Aesthetic Dermatology

In 2013, the Centers for Medicare and Medicaid Services (CMS) issued a guidance to reduce reimbursement issues for Mohs micrographic surgery (MMS).¹ One crucial question that remains is when and if these documentation guidelines will be formally implemented. The guidelines outlined by the CMS currently are regarded as suggestions until Medicare contractors adopt them into the local coverage determinations (LCDs).

Key Documentation Guidelines

To reduce MMS reimbursement issues, documentation in the patient’s medical record should support the medical necessity of the procedure and reflect the number and anatomic locations of specimens taken and the reason for the procedure should be clearly communicated. The specific tumor type also should be approved for treatment with MMS in the respective LCD.

Nonphysician providers are not authorized by Medicare to perform MMS. To ensure proper coding, both surgery and pathology must be performed by a single physician and should be supported by documentation in the patient’s medical record (eg, relevant chart notes should be made under the provider’s signature). These documentation guidelines are not new but are included in the CMS guidance to reiterate their importance in reducing MMS reimbursement issues.

Per customary clinical practice, the CMS guidance specifies that MMS documentation should include gross description of the tissue removed, including the location, number, and size of the lesions, as well as how many specimens were removed for each stage. However, the guidance diverges from routine MMS documentation requirements in its emphasis on providing a histologic description of the tissue removed. The guidance suggests that the depth of tumor invasion, pathologic pattern, cell morphology (which is not typically specified for skin cancers), and, if present, the existence of perineural invasion or scar tissue should be documented. If these features are constant across stages, they only need to be noted for the first stage.

Adapting Guidelines for Clinical Practice

The CMS guidance may create some conundrums for physicians regarding MMS documentation; for instance, if a tumor is cleared in one stage, as is often the case, no tumor will be seen on glass slides prepared to assess tissue margins during the procedure and therefore documentation of characteristics like depth and pattern will be impossible. Similarly, cell morphology is not a feature that usually is relevant for most squamous and basal cell carcinomas, although it may be useful in certain unusual instances, such as in cases of rare tumors with particular histologic features that may influence management and/or prognosis. When in doubt regarding the appropriate documentation method for MMS, the surgeon should use his or her best judgment based on clinical experience rather than simply following guidelines that may not be applicable.

Final Thoughts

The CMS guidance serves as a reminder of the documentation requirements for MMS and extends current practice by suggesting a detailed microscopic description of the removed tissue. The American Academy of Dermatology has developed a guide to help Mohs surgeons provide the necessary documentation without creating cumbersome chart notes.² Mohs surgeons should consult the most recent version of the LCD that applies to their geographic area to determine if the new documentation guidelines have been adopted.

In 2013, the Centers for Medicare and Medicaid Services (CMS) issued a guidance to reduce reimbursement issues for Mohs micrographic surgery (MMS).¹ One crucial question that remains is when and if these documentation guidelines will be formally implemented. The guidelines outlined by the CMS currently are regarded as suggestions until Medicare contractors adopt them into the local coverage determinations (LCDs).

Key Documentation Guidelines

To reduce MMS reimbursement issues, documentation in the patient’s medical record should support the medical necessity of the procedure and reflect the number and anatomic locations of specimens taken and the reason for the procedure should be clearly communicated. The specific tumor type also should be approved for treatment with MMS in the respective LCD.

Nonphysician providers are not authorized by Medicare to perform MMS. To ensure proper coding, both surgery and pathology must be performed by a single physician and should be supported by documentation in the patient’s medical record (eg, relevant chart notes should be made under the provider’s signature). These documentation guidelines are not new but are included in the CMS guidance to reiterate their importance in reducing MMS reimbursement issues.

Per customary clinical practice, the CMS guidance specifies that MMS documentation should include gross description of the tissue removed, including the location, number, and size of the lesions, as well as how many specimens were removed for each stage. However, the guidance diverges from routine MMS documentation requirements in its emphasis on providing a histologic description of the tissue removed. The guidance suggests that the depth of tumor invasion, pathologic pattern, cell morphology (which is not typically specified for skin cancers), and, if present, the existence of perineural invasion or scar tissue should be documented. If these features are constant across stages, they only need to be noted for the first stage.

Adapting Guidelines for Clinical Practice

The CMS guidance may create some conundrums for physicians regarding MMS documentation; for instance, if a tumor is cleared in one stage, as is often the case, no tumor will be seen on glass slides prepared to assess tissue margins during the procedure and therefore documentation of characteristics like depth and pattern will be impossible. Similarly, cell morphology is not a feature that usually is relevant for most squamous and basal cell carcinomas, although it may be useful in certain unusual instances, such as in cases of rare tumors with particular histologic features that may influence management and/or prognosis. When in doubt regarding the appropriate documentation method for MMS, the surgeon should use his or her best judgment based on clinical experience rather than simply following guidelines that may not be applicable.

Final Thoughts

The CMS guidance serves as a reminder of the documentation requirements for MMS and extends current practice by suggesting a detailed microscopic description of the removed tissue. The American Academy of Dermatology has developed a guide to help Mohs surgeons provide the necessary documentation without creating cumbersome chart notes.² Mohs surgeons should consult the most recent version of the LCD that applies to their geographic area to determine if the new documentation guidelines have been adopted.

In 2013, the Centers for Medicare and Medicaid Services (CMS) issued a guidance to reduce reimbursement issues for Mohs micrographic surgery (MMS).¹ One crucial question that remains is when and if these documentation guidelines will be formally implemented. The guidelines outlined by the CMS currently are regarded as suggestions until Medicare contractors adopt them into the local coverage determinations (LCDs).

Key Documentation Guidelines

To reduce MMS reimbursement issues, documentation in the patient’s medical record should support the medical necessity of the procedure and reflect the number and anatomic locations of specimens taken and the reason for the procedure should be clearly communicated. The specific tumor type also should be approved for treatment with MMS in the respective LCD.

Nonphysician providers are not authorized by Medicare to perform MMS. To ensure proper coding, both surgery and pathology must be performed by a single physician and should be supported by documentation in the patient’s medical record (eg, relevant chart notes should be made under the provider’s signature). These documentation guidelines are not new but are included in the CMS guidance to reiterate their importance in reducing MMS reimbursement issues.

Per customary clinical practice, the CMS guidance specifies that MMS documentation should include gross description of the tissue removed, including the location, number, and size of the lesions, as well as how many specimens were removed for each stage. However, the guidance diverges from routine MMS documentation requirements in its emphasis on providing a histologic description of the tissue removed. The guidance suggests that the depth of tumor invasion, pathologic pattern, cell morphology (which is not typically specified for skin cancers), and, if present, the existence of perineural invasion or scar tissue should be documented. If these features are constant across stages, they only need to be noted for the first stage.

Adapting Guidelines for Clinical Practice

The CMS guidance may create some conundrums for physicians regarding MMS documentation; for instance, if a tumor is cleared in one stage, as is often the case, no tumor will be seen on glass slides prepared to assess tissue margins during the procedure and therefore documentation of characteristics like depth and pattern will be impossible. Similarly, cell morphology is not a feature that usually is relevant for most squamous and basal cell carcinomas, although it may be useful in certain unusual instances, such as in cases of rare tumors with particular histologic features that may influence management and/or prognosis. When in doubt regarding the appropriate documentation method for MMS, the surgeon should use his or her best judgment based on clinical experience rather than simply following guidelines that may not be applicable.

Final Thoughts

The CMS guidance serves as a reminder of the documentation requirements for MMS and extends current practice by suggesting a detailed microscopic description of the removed tissue. The American Academy of Dermatology has developed a guide to help Mohs surgeons provide the necessary documentation without creating cumbersome chart notes.² Mohs surgeons should consult the most recent version of the LCD that applies to their geographic area to determine if the new documentation guidelines have been adopted.

Native to China, India, and Iran, Melia azedarach – also known as Chinaberry (Ku-lian), Pride of China, Indian lilac, Persian lilac, and white cedar – is a large nondeciduous tree now cultivated throughout the world.^1-3 The leaves and fruits of this member of the Meliaceae family have been found to exhibit anthelmintic and antifeedant activity toward insects.⁴ The root bark or dried stem bark of the plant is used in traditional Chinese medicine to treat dermatoses and to expel and repel worms.^5,6M. azedarach has also been used in Ayurveda³; it is known as Bakayn in India and Pakistan, where it has been used in traditional medicine to treat leprosy, scrofula, nausea, vomiting, thirst, and eruptive skin conditions.^3,7

Traditional indications

Cropley and Hasegawa noted in 2007 that M. azedarach was used in the 19th century in the United States primarily as an anthelmintic, but also to treat tinea capitis and to eliminate lice.Further, they noted that the plant, which was widely cultivated in the South, was used, according to the literature of the 1800s, as a diuretic, as well as to promote hair growth, and treat scalp eruptions, fever, and malaria.⁸

A 2006 ethnopharmacologic study by Saikia et al. of medicinal plants used in Assam (Northeast India) to treat skin disorders and for cosmetic purposes revealed that M. azedarach was one of the primary plants used for medicinal purposes, including 18 skin conditions such as acne, burns, carbuncles, abscesses, measles, pediculosis, cellulitis, and prickly heat.⁹

Four years later, in an ethnopharmacologic study of medicinal plants used to treat cutaneous disorders and in folk cosmetics, Abbasi et al. interviewed residents in 30 remote tribal communities in the Northwest Frontier Province of Pakistan, finding that M. azedarach was one of 15 plant species identified as curative for numerous skin diseases, including boils, acne, and scabies.¹⁰

Biologic activity

Various constituents of M. azedarach have been associated with a wide range of biologic activity. The antifungal activity of the plant has been attributed to its hydroxycoumarin content; anti-inflammatory activity to its monoterpenes; bacteriostatic properties to its beta-carboline alkaloids; antiviral effects to its meliacin and meliacarpin; and insecticidal and antifeedant activity to its limonoids, which belong to the tetranortriterpenoid class of compounds.^7,11 Limonoids also are reputed to confer antibacterial, antiviral, and antifungal activities.¹² Recent research suggests the potential of M. azedarach to offer a correspondingly broad impact on various conditions.

Forest & Kim Starr

Anticancer potential

Zhou et al. isolated new ring C-seco limonoids from Brazilian M. azedarach in 2004 and evaluated their cytotoxic activity, finding that two limonoids significantly inhibited HeLa S3 cancer cells.^4,11

In 2009, He et al. extracted water-soluble polysaccharides from the fruit of M. azedarach and assessed their cytotoxic activity against four human cell lines in vitro. They found that the major polysaccharide component exhibited potent cytotoxic activity in the BGC-823 cell line.³ Also that year, Wu et al. isolated three new and multiple known steroids from the leaves of Chinese M. azedarach, finding that two of the newly identified steroids – (20S)-5,24(28)-ergostadiene-3-beta,7-alpha,16-beta,20-tetrol and (20S)-5-ergostene-3-beta,7-alpha,16-beta,20-tetrol – and one of the known ones exerted significant cytotoxic impact in three human cancer cell lines (A-549, H460, U251).¹

Two years later, Wu et al. isolated two new triterpenoids (21,24-cycloeupha-7-ene-3-beta,16beta,21-alpha,25-tetrol and 3-beta-acetoxy-12-beta-hydroxy-eupha-7,24-dien-21,16-beta-olide) and two new steroids (29-hydroperoxy-stigmasta-7,24(28) xi-dien-3-beta-ol and 24-xi-hydroperoxy-24-vinyl-lathosterol) along with several known related substances from M. azedarach bark. Five of the known compounds demonstrated cytotoxic activity against three human cancer cell lines (A-549, H460, HGC27).⁶

More recently, Yuan et al. isolated two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, as well as nine known limonoids from the bark of M. azedarach. In addition, the investigators observed that seven of the limonoids exhibited significant inhibitory properties against five human tumor cell lines (HL-60, SMM-C7721, A-549, MCF-7, and SW480).⁵

Efficacy against head lice

In 2007, Carpinella et al. investigated in vitro the pediculicidal and ovicidal activity of an M. azedarach extract against Pediculus humanus capitis, noting the increasing resistance of head lice to synthetic drugs. A combination of 20% ripe fruit extract with 10% ripe fruit oil was found to be the most effective in eradicating adult lice (96.5%). The investigators also prepared a formulation of extract and oil at 10% combined with an emulsifier and preservatives that yielded 92.3% mortality of adult lice and complete inhibition of nymph emergence. They concluded that the use of M. azedarach formulations may be a viable and natural way to control head lice.²M. azedarach also has been the key active ingredient in an antimicrobial cream and a preparation to treat tinea pedis.⁷

Topical cream

Saleem et al. reported in 2008 on an herbal cream preparation using a standardized extract of M. azedarach flowers that displayed strong antibacterial activity against cellulitis, pustules, and pyogenic infections, and other conditions in clinical trials in children under the age of 10 years in four different villages in Pakistan. Subjects with bacterial infections anywhere on the body were divided into three groups, one treated with M. azedarach cream, one with placebo (negative control), and one with neomycin (positive control). Each treatment was applied twice daily for 15 days. The investigators observed that the healing effects of M. azedarach were similar to those rendered by neomycin.⁷

Conclusion

Not only has M. azedarach been used in several traditional medical systems, but its uses have consistently included cutaneous indications. Its most convincing modern application may be for head lice, but recent evidence and traditional uses suggest that this versatile plant may indeed warrant a more prominent role in the current dermatologic armamentarium. Future research is needed, and should provide some interesting answers.

References

1. Steroids. 2009 Sep;74(9):761-5.

2. J Am Acad Dermatol. 2007 Feb;56(2):250-6.

3. Fitoterapia. 2009 Oct;80(7):399-403.

4. Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1362-5.

5. Planta Med. 2013 Jan;79(2):163-8.

6. Planta Med. 2011 Jun;77(9):922-8.

7. Phytomedicine. 2008 Apr;15(4):231-6.

8. J Am Acad Dermatol. 2007 Aug;57(2):366-7.

9. J Ethnopharmacol. 2006 Jun 30;106(2):149-57.

10. J Ethnopharmacol. 2010 Mar 24;128(2):322-35.

11. J Nat Prod. 2004 Sep;67(9):1544-7.

12. Chem Biodivers. 2010 Apr;7(4):839-59.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Native to China, India, and Iran, Melia azedarach – also known as Chinaberry (Ku-lian), Pride of China, Indian lilac, Persian lilac, and white cedar – is a large nondeciduous tree now cultivated throughout the world.^1-3 The leaves and fruits of this member of the Meliaceae family have been found to exhibit anthelmintic and antifeedant activity toward insects.⁴ The root bark or dried stem bark of the plant is used in traditional Chinese medicine to treat dermatoses and to expel and repel worms.^5,6M. azedarach has also been used in Ayurveda³; it is known as Bakayn in India and Pakistan, where it has been used in traditional medicine to treat leprosy, scrofula, nausea, vomiting, thirst, and eruptive skin conditions.^3,7

Traditional indications

Cropley and Hasegawa noted in 2007 that M. azedarach was used in the 19th century in the United States primarily as an anthelmintic, but also to treat tinea capitis and to eliminate lice.Further, they noted that the plant, which was widely cultivated in the South, was used, according to the literature of the 1800s, as a diuretic, as well as to promote hair growth, and treat scalp eruptions, fever, and malaria.⁸

A 2006 ethnopharmacologic study by Saikia et al. of medicinal plants used in Assam (Northeast India) to treat skin disorders and for cosmetic purposes revealed that M. azedarach was one of the primary plants used for medicinal purposes, including 18 skin conditions such as acne, burns, carbuncles, abscesses, measles, pediculosis, cellulitis, and prickly heat.⁹

Four years later, in an ethnopharmacologic study of medicinal plants used to treat cutaneous disorders and in folk cosmetics, Abbasi et al. interviewed residents in 30 remote tribal communities in the Northwest Frontier Province of Pakistan, finding that M. azedarach was one of 15 plant species identified as curative for numerous skin diseases, including boils, acne, and scabies.¹⁰

Biologic activity

Various constituents of M. azedarach have been associated with a wide range of biologic activity. The antifungal activity of the plant has been attributed to its hydroxycoumarin content; anti-inflammatory activity to its monoterpenes; bacteriostatic properties to its beta-carboline alkaloids; antiviral effects to its meliacin and meliacarpin; and insecticidal and antifeedant activity to its limonoids, which belong to the tetranortriterpenoid class of compounds.^7,11 Limonoids also are reputed to confer antibacterial, antiviral, and antifungal activities.¹² Recent research suggests the potential of M. azedarach to offer a correspondingly broad impact on various conditions.

Forest & Kim Starr

Anticancer potential

Zhou et al. isolated new ring C-seco limonoids from Brazilian M. azedarach in 2004 and evaluated their cytotoxic activity, finding that two limonoids significantly inhibited HeLa S3 cancer cells.^4,11

In 2009, He et al. extracted water-soluble polysaccharides from the fruit of M. azedarach and assessed their cytotoxic activity against four human cell lines in vitro. They found that the major polysaccharide component exhibited potent cytotoxic activity in the BGC-823 cell line.³ Also that year, Wu et al. isolated three new and multiple known steroids from the leaves of Chinese M. azedarach, finding that two of the newly identified steroids – (20S)-5,24(28)-ergostadiene-3-beta,7-alpha,16-beta,20-tetrol and (20S)-5-ergostene-3-beta,7-alpha,16-beta,20-tetrol – and one of the known ones exerted significant cytotoxic impact in three human cancer cell lines (A-549, H460, U251).¹

Two years later, Wu et al. isolated two new triterpenoids (21,24-cycloeupha-7-ene-3-beta,16beta,21-alpha,25-tetrol and 3-beta-acetoxy-12-beta-hydroxy-eupha-7,24-dien-21,16-beta-olide) and two new steroids (29-hydroperoxy-stigmasta-7,24(28) xi-dien-3-beta-ol and 24-xi-hydroperoxy-24-vinyl-lathosterol) along with several known related substances from M. azedarach bark. Five of the known compounds demonstrated cytotoxic activity against three human cancer cell lines (A-549, H460, HGC27).⁶

More recently, Yuan et al. isolated two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, as well as nine known limonoids from the bark of M. azedarach. In addition, the investigators observed that seven of the limonoids exhibited significant inhibitory properties against five human tumor cell lines (HL-60, SMM-C7721, A-549, MCF-7, and SW480).⁵

Efficacy against head lice

In 2007, Carpinella et al. investigated in vitro the pediculicidal and ovicidal activity of an M. azedarach extract against Pediculus humanus capitis, noting the increasing resistance of head lice to synthetic drugs. A combination of 20% ripe fruit extract with 10% ripe fruit oil was found to be the most effective in eradicating adult lice (96.5%). The investigators also prepared a formulation of extract and oil at 10% combined with an emulsifier and preservatives that yielded 92.3% mortality of adult lice and complete inhibition of nymph emergence. They concluded that the use of M. azedarach formulations may be a viable and natural way to control head lice.²M. azedarach also has been the key active ingredient in an antimicrobial cream and a preparation to treat tinea pedis.⁷

Topical cream

Saleem et al. reported in 2008 on an herbal cream preparation using a standardized extract of M. azedarach flowers that displayed strong antibacterial activity against cellulitis, pustules, and pyogenic infections, and other conditions in clinical trials in children under the age of 10 years in four different villages in Pakistan. Subjects with bacterial infections anywhere on the body were divided into three groups, one treated with M. azedarach cream, one with placebo (negative control), and one with neomycin (positive control). Each treatment was applied twice daily for 15 days. The investigators observed that the healing effects of M. azedarach were similar to those rendered by neomycin.⁷

Conclusion

Not only has M. azedarach been used in several traditional medical systems, but its uses have consistently included cutaneous indications. Its most convincing modern application may be for head lice, but recent evidence and traditional uses suggest that this versatile plant may indeed warrant a more prominent role in the current dermatologic armamentarium. Future research is needed, and should provide some interesting answers.

References

1. Steroids. 2009 Sep;74(9):761-5.

2. J Am Acad Dermatol. 2007 Feb;56(2):250-6.

3. Fitoterapia. 2009 Oct;80(7):399-403.

4. Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1362-5.

5. Planta Med. 2013 Jan;79(2):163-8.

6. Planta Med. 2011 Jun;77(9):922-8.

7. Phytomedicine. 2008 Apr;15(4):231-6.

8. J Am Acad Dermatol. 2007 Aug;57(2):366-7.

9. J Ethnopharmacol. 2006 Jun 30;106(2):149-57.

10. J Ethnopharmacol. 2010 Mar 24;128(2):322-35.

11. J Nat Prod. 2004 Sep;67(9):1544-7.

12. Chem Biodivers. 2010 Apr;7(4):839-59.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Native to China, India, and Iran, Melia azedarach – also known as Chinaberry (Ku-lian), Pride of China, Indian lilac, Persian lilac, and white cedar – is a large nondeciduous tree now cultivated throughout the world.^1-3 The leaves and fruits of this member of the Meliaceae family have been found to exhibit anthelmintic and antifeedant activity toward insects.⁴ The root bark or dried stem bark of the plant is used in traditional Chinese medicine to treat dermatoses and to expel and repel worms.^5,6M. azedarach has also been used in Ayurveda³; it is known as Bakayn in India and Pakistan, where it has been used in traditional medicine to treat leprosy, scrofula, nausea, vomiting, thirst, and eruptive skin conditions.^3,7

Traditional indications

Cropley and Hasegawa noted in 2007 that M. azedarach was used in the 19th century in the United States primarily as an anthelmintic, but also to treat tinea capitis and to eliminate lice.Further, they noted that the plant, which was widely cultivated in the South, was used, according to the literature of the 1800s, as a diuretic, as well as to promote hair growth, and treat scalp eruptions, fever, and malaria.⁸

A 2006 ethnopharmacologic study by Saikia et al. of medicinal plants used in Assam (Northeast India) to treat skin disorders and for cosmetic purposes revealed that M. azedarach was one of the primary plants used for medicinal purposes, including 18 skin conditions such as acne, burns, carbuncles, abscesses, measles, pediculosis, cellulitis, and prickly heat.⁹

Four years later, in an ethnopharmacologic study of medicinal plants used to treat cutaneous disorders and in folk cosmetics, Abbasi et al. interviewed residents in 30 remote tribal communities in the Northwest Frontier Province of Pakistan, finding that M. azedarach was one of 15 plant species identified as curative for numerous skin diseases, including boils, acne, and scabies.¹⁰

Biologic activity

Various constituents of M. azedarach have been associated with a wide range of biologic activity. The antifungal activity of the plant has been attributed to its hydroxycoumarin content; anti-inflammatory activity to its monoterpenes; bacteriostatic properties to its beta-carboline alkaloids; antiviral effects to its meliacin and meliacarpin; and insecticidal and antifeedant activity to its limonoids, which belong to the tetranortriterpenoid class of compounds.^7,11 Limonoids also are reputed to confer antibacterial, antiviral, and antifungal activities.¹² Recent research suggests the potential of M. azedarach to offer a correspondingly broad impact on various conditions.

Forest & Kim Starr

Anticancer potential

Zhou et al. isolated new ring C-seco limonoids from Brazilian M. azedarach in 2004 and evaluated their cytotoxic activity, finding that two limonoids significantly inhibited HeLa S3 cancer cells.^4,11

In 2009, He et al. extracted water-soluble polysaccharides from the fruit of M. azedarach and assessed their cytotoxic activity against four human cell lines in vitro. They found that the major polysaccharide component exhibited potent cytotoxic activity in the BGC-823 cell line.³ Also that year, Wu et al. isolated three new and multiple known steroids from the leaves of Chinese M. azedarach, finding that two of the newly identified steroids – (20S)-5,24(28)-ergostadiene-3-beta,7-alpha,16-beta,20-tetrol and (20S)-5-ergostene-3-beta,7-alpha,16-beta,20-tetrol – and one of the known ones exerted significant cytotoxic impact in three human cancer cell lines (A-549, H460, U251).¹

Two years later, Wu et al. isolated two new triterpenoids (21,24-cycloeupha-7-ene-3-beta,16beta,21-alpha,25-tetrol and 3-beta-acetoxy-12-beta-hydroxy-eupha-7,24-dien-21,16-beta-olide) and two new steroids (29-hydroperoxy-stigmasta-7,24(28) xi-dien-3-beta-ol and 24-xi-hydroperoxy-24-vinyl-lathosterol) along with several known related substances from M. azedarach bark. Five of the known compounds demonstrated cytotoxic activity against three human cancer cell lines (A-549, H460, HGC27).⁶

More recently, Yuan et al. isolated two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, as well as nine known limonoids from the bark of M. azedarach. In addition, the investigators observed that seven of the limonoids exhibited significant inhibitory properties against five human tumor cell lines (HL-60, SMM-C7721, A-549, MCF-7, and SW480).⁵

Efficacy against head lice

In 2007, Carpinella et al. investigated in vitro the pediculicidal and ovicidal activity of an M. azedarach extract against Pediculus humanus capitis, noting the increasing resistance of head lice to synthetic drugs. A combination of 20% ripe fruit extract with 10% ripe fruit oil was found to be the most effective in eradicating adult lice (96.5%). The investigators also prepared a formulation of extract and oil at 10% combined with an emulsifier and preservatives that yielded 92.3% mortality of adult lice and complete inhibition of nymph emergence. They concluded that the use of M. azedarach formulations may be a viable and natural way to control head lice.²M. azedarach also has been the key active ingredient in an antimicrobial cream and a preparation to treat tinea pedis.⁷

Topical cream

Saleem et al. reported in 2008 on an herbal cream preparation using a standardized extract of M. azedarach flowers that displayed strong antibacterial activity against cellulitis, pustules, and pyogenic infections, and other conditions in clinical trials in children under the age of 10 years in four different villages in Pakistan. Subjects with bacterial infections anywhere on the body were divided into three groups, one treated with M. azedarach cream, one with placebo (negative control), and one with neomycin (positive control). Each treatment was applied twice daily for 15 days. The investigators observed that the healing effects of M. azedarach were similar to those rendered by neomycin.⁷

Conclusion

Not only has M. azedarach been used in several traditional medical systems, but its uses have consistently included cutaneous indications. Its most convincing modern application may be for head lice, but recent evidence and traditional uses suggest that this versatile plant may indeed warrant a more prominent role in the current dermatologic armamentarium. Future research is needed, and should provide some interesting answers.

References

1. Steroids. 2009 Sep;74(9):761-5.

2. J Am Acad Dermatol. 2007 Feb;56(2):250-6.

3. Fitoterapia. 2009 Oct;80(7):399-403.

4. Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1362-5.

5. Planta Med. 2013 Jan;79(2):163-8.

6. Planta Med. 2011 Jun;77(9):922-8.

7. Phytomedicine. 2008 Apr;15(4):231-6.

8. J Am Acad Dermatol. 2007 Aug;57(2):366-7.

9. J Ethnopharmacol. 2006 Jun 30;106(2):149-57.

10. J Ethnopharmacol. 2010 Mar 24;128(2):322-35.

11. J Nat Prod. 2004 Sep;67(9):1544-7.

12. Chem Biodivers. 2010 Apr;7(4):839-59.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

As more patients undergo facial rejuvenation procedures for a more youthful look, there is a growing demand for rejuvenation of the décolletage (neck and chest) to achieve a more natural and seamless transition from the skin of the face to the chest. The same modalities that are used on the face to treat skin rhytides, texture, and discoloration have been used successfully in the décolletage area.

Vanaman and Fabi (Plast Reconstr Surg. 2015;136[suppl 5]:276S-281S) recently reviewed the chest anatomy and discussed the safe and effective use of cosmetic injectables alone or in combination with other modalities to address rhytides of the décolletage. The relatively low density of skin pilosebaceous units on the chest allows for slower healing and thus makes the area more vulnerable to scarring with the use of more invasive resurfacing modalities (eg, deeper chemical peels, ablative lasers). The use of cosmetic injectables offers a safer treatment option of chest rhytides. Furthermore, proper candidate selection excludes patients with known sensitivity to cosmetic injectables or their components, history of keloid or hypertrophic scar formation, and active inflammation in the treatment area.

Poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, semipermanent, synthetic soft tissue biostimulator that promotes neocollagenesis by fibroblasts over time (3–6 months). The manufacturer’s recommendation for PLLA reconstitution is at least 2 hours prior to injection with sterile water of no less than 5 mL dilution. Vanaman and Fabi reported usually diluting the day prior to injection with 16 mL total volume. This technique showed the greatest improvement in chest rhytides with no adverse events reported in a retrospective analysis. Poly-L-lactic acid should be injected in a retrograde linear fashion in the plane of the subcutaneous fat, with injection boundaries on the suprasternal notch superiorly, the midclavicular line laterally, and the fourth rib inferolaterally for rejuvenation of the décolletage.

Nodule formation is a well-known complication of PLLA injection, although pain, bruising, edema, pruritus, and hematomas are more commonly seen. The risk of nodule formation can be decreased using several techniques, including avoiding overcorrection and excessive use of product in each individual session, avoiding intradermal injection, diluting to more than 5 mL with reconstitution at least overnight, massaging the area posttreatment (in office by the clinician and at home by the patient), and scheduling treatment sessions at least 4 weeks apart. Usually, 3 to 4 treatments are required and the results can last 2 years or longer without touch-ups.

Nonanimal stabilized hyaluronic acid (NASHA) fillers also can be used to correct chest rhytides; however, using NASHA fillers requires more syringes and results typically last only 6 to 8 months, making it more cost effective to use 2 to 3 vials of PLLA. Moreover, in Vanaman and Fabi’s experience, PLLA is associated with fewer nodules, possibly due to the depth of injection of PLLA into the subcutaneous fat versus injection into the deep dermis with NASHA fillers. Vanaman and Fabi currently are investigating the use of calcium hydroxylapatite fillers alone or in combination with an energy-based modality (microfocused ultrasound) with visualization in the treatment of rhytides in the décolletage.

What’s the Issue?

The availability of many modalities to keep facial skin looking fresh and rejuvenated has led to an increased demand for products and procedures to rejuvenate the décolletage. It is important for dermatologists to acknowledge the more delicate nature of the décolletage versus the face. Less invasive modalities such as cosmetic injectables can be employed in a safe and effective manner to correct rhytides of the chest with proper techniques, products, and patient selection. For a more natural transition from the skin of the face to the décolletage, it also may be necessary to adopt a multimodal approach by using botulinum toxin and fillers, as well as going beyond correction of rhytides to address skin texture and discoloration with chemical peels and lasers. Have you seen an increased demand for procedures to rejuvenate the décolletage in your practice?

We want to know your views! Tell us what you think.

As more patients undergo facial rejuvenation procedures for a more youthful look, there is a growing demand for rejuvenation of the décolletage (neck and chest) to achieve a more natural and seamless transition from the skin of the face to the chest. The same modalities that are used on the face to treat skin rhytides, texture, and discoloration have been used successfully in the décolletage area.

Vanaman and Fabi (Plast Reconstr Surg. 2015;136[suppl 5]:276S-281S) recently reviewed the chest anatomy and discussed the safe and effective use of cosmetic injectables alone or in combination with other modalities to address rhytides of the décolletage. The relatively low density of skin pilosebaceous units on the chest allows for slower healing and thus makes the area more vulnerable to scarring with the use of more invasive resurfacing modalities (eg, deeper chemical peels, ablative lasers). The use of cosmetic injectables offers a safer treatment option of chest rhytides. Furthermore, proper candidate selection excludes patients with known sensitivity to cosmetic injectables or their components, history of keloid or hypertrophic scar formation, and active inflammation in the treatment area.

Poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, semipermanent, synthetic soft tissue biostimulator that promotes neocollagenesis by fibroblasts over time (3–6 months). The manufacturer’s recommendation for PLLA reconstitution is at least 2 hours prior to injection with sterile water of no less than 5 mL dilution. Vanaman and Fabi reported usually diluting the day prior to injection with 16 mL total volume. This technique showed the greatest improvement in chest rhytides with no adverse events reported in a retrospective analysis. Poly-L-lactic acid should be injected in a retrograde linear fashion in the plane of the subcutaneous fat, with injection boundaries on the suprasternal notch superiorly, the midclavicular line laterally, and the fourth rib inferolaterally for rejuvenation of the décolletage.

Nodule formation is a well-known complication of PLLA injection, although pain, bruising, edema, pruritus, and hematomas are more commonly seen. The risk of nodule formation can be decreased using several techniques, including avoiding overcorrection and excessive use of product in each individual session, avoiding intradermal injection, diluting to more than 5 mL with reconstitution at least overnight, massaging the area posttreatment (in office by the clinician and at home by the patient), and scheduling treatment sessions at least 4 weeks apart. Usually, 3 to 4 treatments are required and the results can last 2 years or longer without touch-ups.

Nonanimal stabilized hyaluronic acid (NASHA) fillers also can be used to correct chest rhytides; however, using NASHA fillers requires more syringes and results typically last only 6 to 8 months, making it more cost effective to use 2 to 3 vials of PLLA. Moreover, in Vanaman and Fabi’s experience, PLLA is associated with fewer nodules, possibly due to the depth of injection of PLLA into the subcutaneous fat versus injection into the deep dermis with NASHA fillers. Vanaman and Fabi currently are investigating the use of calcium hydroxylapatite fillers alone or in combination with an energy-based modality (microfocused ultrasound) with visualization in the treatment of rhytides in the décolletage.

What’s the Issue?

The availability of many modalities to keep facial skin looking fresh and rejuvenated has led to an increased demand for products and procedures to rejuvenate the décolletage. It is important for dermatologists to acknowledge the more delicate nature of the décolletage versus the face. Less invasive modalities such as cosmetic injectables can be employed in a safe and effective manner to correct rhytides of the chest with proper techniques, products, and patient selection. For a more natural transition from the skin of the face to the décolletage, it also may be necessary to adopt a multimodal approach by using botulinum toxin and fillers, as well as going beyond correction of rhytides to address skin texture and discoloration with chemical peels and lasers. Have you seen an increased demand for procedures to rejuvenate the décolletage in your practice?

We want to know your views! Tell us what you think.

As more patients undergo facial rejuvenation procedures for a more youthful look, there is a growing demand for rejuvenation of the décolletage (neck and chest) to achieve a more natural and seamless transition from the skin of the face to the chest. The same modalities that are used on the face to treat skin rhytides, texture, and discoloration have been used successfully in the décolletage area.

Vanaman and Fabi (Plast Reconstr Surg. 2015;136[suppl 5]:276S-281S) recently reviewed the chest anatomy and discussed the safe and effective use of cosmetic injectables alone or in combination with other modalities to address rhytides of the décolletage. The relatively low density of skin pilosebaceous units on the chest allows for slower healing and thus makes the area more vulnerable to scarring with the use of more invasive resurfacing modalities (eg, deeper chemical peels, ablative lasers). The use of cosmetic injectables offers a safer treatment option of chest rhytides. Furthermore, proper candidate selection excludes patients with known sensitivity to cosmetic injectables or their components, history of keloid or hypertrophic scar formation, and active inflammation in the treatment area.

Poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, semipermanent, synthetic soft tissue biostimulator that promotes neocollagenesis by fibroblasts over time (3–6 months). The manufacturer’s recommendation for PLLA reconstitution is at least 2 hours prior to injection with sterile water of no less than 5 mL dilution. Vanaman and Fabi reported usually diluting the day prior to injection with 16 mL total volume. This technique showed the greatest improvement in chest rhytides with no adverse events reported in a retrospective analysis. Poly-L-lactic acid should be injected in a retrograde linear fashion in the plane of the subcutaneous fat, with injection boundaries on the suprasternal notch superiorly, the midclavicular line laterally, and the fourth rib inferolaterally for rejuvenation of the décolletage.

Nodule formation is a well-known complication of PLLA injection, although pain, bruising, edema, pruritus, and hematomas are more commonly seen. The risk of nodule formation can be decreased using several techniques, including avoiding overcorrection and excessive use of product in each individual session, avoiding intradermal injection, diluting to more than 5 mL with reconstitution at least overnight, massaging the area posttreatment (in office by the clinician and at home by the patient), and scheduling treatment sessions at least 4 weeks apart. Usually, 3 to 4 treatments are required and the results can last 2 years or longer without touch-ups.

Nonanimal stabilized hyaluronic acid (NASHA) fillers also can be used to correct chest rhytides; however, using NASHA fillers requires more syringes and results typically last only 6 to 8 months, making it more cost effective to use 2 to 3 vials of PLLA. Moreover, in Vanaman and Fabi’s experience, PLLA is associated with fewer nodules, possibly due to the depth of injection of PLLA into the subcutaneous fat versus injection into the deep dermis with NASHA fillers. Vanaman and Fabi currently are investigating the use of calcium hydroxylapatite fillers alone or in combination with an energy-based modality (microfocused ultrasound) with visualization in the treatment of rhytides in the décolletage.

What’s the Issue?

The availability of many modalities to keep facial skin looking fresh and rejuvenated has led to an increased demand for products and procedures to rejuvenate the décolletage. It is important for dermatologists to acknowledge the more delicate nature of the décolletage versus the face. Less invasive modalities such as cosmetic injectables can be employed in a safe and effective manner to correct rhytides of the chest with proper techniques, products, and patient selection. For a more natural transition from the skin of the face to the décolletage, it also may be necessary to adopt a multimodal approach by using botulinum toxin and fillers, as well as going beyond correction of rhytides to address skin texture and discoloration with chemical peels and lasers. Have you seen an increased demand for procedures to rejuvenate the décolletage in your practice?

We want to know your views! Tell us what you think.

Clearance rates for actinic keratoses (AKs) on the extremities were prolonged by adding thermal modulation to photodynamic therapy (PDT), a study has shown.

The single-site study of 17 adults with 10 or more AKs on their arms or legs evaluated thermally modulated PDT: 20% 5-aminolevulinic acid (ALA) applied to skin, occluded with plastic wrap and warmed with an electric heating pad to a median 41.2° C for one hour, then exposed to blue light. Treatment resulted in 90% clearance rates at 3 months and 12 months, reported Dr. Andrea Willey, a dermatologist in Sacramento, Calif., and her associates (Dermatol Surg. 2015 Nov;41[11]:1290-5).

They were inspired to conduct the study as a follow-on to a recently published pilot study of three patients, which found that clearance rates of AKs on the arm treated with thermally modulated 5-ALA blue light PDT persisted up to 14 months after treatment, when compared with the control arm, which was not heated.

In their study, there were 724 grade 1 and 2 AKs at baseline – a median of 15 per extremity; patients were followed up at 3, 6, 9, and 12 months. The total lesion count across the entire cohort was 70 at 3 months, 69 at 6 months, 64 at 9 months, and 72 at 1 year. No new AKs were seen in the treated areas during the 1-year follow-up.

There were 13 grade 3 hypertrophic AK lesions among all study participants. Although these lesions persisted, Dr. Willey and her coauthors noted that they did shrink initially after treatment.

Adverse events associated with the combination therapy were low, and included mild erythema and crusting up to 1 week post treatment, indicating the therapy was well tolerated, and patient satisfaction was high.

The results “suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice,” the authors wrote.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Clearance rates for actinic keratoses (AKs) on the extremities were prolonged by adding thermal modulation to photodynamic therapy (PDT), a study has shown.

The single-site study of 17 adults with 10 or more AKs on their arms or legs evaluated thermally modulated PDT: 20% 5-aminolevulinic acid (ALA) applied to skin, occluded with plastic wrap and warmed with an electric heating pad to a median 41.2° C for one hour, then exposed to blue light. Treatment resulted in 90% clearance rates at 3 months and 12 months, reported Dr. Andrea Willey, a dermatologist in Sacramento, Calif., and her associates (Dermatol Surg. 2015 Nov;41[11]:1290-5).

They were inspired to conduct the study as a follow-on to a recently published pilot study of three patients, which found that clearance rates of AKs on the arm treated with thermally modulated 5-ALA blue light PDT persisted up to 14 months after treatment, when compared with the control arm, which was not heated.

In their study, there were 724 grade 1 and 2 AKs at baseline – a median of 15 per extremity; patients were followed up at 3, 6, 9, and 12 months. The total lesion count across the entire cohort was 70 at 3 months, 69 at 6 months, 64 at 9 months, and 72 at 1 year. No new AKs were seen in the treated areas during the 1-year follow-up.

There were 13 grade 3 hypertrophic AK lesions among all study participants. Although these lesions persisted, Dr. Willey and her coauthors noted that they did shrink initially after treatment.

Adverse events associated with the combination therapy were low, and included mild erythema and crusting up to 1 week post treatment, indicating the therapy was well tolerated, and patient satisfaction was high.

The results “suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice,” the authors wrote.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Clearance rates for actinic keratoses (AKs) on the extremities were prolonged by adding thermal modulation to photodynamic therapy (PDT), a study has shown.

The single-site study of 17 adults with 10 or more AKs on their arms or legs evaluated thermally modulated PDT: 20% 5-aminolevulinic acid (ALA) applied to skin, occluded with plastic wrap and warmed with an electric heating pad to a median 41.2° C for one hour, then exposed to blue light. Treatment resulted in 90% clearance rates at 3 months and 12 months, reported Dr. Andrea Willey, a dermatologist in Sacramento, Calif., and her associates (Dermatol Surg. 2015 Nov;41[11]:1290-5).

They were inspired to conduct the study as a follow-on to a recently published pilot study of three patients, which found that clearance rates of AKs on the arm treated with thermally modulated 5-ALA blue light PDT persisted up to 14 months after treatment, when compared with the control arm, which was not heated.

In their study, there were 724 grade 1 and 2 AKs at baseline – a median of 15 per extremity; patients were followed up at 3, 6, 9, and 12 months. The total lesion count across the entire cohort was 70 at 3 months, 69 at 6 months, 64 at 9 months, and 72 at 1 year. No new AKs were seen in the treated areas during the 1-year follow-up.

There were 13 grade 3 hypertrophic AK lesions among all study participants. Although these lesions persisted, Dr. Willey and her coauthors noted that they did shrink initially after treatment.

Adverse events associated with the combination therapy were low, and included mild erythema and crusting up to 1 week post treatment, indicating the therapy was well tolerated, and patient satisfaction was high.

The results “suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice,” the authors wrote.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Fillers are products that are injected into soft tissue and are classified as either resorbable or nonresorbable (permanent). Several dermal and subcutaneous fillers for soft tissue augmentation currently are available. This article provides a brief review of the history of filler agents currently available for soft tissue augmentation. Cadaveric-derived fillers and implants will not be discussed, as these materials are expensive, are not all approved by the US Food and Drug Administration (FDA), and are more commonly used in burn victims than in cosmetic patients.

History of Fillers in Dermatology

The first known injectable agent was paraffin, but its use as a dermal filler was abandoned after complications including embolization, migration (ie, movement into surrounding tissue), and granuloma formation were reported.¹ Silicone also was banned by the FDA for use as a soft tissue filler due to similar complications. Bovine collagen was the first agent to be approved by the FDA for cosmetic injection, and since then many filler agents have revolutionized a new era of cosmetic enhancement.¹ Injectable soft tissue fillers now can be classified based on several characteristics, including site of placement (ie, dermal or subcutaneous), animal versus nonanimal derivation (eg, autologous, xenograft, semisynthetic, synthetic), and duration of effects (temporary [<6 months], long-lasting [6 months– 2 years], semipermanent [2–5 years], permanent [>5 years]).²

In the 19th century, early instances of soft tissue augmentation using dermal fillers included autologous fat harvested from the arms for correction of depressed facial defects and scars in a patient with tuberculous osteitis as well as injection of paraffin into the scrotum as a testicular prosthesis in a patient with advanced tuberculosis.¹ Later, a technique using a syringe to transfer autologous fat from the extremities was used for facial soft tissue augmentation and contouring, and permanent facial soft tissue augmentation using liquid silicone also was performed. In 1981, purified bovine dermal collagen was first approved by the FDA as a xenogenic agent for dermal injection.³

In 2003, the FDA began to approve new fillers for temporary soft tissue augmentation.³ Approval of injectable purified human collagen derived from fibroblasts was followed by another class of new agents: hyaluronic acid fillers.¹ A biodegradable non–animal based stabilized hyaluronic acid was followed by more agents derived from rooster combs. Further investigations and research have continued, and more long-lasting synthetic fillers have become available, including calcium hydroxylapatite and poly-L-lactic acid. A renewed interest in permanent agents and longer lasting products such as silicone oil and polymethyl methacrylate also has emerged.⁴

The Future of Fillers

While earlier filler materials were limited, those used today are composed of a wide range of substances including collagen, hyaluronic acid, calcium hydroxylapatite, poly-L-lactic acid, and synthetic or manmade polymers (Table). The FDA has approved approximately 21 filler products for dermatologic indications, each with unique properties, advantages, and disadvantages.³ For example, there are several fillers that not only provide soft tissue augmentation but also stimulate collagen production. However, complications can occur, often many years after the initial treatment. Side effects such as swelling, erythema, and nodules may occur and in rare instances foreign body granulomas may develop and may be difficult to eradicate.⁵ Except for autologous fat, all fillers are foreign bodies and therefore can cause foreign body granulomatous reactions ranging from common (eg, with paraffin) to rare (eg, with hyaluronic acid) in occurrence.⁶ The clinical presentation of these reactions is variable, ranging from single to multiple nodules at the injection site to diffuse, hard swelling of the face accompanied by reddening of the skin.

With the increasing desire for a youthful appearance among the aging population, the pharmaceutical industry has responded by increasing the number of available treatment options to meet the demands of cosmetic patients, one of the fastest growing subpopulations in the field of dermatology. Fillers also have provided new options for patients who are unable to afford plastic surgery or those who are poor surgical candidates. The ideal filler material is nonallergenic, noncarcinogenic, and nonteratogenic. It should be stable, affordable, malleable, reversible, and durable with results that can be reproduced and should cause minimal inflammation, migration, and detectable changes. The ideal filler also should have predictable and consistent results, feel natural, take little time to administer, require minimal preparation, cause no patient downtime, and have a low risk for complications. Ideal administration should be painless, user-friendly, and conducted in an outpatient setting with minimal recovery and easy storage. Although no single filler is ideal for all patients, indications, and situations, residents should be aware of the properties and characteristics that make each product unique in order to optimize treatment in all patients.

As demands for cosmetic procedures increase, it is important to incorporate knowledge of cosmetic procedures (eg, fillers for soft tissue augmentation) in resident education and training. Although cosmetic dermatology has been featured prominently in dermatology residency, surveys have shown that residents desire more training in this area.⁷ Although lectures on soft tissue augmentation are popular topics in dermatology, hands-on experience performing these procedures varies widely depending on different training programs. My institution offers several lectures on cosmetic dermatology, and residents are able to perform procedures for soft tissue augmentation as the first assistant or first surgeon during our cosmetic clinic sessions twice weekly.

Final Thoughts

There are a variety of fillers on the horizon to improve aging and volume loss and the science behind cosmetic injections is evolving. Regardless of the filler material chosen, optimal results are yielded by the combination of patient expectations, physician judgment based on clinical experience, and injection technique.

Fillers are products that are injected into soft tissue and are classified as either resorbable or nonresorbable (permanent). Several dermal and subcutaneous fillers for soft tissue augmentation currently are available. This article provides a brief review of the history of filler agents currently available for soft tissue augmentation. Cadaveric-derived fillers and implants will not be discussed, as these materials are expensive, are not all approved by the US Food and Drug Administration (FDA), and are more commonly used in burn victims than in cosmetic patients.

History of Fillers in Dermatology

The first known injectable agent was paraffin, but its use as a dermal filler was abandoned after complications including embolization, migration (ie, movement into surrounding tissue), and granuloma formation were reported.¹ Silicone also was banned by the FDA for use as a soft tissue filler due to similar complications. Bovine collagen was the first agent to be approved by the FDA for cosmetic injection, and since then many filler agents have revolutionized a new era of cosmetic enhancement.¹ Injectable soft tissue fillers now can be classified based on several characteristics, including site of placement (ie, dermal or subcutaneous), animal versus nonanimal derivation (eg, autologous, xenograft, semisynthetic, synthetic), and duration of effects (temporary [<6 months], long-lasting [6 months– 2 years], semipermanent [2–5 years], permanent [>5 years]).²

In the 19th century, early instances of soft tissue augmentation using dermal fillers included autologous fat harvested from the arms for correction of depressed facial defects and scars in a patient with tuberculous osteitis as well as injection of paraffin into the scrotum as a testicular prosthesis in a patient with advanced tuberculosis.¹ Later, a technique using a syringe to transfer autologous fat from the extremities was used for facial soft tissue augmentation and contouring, and permanent facial soft tissue augmentation using liquid silicone also was performed. In 1981, purified bovine dermal collagen was first approved by the FDA as a xenogenic agent for dermal injection.³

In 2003, the FDA began to approve new fillers for temporary soft tissue augmentation.³ Approval of injectable purified human collagen derived from fibroblasts was followed by another class of new agents: hyaluronic acid fillers.¹ A biodegradable non–animal based stabilized hyaluronic acid was followed by more agents derived from rooster combs. Further investigations and research have continued, and more long-lasting synthetic fillers have become available, including calcium hydroxylapatite and poly-L-lactic acid. A renewed interest in permanent agents and longer lasting products such as silicone oil and polymethyl methacrylate also has emerged.⁴

The Future of Fillers

While earlier filler materials were limited, those used today are composed of a wide range of substances including collagen, hyaluronic acid, calcium hydroxylapatite, poly-L-lactic acid, and synthetic or manmade polymers (Table). The FDA has approved approximately 21 filler products for dermatologic indications, each with unique properties, advantages, and disadvantages.³ For example, there are several fillers that not only provide soft tissue augmentation but also stimulate collagen production. However, complications can occur, often many years after the initial treatment. Side effects such as swelling, erythema, and nodules may occur and in rare instances foreign body granulomas may develop and may be difficult to eradicate.⁵ Except for autologous fat, all fillers are foreign bodies and therefore can cause foreign body granulomatous reactions ranging from common (eg, with paraffin) to rare (eg, with hyaluronic acid) in occurrence.⁶ The clinical presentation of these reactions is variable, ranging from single to multiple nodules at the injection site to diffuse, hard swelling of the face accompanied by reddening of the skin.

With the increasing desire for a youthful appearance among the aging population, the pharmaceutical industry has responded by increasing the number of available treatment options to meet the demands of cosmetic patients, one of the fastest growing subpopulations in the field of dermatology. Fillers also have provided new options for patients who are unable to afford plastic surgery or those who are poor surgical candidates. The ideal filler material is nonallergenic, noncarcinogenic, and nonteratogenic. It should be stable, affordable, malleable, reversible, and durable with results that can be reproduced and should cause minimal inflammation, migration, and detectable changes. The ideal filler also should have predictable and consistent results, feel natural, take little time to administer, require minimal preparation, cause no patient downtime, and have a low risk for complications. Ideal administration should be painless, user-friendly, and conducted in an outpatient setting with minimal recovery and easy storage. Although no single filler is ideal for all patients, indications, and situations, residents should be aware of the properties and characteristics that make each product unique in order to optimize treatment in all patients.

As demands for cosmetic procedures increase, it is important to incorporate knowledge of cosmetic procedures (eg, fillers for soft tissue augmentation) in resident education and training. Although cosmetic dermatology has been featured prominently in dermatology residency, surveys have shown that residents desire more training in this area.⁷ Although lectures on soft tissue augmentation are popular topics in dermatology, hands-on experience performing these procedures varies widely depending on different training programs. My institution offers several lectures on cosmetic dermatology, and residents are able to perform procedures for soft tissue augmentation as the first assistant or first surgeon during our cosmetic clinic sessions twice weekly.

Final Thoughts

There are a variety of fillers on the horizon to improve aging and volume loss and the science behind cosmetic injections is evolving. Regardless of the filler material chosen, optimal results are yielded by the combination of patient expectations, physician judgment based on clinical experience, and injection technique.

Fillers are products that are injected into soft tissue and are classified as either resorbable or nonresorbable (permanent). Several dermal and subcutaneous fillers for soft tissue augmentation currently are available. This article provides a brief review of the history of filler agents currently available for soft tissue augmentation. Cadaveric-derived fillers and implants will not be discussed, as these materials are expensive, are not all approved by the US Food and Drug Administration (FDA), and are more commonly used in burn victims than in cosmetic patients.

History of Fillers in Dermatology

The first known injectable agent was paraffin, but its use as a dermal filler was abandoned after complications including embolization, migration (ie, movement into surrounding tissue), and granuloma formation were reported.¹ Silicone also was banned by the FDA for use as a soft tissue filler due to similar complications. Bovine collagen was the first agent to be approved by the FDA for cosmetic injection, and since then many filler agents have revolutionized a new era of cosmetic enhancement.¹ Injectable soft tissue fillers now can be classified based on several characteristics, including site of placement (ie, dermal or subcutaneous), animal versus nonanimal derivation (eg, autologous, xenograft, semisynthetic, synthetic), and duration of effects (temporary [<6 months], long-lasting [6 months– 2 years], semipermanent [2–5 years], permanent [>5 years]).²

In the 19th century, early instances of soft tissue augmentation using dermal fillers included autologous fat harvested from the arms for correction of depressed facial defects and scars in a patient with tuberculous osteitis as well as injection of paraffin into the scrotum as a testicular prosthesis in a patient with advanced tuberculosis.¹ Later, a technique using a syringe to transfer autologous fat from the extremities was used for facial soft tissue augmentation and contouring, and permanent facial soft tissue augmentation using liquid silicone also was performed. In 1981, purified bovine dermal collagen was first approved by the FDA as a xenogenic agent for dermal injection.³

In 2003, the FDA began to approve new fillers for temporary soft tissue augmentation.³ Approval of injectable purified human collagen derived from fibroblasts was followed by another class of new agents: hyaluronic acid fillers.¹ A biodegradable non–animal based stabilized hyaluronic acid was followed by more agents derived from rooster combs. Further investigations and research have continued, and more long-lasting synthetic fillers have become available, including calcium hydroxylapatite and poly-L-lactic acid. A renewed interest in permanent agents and longer lasting products such as silicone oil and polymethyl methacrylate also has emerged.⁴

The Future of Fillers

While earlier filler materials were limited, those used today are composed of a wide range of substances including collagen, hyaluronic acid, calcium hydroxylapatite, poly-L-lactic acid, and synthetic or manmade polymers (Table). The FDA has approved approximately 21 filler products for dermatologic indications, each with unique properties, advantages, and disadvantages.³ For example, there are several fillers that not only provide soft tissue augmentation but also stimulate collagen production. However, complications can occur, often many years after the initial treatment. Side effects such as swelling, erythema, and nodules may occur and in rare instances foreign body granulomas may develop and may be difficult to eradicate.⁵ Except for autologous fat, all fillers are foreign bodies and therefore can cause foreign body granulomatous reactions ranging from common (eg, with paraffin) to rare (eg, with hyaluronic acid) in occurrence.⁶ The clinical presentation of these reactions is variable, ranging from single to multiple nodules at the injection site to diffuse, hard swelling of the face accompanied by reddening of the skin.

With the increasing desire for a youthful appearance among the aging population, the pharmaceutical industry has responded by increasing the number of available treatment options to meet the demands of cosmetic patients, one of the fastest growing subpopulations in the field of dermatology. Fillers also have provided new options for patients who are unable to afford plastic surgery or those who are poor surgical candidates. The ideal filler material is nonallergenic, noncarcinogenic, and nonteratogenic. It should be stable, affordable, malleable, reversible, and durable with results that can be reproduced and should cause minimal inflammation, migration, and detectable changes. The ideal filler also should have predictable and consistent results, feel natural, take little time to administer, require minimal preparation, cause no patient downtime, and have a low risk for complications. Ideal administration should be painless, user-friendly, and conducted in an outpatient setting with minimal recovery and easy storage. Although no single filler is ideal for all patients, indications, and situations, residents should be aware of the properties and characteristics that make each product unique in order to optimize treatment in all patients.

As demands for cosmetic procedures increase, it is important to incorporate knowledge of cosmetic procedures (eg, fillers for soft tissue augmentation) in resident education and training. Although cosmetic dermatology has been featured prominently in dermatology residency, surveys have shown that residents desire more training in this area.⁷ Although lectures on soft tissue augmentation are popular topics in dermatology, hands-on experience performing these procedures varies widely depending on different training programs. My institution offers several lectures on cosmetic dermatology, and residents are able to perform procedures for soft tissue augmentation as the first assistant or first surgeon during our cosmetic clinic sessions twice weekly.

Final Thoughts

There are a variety of fillers on the horizon to improve aging and volume loss and the science behind cosmetic injections is evolving. Regardless of the filler material chosen, optimal results are yielded by the combination of patient expectations, physician judgment based on clinical experience, and injection technique.