Article

To the Editor:

Female pattern hair loss (FPHL), or androgenetic alopecia (AGA), is the most common form of alopecia worldwide and is characterized by a reduction of hair follicles spent in the anagen phase of growth as well as progressive terminal hair loss.¹ It is caused by an excessive response to androgens and leads to the characteristic distribution of hair loss in both sexes. Studies have shown a notable association between AGA and markers of metabolic syndrome such as dyslipidemia, insulin resistance, and obesity in age- and sex-matched controls.^2,3 However, research describing the relationship between AGA severity and these markers is scarce.

To understand the relationship between FPHL severity and abnormal cholesterol levels, we performed a retrospective chart review of patients diagnosed with FPHL at a specialty alopecia clinic from June 2022 to December 2022. Patient age and age at onset of FPHL were collected. The severity of FPHL was measured using the Sinclair scale (score range, 1–5) and unidentifiable patient photographs. Laboratory values were collected; abnormal cholesterol was defined by the American Heart Association as having a low-density lipoprotein cholesterol (LDL-C) level of 100 mg/dL or higher.⁴ Finally, data on medication use were noted to understand patient treatment status (Table).

We identified 54 female patients with FPHL with an average age of 59 years (range, 34–80 years). Thirty-three females (61.11%) had a normal LDL-C level and 21 (38.89%) had an abnormal level. The mean (SD) LDL-C level was 66.02 (15.20) mg/dL (range, 29–92 mg/dL) in the group with normal levels and 138.81 (29.90) mg/dL (range, 100–193 mg/dL) in the group with abnormal levels. Patients with abnormal LDL-C had significantly higher Sinclair scale scores compared to those with normal levels (2.43 vs 1.91; P=.01). There were no significant differences in patient age (58.71 vs 59.70 years; P=.39), age at onset of AGA (47.75 vs 47.65 years; P=.49), history of polycystic ovary syndrome (9.52% vs 6.06%; P=.64), or statin use (38.09% vs 36.36%; P=.89) between patients with abnormal and normal LDL-C levels, respectively. There also were no significant differences in ferritin (96.42 vs 91.54 ng/mL; P=.40), vitamin D (42.35 vs 48.96 ng/mL; P=.09), or hemoglobin A_1c levels (5.60 ng/mL vs 5.38 ng/mL; P=.06)—variables that could have confounded this relationship. Triglycerides were within reference range in both groups (121.36 vs 116.16 mg/dL; P=.32), while total cholesterol was mildly elevated in both groups but not significantly different (213.19 vs 201.21 mg/dL; P=.13). Use of hair loss treatments such as topical minoxidil (14.29% vs 21.21%; P=.53), oral low-dose minoxidil (57.14% vs 66.67%; P=.48), oral spironolactone (47.62% vs 57.58%; P=.47), and platelet-rich plasma injections (47.62% vs 27.27%; P=.90) were not significantly different across both groups.

The data suggest a significant (P<.05) association between abnormal LDL-C and hair loss severity in FPHL patients. Our study was limited by its small sample size and lack of causality; however, it coincides with and reiterates the findings established in the literature. The mechanism of the association between hyperlipidemia and AGA is not well understood but is thought to stem from the homology between cholesterol and androgens. Increased cholesterol release from dermal adipocytes and subsequent absorption into hair follicle cell populations may increase hair follicle steroidogenesis, thereby accelerating the anagen-catagen transition and inducing AGA. Alternatively, impaired cholesterol homeostasis may disrupt normal hair follicle cycling by interrupting signaling pathways in follicle proliferation and differentiation.⁵ Adequate control and monitoring of LDL-C levels may be important, particularly in patients with more severe FPHL.

To the Editor:

Female pattern hair loss (FPHL), or androgenetic alopecia (AGA), is the most common form of alopecia worldwide and is characterized by a reduction of hair follicles spent in the anagen phase of growth as well as progressive terminal hair loss.¹ It is caused by an excessive response to androgens and leads to the characteristic distribution of hair loss in both sexes. Studies have shown a notable association between AGA and markers of metabolic syndrome such as dyslipidemia, insulin resistance, and obesity in age- and sex-matched controls.^2,3 However, research describing the relationship between AGA severity and these markers is scarce.

To understand the relationship between FPHL severity and abnormal cholesterol levels, we performed a retrospective chart review of patients diagnosed with FPHL at a specialty alopecia clinic from June 2022 to December 2022. Patient age and age at onset of FPHL were collected. The severity of FPHL was measured using the Sinclair scale (score range, 1–5) and unidentifiable patient photographs. Laboratory values were collected; abnormal cholesterol was defined by the American Heart Association as having a low-density lipoprotein cholesterol (LDL-C) level of 100 mg/dL or higher.⁴ Finally, data on medication use were noted to understand patient treatment status (Table).

We identified 54 female patients with FPHL with an average age of 59 years (range, 34–80 years). Thirty-three females (61.11%) had a normal LDL-C level and 21 (38.89%) had an abnormal level. The mean (SD) LDL-C level was 66.02 (15.20) mg/dL (range, 29–92 mg/dL) in the group with normal levels and 138.81 (29.90) mg/dL (range, 100–193 mg/dL) in the group with abnormal levels. Patients with abnormal LDL-C had significantly higher Sinclair scale scores compared to those with normal levels (2.43 vs 1.91; P=.01). There were no significant differences in patient age (58.71 vs 59.70 years; P=.39), age at onset of AGA (47.75 vs 47.65 years; P=.49), history of polycystic ovary syndrome (9.52% vs 6.06%; P=.64), or statin use (38.09% vs 36.36%; P=.89) between patients with abnormal and normal LDL-C levels, respectively. There also were no significant differences in ferritin (96.42 vs 91.54 ng/mL; P=.40), vitamin D (42.35 vs 48.96 ng/mL; P=.09), or hemoglobin A_1c levels (5.60 ng/mL vs 5.38 ng/mL; P=.06)—variables that could have confounded this relationship. Triglycerides were within reference range in both groups (121.36 vs 116.16 mg/dL; P=.32), while total cholesterol was mildly elevated in both groups but not significantly different (213.19 vs 201.21 mg/dL; P=.13). Use of hair loss treatments such as topical minoxidil (14.29% vs 21.21%; P=.53), oral low-dose minoxidil (57.14% vs 66.67%; P=.48), oral spironolactone (47.62% vs 57.58%; P=.47), and platelet-rich plasma injections (47.62% vs 27.27%; P=.90) were not significantly different across both groups.

The data suggest a significant (P<.05) association between abnormal LDL-C and hair loss severity in FPHL patients. Our study was limited by its small sample size and lack of causality; however, it coincides with and reiterates the findings established in the literature. The mechanism of the association between hyperlipidemia and AGA is not well understood but is thought to stem from the homology between cholesterol and androgens. Increased cholesterol release from dermal adipocytes and subsequent absorption into hair follicle cell populations may increase hair follicle steroidogenesis, thereby accelerating the anagen-catagen transition and inducing AGA. Alternatively, impaired cholesterol homeostasis may disrupt normal hair follicle cycling by interrupting signaling pathways in follicle proliferation and differentiation.⁵ Adequate control and monitoring of LDL-C levels may be important, particularly in patients with more severe FPHL.

To the Editor:

Female pattern hair loss (FPHL), or androgenetic alopecia (AGA), is the most common form of alopecia worldwide and is characterized by a reduction of hair follicles spent in the anagen phase of growth as well as progressive terminal hair loss.¹ It is caused by an excessive response to androgens and leads to the characteristic distribution of hair loss in both sexes. Studies have shown a notable association between AGA and markers of metabolic syndrome such as dyslipidemia, insulin resistance, and obesity in age- and sex-matched controls.^2,3 However, research describing the relationship between AGA severity and these markers is scarce.

To understand the relationship between FPHL severity and abnormal cholesterol levels, we performed a retrospective chart review of patients diagnosed with FPHL at a specialty alopecia clinic from June 2022 to December 2022. Patient age and age at onset of FPHL were collected. The severity of FPHL was measured using the Sinclair scale (score range, 1–5) and unidentifiable patient photographs. Laboratory values were collected; abnormal cholesterol was defined by the American Heart Association as having a low-density lipoprotein cholesterol (LDL-C) level of 100 mg/dL or higher.⁴ Finally, data on medication use were noted to understand patient treatment status (Table).

We identified 54 female patients with FPHL with an average age of 59 years (range, 34–80 years). Thirty-three females (61.11%) had a normal LDL-C level and 21 (38.89%) had an abnormal level. The mean (SD) LDL-C level was 66.02 (15.20) mg/dL (range, 29–92 mg/dL) in the group with normal levels and 138.81 (29.90) mg/dL (range, 100–193 mg/dL) in the group with abnormal levels. Patients with abnormal LDL-C had significantly higher Sinclair scale scores compared to those with normal levels (2.43 vs 1.91; P=.01). There were no significant differences in patient age (58.71 vs 59.70 years; P=.39), age at onset of AGA (47.75 vs 47.65 years; P=.49), history of polycystic ovary syndrome (9.52% vs 6.06%; P=.64), or statin use (38.09% vs 36.36%; P=.89) between patients with abnormal and normal LDL-C levels, respectively. There also were no significant differences in ferritin (96.42 vs 91.54 ng/mL; P=.40), vitamin D (42.35 vs 48.96 ng/mL; P=.09), or hemoglobin A_1c levels (5.60 ng/mL vs 5.38 ng/mL; P=.06)—variables that could have confounded this relationship. Triglycerides were within reference range in both groups (121.36 vs 116.16 mg/dL; P=.32), while total cholesterol was mildly elevated in both groups but not significantly different (213.19 vs 201.21 mg/dL; P=.13). Use of hair loss treatments such as topical minoxidil (14.29% vs 21.21%; P=.53), oral low-dose minoxidil (57.14% vs 66.67%; P=.48), oral spironolactone (47.62% vs 57.58%; P=.47), and platelet-rich plasma injections (47.62% vs 27.27%; P=.90) were not significantly different across both groups.

The data suggest a significant (P<.05) association between abnormal LDL-C and hair loss severity in FPHL patients. Our study was limited by its small sample size and lack of causality; however, it coincides with and reiterates the findings established in the literature. The mechanism of the association between hyperlipidemia and AGA is not well understood but is thought to stem from the homology between cholesterol and androgens. Increased cholesterol release from dermal adipocytes and subsequent absorption into hair follicle cell populations may increase hair follicle steroidogenesis, thereby accelerating the anagen-catagen transition and inducing AGA. Alternatively, impaired cholesterol homeostasis may disrupt normal hair follicle cycling by interrupting signaling pathways in follicle proliferation and differentiation.⁵ Adequate control and monitoring of LDL-C levels may be important, particularly in patients with more severe FPHL.

Acne vulgaris, or acne, is a highly common inflammatory skin disorder affecting up to 85% of the population, and it constitutes the most commonly presenting chief concern in routine dermatology practice.¹ Older teenagers and young adults are most often affected by acne.² Although acne generally is more common in males, adult-onset acne occurs more frequently in women.^2,3 Black and Hispanic women are at higher risk for acne compared to those of Asian, White, or Continental Indian descent.⁴ As such, acne is a common concern in all women of childbearing age.

Concerns for maternal and fetal safety are important therapeutic considerations, especially because hormonal and physiologic changes in pregnancy can lead to onset of inflammatory acne lesions, particularly during the second and third trimesters.⁵ Female patients younger than 25 years; with a higher body mass index, prior irregular menstruation, or polycystic ovary syndrome; or those experiencing their first pregnancy are thought to be more commonly affected.^5-7 In fact, acne affects up to 43% of pregnant women, and lesions typically extend beyond the face to involve the trunk.^6,8-10 Importantly, one-third of women with a history of acne experience symptom relapse after disease-free periods, while two-thirds of those with ongoing disease experience symptom deterioration during pregnancy.¹⁰ Although acne is not a life-threatening condition, it has a well-documented, detrimental impact on social, emotional, and psychological well-being, namely self-perception, social interactions, quality-of-life scores, depression, and anxiety.¹¹

Therefore, safe and effective treatment of pregnant women is of paramount importance. Because pregnant women are not included in clinical trials, there is a paucity of medication safety data, further augmented by inefficient access to available information. The US Food and Drug Administration (FDA) pregnancy safety categories were updated in 2015, letting go of the traditional A, B, C, D, and X categories.¹² The Table reviews the current pregnancy classification system. In this narrative review, we summarize the most recent available data and recommendations on the safety and efficacy of acne treatment during pregnancy.

Topical Treatments for Acne

Benzoyl Peroxide—Benzoyl peroxide commonly is used as first-line therapy alone or in combination with other agents for the treatment of mild to moderate acne.¹³ It is safe for use during pregnancy.¹⁴ Although the medication is systemically absorbed, it undergoes complete metabolism to benzoic acid, a commonly used food additive.^15,16 Benzoic acid has low bioavailability, as it gets rapidly metabolized by the kidneys; therefore, benzoyl peroxide is unlikely to reach clinically significant levels in the maternal circulation and consequently the fetal circulation. Additionally, it has a low risk for causing congenital malformations.¹⁷

Salicylic Acid—For mild to moderate acne, salicylic acid is a second-line agent that likely is safe for use by pregnant women at low concentrations and over limited body surface areas.^14,18,19 There is minimal systemic absorption of the drug.²⁰ Additionally, aspirin, which is broken down in the body into salicylic acid, is used in low doses for the treatment of pre-eclampsia during pregnancy.²¹

Dapsone—The use of dapsone gel 5% as a second-line agent has shown efficacy for mild to moderate acne.²² The oral formulation, commonly used for malaria and leprosy prophylaxis, has failed to show associated fetal toxicity or congenital anomalies.^23,24 It also has been used as a first-line treatment for dermatitis herpetiformis in pregnancy.²⁵ Although the medication likely is safe, it is better to minimize its use during the third trimester to reduce the theoretical risk for hyperbilirubinemia in the neonate.^17,26-29

Azelaic Acid—Azelaic acid effectively targets noninflammatory and inflammatory acne and generally is well tolerated, harboring a good safety profile.³⁰ Topical 20% azelaic acid has localized antibacterial and comedolytic effects and is safe for use during pregnancy.^31,32

Glycolic Acid—Limited data exist on the safety of glycolic acid during pregnancy. In vitro studies have shown up to 27% systemic absorption depending on pH, concentration, and duration of application.³³ Animal reproductive studies involving rats have shown fetal multisystem malformations and developmental abnormalities with oral administration of glycolic acid at doses far exceeding those used in humans.³⁴ Although no human reproductive studies exist, topical glycolic acid is unlikely to reach the developing fetus in notable amounts, and the medication is likely safe for use.^17,35

Clindamycin—Topical clindamycin phosphate is an effective and well-tolerated agent for the treatment of mild to moderate acne.³⁶ Its systemic absorption is minimal, and it is considered safe for use during all trimesters of pregnancy.^{14,17,26,27,35,37}

Erythromycin—Topical erythromycin is another commonly prescribed topical antibiotic used to target mild to moderate acne. However, its use recently has been associated with a decrease in efficacy secondary to the rise of antibacterial resistance in the community.^38-40 Nevertheless, it remains a safe treatment for use during all trimesters of pregnancy.^{14,17,26,27,35,37}

Topical Retinoids—Vitamin A derivatives (also known as retinoids) are the mainstay for the treatment of mild to moderate acne. Limited data exist regarding pregnancy outcomes after in utero exposure.⁴¹ A rare case report suggested topical tretinoin has been associated with fetal otocerebral anomalies.⁴² For tazarotene, teratogenic effects were seen in animal reproductive studies at doses exceeding maximum recommended human doses.^41,43 However, a large meta-analysis failed to find a clear risk for increased congenital malformations, spontaneous abortions, stillbirth, elective termination of pregnancy, low birthweight, or prematurity following first-trimester exposure to topical retinoids.⁴⁴ As the level of exposure that could lead to teratogenicity in humans is unknown, avoidance of both tretinoin and tazarotene is recommended in pregnant women.^41,45 Nevertheless, women inadvertently exposed should be reassured.⁴⁴

Conversely, adapalene has been associated with 1 case of anophthalmia and agenesis of the optic chiasma in a fetus following exposure until 13 weeks’ gestation.⁴⁶ However, a large, open-label trial prior to the patient transitioning from adapalene to over-the-counter treatment showed that the drug harbors a large and reassuring margin of safety and no risk for teratogenicity in a maximal usage trial and Pregnancy Safety Review.⁴⁷ Therefore, adapalene gel 0.1% is a safe and effective medication for the treatment of acne in a nonprescription environment and does not pose harm to the fetus.

Clascoterone—Clascoterone is a novel topical antiandrogenic drug approved for the treatment of hormonal and inflammatory moderate to severe acne.^48-51 Human reproductive data are limited to 1 case of pregnancy that occurred during phase 3 trial investigations, and no adverse outcomes were reported.⁵¹ Minimal systemic absorption follows topical use.⁵² Nonetheless, dose-independent malformations were reported in animal reproductive studies.⁵³ As such, it remains better to avoid the use of clascoterone during pregnancy pending further safety data.

Minocycline Foam—Minocycline foam 4% is approved to treat inflammatory lesions of nonnodular moderate to severe acne in patients 9 years and older.⁵⁴ Systemic absorption is minimal, and the drug has limited bioavailability with minimal systemic accumulation in the patient’s serum.⁵⁵ Given this information, it is unlikely that topical minocycline will reach notable levels in the fetal serum or harbor teratogenic effects, as seen with the oral formulation.⁵⁶ However, it may be best to avoid its use during the second and third trimesters given the potential risk for tooth discoloration in the fetus.^57,58

Systemic Treatments for Acne

Isotretinoin—Isotretinoin is the most effective treatment for moderate to severe acne with a well-documented potential for long-term clearance.⁵⁹ Its use during pregnancy is absolutely contraindicated, as the medication is a well-known teratogen. Associated congenital malformations include numerous craniofacial defects, cardiovascular and neurologic malformations, or thymic disorders that are estimated to affect 20% to 35% of infants exposed in utero.⁶⁰ Furthermore, strict contraception use during treatment is mandated for patients who can become pregnant. It is recommended to wait at least 1 month and 1 menstrual cycle after medication discontinuation before attempting to conceive.¹⁷ Pregnancy termination is recommended if conception occurs during treatment with isotretinoin.

Spironolactone—Spironolactone is an androgen-receptor antagonist commonly prescribed off label for mild to severe acne in females.^61,62 Spironolactone promotes the feminization of male fetuses and should be avoided in pregnancy.⁶³

Doxycycline/Minocycline—Tetracyclines are the most commonly prescribed oral antibiotics for moderate to severe acne.⁶⁴ Although highly effective at treating acne, tetracyclines generally should be avoided in pregnancy. First-trimester use of doxycycline is not absolutely contraindicated but should be reserved for severe illness and not employed for the treatment of acne. However, accidental exposure to doxycycline has not been associated with congenital malformations.⁶⁵ Nevertheless, after the 15th week of gestation, permanent tooth discoloration and bone growth inhibition in the fetus are serious and well-documented risks.^14,17 Additional adverse events following in utero exposure include infantile inguinal hernia, hypospadias, and limb hypoplasia.⁶³

Sarecycline—Sarecycline is a novel tetracycline-class antibiotic for the treatment of moderate to severe inflammatory acne. It has a narrower spectrum of activity compared to its counterparts within its class, which translates to an improved safety profile, namely when it comes to gastrointestinal tract microbiome disruption and potentially decreased likelihood of developing bacterial resistance.⁶⁶ Data on human reproductive studies are limited, but it is advisable to avoid sarecycline in pregnancy, as it may cause adverse developmental effects in the fetus, such as reduced bone growth, in addition to the well-known tetracycline-associated risk for permanent discoloration of the teeth if used during the second and third trimesters.^67,68

Erythromycin—Oral erythromycin targets moderate to severe inflammatory acne and is considered safe for use during pregnancy.^69,70 There has been 1 study reporting an increased risk for atrial and ventricular septal defects (1.8%) and pyloric stenosis (0.2%), but these risks are still uncertain, and erythromycin is considered compatible with pregnancy.⁷¹ However, erythromycin estolate formulations should be avoided given the associated 10% to 15% risk for reversible cholestatic liver injury.⁷² Erythromycin base or erythromycin ethylsuccinate formulations should be favored.

Systemic Steroids—Prednisone is indicated for severe acne with scarring and should only be used during pregnancy after clearance from the patient’s obstetrician. Doses of 0.5 mg/kg or less should be prescribed in combination with systemic antibiotics as well as agents for bone and gastrointestinal tract prophylaxis.²⁹

Zinc—The exact mechanism by which zinc exerts its effects to improve acne remains largely obscure. It has been found effective against inflammatory lesions of mild to moderate acne.⁷³ Generally recommended dosages range from 30 to 200 mg/d but may be associated with gastrointestinal tract disturbances. Dosages of 75 mg/d have shown no harm to the fetus.⁷⁴ When taking this supplement, patients should not exceed the recommended doses given the risk for hypocupremia associated with high-dose zinc supplementation.

Light-Based Therapies

Phototherapy—Narrowband UVB phototherapy is effective for the treatment of mild to moderate acne.⁷⁵ It has been proven to be a safe treatment option during pregnancy, but its use has been associated with decreased folic acid levels.^76-79 Therefore, in addition to attaining baseline folic acid serum levels, supplementation with folic acid prior to treatment, as per routine prenatal guidelines, should be sought.⁸⁰

AviClear—The AviClear (Cutera) laser is the first device cleared by the FDA for mild to severe acne in March 2022.⁸¹ The FDA clearance for the Accure (Accure Acne Inc) laser, also targeting mild to severe acne, followed soon after (November 2022). Both lasers harbor a wavelength of 1726 nm and target sebaceous glands with electrothermolysis.^82,83 Further research and long-term safety data are required before using them in pregnancy.

Other Therapies

Cosmetic Peels—Glycolic acid peels induce epidermolysis and desquamation.⁸⁴ Although data on use during pregnancy are limited, these peels have limited dermal penetration and are considered safe for use in pregnancy.^33,85,86 Similarly, keratolytic lactic acid peels harbor limited dermal penetration and can be safely used in pregnant women.^87-89 Salicylic acid peels also work through epidermolysis and desquamation⁸⁴; however, they tend to penetrate deeper into the skin, reaching down to the basal layer, if large areas are treated or when applied under occlusion.^86,90 Although their use is not contraindicated in pregnancy, they should be limited to small areas of coverage.⁹¹

Intralesional Triamcinolone—Acne cysts and inflammatory papules can be treated with intralesional triamcinolone injections to relieve acute symptoms such as pain.⁹² Low doses at concentrations of 2.5 mg/mL are considered compatible with pregnancy when indicated.²⁹

Approaching the Patient Clinical Encounter

In patients seeking treatment prior to conception, a few recommendations can be made to minimize the risk for acne recurrence or flares during pregnancy. For instance, because data show an association between increased acne severity in those with a higher body mass index and in pregnancy, weight loss may be recommended prior to pregnancy to help mitigate symptoms after conception.⁷ The Figure summarizes our recommendations for approaching and treating acne in pregnancy.

In all patients, grading the severity of the patient’s acne as mild, moderate, or severe is the first step. The presence of scarring is an additional consideration during the physical examination and should be documented. A careful discussion of treatment expectations and prognosis should be the focus before treatment initiation. Meticulous documentation of the physical examination and discussion with the patient should be prioritized.

To minimize toxicity and risks to the developing fetus, monotherapy is favored. Topical therapy should be considered first line. Safe regimens include mild nonabrasive washes, such as those containing benzoyl peroxide or glycolic acid, or topical azelaic acid or clindamycin phosphate for mild to moderate acne. More severe cases warrant the consideration of systemic medications as second line, as more severe acne is better treated with oral antibiotics such as the macrolides erythromycin or clindamycin or systemic corticosteroids when concern exists for severe scarring. The additional use of physical sunscreen also is recommended.

An important topic to address during the clinical encounter is cautious intake of oral supplements for acne during pregnancy, as they may contain harmful and teratogenic ingredients. A recent search focusing on acne supplements available online between March and May 2020 uncovered 49 different supplements, 26 (53%) of which contained vitamin A.⁹³ Importantly, 3 (6%) of these 49 supplements were likely teratogenic, 4 (8%) contained vitamin A doses exceeding the recommended daily nutritional intake level, and 15 (31%) harbored an unknown teratogenic risk. Furthermore, among the 6 (12%) supplements with vitamin A levels exceeding 10,000 IU, 2 lacked any mention of pregnancy warning, including the supplement with the highest vitamin A dose found in this study.⁹³ Because dietary supplements are not subject to the same stringent regulations by the FDA as drugs, inadvertent use by unaware patients ought to be prevented by careful counseling and education.

Finally, patients should be counseled to seek care following delivery for potentially updated medication management of acne, especially if they are breastfeeding. Co-management with a pediatrician may be indicated during lactation, particularly when newborns are born preterm or with other health conditions that may warrant additional caution with the use of certain agents.

Acne vulgaris, or acne, is a highly common inflammatory skin disorder affecting up to 85% of the population, and it constitutes the most commonly presenting chief concern in routine dermatology practice.¹ Older teenagers and young adults are most often affected by acne.² Although acne generally is more common in males, adult-onset acne occurs more frequently in women.^2,3 Black and Hispanic women are at higher risk for acne compared to those of Asian, White, or Continental Indian descent.⁴ As such, acne is a common concern in all women of childbearing age.

Concerns for maternal and fetal safety are important therapeutic considerations, especially because hormonal and physiologic changes in pregnancy can lead to onset of inflammatory acne lesions, particularly during the second and third trimesters.⁵ Female patients younger than 25 years; with a higher body mass index, prior irregular menstruation, or polycystic ovary syndrome; or those experiencing their first pregnancy are thought to be more commonly affected.^5-7 In fact, acne affects up to 43% of pregnant women, and lesions typically extend beyond the face to involve the trunk.^6,8-10 Importantly, one-third of women with a history of acne experience symptom relapse after disease-free periods, while two-thirds of those with ongoing disease experience symptom deterioration during pregnancy.¹⁰ Although acne is not a life-threatening condition, it has a well-documented, detrimental impact on social, emotional, and psychological well-being, namely self-perception, social interactions, quality-of-life scores, depression, and anxiety.¹¹

Therefore, safe and effective treatment of pregnant women is of paramount importance. Because pregnant women are not included in clinical trials, there is a paucity of medication safety data, further augmented by inefficient access to available information. The US Food and Drug Administration (FDA) pregnancy safety categories were updated in 2015, letting go of the traditional A, B, C, D, and X categories.¹² The Table reviews the current pregnancy classification system. In this narrative review, we summarize the most recent available data and recommendations on the safety and efficacy of acne treatment during pregnancy.

Topical Treatments for Acne

Benzoyl Peroxide—Benzoyl peroxide commonly is used as first-line therapy alone or in combination with other agents for the treatment of mild to moderate acne.¹³ It is safe for use during pregnancy.¹⁴ Although the medication is systemically absorbed, it undergoes complete metabolism to benzoic acid, a commonly used food additive.^15,16 Benzoic acid has low bioavailability, as it gets rapidly metabolized by the kidneys; therefore, benzoyl peroxide is unlikely to reach clinically significant levels in the maternal circulation and consequently the fetal circulation. Additionally, it has a low risk for causing congenital malformations.¹⁷

Salicylic Acid—For mild to moderate acne, salicylic acid is a second-line agent that likely is safe for use by pregnant women at low concentrations and over limited body surface areas.^14,18,19 There is minimal systemic absorption of the drug.²⁰ Additionally, aspirin, which is broken down in the body into salicylic acid, is used in low doses for the treatment of pre-eclampsia during pregnancy.²¹

Dapsone—The use of dapsone gel 5% as a second-line agent has shown efficacy for mild to moderate acne.²² The oral formulation, commonly used for malaria and leprosy prophylaxis, has failed to show associated fetal toxicity or congenital anomalies.^23,24 It also has been used as a first-line treatment for dermatitis herpetiformis in pregnancy.²⁵ Although the medication likely is safe, it is better to minimize its use during the third trimester to reduce the theoretical risk for hyperbilirubinemia in the neonate.^17,26-29

Azelaic Acid—Azelaic acid effectively targets noninflammatory and inflammatory acne and generally is well tolerated, harboring a good safety profile.³⁰ Topical 20% azelaic acid has localized antibacterial and comedolytic effects and is safe for use during pregnancy.^31,32

Glycolic Acid—Limited data exist on the safety of glycolic acid during pregnancy. In vitro studies have shown up to 27% systemic absorption depending on pH, concentration, and duration of application.³³ Animal reproductive studies involving rats have shown fetal multisystem malformations and developmental abnormalities with oral administration of glycolic acid at doses far exceeding those used in humans.³⁴ Although no human reproductive studies exist, topical glycolic acid is unlikely to reach the developing fetus in notable amounts, and the medication is likely safe for use.^17,35

Clindamycin—Topical clindamycin phosphate is an effective and well-tolerated agent for the treatment of mild to moderate acne.³⁶ Its systemic absorption is minimal, and it is considered safe for use during all trimesters of pregnancy.^{14,17,26,27,35,37}

Erythromycin—Topical erythromycin is another commonly prescribed topical antibiotic used to target mild to moderate acne. However, its use recently has been associated with a decrease in efficacy secondary to the rise of antibacterial resistance in the community.^38-40 Nevertheless, it remains a safe treatment for use during all trimesters of pregnancy.^{14,17,26,27,35,37}

Topical Retinoids—Vitamin A derivatives (also known as retinoids) are the mainstay for the treatment of mild to moderate acne. Limited data exist regarding pregnancy outcomes after in utero exposure.⁴¹ A rare case report suggested topical tretinoin has been associated with fetal otocerebral anomalies.⁴² For tazarotene, teratogenic effects were seen in animal reproductive studies at doses exceeding maximum recommended human doses.^41,43 However, a large meta-analysis failed to find a clear risk for increased congenital malformations, spontaneous abortions, stillbirth, elective termination of pregnancy, low birthweight, or prematurity following first-trimester exposure to topical retinoids.⁴⁴ As the level of exposure that could lead to teratogenicity in humans is unknown, avoidance of both tretinoin and tazarotene is recommended in pregnant women.^41,45 Nevertheless, women inadvertently exposed should be reassured.⁴⁴

Conversely, adapalene has been associated with 1 case of anophthalmia and agenesis of the optic chiasma in a fetus following exposure until 13 weeks’ gestation.⁴⁶ However, a large, open-label trial prior to the patient transitioning from adapalene to over-the-counter treatment showed that the drug harbors a large and reassuring margin of safety and no risk for teratogenicity in a maximal usage trial and Pregnancy Safety Review.⁴⁷ Therefore, adapalene gel 0.1% is a safe and effective medication for the treatment of acne in a nonprescription environment and does not pose harm to the fetus.

Clascoterone—Clascoterone is a novel topical antiandrogenic drug approved for the treatment of hormonal and inflammatory moderate to severe acne.^48-51 Human reproductive data are limited to 1 case of pregnancy that occurred during phase 3 trial investigations, and no adverse outcomes were reported.⁵¹ Minimal systemic absorption follows topical use.⁵² Nonetheless, dose-independent malformations were reported in animal reproductive studies.⁵³ As such, it remains better to avoid the use of clascoterone during pregnancy pending further safety data.

Minocycline Foam—Minocycline foam 4% is approved to treat inflammatory lesions of nonnodular moderate to severe acne in patients 9 years and older.⁵⁴ Systemic absorption is minimal, and the drug has limited bioavailability with minimal systemic accumulation in the patient’s serum.⁵⁵ Given this information, it is unlikely that topical minocycline will reach notable levels in the fetal serum or harbor teratogenic effects, as seen with the oral formulation.⁵⁶ However, it may be best to avoid its use during the second and third trimesters given the potential risk for tooth discoloration in the fetus.^57,58

Systemic Treatments for Acne

Isotretinoin—Isotretinoin is the most effective treatment for moderate to severe acne with a well-documented potential for long-term clearance.⁵⁹ Its use during pregnancy is absolutely contraindicated, as the medication is a well-known teratogen. Associated congenital malformations include numerous craniofacial defects, cardiovascular and neurologic malformations, or thymic disorders that are estimated to affect 20% to 35% of infants exposed in utero.⁶⁰ Furthermore, strict contraception use during treatment is mandated for patients who can become pregnant. It is recommended to wait at least 1 month and 1 menstrual cycle after medication discontinuation before attempting to conceive.¹⁷ Pregnancy termination is recommended if conception occurs during treatment with isotretinoin.

Spironolactone—Spironolactone is an androgen-receptor antagonist commonly prescribed off label for mild to severe acne in females.^61,62 Spironolactone promotes the feminization of male fetuses and should be avoided in pregnancy.⁶³

Doxycycline/Minocycline—Tetracyclines are the most commonly prescribed oral antibiotics for moderate to severe acne.⁶⁴ Although highly effective at treating acne, tetracyclines generally should be avoided in pregnancy. First-trimester use of doxycycline is not absolutely contraindicated but should be reserved for severe illness and not employed for the treatment of acne. However, accidental exposure to doxycycline has not been associated with congenital malformations.⁶⁵ Nevertheless, after the 15th week of gestation, permanent tooth discoloration and bone growth inhibition in the fetus are serious and well-documented risks.^14,17 Additional adverse events following in utero exposure include infantile inguinal hernia, hypospadias, and limb hypoplasia.⁶³

Sarecycline—Sarecycline is a novel tetracycline-class antibiotic for the treatment of moderate to severe inflammatory acne. It has a narrower spectrum of activity compared to its counterparts within its class, which translates to an improved safety profile, namely when it comes to gastrointestinal tract microbiome disruption and potentially decreased likelihood of developing bacterial resistance.⁶⁶ Data on human reproductive studies are limited, but it is advisable to avoid sarecycline in pregnancy, as it may cause adverse developmental effects in the fetus, such as reduced bone growth, in addition to the well-known tetracycline-associated risk for permanent discoloration of the teeth if used during the second and third trimesters.^67,68

Erythromycin—Oral erythromycin targets moderate to severe inflammatory acne and is considered safe for use during pregnancy.^69,70 There has been 1 study reporting an increased risk for atrial and ventricular septal defects (1.8%) and pyloric stenosis (0.2%), but these risks are still uncertain, and erythromycin is considered compatible with pregnancy.⁷¹ However, erythromycin estolate formulations should be avoided given the associated 10% to 15% risk for reversible cholestatic liver injury.⁷² Erythromycin base or erythromycin ethylsuccinate formulations should be favored.

Systemic Steroids—Prednisone is indicated for severe acne with scarring and should only be used during pregnancy after clearance from the patient’s obstetrician. Doses of 0.5 mg/kg or less should be prescribed in combination with systemic antibiotics as well as agents for bone and gastrointestinal tract prophylaxis.²⁹

Zinc—The exact mechanism by which zinc exerts its effects to improve acne remains largely obscure. It has been found effective against inflammatory lesions of mild to moderate acne.⁷³ Generally recommended dosages range from 30 to 200 mg/d but may be associated with gastrointestinal tract disturbances. Dosages of 75 mg/d have shown no harm to the fetus.⁷⁴ When taking this supplement, patients should not exceed the recommended doses given the risk for hypocupremia associated with high-dose zinc supplementation.

Light-Based Therapies

Phototherapy—Narrowband UVB phototherapy is effective for the treatment of mild to moderate acne.⁷⁵ It has been proven to be a safe treatment option during pregnancy, but its use has been associated with decreased folic acid levels.^76-79 Therefore, in addition to attaining baseline folic acid serum levels, supplementation with folic acid prior to treatment, as per routine prenatal guidelines, should be sought.⁸⁰

AviClear—The AviClear (Cutera) laser is the first device cleared by the FDA for mild to severe acne in March 2022.⁸¹ The FDA clearance for the Accure (Accure Acne Inc) laser, also targeting mild to severe acne, followed soon after (November 2022). Both lasers harbor a wavelength of 1726 nm and target sebaceous glands with electrothermolysis.^82,83 Further research and long-term safety data are required before using them in pregnancy.

Other Therapies

Cosmetic Peels—Glycolic acid peels induce epidermolysis and desquamation.⁸⁴ Although data on use during pregnancy are limited, these peels have limited dermal penetration and are considered safe for use in pregnancy.^33,85,86 Similarly, keratolytic lactic acid peels harbor limited dermal penetration and can be safely used in pregnant women.^87-89 Salicylic acid peels also work through epidermolysis and desquamation⁸⁴; however, they tend to penetrate deeper into the skin, reaching down to the basal layer, if large areas are treated or when applied under occlusion.^86,90 Although their use is not contraindicated in pregnancy, they should be limited to small areas of coverage.⁹¹

Intralesional Triamcinolone—Acne cysts and inflammatory papules can be treated with intralesional triamcinolone injections to relieve acute symptoms such as pain.⁹² Low doses at concentrations of 2.5 mg/mL are considered compatible with pregnancy when indicated.²⁹

Approaching the Patient Clinical Encounter

In patients seeking treatment prior to conception, a few recommendations can be made to minimize the risk for acne recurrence or flares during pregnancy. For instance, because data show an association between increased acne severity in those with a higher body mass index and in pregnancy, weight loss may be recommended prior to pregnancy to help mitigate symptoms after conception.⁷ The Figure summarizes our recommendations for approaching and treating acne in pregnancy.

In all patients, grading the severity of the patient’s acne as mild, moderate, or severe is the first step. The presence of scarring is an additional consideration during the physical examination and should be documented. A careful discussion of treatment expectations and prognosis should be the focus before treatment initiation. Meticulous documentation of the physical examination and discussion with the patient should be prioritized.

To minimize toxicity and risks to the developing fetus, monotherapy is favored. Topical therapy should be considered first line. Safe regimens include mild nonabrasive washes, such as those containing benzoyl peroxide or glycolic acid, or topical azelaic acid or clindamycin phosphate for mild to moderate acne. More severe cases warrant the consideration of systemic medications as second line, as more severe acne is better treated with oral antibiotics such as the macrolides erythromycin or clindamycin or systemic corticosteroids when concern exists for severe scarring. The additional use of physical sunscreen also is recommended.

An important topic to address during the clinical encounter is cautious intake of oral supplements for acne during pregnancy, as they may contain harmful and teratogenic ingredients. A recent search focusing on acne supplements available online between March and May 2020 uncovered 49 different supplements, 26 (53%) of which contained vitamin A.⁹³ Importantly, 3 (6%) of these 49 supplements were likely teratogenic, 4 (8%) contained vitamin A doses exceeding the recommended daily nutritional intake level, and 15 (31%) harbored an unknown teratogenic risk. Furthermore, among the 6 (12%) supplements with vitamin A levels exceeding 10,000 IU, 2 lacked any mention of pregnancy warning, including the supplement with the highest vitamin A dose found in this study.⁹³ Because dietary supplements are not subject to the same stringent regulations by the FDA as drugs, inadvertent use by unaware patients ought to be prevented by careful counseling and education.

Finally, patients should be counseled to seek care following delivery for potentially updated medication management of acne, especially if they are breastfeeding. Co-management with a pediatrician may be indicated during lactation, particularly when newborns are born preterm or with other health conditions that may warrant additional caution with the use of certain agents.

Acne vulgaris, or acne, is a highly common inflammatory skin disorder affecting up to 85% of the population, and it constitutes the most commonly presenting chief concern in routine dermatology practice.¹ Older teenagers and young adults are most often affected by acne.² Although acne generally is more common in males, adult-onset acne occurs more frequently in women.^2,3 Black and Hispanic women are at higher risk for acne compared to those of Asian, White, or Continental Indian descent.⁴ As such, acne is a common concern in all women of childbearing age.

Concerns for maternal and fetal safety are important therapeutic considerations, especially because hormonal and physiologic changes in pregnancy can lead to onset of inflammatory acne lesions, particularly during the second and third trimesters.⁵ Female patients younger than 25 years; with a higher body mass index, prior irregular menstruation, or polycystic ovary syndrome; or those experiencing their first pregnancy are thought to be more commonly affected.^5-7 In fact, acne affects up to 43% of pregnant women, and lesions typically extend beyond the face to involve the trunk.^6,8-10 Importantly, one-third of women with a history of acne experience symptom relapse after disease-free periods, while two-thirds of those with ongoing disease experience symptom deterioration during pregnancy.¹⁰ Although acne is not a life-threatening condition, it has a well-documented, detrimental impact on social, emotional, and psychological well-being, namely self-perception, social interactions, quality-of-life scores, depression, and anxiety.¹¹

Therefore, safe and effective treatment of pregnant women is of paramount importance. Because pregnant women are not included in clinical trials, there is a paucity of medication safety data, further augmented by inefficient access to available information. The US Food and Drug Administration (FDA) pregnancy safety categories were updated in 2015, letting go of the traditional A, B, C, D, and X categories.¹² The Table reviews the current pregnancy classification system. In this narrative review, we summarize the most recent available data and recommendations on the safety and efficacy of acne treatment during pregnancy.

Topical Treatments for Acne

Benzoyl Peroxide—Benzoyl peroxide commonly is used as first-line therapy alone or in combination with other agents for the treatment of mild to moderate acne.¹³ It is safe for use during pregnancy.¹⁴ Although the medication is systemically absorbed, it undergoes complete metabolism to benzoic acid, a commonly used food additive.^15,16 Benzoic acid has low bioavailability, as it gets rapidly metabolized by the kidneys; therefore, benzoyl peroxide is unlikely to reach clinically significant levels in the maternal circulation and consequently the fetal circulation. Additionally, it has a low risk for causing congenital malformations.¹⁷

Salicylic Acid—For mild to moderate acne, salicylic acid is a second-line agent that likely is safe for use by pregnant women at low concentrations and over limited body surface areas.^14,18,19 There is minimal systemic absorption of the drug.²⁰ Additionally, aspirin, which is broken down in the body into salicylic acid, is used in low doses for the treatment of pre-eclampsia during pregnancy.²¹

Dapsone—The use of dapsone gel 5% as a second-line agent has shown efficacy for mild to moderate acne.²² The oral formulation, commonly used for malaria and leprosy prophylaxis, has failed to show associated fetal toxicity or congenital anomalies.^23,24 It also has been used as a first-line treatment for dermatitis herpetiformis in pregnancy.²⁵ Although the medication likely is safe, it is better to minimize its use during the third trimester to reduce the theoretical risk for hyperbilirubinemia in the neonate.^17,26-29

Azelaic Acid—Azelaic acid effectively targets noninflammatory and inflammatory acne and generally is well tolerated, harboring a good safety profile.³⁰ Topical 20% azelaic acid has localized antibacterial and comedolytic effects and is safe for use during pregnancy.^31,32

Glycolic Acid—Limited data exist on the safety of glycolic acid during pregnancy. In vitro studies have shown up to 27% systemic absorption depending on pH, concentration, and duration of application.³³ Animal reproductive studies involving rats have shown fetal multisystem malformations and developmental abnormalities with oral administration of glycolic acid at doses far exceeding those used in humans.³⁴ Although no human reproductive studies exist, topical glycolic acid is unlikely to reach the developing fetus in notable amounts, and the medication is likely safe for use.^17,35

Clindamycin—Topical clindamycin phosphate is an effective and well-tolerated agent for the treatment of mild to moderate acne.³⁶ Its systemic absorption is minimal, and it is considered safe for use during all trimesters of pregnancy.^{14,17,26,27,35,37}

Erythromycin—Topical erythromycin is another commonly prescribed topical antibiotic used to target mild to moderate acne. However, its use recently has been associated with a decrease in efficacy secondary to the rise of antibacterial resistance in the community.^38-40 Nevertheless, it remains a safe treatment for use during all trimesters of pregnancy.^{14,17,26,27,35,37}

Topical Retinoids—Vitamin A derivatives (also known as retinoids) are the mainstay for the treatment of mild to moderate acne. Limited data exist regarding pregnancy outcomes after in utero exposure.⁴¹ A rare case report suggested topical tretinoin has been associated with fetal otocerebral anomalies.⁴² For tazarotene, teratogenic effects were seen in animal reproductive studies at doses exceeding maximum recommended human doses.^41,43 However, a large meta-analysis failed to find a clear risk for increased congenital malformations, spontaneous abortions, stillbirth, elective termination of pregnancy, low birthweight, or prematurity following first-trimester exposure to topical retinoids.⁴⁴ As the level of exposure that could lead to teratogenicity in humans is unknown, avoidance of both tretinoin and tazarotene is recommended in pregnant women.^41,45 Nevertheless, women inadvertently exposed should be reassured.⁴⁴

Conversely, adapalene has been associated with 1 case of anophthalmia and agenesis of the optic chiasma in a fetus following exposure until 13 weeks’ gestation.⁴⁶ However, a large, open-label trial prior to the patient transitioning from adapalene to over-the-counter treatment showed that the drug harbors a large and reassuring margin of safety and no risk for teratogenicity in a maximal usage trial and Pregnancy Safety Review.⁴⁷ Therefore, adapalene gel 0.1% is a safe and effective medication for the treatment of acne in a nonprescription environment and does not pose harm to the fetus.

Clascoterone—Clascoterone is a novel topical antiandrogenic drug approved for the treatment of hormonal and inflammatory moderate to severe acne.^48-51 Human reproductive data are limited to 1 case of pregnancy that occurred during phase 3 trial investigations, and no adverse outcomes were reported.⁵¹ Minimal systemic absorption follows topical use.⁵² Nonetheless, dose-independent malformations were reported in animal reproductive studies.⁵³ As such, it remains better to avoid the use of clascoterone during pregnancy pending further safety data.

Minocycline Foam—Minocycline foam 4% is approved to treat inflammatory lesions of nonnodular moderate to severe acne in patients 9 years and older.⁵⁴ Systemic absorption is minimal, and the drug has limited bioavailability with minimal systemic accumulation in the patient’s serum.⁵⁵ Given this information, it is unlikely that topical minocycline will reach notable levels in the fetal serum or harbor teratogenic effects, as seen with the oral formulation.⁵⁶ However, it may be best to avoid its use during the second and third trimesters given the potential risk for tooth discoloration in the fetus.^57,58

Systemic Treatments for Acne

Isotretinoin—Isotretinoin is the most effective treatment for moderate to severe acne with a well-documented potential for long-term clearance.⁵⁹ Its use during pregnancy is absolutely contraindicated, as the medication is a well-known teratogen. Associated congenital malformations include numerous craniofacial defects, cardiovascular and neurologic malformations, or thymic disorders that are estimated to affect 20% to 35% of infants exposed in utero.⁶⁰ Furthermore, strict contraception use during treatment is mandated for patients who can become pregnant. It is recommended to wait at least 1 month and 1 menstrual cycle after medication discontinuation before attempting to conceive.¹⁷ Pregnancy termination is recommended if conception occurs during treatment with isotretinoin.

Spironolactone—Spironolactone is an androgen-receptor antagonist commonly prescribed off label for mild to severe acne in females.^61,62 Spironolactone promotes the feminization of male fetuses and should be avoided in pregnancy.⁶³

Doxycycline/Minocycline—Tetracyclines are the most commonly prescribed oral antibiotics for moderate to severe acne.⁶⁴ Although highly effective at treating acne, tetracyclines generally should be avoided in pregnancy. First-trimester use of doxycycline is not absolutely contraindicated but should be reserved for severe illness and not employed for the treatment of acne. However, accidental exposure to doxycycline has not been associated with congenital malformations.⁶⁵ Nevertheless, after the 15th week of gestation, permanent tooth discoloration and bone growth inhibition in the fetus are serious and well-documented risks.^14,17 Additional adverse events following in utero exposure include infantile inguinal hernia, hypospadias, and limb hypoplasia.⁶³

Sarecycline—Sarecycline is a novel tetracycline-class antibiotic for the treatment of moderate to severe inflammatory acne. It has a narrower spectrum of activity compared to its counterparts within its class, which translates to an improved safety profile, namely when it comes to gastrointestinal tract microbiome disruption and potentially decreased likelihood of developing bacterial resistance.⁶⁶ Data on human reproductive studies are limited, but it is advisable to avoid sarecycline in pregnancy, as it may cause adverse developmental effects in the fetus, such as reduced bone growth, in addition to the well-known tetracycline-associated risk for permanent discoloration of the teeth if used during the second and third trimesters.^67,68

Erythromycin—Oral erythromycin targets moderate to severe inflammatory acne and is considered safe for use during pregnancy.^69,70 There has been 1 study reporting an increased risk for atrial and ventricular septal defects (1.8%) and pyloric stenosis (0.2%), but these risks are still uncertain, and erythromycin is considered compatible with pregnancy.⁷¹ However, erythromycin estolate formulations should be avoided given the associated 10% to 15% risk for reversible cholestatic liver injury.⁷² Erythromycin base or erythromycin ethylsuccinate formulations should be favored.

Systemic Steroids—Prednisone is indicated for severe acne with scarring and should only be used during pregnancy after clearance from the patient’s obstetrician. Doses of 0.5 mg/kg or less should be prescribed in combination with systemic antibiotics as well as agents for bone and gastrointestinal tract prophylaxis.²⁹

Zinc—The exact mechanism by which zinc exerts its effects to improve acne remains largely obscure. It has been found effective against inflammatory lesions of mild to moderate acne.⁷³ Generally recommended dosages range from 30 to 200 mg/d but may be associated with gastrointestinal tract disturbances. Dosages of 75 mg/d have shown no harm to the fetus.⁷⁴ When taking this supplement, patients should not exceed the recommended doses given the risk for hypocupremia associated with high-dose zinc supplementation.

Light-Based Therapies

Phototherapy—Narrowband UVB phototherapy is effective for the treatment of mild to moderate acne.⁷⁵ It has been proven to be a safe treatment option during pregnancy, but its use has been associated with decreased folic acid levels.^76-79 Therefore, in addition to attaining baseline folic acid serum levels, supplementation with folic acid prior to treatment, as per routine prenatal guidelines, should be sought.⁸⁰

AviClear—The AviClear (Cutera) laser is the first device cleared by the FDA for mild to severe acne in March 2022.⁸¹ The FDA clearance for the Accure (Accure Acne Inc) laser, also targeting mild to severe acne, followed soon after (November 2022). Both lasers harbor a wavelength of 1726 nm and target sebaceous glands with electrothermolysis.^82,83 Further research and long-term safety data are required before using them in pregnancy.

Other Therapies

Cosmetic Peels—Glycolic acid peels induce epidermolysis and desquamation.⁸⁴ Although data on use during pregnancy are limited, these peels have limited dermal penetration and are considered safe for use in pregnancy.^33,85,86 Similarly, keratolytic lactic acid peels harbor limited dermal penetration and can be safely used in pregnant women.^87-89 Salicylic acid peels also work through epidermolysis and desquamation⁸⁴; however, they tend to penetrate deeper into the skin, reaching down to the basal layer, if large areas are treated or when applied under occlusion.^86,90 Although their use is not contraindicated in pregnancy, they should be limited to small areas of coverage.⁹¹

Intralesional Triamcinolone—Acne cysts and inflammatory papules can be treated with intralesional triamcinolone injections to relieve acute symptoms such as pain.⁹² Low doses at concentrations of 2.5 mg/mL are considered compatible with pregnancy when indicated.²⁹

Approaching the Patient Clinical Encounter

In patients seeking treatment prior to conception, a few recommendations can be made to minimize the risk for acne recurrence or flares during pregnancy. For instance, because data show an association between increased acne severity in those with a higher body mass index and in pregnancy, weight loss may be recommended prior to pregnancy to help mitigate symptoms after conception.⁷ The Figure summarizes our recommendations for approaching and treating acne in pregnancy.

In all patients, grading the severity of the patient’s acne as mild, moderate, or severe is the first step. The presence of scarring is an additional consideration during the physical examination and should be documented. A careful discussion of treatment expectations and prognosis should be the focus before treatment initiation. Meticulous documentation of the physical examination and discussion with the patient should be prioritized.

To minimize toxicity and risks to the developing fetus, monotherapy is favored. Topical therapy should be considered first line. Safe regimens include mild nonabrasive washes, such as those containing benzoyl peroxide or glycolic acid, or topical azelaic acid or clindamycin phosphate for mild to moderate acne. More severe cases warrant the consideration of systemic medications as second line, as more severe acne is better treated with oral antibiotics such as the macrolides erythromycin or clindamycin or systemic corticosteroids when concern exists for severe scarring. The additional use of physical sunscreen also is recommended.

An important topic to address during the clinical encounter is cautious intake of oral supplements for acne during pregnancy, as they may contain harmful and teratogenic ingredients. A recent search focusing on acne supplements available online between March and May 2020 uncovered 49 different supplements, 26 (53%) of which contained vitamin A.⁹³ Importantly, 3 (6%) of these 49 supplements were likely teratogenic, 4 (8%) contained vitamin A doses exceeding the recommended daily nutritional intake level, and 15 (31%) harbored an unknown teratogenic risk. Furthermore, among the 6 (12%) supplements with vitamin A levels exceeding 10,000 IU, 2 lacked any mention of pregnancy warning, including the supplement with the highest vitamin A dose found in this study.⁹³ Because dietary supplements are not subject to the same stringent regulations by the FDA as drugs, inadvertent use by unaware patients ought to be prevented by careful counseling and education.

Finally, patients should be counseled to seek care following delivery for potentially updated medication management of acne, especially if they are breastfeeding. Co-management with a pediatrician may be indicated during lactation, particularly when newborns are born preterm or with other health conditions that may warrant additional caution with the use of certain agents.

But here's the thing: We should not be making clinical judgments on the basis of differences in relative risk; clinical decisions should be based on absolute risks. Should we worry about VTE risk when treating patients with AD? This paper did not focus on absolute risk, but we can get an idea of the absolute risk by looking at the data presented in the figures in the paper. The risk for VTE in patients without AD was about 1 in 400, whereas with AD the risk was about 1 in 300, even before controlling for risk factors. This rate is sufficiently low for both groups that it doesn't seem like this risk would affect whether we would use a drug that might be associated with some minimal or theoretical increased risk for VTE.

The bottom line is that the findings of this study are reassuring, at least to me.

I'm already convinced that dupilumab is a very safe treatment for our patients with AD. The study by Simpson and colleagues looked at data from a registry of patients followed in real-life practice. The 2-year study showed no new concerns for dupilumab treatment of AD. The most common adverse event was conjunctivitis, and that was seen in only 2.4% of the patients. Perhaps the most interesting finding was that 83% of the patients who started in the study were still on dupilumab treatment at the end of 2 years. Dupilumab has a good level of efficacy and safety such that the great majority of patients who start on it seem to do well.

Dupilumab is a highly effective, very safe treatment for AD. Rademikibart Is another interleukin-4 receptor alpha-chain blocker. Not surprisingly, rademikibart also seems to be an effective, safe treatment for AD (Silverberg et al). Rademikibart may serve as another option for AD, and I imagine that it could be used if a patient on dupilumab were to develop an anti-drug antibody and lose effectiveness.

The very interesting analysis by Silverberg and colleagues looks at a new way to compare the effectiveness of different drugs for AD. They use this new approach to compare upadacitinib and dupilumab. What they found, not surprisingly, was that upadacitinib was generally more effective for AD than dupilumab. I used to think I would never see anything more effective for AD than dupilumab, but, clearly, based on head-to-head trials, upadacitinib is more effective for AD than is dupilumab. But does that greater efficacy mean that we should use upadacitinib first? We need to consider safety, too. Dupilumab works well enough for the great majority of patients and is extremely safe. I think upadacitinib is a great choice for patients who did not respond to dupilumab and could also be considered for those patients who want to take the most effective treatment option.

Trimeche and colleagues' study of contact allergens in patients with AD may change how I practice. In this study, 60% of the AD patients had positive patch test results of which 71% were considered relevant. The most frequent allergens included textile dye mix (25%), nickel (20%), cobalt (13%), isothiazolinone (9%), quanterium-15 (4%), and balsam of Peru (4%). Two patients were allergic to corticosteroids. Avoidance of relevant allergens resulted in improvement. I need to warn my AD patients to be on the lookout for contact allergens that may be causing or exacerbating their skin disease.

But here's the thing: We should not be making clinical judgments on the basis of differences in relative risk; clinical decisions should be based on absolute risks. Should we worry about VTE risk when treating patients with AD? This paper did not focus on absolute risk, but we can get an idea of the absolute risk by looking at the data presented in the figures in the paper. The risk for VTE in patients without AD was about 1 in 400, whereas with AD the risk was about 1 in 300, even before controlling for risk factors. This rate is sufficiently low for both groups that it doesn't seem like this risk would affect whether we would use a drug that might be associated with some minimal or theoretical increased risk for VTE.

The bottom line is that the findings of this study are reassuring, at least to me.

I'm already convinced that dupilumab is a very safe treatment for our patients with AD. The study by Simpson and colleagues looked at data from a registry of patients followed in real-life practice. The 2-year study showed no new concerns for dupilumab treatment of AD. The most common adverse event was conjunctivitis, and that was seen in only 2.4% of the patients. Perhaps the most interesting finding was that 83% of the patients who started in the study were still on dupilumab treatment at the end of 2 years. Dupilumab has a good level of efficacy and safety such that the great majority of patients who start on it seem to do well.

Dupilumab is a highly effective, very safe treatment for AD. Rademikibart Is another interleukin-4 receptor alpha-chain blocker. Not surprisingly, rademikibart also seems to be an effective, safe treatment for AD (Silverberg et al). Rademikibart may serve as another option for AD, and I imagine that it could be used if a patient on dupilumab were to develop an anti-drug antibody and lose effectiveness.

The very interesting analysis by Silverberg and colleagues looks at a new way to compare the effectiveness of different drugs for AD. They use this new approach to compare upadacitinib and dupilumab. What they found, not surprisingly, was that upadacitinib was generally more effective for AD than dupilumab. I used to think I would never see anything more effective for AD than dupilumab, but, clearly, based on head-to-head trials, upadacitinib is more effective for AD than is dupilumab. But does that greater efficacy mean that we should use upadacitinib first? We need to consider safety, too. Dupilumab works well enough for the great majority of patients and is extremely safe. I think upadacitinib is a great choice for patients who did not respond to dupilumab and could also be considered for those patients who want to take the most effective treatment option.

Trimeche and colleagues' study of contact allergens in patients with AD may change how I practice. In this study, 60% of the AD patients had positive patch test results of which 71% were considered relevant. The most frequent allergens included textile dye mix (25%), nickel (20%), cobalt (13%), isothiazolinone (9%), quanterium-15 (4%), and balsam of Peru (4%). Two patients were allergic to corticosteroids. Avoidance of relevant allergens resulted in improvement. I need to warn my AD patients to be on the lookout for contact allergens that may be causing or exacerbating their skin disease.

But here's the thing: We should not be making clinical judgments on the basis of differences in relative risk; clinical decisions should be based on absolute risks. Should we worry about VTE risk when treating patients with AD? This paper did not focus on absolute risk, but we can get an idea of the absolute risk by looking at the data presented in the figures in the paper. The risk for VTE in patients without AD was about 1 in 400, whereas with AD the risk was about 1 in 300, even before controlling for risk factors. This rate is sufficiently low for both groups that it doesn't seem like this risk would affect whether we would use a drug that might be associated with some minimal or theoretical increased risk for VTE.

The bottom line is that the findings of this study are reassuring, at least to me.

I'm already convinced that dupilumab is a very safe treatment for our patients with AD. The study by Simpson and colleagues looked at data from a registry of patients followed in real-life practice. The 2-year study showed no new concerns for dupilumab treatment of AD. The most common adverse event was conjunctivitis, and that was seen in only 2.4% of the patients. Perhaps the most interesting finding was that 83% of the patients who started in the study were still on dupilumab treatment at the end of 2 years. Dupilumab has a good level of efficacy and safety such that the great majority of patients who start on it seem to do well.

Dupilumab is a highly effective, very safe treatment for AD. Rademikibart Is another interleukin-4 receptor alpha-chain blocker. Not surprisingly, rademikibart also seems to be an effective, safe treatment for AD (Silverberg et al). Rademikibart may serve as another option for AD, and I imagine that it could be used if a patient on dupilumab were to develop an anti-drug antibody and lose effectiveness.

The very interesting analysis by Silverberg and colleagues looks at a new way to compare the effectiveness of different drugs for AD. They use this new approach to compare upadacitinib and dupilumab. What they found, not surprisingly, was that upadacitinib was generally more effective for AD than dupilumab. I used to think I would never see anything more effective for AD than dupilumab, but, clearly, based on head-to-head trials, upadacitinib is more effective for AD than is dupilumab. But does that greater efficacy mean that we should use upadacitinib first? We need to consider safety, too. Dupilumab works well enough for the great majority of patients and is extremely safe. I think upadacitinib is a great choice for patients who did not respond to dupilumab and could also be considered for those patients who want to take the most effective treatment option.

Trimeche and colleagues' study of contact allergens in patients with AD may change how I practice. In this study, 60% of the AD patients had positive patch test results of which 71% were considered relevant. The most frequent allergens included textile dye mix (25%), nickel (20%), cobalt (13%), isothiazolinone (9%), quanterium-15 (4%), and balsam of Peru (4%). Two patients were allergic to corticosteroids. Avoidance of relevant allergens resulted in improvement. I need to warn my AD patients to be on the lookout for contact allergens that may be causing or exacerbating their skin disease.

To the Editor:

Partial or total nail plate excisions commonly are used for the treatment of onychocryptosis and nail spicules. Procedures involving the nail unit require advanced technical skills to achieve optimal functional and aesthetic outcomes, avoid complications, and minimize health care costs. Data on the frequency of nail plate excisions performed by dermatologists and their relative frequency compared to other medical providers are limited. The objective of our study was to analyze trends in nail excision practice patterns among medical providers in the United States.

A retrospective analysis on nail excisions using the Current Procedural Terminology (CPT) code 11750 (excision of nail and nail matrix, partial or complete [eg, ingrown or deformed nail] for permanent removal), which is distinct from code 11755 (biopsy of nail unit [eg, plate, bed, matrix, hyponychium, proximal and lateral nail folds][separate procedure]), was performed using data from the Medicare Provider Utilization and Payment Database 2012-2017.^1,2 This file also is used by Peck et al³ in an article submitted to the Journal of the American Podiatric Medical Association and currently under consideration for publication. Procedures were recorded by year and provider type—dermatologist, podiatrist, physician assistant (PA)/nurse practitioner (NP), nondermatologist physician—and subcategorized by provider specialty (Table). Practice locations subcategorized by provider type were mapped using Tableau Software (Salesforce)(Figure). Descriptive statistics including number of providers, mean and median excisions per provider, and minimum/maximum nail excisions were calculated (Table). Practice types of PAs/NPs and specialization of nondermatologist physicians were determined using provider name, identification number, and practice address. This study did not require institutional review board review, as only publicly available data were utilized in our analysis.

A total of 6936 podiatrists, 58 nondermatologist physicians, 25 PAs/NPs, and 4 dermatologists performed 10 or more nail excisions annually under CPT code 11750 from January 2012 to December 2017 with annual means of 31, 31, 25, and 34, respectively (Table). No PAs/NPs included in the dataset worked in dermatology practices during the study period. Physician assistants and NPs most often practiced in podiatry and family medicine (FM) settings (both 40% [10/25]). Nondermatologist physicians most often specialized in FM (40% [23/58])(Table). The greatest number of providers practiced in 3 of the 4 most-populous states: California, Texas, and Florida; the fewest number practiced in 3 of the 10 least-populous states: Alaska, Hawaii, and Vermont. Vermont, Wyoming, and North Dakota—3 of the 5 least-populous states—had the fewest practitioners among the contiguous United States (Figure).

Figure generated using Tableau, which integrates with Mapbox. © Mapbox (https://www.mapbox.com/about/maps/), © OpenStreetMap (http://www.openstreetmap.org/copyright).

Our study showed that from January 2012 to December 2017, fewer dermatologists performed nail excisions than any other provider type (0.06%, 4 dermatologists of 7023 total providers), and dermatologists performed 1734-fold fewer nail excisions than podiatrists (99%, 6936 podiatrists of 7023 total providers). Only dermatologists practicing in California, Georgia, Indiana, and Oklahoma performed nail excisions. Conversely, podiatrists were more geographically distributed across the United States and other territories, with representation in all 50 states as well as the District of Columbia, Puerto Rico, and Guam.

Reasons for these large discrepancies in practice between dermatologists and other providers likely are multifactorial, encompassing a lack of emphasis on nail procedures in dermatology training, patient perception of the scope of dermatologic practice, and nail excision reimbursement patterns. Most dermatologists likely lack experience in performing nail procedures. The Accreditation Council for Graduate Medical Education requirements mandate that dermatology residents observe or perform 3 nail procedures over 3 years of residency, including 1 that may be performed on a human cadaver.⁴ In contrast, podiatry trainees must gain competency in toenail avulsion (both partial and complete), participate in anesthesia workshops, and become proficient in administering lower extremity blocks by the end of their training.⁵ Therefore, incorporating aspects of podiatric surgical training into dermatology residency requirements may increase the competency and comfort of dermatologists in performing nail excisions and practicing as nail experts as attending physicians.

It is likely that US patients do not perceive dermatologists as nail specialists and instead primarily consult podiatrists or FM and/or internal medicine physicians for treatment; for example, nail disease was one of the least common reasons for consulting a dermatologist (5%) in a German nationwide survey-based study (N=1015).⁶ Therefore, increased efforts are needed to educate the general public about the expertise of dermatologists in the diagnosis and management of nail conditions.

Reimbursement also may be a barrier to dermatologists performing nail procedures as part of their scope of practice; for example, in a retrospective study of nail biopsies using the Medicare Provider Utilization and Payment Database, there was no statistically significant difference in reimbursements for nail biopsies vs skin biopsies from 2012 to 2017 (P=0.69).⁷ Similar to nail biopsies, nail excisions typically are much more time consuming and technically demanding than skin biopsies, which may discourage dermatologists from routinely performing nail excision procedures.

Our study is subject to a number of limitations. The data reflected only US-based practice patterns and may not be applicable to nail procedures globally. There also is the potential for miscoding of procedures in the Medicare database. The data included only Part B Medicare fee-for-service and excludes non-Medicare insured, uninsured, and self-pay patients, as well as aggregated records from 10 or fewer Medicare beneficiaries.

Dermatologists rarely perform nail excisions and perform fewer nail excisions than any other provider type in the United States. There currently is an unmet need for comprehensive nail surgery education in US-based dermatology residency programs. We hope that our study fosters interdisciplinary collegiality and training between podiatrists and dermatologists and promotes expanded access to care across the United States to serve patients with nail disorders.

To the Editor:

Partial or total nail plate excisions commonly are used for the treatment of onychocryptosis and nail spicules. Procedures involving the nail unit require advanced technical skills to achieve optimal functional and aesthetic outcomes, avoid complications, and minimize health care costs. Data on the frequency of nail plate excisions performed by dermatologists and their relative frequency compared to other medical providers are limited. The objective of our study was to analyze trends in nail excision practice patterns among medical providers in the United States.

A retrospective analysis on nail excisions using the Current Procedural Terminology (CPT) code 11750 (excision of nail and nail matrix, partial or complete [eg, ingrown or deformed nail] for permanent removal), which is distinct from code 11755 (biopsy of nail unit [eg, plate, bed, matrix, hyponychium, proximal and lateral nail folds][separate procedure]), was performed using data from the Medicare Provider Utilization and Payment Database 2012-2017.^1,2 This file also is used by Peck et al³ in an article submitted to the Journal of the American Podiatric Medical Association and currently under consideration for publication. Procedures were recorded by year and provider type—dermatologist, podiatrist, physician assistant (PA)/nurse practitioner (NP), nondermatologist physician—and subcategorized by provider specialty (Table). Practice locations subcategorized by provider type were mapped using Tableau Software (Salesforce)(Figure). Descriptive statistics including number of providers, mean and median excisions per provider, and minimum/maximum nail excisions were calculated (Table). Practice types of PAs/NPs and specialization of nondermatologist physicians were determined using provider name, identification number, and practice address. This study did not require institutional review board review, as only publicly available data were utilized in our analysis.

A total of 6936 podiatrists, 58 nondermatologist physicians, 25 PAs/NPs, and 4 dermatologists performed 10 or more nail excisions annually under CPT code 11750 from January 2012 to December 2017 with annual means of 31, 31, 25, and 34, respectively (Table). No PAs/NPs included in the dataset worked in dermatology practices during the study period. Physician assistants and NPs most often practiced in podiatry and family medicine (FM) settings (both 40% [10/25]). Nondermatologist physicians most often specialized in FM (40% [23/58])(Table). The greatest number of providers practiced in 3 of the 4 most-populous states: California, Texas, and Florida; the fewest number practiced in 3 of the 10 least-populous states: Alaska, Hawaii, and Vermont. Vermont, Wyoming, and North Dakota—3 of the 5 least-populous states—had the fewest practitioners among the contiguous United States (Figure).

Figure generated using Tableau, which integrates with Mapbox. © Mapbox (https://www.mapbox.com/about/maps/), © OpenStreetMap (http://www.openstreetmap.org/copyright).

Our study showed that from January 2012 to December 2017, fewer dermatologists performed nail excisions than any other provider type (0.06%, 4 dermatologists of 7023 total providers), and dermatologists performed 1734-fold fewer nail excisions than podiatrists (99%, 6936 podiatrists of 7023 total providers). Only dermatologists practicing in California, Georgia, Indiana, and Oklahoma performed nail excisions. Conversely, podiatrists were more geographically distributed across the United States and other territories, with representation in all 50 states as well as the District of Columbia, Puerto Rico, and Guam.

Reasons for these large discrepancies in practice between dermatologists and other providers likely are multifactorial, encompassing a lack of emphasis on nail procedures in dermatology training, patient perception of the scope of dermatologic practice, and nail excision reimbursement patterns. Most dermatologists likely lack experience in performing nail procedures. The Accreditation Council for Graduate Medical Education requirements mandate that dermatology residents observe or perform 3 nail procedures over 3 years of residency, including 1 that may be performed on a human cadaver.⁴ In contrast, podiatry trainees must gain competency in toenail avulsion (both partial and complete), participate in anesthesia workshops, and become proficient in administering lower extremity blocks by the end of their training.⁵ Therefore, incorporating aspects of podiatric surgical training into dermatology residency requirements may increase the competency and comfort of dermatologists in performing nail excisions and practicing as nail experts as attending physicians.

It is likely that US patients do not perceive dermatologists as nail specialists and instead primarily consult podiatrists or FM and/or internal medicine physicians for treatment; for example, nail disease was one of the least common reasons for consulting a dermatologist (5%) in a German nationwide survey-based study (N=1015).⁶ Therefore, increased efforts are needed to educate the general public about the expertise of dermatologists in the diagnosis and management of nail conditions.

Reimbursement also may be a barrier to dermatologists performing nail procedures as part of their scope of practice; for example, in a retrospective study of nail biopsies using the Medicare Provider Utilization and Payment Database, there was no statistically significant difference in reimbursements for nail biopsies vs skin biopsies from 2012 to 2017 (P=0.69).⁷ Similar to nail biopsies, nail excisions typically are much more time consuming and technically demanding than skin biopsies, which may discourage dermatologists from routinely performing nail excision procedures.

Our study is subject to a number of limitations. The data reflected only US-based practice patterns and may not be applicable to nail procedures globally. There also is the potential for miscoding of procedures in the Medicare database. The data included only Part B Medicare fee-for-service and excludes non-Medicare insured, uninsured, and self-pay patients, as well as aggregated records from 10 or fewer Medicare beneficiaries.

Dermatologists rarely perform nail excisions and perform fewer nail excisions than any other provider type in the United States. There currently is an unmet need for comprehensive nail surgery education in US-based dermatology residency programs. We hope that our study fosters interdisciplinary collegiality and training between podiatrists and dermatologists and promotes expanded access to care across the United States to serve patients with nail disorders.

To the Editor:

Partial or total nail plate excisions commonly are used for the treatment of onychocryptosis and nail spicules. Procedures involving the nail unit require advanced technical skills to achieve optimal functional and aesthetic outcomes, avoid complications, and minimize health care costs. Data on the frequency of nail plate excisions performed by dermatologists and their relative frequency compared to other medical providers are limited. The objective of our study was to analyze trends in nail excision practice patterns among medical providers in the United States.

A retrospective analysis on nail excisions using the Current Procedural Terminology (CPT) code 11750 (excision of nail and nail matrix, partial or complete [eg, ingrown or deformed nail] for permanent removal), which is distinct from code 11755 (biopsy of nail unit [eg, plate, bed, matrix, hyponychium, proximal and lateral nail folds][separate procedure]), was performed using data from the Medicare Provider Utilization and Payment Database 2012-2017.^1,2 This file also is used by Peck et al³ in an article submitted to the Journal of the American Podiatric Medical Association and currently under consideration for publication. Procedures were recorded by year and provider type—dermatologist, podiatrist, physician assistant (PA)/nurse practitioner (NP), nondermatologist physician—and subcategorized by provider specialty (Table). Practice locations subcategorized by provider type were mapped using Tableau Software (Salesforce)(Figure). Descriptive statistics including number of providers, mean and median excisions per provider, and minimum/maximum nail excisions were calculated (Table). Practice types of PAs/NPs and specialization of nondermatologist physicians were determined using provider name, identification number, and practice address. This study did not require institutional review board review, as only publicly available data were utilized in our analysis.

A total of 6936 podiatrists, 58 nondermatologist physicians, 25 PAs/NPs, and 4 dermatologists performed 10 or more nail excisions annually under CPT code 11750 from January 2012 to December 2017 with annual means of 31, 31, 25, and 34, respectively (Table). No PAs/NPs included in the dataset worked in dermatology practices during the study period. Physician assistants and NPs most often practiced in podiatry and family medicine (FM) settings (both 40% [10/25]). Nondermatologist physicians most often specialized in FM (40% [23/58])(Table). The greatest number of providers practiced in 3 of the 4 most-populous states: California, Texas, and Florida; the fewest number practiced in 3 of the 10 least-populous states: Alaska, Hawaii, and Vermont. Vermont, Wyoming, and North Dakota—3 of the 5 least-populous states—had the fewest practitioners among the contiguous United States (Figure).

Figure generated using Tableau, which integrates with Mapbox. © Mapbox (https://www.mapbox.com/about/maps/), © OpenStreetMap (http://www.openstreetmap.org/copyright).

Our study showed that from January 2012 to December 2017, fewer dermatologists performed nail excisions than any other provider type (0.06%, 4 dermatologists of 7023 total providers), and dermatologists performed 1734-fold fewer nail excisions than podiatrists (99%, 6936 podiatrists of 7023 total providers). Only dermatologists practicing in California, Georgia, Indiana, and Oklahoma performed nail excisions. Conversely, podiatrists were more geographically distributed across the United States and other territories, with representation in all 50 states as well as the District of Columbia, Puerto Rico, and Guam.

Reasons for these large discrepancies in practice between dermatologists and other providers likely are multifactorial, encompassing a lack of emphasis on nail procedures in dermatology training, patient perception of the scope of dermatologic practice, and nail excision reimbursement patterns. Most dermatologists likely lack experience in performing nail procedures. The Accreditation Council for Graduate Medical Education requirements mandate that dermatology residents observe or perform 3 nail procedures over 3 years of residency, including 1 that may be performed on a human cadaver.⁴ In contrast, podiatry trainees must gain competency in toenail avulsion (both partial and complete), participate in anesthesia workshops, and become proficient in administering lower extremity blocks by the end of their training.⁵ Therefore, incorporating aspects of podiatric surgical training into dermatology residency requirements may increase the competency and comfort of dermatologists in performing nail excisions and practicing as nail experts as attending physicians.

It is likely that US patients do not perceive dermatologists as nail specialists and instead primarily consult podiatrists or FM and/or internal medicine physicians for treatment; for example, nail disease was one of the least common reasons for consulting a dermatologist (5%) in a German nationwide survey-based study (N=1015).⁶ Therefore, increased efforts are needed to educate the general public about the expertise of dermatologists in the diagnosis and management of nail conditions.

Reimbursement also may be a barrier to dermatologists performing nail procedures as part of their scope of practice; for example, in a retrospective study of nail biopsies using the Medicare Provider Utilization and Payment Database, there was no statistically significant difference in reimbursements for nail biopsies vs skin biopsies from 2012 to 2017 (P=0.69).⁷ Similar to nail biopsies, nail excisions typically are much more time consuming and technically demanding than skin biopsies, which may discourage dermatologists from routinely performing nail excision procedures.

Our study is subject to a number of limitations. The data reflected only US-based practice patterns and may not be applicable to nail procedures globally. There also is the potential for miscoding of procedures in the Medicare database. The data included only Part B Medicare fee-for-service and excludes non-Medicare insured, uninsured, and self-pay patients, as well as aggregated records from 10 or fewer Medicare beneficiaries.

Dermatologists rarely perform nail excisions and perform fewer nail excisions than any other provider type in the United States. There currently is an unmet need for comprehensive nail surgery education in US-based dermatology residency programs. We hope that our study fosters interdisciplinary collegiality and training between podiatrists and dermatologists and promotes expanded access to care across the United States to serve patients with nail disorders.

The Diagnosis: Argyria-Induced Azure Lunulae

Argyria is an acquired condition resulting from excessive exogenous exposure to silver with subsequent gastrointestinal absorption and pigmentary tissue deposition. Upon further questioning, our patient disclosed a lifetime history of colloidal silver use, both as a topical antiseptic agent and intraorally for aphthous ulcers. Silver has a predilection for granular deposition in stromal tissues and basement membranes with sparing of the epidermis, manifesting as progressive, permanent, blue to slate gray discoloration of sunexposed skin, mucous membranes, and nail beds.¹ The patient was advised to discontinue use of colloidal silver to avoid development of further pigmentary changes. The appearance of his nails remained unchanged in the months following initial presentation, as expected, since argyria pigmentation is not anticipated to reverse upon colloidal silver cessation.

Nail involvement may be an early presentation of generalized argyria or may be found in isolation, as seen in our patient. Early recognition and patient education are essential to minimize cumulative silver deposition. Although dyspigmentation may impact psychosocial well-being secondary to aesthetic concerns, there is limited research supporting adverse systemic effects of argyria confined to the nail beds. Similarly, the majority of generalized cases are not associated with systemic complications; however, potential toxicities, as described in isolated case reports without conclusive causal relationships, include nyctalopia, renal or hepatic toxicity, pulmonary fibrosis, and neuropsychiatric events.^1-6 Successful treatment of cutaneous argyria has been reported with the 1064-nm Q-switched Nd:YAG laser; however, there have been no reported treatments for nail bed involvement.⁷ Due to the absence of systemic symptoms, additional mucocutaneous dyspigmentation, or cosmetic concerns regarding nail bed lunulae discoloration in our patient, no further intervention was pursued, except for continued colloidal silver cessation.

The differential diagnosis of blue-gray nail bed dyspigmentation is broad and includes cyanosis secondary to cardiopulmonary disease, drug-induced dyspigmentation, Wilson disease, argyria, chrysiasis, hereditary acrolabial telangiectasia, and pseudomonal infection or chloronychia.^1,8,9 Etiologic insight may be provided from a thorough review of prescription and over-the-counter medications as well as careful attention to the distribution of dyspigmentation. Medications commonly associated with bluish nail bed dyspigmentation include antimalarials, amiodarone, minocycline, clofazimine, chlorpromazine/phenothiazines, and various chemotherapeutic drugs; our patient was not taking any of these.^1,9

Cyanotic nail bed dyspigmentation secondary to cardiopulmonary disease likely manifests with more diffuse nail bed dyspigmentation and is not confined solely to the lunulae. Only drug-induced dyspigmentation, classically due to phenolphthalein-containing laxatives; Wilson disease; and argyria have a tendency to spare the distal nail bed, which is a presentation termed azure lunulae.⁸ The toenails typically are spared in argyria, while toenail involvement is variable in Wilson disease, and additional systemic symptoms—including hepatic, ophthalmologic, and neuropsychiatric—as well as potential family history would be expected.⁸ Phenolphthalein is no longer available in over-the-counter laxatives, as it was formally banned by the US Food and Drug Administration in 1999 due to concerns of carcinogenicity.¹⁰

Hereditary acrolabial telangiectasia is a familial condition with autosomal-dominant inheritance that can manifest similarly to argyria with blue-gray discoloration of the proximal nail bed; however, this condition also would demonstrate involvement of the vermilion border and nipple areolae, often with associated telangiectasia and migraine headaches.¹¹

Chloronychia (also known as green nail syndrome) is an infection of the nail bed with Pseudomonas aeruginosa that more commonly presents with greenblack discoloration with variable involvement of the fingernails and toenails. Chloronychia, often with associated onycholysis, typically is found in individuals with repeated exposure to water, soaps, and detergents.¹² Our patient’s long-standing and unwavering nail bed appearance, involvement of all fingernail lunulae, lack of additional symptoms, and disclosed use of over-the-counter colloidal silver supported a clinical diagnosis of argyriainduced azure lunulae.

Argyria-induced azure lunulae secondary to colloidal silver exposure is an uncommon yet clinically significant cause of nail bed dyspigmentation. Prompt identification and cessation of the offending agent can prevent progression of mucocutaneous dyspigmentation and avoid potential long-term sequelae from systemic deposition.

The Diagnosis: Argyria-Induced Azure Lunulae

Argyria is an acquired condition resulting from excessive exogenous exposure to silver with subsequent gastrointestinal absorption and pigmentary tissue deposition. Upon further questioning, our patient disclosed a lifetime history of colloidal silver use, both as a topical antiseptic agent and intraorally for aphthous ulcers. Silver has a predilection for granular deposition in stromal tissues and basement membranes with sparing of the epidermis, manifesting as progressive, permanent, blue to slate gray discoloration of sunexposed skin, mucous membranes, and nail beds.¹ The patient was advised to discontinue use of colloidal silver to avoid development of further pigmentary changes. The appearance of his nails remained unchanged in the months following initial presentation, as expected, since argyria pigmentation is not anticipated to reverse upon colloidal silver cessation.

Nail involvement may be an early presentation of generalized argyria or may be found in isolation, as seen in our patient. Early recognition and patient education are essential to minimize cumulative silver deposition. Although dyspigmentation may impact psychosocial well-being secondary to aesthetic concerns, there is limited research supporting adverse systemic effects of argyria confined to the nail beds. Similarly, the majority of generalized cases are not associated with systemic complications; however, potential toxicities, as described in isolated case reports without conclusive causal relationships, include nyctalopia, renal or hepatic toxicity, pulmonary fibrosis, and neuropsychiatric events.^1-6 Successful treatment of cutaneous argyria has been reported with the 1064-nm Q-switched Nd:YAG laser; however, there have been no reported treatments for nail bed involvement.⁷ Due to the absence of systemic symptoms, additional mucocutaneous dyspigmentation, or cosmetic concerns regarding nail bed lunulae discoloration in our patient, no further intervention was pursued, except for continued colloidal silver cessation.

The differential diagnosis of blue-gray nail bed dyspigmentation is broad and includes cyanosis secondary to cardiopulmonary disease, drug-induced dyspigmentation, Wilson disease, argyria, chrysiasis, hereditary acrolabial telangiectasia, and pseudomonal infection or chloronychia.^1,8,9 Etiologic insight may be provided from a thorough review of prescription and over-the-counter medications as well as careful attention to the distribution of dyspigmentation. Medications commonly associated with bluish nail bed dyspigmentation include antimalarials, amiodarone, minocycline, clofazimine, chlorpromazine/phenothiazines, and various chemotherapeutic drugs; our patient was not taking any of these.^1,9

Cyanotic nail bed dyspigmentation secondary to cardiopulmonary disease likely manifests with more diffuse nail bed dyspigmentation and is not confined solely to the lunulae. Only drug-induced dyspigmentation, classically due to phenolphthalein-containing laxatives; Wilson disease; and argyria have a tendency to spare the distal nail bed, which is a presentation termed azure lunulae.⁸ The toenails typically are spared in argyria, while toenail involvement is variable in Wilson disease, and additional systemic symptoms—including hepatic, ophthalmologic, and neuropsychiatric—as well as potential family history would be expected.⁸ Phenolphthalein is no longer available in over-the-counter laxatives, as it was formally banned by the US Food and Drug Administration in 1999 due to concerns of carcinogenicity.¹⁰

Hereditary acrolabial telangiectasia is a familial condition with autosomal-dominant inheritance that can manifest similarly to argyria with blue-gray discoloration of the proximal nail bed; however, this condition also would demonstrate involvement of the vermilion border and nipple areolae, often with associated telangiectasia and migraine headaches.¹¹

Chloronychia (also known as green nail syndrome) is an infection of the nail bed with Pseudomonas aeruginosa that more commonly presents with greenblack discoloration with variable involvement of the fingernails and toenails. Chloronychia, often with associated onycholysis, typically is found in individuals with repeated exposure to water, soaps, and detergents.¹² Our patient’s long-standing and unwavering nail bed appearance, involvement of all fingernail lunulae, lack of additional symptoms, and disclosed use of over-the-counter colloidal silver supported a clinical diagnosis of argyriainduced azure lunulae.

Argyria-induced azure lunulae secondary to colloidal silver exposure is an uncommon yet clinically significant cause of nail bed dyspigmentation. Prompt identification and cessation of the offending agent can prevent progression of mucocutaneous dyspigmentation and avoid potential long-term sequelae from systemic deposition.

The Diagnosis: Argyria-Induced Azure Lunulae

Argyria is an acquired condition resulting from excessive exogenous exposure to silver with subsequent gastrointestinal absorption and pigmentary tissue deposition. Upon further questioning, our patient disclosed a lifetime history of colloidal silver use, both as a topical antiseptic agent and intraorally for aphthous ulcers. Silver has a predilection for granular deposition in stromal tissues and basement membranes with sparing of the epidermis, manifesting as progressive, permanent, blue to slate gray discoloration of sunexposed skin, mucous membranes, and nail beds.¹ The patient was advised to discontinue use of colloidal silver to avoid development of further pigmentary changes. The appearance of his nails remained unchanged in the months following initial presentation, as expected, since argyria pigmentation is not anticipated to reverse upon colloidal silver cessation.

Nail involvement may be an early presentation of generalized argyria or may be found in isolation, as seen in our patient. Early recognition and patient education are essential to minimize cumulative silver deposition. Although dyspigmentation may impact psychosocial well-being secondary to aesthetic concerns, there is limited research supporting adverse systemic effects of argyria confined to the nail beds. Similarly, the majority of generalized cases are not associated with systemic complications; however, potential toxicities, as described in isolated case reports without conclusive causal relationships, include nyctalopia, renal or hepatic toxicity, pulmonary fibrosis, and neuropsychiatric events.^1-6 Successful treatment of cutaneous argyria has been reported with the 1064-nm Q-switched Nd:YAG laser; however, there have been no reported treatments for nail bed involvement.⁷ Due to the absence of systemic symptoms, additional mucocutaneous dyspigmentation, or cosmetic concerns regarding nail bed lunulae discoloration in our patient, no further intervention was pursued, except for continued colloidal silver cessation.

The differential diagnosis of blue-gray nail bed dyspigmentation is broad and includes cyanosis secondary to cardiopulmonary disease, drug-induced dyspigmentation, Wilson disease, argyria, chrysiasis, hereditary acrolabial telangiectasia, and pseudomonal infection or chloronychia.^1,8,9 Etiologic insight may be provided from a thorough review of prescription and over-the-counter medications as well as careful attention to the distribution of dyspigmentation. Medications commonly associated with bluish nail bed dyspigmentation include antimalarials, amiodarone, minocycline, clofazimine, chlorpromazine/phenothiazines, and various chemotherapeutic drugs; our patient was not taking any of these.^1,9

Cyanotic nail bed dyspigmentation secondary to cardiopulmonary disease likely manifests with more diffuse nail bed dyspigmentation and is not confined solely to the lunulae. Only drug-induced dyspigmentation, classically due to phenolphthalein-containing laxatives; Wilson disease; and argyria have a tendency to spare the distal nail bed, which is a presentation termed azure lunulae.⁸ The toenails typically are spared in argyria, while toenail involvement is variable in Wilson disease, and additional systemic symptoms—including hepatic, ophthalmologic, and neuropsychiatric—as well as potential family history would be expected.⁸ Phenolphthalein is no longer available in over-the-counter laxatives, as it was formally banned by the US Food and Drug Administration in 1999 due to concerns of carcinogenicity.¹⁰

Hereditary acrolabial telangiectasia is a familial condition with autosomal-dominant inheritance that can manifest similarly to argyria with blue-gray discoloration of the proximal nail bed; however, this condition also would demonstrate involvement of the vermilion border and nipple areolae, often with associated telangiectasia and migraine headaches.¹¹

Chloronychia (also known as green nail syndrome) is an infection of the nail bed with Pseudomonas aeruginosa that more commonly presents with greenblack discoloration with variable involvement of the fingernails and toenails. Chloronychia, often with associated onycholysis, typically is found in individuals with repeated exposure to water, soaps, and detergents.¹² Our patient’s long-standing and unwavering nail bed appearance, involvement of all fingernail lunulae, lack of additional symptoms, and disclosed use of over-the-counter colloidal silver supported a clinical diagnosis of argyriainduced azure lunulae.

Argyria-induced azure lunulae secondary to colloidal silver exposure is an uncommon yet clinically significant cause of nail bed dyspigmentation. Prompt identification and cessation of the offending agent can prevent progression of mucocutaneous dyspigmentation and avoid potential long-term sequelae from systemic deposition.

Key clinical point: The serum levels of vitamin D are significantly lower in patients with newly diagnosed eosinophilic esophagitis (EoE) than in control individuals without EoE; however, vitamin D levels are not strongly linked with the clinical, endoscopic, or histologic features of EoE.

Major finding: Mean serum 25-hydroxy-vitamin D₃ levels were lower by 10.8 ng/mL in patients with EoE vs control individuals (95% CI −19.0 to −2.51). However, these levels were neither associated with differences in clinical or endoscopic features of EoE nor did they significantly correlate with EoE Endoscopic Reference Scores and eosinophil counts (Pearson’s R −0.28, P = .08; and −0.01, P = .93, respectively).

Study details: This secondary analysis of a prospective cohort study used the data of adults who underwent endoscopy and biopsy for upper gastrointestinal symptoms, of whom 40 were diagnosed with EoE and 40 were control individuals without EoE.

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cameron BA et al. Vitamin D levels as a potential modifier of eosinophilic esophagitis severity in adults. Dig Dis Sci. 2024 (Jan 6). doi: 10.1007/s10620-023-08264-x

Key clinical point: The serum levels of vitamin D are significantly lower in patients with newly diagnosed eosinophilic esophagitis (EoE) than in control individuals without EoE; however, vitamin D levels are not strongly linked with the clinical, endoscopic, or histologic features of EoE.

Major finding: Mean serum 25-hydroxy-vitamin D₃ levels were lower by 10.8 ng/mL in patients with EoE vs control individuals (95% CI −19.0 to −2.51). However, these levels were neither associated with differences in clinical or endoscopic features of EoE nor did they significantly correlate with EoE Endoscopic Reference Scores and eosinophil counts (Pearson’s R −0.28, P = .08; and −0.01, P = .93, respectively).

Study details: This secondary analysis of a prospective cohort study used the data of adults who underwent endoscopy and biopsy for upper gastrointestinal symptoms, of whom 40 were diagnosed with EoE and 40 were control individuals without EoE.

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cameron BA et al. Vitamin D levels as a potential modifier of eosinophilic esophagitis severity in adults. Dig Dis Sci. 2024 (Jan 6). doi: 10.1007/s10620-023-08264-x

Key clinical point: The serum levels of vitamin D are significantly lower in patients with newly diagnosed eosinophilic esophagitis (EoE) than in control individuals without EoE; however, vitamin D levels are not strongly linked with the clinical, endoscopic, or histologic features of EoE.

Major finding: Mean serum 25-hydroxy-vitamin D₃ levels were lower by 10.8 ng/mL in patients with EoE vs control individuals (95% CI −19.0 to −2.51). However, these levels were neither associated with differences in clinical or endoscopic features of EoE nor did they significantly correlate with EoE Endoscopic Reference Scores and eosinophil counts (Pearson’s R −0.28, P = .08; and −0.01, P = .93, respectively).

Study details: This secondary analysis of a prospective cohort study used the data of adults who underwent endoscopy and biopsy for upper gastrointestinal symptoms, of whom 40 were diagnosed with EoE and 40 were control individuals without EoE.

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cameron BA et al. Vitamin D levels as a potential modifier of eosinophilic esophagitis severity in adults. Dig Dis Sci. 2024 (Jan 6). doi: 10.1007/s10620-023-08264-x

Key clinical point: Patients with eosinophilic esophagitis (EoE) who test positive for food and environmental allergens may report a lower response to proton-pump inhibitor (PPI) treatment, a first-line treatment for EoE.

Major finding: Positive food allergen testing predicted lower odds of histologic response (adjusted odds ratio [aOR] 0.15; P = .0006) and symptom response (aOR 0.22; P = .03) to PPI therapy. Patients with a higher number of positive environmental allergens detected on skin-prick testing (≥10 vs <10) were less likely to respond to PPI (21.0% vs 53.9%; P = .03).

Study details: Findings are from a retrospective study including 61 adults with newly diagnosed EoE who underwent formal allergy testing for food and environmental allergens and received PPI therapy twice daily after EoE diagnosis.

Disclosures: The corresponding author WW Chan declared serving on the scientific advisory board for a several pharmaceutical companies.

Source: Muftah M et al. Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis. J Gastroenterol Hepatol. 2024 (Jan 7). doi: 10.1111/jgh.16469

Key clinical point: Patients with eosinophilic esophagitis (EoE) who test positive for food and environmental allergens may report a lower response to proton-pump inhibitor (PPI) treatment, a first-line treatment for EoE.

Major finding: Positive food allergen testing predicted lower odds of histologic response (adjusted odds ratio [aOR] 0.15; P = .0006) and symptom response (aOR 0.22; P = .03) to PPI therapy. Patients with a higher number of positive environmental allergens detected on skin-prick testing (≥10 vs <10) were less likely to respond to PPI (21.0% vs 53.9%; P = .03).

Study details: Findings are from a retrospective study including 61 adults with newly diagnosed EoE who underwent formal allergy testing for food and environmental allergens and received PPI therapy twice daily after EoE diagnosis.

Disclosures: The corresponding author WW Chan declared serving on the scientific advisory board for a several pharmaceutical companies.

Source: Muftah M et al. Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis. J Gastroenterol Hepatol. 2024 (Jan 7). doi: 10.1111/jgh.16469

Key clinical point: Patients with eosinophilic esophagitis (EoE) who test positive for food and environmental allergens may report a lower response to proton-pump inhibitor (PPI) treatment, a first-line treatment for EoE.

Major finding: Positive food allergen testing predicted lower odds of histologic response (adjusted odds ratio [aOR] 0.15; P = .0006) and symptom response (aOR 0.22; P = .03) to PPI therapy. Patients with a higher number of positive environmental allergens detected on skin-prick testing (≥10 vs <10) were less likely to respond to PPI (21.0% vs 53.9%; P = .03).

Study details: Findings are from a retrospective study including 61 adults with newly diagnosed EoE who underwent formal allergy testing for food and environmental allergens and received PPI therapy twice daily after EoE diagnosis.

Disclosures: The corresponding author WW Chan declared serving on the scientific advisory board for a several pharmaceutical companies.

Source: Muftah M et al. Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis. J Gastroenterol Hepatol. 2024 (Jan 7). doi: 10.1111/jgh.16469

Key clinical point: Budesonide orodispersible tablet (BOT) induces clinicohistological remission irrespective of the distribution of esophageal eosinophilia. Histological categories are not predictors of treatment response in patients with eosinophilic esophagitis (EoE).

Major finding: Histological categories were not found to be significantly associated with treatment outcome (mid: adjusted odds ratio [aOR] 1.75; 95% CI 0.588-5.25; distal: aOR 1.42; 95% CI 0.535-3.60; diffuse: aOR 0.910; 95% CI 0.358-2.19).

Study details: This post hoc analysis of the phase 3 EOS-1 and EOS-2 trials included 263 patients with EoE having either proximal, mid, or distal esophagus predominant disease or diffuse disease who received a 6-week induction treatment with BOT.

Disclosures: This study was supported by the Swiss National Science Foundation and others. Some authors declared serving as consultants for or receiving speaker or consulting fees or travel grants from various sources.

Source: Godat A et al on behalf of the EoE eosinophil distribution research group. Eosinophil distribution in eosinophilic esophagitis and its impact on disease activity and response to treatment. Clin Gastroenterol Hepatol. 2023 (Dec 15). doi: 10.1016/j.cgh.2023.12.003

Key clinical point: Budesonide orodispersible tablet (BOT) induces clinicohistological remission irrespective of the distribution of esophageal eosinophilia. Histological categories are not predictors of treatment response in patients with eosinophilic esophagitis (EoE).

Major finding: Histological categories were not found to be significantly associated with treatment outcome (mid: adjusted odds ratio [aOR] 1.75; 95% CI 0.588-5.25; distal: aOR 1.42; 95% CI 0.535-3.60; diffuse: aOR 0.910; 95% CI 0.358-2.19).

Study details: This post hoc analysis of the phase 3 EOS-1 and EOS-2 trials included 263 patients with EoE having either proximal, mid, or distal esophagus predominant disease or diffuse disease who received a 6-week induction treatment with BOT.

Disclosures: This study was supported by the Swiss National Science Foundation and others. Some authors declared serving as consultants for or receiving speaker or consulting fees or travel grants from various sources.

Source: Godat A et al on behalf of the EoE eosinophil distribution research group. Eosinophil distribution in eosinophilic esophagitis and its impact on disease activity and response to treatment. Clin Gastroenterol Hepatol. 2023 (Dec 15). doi: 10.1016/j.cgh.2023.12.003

Key clinical point: Budesonide orodispersible tablet (BOT) induces clinicohistological remission irrespective of the distribution of esophageal eosinophilia. Histological categories are not predictors of treatment response in patients with eosinophilic esophagitis (EoE).

Major finding: Histological categories were not found to be significantly associated with treatment outcome (mid: adjusted odds ratio [aOR] 1.75; 95% CI 0.588-5.25; distal: aOR 1.42; 95% CI 0.535-3.60; diffuse: aOR 0.910; 95% CI 0.358-2.19).

Study details: This post hoc analysis of the phase 3 EOS-1 and EOS-2 trials included 263 patients with EoE having either proximal, mid, or distal esophagus predominant disease or diffuse disease who received a 6-week induction treatment with BOT.

Disclosures: This study was supported by the Swiss National Science Foundation and others. Some authors declared serving as consultants for or receiving speaker or consulting fees or travel grants from various sources.

Source: Godat A et al on behalf of the EoE eosinophil distribution research group. Eosinophil distribution in eosinophilic esophagitis and its impact on disease activity and response to treatment. Clin Gastroenterol Hepatol. 2023 (Dec 15). doi: 10.1016/j.cgh.2023.12.003

Key clinical point: The levels of eosinophil-derived neurotoxin (EDN) may be used to track disease activity in patients with eosinophilic esophagitis (EoE) patients and may aid the diagnosis of EoE in patients with challenging conditions, such as distal eosinophilia.

Major finding: The average endoscopic reference score (EREFS; 3.4 vs 0.4; P < .001) and EDN concentrations (135.8 µg/mL vs 3.2 µg/mL; P < .001) were significantly higher in patients with active EoE vs control individuals. In patients with exclusive distant eosinophilia, positive (≥10 µg/mL) vs negative EDN concentrations correlated with significantly higher EREFS (3.33 vs 1.35, P < .001), which indicated a diagnosis of EoE.

Study details: Findings are from a retrospective study that included children and young adults who underwent routine endoscopy with biopsy and EDN esophageal epithelial brushings, of whom 140 had EoE and 91 were control individuals without EoE.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Thomas J et al. Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin. J Pediatr Gastroenterol Nutr. 2023 (Dec 27). doi: 10.1002/jpn3.12054

Key clinical point: The levels of eosinophil-derived neurotoxin (EDN) may be used to track disease activity in patients with eosinophilic esophagitis (EoE) patients and may aid the diagnosis of EoE in patients with challenging conditions, such as distal eosinophilia.

Major finding: The average endoscopic reference score (EREFS; 3.4 vs 0.4; P < .001) and EDN concentrations (135.8 µg/mL vs 3.2 µg/mL; P < .001) were significantly higher in patients with active EoE vs control individuals. In patients with exclusive distant eosinophilia, positive (≥10 µg/mL) vs negative EDN concentrations correlated with significantly higher EREFS (3.33 vs 1.35, P < .001), which indicated a diagnosis of EoE.

Study details: Findings are from a retrospective study that included children and young adults who underwent routine endoscopy with biopsy and EDN esophageal epithelial brushings, of whom 140 had EoE and 91 were control individuals without EoE.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Thomas J et al. Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin. J Pediatr Gastroenterol Nutr. 2023 (Dec 27). doi: 10.1002/jpn3.12054

Key clinical point: The levels of eosinophil-derived neurotoxin (EDN) may be used to track disease activity in patients with eosinophilic esophagitis (EoE) patients and may aid the diagnosis of EoE in patients with challenging conditions, such as distal eosinophilia.

Major finding: The average endoscopic reference score (EREFS; 3.4 vs 0.4; P < .001) and EDN concentrations (135.8 µg/mL vs 3.2 µg/mL; P < .001) were significantly higher in patients with active EoE vs control individuals. In patients with exclusive distant eosinophilia, positive (≥10 µg/mL) vs negative EDN concentrations correlated with significantly higher EREFS (3.33 vs 1.35, P < .001), which indicated a diagnosis of EoE.

Study details: Findings are from a retrospective study that included children and young adults who underwent routine endoscopy with biopsy and EDN esophageal epithelial brushings, of whom 140 had EoE and 91 were control individuals without EoE.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Thomas J et al. Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin. J Pediatr Gastroenterol Nutr. 2023 (Dec 27). doi: 10.1002/jpn3.12054

Key clinical point: Patients with eosinophilic esophagitis (EoE) may also present with non-EoE eosinophilic gastrointestinal diseases (EGID) with esophageal involvement (EI; EGID + EI) if they have high levels of peripheral blood eosinophils.

Major finding: Patients with EGID + EI vs EoE were more likely to have eczema (P = .003), food allergy (P < .001), abdominal pain (60.9% vs 45.0%; P = .002), and higher peripheral blood eosinophil levels (0.44 × 10³/µL vs 0.38 × 10³/µL; P = .027).

Study details: Findings are from an observational cohort study including 592 patients with isolated EoE and 190 patients with EGID + EI.

Disclosures: This study was supported by a grant from the US National Institutes of Health. ME Rothenberg and corresponding author T Shoda declared serving as a consultant or being inventors or co-inventors of patents.

Source: Sato H et al. Eosinophil involvement outside the esophagus in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2023 (Dec 14). doi: 10.1016/j.cgh.2023.12.004

Key clinical point: Patients with eosinophilic esophagitis (EoE) may also present with non-EoE eosinophilic gastrointestinal diseases (EGID) with esophageal involvement (EI; EGID + EI) if they have high levels of peripheral blood eosinophils.

Major finding: Patients with EGID + EI vs EoE were more likely to have eczema (P = .003), food allergy (P < .001), abdominal pain (60.9% vs 45.0%; P = .002), and higher peripheral blood eosinophil levels (0.44 × 10³/µL vs 0.38 × 10³/µL; P = .027).

Study details: Findings are from an observational cohort study including 592 patients with isolated EoE and 190 patients with EGID + EI.

Disclosures: This study was supported by a grant from the US National Institutes of Health. ME Rothenberg and corresponding author T Shoda declared serving as a consultant or being inventors or co-inventors of patents.

Source: Sato H et al. Eosinophil involvement outside the esophagus in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2023 (Dec 14). doi: 10.1016/j.cgh.2023.12.004

Key clinical point: Patients with eosinophilic esophagitis (EoE) may also present with non-EoE eosinophilic gastrointestinal diseases (EGID) with esophageal involvement (EI; EGID + EI) if they have high levels of peripheral blood eosinophils.

Major finding: Patients with EGID + EI vs EoE were more likely to have eczema (P = .003), food allergy (P < .001), abdominal pain (60.9% vs 45.0%; P = .002), and higher peripheral blood eosinophil levels (0.44 × 10³/µL vs 0.38 × 10³/µL; P = .027).

Study details: Findings are from an observational cohort study including 592 patients with isolated EoE and 190 patients with EGID + EI.

Disclosures: This study was supported by a grant from the US National Institutes of Health. ME Rothenberg and corresponding author T Shoda declared serving as a consultant or being inventors or co-inventors of patents.

Source: Sato H et al. Eosinophil involvement outside the esophagus in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2023 (Dec 14). doi: 10.1016/j.cgh.2023.12.004