledgments
This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH, the U.S. Department of Health and Human Services.
Footnotes
Funding sources: None.
Patient consent: The authors obtained written consent from the patient(s) for their photographs and medical information to be published in print and online, with the understanding that this information may be publicly available. Patient consent forms were not provided to the journal but are retained by the authors.
IRB approval status: Not applicable.
References
- 1.Young N.S., Scheinberg P., Calado R.T. Aplastic anemia. Curr Opin Hematol. 2008;15(3):162–168. doi: 10.1097/MOH.0b013e3282fa7470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Baumrin E., Shin D.B., Mitra N., et al. Patient-reported outcomes and mortality in cutaneous chronic graft-vs-host disease. JAMA Dermatol. 2024;160(4):393–401. doi: 10.1001/jamadermatol.2023.6277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Zeiser R., Blazar B.R. Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med. 2017;377(26):2565–2579. doi: 10.1056/NEJMra1703472. [DOI] [PubMed] [Google Scholar]
- 4.Morishita T., Inamoto Y. Advances in treatment of chronic graft-versus-host disease. Int J Hematol. 2025 doi: 10.1007/s12185-025-04102-0. [DOI] [PubMed] [Google Scholar]
- 5.Berg B.B., Soares J.S., Paiva I.R., et al. Cannabidiol enhances intestinal cannabinoid receptor type 2 receptor expression and activation increasing regulatory T cells and reduces murine acute graft-versus-host disease without interfering with the graft-versus-leukemia response. J Pharmacol Exp Ther. 2021;377(2):273–283. doi: 10.1124/jpet.120.000479. [DOI] [PubMed] [Google Scholar]
- 6.Bailey J., Schwehr M., Beattie A. Management of keloids and hypertrophic scars. Am Fam Physician. 2024;110(6):605–611. [PubMed] [Google Scholar]
- 7.Rajesh M., Mukhopadhyay P., Bátkai S., et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol. 2010;56(25):2115–2125. doi: 10.1016/j.jacc.2010.07.033. [DOI] [PMC free article] [PubMed] [Google Scholar]