Commentary

With increasing reports of terbinafine resistance, how has your strategy for treating dermatophyte onychomycosis evolved?

DR. LIPNER: Most cases of onychomycosis are not resistant to terbinafine, so for a patient newly diagnosed with onychomycosis, my approach involves evaluating the severity of disease, number of nails affected, comorbid conditions, and concomitant medications and then discussing the risks and benefits of oral vs topical treatment. If a patient’s onychomycosis previously did not resolve with oral terbinafine, I would test for terbinafine resistance. If positive, I would treat with itraconazole for more severe cases and efinaconazole for mild to moderate cases.

Are there any new systemic or topical antifungals for onychomycosis that dermatologists should be aware of?

DR. LIPNER: There have been no new US Food and Drug Administration–approved antifungals for onychomycosis since 2014 (efinaconazole and tavaborole). For most patients, our current antifungals generally have good efficacy. For treatment failures, I would recommend reconfirming the diagnosis and testing for terbinafine resistance.

When do you choose oral antifungal therapy vs topical/combination therapy?

DR. LIPNER: almost never prescribe combination antifungal therapy because monotherapy alone is usually effective, and there is no obvious benefit to combination therapy. If treatment is working (or not working), it is hard to know which agent (if any) is effective. The one time I would use combination therapy (eg, oral terbinafine and topical efinaconazole) would be if the patient has distal lateral subungual onychomycosis and a dermatophytoma. Oral terbinafine would generally be most effective for distal lateral subungual onychomycosis, and topical efinaconazole would likely be most effective for dermatophytoma.

What is the role of adjunctive therapies in onychomycosis?

DR. LIPNER: Debridement can be effective for patients with very thick nails, combined with oral or topical antifungals. Nail avulsion generally is not helpful and should be avoided because it causes permanent shortening of the nail bed. Devices (eg, lasers, photodynamic therapy) are not subject to the same stringent endpoints as medication-based approvals. Because studies to date are small and have different efficacy endpoints, I do not use devices for treatment of onychomycosis.

How do you counsel patients about expectations and timelines for onychomycosis therapy and cure vs improvement?

DR. LIPNER: Oral treatments for toenail onychomycosis are generally given for 3-month courses, but patients should be counseled that the nail could take up to 12 to 18 months to fully grow out and look normal. If patients also have mechanical nail dystrophy, the fungus may be cured with antifungal therapy, but the nail may look better but not perfect, so it is important to manage long-term expectations.

With increasing reports of terbinafine resistance, how has your strategy for treating dermatophyte onychomycosis evolved?

DR. LIPNER: Most cases of onychomycosis are not resistant to terbinafine, so for a patient newly diagnosed with onychomycosis, my approach involves evaluating the severity of disease, number of nails affected, comorbid conditions, and concomitant medications and then discussing the risks and benefits of oral vs topical treatment. If a patient’s onychomycosis previously did not resolve with oral terbinafine, I would test for terbinafine resistance. If positive, I would treat with itraconazole for more severe cases and efinaconazole for mild to moderate cases.

Are there any new systemic or topical antifungals for onychomycosis that dermatologists should be aware of?

DR. LIPNER: There have been no new US Food and Drug Administration–approved antifungals for onychomycosis since 2014 (efinaconazole and tavaborole). For most patients, our current antifungals generally have good efficacy. For treatment failures, I would recommend reconfirming the diagnosis and testing for terbinafine resistance.

When do you choose oral antifungal therapy vs topical/combination therapy?

DR. LIPNER: almost never prescribe combination antifungal therapy because monotherapy alone is usually effective, and there is no obvious benefit to combination therapy. If treatment is working (or not working), it is hard to know which agent (if any) is effective. The one time I would use combination therapy (eg, oral terbinafine and topical efinaconazole) would be if the patient has distal lateral subungual onychomycosis and a dermatophytoma. Oral terbinafine would generally be most effective for distal lateral subungual onychomycosis, and topical efinaconazole would likely be most effective for dermatophytoma.

What is the role of adjunctive therapies in onychomycosis?

DR. LIPNER: Debridement can be effective for patients with very thick nails, combined with oral or topical antifungals. Nail avulsion generally is not helpful and should be avoided because it causes permanent shortening of the nail bed. Devices (eg, lasers, photodynamic therapy) are not subject to the same stringent endpoints as medication-based approvals. Because studies to date are small and have different efficacy endpoints, I do not use devices for treatment of onychomycosis.

How do you counsel patients about expectations and timelines for onychomycosis therapy and cure vs improvement?

DR. LIPNER: Oral treatments for toenail onychomycosis are generally given for 3-month courses, but patients should be counseled that the nail could take up to 12 to 18 months to fully grow out and look normal. If patients also have mechanical nail dystrophy, the fungus may be cured with antifungal therapy, but the nail may look better but not perfect, so it is important to manage long-term expectations.

With increasing reports of terbinafine resistance, how has your strategy for treating dermatophyte onychomycosis evolved?

DR. LIPNER: Most cases of onychomycosis are not resistant to terbinafine, so for a patient newly diagnosed with onychomycosis, my approach involves evaluating the severity of disease, number of nails affected, comorbid conditions, and concomitant medications and then discussing the risks and benefits of oral vs topical treatment. If a patient’s onychomycosis previously did not resolve with oral terbinafine, I would test for terbinafine resistance. If positive, I would treat with itraconazole for more severe cases and efinaconazole for mild to moderate cases.

Are there any new systemic or topical antifungals for onychomycosis that dermatologists should be aware of?

DR. LIPNER: There have been no new US Food and Drug Administration–approved antifungals for onychomycosis since 2014 (efinaconazole and tavaborole). For most patients, our current antifungals generally have good efficacy. For treatment failures, I would recommend reconfirming the diagnosis and testing for terbinafine resistance.

When do you choose oral antifungal therapy vs topical/combination therapy?

DR. LIPNER: almost never prescribe combination antifungal therapy because monotherapy alone is usually effective, and there is no obvious benefit to combination therapy. If treatment is working (or not working), it is hard to know which agent (if any) is effective. The one time I would use combination therapy (eg, oral terbinafine and topical efinaconazole) would be if the patient has distal lateral subungual onychomycosis and a dermatophytoma. Oral terbinafine would generally be most effective for distal lateral subungual onychomycosis, and topical efinaconazole would likely be most effective for dermatophytoma.

What is the role of adjunctive therapies in onychomycosis?

DR. LIPNER: Debridement can be effective for patients with very thick nails, combined with oral or topical antifungals. Nail avulsion generally is not helpful and should be avoided because it causes permanent shortening of the nail bed. Devices (eg, lasers, photodynamic therapy) are not subject to the same stringent endpoints as medication-based approvals. Because studies to date are small and have different efficacy endpoints, I do not use devices for treatment of onychomycosis.

How do you counsel patients about expectations and timelines for onychomycosis therapy and cure vs improvement?

DR. LIPNER: Oral treatments for toenail onychomycosis are generally given for 3-month courses, but patients should be counseled that the nail could take up to 12 to 18 months to fully grow out and look normal. If patients also have mechanical nail dystrophy, the fungus may be cured with antifungal therapy, but the nail may look better but not perfect, so it is important to manage long-term expectations.

When Skin Cancer Awareness Month rolls around every May, my social media feed is inundated with posts extolling the benefits of total body skin examinations and the life-saving potential of skin cancer screenings; however, time and again the US Preventive Services Task Force (USPSTF)—the leading authority on evidence-based public health recommendations in the United States—has found the evidence supporting skin cancer screenings to be insufficient. The USPSTF has cited a lack of high-quality studies and inadequate data to recommend screening for the general population, excluding those at elevated risk due to personal, family, or occupational history.¹ A 2019 Cochrane review went further, concluding that current evidence refutes the utility of population-based screening for melanoma.²

Despite these findings, skin cancer screenings and total body skin examinations remain popular among patients both with and without a personal or family history of cutaneous malignancy. Indeed, the anecdotal experience of dermatologists worldwide suggests an intangible benefit to screening that persists, even if robust data to support it remain elusive.

Putting aside studies that suggest these screenings help identify melanomas at earlier stages and with reduced Breslow thicknesses,³ there is a crucial benefit from face-to-face interaction between medical professionals and the public during skin cancer screening events or health fairs. This interaction has become especially important in an era when misinformation thrives online and so-called skin care “experts” with no formal training can amass tens of thousands—or even millions—of followers on social media.

So, what are the intangible benefits of the face-to-face interactions that occur naturally during skin cancer screenings? The most obvious is education. While the USPSTF may not recommend routine screening for skin cancer in the general population, it does endorse education for children, adolescents, and adults on the importance of minimizing exposure to UV radiation, particularly those with lighter skin tones.⁴ Publicly advertised skin cancer screenings at health fairs or other community events may offer an opportunity to raise awareness about sun safety and protection, including the value of peak UV avoidance, sun-protective clothing, and proper sunscreen use; these settings also serve as platforms for health care providers to counter misinformation, including concerns about sunscreen safety both for the patient and the environment, overhyped risks for vitamin D deficiency from sun avoidance, and myths about low skin cancer risk in patients with skin of color.

While the benefits of skin self-examination (SSE) remain uncertain, especially in low-risk populations, screening events provide an opportunity to educate patients on who is most likely to benefit from SSE and in whom the practice may cause more harm than good.⁵ For higher-risk individuals such as melanoma survivors or those with a strong family history, screening fairs can serve as meaningful touchpoints that reinforce the importance of sun protection and regular examinations with a health care provider. For those eager to perform SSEs, these events offer the chance to teach best ­practices—how to conduct SSEs effectively, what features to look for (eg, the ABCDE method or the ugly duckling sign), and when to seek professional care.

Finally (and importantly), skin cancer screening events provide peace of mind for patients. Reassurance from a professional about a benign skin lesion can alleviate anxiety that might otherwise lead to emergency or urgent care visits. While cellulitis and other skin infections are the most common dermatologic conditions seen in emergency settings, benign neoplasms and similar nonurgent conditions still contribute a substantial burden to urgent care systems in the United States.⁶ Outside emergency care, systems-level data support what many of us observe in practice: two of the most common reasons for referral to dermatology are benign neoplasms and epidermoid cysts, accounting for millions of visits annually.⁷ In fact, recent claims data suggest that the most common diagnosis made in US dermatology clinics in 2023 was (you guessed it!) seborrheic keratosis.⁸

What if instead of requiring a patient to wait weeks for a primary care appointment and months for a dermatology referral—all while worrying about a rapidly growing pigmented lesion and incurring costs in copays, travel, lost wages, and time away from work—we offered a fast, trustworthy, and free evaluation that meets the patient where they live, work, or socialize? An evaluation that not only eases their fears but also provides meaningful education about skin cancer prevention and screening guidelines? While precautions must of course be taken to ensure that the quality and completeness of such an examination equals that of an in-clinic evaluation, if services of this quality can be provided, public screening events may offer a simple, accessible, and valuable solution that delivers peace of mind and helps reduce unnecessary strain on emergency, primary, and specialty care networks.

When Skin Cancer Awareness Month rolls around every May, my social media feed is inundated with posts extolling the benefits of total body skin examinations and the life-saving potential of skin cancer screenings; however, time and again the US Preventive Services Task Force (USPSTF)—the leading authority on evidence-based public health recommendations in the United States—has found the evidence supporting skin cancer screenings to be insufficient. The USPSTF has cited a lack of high-quality studies and inadequate data to recommend screening for the general population, excluding those at elevated risk due to personal, family, or occupational history.¹ A 2019 Cochrane review went further, concluding that current evidence refutes the utility of population-based screening for melanoma.²

Despite these findings, skin cancer screenings and total body skin examinations remain popular among patients both with and without a personal or family history of cutaneous malignancy. Indeed, the anecdotal experience of dermatologists worldwide suggests an intangible benefit to screening that persists, even if robust data to support it remain elusive.

Putting aside studies that suggest these screenings help identify melanomas at earlier stages and with reduced Breslow thicknesses,³ there is a crucial benefit from face-to-face interaction between medical professionals and the public during skin cancer screening events or health fairs. This interaction has become especially important in an era when misinformation thrives online and so-called skin care “experts” with no formal training can amass tens of thousands—or even millions—of followers on social media.

So, what are the intangible benefits of the face-to-face interactions that occur naturally during skin cancer screenings? The most obvious is education. While the USPSTF may not recommend routine screening for skin cancer in the general population, it does endorse education for children, adolescents, and adults on the importance of minimizing exposure to UV radiation, particularly those with lighter skin tones.⁴ Publicly advertised skin cancer screenings at health fairs or other community events may offer an opportunity to raise awareness about sun safety and protection, including the value of peak UV avoidance, sun-protective clothing, and proper sunscreen use; these settings also serve as platforms for health care providers to counter misinformation, including concerns about sunscreen safety both for the patient and the environment, overhyped risks for vitamin D deficiency from sun avoidance, and myths about low skin cancer risk in patients with skin of color.

While the benefits of skin self-examination (SSE) remain uncertain, especially in low-risk populations, screening events provide an opportunity to educate patients on who is most likely to benefit from SSE and in whom the practice may cause more harm than good.⁵ For higher-risk individuals such as melanoma survivors or those with a strong family history, screening fairs can serve as meaningful touchpoints that reinforce the importance of sun protection and regular examinations with a health care provider. For those eager to perform SSEs, these events offer the chance to teach best ­practices—how to conduct SSEs effectively, what features to look for (eg, the ABCDE method or the ugly duckling sign), and when to seek professional care.

Finally (and importantly), skin cancer screening events provide peace of mind for patients. Reassurance from a professional about a benign skin lesion can alleviate anxiety that might otherwise lead to emergency or urgent care visits. While cellulitis and other skin infections are the most common dermatologic conditions seen in emergency settings, benign neoplasms and similar nonurgent conditions still contribute a substantial burden to urgent care systems in the United States.⁶ Outside emergency care, systems-level data support what many of us observe in practice: two of the most common reasons for referral to dermatology are benign neoplasms and epidermoid cysts, accounting for millions of visits annually.⁷ In fact, recent claims data suggest that the most common diagnosis made in US dermatology clinics in 2023 was (you guessed it!) seborrheic keratosis.⁸

What if instead of requiring a patient to wait weeks for a primary care appointment and months for a dermatology referral—all while worrying about a rapidly growing pigmented lesion and incurring costs in copays, travel, lost wages, and time away from work—we offered a fast, trustworthy, and free evaluation that meets the patient where they live, work, or socialize? An evaluation that not only eases their fears but also provides meaningful education about skin cancer prevention and screening guidelines? While precautions must of course be taken to ensure that the quality and completeness of such an examination equals that of an in-clinic evaluation, if services of this quality can be provided, public screening events may offer a simple, accessible, and valuable solution that delivers peace of mind and helps reduce unnecessary strain on emergency, primary, and specialty care networks.

When Skin Cancer Awareness Month rolls around every May, my social media feed is inundated with posts extolling the benefits of total body skin examinations and the life-saving potential of skin cancer screenings; however, time and again the US Preventive Services Task Force (USPSTF)—the leading authority on evidence-based public health recommendations in the United States—has found the evidence supporting skin cancer screenings to be insufficient. The USPSTF has cited a lack of high-quality studies and inadequate data to recommend screening for the general population, excluding those at elevated risk due to personal, family, or occupational history.¹ A 2019 Cochrane review went further, concluding that current evidence refutes the utility of population-based screening for melanoma.²

Despite these findings, skin cancer screenings and total body skin examinations remain popular among patients both with and without a personal or family history of cutaneous malignancy. Indeed, the anecdotal experience of dermatologists worldwide suggests an intangible benefit to screening that persists, even if robust data to support it remain elusive.

Putting aside studies that suggest these screenings help identify melanomas at earlier stages and with reduced Breslow thicknesses,³ there is a crucial benefit from face-to-face interaction between medical professionals and the public during skin cancer screening events or health fairs. This interaction has become especially important in an era when misinformation thrives online and so-called skin care “experts” with no formal training can amass tens of thousands—or even millions—of followers on social media.

So, what are the intangible benefits of the face-to-face interactions that occur naturally during skin cancer screenings? The most obvious is education. While the USPSTF may not recommend routine screening for skin cancer in the general population, it does endorse education for children, adolescents, and adults on the importance of minimizing exposure to UV radiation, particularly those with lighter skin tones.⁴ Publicly advertised skin cancer screenings at health fairs or other community events may offer an opportunity to raise awareness about sun safety and protection, including the value of peak UV avoidance, sun-protective clothing, and proper sunscreen use; these settings also serve as platforms for health care providers to counter misinformation, including concerns about sunscreen safety both for the patient and the environment, overhyped risks for vitamin D deficiency from sun avoidance, and myths about low skin cancer risk in patients with skin of color.

While the benefits of skin self-examination (SSE) remain uncertain, especially in low-risk populations, screening events provide an opportunity to educate patients on who is most likely to benefit from SSE and in whom the practice may cause more harm than good.⁵ For higher-risk individuals such as melanoma survivors or those with a strong family history, screening fairs can serve as meaningful touchpoints that reinforce the importance of sun protection and regular examinations with a health care provider. For those eager to perform SSEs, these events offer the chance to teach best ­practices—how to conduct SSEs effectively, what features to look for (eg, the ABCDE method or the ugly duckling sign), and when to seek professional care.

Finally (and importantly), skin cancer screening events provide peace of mind for patients. Reassurance from a professional about a benign skin lesion can alleviate anxiety that might otherwise lead to emergency or urgent care visits. While cellulitis and other skin infections are the most common dermatologic conditions seen in emergency settings, benign neoplasms and similar nonurgent conditions still contribute a substantial burden to urgent care systems in the United States.⁶ Outside emergency care, systems-level data support what many of us observe in practice: two of the most common reasons for referral to dermatology are benign neoplasms and epidermoid cysts, accounting for millions of visits annually.⁷ In fact, recent claims data suggest that the most common diagnosis made in US dermatology clinics in 2023 was (you guessed it!) seborrheic keratosis.⁸

What if instead of requiring a patient to wait weeks for a primary care appointment and months for a dermatology referral—all while worrying about a rapidly growing pigmented lesion and incurring costs in copays, travel, lost wages, and time away from work—we offered a fast, trustworthy, and free evaluation that meets the patient where they live, work, or socialize? An evaluation that not only eases their fears but also provides meaningful education about skin cancer prevention and screening guidelines? While precautions must of course be taken to ensure that the quality and completeness of such an examination equals that of an in-clinic evaluation, if services of this quality can be provided, public screening events may offer a simple, accessible, and valuable solution that delivers peace of mind and helps reduce unnecessary strain on emergency, primary, and specialty care networks.

What clinical signs suggest antimicrobial resistance is affecting acne treatment response, and how can dermatologists identify them early? 

DR. ROSAMILIA: Antibiotic resistance is a difficult phenomenon to define clinically for acne due to many pathogenic contributors, namely the increase in sebum production stoked by hormonal changes, which further provokes Cutibacterium acnes biofilms, follicular plugs, and various inflammatory cascades. The sequence and primacy of these steps are enigmatic in each patient, therefore the role and extent of true antimicrobial therapy are debatable. Acne is more complex than other conditions that utilize antimicrobials, such as tinea corporis. In acne, lack of treatment response may be due to various factors, including long-term adherence challenges (such as inconsistent home dosing and trending complex over-the-counter [OTC] regimens), hormonal fluctuation, and confounders such as gram-negative or pityrosporum folliculitis. Therefore, determining if resistant bacteria are “causal” in acne recalcitrance or exacerbation is vague. In older patients (or younger patients with chronic conditions), proof of bacterial resistance from wound, pulmonary, or gastrointestinal studies might be available, but a typical acne patient would not present with these data. 

Do you routinely rotate patients off oral antibiotics after a fixed treatment period, or is it symptom based? How do you balance the risk for disease recurrence with resistance concerns? 

DR. ROSAMILIA: For my patients, the typical “triple threat” for moderate acne—oral antibiotics, topical benzoyl peroxide, and topical retinoids—still is tried and true. I typically prescribe 6 weeks of low-dose antibiotic therapy (doxycycline 50 mg daily) and arrange a telemedicine visit at 4 to 6 weeks to assess progress and adherence. Subsequently, I might substitute topical for oral antibiotics, with long-term plans to discontinue all antibiotics. In females, I might add spironolactone and/or oral contraceptive pills, and for recalcitrant or progressive acne, I would discuss isotretinoin. If the patient’s acne is under good control without antibiotics but they still experience intermittent deeper papules, I consider adding burst therapy of low-dose doxycycline for 1 week as needed, or for instance, during sports seasons. I try to maintain the lowest possible dosage of doxycycline while toeing the line between short-term antibacterial and longer-term anti-inflammatory control. In fact, I typically recommend that patients take it with their morning meal to absorb slightly less than the full 50-mg dosage, mitigate adverse effects, and increase adherence. All of these regimens include a benzoyl peroxide wash for its many anti-acne properties and in the context of this discussion to mitigate C acnes on acne-prone skin without creating antibiotic resistance. 

Do you see a future for point-of-care microbiome or resistance testing in acne management? 

DR. ROSAMILIA: I think we should be receptive to the evolution of these tests, and depending on the patient’s insurance coverage, efficient collection methods, and applicability to all patients, we someday may approach antimicrobial pharmacotherapy in a more personalized way. The microbiome is a broad topic with protean approaches to testing and prebiotic/probiotic supplementation, so openminded but cautious and well-studied utilization is key. 

What language do you find effective when setting expectations for acne treatment that avoids overreliance on antibiotics? 

DR. ROSAMILIA: I find it important to first determine the patient’s prior therapies. Many patients with acne present to dermatology after taking a full dosage of various antibiotics for broad amounts of time, and they may have experienced acne exacerbation (or at least perception of such) when the refills ran out. Also, I ask them to outline their past and current OTC regimens, which provides context for where and how the patient gets their information and advice. I like providing the patient’s next steps in written form, even telling them to tape the instructions to their bathroom mirror. It is just as vital to take time at the first office visit to explain the expected time to improvement and why acne is a multifactorial condition for which antibiotics are only part of the approach with benzoyl peroxide and retinoids. 

What are your top practical tips for incoming dermatologists to practice antibiotic stewardship in acne management? 

DR. ROSAMILIA: The American Academy of Dermatology (AAD) guidelines recommend 3 to 4 months as the maximum threshold for systemic antibiotics for moderate to severe acne, with tetracyclines having the best evidence for efficacy and safety. The AAD recommends never utilizing these as monotherapy and always including concomitant benzoyl peroxide to avoid bacterial resistance and topicals such as retinoids to provide a bridge to a maintenance phase without antibiotics. Starting there gives trainees structure within which to build their own acne management approach and style for their patient population. Some dermatologists might prescribe middle to high antibiotic dosages at first followed by a taper or initiate low antibiotic dosages with a standard 3- to 4-month follow-up, or a bit of a hybrid of these, as outlined in my approach. As mentioned, standardized testing for resistance to guide our dosing is not mainstream. There are countless ways to apply these guardrails, consider a place for hormonal or future isotretinoin therapy, and include the many varieties of OTC and prescription acne topicals to round out a personalized regimen for each patient based on their schedule, medication intolerances, skin type, fertility plans, and lifestyle. 

What’s the single most impactful change a busy dermatology clinic could make right now to reduce antibiotic overuse in acne care? 

DR. ROSAMILIA: I think telemedicine or in-person check-ins at the 1- or 2-month mark are vital to the assessment of the patient’s and/or family’s understanding of the treatment schedule, their ability to procure the prescription and OTC products successfully, and their consistency in using them. This is a good opportunity to remind them that our goal is to see true acne improvement; take fewer medications, not more; and create a reality where their acne regimen is intuitive and safe.

What clinical signs suggest antimicrobial resistance is affecting acne treatment response, and how can dermatologists identify them early? 

DR. ROSAMILIA: Antibiotic resistance is a difficult phenomenon to define clinically for acne due to many pathogenic contributors, namely the increase in sebum production stoked by hormonal changes, which further provokes Cutibacterium acnes biofilms, follicular plugs, and various inflammatory cascades. The sequence and primacy of these steps are enigmatic in each patient, therefore the role and extent of true antimicrobial therapy are debatable. Acne is more complex than other conditions that utilize antimicrobials, such as tinea corporis. In acne, lack of treatment response may be due to various factors, including long-term adherence challenges (such as inconsistent home dosing and trending complex over-the-counter [OTC] regimens), hormonal fluctuation, and confounders such as gram-negative or pityrosporum folliculitis. Therefore, determining if resistant bacteria are “causal” in acne recalcitrance or exacerbation is vague. In older patients (or younger patients with chronic conditions), proof of bacterial resistance from wound, pulmonary, or gastrointestinal studies might be available, but a typical acne patient would not present with these data. 

Do you routinely rotate patients off oral antibiotics after a fixed treatment period, or is it symptom based? How do you balance the risk for disease recurrence with resistance concerns? 

DR. ROSAMILIA: For my patients, the typical “triple threat” for moderate acne—oral antibiotics, topical benzoyl peroxide, and topical retinoids—still is tried and true. I typically prescribe 6 weeks of low-dose antibiotic therapy (doxycycline 50 mg daily) and arrange a telemedicine visit at 4 to 6 weeks to assess progress and adherence. Subsequently, I might substitute topical for oral antibiotics, with long-term plans to discontinue all antibiotics. In females, I might add spironolactone and/or oral contraceptive pills, and for recalcitrant or progressive acne, I would discuss isotretinoin. If the patient’s acne is under good control without antibiotics but they still experience intermittent deeper papules, I consider adding burst therapy of low-dose doxycycline for 1 week as needed, or for instance, during sports seasons. I try to maintain the lowest possible dosage of doxycycline while toeing the line between short-term antibacterial and longer-term anti-inflammatory control. In fact, I typically recommend that patients take it with their morning meal to absorb slightly less than the full 50-mg dosage, mitigate adverse effects, and increase adherence. All of these regimens include a benzoyl peroxide wash for its many anti-acne properties and in the context of this discussion to mitigate C acnes on acne-prone skin without creating antibiotic resistance. 

Do you see a future for point-of-care microbiome or resistance testing in acne management? 

DR. ROSAMILIA: I think we should be receptive to the evolution of these tests, and depending on the patient’s insurance coverage, efficient collection methods, and applicability to all patients, we someday may approach antimicrobial pharmacotherapy in a more personalized way. The microbiome is a broad topic with protean approaches to testing and prebiotic/probiotic supplementation, so openminded but cautious and well-studied utilization is key. 

What language do you find effective when setting expectations for acne treatment that avoids overreliance on antibiotics? 

DR. ROSAMILIA: I find it important to first determine the patient’s prior therapies. Many patients with acne present to dermatology after taking a full dosage of various antibiotics for broad amounts of time, and they may have experienced acne exacerbation (or at least perception of such) when the refills ran out. Also, I ask them to outline their past and current OTC regimens, which provides context for where and how the patient gets their information and advice. I like providing the patient’s next steps in written form, even telling them to tape the instructions to their bathroom mirror. It is just as vital to take time at the first office visit to explain the expected time to improvement and why acne is a multifactorial condition for which antibiotics are only part of the approach with benzoyl peroxide and retinoids. 

What are your top practical tips for incoming dermatologists to practice antibiotic stewardship in acne management? 

DR. ROSAMILIA: The American Academy of Dermatology (AAD) guidelines recommend 3 to 4 months as the maximum threshold for systemic antibiotics for moderate to severe acne, with tetracyclines having the best evidence for efficacy and safety. The AAD recommends never utilizing these as monotherapy and always including concomitant benzoyl peroxide to avoid bacterial resistance and topicals such as retinoids to provide a bridge to a maintenance phase without antibiotics. Starting there gives trainees structure within which to build their own acne management approach and style for their patient population. Some dermatologists might prescribe middle to high antibiotic dosages at first followed by a taper or initiate low antibiotic dosages with a standard 3- to 4-month follow-up, or a bit of a hybrid of these, as outlined in my approach. As mentioned, standardized testing for resistance to guide our dosing is not mainstream. There are countless ways to apply these guardrails, consider a place for hormonal or future isotretinoin therapy, and include the many varieties of OTC and prescription acne topicals to round out a personalized regimen for each patient based on their schedule, medication intolerances, skin type, fertility plans, and lifestyle. 

What’s the single most impactful change a busy dermatology clinic could make right now to reduce antibiotic overuse in acne care? 

DR. ROSAMILIA: I think telemedicine or in-person check-ins at the 1- or 2-month mark are vital to the assessment of the patient’s and/or family’s understanding of the treatment schedule, their ability to procure the prescription and OTC products successfully, and their consistency in using them. This is a good opportunity to remind them that our goal is to see true acne improvement; take fewer medications, not more; and create a reality where their acne regimen is intuitive and safe.

What clinical signs suggest antimicrobial resistance is affecting acne treatment response, and how can dermatologists identify them early? 

DR. ROSAMILIA: Antibiotic resistance is a difficult phenomenon to define clinically for acne due to many pathogenic contributors, namely the increase in sebum production stoked by hormonal changes, which further provokes Cutibacterium acnes biofilms, follicular plugs, and various inflammatory cascades. The sequence and primacy of these steps are enigmatic in each patient, therefore the role and extent of true antimicrobial therapy are debatable. Acne is more complex than other conditions that utilize antimicrobials, such as tinea corporis. In acne, lack of treatment response may be due to various factors, including long-term adherence challenges (such as inconsistent home dosing and trending complex over-the-counter [OTC] regimens), hormonal fluctuation, and confounders such as gram-negative or pityrosporum folliculitis. Therefore, determining if resistant bacteria are “causal” in acne recalcitrance or exacerbation is vague. In older patients (or younger patients with chronic conditions), proof of bacterial resistance from wound, pulmonary, or gastrointestinal studies might be available, but a typical acne patient would not present with these data. 

Do you routinely rotate patients off oral antibiotics after a fixed treatment period, or is it symptom based? How do you balance the risk for disease recurrence with resistance concerns? 

DR. ROSAMILIA: For my patients, the typical “triple threat” for moderate acne—oral antibiotics, topical benzoyl peroxide, and topical retinoids—still is tried and true. I typically prescribe 6 weeks of low-dose antibiotic therapy (doxycycline 50 mg daily) and arrange a telemedicine visit at 4 to 6 weeks to assess progress and adherence. Subsequently, I might substitute topical for oral antibiotics, with long-term plans to discontinue all antibiotics. In females, I might add spironolactone and/or oral contraceptive pills, and for recalcitrant or progressive acne, I would discuss isotretinoin. If the patient’s acne is under good control without antibiotics but they still experience intermittent deeper papules, I consider adding burst therapy of low-dose doxycycline for 1 week as needed, or for instance, during sports seasons. I try to maintain the lowest possible dosage of doxycycline while toeing the line between short-term antibacterial and longer-term anti-inflammatory control. In fact, I typically recommend that patients take it with their morning meal to absorb slightly less than the full 50-mg dosage, mitigate adverse effects, and increase adherence. All of these regimens include a benzoyl peroxide wash for its many anti-acne properties and in the context of this discussion to mitigate C acnes on acne-prone skin without creating antibiotic resistance. 

Do you see a future for point-of-care microbiome or resistance testing in acne management? 

DR. ROSAMILIA: I think we should be receptive to the evolution of these tests, and depending on the patient’s insurance coverage, efficient collection methods, and applicability to all patients, we someday may approach antimicrobial pharmacotherapy in a more personalized way. The microbiome is a broad topic with protean approaches to testing and prebiotic/probiotic supplementation, so openminded but cautious and well-studied utilization is key. 

What language do you find effective when setting expectations for acne treatment that avoids overreliance on antibiotics? 

DR. ROSAMILIA: I find it important to first determine the patient’s prior therapies. Many patients with acne present to dermatology after taking a full dosage of various antibiotics for broad amounts of time, and they may have experienced acne exacerbation (or at least perception of such) when the refills ran out. Also, I ask them to outline their past and current OTC regimens, which provides context for where and how the patient gets their information and advice. I like providing the patient’s next steps in written form, even telling them to tape the instructions to their bathroom mirror. It is just as vital to take time at the first office visit to explain the expected time to improvement and why acne is a multifactorial condition for which antibiotics are only part of the approach with benzoyl peroxide and retinoids. 

What are your top practical tips for incoming dermatologists to practice antibiotic stewardship in acne management? 

DR. ROSAMILIA: The American Academy of Dermatology (AAD) guidelines recommend 3 to 4 months as the maximum threshold for systemic antibiotics for moderate to severe acne, with tetracyclines having the best evidence for efficacy and safety. The AAD recommends never utilizing these as monotherapy and always including concomitant benzoyl peroxide to avoid bacterial resistance and topicals such as retinoids to provide a bridge to a maintenance phase without antibiotics. Starting there gives trainees structure within which to build their own acne management approach and style for their patient population. Some dermatologists might prescribe middle to high antibiotic dosages at first followed by a taper or initiate low antibiotic dosages with a standard 3- to 4-month follow-up, or a bit of a hybrid of these, as outlined in my approach. As mentioned, standardized testing for resistance to guide our dosing is not mainstream. There are countless ways to apply these guardrails, consider a place for hormonal or future isotretinoin therapy, and include the many varieties of OTC and prescription acne topicals to round out a personalized regimen for each patient based on their schedule, medication intolerances, skin type, fertility plans, and lifestyle. 

What’s the single most impactful change a busy dermatology clinic could make right now to reduce antibiotic overuse in acne care? 

DR. ROSAMILIA: I think telemedicine or in-person check-ins at the 1- or 2-month mark are vital to the assessment of the patient’s and/or family’s understanding of the treatment schedule, their ability to procure the prescription and OTC products successfully, and their consistency in using them. This is a good opportunity to remind them that our goal is to see true acne improvement; take fewer medications, not more; and create a reality where their acne regimen is intuitive and safe.

Visible light is part of the electromagnetic spectrum and is confined to a range of 400 to 700 nm. Visible light phototherapy can be delivered across various wavelengths within this spectrum, with most research focusing on blue light (BL)(400-500 nm) and red light (RL)(600-700 nm). Blue light commonly is used to treat acne as well as actinic keratosis and other inflammatory disorders,^1,2 while RL largely targets signs of skin aging and fibrosis.^2,3 Because of its shorter wavelength, the clinically meaningful skin penetration of BL reaches up to1 mm and is confined to the epidermis; in contrast, RL can access the dermal adnexa due to its penetration depth of more than 2 mm.⁴ Therapeutically, visible light can be utilized alone (eg, photobiomodulation [PBM]) or in combination with a photosensitizing agent (eg, photodynamic therapy [PDT]).^5,6

Our laboratory’s prior research has contributed to a greater understanding of the safety profile of visible light at various wavelengths.^1,3 Specifically, our work has shown that BL (417 nm [range, 412-422 nm]) and RL (633 nm [range, 627-639 nm]) demonstrated no evidence of DNA damage—via no formation of cyclobutane pyrimidine dimers and/or 6-4 photoproducts, the hallmark photolesions caused by UV exposure—in human dermal fibroblasts following visible light exposure at all fluences tested.^1,3 This evidence reinforces the safety of visible light at clinically relevant wavelengths, supporting its integration into dermatologic practice. In this editorial, we highlight the key clinical applications of PBM and PDT and outline safety considerations for visible light-based therapies in dermatologic practice.

Photobiomodulation

Photobiomodulation is a noninvasive treatment in which low-level lasers or light-emitting diodes deliver photons from a nonionizing light source to endogenous photoreceptors, primarily cytochrome C oxidase.^7-9 On the visible light spectrum, PBM primarily encompasses RL.^7-9 Photoactivation leads to production of reactive oxygen species as well as mitochondrial alterations, with resulting modulation of cellular activity.^7-9 Upregulation of cellular activity generally occurs at lower fluences (ie, energy delivered per unit area) of light, whereas higher fluences cause downregulation of cellular activity.⁵

Recent consensus guidelines, established with expert colleagues, define additional key parameters that are crucial to optimizing PBM treatment, including distance from the light source, area of the light beam, wavelength, length of treatment time, and number of treatments.⁵ Understanding the effects of different parameter combinations is essential for clinicians to select the best treatment regimen for each patient. Our laboratory has conducted National Institutes of Health–funded phase 1 and phase 2 clinical trials to determine the safety and efficacy of red-light PBM.^10-13 Additionally, we completed several pilot phase 2 clinical studies with commercially available light-emitting diode face masks using PBM technology, which demonstrated a favorable safety profile and high patient satisfaction across multiple self-reported measures.^14,15 These findings highlight PBM as a reliable and well-tolerated therapeutic approach that can be administered in clinical settings or by patients at home.

Adverse effects of PBM therapy generally are mild and transient, most commonly manifesting as slight irritation and erythema.⁵ Overall, PBM is widely regarded as safe with a favorable and nontoxic profile across treatment settings. Growing evidence supports the role of PBM in managing wound healing, acne, alopecia, and skin aging, among other dermatologic concerns.⁸

Photodynamic Therapy

Photodynamic therapy is a noninvasive procedure during which a photosensitizer—typically 5-aminolevulinic acid (5-ALA) or a derivative, methyl aminolevulinate—reacts with a light source and oxygen, resulting in reactive oxygen species.^6,16 This reaction ultimately triggers targeted cellular destruction of the intended lesional skin but with negligible effects on adjacent nonlesional tissue.⁶ The efficacy of PDT is determined by several parameters, including composition and concentration of the photosensitizer, photosensitizer incubation temperature, and incubation time with the photosensitizer. Methyl aminolevulinate is a lipophilic molecule and may promote greater skin penetration and cellular uptake than 5-ALA, which is a hydrophilic molecule.⁶

Our research further demonstrated that apoptosis increases in a dose- and temperature-dependent manner following 5-ALA exposure, both in cutaneous and mucosal squamous cell carcinoma cells and in human dermal fibroblasts.^17,18 Our mechanistic insights have clinical relevance, as evidenced by an independent pilot study demonstrating that temperature-modulated PDT significantly improved actinic keratosis lesion clearance rates (P<.0001).¹⁹ Additionally, we determined that even short periods of incubation with 5-ALA (ie, 15-30 minutes) result in statistically significant increases in apoptosis (P<.05).²⁰ Thus, these findings highlight that the choice of photosensitizing agent and the administration parameters are critical in determining PDT efficacy as well as the need to optimize clinical protocols.

Photodynamic therapy also has demonstrated general clinical and genotoxic safety, with the most common potential adverse events limited to temporary inflammation, erythema, and discomfort.²¹ A study in murine skin and human keratinocytes revealed that 5-ALA PDT had a photoprotective effect against previous irradiation with UVB (a known inducer of DNA damage) via removal of cyclobutane pyrimidine dimers.²² Thus, PDT has been recognized as a safe and effective therapeutic modality with broad applications in dermatology, including treatment of actinic keratosis and nonmelanoma skin cancers.¹⁶

Clinical Safety, Photoprotection, and Precautions

While visible light has shown substantial therapeutic potential in dermatology, there are several safety measures and precautions to be aware of. Visible light constitutes approximately 44% of the solar output; therefore, precautions against both UV and visible light are recommended for the general population.²³ Cumulative exposure to visible light has been shown to trigger melanogenesis, resulting in persistent erythema, hyperpigmentation, and uneven skin tones across all Fitzpatrick skin types.²⁴ Individuals with skin of color are more photosensitive to visible light due to increased baseline melanin levels.²⁴ Similarly, patients with pigmentary conditions such as melasma and postinflammatory hyperpigmentation may experience worsening of their dermatologic symptoms due to underlying visible light photosensitivity.²⁵

Patients undergoing PBM or PDT could benefit from visible light protection. The primary form of photoprotection against visible light is tinted sunscreen, which contains iron oxides and titanium dioxide.²⁶ Iron (III) oxide is capable of blocking nearly all visible light damage.²⁶ Use of physical barriers such as wavelength-specific sunglasses and wide-brimmed hats also is important for preventing photodamage from visible light.²⁶

Final Thoughts

Visible light has a role in the treatment of a variety of skin conditions, including actinic keratosis, nonmelanoma skin cancers, acne, wound healing, skin fibrosis, and photodamage. Photobiomodulation and PDT represent 2 noninvasive phototherapeutic options that utilize visible light to enact cellular changes necessary to improve skin health. Integrating visible light phototherapy into standard clinical practice is important for enhancing patient outcomes. Clinicians should remain mindful of the rare pigmentary risks associated with visible light therapy devices. Future research should prioritize optimization of standardized protocols and expansion of clinical indications for visible light phototherapy.

Visible light is part of the electromagnetic spectrum and is confined to a range of 400 to 700 nm. Visible light phototherapy can be delivered across various wavelengths within this spectrum, with most research focusing on blue light (BL)(400-500 nm) and red light (RL)(600-700 nm). Blue light commonly is used to treat acne as well as actinic keratosis and other inflammatory disorders,^1,2 while RL largely targets signs of skin aging and fibrosis.^2,3 Because of its shorter wavelength, the clinically meaningful skin penetration of BL reaches up to1 mm and is confined to the epidermis; in contrast, RL can access the dermal adnexa due to its penetration depth of more than 2 mm.⁴ Therapeutically, visible light can be utilized alone (eg, photobiomodulation [PBM]) or in combination with a photosensitizing agent (eg, photodynamic therapy [PDT]).^5,6

Our laboratory’s prior research has contributed to a greater understanding of the safety profile of visible light at various wavelengths.^1,3 Specifically, our work has shown that BL (417 nm [range, 412-422 nm]) and RL (633 nm [range, 627-639 nm]) demonstrated no evidence of DNA damage—via no formation of cyclobutane pyrimidine dimers and/or 6-4 photoproducts, the hallmark photolesions caused by UV exposure—in human dermal fibroblasts following visible light exposure at all fluences tested.^1,3 This evidence reinforces the safety of visible light at clinically relevant wavelengths, supporting its integration into dermatologic practice. In this editorial, we highlight the key clinical applications of PBM and PDT and outline safety considerations for visible light-based therapies in dermatologic practice.

Photobiomodulation

Photobiomodulation is a noninvasive treatment in which low-level lasers or light-emitting diodes deliver photons from a nonionizing light source to endogenous photoreceptors, primarily cytochrome C oxidase.^7-9 On the visible light spectrum, PBM primarily encompasses RL.^7-9 Photoactivation leads to production of reactive oxygen species as well as mitochondrial alterations, with resulting modulation of cellular activity.^7-9 Upregulation of cellular activity generally occurs at lower fluences (ie, energy delivered per unit area) of light, whereas higher fluences cause downregulation of cellular activity.⁵

Recent consensus guidelines, established with expert colleagues, define additional key parameters that are crucial to optimizing PBM treatment, including distance from the light source, area of the light beam, wavelength, length of treatment time, and number of treatments.⁵ Understanding the effects of different parameter combinations is essential for clinicians to select the best treatment regimen for each patient. Our laboratory has conducted National Institutes of Health–funded phase 1 and phase 2 clinical trials to determine the safety and efficacy of red-light PBM.^10-13 Additionally, we completed several pilot phase 2 clinical studies with commercially available light-emitting diode face masks using PBM technology, which demonstrated a favorable safety profile and high patient satisfaction across multiple self-reported measures.^14,15 These findings highlight PBM as a reliable and well-tolerated therapeutic approach that can be administered in clinical settings or by patients at home.

Adverse effects of PBM therapy generally are mild and transient, most commonly manifesting as slight irritation and erythema.⁵ Overall, PBM is widely regarded as safe with a favorable and nontoxic profile across treatment settings. Growing evidence supports the role of PBM in managing wound healing, acne, alopecia, and skin aging, among other dermatologic concerns.⁸

Photodynamic Therapy

Photodynamic therapy is a noninvasive procedure during which a photosensitizer—typically 5-aminolevulinic acid (5-ALA) or a derivative, methyl aminolevulinate—reacts with a light source and oxygen, resulting in reactive oxygen species.^6,16 This reaction ultimately triggers targeted cellular destruction of the intended lesional skin but with negligible effects on adjacent nonlesional tissue.⁶ The efficacy of PDT is determined by several parameters, including composition and concentration of the photosensitizer, photosensitizer incubation temperature, and incubation time with the photosensitizer. Methyl aminolevulinate is a lipophilic molecule and may promote greater skin penetration and cellular uptake than 5-ALA, which is a hydrophilic molecule.⁶

Our research further demonstrated that apoptosis increases in a dose- and temperature-dependent manner following 5-ALA exposure, both in cutaneous and mucosal squamous cell carcinoma cells and in human dermal fibroblasts.^17,18 Our mechanistic insights have clinical relevance, as evidenced by an independent pilot study demonstrating that temperature-modulated PDT significantly improved actinic keratosis lesion clearance rates (P<.0001).¹⁹ Additionally, we determined that even short periods of incubation with 5-ALA (ie, 15-30 minutes) result in statistically significant increases in apoptosis (P<.05).²⁰ Thus, these findings highlight that the choice of photosensitizing agent and the administration parameters are critical in determining PDT efficacy as well as the need to optimize clinical protocols.

Photodynamic therapy also has demonstrated general clinical and genotoxic safety, with the most common potential adverse events limited to temporary inflammation, erythema, and discomfort.²¹ A study in murine skin and human keratinocytes revealed that 5-ALA PDT had a photoprotective effect against previous irradiation with UVB (a known inducer of DNA damage) via removal of cyclobutane pyrimidine dimers.²² Thus, PDT has been recognized as a safe and effective therapeutic modality with broad applications in dermatology, including treatment of actinic keratosis and nonmelanoma skin cancers.¹⁶

Clinical Safety, Photoprotection, and Precautions

While visible light has shown substantial therapeutic potential in dermatology, there are several safety measures and precautions to be aware of. Visible light constitutes approximately 44% of the solar output; therefore, precautions against both UV and visible light are recommended for the general population.²³ Cumulative exposure to visible light has been shown to trigger melanogenesis, resulting in persistent erythema, hyperpigmentation, and uneven skin tones across all Fitzpatrick skin types.²⁴ Individuals with skin of color are more photosensitive to visible light due to increased baseline melanin levels.²⁴ Similarly, patients with pigmentary conditions such as melasma and postinflammatory hyperpigmentation may experience worsening of their dermatologic symptoms due to underlying visible light photosensitivity.²⁵

Patients undergoing PBM or PDT could benefit from visible light protection. The primary form of photoprotection against visible light is tinted sunscreen, which contains iron oxides and titanium dioxide.²⁶ Iron (III) oxide is capable of blocking nearly all visible light damage.²⁶ Use of physical barriers such as wavelength-specific sunglasses and wide-brimmed hats also is important for preventing photodamage from visible light.²⁶

Final Thoughts

Visible light has a role in the treatment of a variety of skin conditions, including actinic keratosis, nonmelanoma skin cancers, acne, wound healing, skin fibrosis, and photodamage. Photobiomodulation and PDT represent 2 noninvasive phototherapeutic options that utilize visible light to enact cellular changes necessary to improve skin health. Integrating visible light phototherapy into standard clinical practice is important for enhancing patient outcomes. Clinicians should remain mindful of the rare pigmentary risks associated with visible light therapy devices. Future research should prioritize optimization of standardized protocols and expansion of clinical indications for visible light phototherapy.

Visible light is part of the electromagnetic spectrum and is confined to a range of 400 to 700 nm. Visible light phototherapy can be delivered across various wavelengths within this spectrum, with most research focusing on blue light (BL)(400-500 nm) and red light (RL)(600-700 nm). Blue light commonly is used to treat acne as well as actinic keratosis and other inflammatory disorders,^1,2 while RL largely targets signs of skin aging and fibrosis.^2,3 Because of its shorter wavelength, the clinically meaningful skin penetration of BL reaches up to1 mm and is confined to the epidermis; in contrast, RL can access the dermal adnexa due to its penetration depth of more than 2 mm.⁴ Therapeutically, visible light can be utilized alone (eg, photobiomodulation [PBM]) or in combination with a photosensitizing agent (eg, photodynamic therapy [PDT]).^5,6

Our laboratory’s prior research has contributed to a greater understanding of the safety profile of visible light at various wavelengths.^1,3 Specifically, our work has shown that BL (417 nm [range, 412-422 nm]) and RL (633 nm [range, 627-639 nm]) demonstrated no evidence of DNA damage—via no formation of cyclobutane pyrimidine dimers and/or 6-4 photoproducts, the hallmark photolesions caused by UV exposure—in human dermal fibroblasts following visible light exposure at all fluences tested.^1,3 This evidence reinforces the safety of visible light at clinically relevant wavelengths, supporting its integration into dermatologic practice. In this editorial, we highlight the key clinical applications of PBM and PDT and outline safety considerations for visible light-based therapies in dermatologic practice.

Photobiomodulation

Photobiomodulation is a noninvasive treatment in which low-level lasers or light-emitting diodes deliver photons from a nonionizing light source to endogenous photoreceptors, primarily cytochrome C oxidase.^7-9 On the visible light spectrum, PBM primarily encompasses RL.^7-9 Photoactivation leads to production of reactive oxygen species as well as mitochondrial alterations, with resulting modulation of cellular activity.^7-9 Upregulation of cellular activity generally occurs at lower fluences (ie, energy delivered per unit area) of light, whereas higher fluences cause downregulation of cellular activity.⁵

Recent consensus guidelines, established with expert colleagues, define additional key parameters that are crucial to optimizing PBM treatment, including distance from the light source, area of the light beam, wavelength, length of treatment time, and number of treatments.⁵ Understanding the effects of different parameter combinations is essential for clinicians to select the best treatment regimen for each patient. Our laboratory has conducted National Institutes of Health–funded phase 1 and phase 2 clinical trials to determine the safety and efficacy of red-light PBM.^10-13 Additionally, we completed several pilot phase 2 clinical studies with commercially available light-emitting diode face masks using PBM technology, which demonstrated a favorable safety profile and high patient satisfaction across multiple self-reported measures.^14,15 These findings highlight PBM as a reliable and well-tolerated therapeutic approach that can be administered in clinical settings or by patients at home.

Adverse effects of PBM therapy generally are mild and transient, most commonly manifesting as slight irritation and erythema.⁵ Overall, PBM is widely regarded as safe with a favorable and nontoxic profile across treatment settings. Growing evidence supports the role of PBM in managing wound healing, acne, alopecia, and skin aging, among other dermatologic concerns.⁸

Photodynamic Therapy

Photodynamic therapy is a noninvasive procedure during which a photosensitizer—typically 5-aminolevulinic acid (5-ALA) or a derivative, methyl aminolevulinate—reacts with a light source and oxygen, resulting in reactive oxygen species.^6,16 This reaction ultimately triggers targeted cellular destruction of the intended lesional skin but with negligible effects on adjacent nonlesional tissue.⁶ The efficacy of PDT is determined by several parameters, including composition and concentration of the photosensitizer, photosensitizer incubation temperature, and incubation time with the photosensitizer. Methyl aminolevulinate is a lipophilic molecule and may promote greater skin penetration and cellular uptake than 5-ALA, which is a hydrophilic molecule.⁶

Our research further demonstrated that apoptosis increases in a dose- and temperature-dependent manner following 5-ALA exposure, both in cutaneous and mucosal squamous cell carcinoma cells and in human dermal fibroblasts.^17,18 Our mechanistic insights have clinical relevance, as evidenced by an independent pilot study demonstrating that temperature-modulated PDT significantly improved actinic keratosis lesion clearance rates (P<.0001).¹⁹ Additionally, we determined that even short periods of incubation with 5-ALA (ie, 15-30 minutes) result in statistically significant increases in apoptosis (P<.05).²⁰ Thus, these findings highlight that the choice of photosensitizing agent and the administration parameters are critical in determining PDT efficacy as well as the need to optimize clinical protocols.

Photodynamic therapy also has demonstrated general clinical and genotoxic safety, with the most common potential adverse events limited to temporary inflammation, erythema, and discomfort.²¹ A study in murine skin and human keratinocytes revealed that 5-ALA PDT had a photoprotective effect against previous irradiation with UVB (a known inducer of DNA damage) via removal of cyclobutane pyrimidine dimers.²² Thus, PDT has been recognized as a safe and effective therapeutic modality with broad applications in dermatology, including treatment of actinic keratosis and nonmelanoma skin cancers.¹⁶

Clinical Safety, Photoprotection, and Precautions

While visible light has shown substantial therapeutic potential in dermatology, there are several safety measures and precautions to be aware of. Visible light constitutes approximately 44% of the solar output; therefore, precautions against both UV and visible light are recommended for the general population.²³ Cumulative exposure to visible light has been shown to trigger melanogenesis, resulting in persistent erythema, hyperpigmentation, and uneven skin tones across all Fitzpatrick skin types.²⁴ Individuals with skin of color are more photosensitive to visible light due to increased baseline melanin levels.²⁴ Similarly, patients with pigmentary conditions such as melasma and postinflammatory hyperpigmentation may experience worsening of their dermatologic symptoms due to underlying visible light photosensitivity.²⁵

Patients undergoing PBM or PDT could benefit from visible light protection. The primary form of photoprotection against visible light is tinted sunscreen, which contains iron oxides and titanium dioxide.²⁶ Iron (III) oxide is capable of blocking nearly all visible light damage.²⁶ Use of physical barriers such as wavelength-specific sunglasses and wide-brimmed hats also is important for preventing photodamage from visible light.²⁶

Final Thoughts

Visible light has a role in the treatment of a variety of skin conditions, including actinic keratosis, nonmelanoma skin cancers, acne, wound healing, skin fibrosis, and photodamage. Photobiomodulation and PDT represent 2 noninvasive phototherapeutic options that utilize visible light to enact cellular changes necessary to improve skin health. Integrating visible light phototherapy into standard clinical practice is important for enhancing patient outcomes. Clinicians should remain mindful of the rare pigmentary risks associated with visible light therapy devices. Future research should prioritize optimization of standardized protocols and expansion of clinical indications for visible light phototherapy.

The original four HPEER Advanced Fellowship sites were established by the Department of Veterans Affairs (VA) Office of Academic Affiliation in 2014, and expanded in 2020 to include 8 sites and a national coordinating center with leadership shared between VA facilities in Houston and White River Junction. The VA invests heavily in training the nation’s healthcare professionals. The mission of HPEER is to develop leaders who can educate, evaluate, and innovate in Health Professions Education for the VA and the nation. All HPEER sites take part in a nationally coordinated curriculum covering topics in curriculum design, learner assessment, leadership, interprofessional education, as well as scholarship and educational research.

As part of the national HPEER curriculum covering scholarship and educational research, and in concert with Wednesday, May 14, 2025 VA Research Week 2025, HPEER organized a joint conference with the Center for Health Professions Education at the Uniformed Services University of the Health Sciences (USUHS). This interagency online event included poster sessions and oral presentations from HPEER fellows and students in USUHS certificate and graduate degree programs.

Education scholarship is broad, ranging from descriptions of curricular innovations and works in progress to advanced research using techniques drawn from psychology, sociology, anthropology, economics, and other scientific disciplines. The abstracts presented here summarize some of the work being done by HPEER fellows. Dougherty et al (Boston) described a project to create a primer outlining methodology for conducting and interpreting cost-effectiveness evaluations in the context of proposed HPE innovations. Cohen et al (Cleveland) found reduction in potentially problematic orders in the context of life-sustaining treatment following a multifaceted intervention program. Sorenson (Dublin, Georgia) reported an expanded Tai Chi program that included modifications allowing seated positions for veterans with mobility limitations. Young et al (Dublin) described an interprofessional curriculum to strengthen communication between nurses and social workers in their conversations with women veterans living in rural settings. Misedah-Robinson et al (Houston) showed that a new training program strengthened coordinators’ self-reports of preparedness and confidence in their ability to support veterans who have experienced human trafficking. Tovar et al (Salt Lake City) describe a methodology for using data from the VHA Corporate Data Warehouse to optimize schedules of HPE students assigned to VA clinical rotations. Yanez et al (San Francisco) presented initial observations of learner-centered outcomes following participation in a new multidisciplinary integrative health elective. Resto et al (West Haven) reported that implementation of self-serve kiosks increased distribution of substance use harm reduction resources beyond usual clinical care.

A second joint conference between VA HPEER and USUHS is planned for VA Research Week 2026; we look forward to the abstracts that will be produced by this new cohort of fellows, as well as to the future scholarship and contributions to the field that will be made by alumni of the HPEER Advanced Fellowship.

The original four HPEER Advanced Fellowship sites were established by the Department of Veterans Affairs (VA) Office of Academic Affiliation in 2014, and expanded in 2020 to include 8 sites and a national coordinating center with leadership shared between VA facilities in Houston and White River Junction. The VA invests heavily in training the nation’s healthcare professionals. The mission of HPEER is to develop leaders who can educate, evaluate, and innovate in Health Professions Education for the VA and the nation. All HPEER sites take part in a nationally coordinated curriculum covering topics in curriculum design, learner assessment, leadership, interprofessional education, as well as scholarship and educational research.

As part of the national HPEER curriculum covering scholarship and educational research, and in concert with Wednesday, May 14, 2025 VA Research Week 2025, HPEER organized a joint conference with the Center for Health Professions Education at the Uniformed Services University of the Health Sciences (USUHS). This interagency online event included poster sessions and oral presentations from HPEER fellows and students in USUHS certificate and graduate degree programs.

Education scholarship is broad, ranging from descriptions of curricular innovations and works in progress to advanced research using techniques drawn from psychology, sociology, anthropology, economics, and other scientific disciplines. The abstracts presented here summarize some of the work being done by HPEER fellows. Dougherty et al (Boston) described a project to create a primer outlining methodology for conducting and interpreting cost-effectiveness evaluations in the context of proposed HPE innovations. Cohen et al (Cleveland) found reduction in potentially problematic orders in the context of life-sustaining treatment following a multifaceted intervention program. Sorenson (Dublin, Georgia) reported an expanded Tai Chi program that included modifications allowing seated positions for veterans with mobility limitations. Young et al (Dublin) described an interprofessional curriculum to strengthen communication between nurses and social workers in their conversations with women veterans living in rural settings. Misedah-Robinson et al (Houston) showed that a new training program strengthened coordinators’ self-reports of preparedness and confidence in their ability to support veterans who have experienced human trafficking. Tovar et al (Salt Lake City) describe a methodology for using data from the VHA Corporate Data Warehouse to optimize schedules of HPE students assigned to VA clinical rotations. Yanez et al (San Francisco) presented initial observations of learner-centered outcomes following participation in a new multidisciplinary integrative health elective. Resto et al (West Haven) reported that implementation of self-serve kiosks increased distribution of substance use harm reduction resources beyond usual clinical care.

A second joint conference between VA HPEER and USUHS is planned for VA Research Week 2026; we look forward to the abstracts that will be produced by this new cohort of fellows, as well as to the future scholarship and contributions to the field that will be made by alumni of the HPEER Advanced Fellowship.

The original four HPEER Advanced Fellowship sites were established by the Department of Veterans Affairs (VA) Office of Academic Affiliation in 2014, and expanded in 2020 to include 8 sites and a national coordinating center with leadership shared between VA facilities in Houston and White River Junction. The VA invests heavily in training the nation’s healthcare professionals. The mission of HPEER is to develop leaders who can educate, evaluate, and innovate in Health Professions Education for the VA and the nation. All HPEER sites take part in a nationally coordinated curriculum covering topics in curriculum design, learner assessment, leadership, interprofessional education, as well as scholarship and educational research.

As part of the national HPEER curriculum covering scholarship and educational research, and in concert with Wednesday, May 14, 2025 VA Research Week 2025, HPEER organized a joint conference with the Center for Health Professions Education at the Uniformed Services University of the Health Sciences (USUHS). This interagency online event included poster sessions and oral presentations from HPEER fellows and students in USUHS certificate and graduate degree programs.

Education scholarship is broad, ranging from descriptions of curricular innovations and works in progress to advanced research using techniques drawn from psychology, sociology, anthropology, economics, and other scientific disciplines. The abstracts presented here summarize some of the work being done by HPEER fellows. Dougherty et al (Boston) described a project to create a primer outlining methodology for conducting and interpreting cost-effectiveness evaluations in the context of proposed HPE innovations. Cohen et al (Cleveland) found reduction in potentially problematic orders in the context of life-sustaining treatment following a multifaceted intervention program. Sorenson (Dublin, Georgia) reported an expanded Tai Chi program that included modifications allowing seated positions for veterans with mobility limitations. Young et al (Dublin) described an interprofessional curriculum to strengthen communication between nurses and social workers in their conversations with women veterans living in rural settings. Misedah-Robinson et al (Houston) showed that a new training program strengthened coordinators’ self-reports of preparedness and confidence in their ability to support veterans who have experienced human trafficking. Tovar et al (Salt Lake City) describe a methodology for using data from the VHA Corporate Data Warehouse to optimize schedules of HPE students assigned to VA clinical rotations. Yanez et al (San Francisco) presented initial observations of learner-centered outcomes following participation in a new multidisciplinary integrative health elective. Resto et al (West Haven) reported that implementation of self-serve kiosks increased distribution of substance use harm reduction resources beyond usual clinical care.

A second joint conference between VA HPEER and USUHS is planned for VA Research Week 2026; we look forward to the abstracts that will be produced by this new cohort of fellows, as well as to the future scholarship and contributions to the field that will be made by alumni of the HPEER Advanced Fellowship.

What qualities are dermatology programs looking for that may be different from 5 years ago? 

DR. WORSWICK: Every dermatology residency program is different, and as a result, each program is looking for different qualities in its applicants. Overall, I don’t think there has been a huge change in what programs are generally looking for, though. While each program may have a particular trait it values more than another, in general, programs are looking to find residents who will be competent and caring doctors, who work well in teams, and who could be future leaders in our field. 

What are common mistakes you see in dermatology residency interviews, and how can applicants avoid them? 

DR. WORSWICK: Most dermatology applicants are highly accomplished and empathic soon-to-be physicians, so I haven’t found a lot of “mistakes” from this incredible group of people that we have the privilege of interviewing. From time to time, an applicant will lie in an interview, usually out of a desire to appear to be a certain way, and occasionally, they may be nervous and stumble over their words. The former is a really big problem when it happens, and I would recommend that applicants be honest in all their encounters. The latter is not a major problem, and in some cases, might be avoided by lots of practice in advance. 

What types of questions do you recommend applicants ask their interviewers to demonstrate genuine interest in the program? 

DR. WORSWICK: Because of the signaling system, I think that programs assume interest at baseline once an applicant has sent the signal. So, “demonstrating interest” is generally not something I would recommend to applicants during the interview day. It is important for applicants to determine on interview day if a program is a fit for them, so applicants should showcase their unique strengths and skills and find out about what makes any given program different from another. The match generally works well and gets applicants into a program that closely aligns with their strengths and interests. So, think of interview day as your time to figure out how good a fit a program is for you, and not the other way around. 

How can applicants who feel they don't have standout research or leadership credentials differentiate themselves in the interview? 

DR. WORSWICK: While leadership, and less so research experience, is a trait valued highly by most if not all dermatology programs, it is only a part of what an applicant can offer a program. Most programs employ holistic review and consider several factors, probably most commonly grades in medical school, leadership experience, mentorship, teaching, volunteering, Step 2 scores, and letters of recommendation. Any given applicant does not need to excel in all of these. If an applicant has not done a lot of research, they may not match into a research-heavy program, but it doesn’t mean they won’t match. They should determine in which areas they shine and signal the programs that align with those interests/strengths. 

How should applicants discuss nontraditional experiences in a way that adds value rather than raising red flags? 

DR. WORSWICK: In general, my recommendation would be to explain what happened leading up to the change or challenge so that someone reading the application clearly understands the circumstances of the experience, then add value to the description by explaining what was learned and how this might relate to the applicant being a dermatology resident. For example, if a resident took time off for financial reasons and had to work as a medical assitant for a year, a concise description that explains the need for the leave (financial) as well as what value was gained (a year of hands-on patient care experience that validated their choice of going into medicine) could be very helpful.

What qualities are dermatology programs looking for that may be different from 5 years ago? 

DR. WORSWICK: Every dermatology residency program is different, and as a result, each program is looking for different qualities in its applicants. Overall, I don’t think there has been a huge change in what programs are generally looking for, though. While each program may have a particular trait it values more than another, in general, programs are looking to find residents who will be competent and caring doctors, who work well in teams, and who could be future leaders in our field. 

What are common mistakes you see in dermatology residency interviews, and how can applicants avoid them? 

DR. WORSWICK: Most dermatology applicants are highly accomplished and empathic soon-to-be physicians, so I haven’t found a lot of “mistakes” from this incredible group of people that we have the privilege of interviewing. From time to time, an applicant will lie in an interview, usually out of a desire to appear to be a certain way, and occasionally, they may be nervous and stumble over their words. The former is a really big problem when it happens, and I would recommend that applicants be honest in all their encounters. The latter is not a major problem, and in some cases, might be avoided by lots of practice in advance. 

What types of questions do you recommend applicants ask their interviewers to demonstrate genuine interest in the program? 

DR. WORSWICK: Because of the signaling system, I think that programs assume interest at baseline once an applicant has sent the signal. So, “demonstrating interest” is generally not something I would recommend to applicants during the interview day. It is important for applicants to determine on interview day if a program is a fit for them, so applicants should showcase their unique strengths and skills and find out about what makes any given program different from another. The match generally works well and gets applicants into a program that closely aligns with their strengths and interests. So, think of interview day as your time to figure out how good a fit a program is for you, and not the other way around. 

How can applicants who feel they don't have standout research or leadership credentials differentiate themselves in the interview? 

DR. WORSWICK: While leadership, and less so research experience, is a trait valued highly by most if not all dermatology programs, it is only a part of what an applicant can offer a program. Most programs employ holistic review and consider several factors, probably most commonly grades in medical school, leadership experience, mentorship, teaching, volunteering, Step 2 scores, and letters of recommendation. Any given applicant does not need to excel in all of these. If an applicant has not done a lot of research, they may not match into a research-heavy program, but it doesn’t mean they won’t match. They should determine in which areas they shine and signal the programs that align with those interests/strengths. 

How should applicants discuss nontraditional experiences in a way that adds value rather than raising red flags? 

DR. WORSWICK: In general, my recommendation would be to explain what happened leading up to the change or challenge so that someone reading the application clearly understands the circumstances of the experience, then add value to the description by explaining what was learned and how this might relate to the applicant being a dermatology resident. For example, if a resident took time off for financial reasons and had to work as a medical assitant for a year, a concise description that explains the need for the leave (financial) as well as what value was gained (a year of hands-on patient care experience that validated their choice of going into medicine) could be very helpful.

What qualities are dermatology programs looking for that may be different from 5 years ago? 

DR. WORSWICK: Every dermatology residency program is different, and as a result, each program is looking for different qualities in its applicants. Overall, I don’t think there has been a huge change in what programs are generally looking for, though. While each program may have a particular trait it values more than another, in general, programs are looking to find residents who will be competent and caring doctors, who work well in teams, and who could be future leaders in our field. 

What are common mistakes you see in dermatology residency interviews, and how can applicants avoid them? 

DR. WORSWICK: Most dermatology applicants are highly accomplished and empathic soon-to-be physicians, so I haven’t found a lot of “mistakes” from this incredible group of people that we have the privilege of interviewing. From time to time, an applicant will lie in an interview, usually out of a desire to appear to be a certain way, and occasionally, they may be nervous and stumble over their words. The former is a really big problem when it happens, and I would recommend that applicants be honest in all their encounters. The latter is not a major problem, and in some cases, might be avoided by lots of practice in advance. 

What types of questions do you recommend applicants ask their interviewers to demonstrate genuine interest in the program? 

DR. WORSWICK: Because of the signaling system, I think that programs assume interest at baseline once an applicant has sent the signal. So, “demonstrating interest” is generally not something I would recommend to applicants during the interview day. It is important for applicants to determine on interview day if a program is a fit for them, so applicants should showcase their unique strengths and skills and find out about what makes any given program different from another. The match generally works well and gets applicants into a program that closely aligns with their strengths and interests. So, think of interview day as your time to figure out how good a fit a program is for you, and not the other way around. 

How can applicants who feel they don't have standout research or leadership credentials differentiate themselves in the interview? 

DR. WORSWICK: While leadership, and less so research experience, is a trait valued highly by most if not all dermatology programs, it is only a part of what an applicant can offer a program. Most programs employ holistic review and consider several factors, probably most commonly grades in medical school, leadership experience, mentorship, teaching, volunteering, Step 2 scores, and letters of recommendation. Any given applicant does not need to excel in all of these. If an applicant has not done a lot of research, they may not match into a research-heavy program, but it doesn’t mean they won’t match. They should determine in which areas they shine and signal the programs that align with those interests/strengths. 

How should applicants discuss nontraditional experiences in a way that adds value rather than raising red flags? 

DR. WORSWICK: In general, my recommendation would be to explain what happened leading up to the change or challenge so that someone reading the application clearly understands the circumstances of the experience, then add value to the description by explaining what was learned and how this might relate to the applicant being a dermatology resident. For example, if a resident took time off for financial reasons and had to work as a medical assitant for a year, a concise description that explains the need for the leave (financial) as well as what value was gained (a year of hands-on patient care experience that validated their choice of going into medicine) could be very helpful.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Pediatric alopecia areata (AA) is a chronic autoimmune disease of the hair follicles characterized by nonscarring hair loss. Its incidence in children in the United States ranges from 13.6 to 33.5 per 100,000 person-years, with a prevalence of 0.04% to 0.11%.¹ Alopecia areata has important effects on quality of life, particularly in children. Hair loss at an early age can decrease participation in school, sports, and extracurricular activities² and is associated with increased rates of comorbid anxiety and depression.³ Families also experience psychosocial stress, often comparable to other chronic pediatric illnesses.⁴ Thus, management requires not only medical therapy but also psychosocial support and school-based accommodations.

Systemic therapies for treatment of AA in adolescents and adults are increasingly available, including US Food and Drug Administration (FDA)–approved Janus kinase (JAK) inhibitors such as baricitinib, deuruxolitinib (for adults), and ritlecitinib (for adolescents and adults); however, no systemic therapies have been approved by the FDA for children younger than 12 years. The therapeutic gap is most acute for those aged 6 to 11 years, for whom the psychosocial burden is high but treatment options are limited.³

This article highlights options and strategies for managing AA in children aged 6 to 11 years, emphasizing supportive and psychosocial care (including camouflage techniques), topical therapies, and off-label systemic approaches.

Supportive and Psychosocial Care

Treatment of AA in children extends beyond the affected child to include parents, caregivers, and even school staff (eg, teachers, principals, nurses).⁴ Disease-specific organizations such as the National Alopecia Areata Foundation ­(naaf.org) and the Children’s Alopecia Project (childrensalopeciaproject.org) provide ­education, support groups, and advocacy resources. These organizations assist families in navigating school accommodations, including Section 504 plans that may allow children with AA to wear hats in school to mitigate stigma. Additional resources include handouts for teachers and school nurses developed by the Society for Pediatric Dermatology.⁵

Psychological support for these patients is critical. Many children benefit from seeing a psychologist, particularly if anxiety, depression, and/or bullying is present.³ In clinics without embedded psychology services, dermatologists should maintain referral lists or encourage families to seek guidance from their pediatrician.

Camouflage techniques can help children cope with visible hair loss. Wigs and hairpieces are available free of charge through charitable organizations for patients younger than 17; however, young children often find adhesives uncomfortable, and they will not wear nonadherent wigs for long periods of time. Alternatives include soft hats, bonnets, scarves, and beanies. For partial hair loss, root concealers, scalp powders, or hair mascara can be useful. Temporary eyebrow tattoos are a good cosmetic approach, whereas microblading generally is not advised in children younger than 12 due to procedural risks including pain.

Topical Therapies

Topical agents remain the mainstay of treatment for AA in children aged 6 to 11 years. Potent class 1 or class 2 topical corticosteroids commonly are used, sometimes in combination with calcineurin inhibitors or topical minoxidil. Off-label compounded topical JAK inhibitors also have been tried in this population and may be helpful for eyebrow hair loss,⁶ though data on their efficacy for scalp AA are mixed.⁷ Intralesional corticosteroid injections, effective in adolescents and adults, generally are poorly tolerated by younger children and may cause considerable distress. Contact immunotherapy with squaric acid dibutyl ester or anthralin can be considered, but these agents are designed to elicit irritation, which may be intolerable for young children.⁸ Shared decision-making with families is essential to balance efficacy, tolerability, and treatment burden.

Systemic Therapies

Systemic therapy generally is reserved for children with extensive or refractory AA. Low-dose oral minoxidil is emerging as an off-label option. One systematic review reported that low-dose oral minoxidil was well tolerated in pediatric patients with minimal adverse effects.⁹ Doses of 0.01 to 0.02 mg/kg/d are reasonable starting points, achieved by cutting tablets or compounding oral solutions.¹⁰

In children with AA and concurrent atopic dermatitis, dupilumab may offer dual benefit. A real-world observational study demonstrated hair regrowth in pediatric patients with AA treated with dupilumab.¹¹ Immunosuppressive options such as low-dose methotrexate or pulse corticosteroids (dexamethasone or prednisolone) also may be considered, although use of these agents requires careful monitoring due to increased risk for infection, clinically significant blood count and liver enzyme changes, and metabolic adverse effects related to long-term use of corticosteroids.

Clinical trials of JAK inhibitors in children aged 6 to 11 years are anticipated to begin in late 2025. Until then, off-label use of ritlecitinib, baricitinib, tofacitinib, or other JAK inhibitors may be considered in select cases with considerable disease burden and quality-of-life impairment following thorough discussion with the patient and their caregivers. Currently available pediatric data show few serious adverse events in children—the most common included upper respiratory infections (nasopharyngitis), acne, and headaches—but long-term risks remain unknown. Dosing challenges also exist for children who cannot swallow pills; currently ritlecitinib is available only as a capsule that cannot be opened while other JAK inhibitors are available in more accessible forms (baricitinib can be crushed and dissolved, and tofacitinib is available in liquid formulation for other pediatric indications). Insurance coverage is a major barrier, as these therapies are not FDA approved for AA in this age group.

Final Thoughts

Alopecia areata in children aged 6 to 11 years presents unique therapeutic challenges. While highly effective systemic therapies exist for older patients, younger children have limited options. For the 6-to-11 age group, management strategies should prioritize psychosocial support, topical therapy, and low-burden systemic alternatives such as low-dose oral minoxidil. Family education, school-based accommodations, and access to camouflage techniques are integral to holistic care. The commencement of pediatric clinical trials for JAK inhibitors offers hope for more robust treatment strategies in the near future. In the meantime, clinicians must engage in shared decision-making, tailoring therapy to the child’s disease severity, emotional well-being, and family priorities.

Pediatric alopecia areata (AA) is a chronic autoimmune disease of the hair follicles characterized by nonscarring hair loss. Its incidence in children in the United States ranges from 13.6 to 33.5 per 100,000 person-years, with a prevalence of 0.04% to 0.11%.¹ Alopecia areata has important effects on quality of life, particularly in children. Hair loss at an early age can decrease participation in school, sports, and extracurricular activities² and is associated with increased rates of comorbid anxiety and depression.³ Families also experience psychosocial stress, often comparable to other chronic pediatric illnesses.⁴ Thus, management requires not only medical therapy but also psychosocial support and school-based accommodations.

Systemic therapies for treatment of AA in adolescents and adults are increasingly available, including US Food and Drug Administration (FDA)–approved Janus kinase (JAK) inhibitors such as baricitinib, deuruxolitinib (for adults), and ritlecitinib (for adolescents and adults); however, no systemic therapies have been approved by the FDA for children younger than 12 years. The therapeutic gap is most acute for those aged 6 to 11 years, for whom the psychosocial burden is high but treatment options are limited.³

This article highlights options and strategies for managing AA in children aged 6 to 11 years, emphasizing supportive and psychosocial care (including camouflage techniques), topical therapies, and off-label systemic approaches.

Supportive and Psychosocial Care

Treatment of AA in children extends beyond the affected child to include parents, caregivers, and even school staff (eg, teachers, principals, nurses).⁴ Disease-specific organizations such as the National Alopecia Areata Foundation ­(naaf.org) and the Children’s Alopecia Project (childrensalopeciaproject.org) provide ­education, support groups, and advocacy resources. These organizations assist families in navigating school accommodations, including Section 504 plans that may allow children with AA to wear hats in school to mitigate stigma. Additional resources include handouts for teachers and school nurses developed by the Society for Pediatric Dermatology.⁵

Psychological support for these patients is critical. Many children benefit from seeing a psychologist, particularly if anxiety, depression, and/or bullying is present.³ In clinics without embedded psychology services, dermatologists should maintain referral lists or encourage families to seek guidance from their pediatrician.

Camouflage techniques can help children cope with visible hair loss. Wigs and hairpieces are available free of charge through charitable organizations for patients younger than 17; however, young children often find adhesives uncomfortable, and they will not wear nonadherent wigs for long periods of time. Alternatives include soft hats, bonnets, scarves, and beanies. For partial hair loss, root concealers, scalp powders, or hair mascara can be useful. Temporary eyebrow tattoos are a good cosmetic approach, whereas microblading generally is not advised in children younger than 12 due to procedural risks including pain.

Topical Therapies

Topical agents remain the mainstay of treatment for AA in children aged 6 to 11 years. Potent class 1 or class 2 topical corticosteroids commonly are used, sometimes in combination with calcineurin inhibitors or topical minoxidil. Off-label compounded topical JAK inhibitors also have been tried in this population and may be helpful for eyebrow hair loss,⁶ though data on their efficacy for scalp AA are mixed.⁷ Intralesional corticosteroid injections, effective in adolescents and adults, generally are poorly tolerated by younger children and may cause considerable distress. Contact immunotherapy with squaric acid dibutyl ester or anthralin can be considered, but these agents are designed to elicit irritation, which may be intolerable for young children.⁸ Shared decision-making with families is essential to balance efficacy, tolerability, and treatment burden.

Systemic Therapies

Systemic therapy generally is reserved for children with extensive or refractory AA. Low-dose oral minoxidil is emerging as an off-label option. One systematic review reported that low-dose oral minoxidil was well tolerated in pediatric patients with minimal adverse effects.⁹ Doses of 0.01 to 0.02 mg/kg/d are reasonable starting points, achieved by cutting tablets or compounding oral solutions.¹⁰

In children with AA and concurrent atopic dermatitis, dupilumab may offer dual benefit. A real-world observational study demonstrated hair regrowth in pediatric patients with AA treated with dupilumab.¹¹ Immunosuppressive options such as low-dose methotrexate or pulse corticosteroids (dexamethasone or prednisolone) also may be considered, although use of these agents requires careful monitoring due to increased risk for infection, clinically significant blood count and liver enzyme changes, and metabolic adverse effects related to long-term use of corticosteroids.

Clinical trials of JAK inhibitors in children aged 6 to 11 years are anticipated to begin in late 2025. Until then, off-label use of ritlecitinib, baricitinib, tofacitinib, or other JAK inhibitors may be considered in select cases with considerable disease burden and quality-of-life impairment following thorough discussion with the patient and their caregivers. Currently available pediatric data show few serious adverse events in children—the most common included upper respiratory infections (nasopharyngitis), acne, and headaches—but long-term risks remain unknown. Dosing challenges also exist for children who cannot swallow pills; currently ritlecitinib is available only as a capsule that cannot be opened while other JAK inhibitors are available in more accessible forms (baricitinib can be crushed and dissolved, and tofacitinib is available in liquid formulation for other pediatric indications). Insurance coverage is a major barrier, as these therapies are not FDA approved for AA in this age group.

Final Thoughts

Alopecia areata in children aged 6 to 11 years presents unique therapeutic challenges. While highly effective systemic therapies exist for older patients, younger children have limited options. For the 6-to-11 age group, management strategies should prioritize psychosocial support, topical therapy, and low-burden systemic alternatives such as low-dose oral minoxidil. Family education, school-based accommodations, and access to camouflage techniques are integral to holistic care. The commencement of pediatric clinical trials for JAK inhibitors offers hope for more robust treatment strategies in the near future. In the meantime, clinicians must engage in shared decision-making, tailoring therapy to the child’s disease severity, emotional well-being, and family priorities.

Pediatric alopecia areata (AA) is a chronic autoimmune disease of the hair follicles characterized by nonscarring hair loss. Its incidence in children in the United States ranges from 13.6 to 33.5 per 100,000 person-years, with a prevalence of 0.04% to 0.11%.¹ Alopecia areata has important effects on quality of life, particularly in children. Hair loss at an early age can decrease participation in school, sports, and extracurricular activities² and is associated with increased rates of comorbid anxiety and depression.³ Families also experience psychosocial stress, often comparable to other chronic pediatric illnesses.⁴ Thus, management requires not only medical therapy but also psychosocial support and school-based accommodations.

Systemic therapies for treatment of AA in adolescents and adults are increasingly available, including US Food and Drug Administration (FDA)–approved Janus kinase (JAK) inhibitors such as baricitinib, deuruxolitinib (for adults), and ritlecitinib (for adolescents and adults); however, no systemic therapies have been approved by the FDA for children younger than 12 years. The therapeutic gap is most acute for those aged 6 to 11 years, for whom the psychosocial burden is high but treatment options are limited.³

This article highlights options and strategies for managing AA in children aged 6 to 11 years, emphasizing supportive and psychosocial care (including camouflage techniques), topical therapies, and off-label systemic approaches.

Supportive and Psychosocial Care

Treatment of AA in children extends beyond the affected child to include parents, caregivers, and even school staff (eg, teachers, principals, nurses).⁴ Disease-specific organizations such as the National Alopecia Areata Foundation ­(naaf.org) and the Children’s Alopecia Project (childrensalopeciaproject.org) provide ­education, support groups, and advocacy resources. These organizations assist families in navigating school accommodations, including Section 504 plans that may allow children with AA to wear hats in school to mitigate stigma. Additional resources include handouts for teachers and school nurses developed by the Society for Pediatric Dermatology.⁵

Psychological support for these patients is critical. Many children benefit from seeing a psychologist, particularly if anxiety, depression, and/or bullying is present.³ In clinics without embedded psychology services, dermatologists should maintain referral lists or encourage families to seek guidance from their pediatrician.

Camouflage techniques can help children cope with visible hair loss. Wigs and hairpieces are available free of charge through charitable organizations for patients younger than 17; however, young children often find adhesives uncomfortable, and they will not wear nonadherent wigs for long periods of time. Alternatives include soft hats, bonnets, scarves, and beanies. For partial hair loss, root concealers, scalp powders, or hair mascara can be useful. Temporary eyebrow tattoos are a good cosmetic approach, whereas microblading generally is not advised in children younger than 12 due to procedural risks including pain.

Topical Therapies

Topical agents remain the mainstay of treatment for AA in children aged 6 to 11 years. Potent class 1 or class 2 topical corticosteroids commonly are used, sometimes in combination with calcineurin inhibitors or topical minoxidil. Off-label compounded topical JAK inhibitors also have been tried in this population and may be helpful for eyebrow hair loss,⁶ though data on their efficacy for scalp AA are mixed.⁷ Intralesional corticosteroid injections, effective in adolescents and adults, generally are poorly tolerated by younger children and may cause considerable distress. Contact immunotherapy with squaric acid dibutyl ester or anthralin can be considered, but these agents are designed to elicit irritation, which may be intolerable for young children.⁸ Shared decision-making with families is essential to balance efficacy, tolerability, and treatment burden.

Systemic Therapies

Systemic therapy generally is reserved for children with extensive or refractory AA. Low-dose oral minoxidil is emerging as an off-label option. One systematic review reported that low-dose oral minoxidil was well tolerated in pediatric patients with minimal adverse effects.⁹ Doses of 0.01 to 0.02 mg/kg/d are reasonable starting points, achieved by cutting tablets or compounding oral solutions.¹⁰

In children with AA and concurrent atopic dermatitis, dupilumab may offer dual benefit. A real-world observational study demonstrated hair regrowth in pediatric patients with AA treated with dupilumab.¹¹ Immunosuppressive options such as low-dose methotrexate or pulse corticosteroids (dexamethasone or prednisolone) also may be considered, although use of these agents requires careful monitoring due to increased risk for infection, clinically significant blood count and liver enzyme changes, and metabolic adverse effects related to long-term use of corticosteroids.

Clinical trials of JAK inhibitors in children aged 6 to 11 years are anticipated to begin in late 2025. Until then, off-label use of ritlecitinib, baricitinib, tofacitinib, or other JAK inhibitors may be considered in select cases with considerable disease burden and quality-of-life impairment following thorough discussion with the patient and their caregivers. Currently available pediatric data show few serious adverse events in children—the most common included upper respiratory infections (nasopharyngitis), acne, and headaches—but long-term risks remain unknown. Dosing challenges also exist for children who cannot swallow pills; currently ritlecitinib is available only as a capsule that cannot be opened while other JAK inhibitors are available in more accessible forms (baricitinib can be crushed and dissolved, and tofacitinib is available in liquid formulation for other pediatric indications). Insurance coverage is a major barrier, as these therapies are not FDA approved for AA in this age group.

Final Thoughts

Alopecia areata in children aged 6 to 11 years presents unique therapeutic challenges. While highly effective systemic therapies exist for older patients, younger children have limited options. For the 6-to-11 age group, management strategies should prioritize psychosocial support, topical therapy, and low-burden systemic alternatives such as low-dose oral minoxidil. Family education, school-based accommodations, and access to camouflage techniques are integral to holistic care. The commencement of pediatric clinical trials for JAK inhibitors offers hope for more robust treatment strategies in the near future. In the meantime, clinicians must engage in shared decision-making, tailoring therapy to the child’s disease severity, emotional well-being, and family priorities.

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me (tjudy@wustl.edu) or Danielle Kiefer (dkiefer@gastro.org), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me (tjudy@wustl.edu) or Danielle Kiefer (dkiefer@gastro.org), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me (tjudy@wustl.edu) or Danielle Kiefer (dkiefer@gastro.org), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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