Wounds

Keloids are fibroproliferative lesions caused by aberrant wound healing in predisposed individuals.¹ While keloids have been reported in patients of all races and ethnicities, they most commonly develop in individuals of African or Asian descent.² Often associated with symptoms such as pain and itching, keloids can be disfiguring and result in poorer quality of life.³ There is a paucity of research on keloid pathogenesis and efficacious therapeutics, particularly in patients with skin of color (SOC). Herein, we outline the current research on keloid treatment and highlight promising new therapies ranging from innovative intralesional techniques to advanced laser-based and biologic therapies.

Deficiencies in Skin of Color Research

Although keloids are 17 times more prevalent in patients with SOC,⁴ there is a considerable lack of focus on this population in the literature.⁵ Studies on keloids that include individuals with SOC often group patients of all skin types together, and subgroup analyses are not always performed.^6,7 As a result, dermatologists may face considerable challenges in providing effective treatments for keloids in patients with SOC. With few evidence-based options available, patients with SOC who have keloids continue to experience impairments in quality of life.

Common Keloid Therapies

There currently is no gold-standard treatment for keloids. Common therapeutic modalities include intralesional corticosteroids (ILCs), antineoplastic agents and neuromodulators, laser-based devices, and surgical therapies (eg, excision), as well as combined medical and surgical techniques.⁸

Intralesional Corticosteroids—Minimally invasive ILCs are the first-line treatment in all patients with keloids, regardless of skin phototype. Because keloid formation results from trauma to the skin, ILCs often are recommended to minimize further skin damage.⁵ One meta-analysis found that ILCs have demonstrated success rates of 50% to 100%⁹; however, these studies frequently combine ILCs with other treatment modalities, and few studies have focused on the efficacy of ILC monotherapy in patients with SOC.^6,10-13

Antineoplastic Agents and Neuromodulators—Certain antineoplastic agents (eg, 5-fluorouracil [5-FU] and bleomycin) and neuromodulators (eg, botulinum toxin A [BTA]) also have been studied in keloid management.⁸

5-Fluorouracil frequently is combined with ILCs such as triamcinolone (TAC). Combined therapy is more effective than TAC monotherapy in scar height reduction.^14,15 Rates of adverse events such as dyspigmentation, atrophy, and telangiectasias also were lower in patients who received combined therapy.^14,15 A systematic review found that intralesional bleomycin may be more effective than TAC alone, 5-FU alone, TAC combined with 5-FU, and TAC combined with cryotherapy; however, hyperpigmentation was a common adverse event, occurring in roughly 70% (42/60) of patients.^16,17 Additionally, a 2024 meta-analysis evaluated 20 randomized controlled trials comprising 1114 patients treated with intralesional TAC, 5-FU, BTA, verapamil, and/or bleomycin. Botulinum toxin A and TAC plus 5-FU were found to have outstanding therapeutic efficacy for keloids, and rates of adverse events were similar among users of TAC, 5-FU, BTA, and TAC plus 5-FU.¹⁸

While antineoplastic agents and BTA may be promising keloid therapies, further studies demonstrating their efficacy and safety profiles are necessary, particularly regarding dyspigmentation as a potential adverse event, as this may be of concern in patients with darker phototypes.

Laser Therapies—Of all treatment modalities, laser-based keloid therapies have been the most robustly studied in SOC. The 2 main types are ablative (eg, CO₂, Er:YAG) and nonablative (eg, pulsed dye, Nd:YAG) lasers. Ablative lasers rapidly heat water molecules within the skin, thereby vaporizing the skin cells in a controlled precise process that reduces scar tissue by removing layers of skin. Nonablative lasers target hemoglobin in blood vessels, reducing oxygen supply and inducing collagen remodeling without damaging the epidermis.¹⁹

For patients with SOC, lasers carry a risk for postinflammatory hyperpigmentation.²⁰ To address this risk, recent advancements in laser technology and procedural protocols have aimed to minimize the number of passes and utilize cooling devices²¹; however, many of these recommendations are based on retrospective reviews and small case series. A 2024 meta-analysis comprising 550 patients found that the combination of fractional CO₂ laser therapy and 5-FU was the most effective intervention, markedly reducing Vancouver Scar Scale and pliability scores as well as keloid thickness.²² Conversely, pulsed dye lasers were the least effective in terms of improving scar thickness, pigmentation, and pliability when compared to other treatments.

Randomized controlled trials of laser-based therapies in patients with SOC are lacking in the literature. Future studies should focus on calibrating laser-based therapies for those with darker skin tones and examine the efficacy and adverse effects of ablative and nonablative lasers in patients with SOC.

Promising New Keloid Therapies

Keloid disease pathogenesis is incompletely understood, but several new therapeutic targets have been highlighted in the literature, including dupilumab, pentoxifylline, sirtuin 6 (SIRT6) modulators, remdesivir, and needle-assisted electrocoagulation plus pharmacotherapy.

Dupilumab—An anti–IL-4 and IL-13 monoclonal antibody, dupilumab was first approved for the treatment of severe atopic dermatitis. Its use has broadened since its approval, and keloids have been identified as a potential therapeutic target. A 2019 case study described a 53-year-old Black man with severe atopic dermatitis and chronic keloids that regressed with systemic dupilumab therapy.²³ This prompted a follow-up case-control study using real-time polymerase chain reaction testing to evaluate Th2 gene expression (IL-4R, IL-13, and CCL18) of lesional and nonlesional tissue in 3 Black patients with chronic keloids and no concurrent atopic dermatitis vs 5 healthy Black controls.Despite the limited sample size, a significant increase in IL-13 and the Th2 chemokine CCL18 was found in patients with keloids compared to controls (P<.05), suggesting that the entire integument of patients with severe keloids is abnormal.²³ This finding supports the use of systemic treatments for chronic and multifocal keloid disease. Several subsequent case reports have corroborated the efficacy of systemic and/or intralesional dupilumab.^24,25 However, some studies have reported contradictory findings, suggesting the need for high-quality clinical trials.^26,27

Pentoxifylline—Pentoxifylline is a methylated xanthine derivative and a nonspecific phosphodiesterase ­inhibitor used to treat claudication from peripheral artery disease. It also inhibits the proliferation and rate of collagen synthesis of fibroblasts from keloids in vitro.^28,29 A 2019 retrospective, open-label pilot study analyzed postsurgical keloid recurrence in 45 patients with 67 unique keloids that were stratified into low- and high-risk groups based on clinical factors including multiple symptomatic keloids, history of recurrence, and family history.³⁰ Both the low- and the high-risk groups were treated with 40 mg/mL intralesional triamcinolone acetonide monthly for 6 months; however, some of the high-risk keloids also received pentoxifylline 300 mg 3 times daily for 6 months. There was a statistically significant decrease in keloid recurrence rate between the high-risk group treated with pentoxifylline and the low-risk group for whom pentoxifylline was not prescribed (P=.015).

Similarly, a randomized clinical trial comparing the efficacy of combination intralesional pentoxifylline and intralesional triamcinolone vs monotherapy with pentoxifylline or triamcinolone found the most significant improvement in the combination cohort with reduction in keloid height (P=.04), pliability (P=.003), and vascularity (P=.05).³¹ These findings highlight the need for supplementary studies on the use of pentoxifylline for keloid therapy.

SIRT6 Modulators—SIRT6 modulators are an exciting future therapeutic target. In a recent case-control study evaluating the histologic milieu of keloid tissue vs normal skin specimens, the researchers found that selective overexpression of SIRT6 via the use of a recombinant adenovirus in keloid fibroblasts attenuated proliferation, invasion, and collagen synthesis while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity.³²

Remdesivir—The antiviral drug remdesivir has been reported to have pharmacologic activities in a wide range of fibrotic diseases, including keloids. A 2024 study explored the potential effect and mechanisms of remdesivir on skin fibrosis both in vitro and in rodents.³³ Remdesivir was found to decrease skin fibrosis and attenuate the gross weight of keloid tissues in vivo, suppress fibroblast activation and autophagy both in vivo and in vitro, dampen fibroblast activation by the TGF-β1/Smad signaling pathway, and inhibit fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. These results demonstrate the therapeutic potential of remdesivir for keloid management.

Needle-Assisted Electrocoagulation Plus Pharmacotherapy—A novel needle-assisted electrocoagulation technique combined with pharmacotherapy (corticosteroid and 5-FU injections) was effective in a Chinese clinical trial involving 6 patients with keloids.³⁴ Investigators used Vancouver Scar Scale and both Patient and Observer Scar Assessment Scale scores to grade patients’ scars before treatment and 1 month after the first treatment cycle. They found that ablation combined with pharmacotherapy significantly reduced all 3 scores without any obvious adverse events (P=.004, P=.006, and P=.017, respectively). This novel combination treatment may serve as a safe and effective therapeutic approach for keloid removal.

Final Thoughts

Emerging treatments offer promising new horizons in keloid management; however, the lack of robust, high-quality clinical trials, especially those focusing on SOC, underscores a pressing need for comprehensive and inclusive studies. There is much work to be done to close the existing knowledge gap, and future studies must be more intentional with recruitment, assuring that the patients who are disproportionately affected by these lesions are represented in study populations.

Keloids are fibroproliferative lesions caused by aberrant wound healing in predisposed individuals.¹ While keloids have been reported in patients of all races and ethnicities, they most commonly develop in individuals of African or Asian descent.² Often associated with symptoms such as pain and itching, keloids can be disfiguring and result in poorer quality of life.³ There is a paucity of research on keloid pathogenesis and efficacious therapeutics, particularly in patients with skin of color (SOC). Herein, we outline the current research on keloid treatment and highlight promising new therapies ranging from innovative intralesional techniques to advanced laser-based and biologic therapies.

Deficiencies in Skin of Color Research

Although keloids are 17 times more prevalent in patients with SOC,⁴ there is a considerable lack of focus on this population in the literature.⁵ Studies on keloids that include individuals with SOC often group patients of all skin types together, and subgroup analyses are not always performed.^6,7 As a result, dermatologists may face considerable challenges in providing effective treatments for keloids in patients with SOC. With few evidence-based options available, patients with SOC who have keloids continue to experience impairments in quality of life.

Common Keloid Therapies

There currently is no gold-standard treatment for keloids. Common therapeutic modalities include intralesional corticosteroids (ILCs), antineoplastic agents and neuromodulators, laser-based devices, and surgical therapies (eg, excision), as well as combined medical and surgical techniques.⁸

Intralesional Corticosteroids—Minimally invasive ILCs are the first-line treatment in all patients with keloids, regardless of skin phototype. Because keloid formation results from trauma to the skin, ILCs often are recommended to minimize further skin damage.⁵ One meta-analysis found that ILCs have demonstrated success rates of 50% to 100%⁹; however, these studies frequently combine ILCs with other treatment modalities, and few studies have focused on the efficacy of ILC monotherapy in patients with SOC.^6,10-13

Antineoplastic Agents and Neuromodulators—Certain antineoplastic agents (eg, 5-fluorouracil [5-FU] and bleomycin) and neuromodulators (eg, botulinum toxin A [BTA]) also have been studied in keloid management.⁸

5-Fluorouracil frequently is combined with ILCs such as triamcinolone (TAC). Combined therapy is more effective than TAC monotherapy in scar height reduction.^14,15 Rates of adverse events such as dyspigmentation, atrophy, and telangiectasias also were lower in patients who received combined therapy.^14,15 A systematic review found that intralesional bleomycin may be more effective than TAC alone, 5-FU alone, TAC combined with 5-FU, and TAC combined with cryotherapy; however, hyperpigmentation was a common adverse event, occurring in roughly 70% (42/60) of patients.^16,17 Additionally, a 2024 meta-analysis evaluated 20 randomized controlled trials comprising 1114 patients treated with intralesional TAC, 5-FU, BTA, verapamil, and/or bleomycin. Botulinum toxin A and TAC plus 5-FU were found to have outstanding therapeutic efficacy for keloids, and rates of adverse events were similar among users of TAC, 5-FU, BTA, and TAC plus 5-FU.¹⁸

While antineoplastic agents and BTA may be promising keloid therapies, further studies demonstrating their efficacy and safety profiles are necessary, particularly regarding dyspigmentation as a potential adverse event, as this may be of concern in patients with darker phototypes.

Laser Therapies—Of all treatment modalities, laser-based keloid therapies have been the most robustly studied in SOC. The 2 main types are ablative (eg, CO₂, Er:YAG) and nonablative (eg, pulsed dye, Nd:YAG) lasers. Ablative lasers rapidly heat water molecules within the skin, thereby vaporizing the skin cells in a controlled precise process that reduces scar tissue by removing layers of skin. Nonablative lasers target hemoglobin in blood vessels, reducing oxygen supply and inducing collagen remodeling without damaging the epidermis.¹⁹

For patients with SOC, lasers carry a risk for postinflammatory hyperpigmentation.²⁰ To address this risk, recent advancements in laser technology and procedural protocols have aimed to minimize the number of passes and utilize cooling devices²¹; however, many of these recommendations are based on retrospective reviews and small case series. A 2024 meta-analysis comprising 550 patients found that the combination of fractional CO₂ laser therapy and 5-FU was the most effective intervention, markedly reducing Vancouver Scar Scale and pliability scores as well as keloid thickness.²² Conversely, pulsed dye lasers were the least effective in terms of improving scar thickness, pigmentation, and pliability when compared to other treatments.

Randomized controlled trials of laser-based therapies in patients with SOC are lacking in the literature. Future studies should focus on calibrating laser-based therapies for those with darker skin tones and examine the efficacy and adverse effects of ablative and nonablative lasers in patients with SOC.

Promising New Keloid Therapies

Keloid disease pathogenesis is incompletely understood, but several new therapeutic targets have been highlighted in the literature, including dupilumab, pentoxifylline, sirtuin 6 (SIRT6) modulators, remdesivir, and needle-assisted electrocoagulation plus pharmacotherapy.

Dupilumab—An anti–IL-4 and IL-13 monoclonal antibody, dupilumab was first approved for the treatment of severe atopic dermatitis. Its use has broadened since its approval, and keloids have been identified as a potential therapeutic target. A 2019 case study described a 53-year-old Black man with severe atopic dermatitis and chronic keloids that regressed with systemic dupilumab therapy.²³ This prompted a follow-up case-control study using real-time polymerase chain reaction testing to evaluate Th2 gene expression (IL-4R, IL-13, and CCL18) of lesional and nonlesional tissue in 3 Black patients with chronic keloids and no concurrent atopic dermatitis vs 5 healthy Black controls.Despite the limited sample size, a significant increase in IL-13 and the Th2 chemokine CCL18 was found in patients with keloids compared to controls (P<.05), suggesting that the entire integument of patients with severe keloids is abnormal.²³ This finding supports the use of systemic treatments for chronic and multifocal keloid disease. Several subsequent case reports have corroborated the efficacy of systemic and/or intralesional dupilumab.^24,25 However, some studies have reported contradictory findings, suggesting the need for high-quality clinical trials.^26,27

Pentoxifylline—Pentoxifylline is a methylated xanthine derivative and a nonspecific phosphodiesterase ­inhibitor used to treat claudication from peripheral artery disease. It also inhibits the proliferation and rate of collagen synthesis of fibroblasts from keloids in vitro.^28,29 A 2019 retrospective, open-label pilot study analyzed postsurgical keloid recurrence in 45 patients with 67 unique keloids that were stratified into low- and high-risk groups based on clinical factors including multiple symptomatic keloids, history of recurrence, and family history.³⁰ Both the low- and the high-risk groups were treated with 40 mg/mL intralesional triamcinolone acetonide monthly for 6 months; however, some of the high-risk keloids also received pentoxifylline 300 mg 3 times daily for 6 months. There was a statistically significant decrease in keloid recurrence rate between the high-risk group treated with pentoxifylline and the low-risk group for whom pentoxifylline was not prescribed (P=.015).

Similarly, a randomized clinical trial comparing the efficacy of combination intralesional pentoxifylline and intralesional triamcinolone vs monotherapy with pentoxifylline or triamcinolone found the most significant improvement in the combination cohort with reduction in keloid height (P=.04), pliability (P=.003), and vascularity (P=.05).³¹ These findings highlight the need for supplementary studies on the use of pentoxifylline for keloid therapy.

SIRT6 Modulators—SIRT6 modulators are an exciting future therapeutic target. In a recent case-control study evaluating the histologic milieu of keloid tissue vs normal skin specimens, the researchers found that selective overexpression of SIRT6 via the use of a recombinant adenovirus in keloid fibroblasts attenuated proliferation, invasion, and collagen synthesis while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity.³²

Remdesivir—The antiviral drug remdesivir has been reported to have pharmacologic activities in a wide range of fibrotic diseases, including keloids. A 2024 study explored the potential effect and mechanisms of remdesivir on skin fibrosis both in vitro and in rodents.³³ Remdesivir was found to decrease skin fibrosis and attenuate the gross weight of keloid tissues in vivo, suppress fibroblast activation and autophagy both in vivo and in vitro, dampen fibroblast activation by the TGF-β1/Smad signaling pathway, and inhibit fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. These results demonstrate the therapeutic potential of remdesivir for keloid management.

Needle-Assisted Electrocoagulation Plus Pharmacotherapy—A novel needle-assisted electrocoagulation technique combined with pharmacotherapy (corticosteroid and 5-FU injections) was effective in a Chinese clinical trial involving 6 patients with keloids.³⁴ Investigators used Vancouver Scar Scale and both Patient and Observer Scar Assessment Scale scores to grade patients’ scars before treatment and 1 month after the first treatment cycle. They found that ablation combined with pharmacotherapy significantly reduced all 3 scores without any obvious adverse events (P=.004, P=.006, and P=.017, respectively). This novel combination treatment may serve as a safe and effective therapeutic approach for keloid removal.

Final Thoughts

Emerging treatments offer promising new horizons in keloid management; however, the lack of robust, high-quality clinical trials, especially those focusing on SOC, underscores a pressing need for comprehensive and inclusive studies. There is much work to be done to close the existing knowledge gap, and future studies must be more intentional with recruitment, assuring that the patients who are disproportionately affected by these lesions are represented in study populations.

Keloids are fibroproliferative lesions caused by aberrant wound healing in predisposed individuals.¹ While keloids have been reported in patients of all races and ethnicities, they most commonly develop in individuals of African or Asian descent.² Often associated with symptoms such as pain and itching, keloids can be disfiguring and result in poorer quality of life.³ There is a paucity of research on keloid pathogenesis and efficacious therapeutics, particularly in patients with skin of color (SOC). Herein, we outline the current research on keloid treatment and highlight promising new therapies ranging from innovative intralesional techniques to advanced laser-based and biologic therapies.

Deficiencies in Skin of Color Research

Although keloids are 17 times more prevalent in patients with SOC,⁴ there is a considerable lack of focus on this population in the literature.⁵ Studies on keloids that include individuals with SOC often group patients of all skin types together, and subgroup analyses are not always performed.^6,7 As a result, dermatologists may face considerable challenges in providing effective treatments for keloids in patients with SOC. With few evidence-based options available, patients with SOC who have keloids continue to experience impairments in quality of life.

Common Keloid Therapies

There currently is no gold-standard treatment for keloids. Common therapeutic modalities include intralesional corticosteroids (ILCs), antineoplastic agents and neuromodulators, laser-based devices, and surgical therapies (eg, excision), as well as combined medical and surgical techniques.⁸

Intralesional Corticosteroids—Minimally invasive ILCs are the first-line treatment in all patients with keloids, regardless of skin phototype. Because keloid formation results from trauma to the skin, ILCs often are recommended to minimize further skin damage.⁵ One meta-analysis found that ILCs have demonstrated success rates of 50% to 100%⁹; however, these studies frequently combine ILCs with other treatment modalities, and few studies have focused on the efficacy of ILC monotherapy in patients with SOC.^6,10-13

Antineoplastic Agents and Neuromodulators—Certain antineoplastic agents (eg, 5-fluorouracil [5-FU] and bleomycin) and neuromodulators (eg, botulinum toxin A [BTA]) also have been studied in keloid management.⁸

5-Fluorouracil frequently is combined with ILCs such as triamcinolone (TAC). Combined therapy is more effective than TAC monotherapy in scar height reduction.^14,15 Rates of adverse events such as dyspigmentation, atrophy, and telangiectasias also were lower in patients who received combined therapy.^14,15 A systematic review found that intralesional bleomycin may be more effective than TAC alone, 5-FU alone, TAC combined with 5-FU, and TAC combined with cryotherapy; however, hyperpigmentation was a common adverse event, occurring in roughly 70% (42/60) of patients.^16,17 Additionally, a 2024 meta-analysis evaluated 20 randomized controlled trials comprising 1114 patients treated with intralesional TAC, 5-FU, BTA, verapamil, and/or bleomycin. Botulinum toxin A and TAC plus 5-FU were found to have outstanding therapeutic efficacy for keloids, and rates of adverse events were similar among users of TAC, 5-FU, BTA, and TAC plus 5-FU.¹⁸

While antineoplastic agents and BTA may be promising keloid therapies, further studies demonstrating their efficacy and safety profiles are necessary, particularly regarding dyspigmentation as a potential adverse event, as this may be of concern in patients with darker phototypes.

Laser Therapies—Of all treatment modalities, laser-based keloid therapies have been the most robustly studied in SOC. The 2 main types are ablative (eg, CO₂, Er:YAG) and nonablative (eg, pulsed dye, Nd:YAG) lasers. Ablative lasers rapidly heat water molecules within the skin, thereby vaporizing the skin cells in a controlled precise process that reduces scar tissue by removing layers of skin. Nonablative lasers target hemoglobin in blood vessels, reducing oxygen supply and inducing collagen remodeling without damaging the epidermis.¹⁹

For patients with SOC, lasers carry a risk for postinflammatory hyperpigmentation.²⁰ To address this risk, recent advancements in laser technology and procedural protocols have aimed to minimize the number of passes and utilize cooling devices²¹; however, many of these recommendations are based on retrospective reviews and small case series. A 2024 meta-analysis comprising 550 patients found that the combination of fractional CO₂ laser therapy and 5-FU was the most effective intervention, markedly reducing Vancouver Scar Scale and pliability scores as well as keloid thickness.²² Conversely, pulsed dye lasers were the least effective in terms of improving scar thickness, pigmentation, and pliability when compared to other treatments.

Randomized controlled trials of laser-based therapies in patients with SOC are lacking in the literature. Future studies should focus on calibrating laser-based therapies for those with darker skin tones and examine the efficacy and adverse effects of ablative and nonablative lasers in patients with SOC.

Promising New Keloid Therapies

Keloid disease pathogenesis is incompletely understood, but several new therapeutic targets have been highlighted in the literature, including dupilumab, pentoxifylline, sirtuin 6 (SIRT6) modulators, remdesivir, and needle-assisted electrocoagulation plus pharmacotherapy.

Dupilumab—An anti–IL-4 and IL-13 monoclonal antibody, dupilumab was first approved for the treatment of severe atopic dermatitis. Its use has broadened since its approval, and keloids have been identified as a potential therapeutic target. A 2019 case study described a 53-year-old Black man with severe atopic dermatitis and chronic keloids that regressed with systemic dupilumab therapy.²³ This prompted a follow-up case-control study using real-time polymerase chain reaction testing to evaluate Th2 gene expression (IL-4R, IL-13, and CCL18) of lesional and nonlesional tissue in 3 Black patients with chronic keloids and no concurrent atopic dermatitis vs 5 healthy Black controls.Despite the limited sample size, a significant increase in IL-13 and the Th2 chemokine CCL18 was found in patients with keloids compared to controls (P<.05), suggesting that the entire integument of patients with severe keloids is abnormal.²³ This finding supports the use of systemic treatments for chronic and multifocal keloid disease. Several subsequent case reports have corroborated the efficacy of systemic and/or intralesional dupilumab.^24,25 However, some studies have reported contradictory findings, suggesting the need for high-quality clinical trials.^26,27

Pentoxifylline—Pentoxifylline is a methylated xanthine derivative and a nonspecific phosphodiesterase ­inhibitor used to treat claudication from peripheral artery disease. It also inhibits the proliferation and rate of collagen synthesis of fibroblasts from keloids in vitro.^28,29 A 2019 retrospective, open-label pilot study analyzed postsurgical keloid recurrence in 45 patients with 67 unique keloids that were stratified into low- and high-risk groups based on clinical factors including multiple symptomatic keloids, history of recurrence, and family history.³⁰ Both the low- and the high-risk groups were treated with 40 mg/mL intralesional triamcinolone acetonide monthly for 6 months; however, some of the high-risk keloids also received pentoxifylline 300 mg 3 times daily for 6 months. There was a statistically significant decrease in keloid recurrence rate between the high-risk group treated with pentoxifylline and the low-risk group for whom pentoxifylline was not prescribed (P=.015).

Similarly, a randomized clinical trial comparing the efficacy of combination intralesional pentoxifylline and intralesional triamcinolone vs monotherapy with pentoxifylline or triamcinolone found the most significant improvement in the combination cohort with reduction in keloid height (P=.04), pliability (P=.003), and vascularity (P=.05).³¹ These findings highlight the need for supplementary studies on the use of pentoxifylline for keloid therapy.

SIRT6 Modulators—SIRT6 modulators are an exciting future therapeutic target. In a recent case-control study evaluating the histologic milieu of keloid tissue vs normal skin specimens, the researchers found that selective overexpression of SIRT6 via the use of a recombinant adenovirus in keloid fibroblasts attenuated proliferation, invasion, and collagen synthesis while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity.³²

Remdesivir—The antiviral drug remdesivir has been reported to have pharmacologic activities in a wide range of fibrotic diseases, including keloids. A 2024 study explored the potential effect and mechanisms of remdesivir on skin fibrosis both in vitro and in rodents.³³ Remdesivir was found to decrease skin fibrosis and attenuate the gross weight of keloid tissues in vivo, suppress fibroblast activation and autophagy both in vivo and in vitro, dampen fibroblast activation by the TGF-β1/Smad signaling pathway, and inhibit fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. These results demonstrate the therapeutic potential of remdesivir for keloid management.

Needle-Assisted Electrocoagulation Plus Pharmacotherapy—A novel needle-assisted electrocoagulation technique combined with pharmacotherapy (corticosteroid and 5-FU injections) was effective in a Chinese clinical trial involving 6 patients with keloids.³⁴ Investigators used Vancouver Scar Scale and both Patient and Observer Scar Assessment Scale scores to grade patients’ scars before treatment and 1 month after the first treatment cycle. They found that ablation combined with pharmacotherapy significantly reduced all 3 scores without any obvious adverse events (P=.004, P=.006, and P=.017, respectively). This novel combination treatment may serve as a safe and effective therapeutic approach for keloid removal.

Final Thoughts

Emerging treatments offer promising new horizons in keloid management; however, the lack of robust, high-quality clinical trials, especially those focusing on SOC, underscores a pressing need for comprehensive and inclusive studies. There is much work to be done to close the existing knowledge gap, and future studies must be more intentional with recruitment, assuring that the patients who are disproportionately affected by these lesions are represented in study populations.

A member of the Elaeagnaceae family, Hippophae rhamnoides, better known as sea buckthorn, is a high-altitude wild shrub endemic to Europe and Asia with edible fruits and a lengthy record of use in traditional Chinese medicine.^1-6 Used as a health supplement and consumed in the diet throughout the world,⁵ sea buckthorn berries, seeds, and leaves have been used in traditional medicine to treat burns/injuries, edema, hypertension, inflammation, skin grafts, ulcers, and wounds.^4,7

This hardy plant is associated with a wide range of biologic activities, including anti-atherogenic, anti-atopic dermatitis, antibacterial, anticancer, antifungal, anti-inflammatory, antimicrobial, antioxidant, anti-psoriasis, anti-sebum, anti-stress, anti-tumor, cytoprotective, hepatoprotective, immunomodulatory, neuroprotective, radioprotective, and tissue regenerative functions.^4,5,8-11Sea buckthorn has also been included in several cosmeceutical formulations to treat wrinkles, scars, pigmentary conditions, and hair disorders, as well as to rejuvenate, even, and smooth the skin.⁴

Indre Brazauskaite/EyeEm/Getty Images

Key Constituents

Functional constituents identified in sea buckthorn include alkaloids, carotenoids, flavonoids, lignans, organic acids, phenolic acids, proanthocyanidins, polyunsaturated acids (including omega-3, -6, -7, and -9), steroids, tannins, terpenoids, and volatile oils, as well as nutritional compounds such as minerals, proteins, and vitamins.^4,5,11 Sea buckthorn pericarp oil contains copious amounts of saturated palmitic acid (29%-36%) and omega-7 unsaturated palmitoleic acid (36%-48%), which fosters cutaneous and mucosal epithelialization, as well as linoleic (10%-12%) and oleic (4%-6%) acids.^12,6 Significant amounts of carotenoids as well as alpha‐linolenic fatty acid (38%), linoleic (36%), oleic (13%), and palmitic (7%) acids are present in sea buckthorn seed oil.⁶

Polysaccharides

In an expansive review on the pharmacological activities of sea buckthorn polysaccharides, Teng and colleagues reported in April 2024 that 20 diverse polysaccharides have been culled from sea buckthorn and exhibited various healthy activities, including antioxidant, anti-fatigue, anti-inflammatory, anti-obesity, anti-tumor, hepatoprotective, hypoglycemic, and immunoregulation, and regulation of intestinal flora activities.¹

Proanthocyanidins and Anti-Aging

In 2023, Liu and colleagues investigated the anti–skin aging impact of sea buckthorn proanthocyanidins in D-galactose-induced aging in mice given the known free radical scavenging activity of these compounds. They found the proanthocyanidins mitigated D-galactose-induced aging and can augment the total antioxidant capacity of the body. Sea buckthorn proanthocyanidins can further attenuate the effects of skin aging by regulating the TGF-beta¹/Smads pathway and MMPs/TIMP system, thus amplifying collagen I and tropoelastin content.¹³

Baumann Cosmetic &amp; Research Institute

A year earlier, many of the same investigators assessed the possible protective activity of sea buckthorn proanthocyanidins against cutaneous aging engendered by oxidative stress from hydrogen peroxide. The compounds amplified superoxide dismutase and glutathione antioxidant functions. The extracts also fostered collagen I production in aging human skin fibroblasts via the TGF-beta1/Smads pathway and hindered collagen I degradation by regulating the MMPs/TIMPs system, which maintained extracellular matrix integrity. Senescent cell migration was also promoted with 100 mcg/mL of sea buckthorn proanthocyanidins. The researchers concluded that this sets the stage for investigating how sea buckthorn proanthocyanidins can be incorporated in cosmetic formulations.14 In a separate study, Liu and colleagues demonstrated that sea buckthorn proanthocyanidins can attenuate oxidative damage and protect mitochondrial function.⁹

Acne and Barrier Functions

The extracts of H rhamnoides and Cassia fistula in a combined formulation were found to be effective in lowering skin sebum content in humans with grade I and grade II acne vulgaris in a 2014 single-blind, randomized, placebo-controlled, split-face study with two groups of 25 patients each (aged 18-37 years).¹⁵ Khan and colleagues have also reported that a sea buckthorn oil-in-water emulsion improved barrier function in human skin as tested by a tewameter and corneometer (noninvasive probes) in 13 healthy males with a mean age of 27 ± 4.8 years.¹⁶

Anti-Aging, Antioxidant, Antibacterial, Skin-Whitening Activity

Zaman and colleagues reported in 2011 that results from an in vivo study of the effects of a sea buckthorn fruit extract topical cream on stratum corneum water content and transepidermal water loss indicated that the formulation enhanced cell surface integrin expression thus facilitating collagen contraction.¹⁷

In 2012, Khan and colleagues reported amelioration in skin elasticity, thus achieving an anti-aging result, from the use of a water-in-oil–based hydroalcoholic cream loaded with fruit extract of H rhamnoides, as measured with a Cutometer.¹⁸ The previous year, some of the same researchers reported that the antioxidants and flavonoids found in a topical sea buckthorn formulation could decrease cutaneous melanin and erythema levels.

More recently, Gęgotek and colleagues found that sea buckthorn seed oil prevented redox balance and lipid metabolism disturbances in skin fibroblasts and keratinocytes caused by UVA or UVB. They suggested that such findings point to the potential of this natural agent to confer anti-inflammatory properties and photoprotection to the skin.¹⁹

In 2020, Ivanišová and colleagues investigated the antioxidant and antimicrobial activities of H rhamnoides 100% oil, 100% juice, dry berries, and tea (dry berries, leaves, and twigs). They found that all of the studied sea buckthorn products displayed high antioxidant activity (identified through DPPH radical scavenging and molybdenum reducing antioxidant power tests). Sea buckthorn juice contained the highest total content of polyphenols, flavonoids, and carotenoids. All of the tested products also exhibited substantial antibacterial activity against the tested microbes.²⁰

Burns and Wound Healing

In a preclinical study of the effects of sea buckthorn leaf extracts on wound healing in albino rats using an excision-punch wound model in 2005, Gupta and colleagues found that twice daily topical application of the aqueous leaf extract fostered wound healing. This was indicated by higher hydroxyproline and protein levels, a diminished wound area, and lower lipid peroxide levels. The investigators suggested that sea buckthorn may facilitate wound healing at least in part because of elevated antioxidant activity in the granulation tissue.³

A year later, Wang and colleagues reported on observations of using H rhamnoides oil, a traditional Chinese herbal medicine derived from sea buckthorn fruit, as a burn treatment. In the study, 151 burn patients received an H rhamnoides oil dressing (changed every other day until wound healing) that was covered with a disinfecting dressing. The dressing reduced swelling and effusion, and alleviated pain, with patients receiving the sea buckthorn dressing experiencing greater apparent exudation reduction, pain reduction, and more rapid epithelial cell growth and wound healing than controls (treated only with Vaseline gauze). The difference between the two groups was statistically significant.²¹

Conclusion

Sea buckthorn has been used for hundreds if not thousands of years in traditional medical applications, including for dermatologic purposes. Emerging data appear to support the use of this dynamic plant for consideration in dermatologic applications. As is often the case, much more work is necessary in the form of randomized controlled trials to determine the effectiveness of sea buckthorn formulations as well as the most appropriate avenues of research or uses for dermatologic application of this traditionally used botanical agent.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a e-commerce solution. Write to her at dermnews@mdedge.com.

References

1. Teng H et al. J Ethnopharmacol. 2024 Apr 24;324:117809. doi: 10.1016/j.jep.2024.117809.

2. Wang Z et al. Int J Biol Macromol. 2024 Apr;263(Pt 1):130206. doi: 10.1016/j.ijbiomac.2024.130206.

3. Gupta A et al. Int J Low Extrem Wounds. 2005 Jun;4(2):88-92. doi: 10.1177/1534734605277401.

4. Pundir S et al. J Ethnopharmacol. 2021 Feb 10;266:113434. doi: 10.1016/j.jep.2020.113434.

5. Ma QG et al. J Agric Food Chem. 2023 Mar 29;71(12):4769-4788. doi: 10.1021/acs.jafc.2c06916.

6. Poljšak N et al. Phytother Res. 2020 Feb;34(2):254-269. doi: 10.1002/ptr.6524. doi: 10.1002/ptr.6524.

7. Upadhyay NK et al. Evid Based Complement Alternat Med. 2011;2011:659705. doi: 10.1093/ecam/nep189.

8. Suryakumar G, Gupta A. J Ethnopharmacol. 2011 Nov 18;138(2):268-78. doi: 10.1016/j.jep.2011.09.024.

9. Liu K et al. Front Pharmacol. 2022 Jul 8;13:914146. doi: 10.3389/fphar.2022.914146.

10. Akhtar N et al. J Pharm Bioallied Sci. 2010 Jan;2(1):13-7. doi: 10.4103/0975-7406.62698.

11. Ren R et al. RSC Adv. 2020 Dec 17;10(73):44654-44671. doi: 10.1039/d0ra06488b.

12. Ito H et al. Burns. 2014 May;40(3):511-9. doi: 10.1016/j.burns.2013.08.011.

13. Liu X et al. Food Sci Nutr. 2023 Dec 7;12(2):1082-1094. doi: 10.1002/fsn3.3823.

14. Liu X at al. Antioxidants (Basel). 2022 Sep 25;11(10):1900. doi: 10.3390/antiox11101900.

15. Khan BA, Akhtar N. Postepy Dermatol Alergol. 2014 Aug;31(4):229-234. doi: 10.5114/pdia.2014.40934.

16. Khan BA, Akhtar N. Pak J Pharm Sci. 2014 Nov;27(6):1919-22.

17. Khan AB et al. African J Pharm Pharmacol. 2011 Aug;5(8):1092-5.

18. Khan BA, Akhtar N, Braga VA. Trop J Pharm Res. 2012;11(6):955-62.

19. Gęgotek A et al. Antioxidants (Basel). 2018 Aug 23;7(9):110. doi: 10.3390/antiox7090110.

20. Ivanišová E et al. Acta Sci Pol Technol Aliment. 2020 Apr-Jun;19(2):195-205. doi: 10.17306/J.AFS.0809.

21. Wang ZY, Luo XL, He CP. Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jan;26(1):124-5.

A member of the Elaeagnaceae family, Hippophae rhamnoides, better known as sea buckthorn, is a high-altitude wild shrub endemic to Europe and Asia with edible fruits and a lengthy record of use in traditional Chinese medicine.^1-6 Used as a health supplement and consumed in the diet throughout the world,⁵ sea buckthorn berries, seeds, and leaves have been used in traditional medicine to treat burns/injuries, edema, hypertension, inflammation, skin grafts, ulcers, and wounds.^4,7

This hardy plant is associated with a wide range of biologic activities, including anti-atherogenic, anti-atopic dermatitis, antibacterial, anticancer, antifungal, anti-inflammatory, antimicrobial, antioxidant, anti-psoriasis, anti-sebum, anti-stress, anti-tumor, cytoprotective, hepatoprotective, immunomodulatory, neuroprotective, radioprotective, and tissue regenerative functions.^4,5,8-11Sea buckthorn has also been included in several cosmeceutical formulations to treat wrinkles, scars, pigmentary conditions, and hair disorders, as well as to rejuvenate, even, and smooth the skin.⁴

Indre Brazauskaite/EyeEm/Getty Images

Key Constituents

Functional constituents identified in sea buckthorn include alkaloids, carotenoids, flavonoids, lignans, organic acids, phenolic acids, proanthocyanidins, polyunsaturated acids (including omega-3, -6, -7, and -9), steroids, tannins, terpenoids, and volatile oils, as well as nutritional compounds such as minerals, proteins, and vitamins.^4,5,11 Sea buckthorn pericarp oil contains copious amounts of saturated palmitic acid (29%-36%) and omega-7 unsaturated palmitoleic acid (36%-48%), which fosters cutaneous and mucosal epithelialization, as well as linoleic (10%-12%) and oleic (4%-6%) acids.^12,6 Significant amounts of carotenoids as well as alpha‐linolenic fatty acid (38%), linoleic (36%), oleic (13%), and palmitic (7%) acids are present in sea buckthorn seed oil.⁶

Polysaccharides

In an expansive review on the pharmacological activities of sea buckthorn polysaccharides, Teng and colleagues reported in April 2024 that 20 diverse polysaccharides have been culled from sea buckthorn and exhibited various healthy activities, including antioxidant, anti-fatigue, anti-inflammatory, anti-obesity, anti-tumor, hepatoprotective, hypoglycemic, and immunoregulation, and regulation of intestinal flora activities.¹

Proanthocyanidins and Anti-Aging

In 2023, Liu and colleagues investigated the anti–skin aging impact of sea buckthorn proanthocyanidins in D-galactose-induced aging in mice given the known free radical scavenging activity of these compounds. They found the proanthocyanidins mitigated D-galactose-induced aging and can augment the total antioxidant capacity of the body. Sea buckthorn proanthocyanidins can further attenuate the effects of skin aging by regulating the TGF-beta¹/Smads pathway and MMPs/TIMP system, thus amplifying collagen I and tropoelastin content.¹³

Baumann Cosmetic &amp; Research Institute

A year earlier, many of the same investigators assessed the possible protective activity of sea buckthorn proanthocyanidins against cutaneous aging engendered by oxidative stress from hydrogen peroxide. The compounds amplified superoxide dismutase and glutathione antioxidant functions. The extracts also fostered collagen I production in aging human skin fibroblasts via the TGF-beta1/Smads pathway and hindered collagen I degradation by regulating the MMPs/TIMPs system, which maintained extracellular matrix integrity. Senescent cell migration was also promoted with 100 mcg/mL of sea buckthorn proanthocyanidins. The researchers concluded that this sets the stage for investigating how sea buckthorn proanthocyanidins can be incorporated in cosmetic formulations.14 In a separate study, Liu and colleagues demonstrated that sea buckthorn proanthocyanidins can attenuate oxidative damage and protect mitochondrial function.⁹

Acne and Barrier Functions

The extracts of H rhamnoides and Cassia fistula in a combined formulation were found to be effective in lowering skin sebum content in humans with grade I and grade II acne vulgaris in a 2014 single-blind, randomized, placebo-controlled, split-face study with two groups of 25 patients each (aged 18-37 years).¹⁵ Khan and colleagues have also reported that a sea buckthorn oil-in-water emulsion improved barrier function in human skin as tested by a tewameter and corneometer (noninvasive probes) in 13 healthy males with a mean age of 27 ± 4.8 years.¹⁶

Anti-Aging, Antioxidant, Antibacterial, Skin-Whitening Activity

Zaman and colleagues reported in 2011 that results from an in vivo study of the effects of a sea buckthorn fruit extract topical cream on stratum corneum water content and transepidermal water loss indicated that the formulation enhanced cell surface integrin expression thus facilitating collagen contraction.¹⁷

In 2012, Khan and colleagues reported amelioration in skin elasticity, thus achieving an anti-aging result, from the use of a water-in-oil–based hydroalcoholic cream loaded with fruit extract of H rhamnoides, as measured with a Cutometer.¹⁸ The previous year, some of the same researchers reported that the antioxidants and flavonoids found in a topical sea buckthorn formulation could decrease cutaneous melanin and erythema levels.

More recently, Gęgotek and colleagues found that sea buckthorn seed oil prevented redox balance and lipid metabolism disturbances in skin fibroblasts and keratinocytes caused by UVA or UVB. They suggested that such findings point to the potential of this natural agent to confer anti-inflammatory properties and photoprotection to the skin.¹⁹

In 2020, Ivanišová and colleagues investigated the antioxidant and antimicrobial activities of H rhamnoides 100% oil, 100% juice, dry berries, and tea (dry berries, leaves, and twigs). They found that all of the studied sea buckthorn products displayed high antioxidant activity (identified through DPPH radical scavenging and molybdenum reducing antioxidant power tests). Sea buckthorn juice contained the highest total content of polyphenols, flavonoids, and carotenoids. All of the tested products also exhibited substantial antibacterial activity against the tested microbes.²⁰

Burns and Wound Healing

In a preclinical study of the effects of sea buckthorn leaf extracts on wound healing in albino rats using an excision-punch wound model in 2005, Gupta and colleagues found that twice daily topical application of the aqueous leaf extract fostered wound healing. This was indicated by higher hydroxyproline and protein levels, a diminished wound area, and lower lipid peroxide levels. The investigators suggested that sea buckthorn may facilitate wound healing at least in part because of elevated antioxidant activity in the granulation tissue.³

A year later, Wang and colleagues reported on observations of using H rhamnoides oil, a traditional Chinese herbal medicine derived from sea buckthorn fruit, as a burn treatment. In the study, 151 burn patients received an H rhamnoides oil dressing (changed every other day until wound healing) that was covered with a disinfecting dressing. The dressing reduced swelling and effusion, and alleviated pain, with patients receiving the sea buckthorn dressing experiencing greater apparent exudation reduction, pain reduction, and more rapid epithelial cell growth and wound healing than controls (treated only with Vaseline gauze). The difference between the two groups was statistically significant.²¹

Conclusion

Sea buckthorn has been used for hundreds if not thousands of years in traditional medical applications, including for dermatologic purposes. Emerging data appear to support the use of this dynamic plant for consideration in dermatologic applications. As is often the case, much more work is necessary in the form of randomized controlled trials to determine the effectiveness of sea buckthorn formulations as well as the most appropriate avenues of research or uses for dermatologic application of this traditionally used botanical agent.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a e-commerce solution. Write to her at dermnews@mdedge.com.

References

1. Teng H et al. J Ethnopharmacol. 2024 Apr 24;324:117809. doi: 10.1016/j.jep.2024.117809.

2. Wang Z et al. Int J Biol Macromol. 2024 Apr;263(Pt 1):130206. doi: 10.1016/j.ijbiomac.2024.130206.

3. Gupta A et al. Int J Low Extrem Wounds. 2005 Jun;4(2):88-92. doi: 10.1177/1534734605277401.

4. Pundir S et al. J Ethnopharmacol. 2021 Feb 10;266:113434. doi: 10.1016/j.jep.2020.113434.

5. Ma QG et al. J Agric Food Chem. 2023 Mar 29;71(12):4769-4788. doi: 10.1021/acs.jafc.2c06916.

6. Poljšak N et al. Phytother Res. 2020 Feb;34(2):254-269. doi: 10.1002/ptr.6524. doi: 10.1002/ptr.6524.

7. Upadhyay NK et al. Evid Based Complement Alternat Med. 2011;2011:659705. doi: 10.1093/ecam/nep189.

8. Suryakumar G, Gupta A. J Ethnopharmacol. 2011 Nov 18;138(2):268-78. doi: 10.1016/j.jep.2011.09.024.

9. Liu K et al. Front Pharmacol. 2022 Jul 8;13:914146. doi: 10.3389/fphar.2022.914146.

10. Akhtar N et al. J Pharm Bioallied Sci. 2010 Jan;2(1):13-7. doi: 10.4103/0975-7406.62698.

11. Ren R et al. RSC Adv. 2020 Dec 17;10(73):44654-44671. doi: 10.1039/d0ra06488b.

12. Ito H et al. Burns. 2014 May;40(3):511-9. doi: 10.1016/j.burns.2013.08.011.

13. Liu X et al. Food Sci Nutr. 2023 Dec 7;12(2):1082-1094. doi: 10.1002/fsn3.3823.

14. Liu X at al. Antioxidants (Basel). 2022 Sep 25;11(10):1900. doi: 10.3390/antiox11101900.

15. Khan BA, Akhtar N. Postepy Dermatol Alergol. 2014 Aug;31(4):229-234. doi: 10.5114/pdia.2014.40934.

16. Khan BA, Akhtar N. Pak J Pharm Sci. 2014 Nov;27(6):1919-22.

17. Khan AB et al. African J Pharm Pharmacol. 2011 Aug;5(8):1092-5.

18. Khan BA, Akhtar N, Braga VA. Trop J Pharm Res. 2012;11(6):955-62.

19. Gęgotek A et al. Antioxidants (Basel). 2018 Aug 23;7(9):110. doi: 10.3390/antiox7090110.

20. Ivanišová E et al. Acta Sci Pol Technol Aliment. 2020 Apr-Jun;19(2):195-205. doi: 10.17306/J.AFS.0809.

21. Wang ZY, Luo XL, He CP. Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jan;26(1):124-5.

A member of the Elaeagnaceae family, Hippophae rhamnoides, better known as sea buckthorn, is a high-altitude wild shrub endemic to Europe and Asia with edible fruits and a lengthy record of use in traditional Chinese medicine.^1-6 Used as a health supplement and consumed in the diet throughout the world,⁵ sea buckthorn berries, seeds, and leaves have been used in traditional medicine to treat burns/injuries, edema, hypertension, inflammation, skin grafts, ulcers, and wounds.^4,7

This hardy plant is associated with a wide range of biologic activities, including anti-atherogenic, anti-atopic dermatitis, antibacterial, anticancer, antifungal, anti-inflammatory, antimicrobial, antioxidant, anti-psoriasis, anti-sebum, anti-stress, anti-tumor, cytoprotective, hepatoprotective, immunomodulatory, neuroprotective, radioprotective, and tissue regenerative functions.^4,5,8-11Sea buckthorn has also been included in several cosmeceutical formulations to treat wrinkles, scars, pigmentary conditions, and hair disorders, as well as to rejuvenate, even, and smooth the skin.⁴

Indre Brazauskaite/EyeEm/Getty Images

Key Constituents

Functional constituents identified in sea buckthorn include alkaloids, carotenoids, flavonoids, lignans, organic acids, phenolic acids, proanthocyanidins, polyunsaturated acids (including omega-3, -6, -7, and -9), steroids, tannins, terpenoids, and volatile oils, as well as nutritional compounds such as minerals, proteins, and vitamins.^4,5,11 Sea buckthorn pericarp oil contains copious amounts of saturated palmitic acid (29%-36%) and omega-7 unsaturated palmitoleic acid (36%-48%), which fosters cutaneous and mucosal epithelialization, as well as linoleic (10%-12%) and oleic (4%-6%) acids.^12,6 Significant amounts of carotenoids as well as alpha‐linolenic fatty acid (38%), linoleic (36%), oleic (13%), and palmitic (7%) acids are present in sea buckthorn seed oil.⁶

Polysaccharides

In an expansive review on the pharmacological activities of sea buckthorn polysaccharides, Teng and colleagues reported in April 2024 that 20 diverse polysaccharides have been culled from sea buckthorn and exhibited various healthy activities, including antioxidant, anti-fatigue, anti-inflammatory, anti-obesity, anti-tumor, hepatoprotective, hypoglycemic, and immunoregulation, and regulation of intestinal flora activities.¹

Proanthocyanidins and Anti-Aging

In 2023, Liu and colleagues investigated the anti–skin aging impact of sea buckthorn proanthocyanidins in D-galactose-induced aging in mice given the known free radical scavenging activity of these compounds. They found the proanthocyanidins mitigated D-galactose-induced aging and can augment the total antioxidant capacity of the body. Sea buckthorn proanthocyanidins can further attenuate the effects of skin aging by regulating the TGF-beta¹/Smads pathway and MMPs/TIMP system, thus amplifying collagen I and tropoelastin content.¹³

Baumann Cosmetic &amp; Research Institute

A year earlier, many of the same investigators assessed the possible protective activity of sea buckthorn proanthocyanidins against cutaneous aging engendered by oxidative stress from hydrogen peroxide. The compounds amplified superoxide dismutase and glutathione antioxidant functions. The extracts also fostered collagen I production in aging human skin fibroblasts via the TGF-beta1/Smads pathway and hindered collagen I degradation by regulating the MMPs/TIMPs system, which maintained extracellular matrix integrity. Senescent cell migration was also promoted with 100 mcg/mL of sea buckthorn proanthocyanidins. The researchers concluded that this sets the stage for investigating how sea buckthorn proanthocyanidins can be incorporated in cosmetic formulations.14 In a separate study, Liu and colleagues demonstrated that sea buckthorn proanthocyanidins can attenuate oxidative damage and protect mitochondrial function.⁹

Acne and Barrier Functions

The extracts of H rhamnoides and Cassia fistula in a combined formulation were found to be effective in lowering skin sebum content in humans with grade I and grade II acne vulgaris in a 2014 single-blind, randomized, placebo-controlled, split-face study with two groups of 25 patients each (aged 18-37 years).¹⁵ Khan and colleagues have also reported that a sea buckthorn oil-in-water emulsion improved barrier function in human skin as tested by a tewameter and corneometer (noninvasive probes) in 13 healthy males with a mean age of 27 ± 4.8 years.¹⁶

Anti-Aging, Antioxidant, Antibacterial, Skin-Whitening Activity

Zaman and colleagues reported in 2011 that results from an in vivo study of the effects of a sea buckthorn fruit extract topical cream on stratum corneum water content and transepidermal water loss indicated that the formulation enhanced cell surface integrin expression thus facilitating collagen contraction.¹⁷

In 2012, Khan and colleagues reported amelioration in skin elasticity, thus achieving an anti-aging result, from the use of a water-in-oil–based hydroalcoholic cream loaded with fruit extract of H rhamnoides, as measured with a Cutometer.¹⁸ The previous year, some of the same researchers reported that the antioxidants and flavonoids found in a topical sea buckthorn formulation could decrease cutaneous melanin and erythema levels.

More recently, Gęgotek and colleagues found that sea buckthorn seed oil prevented redox balance and lipid metabolism disturbances in skin fibroblasts and keratinocytes caused by UVA or UVB. They suggested that such findings point to the potential of this natural agent to confer anti-inflammatory properties and photoprotection to the skin.¹⁹

In 2020, Ivanišová and colleagues investigated the antioxidant and antimicrobial activities of H rhamnoides 100% oil, 100% juice, dry berries, and tea (dry berries, leaves, and twigs). They found that all of the studied sea buckthorn products displayed high antioxidant activity (identified through DPPH radical scavenging and molybdenum reducing antioxidant power tests). Sea buckthorn juice contained the highest total content of polyphenols, flavonoids, and carotenoids. All of the tested products also exhibited substantial antibacterial activity against the tested microbes.²⁰

Burns and Wound Healing

In a preclinical study of the effects of sea buckthorn leaf extracts on wound healing in albino rats using an excision-punch wound model in 2005, Gupta and colleagues found that twice daily topical application of the aqueous leaf extract fostered wound healing. This was indicated by higher hydroxyproline and protein levels, a diminished wound area, and lower lipid peroxide levels. The investigators suggested that sea buckthorn may facilitate wound healing at least in part because of elevated antioxidant activity in the granulation tissue.³

A year later, Wang and colleagues reported on observations of using H rhamnoides oil, a traditional Chinese herbal medicine derived from sea buckthorn fruit, as a burn treatment. In the study, 151 burn patients received an H rhamnoides oil dressing (changed every other day until wound healing) that was covered with a disinfecting dressing. The dressing reduced swelling and effusion, and alleviated pain, with patients receiving the sea buckthorn dressing experiencing greater apparent exudation reduction, pain reduction, and more rapid epithelial cell growth and wound healing than controls (treated only with Vaseline gauze). The difference between the two groups was statistically significant.²¹

Conclusion

Sea buckthorn has been used for hundreds if not thousands of years in traditional medical applications, including for dermatologic purposes. Emerging data appear to support the use of this dynamic plant for consideration in dermatologic applications. As is often the case, much more work is necessary in the form of randomized controlled trials to determine the effectiveness of sea buckthorn formulations as well as the most appropriate avenues of research or uses for dermatologic application of this traditionally used botanical agent.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a e-commerce solution. Write to her at dermnews@mdedge.com.

References

1. Teng H et al. J Ethnopharmacol. 2024 Apr 24;324:117809. doi: 10.1016/j.jep.2024.117809.

2. Wang Z et al. Int J Biol Macromol. 2024 Apr;263(Pt 1):130206. doi: 10.1016/j.ijbiomac.2024.130206.

3. Gupta A et al. Int J Low Extrem Wounds. 2005 Jun;4(2):88-92. doi: 10.1177/1534734605277401.

4. Pundir S et al. J Ethnopharmacol. 2021 Feb 10;266:113434. doi: 10.1016/j.jep.2020.113434.

5. Ma QG et al. J Agric Food Chem. 2023 Mar 29;71(12):4769-4788. doi: 10.1021/acs.jafc.2c06916.

6. Poljšak N et al. Phytother Res. 2020 Feb;34(2):254-269. doi: 10.1002/ptr.6524. doi: 10.1002/ptr.6524.

7. Upadhyay NK et al. Evid Based Complement Alternat Med. 2011;2011:659705. doi: 10.1093/ecam/nep189.

8. Suryakumar G, Gupta A. J Ethnopharmacol. 2011 Nov 18;138(2):268-78. doi: 10.1016/j.jep.2011.09.024.

9. Liu K et al. Front Pharmacol. 2022 Jul 8;13:914146. doi: 10.3389/fphar.2022.914146.

10. Akhtar N et al. J Pharm Bioallied Sci. 2010 Jan;2(1):13-7. doi: 10.4103/0975-7406.62698.

11. Ren R et al. RSC Adv. 2020 Dec 17;10(73):44654-44671. doi: 10.1039/d0ra06488b.

12. Ito H et al. Burns. 2014 May;40(3):511-9. doi: 10.1016/j.burns.2013.08.011.

13. Liu X et al. Food Sci Nutr. 2023 Dec 7;12(2):1082-1094. doi: 10.1002/fsn3.3823.

14. Liu X at al. Antioxidants (Basel). 2022 Sep 25;11(10):1900. doi: 10.3390/antiox11101900.

15. Khan BA, Akhtar N. Postepy Dermatol Alergol. 2014 Aug;31(4):229-234. doi: 10.5114/pdia.2014.40934.

16. Khan BA, Akhtar N. Pak J Pharm Sci. 2014 Nov;27(6):1919-22.

17. Khan AB et al. African J Pharm Pharmacol. 2011 Aug;5(8):1092-5.

18. Khan BA, Akhtar N, Braga VA. Trop J Pharm Res. 2012;11(6):955-62.

19. Gęgotek A et al. Antioxidants (Basel). 2018 Aug 23;7(9):110. doi: 10.3390/antiox7090110.

20. Ivanišová E et al. Acta Sci Pol Technol Aliment. 2020 Apr-Jun;19(2):195-205. doi: 10.17306/J.AFS.0809.

21. Wang ZY, Luo XL, He CP. Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jan;26(1):124-5.

TOPLINE:

Intact fish skin grafts, sourced from Atlantic cod, show superior and faster healing than standard wound care practices in patients with deep and penetrating diabetic foot ulcers.

METHODOLOGY:

• Standard wound care for diabetic foot ulcers involves vascular assessment, surgical debridement, use of appropriate dressings, infection management, and glycemic control; however, standard care is typically associated with poor outcomes.
• Researchers conducted a multicenter clinical trial in 15 tertiary care centers with diabetic foot units across France, Italy, Germany, and Sweden to evaluate the efficacy and safety of intact fish skin grafts over standard-of-care practices in treating complex diabetic foot ulcers.
• A total of 255 patients aged 18 years or older with diabetes and lower limb wounds penetrating to the tendon, capsule, bone, or joint were randomly assigned to receive either an intact fish skin graft or standard wound care for 14 weeks.
• The primary endpoint was the percentage of wounds achieving complete closure by 16 weeks.
• Wound healing was also assessed at 20 and 24 weeks.

TAKEAWAY:

• The proportion of wounds healed at 16 weeks was higher with intact fish skin grafts than with standard-of-care (44.0% vs 26.4% adjusted odds ratio [aOR], 2.58; 95% CI, 1.48-4.56).
• The fish skin grafts continued to be more effective than standard wound care practices at weeks 20 (aOR, 2.15; 95% CI, 1.27–3.70) and 24 (aOR, 2.19; 95% CI, 1.31–3.70).
• The mean time to healing was 17.31 weeks for the intact fish skin graft group and 19.37 weeks for the standard-of-care group; intact fish skin grafts were also associated with faster healing times than standard wound care (hazard ratio, 1.59; 95% CI, 1.07-2.36).
• Target wound infections were the most common adverse events, occurring in a similar number of patients in both the groups.

IN PRACTICE:

“Our trial demonstrated treatment of complex diabetic foot ulcers with intact fish skin grafts achieved a significantly greater proportion of diabetic foot ulcers healed at 16 weeks than standard of care, and was associated with increased healing at 20 and 24 weeks. That these results were achieved in non-superficial UT [University of Texas diabetic wound classification system] grade 2 and 3 diabetic foot ulcers and included ischemic and/or infected diabetic foot ulcers is of importance,” the authors wrote.

SOURCE:

The study was led by Dured Dardari, MD, PhD, Center Hospitalier Sud Francilien, Corbeil-Essonnes, France, and was published online in NEJM Evidence.

LIMITATIONS:

No limitations were discussed for this study.

DISCLOSURES:

The study was funded by European Commission Fast Track to Innovation Horizon 2020 and Kerecis. Two authors reported being employees with or without stock options at Kerecis, and other authors reported having ties with many sources including Kerecis.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Intact fish skin grafts, sourced from Atlantic cod, show superior and faster healing than standard wound care practices in patients with deep and penetrating diabetic foot ulcers.

METHODOLOGY:

• Standard wound care for diabetic foot ulcers involves vascular assessment, surgical debridement, use of appropriate dressings, infection management, and glycemic control; however, standard care is typically associated with poor outcomes.
• Researchers conducted a multicenter clinical trial in 15 tertiary care centers with diabetic foot units across France, Italy, Germany, and Sweden to evaluate the efficacy and safety of intact fish skin grafts over standard-of-care practices in treating complex diabetic foot ulcers.
• A total of 255 patients aged 18 years or older with diabetes and lower limb wounds penetrating to the tendon, capsule, bone, or joint were randomly assigned to receive either an intact fish skin graft or standard wound care for 14 weeks.
• The primary endpoint was the percentage of wounds achieving complete closure by 16 weeks.
• Wound healing was also assessed at 20 and 24 weeks.

TAKEAWAY:

• The proportion of wounds healed at 16 weeks was higher with intact fish skin grafts than with standard-of-care (44.0% vs 26.4% adjusted odds ratio [aOR], 2.58; 95% CI, 1.48-4.56).
• The fish skin grafts continued to be more effective than standard wound care practices at weeks 20 (aOR, 2.15; 95% CI, 1.27–3.70) and 24 (aOR, 2.19; 95% CI, 1.31–3.70).
• The mean time to healing was 17.31 weeks for the intact fish skin graft group and 19.37 weeks for the standard-of-care group; intact fish skin grafts were also associated with faster healing times than standard wound care (hazard ratio, 1.59; 95% CI, 1.07-2.36).
• Target wound infections were the most common adverse events, occurring in a similar number of patients in both the groups.

IN PRACTICE:

“Our trial demonstrated treatment of complex diabetic foot ulcers with intact fish skin grafts achieved a significantly greater proportion of diabetic foot ulcers healed at 16 weeks than standard of care, and was associated with increased healing at 20 and 24 weeks. That these results were achieved in non-superficial UT [University of Texas diabetic wound classification system] grade 2 and 3 diabetic foot ulcers and included ischemic and/or infected diabetic foot ulcers is of importance,” the authors wrote.

SOURCE:

The study was led by Dured Dardari, MD, PhD, Center Hospitalier Sud Francilien, Corbeil-Essonnes, France, and was published online in NEJM Evidence.

LIMITATIONS:

No limitations were discussed for this study.

DISCLOSURES:

The study was funded by European Commission Fast Track to Innovation Horizon 2020 and Kerecis. Two authors reported being employees with or without stock options at Kerecis, and other authors reported having ties with many sources including Kerecis.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Intact fish skin grafts, sourced from Atlantic cod, show superior and faster healing than standard wound care practices in patients with deep and penetrating diabetic foot ulcers.

METHODOLOGY:

• Standard wound care for diabetic foot ulcers involves vascular assessment, surgical debridement, use of appropriate dressings, infection management, and glycemic control; however, standard care is typically associated with poor outcomes.
• Researchers conducted a multicenter clinical trial in 15 tertiary care centers with diabetic foot units across France, Italy, Germany, and Sweden to evaluate the efficacy and safety of intact fish skin grafts over standard-of-care practices in treating complex diabetic foot ulcers.
• A total of 255 patients aged 18 years or older with diabetes and lower limb wounds penetrating to the tendon, capsule, bone, or joint were randomly assigned to receive either an intact fish skin graft or standard wound care for 14 weeks.
• The primary endpoint was the percentage of wounds achieving complete closure by 16 weeks.
• Wound healing was also assessed at 20 and 24 weeks.

TAKEAWAY:

• The proportion of wounds healed at 16 weeks was higher with intact fish skin grafts than with standard-of-care (44.0% vs 26.4% adjusted odds ratio [aOR], 2.58; 95% CI, 1.48-4.56).
• The fish skin grafts continued to be more effective than standard wound care practices at weeks 20 (aOR, 2.15; 95% CI, 1.27–3.70) and 24 (aOR, 2.19; 95% CI, 1.31–3.70).
• The mean time to healing was 17.31 weeks for the intact fish skin graft group and 19.37 weeks for the standard-of-care group; intact fish skin grafts were also associated with faster healing times than standard wound care (hazard ratio, 1.59; 95% CI, 1.07-2.36).
• Target wound infections were the most common adverse events, occurring in a similar number of patients in both the groups.

IN PRACTICE:

“Our trial demonstrated treatment of complex diabetic foot ulcers with intact fish skin grafts achieved a significantly greater proportion of diabetic foot ulcers healed at 16 weeks than standard of care, and was associated with increased healing at 20 and 24 weeks. That these results were achieved in non-superficial UT [University of Texas diabetic wound classification system] grade 2 and 3 diabetic foot ulcers and included ischemic and/or infected diabetic foot ulcers is of importance,” the authors wrote.

SOURCE:

The study was led by Dured Dardari, MD, PhD, Center Hospitalier Sud Francilien, Corbeil-Essonnes, France, and was published online in NEJM Evidence.

LIMITATIONS:

No limitations were discussed for this study.

DISCLOSURES:

The study was funded by European Commission Fast Track to Innovation Horizon 2020 and Kerecis. Two authors reported being employees with or without stock options at Kerecis, and other authors reported having ties with many sources including Kerecis.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

TOPLINE:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In a groundbreaking procedure, a team of surgeons from New York University Langone Health successfully performed the first combined face and eye transplant on a patient with extensive craniofacial tissue loss after an electrical accident.

The highly complex surgery lasted for 21 hours and involved more than 140 surgeons, nurses, and other healthcare professionals under the leadership of Eduardo D. Rodriguez. MD. It not only restored the patient’s facial features, but also integrated a functional eyeball, potentially setting a new standard for future treatments in similar cases.

The transplant took place in May 2023, and the case report was published on September 5 this year in JAMA.

The 46-year-old man lost a large part of his craniofacial tissue and his left eyeball. The approach was highly specialized. Advanced microsurgical techniques such as anastomoses of microscopic vessels and delicate suturing techniques were crucial for the transplant’s success.

Moreover, customized surgical devices, specific implants, and tissue manipulation tools were developed specifically for this case, thus ensuring the viability of the transplant and adequate perfusion of the transplanted ocular tissue.

The initial results are encouraging. Retinal arterial perfusion has been maintained, and retinal architecture has been preserved, as demonstrated by optical coherence tomography. Electroretinography confirmed retinal responses to light, suggesting that the transplanted eye may eventually contribute to the patient’s visual perception. These results are comparable to those of previous facial tissue transplants, but with the significant addition of ocular functionality, which is a notable advance.

“The successful revascularization of the transplanted eye achieved in this study may serve as a step toward the goal of globe transplant for restoration of vision,” wrote the authors.

The complexity of the combined transplant required a deep understanding of facial and ocular anatomy, as well as tissue preservation techniques. The surgical team reported significant challenges, including the need to align delicate anatomical structures and ensure immunological compatibility between the donor and recipient. Meticulous planning from donor selection to postoperative follow-up was considered essential to maximize the likelihood of success and minimize the risk for allograft rejection.

The patient will now be continuously monitored and receive treatment with immunosuppressants such as tacrolimus and prednisone, adjusted according to his response to the transplant. According to the researchers, further studies will be needed to assess the long-term functionality of the transplanted eye and its integration with the central nervous system.

Despite being the fifth facial transplant surgery performed under Dr. Rodriguez’s leadership, this is the first record of a whole-eye transplant. “The mere fact that we have successfully performed the first whole-eye transplant along with a face transplant is a tremendous achievement that many believed to be impossible,” the doctor said in a statement. “We have taken a giant step forward and paved the way for the next chapter in vision restoration.”
 

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In a groundbreaking procedure, a team of surgeons from New York University Langone Health successfully performed the first combined face and eye transplant on a patient with extensive craniofacial tissue loss after an electrical accident.

The highly complex surgery lasted for 21 hours and involved more than 140 surgeons, nurses, and other healthcare professionals under the leadership of Eduardo D. Rodriguez. MD. It not only restored the patient’s facial features, but also integrated a functional eyeball, potentially setting a new standard for future treatments in similar cases.

The transplant took place in May 2023, and the case report was published on September 5 this year in JAMA.

The 46-year-old man lost a large part of his craniofacial tissue and his left eyeball. The approach was highly specialized. Advanced microsurgical techniques such as anastomoses of microscopic vessels and delicate suturing techniques were crucial for the transplant’s success.

Moreover, customized surgical devices, specific implants, and tissue manipulation tools were developed specifically for this case, thus ensuring the viability of the transplant and adequate perfusion of the transplanted ocular tissue.

The initial results are encouraging. Retinal arterial perfusion has been maintained, and retinal architecture has been preserved, as demonstrated by optical coherence tomography. Electroretinography confirmed retinal responses to light, suggesting that the transplanted eye may eventually contribute to the patient’s visual perception. These results are comparable to those of previous facial tissue transplants, but with the significant addition of ocular functionality, which is a notable advance.

“The successful revascularization of the transplanted eye achieved in this study may serve as a step toward the goal of globe transplant for restoration of vision,” wrote the authors.

The complexity of the combined transplant required a deep understanding of facial and ocular anatomy, as well as tissue preservation techniques. The surgical team reported significant challenges, including the need to align delicate anatomical structures and ensure immunological compatibility between the donor and recipient. Meticulous planning from donor selection to postoperative follow-up was considered essential to maximize the likelihood of success and minimize the risk for allograft rejection.

The patient will now be continuously monitored and receive treatment with immunosuppressants such as tacrolimus and prednisone, adjusted according to his response to the transplant. According to the researchers, further studies will be needed to assess the long-term functionality of the transplanted eye and its integration with the central nervous system.

Despite being the fifth facial transplant surgery performed under Dr. Rodriguez’s leadership, this is the first record of a whole-eye transplant. “The mere fact that we have successfully performed the first whole-eye transplant along with a face transplant is a tremendous achievement that many believed to be impossible,” the doctor said in a statement. “We have taken a giant step forward and paved the way for the next chapter in vision restoration.”
 

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In a groundbreaking procedure, a team of surgeons from New York University Langone Health successfully performed the first combined face and eye transplant on a patient with extensive craniofacial tissue loss after an electrical accident.

The highly complex surgery lasted for 21 hours and involved more than 140 surgeons, nurses, and other healthcare professionals under the leadership of Eduardo D. Rodriguez. MD. It not only restored the patient’s facial features, but also integrated a functional eyeball, potentially setting a new standard for future treatments in similar cases.

The transplant took place in May 2023, and the case report was published on September 5 this year in JAMA.

The 46-year-old man lost a large part of his craniofacial tissue and his left eyeball. The approach was highly specialized. Advanced microsurgical techniques such as anastomoses of microscopic vessels and delicate suturing techniques were crucial for the transplant’s success.

Moreover, customized surgical devices, specific implants, and tissue manipulation tools were developed specifically for this case, thus ensuring the viability of the transplant and adequate perfusion of the transplanted ocular tissue.

The initial results are encouraging. Retinal arterial perfusion has been maintained, and retinal architecture has been preserved, as demonstrated by optical coherence tomography. Electroretinography confirmed retinal responses to light, suggesting that the transplanted eye may eventually contribute to the patient’s visual perception. These results are comparable to those of previous facial tissue transplants, but with the significant addition of ocular functionality, which is a notable advance.

“The successful revascularization of the transplanted eye achieved in this study may serve as a step toward the goal of globe transplant for restoration of vision,” wrote the authors.

The complexity of the combined transplant required a deep understanding of facial and ocular anatomy, as well as tissue preservation techniques. The surgical team reported significant challenges, including the need to align delicate anatomical structures and ensure immunological compatibility between the donor and recipient. Meticulous planning from donor selection to postoperative follow-up was considered essential to maximize the likelihood of success and minimize the risk for allograft rejection.

The patient will now be continuously monitored and receive treatment with immunosuppressants such as tacrolimus and prednisone, adjusted according to his response to the transplant. According to the researchers, further studies will be needed to assess the long-term functionality of the transplanted eye and its integration with the central nervous system.

Despite being the fifth facial transplant surgery performed under Dr. Rodriguez’s leadership, this is the first record of a whole-eye transplant. “The mere fact that we have successfully performed the first whole-eye transplant along with a face transplant is a tremendous achievement that many believed to be impossible,” the doctor said in a statement. “We have taken a giant step forward and paved the way for the next chapter in vision restoration.”
 

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Skin grafting is a surgical technique used to cover skin defects resulting from the removal of skin tumors, ulcers, or burn injuries.^1-3 Complications can occur at both donor and recipient sites and may include bleeding, hematoma/seroma formation, postoperative pain, infection, scarring, paresthesia, skin pigmentation, graft contracture, and graft failure.^1,2,4,5 The development of epidermal tumors is not commonly reported among the complications of skin grafting; however, cases of epidermal tumor development on skin graft donor sites during the postoperative period have been reported.^6-12

We performed a systematic review of the literature for cases of epidermal tumor development on skin graft donor sites in patients undergoing autologous skin graft surgery. We present the clinical characteristics of these cases and discuss the nature of these tumors.

Methods

Search Strategy and Study Selection—A literature search was conducted by 2 independent researchers (Z.P. and V.P.) for articles published before December 2022 in the following databases: MEDLINE/PubMed, Web of Science, Scopus, Cochrane Library, OpenGrey, Google Scholar, and WorldCat. Search terms included all possible combinations of the following: keratoacanthoma, molluscum sebaceum, basal cell carcinoma, squamous cell carcinoma, acanthoma, wart, Merkel cell carcinoma, verruca, Bowen disease, keratosis, skin cancer, cutaneous cancer, skin neoplasia, cutaneous neoplasia, and skin tumor. The literature search terms were selected based on the World Health Organization classification of skin tumors.¹³ Manual bibliography checks were performed on all eligible search results for possible relevant studies. Discrepancies were resolved through discussion and, if needed, mediation by a third researcher (N.C.). To be included, a study had to report a case(s) of epidermal tumor(s) that was confirmed by histopathology and arose on a graft donor site in a patient receiving autologous skin grafts for any reason. No language, geographic, or report date restrictions were set.

Data Extraction, Quality Assessment, and Statistical Analysis—We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹⁴ Two independent researchers (Z.P. and V.P.) retrieved the data from the included studies. We have used the terms case and patient interchangeably, and 1 month was measured as 4 weeks for simplicity. Disagreements were resolved by discussion and mediation by a third researcher (N.C.). The quality of the included studies was assessed by 2 researchers (M.P. and V.P.) using the tool proposed by Murad et al.¹⁵

We used descriptive statistical analysis to analyze clinical characteristics of the included cases. We performed separate descriptive analyses based on the most frequently reported types of epidermal tumors and compared the differences between different groups using the Mann-Whitney U test, χ2 test, and Fisher exact test. The level of significance was set at P<.05. All statistical analyses were conducted using SPSS (version 29).

Results

Literature Search and Characteristics of Included Studies—The initial literature search identified 1378 studies, which were screened based on title and abstract. After removing duplicate and irrelevant studies and evaluating the full text of eligible studies, 31 studies (4 case series and 27 case reports) were included in the systematic review (Figure).^6-12,16-39 Quality assessment of the included studies is presented in Table 1.

Clinical Characteristics of Included Patients—Our systematic review included 36 patients with a mean age of 63 years and a male to female ratio of 2:1. The 2 most common causes for skin grafting were burn wounds and surgical excision of skin tumors. Most grafts were harvested from the thighs. The development of a solitary lesion on the donor area was reported in two-thirds of the patients, while more than 1 lesion developed in the remaining one-third of patients. The median time to tumor development was 6.5 weeks. In most cases, a split-thickness skin graft was used.

Cutaneous squamous cell carcinomas (CSCCs) were found in 23 patients, with well-differentiated CSCCs in 19 of these cases. Additionally, keratoacanthomas (KAs) were found in 10 patients. The majority of patients underwent surgical excision of the tumor. The median follow-up time was 12 months, during which recurrences were noted in a small percentage of cases. Clinical characteristics of included patients are presented in Table 2.

Comment

Reasons for Tumor Development on Skin Graft Donor Sites—The etiology behind epidermal tumor development on graft donor sites is unclear. According to one theory, iatrogenic contamination of the donor site during the removal of a primary epidermal tumor could be responsible. However, contemporary surgical procedures dictate the use of different sets of instruments for separate surgical sites. Moreover, this theory cannot explain the occurrence of epidermal tumors on donor sites in patients who have undergone skin grafting for the repair of burn wounds.³⁷

Another theory suggests that hematogenous and/or lymphatic spread can occur from the site of the primary epidermal tumor to the donor site, which has increased vascularization.^16,37 However, this theory also fails to provide an explanation for the development of epidermal tumors in patients who receive skin grafts for burn wounds.

A third theory states that the microenvironment of the donor site is key to tumor development. The donor site undergoes acute inflammation due to the trauma from harvesting the skin graft. According to this theory, acute inflammation could promote neoplastic growth and thus explain the development of epidermal tumors on the donor site.^8,26 However, the relationship between acute inflammation and carcinogenesis remains unclear. What is known to date is that the development of CSCC has been documented primarily in chronically inflamed tissues, whereas the development of KA—a variant of CSCC with distinctive and more benign clinical characteristics—can be expected in the setting of acute trauma-related inflammation.^13,40,41

Based on our systematic review, we propose that well-differentiated CSCC on graft donor sites might actually be misdiagnosed KA, given that the histopathologic differential diagnosis between CSCC and KA is extremely challenging.⁴² This hypothesis could explain the development of well-differentiated CSCC and KA on graft donor sites.

Conclusion

Development of CSCC and KA on graft donor sites can be listed among the postoperative complications of autologous skin grafting. Patients and physicians should be aware of this potential complication, and donor sites should be monitored for the occurrence of epidermal tumors.

Skin grafting is a surgical technique used to cover skin defects resulting from the removal of skin tumors, ulcers, or burn injuries.^1-3 Complications can occur at both donor and recipient sites and may include bleeding, hematoma/seroma formation, postoperative pain, infection, scarring, paresthesia, skin pigmentation, graft contracture, and graft failure.^1,2,4,5 The development of epidermal tumors is not commonly reported among the complications of skin grafting; however, cases of epidermal tumor development on skin graft donor sites during the postoperative period have been reported.^6-12

We performed a systematic review of the literature for cases of epidermal tumor development on skin graft donor sites in patients undergoing autologous skin graft surgery. We present the clinical characteristics of these cases and discuss the nature of these tumors.

Methods

Search Strategy and Study Selection—A literature search was conducted by 2 independent researchers (Z.P. and V.P.) for articles published before December 2022 in the following databases: MEDLINE/PubMed, Web of Science, Scopus, Cochrane Library, OpenGrey, Google Scholar, and WorldCat. Search terms included all possible combinations of the following: keratoacanthoma, molluscum sebaceum, basal cell carcinoma, squamous cell carcinoma, acanthoma, wart, Merkel cell carcinoma, verruca, Bowen disease, keratosis, skin cancer, cutaneous cancer, skin neoplasia, cutaneous neoplasia, and skin tumor. The literature search terms were selected based on the World Health Organization classification of skin tumors.¹³ Manual bibliography checks were performed on all eligible search results for possible relevant studies. Discrepancies were resolved through discussion and, if needed, mediation by a third researcher (N.C.). To be included, a study had to report a case(s) of epidermal tumor(s) that was confirmed by histopathology and arose on a graft donor site in a patient receiving autologous skin grafts for any reason. No language, geographic, or report date restrictions were set.

Data Extraction, Quality Assessment, and Statistical Analysis—We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹⁴ Two independent researchers (Z.P. and V.P.) retrieved the data from the included studies. We have used the terms case and patient interchangeably, and 1 month was measured as 4 weeks for simplicity. Disagreements were resolved by discussion and mediation by a third researcher (N.C.). The quality of the included studies was assessed by 2 researchers (M.P. and V.P.) using the tool proposed by Murad et al.¹⁵

We used descriptive statistical analysis to analyze clinical characteristics of the included cases. We performed separate descriptive analyses based on the most frequently reported types of epidermal tumors and compared the differences between different groups using the Mann-Whitney U test, χ2 test, and Fisher exact test. The level of significance was set at P<.05. All statistical analyses were conducted using SPSS (version 29).

Results

Literature Search and Characteristics of Included Studies—The initial literature search identified 1378 studies, which were screened based on title and abstract. After removing duplicate and irrelevant studies and evaluating the full text of eligible studies, 31 studies (4 case series and 27 case reports) were included in the systematic review (Figure).^6-12,16-39 Quality assessment of the included studies is presented in Table 1.

Clinical Characteristics of Included Patients—Our systematic review included 36 patients with a mean age of 63 years and a male to female ratio of 2:1. The 2 most common causes for skin grafting were burn wounds and surgical excision of skin tumors. Most grafts were harvested from the thighs. The development of a solitary lesion on the donor area was reported in two-thirds of the patients, while more than 1 lesion developed in the remaining one-third of patients. The median time to tumor development was 6.5 weeks. In most cases, a split-thickness skin graft was used.

Cutaneous squamous cell carcinomas (CSCCs) were found in 23 patients, with well-differentiated CSCCs in 19 of these cases. Additionally, keratoacanthomas (KAs) were found in 10 patients. The majority of patients underwent surgical excision of the tumor. The median follow-up time was 12 months, during which recurrences were noted in a small percentage of cases. Clinical characteristics of included patients are presented in Table 2.

Comment

Reasons for Tumor Development on Skin Graft Donor Sites—The etiology behind epidermal tumor development on graft donor sites is unclear. According to one theory, iatrogenic contamination of the donor site during the removal of a primary epidermal tumor could be responsible. However, contemporary surgical procedures dictate the use of different sets of instruments for separate surgical sites. Moreover, this theory cannot explain the occurrence of epidermal tumors on donor sites in patients who have undergone skin grafting for the repair of burn wounds.³⁷

Another theory suggests that hematogenous and/or lymphatic spread can occur from the site of the primary epidermal tumor to the donor site, which has increased vascularization.^16,37 However, this theory also fails to provide an explanation for the development of epidermal tumors in patients who receive skin grafts for burn wounds.

A third theory states that the microenvironment of the donor site is key to tumor development. The donor site undergoes acute inflammation due to the trauma from harvesting the skin graft. According to this theory, acute inflammation could promote neoplastic growth and thus explain the development of epidermal tumors on the donor site.^8,26 However, the relationship between acute inflammation and carcinogenesis remains unclear. What is known to date is that the development of CSCC has been documented primarily in chronically inflamed tissues, whereas the development of KA—a variant of CSCC with distinctive and more benign clinical characteristics—can be expected in the setting of acute trauma-related inflammation.^13,40,41

Based on our systematic review, we propose that well-differentiated CSCC on graft donor sites might actually be misdiagnosed KA, given that the histopathologic differential diagnosis between CSCC and KA is extremely challenging.⁴² This hypothesis could explain the development of well-differentiated CSCC and KA on graft donor sites.

Conclusion

Development of CSCC and KA on graft donor sites can be listed among the postoperative complications of autologous skin grafting. Patients and physicians should be aware of this potential complication, and donor sites should be monitored for the occurrence of epidermal tumors.

Skin grafting is a surgical technique used to cover skin defects resulting from the removal of skin tumors, ulcers, or burn injuries.^1-3 Complications can occur at both donor and recipient sites and may include bleeding, hematoma/seroma formation, postoperative pain, infection, scarring, paresthesia, skin pigmentation, graft contracture, and graft failure.^1,2,4,5 The development of epidermal tumors is not commonly reported among the complications of skin grafting; however, cases of epidermal tumor development on skin graft donor sites during the postoperative period have been reported.^6-12

We performed a systematic review of the literature for cases of epidermal tumor development on skin graft donor sites in patients undergoing autologous skin graft surgery. We present the clinical characteristics of these cases and discuss the nature of these tumors.

Methods

Search Strategy and Study Selection—A literature search was conducted by 2 independent researchers (Z.P. and V.P.) for articles published before December 2022 in the following databases: MEDLINE/PubMed, Web of Science, Scopus, Cochrane Library, OpenGrey, Google Scholar, and WorldCat. Search terms included all possible combinations of the following: keratoacanthoma, molluscum sebaceum, basal cell carcinoma, squamous cell carcinoma, acanthoma, wart, Merkel cell carcinoma, verruca, Bowen disease, keratosis, skin cancer, cutaneous cancer, skin neoplasia, cutaneous neoplasia, and skin tumor. The literature search terms were selected based on the World Health Organization classification of skin tumors.¹³ Manual bibliography checks were performed on all eligible search results for possible relevant studies. Discrepancies were resolved through discussion and, if needed, mediation by a third researcher (N.C.). To be included, a study had to report a case(s) of epidermal tumor(s) that was confirmed by histopathology and arose on a graft donor site in a patient receiving autologous skin grafts for any reason. No language, geographic, or report date restrictions were set.

Data Extraction, Quality Assessment, and Statistical Analysis—We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹⁴ Two independent researchers (Z.P. and V.P.) retrieved the data from the included studies. We have used the terms case and patient interchangeably, and 1 month was measured as 4 weeks for simplicity. Disagreements were resolved by discussion and mediation by a third researcher (N.C.). The quality of the included studies was assessed by 2 researchers (M.P. and V.P.) using the tool proposed by Murad et al.¹⁵

We used descriptive statistical analysis to analyze clinical characteristics of the included cases. We performed separate descriptive analyses based on the most frequently reported types of epidermal tumors and compared the differences between different groups using the Mann-Whitney U test, χ2 test, and Fisher exact test. The level of significance was set at P<.05. All statistical analyses were conducted using SPSS (version 29).

Results

Literature Search and Characteristics of Included Studies—The initial literature search identified 1378 studies, which were screened based on title and abstract. After removing duplicate and irrelevant studies and evaluating the full text of eligible studies, 31 studies (4 case series and 27 case reports) were included in the systematic review (Figure).^6-12,16-39 Quality assessment of the included studies is presented in Table 1.

Clinical Characteristics of Included Patients—Our systematic review included 36 patients with a mean age of 63 years and a male to female ratio of 2:1. The 2 most common causes for skin grafting were burn wounds and surgical excision of skin tumors. Most grafts were harvested from the thighs. The development of a solitary lesion on the donor area was reported in two-thirds of the patients, while more than 1 lesion developed in the remaining one-third of patients. The median time to tumor development was 6.5 weeks. In most cases, a split-thickness skin graft was used.

Cutaneous squamous cell carcinomas (CSCCs) were found in 23 patients, with well-differentiated CSCCs in 19 of these cases. Additionally, keratoacanthomas (KAs) were found in 10 patients. The majority of patients underwent surgical excision of the tumor. The median follow-up time was 12 months, during which recurrences were noted in a small percentage of cases. Clinical characteristics of included patients are presented in Table 2.

Comment

Reasons for Tumor Development on Skin Graft Donor Sites—The etiology behind epidermal tumor development on graft donor sites is unclear. According to one theory, iatrogenic contamination of the donor site during the removal of a primary epidermal tumor could be responsible. However, contemporary surgical procedures dictate the use of different sets of instruments for separate surgical sites. Moreover, this theory cannot explain the occurrence of epidermal tumors on donor sites in patients who have undergone skin grafting for the repair of burn wounds.³⁷

Another theory suggests that hematogenous and/or lymphatic spread can occur from the site of the primary epidermal tumor to the donor site, which has increased vascularization.^16,37 However, this theory also fails to provide an explanation for the development of epidermal tumors in patients who receive skin grafts for burn wounds.

A third theory states that the microenvironment of the donor site is key to tumor development. The donor site undergoes acute inflammation due to the trauma from harvesting the skin graft. According to this theory, acute inflammation could promote neoplastic growth and thus explain the development of epidermal tumors on the donor site.^8,26 However, the relationship between acute inflammation and carcinogenesis remains unclear. What is known to date is that the development of CSCC has been documented primarily in chronically inflamed tissues, whereas the development of KA—a variant of CSCC with distinctive and more benign clinical characteristics—can be expected in the setting of acute trauma-related inflammation.^13,40,41

Based on our systematic review, we propose that well-differentiated CSCC on graft donor sites might actually be misdiagnosed KA, given that the histopathologic differential diagnosis between CSCC and KA is extremely challenging.⁴² This hypothesis could explain the development of well-differentiated CSCC and KA on graft donor sites.

Conclusion

Development of CSCC and KA on graft donor sites can be listed among the postoperative complications of autologous skin grafting. Patients and physicians should be aware of this potential complication, and donor sites should be monitored for the occurrence of epidermal tumors.

Colchicine is an effective treatment for most pediatric patients with complex aphthous stomatitis (CAS), results from a small retrospective study showed.

“Complex aphthous stomatitis in children is typically treated with topical supportive care, which is often not effective,” one of the study investigators, Ananya Shah, a third-year medical student at the University of Rochester School of Medicine & Dentistry, Rochester, New York, told this news organization following the Society for Pediatric Dermatology annual meeting, where the study was presented during a poster session. “There is limited research on CAS and its treatment in children. Colchicine is often used for treatment of CAS in adults, but its use in children has not been studied.”

Ms. Shah, in collaboration with Hilary Kunkel, MD, Nessa Aghazadeh, MD, and Megha Tollefson, MD, of the Department of Dermatology, Mayo Clinic, Rochester, Minnesota, retrospectively reviewed the charts of 20 children diagnosed with CAS who were treated with colchicine, an anti-inflammatory drug often used to treat gout, at the clinic between 2000 and 2023. Treatment responses were defined as no response, partial response, and complete response. Half of the patients were girls, and their median age at presentation was 5 years.

Ulcers were most commonly located in the buccal mucosa (80%), followed by the gingiva (50%), the mucosal lip (50%), and the palate (40%). Nearly all patients (95%) reported that the CAS caused difficulties with eating or drinking. Other effects on their quality of life included weight loss (35%), bleeding (30%), and difficulty brushing teeth (25%). “I was surprised by how much CAS impacts pediatric patients’ quality of life,” Ms. Shah said. “Almost all of the patients experienced trouble with basic activities of daily living, including eating and drinking. In addition, CAS negatively impacted mental health and led to missed school for patients.”

The researchers had follow-up data on responses to colchicine for 14 of the 20 patients. Of these, 12 (86%) had symptom improvement, 5 (36%) had a complete response, 8 (57%) had a partial response, and 1 (7%) did not respond. Nine patients (64%) experienced side effects. Of these, six had diarrhea, two had nausea, and one had constipation.

“Colchicine should be considered as a treatment in pediatric patients who have refractory complex aphthous stomatitis as it is generally well tolerated with minimal side effects,” Ms. Shah said. She acknowledged certain limitations of the study, including its single-center, retrospective design.

The researchers reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Colchicine is an effective treatment for most pediatric patients with complex aphthous stomatitis (CAS), results from a small retrospective study showed.

“Complex aphthous stomatitis in children is typically treated with topical supportive care, which is often not effective,” one of the study investigators, Ananya Shah, a third-year medical student at the University of Rochester School of Medicine & Dentistry, Rochester, New York, told this news organization following the Society for Pediatric Dermatology annual meeting, where the study was presented during a poster session. “There is limited research on CAS and its treatment in children. Colchicine is often used for treatment of CAS in adults, but its use in children has not been studied.”

Ms. Shah, in collaboration with Hilary Kunkel, MD, Nessa Aghazadeh, MD, and Megha Tollefson, MD, of the Department of Dermatology, Mayo Clinic, Rochester, Minnesota, retrospectively reviewed the charts of 20 children diagnosed with CAS who were treated with colchicine, an anti-inflammatory drug often used to treat gout, at the clinic between 2000 and 2023. Treatment responses were defined as no response, partial response, and complete response. Half of the patients were girls, and their median age at presentation was 5 years.

Ulcers were most commonly located in the buccal mucosa (80%), followed by the gingiva (50%), the mucosal lip (50%), and the palate (40%). Nearly all patients (95%) reported that the CAS caused difficulties with eating or drinking. Other effects on their quality of life included weight loss (35%), bleeding (30%), and difficulty brushing teeth (25%). “I was surprised by how much CAS impacts pediatric patients’ quality of life,” Ms. Shah said. “Almost all of the patients experienced trouble with basic activities of daily living, including eating and drinking. In addition, CAS negatively impacted mental health and led to missed school for patients.”

The researchers had follow-up data on responses to colchicine for 14 of the 20 patients. Of these, 12 (86%) had symptom improvement, 5 (36%) had a complete response, 8 (57%) had a partial response, and 1 (7%) did not respond. Nine patients (64%) experienced side effects. Of these, six had diarrhea, two had nausea, and one had constipation.

“Colchicine should be considered as a treatment in pediatric patients who have refractory complex aphthous stomatitis as it is generally well tolerated with minimal side effects,” Ms. Shah said. She acknowledged certain limitations of the study, including its single-center, retrospective design.

The researchers reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Colchicine is an effective treatment for most pediatric patients with complex aphthous stomatitis (CAS), results from a small retrospective study showed.

“Complex aphthous stomatitis in children is typically treated with topical supportive care, which is often not effective,” one of the study investigators, Ananya Shah, a third-year medical student at the University of Rochester School of Medicine & Dentistry, Rochester, New York, told this news organization following the Society for Pediatric Dermatology annual meeting, where the study was presented during a poster session. “There is limited research on CAS and its treatment in children. Colchicine is often used for treatment of CAS in adults, but its use in children has not been studied.”

Ms. Shah, in collaboration with Hilary Kunkel, MD, Nessa Aghazadeh, MD, and Megha Tollefson, MD, of the Department of Dermatology, Mayo Clinic, Rochester, Minnesota, retrospectively reviewed the charts of 20 children diagnosed with CAS who were treated with colchicine, an anti-inflammatory drug often used to treat gout, at the clinic between 2000 and 2023. Treatment responses were defined as no response, partial response, and complete response. Half of the patients were girls, and their median age at presentation was 5 years.

Ulcers were most commonly located in the buccal mucosa (80%), followed by the gingiva (50%), the mucosal lip (50%), and the palate (40%). Nearly all patients (95%) reported that the CAS caused difficulties with eating or drinking. Other effects on their quality of life included weight loss (35%), bleeding (30%), and difficulty brushing teeth (25%). “I was surprised by how much CAS impacts pediatric patients’ quality of life,” Ms. Shah said. “Almost all of the patients experienced trouble with basic activities of daily living, including eating and drinking. In addition, CAS negatively impacted mental health and led to missed school for patients.”

The researchers had follow-up data on responses to colchicine for 14 of the 20 patients. Of these, 12 (86%) had symptom improvement, 5 (36%) had a complete response, 8 (57%) had a partial response, and 1 (7%) did not respond. Nine patients (64%) experienced side effects. Of these, six had diarrhea, two had nausea, and one had constipation.

“Colchicine should be considered as a treatment in pediatric patients who have refractory complex aphthous stomatitis as it is generally well tolerated with minimal side effects,” Ms. Shah said. She acknowledged certain limitations of the study, including its single-center, retrospective design.

The researchers reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Illicit use of the veterinary tranquilizer xylazine continues to spread across the United States. The drug, which is increasingly mixed with fentanyl, often fails to respond to the opioid overdose reversal medication naloxone and can cause severe necrotic lesions.

A report released by Millennium Health, a specialty lab that provides medication monitoring for pain management, drug treatment, and behavioral and substance use disorder treatment centers across the country, showed the number of urine specimens collected and tested at the US drug treatment centers were positive for xylazine in the most recent 6 months.

As previously reported by this news organization, in late 2022, the US Food and Drug Administration (FDA) issued a communication alerting clinicians about the special management required for opioid overdoses tainted with xylazine, which is also known as “tranq” or “tranq dope.”

Subsequently, in early 2023, The White House Office of National Drug Control Policy designated xylazine combined with fentanyl as an emerging threat to the United States.

Both the FDA and the Drug Enforcement Administration have taken steps to try to stop trafficking of the combination. However, despite these efforts, xylazine use has continued to spread.

The Millennium Health Signals report showed that the greatest increase in xylazine use was largely in the western United States. In the first 6 months of 2023, 3% of urine drug tests (UDTs) in Washington, Oregon, California, Hawaii, and Alaska were positive for xylazine. From November 2023 to April 2024, this rose to 8%, a 147% increase. In the Mountain West, xylazine-positive UDTs increased from 2% in 2023 to 4% in 2024, an increase of 94%. In addition to growth in the West, the report showed that xylazine use increased by more than 100% in New England — from 14% in 2023 to 28% in 2024.

Nationally, 16% of all urine specimens were positive for xylazine from late 2023 to April 2024, up slightly from 14% from April to October 2023.

Xylazine use was highest in the East and in the mid-Atlantic United States. Still, positivity rates in the mid-Atlantic dropped from 44% to 33%. The states included in that group were New York, Pennsylvania, Delaware, and New Jersey. East North Central states (Ohio, Michigan, Wisconsin, Indiana, and Illinois) also experienced a decline in positive tests from 32% to 30%.

The South Atlantic states, which include Maryland, Virginia, West Virginia, North and South Carolina, Georgia, and Florida, had a 17% increase in positivity — from 22% to 26%.

From April 2023 to April 2024 state-level UDT positivity rates were 40% in Pennsylvania, 37% in New York, and 35% in Ohio. But rates vary by locality. In Clermont and Hamilton counties in Ohio — both in the Cincinnati area — about 70% of specimens were positive for xylazine.

About one third of specimens in Maryland and South Carolina contained xylazine.

“Because xylazine exposure remains a significant challenge in the East and is a growing concern in the West, clinicians across the US need to be prepared to recognize and address the consequences of xylazine use — like diminished responses to naloxone and severe skin wounds that may lead to amputation — among people who use fentanyl,” Millennium Health Chief Clinical Officer Angela Huskey, PharmD, said in a press release.

The Health Signals Alert analyzed more than 50,000 fentanyl-positive UDT specimens collected between April 12, 2023, and April 11, 2024. Millennium Health researchers analyzed xylazine positivity rates in fentanyl-positive UDT specimens by the US Census Division and state.

A version of this article first appeared on Medscape.com.

Illicit use of the veterinary tranquilizer xylazine continues to spread across the United States. The drug, which is increasingly mixed with fentanyl, often fails to respond to the opioid overdose reversal medication naloxone and can cause severe necrotic lesions.

A report released by Millennium Health, a specialty lab that provides medication monitoring for pain management, drug treatment, and behavioral and substance use disorder treatment centers across the country, showed the number of urine specimens collected and tested at the US drug treatment centers were positive for xylazine in the most recent 6 months.

As previously reported by this news organization, in late 2022, the US Food and Drug Administration (FDA) issued a communication alerting clinicians about the special management required for opioid overdoses tainted with xylazine, which is also known as “tranq” or “tranq dope.”

Subsequently, in early 2023, The White House Office of National Drug Control Policy designated xylazine combined with fentanyl as an emerging threat to the United States.

Both the FDA and the Drug Enforcement Administration have taken steps to try to stop trafficking of the combination. However, despite these efforts, xylazine use has continued to spread.

The Millennium Health Signals report showed that the greatest increase in xylazine use was largely in the western United States. In the first 6 months of 2023, 3% of urine drug tests (UDTs) in Washington, Oregon, California, Hawaii, and Alaska were positive for xylazine. From November 2023 to April 2024, this rose to 8%, a 147% increase. In the Mountain West, xylazine-positive UDTs increased from 2% in 2023 to 4% in 2024, an increase of 94%. In addition to growth in the West, the report showed that xylazine use increased by more than 100% in New England — from 14% in 2023 to 28% in 2024.

Nationally, 16% of all urine specimens were positive for xylazine from late 2023 to April 2024, up slightly from 14% from April to October 2023.

Xylazine use was highest in the East and in the mid-Atlantic United States. Still, positivity rates in the mid-Atlantic dropped from 44% to 33%. The states included in that group were New York, Pennsylvania, Delaware, and New Jersey. East North Central states (Ohio, Michigan, Wisconsin, Indiana, and Illinois) also experienced a decline in positive tests from 32% to 30%.

The South Atlantic states, which include Maryland, Virginia, West Virginia, North and South Carolina, Georgia, and Florida, had a 17% increase in positivity — from 22% to 26%.

From April 2023 to April 2024 state-level UDT positivity rates were 40% in Pennsylvania, 37% in New York, and 35% in Ohio. But rates vary by locality. In Clermont and Hamilton counties in Ohio — both in the Cincinnati area — about 70% of specimens were positive for xylazine.

About one third of specimens in Maryland and South Carolina contained xylazine.

“Because xylazine exposure remains a significant challenge in the East and is a growing concern in the West, clinicians across the US need to be prepared to recognize and address the consequences of xylazine use — like diminished responses to naloxone and severe skin wounds that may lead to amputation — among people who use fentanyl,” Millennium Health Chief Clinical Officer Angela Huskey, PharmD, said in a press release.

The Health Signals Alert analyzed more than 50,000 fentanyl-positive UDT specimens collected between April 12, 2023, and April 11, 2024. Millennium Health researchers analyzed xylazine positivity rates in fentanyl-positive UDT specimens by the US Census Division and state.

A version of this article first appeared on Medscape.com.

Illicit use of the veterinary tranquilizer xylazine continues to spread across the United States. The drug, which is increasingly mixed with fentanyl, often fails to respond to the opioid overdose reversal medication naloxone and can cause severe necrotic lesions.

A report released by Millennium Health, a specialty lab that provides medication monitoring for pain management, drug treatment, and behavioral and substance use disorder treatment centers across the country, showed the number of urine specimens collected and tested at the US drug treatment centers were positive for xylazine in the most recent 6 months.

As previously reported by this news organization, in late 2022, the US Food and Drug Administration (FDA) issued a communication alerting clinicians about the special management required for opioid overdoses tainted with xylazine, which is also known as “tranq” or “tranq dope.”

Subsequently, in early 2023, The White House Office of National Drug Control Policy designated xylazine combined with fentanyl as an emerging threat to the United States.

Both the FDA and the Drug Enforcement Administration have taken steps to try to stop trafficking of the combination. However, despite these efforts, xylazine use has continued to spread.

The Millennium Health Signals report showed that the greatest increase in xylazine use was largely in the western United States. In the first 6 months of 2023, 3% of urine drug tests (UDTs) in Washington, Oregon, California, Hawaii, and Alaska were positive for xylazine. From November 2023 to April 2024, this rose to 8%, a 147% increase. In the Mountain West, xylazine-positive UDTs increased from 2% in 2023 to 4% in 2024, an increase of 94%. In addition to growth in the West, the report showed that xylazine use increased by more than 100% in New England — from 14% in 2023 to 28% in 2024.

Nationally, 16% of all urine specimens were positive for xylazine from late 2023 to April 2024, up slightly from 14% from April to October 2023.

Xylazine use was highest in the East and in the mid-Atlantic United States. Still, positivity rates in the mid-Atlantic dropped from 44% to 33%. The states included in that group were New York, Pennsylvania, Delaware, and New Jersey. East North Central states (Ohio, Michigan, Wisconsin, Indiana, and Illinois) also experienced a decline in positive tests from 32% to 30%.

The South Atlantic states, which include Maryland, Virginia, West Virginia, North and South Carolina, Georgia, and Florida, had a 17% increase in positivity — from 22% to 26%.

From April 2023 to April 2024 state-level UDT positivity rates were 40% in Pennsylvania, 37% in New York, and 35% in Ohio. But rates vary by locality. In Clermont and Hamilton counties in Ohio — both in the Cincinnati area — about 70% of specimens were positive for xylazine.

About one third of specimens in Maryland and South Carolina contained xylazine.

“Because xylazine exposure remains a significant challenge in the East and is a growing concern in the West, clinicians across the US need to be prepared to recognize and address the consequences of xylazine use — like diminished responses to naloxone and severe skin wounds that may lead to amputation — among people who use fentanyl,” Millennium Health Chief Clinical Officer Angela Huskey, PharmD, said in a press release.

The Health Signals Alert analyzed more than 50,000 fentanyl-positive UDT specimens collected between April 12, 2023, and April 11, 2024. Millennium Health researchers analyzed xylazine positivity rates in fentanyl-positive UDT specimens by the US Census Division and state.

A version of this article first appeared on Medscape.com.