Due to a submission error, an acknowledgment was missing from the July 2014 article “The Great Mimickers of Rosacea” (Cutis. 2014;94:39-45).

Acknowledgements—The authors thank Jennifer Rullan, MD, San Diego, California, and Jose Gonzalez-Chavez, MD, San Juan, Puerto Rico, for their assistance.

Also, the order of the authors was incorrect in the July 2014 e-only article “Lepromatous Leprosy Associated With Erythema Nodosum Leprosum” (Cutis. 2014;94:E19-E20). The correct order is:

These articles have been corrected online.

Due to a submission error, an acknowledgment was missing from the July 2014 article “The Great Mimickers of Rosacea” (Cutis. 2014;94:39-45).

Acknowledgements—The authors thank Jennifer Rullan, MD, San Diego, California, and Jose Gonzalez-Chavez, MD, San Juan, Puerto Rico, for their assistance.

Also, the order of the authors was incorrect in the July 2014 e-only article “Lepromatous Leprosy Associated With Erythema Nodosum Leprosum” (Cutis. 2014;94:E19-E20). The correct order is:

These articles have been corrected online.

Due to a submission error, an acknowledgment was missing from the July 2014 article “The Great Mimickers of Rosacea” (Cutis. 2014;94:39-45).

Acknowledgements—The authors thank Jennifer Rullan, MD, San Diego, California, and Jose Gonzalez-Chavez, MD, San Juan, Puerto Rico, for their assistance.

Also, the order of the authors was incorrect in the July 2014 e-only article “Lepromatous Leprosy Associated With Erythema Nodosum Leprosum” (Cutis. 2014;94:E19-E20). The correct order is:

These articles have been corrected online.

Cyanoacrylates are widely used in adhesive products, with applications ranging from household products to nail and beauty salons and even dentistry. A topical skin adhesive containing 2-octyl cyanoacrylate was approved in 1998 for topical application for closure of skin edges of wounds from surgical incisions.¹ Usually cyanoacrylates are not strong sensitizers, and despite their extensive use, there have been relatively few reports of associated allergic contact dermatitis (ACD).^2-5 We report 4 cases of ACD to 2-octyl cyanoacrylate used in postsurgical wound closures as confirmed by patch tests.

Case Reports

Patient 1

A 33-year-old woman presented with an intensely pruritic peri-incisional rash on the lower back and right buttock of 1 week’s duration. The eruption started roughly 1 week following surgical implantation of a spinal cord stimulator for treatment of chronic back pain. Both incisions made during the implantation were closed with 2-octyl cyanoacrylate. The patient denied any prior exposure to topical skin adhesives or any history of contact dermatitis to nickel or other materials. The patient did not dress the wounds and did not apply topical agents to the area.

Physical examination revealed 6- to 8-cm linear surgical scars on the midline lumbar back and superior right buttock with surrounding excoriated erythematous papules coalescing into plaques consistent with acute eczematous dermatitis (Figure 1). Similar papules and plaques were scattered across the abdomen and chest. She was given triamcinolone acetonide ointment 0.1% twice daily and hydroxyzine pamoate 25 mg 3 times daily for itching. The surgical wounds healed within 2 weeks of presentation with postinflammatory hyperpigmentation surrounding the scars.

Figure 1. Surgical scars with surrounding excoriated erythematous papules coalescing into plaques on the midline lumbar back (A) and superior right buttock (B).

Six weeks later she underwent patch testing to confirm the diagnosis. She was screened using the North American Contact Dermatitis Group standard 65-allergen series and a miscellaneous tray including hardware obtained from the spinal cord stimulator device manufacturer. A use test to 2-octyl cyanoacrylate also was performed. At 96 hours, true positives included cinnamic aldehyde (1+), nickel (1+), bacitracin (1+), fragrance mix (2+), disperse blue dyes 106 and 124 (2+), and 2-octyl cyanoacrylate (3+)(1+=weak positive; 2+=strong positive; 3+=extreme reaction). There was no response to any components of the device. The pattern of dermatitis and positive patch-test results strongly supported the diagnosis of ACD to 2-octyl cyanoacrylate.

Patients 2, 3, and 4

Three patients—a 65-year-old woman, a 35-year-old woman, and a 44-year-old woman—presented to us with eczematous dermatitis at laparoscopic portal sites that were closed with 2-octyl cyanoacrylate (Figures 2 and 3). They presented approximately 1 week following laparoscopic Nissen fundoplication, laparoscopic left hepatectomy, and laparoscopic cholecystectomy, respectively. None of these  3 patients had been using any topical medications. All of them had a positive reaction (2+) to 2-octyl cyanoacrylate on use testing. Interestingly, use tests for 2 other cyanoacrylates containing 2-butyl cyanoacrylate were negative in 2 patients.

Figure 2. Acute eczematous plaques at wound closures.

Figure 3. Coalescing acute eczematous plaques focused at wound closures.

Although patient 1 reported no prior exposure to 2-octyl cyanoacrylate, these 3 additional patients reported prior exposure with no reaction. Other possible contact allergens associated with wound closure included iodine, topical antibiotics, and dressing tape.

Comment

Contact allergies to acrylates are not uncommon. In a series of 275 patients, Kanerva et al⁶ found that 17.5% of patients had an allergic reaction to at least 1 acrylate or methacrylate. In the same series, no allergic reactions to cyanoacrylates were noted.⁶ The role of methacrylates in the development of occupational ACD and irritant dermatitis has been well characterized among dentists, orthopedic surgeons, beauticians, and industrial workers who are commonly exposed to these agents.^7-12 Partially because of their longer carbon chains, cyanoacrylates have reduced toxicity and improved bonding strength as well as flexibility. Given their availability and the ease and speed of their use, skin adhesives have become widely used in the closure of surgical wounds.^13-16

Postoperative contact dermatitis is problematic, as patients are exposed to many potential allergens during surgery. In our clinical practice, the most common allergens causing ACD associated with surgery are iodine, topical antibiotics (ie, bacitracin, neomycin), tape adhesives, suture materials, and less commonly surgical hardware. Although they are rarely reported, contact allergies to skin adhesives such as cyanoacrylates are of particular importance because they may complicate surgical wounds, leading to dehiscence, infection, and scarring, among other complications. In our patients, there were no adverse outcomes in wound healing with the exception of postinflammatory hyperpigmentation.

Under ideal conditions, 2-octyl cyanoacrylate generally is not a strong sensitizer; however, application to open wounds or thinner skin such as the eyelids may permit exposure of antigen-presenting cells to cyanoacrylate monomers, thereby initiating sensitization. Postsurgical occlusive dressings, which often are left in place for 7 to 14 days, also may contribute to sensitization. The role of the degradation of skin adhesive products in the development of contact dermatitis is unknown.

Management of ACD from skin adhesives should involve the immediate removal of any remaining adhesive. One manufacturer recommends removal of the product using acetone or petroleum jelly.¹ In our experience, rubbing the adhesive with 2×2-in gauze pads or using forceps have been successful methods for removal. The use of petroleum jelly prior to rubbing with gauze also can aid in removal of the adhesive. Warm water soaks and soap also may be helpful but are not expected to immediately loosen the bond. A mid-potency steroid ointment such as triamcinolone may be effective in treating dermatitis, though the use of higher-potency steroids such as clobetasol may be needed for severe reactions.^1,2

As members of the cyano group, cyanoacrylates are highly reactive molecules that polymerize and rapidly bind to the stratum corneum when they come in contact with traces of water. During polymerization, the individual constituents or monomer cyanoacrylate molecules are joined into a polymer chain, which should be trapped by keratinocytes and not reach immunomodulators^2,10; however, as postulated during the first report of contact dermatitis, an arid environment could delay polymerization and increase the risk of sensitization.² The first report was made in Las Vegas, Nevada,² and our cases presented in San Antonio, Texas.

There currently are 2 main cutaneous adhesives containing cyanoacrylate on the market, including 2-octyl cyanoacrylate and 2-butyl cyanoacrylate. These products are known by various trade names and differ primarily in the length of the carbon chain in the cyanoacrylate. A dye is added to allow better visibility of the glue during application, and a plasticizer increases viscosity and accelerates polymerization. The 2 most widely used products contain the same dye (D&C Violet No. 2) and similar but proprietary plasticizers.

Figure 4. When conducting use tests to determine if plasticizers or dyes in acrylate adhesive products may be potential allergens, a reaction only to product 1 would suggest that 2-octyl cyanoacrylate is to blame. A reaction to products 2 and 3 but not product 1 would suggest 2-butyl cyanoacrylate as a sensitizer, while a reaction to products 1 and 2 but not product 3 would suggest that the dye is responsible.

Although plasticizers and dyes may be potential contact allergens, we postulated that the cyanoacrylate was the responsible sensitizer in our cases. Because the individual ingredients were not readily available for use testing, we devised a logical method to attempt to determine the specific component of the skin adhesive that was responsible for contact sensitization (Figure 4). Patients 3 and 4 in our series were tested using this method and were found to be sensitive to the product containing 2-octyl cyanoacrylate but not the products containing 2-butyl cyanoacrylate.

Conclusion

Given the many advantages of cyanoacrylates, it is likely that their use in skin adhesive products will continue to increase. Our 4 patients may represent a rise in the incidence of ACD associated with increased use of skin adhesives, but it is important to look critically at this agent when patients present with postoperative pruritus in the absence of topical bacitracin or neomycin use and surgical dressing irritation. By using the technique we described, it is possible to identify the component responsible for the reaction; however, in the future, the exact mechanisms of sensitization and the specific components should be further elucidated by researchers working in conjunction with the manufacturers. Use testing on abraded skin and/or under occlusive dressings more closely mimics the initial exposure and may have a role in determining true allergy.

Cyanoacrylates are widely used in adhesive products, with applications ranging from household products to nail and beauty salons and even dentistry. A topical skin adhesive containing 2-octyl cyanoacrylate was approved in 1998 for topical application for closure of skin edges of wounds from surgical incisions.¹ Usually cyanoacrylates are not strong sensitizers, and despite their extensive use, there have been relatively few reports of associated allergic contact dermatitis (ACD).^2-5 We report 4 cases of ACD to 2-octyl cyanoacrylate used in postsurgical wound closures as confirmed by patch tests.

Case Reports

Patient 1

A 33-year-old woman presented with an intensely pruritic peri-incisional rash on the lower back and right buttock of 1 week’s duration. The eruption started roughly 1 week following surgical implantation of a spinal cord stimulator for treatment of chronic back pain. Both incisions made during the implantation were closed with 2-octyl cyanoacrylate. The patient denied any prior exposure to topical skin adhesives or any history of contact dermatitis to nickel or other materials. The patient did not dress the wounds and did not apply topical agents to the area.

Physical examination revealed 6- to 8-cm linear surgical scars on the midline lumbar back and superior right buttock with surrounding excoriated erythematous papules coalescing into plaques consistent with acute eczematous dermatitis (Figure 1). Similar papules and plaques were scattered across the abdomen and chest. She was given triamcinolone acetonide ointment 0.1% twice daily and hydroxyzine pamoate 25 mg 3 times daily for itching. The surgical wounds healed within 2 weeks of presentation with postinflammatory hyperpigmentation surrounding the scars.

Figure 1. Surgical scars with surrounding excoriated erythematous papules coalescing into plaques on the midline lumbar back (A) and superior right buttock (B).

Six weeks later she underwent patch testing to confirm the diagnosis. She was screened using the North American Contact Dermatitis Group standard 65-allergen series and a miscellaneous tray including hardware obtained from the spinal cord stimulator device manufacturer. A use test to 2-octyl cyanoacrylate also was performed. At 96 hours, true positives included cinnamic aldehyde (1+), nickel (1+), bacitracin (1+), fragrance mix (2+), disperse blue dyes 106 and 124 (2+), and 2-octyl cyanoacrylate (3+)(1+=weak positive; 2+=strong positive; 3+=extreme reaction). There was no response to any components of the device. The pattern of dermatitis and positive patch-test results strongly supported the diagnosis of ACD to 2-octyl cyanoacrylate.

Patients 2, 3, and 4

Three patients—a 65-year-old woman, a 35-year-old woman, and a 44-year-old woman—presented to us with eczematous dermatitis at laparoscopic portal sites that were closed with 2-octyl cyanoacrylate (Figures 2 and 3). They presented approximately 1 week following laparoscopic Nissen fundoplication, laparoscopic left hepatectomy, and laparoscopic cholecystectomy, respectively. None of these  3 patients had been using any topical medications. All of them had a positive reaction (2+) to 2-octyl cyanoacrylate on use testing. Interestingly, use tests for 2 other cyanoacrylates containing 2-butyl cyanoacrylate were negative in 2 patients.

Figure 2. Acute eczematous plaques at wound closures.

Figure 3. Coalescing acute eczematous plaques focused at wound closures.

Although patient 1 reported no prior exposure to 2-octyl cyanoacrylate, these 3 additional patients reported prior exposure with no reaction. Other possible contact allergens associated with wound closure included iodine, topical antibiotics, and dressing tape.

Comment

Contact allergies to acrylates are not uncommon. In a series of 275 patients, Kanerva et al⁶ found that 17.5% of patients had an allergic reaction to at least 1 acrylate or methacrylate. In the same series, no allergic reactions to cyanoacrylates were noted.⁶ The role of methacrylates in the development of occupational ACD and irritant dermatitis has been well characterized among dentists, orthopedic surgeons, beauticians, and industrial workers who are commonly exposed to these agents.^7-12 Partially because of their longer carbon chains, cyanoacrylates have reduced toxicity and improved bonding strength as well as flexibility. Given their availability and the ease and speed of their use, skin adhesives have become widely used in the closure of surgical wounds.^13-16

Postoperative contact dermatitis is problematic, as patients are exposed to many potential allergens during surgery. In our clinical practice, the most common allergens causing ACD associated with surgery are iodine, topical antibiotics (ie, bacitracin, neomycin), tape adhesives, suture materials, and less commonly surgical hardware. Although they are rarely reported, contact allergies to skin adhesives such as cyanoacrylates are of particular importance because they may complicate surgical wounds, leading to dehiscence, infection, and scarring, among other complications. In our patients, there were no adverse outcomes in wound healing with the exception of postinflammatory hyperpigmentation.

Under ideal conditions, 2-octyl cyanoacrylate generally is not a strong sensitizer; however, application to open wounds or thinner skin such as the eyelids may permit exposure of antigen-presenting cells to cyanoacrylate monomers, thereby initiating sensitization. Postsurgical occlusive dressings, which often are left in place for 7 to 14 days, also may contribute to sensitization. The role of the degradation of skin adhesive products in the development of contact dermatitis is unknown.

Management of ACD from skin adhesives should involve the immediate removal of any remaining adhesive. One manufacturer recommends removal of the product using acetone or petroleum jelly.¹ In our experience, rubbing the adhesive with 2×2-in gauze pads or using forceps have been successful methods for removal. The use of petroleum jelly prior to rubbing with gauze also can aid in removal of the adhesive. Warm water soaks and soap also may be helpful but are not expected to immediately loosen the bond. A mid-potency steroid ointment such as triamcinolone may be effective in treating dermatitis, though the use of higher-potency steroids such as clobetasol may be needed for severe reactions.^1,2

As members of the cyano group, cyanoacrylates are highly reactive molecules that polymerize and rapidly bind to the stratum corneum when they come in contact with traces of water. During polymerization, the individual constituents or monomer cyanoacrylate molecules are joined into a polymer chain, which should be trapped by keratinocytes and not reach immunomodulators^2,10; however, as postulated during the first report of contact dermatitis, an arid environment could delay polymerization and increase the risk of sensitization.² The first report was made in Las Vegas, Nevada,² and our cases presented in San Antonio, Texas.

There currently are 2 main cutaneous adhesives containing cyanoacrylate on the market, including 2-octyl cyanoacrylate and 2-butyl cyanoacrylate. These products are known by various trade names and differ primarily in the length of the carbon chain in the cyanoacrylate. A dye is added to allow better visibility of the glue during application, and a plasticizer increases viscosity and accelerates polymerization. The 2 most widely used products contain the same dye (D&C Violet No. 2) and similar but proprietary plasticizers.

Figure 4. When conducting use tests to determine if plasticizers or dyes in acrylate adhesive products may be potential allergens, a reaction only to product 1 would suggest that 2-octyl cyanoacrylate is to blame. A reaction to products 2 and 3 but not product 1 would suggest 2-butyl cyanoacrylate as a sensitizer, while a reaction to products 1 and 2 but not product 3 would suggest that the dye is responsible.

Although plasticizers and dyes may be potential contact allergens, we postulated that the cyanoacrylate was the responsible sensitizer in our cases. Because the individual ingredients were not readily available for use testing, we devised a logical method to attempt to determine the specific component of the skin adhesive that was responsible for contact sensitization (Figure 4). Patients 3 and 4 in our series were tested using this method and were found to be sensitive to the product containing 2-octyl cyanoacrylate but not the products containing 2-butyl cyanoacrylate.

Conclusion

Given the many advantages of cyanoacrylates, it is likely that their use in skin adhesive products will continue to increase. Our 4 patients may represent a rise in the incidence of ACD associated with increased use of skin adhesives, but it is important to look critically at this agent when patients present with postoperative pruritus in the absence of topical bacitracin or neomycin use and surgical dressing irritation. By using the technique we described, it is possible to identify the component responsible for the reaction; however, in the future, the exact mechanisms of sensitization and the specific components should be further elucidated by researchers working in conjunction with the manufacturers. Use testing on abraded skin and/or under occlusive dressings more closely mimics the initial exposure and may have a role in determining true allergy.

Cyanoacrylates are widely used in adhesive products, with applications ranging from household products to nail and beauty salons and even dentistry. A topical skin adhesive containing 2-octyl cyanoacrylate was approved in 1998 for topical application for closure of skin edges of wounds from surgical incisions.¹ Usually cyanoacrylates are not strong sensitizers, and despite their extensive use, there have been relatively few reports of associated allergic contact dermatitis (ACD).^2-5 We report 4 cases of ACD to 2-octyl cyanoacrylate used in postsurgical wound closures as confirmed by patch tests.

Case Reports

Patient 1

A 33-year-old woman presented with an intensely pruritic peri-incisional rash on the lower back and right buttock of 1 week’s duration. The eruption started roughly 1 week following surgical implantation of a spinal cord stimulator for treatment of chronic back pain. Both incisions made during the implantation were closed with 2-octyl cyanoacrylate. The patient denied any prior exposure to topical skin adhesives or any history of contact dermatitis to nickel or other materials. The patient did not dress the wounds and did not apply topical agents to the area.

Physical examination revealed 6- to 8-cm linear surgical scars on the midline lumbar back and superior right buttock with surrounding excoriated erythematous papules coalescing into plaques consistent with acute eczematous dermatitis (Figure 1). Similar papules and plaques were scattered across the abdomen and chest. She was given triamcinolone acetonide ointment 0.1% twice daily and hydroxyzine pamoate 25 mg 3 times daily for itching. The surgical wounds healed within 2 weeks of presentation with postinflammatory hyperpigmentation surrounding the scars.

Figure 1. Surgical scars with surrounding excoriated erythematous papules coalescing into plaques on the midline lumbar back (A) and superior right buttock (B).

Six weeks later she underwent patch testing to confirm the diagnosis. She was screened using the North American Contact Dermatitis Group standard 65-allergen series and a miscellaneous tray including hardware obtained from the spinal cord stimulator device manufacturer. A use test to 2-octyl cyanoacrylate also was performed. At 96 hours, true positives included cinnamic aldehyde (1+), nickel (1+), bacitracin (1+), fragrance mix (2+), disperse blue dyes 106 and 124 (2+), and 2-octyl cyanoacrylate (3+)(1+=weak positive; 2+=strong positive; 3+=extreme reaction). There was no response to any components of the device. The pattern of dermatitis and positive patch-test results strongly supported the diagnosis of ACD to 2-octyl cyanoacrylate.

Patients 2, 3, and 4

Three patients—a 65-year-old woman, a 35-year-old woman, and a 44-year-old woman—presented to us with eczematous dermatitis at laparoscopic portal sites that were closed with 2-octyl cyanoacrylate (Figures 2 and 3). They presented approximately 1 week following laparoscopic Nissen fundoplication, laparoscopic left hepatectomy, and laparoscopic cholecystectomy, respectively. None of these  3 patients had been using any topical medications. All of them had a positive reaction (2+) to 2-octyl cyanoacrylate on use testing. Interestingly, use tests for 2 other cyanoacrylates containing 2-butyl cyanoacrylate were negative in 2 patients.

Figure 2. Acute eczematous plaques at wound closures.

Figure 3. Coalescing acute eczematous plaques focused at wound closures.

Although patient 1 reported no prior exposure to 2-octyl cyanoacrylate, these 3 additional patients reported prior exposure with no reaction. Other possible contact allergens associated with wound closure included iodine, topical antibiotics, and dressing tape.

Comment

Contact allergies to acrylates are not uncommon. In a series of 275 patients, Kanerva et al⁶ found that 17.5% of patients had an allergic reaction to at least 1 acrylate or methacrylate. In the same series, no allergic reactions to cyanoacrylates were noted.⁶ The role of methacrylates in the development of occupational ACD and irritant dermatitis has been well characterized among dentists, orthopedic surgeons, beauticians, and industrial workers who are commonly exposed to these agents.^7-12 Partially because of their longer carbon chains, cyanoacrylates have reduced toxicity and improved bonding strength as well as flexibility. Given their availability and the ease and speed of their use, skin adhesives have become widely used in the closure of surgical wounds.^13-16

Postoperative contact dermatitis is problematic, as patients are exposed to many potential allergens during surgery. In our clinical practice, the most common allergens causing ACD associated with surgery are iodine, topical antibiotics (ie, bacitracin, neomycin), tape adhesives, suture materials, and less commonly surgical hardware. Although they are rarely reported, contact allergies to skin adhesives such as cyanoacrylates are of particular importance because they may complicate surgical wounds, leading to dehiscence, infection, and scarring, among other complications. In our patients, there were no adverse outcomes in wound healing with the exception of postinflammatory hyperpigmentation.

Under ideal conditions, 2-octyl cyanoacrylate generally is not a strong sensitizer; however, application to open wounds or thinner skin such as the eyelids may permit exposure of antigen-presenting cells to cyanoacrylate monomers, thereby initiating sensitization. Postsurgical occlusive dressings, which often are left in place for 7 to 14 days, also may contribute to sensitization. The role of the degradation of skin adhesive products in the development of contact dermatitis is unknown.

Management of ACD from skin adhesives should involve the immediate removal of any remaining adhesive. One manufacturer recommends removal of the product using acetone or petroleum jelly.¹ In our experience, rubbing the adhesive with 2×2-in gauze pads or using forceps have been successful methods for removal. The use of petroleum jelly prior to rubbing with gauze also can aid in removal of the adhesive. Warm water soaks and soap also may be helpful but are not expected to immediately loosen the bond. A mid-potency steroid ointment such as triamcinolone may be effective in treating dermatitis, though the use of higher-potency steroids such as clobetasol may be needed for severe reactions.^1,2

As members of the cyano group, cyanoacrylates are highly reactive molecules that polymerize and rapidly bind to the stratum corneum when they come in contact with traces of water. During polymerization, the individual constituents or monomer cyanoacrylate molecules are joined into a polymer chain, which should be trapped by keratinocytes and not reach immunomodulators^2,10; however, as postulated during the first report of contact dermatitis, an arid environment could delay polymerization and increase the risk of sensitization.² The first report was made in Las Vegas, Nevada,² and our cases presented in San Antonio, Texas.

There currently are 2 main cutaneous adhesives containing cyanoacrylate on the market, including 2-octyl cyanoacrylate and 2-butyl cyanoacrylate. These products are known by various trade names and differ primarily in the length of the carbon chain in the cyanoacrylate. A dye is added to allow better visibility of the glue during application, and a plasticizer increases viscosity and accelerates polymerization. The 2 most widely used products contain the same dye (D&C Violet No. 2) and similar but proprietary plasticizers.

Figure 4. When conducting use tests to determine if plasticizers or dyes in acrylate adhesive products may be potential allergens, a reaction only to product 1 would suggest that 2-octyl cyanoacrylate is to blame. A reaction to products 2 and 3 but not product 1 would suggest 2-butyl cyanoacrylate as a sensitizer, while a reaction to products 1 and 2 but not product 3 would suggest that the dye is responsible.

Although plasticizers and dyes may be potential contact allergens, we postulated that the cyanoacrylate was the responsible sensitizer in our cases. Because the individual ingredients were not readily available for use testing, we devised a logical method to attempt to determine the specific component of the skin adhesive that was responsible for contact sensitization (Figure 4). Patients 3 and 4 in our series were tested using this method and were found to be sensitive to the product containing 2-octyl cyanoacrylate but not the products containing 2-butyl cyanoacrylate.

Conclusion

Given the many advantages of cyanoacrylates, it is likely that their use in skin adhesive products will continue to increase. Our 4 patients may represent a rise in the incidence of ACD associated with increased use of skin adhesives, but it is important to look critically at this agent when patients present with postoperative pruritus in the absence of topical bacitracin or neomycin use and surgical dressing irritation. By using the technique we described, it is possible to identify the component responsible for the reaction; however, in the future, the exact mechanisms of sensitization and the specific components should be further elucidated by researchers working in conjunction with the manufacturers. Use testing on abraded skin and/or under occlusive dressings more closely mimics the initial exposure and may have a role in determining true allergy.

A drug-coated angioplasty balloon catheter has been approved for treating peripheral artery disease, the first such device approved for this use, the Food and Drug Administration announced on October 10.

The device is the Lutonix 035 Drug Coated Balloon Percutaneous Transluminal Angioplasty Catheter (Lutonix DCB), manufactured by Lutonix; its outer surface is coated with paclitaxel, “which may help to prevent” restenosis after the angioplasty procedure, according to the FDA statement announcing the approval. “The clinical data show that Lutonix DCB may be more effective than traditional balloon angioplasty at helping to prevent further blockage in the artery,” Dr. William Maisel, deputy director for science and chief scientist in the FDA’s Center for Devices and Radiological Health, said in the statement.

Approval was based on the results of three clinical trials and nonclinical testing:

• A randomized, multicenter study of 101 people in Europe, which found that after 6 months, no further treatment for PAD was needed in almost 72% of the patients treated with Lutonix DCB, compared with almost 50% of those treated with conventional balloon angioplasty.

• A single-blind, multicenter, randomized study of 476 people in the United States and Europe, which found that 65% of those randomized to treatment with Lutonix DCB had no restenosis at 12 months, compared with roughly 53% of those randomized to treatment with conventional balloon angioplasty.

• A single-arm, ongoing study that is further evaluating safety and effectiveness in 657 people treated with the device in the United States and Europe, which, at the time of approval, “show that there have been no unanticipated device- or drug-related adverse events,” the FDA said.

These studies also indicated that the safety of Lutonix DCB was comparable to conventional balloon angioplasty. The most common major adverse events included additional intervention, pain as a result of poor blood flow, narrowing of arteries that were not treated, chest pain, and abnormal growth of tissue.

Contraindications include women who are breastfeeding, pregnant, or plan to become pregnant; and men who plan to father children.

The company is required by the FDA to conduct two postapproval studies, the ongoing 5-year study of 657 patients, and a randomized, single-blind, multicenter study that will evaluate safety and effectiveness of the device in women in the United States, “due to differences in observed outcomes in this group as compared to outcomes for the general study population,” according to the FDA.

The device was reviewed at an FDA advisory panel meeting in June.

[email protected]

A drug-coated angioplasty balloon catheter has been approved for treating peripheral artery disease, the first such device approved for this use, the Food and Drug Administration announced on October 10.

The device is the Lutonix 035 Drug Coated Balloon Percutaneous Transluminal Angioplasty Catheter (Lutonix DCB), manufactured by Lutonix; its outer surface is coated with paclitaxel, “which may help to prevent” restenosis after the angioplasty procedure, according to the FDA statement announcing the approval. “The clinical data show that Lutonix DCB may be more effective than traditional balloon angioplasty at helping to prevent further blockage in the artery,” Dr. William Maisel, deputy director for science and chief scientist in the FDA’s Center for Devices and Radiological Health, said in the statement.

Approval was based on the results of three clinical trials and nonclinical testing:

• A randomized, multicenter study of 101 people in Europe, which found that after 6 months, no further treatment for PAD was needed in almost 72% of the patients treated with Lutonix DCB, compared with almost 50% of those treated with conventional balloon angioplasty.

• A single-blind, multicenter, randomized study of 476 people in the United States and Europe, which found that 65% of those randomized to treatment with Lutonix DCB had no restenosis at 12 months, compared with roughly 53% of those randomized to treatment with conventional balloon angioplasty.

• A single-arm, ongoing study that is further evaluating safety and effectiveness in 657 people treated with the device in the United States and Europe, which, at the time of approval, “show that there have been no unanticipated device- or drug-related adverse events,” the FDA said.

These studies also indicated that the safety of Lutonix DCB was comparable to conventional balloon angioplasty. The most common major adverse events included additional intervention, pain as a result of poor blood flow, narrowing of arteries that were not treated, chest pain, and abnormal growth of tissue.

Contraindications include women who are breastfeeding, pregnant, or plan to become pregnant; and men who plan to father children.

The company is required by the FDA to conduct two postapproval studies, the ongoing 5-year study of 657 patients, and a randomized, single-blind, multicenter study that will evaluate safety and effectiveness of the device in women in the United States, “due to differences in observed outcomes in this group as compared to outcomes for the general study population,” according to the FDA.

The device was reviewed at an FDA advisory panel meeting in June.

[email protected]

A drug-coated angioplasty balloon catheter has been approved for treating peripheral artery disease, the first such device approved for this use, the Food and Drug Administration announced on October 10.

The device is the Lutonix 035 Drug Coated Balloon Percutaneous Transluminal Angioplasty Catheter (Lutonix DCB), manufactured by Lutonix; its outer surface is coated with paclitaxel, “which may help to prevent” restenosis after the angioplasty procedure, according to the FDA statement announcing the approval. “The clinical data show that Lutonix DCB may be more effective than traditional balloon angioplasty at helping to prevent further blockage in the artery,” Dr. William Maisel, deputy director for science and chief scientist in the FDA’s Center for Devices and Radiological Health, said in the statement.

Approval was based on the results of three clinical trials and nonclinical testing:

• A randomized, multicenter study of 101 people in Europe, which found that after 6 months, no further treatment for PAD was needed in almost 72% of the patients treated with Lutonix DCB, compared with almost 50% of those treated with conventional balloon angioplasty.

• A single-blind, multicenter, randomized study of 476 people in the United States and Europe, which found that 65% of those randomized to treatment with Lutonix DCB had no restenosis at 12 months, compared with roughly 53% of those randomized to treatment with conventional balloon angioplasty.

• A single-arm, ongoing study that is further evaluating safety and effectiveness in 657 people treated with the device in the United States and Europe, which, at the time of approval, “show that there have been no unanticipated device- or drug-related adverse events,” the FDA said.

These studies also indicated that the safety of Lutonix DCB was comparable to conventional balloon angioplasty. The most common major adverse events included additional intervention, pain as a result of poor blood flow, narrowing of arteries that were not treated, chest pain, and abnormal growth of tissue.

Contraindications include women who are breastfeeding, pregnant, or plan to become pregnant; and men who plan to father children.

The company is required by the FDA to conduct two postapproval studies, the ongoing 5-year study of 657 patients, and a randomized, single-blind, multicenter study that will evaluate safety and effectiveness of the device in women in the United States, “due to differences in observed outcomes in this group as compared to outcomes for the general study population,” according to the FDA.

The device was reviewed at an FDA advisory panel meeting in June.

[email protected]

The management of acne vulgaris (AV) in women has been the subject of considerable attention over the last few years. It has become increasingly recognized that a greater number of patient encounters in dermatology offices involve women with AV who are beyond their adolescent years. Overall, it is estimated that up to approximately 22% of women in the United States are affected by AV, with approximately half of women in their 20s and one-third of women in their 30s reporting some degree of AV.^1-4 Among women, the disease shows no predilection for certain skin types or ethnicities, can start during the preteenaged or adolescent years, can persist or recur in adulthood (persistent acne, 75%), or can start in adulthood (late-onset acne, 25%) in females with minimal or no history of AV occurring earlier in life.^3,5-7 In the subpopulation of adult women, AV occurs at a time when many expect to be far beyond this “teenage affliction.” Women who are affected commonly express feeling embarrassed and frustrated.^5-8

Most of the emphasis in the literature and in presentations at dermatology meetings regarding the management of AV in adult women has focused on excluding underlying disorders that cause excess androgens (eg, polycystic ovary syndrome, congenital adrenal hyperplasia, tumors, exogenous sources) as well as the use of systemic therapies such as oral contraceptives (OCs) and spironolactone.^5-7,9,10 Little attention has been given to the selection of topical therapies in this patient population, especially with regard to evidence from clinical studies. To date, results from published study analyses using topical agents specifically for adult females with facial AV have only included adapalene gel 0.3% applied once daily and dapsone gel 5% applied twice daily.^11-13 Both agents have been evaluated in subset analysis comparisons of outcomes in women aged 18 years and older versus adolescents aged 12 to 17 years based on data from 12-week phase 3 pivotal trials.^14-16

Are there clinically relevant differences between AV in adult versus adolescent females?

Although much has been written about AV in women, epidemiology, demographics, assessment of clinical presentation, and correlation of clinical presentation with excess androgens have not been emphasized,^1-3,5-10,17 likely due to marketing campaigns that emphasize AV as a disorder that predominantly affects teenagers as well as the focus on optimal use of oral spironolactone and/or OCs in the management of AV in the adult female population. Attention to spironolactone use is important because it is not approved by the US Food and Drug Administration for the treatment of AV. Spironolactone carries certain black-box warnings that may not be clinically relevant in all patients but still require attention. It also is associated with risks if taken during pregnancy, and it is a potassium-sparing diuretic with potential for hyperkalemia, especially in patients with reduced renal function or those who are taking potassium supplements or certain other medications.^6,9,11,17 Use of OCs to treat AV also is not without potential risks, with specific warnings and relative contraindications reported, especially in relation to increased risks for cardiac complications, stroke, and thromboembolism.^6,9,11,12 Because adult females are in a different stage of life than teenagers, there are defined psychosocial and medical considerations in managing AV in these patients compared with adolescents.^5-8,17 Importantly for both clinicians and patients, addressing these differences and considerations can have a major impact on whether or not women with AV experience successful treatment outcomes.^{1-3,5,6,8,10,13} Skin color and ethnicity also can affect the psychosocial and physical factors that influence the overall management of adult female patients with AV, including selection of therapies and handling long-term visible sequelae that occur in some AV patients, such as dyschromia (eg, persistent or postinflammatory erythema or hyperpigmentation) and acne scarring.^5-8,13,17-20

Psychosocial Considerations

With regard to psychosocial, emotional, and attitudinal considerations in women with AV, common findings include concern or frustration regarding the presence of AV beyond adolescence; anxiety; symptoms of depression; decreased self-confidence; increased self-consciousness, especially during public interactions or intimate situations; and interference with steady concentration at work or school.^5,6,8,13 Long-term complications of AV, such as dyschromia and acne scarring, are more likely to be encountered in adult patients, especially if they had AV as a teenager, with women reporting that they remain conscious of these adverse sequelae.⁸ It is estimated that approximately three-fourths of women with AV also had AV as teenagers; therefore, most of them have already used many over-the-counter and prescription therapies and are likely to want treatments that are newer, well-tolerated, safe, and known to be effective in adult women.^8,16,17 Convenience and simplicity are vital components of treatment selection and regimen design, as many women with AV frequently face time constraints in their daily routines due to family, social, employment, and home-related demands and responsibilities.^6-8,17

Medical Considerations

It is apparent from reports in the literature as well as from clinical experience that some women with AV present with a U-shaped pattern of involvement on the face,^5-7,10,13,17 which refers to the presence of predominantly inflammatory papules (many of them deep) and some nodules on the lower face, jawline, and anterolateral neck region, with comedones often sparse or absent.^5-7 It often is perceived and may be true that women who present with this pattern of distribution are more androgen sensitive despite having normal serum androgen levels or in some cases exhibit detectable excess androgens (eg, in the setting of polycystic ovary syndrome) and may be more likely to respond to hormonal therapies (eg, spironolactone, OCs) than those with mixed facial AV (ie, multiple comedonal and inflammatory acne lesions, not limited to a U-shaped pattern, similar to adolescent AV), but data are limited to support differentiation between the U-shaped pattern group and the conventional mixed facial AV group.^5-7,17 Adult and adolescent females in both groups sometimes report perimenstrual flares and frequent persistent papular AV that tends to concentrate on the perioral and chin area.

It is also important to consider that the current literature suggests approximately three-fourths of women with AV report that they also had AV as a teenager, with many indicating the same clinical pattern of AV and approximately one-third reporting AV that is more severe in adulthood than adolescence.^5-8,17 The available literature on topical and oral therapies used to treat AV in both adolescent and adult females predominantly focuses on inclusion of both inflammatory and noninflammatory (comedonal) facial AV lesions, does not specifically address or include the U-shaped pattern of AV in adult women for inclusion in studies that evaluate efficacy in this subgroup, and does not include AV involving the neck region and below the jawline margin as part of any study protocols and/or discussions about therapy.^{5-7,9-12,17,21-26} Involvement of the neck and lower jawline is common in women presenting with the U-shaped pattern of AV, and available studies only evaluate AV involving the face and do not include AV lesions present below the jawline margin. As a result, there is a considerable need for well-designed studies with laboratory assessments to include or exclude underlying detectable excess androgens and to assess the efficacy, tolerability, and safety of specific therapeutic agents both alone and in combination in adult women who present with a U-shaped pattern of AV.¹⁷

Other medical considerations that can influence treatment selection and are more likely to be present in adult versus adolescent females include underlying chronic medical disorders; concomitant medications that may interact with other oral agents; potential for pregnancy; age, particularly when prescribing OCs; and the  potential desire to stop taking OCs if already used over a prolonged period.^6,7

Age-Related Differentiation of Female Subgroups With AV

The age-based dividing line that defines AV in adults versus adolescent females has been described in the literature; however, the basis for published definitions of female subgroups with AV is not well-supported by strong scientific evidence.^1-3,5-7,17 The conventional dividing line that was originally selected to define adult females with AV was 25 years of age or older; persistent acne is present both during adolescence and at or after 25 years of age, while late-onset acne is described as AV that first presents at 25 years of age or older.^3,5-7

More recently, a range of 18 years or older has been used to classify adult female AV and a range of 12 to 17 years for adolescent female AV in subset analyses that evaluated treatment outcomes in both patient populations from phase 3 pivotal trials completed with adapalene gel 0.3% applied once daily and dapsone gel 5% applied twice daily.^14-16 These subanalyses included participants with facial AV that was predominantly moderate in severity, mandated specific lesion count ranges for both comedonal and inflammatory lesions, and included only facial AV that was above the mandibular (jawline) margin.^15,16,21,26 Therefore, patients with AV presenting in a U-shaped pattern with involvement below the jawline and on the neck were not included in these study analyses, as these patients were excluded from the phase 3 trials on which the analyses were based. The outcomes of these analyses apply to treatment in women who present with both inflammatory and noninflammatory facial AV lesions, which supports the observation that AV in this patient population is not always predominantly inflammatory and does not always present in a U-shaped distribution.^14-16 In fact, a U-shaped pattern of distribution appears to be less common in women with AV than a mixed inflammatory and comedonal distribution that involves the face more diffusely, though more data are needed from well-designed and large-scale epidemiologic and demographic studies.^5,14,17

Are there data available on the use of benzoyl peroxide with or without a topical antibiotic in women with AV?

There is a conspicuous absence of prospective clinical trials and retrospective analyses evaluating the specific use of individual AV therapies in adult females, with a particular lack of studies with topical agents (eg, benzoyl peroxide [BP]).¹⁴ Subset analyses have been completed for adapalene gel 0.3% and dapsone gel 5%.^15,16 Additionally, an age-based subset analysis in females with facial AV also has been completed with clindamycin phosphate (CP) 1.2%–BP 2.5% gel once daily, with data presented but not yet fully published.¹⁴

Two identical phase 3, double-blind, randomized, 12-week, 4-arm trials compared treatment outcomes in groups treated with an aqueous-based combination gel formulation containing BP 2.5% and CP 1.2% (n=797), active monad gels (BP [n=809] or CP [n=812]), or vehicle gel (n=395), all applied once daily in patients with facial AV.²² Participants were 12 years or older (mean age range, 19.1–19.6 years; age range, 12.1–70.2 years), were of either gender (approximately 50% split in each study arm), and presented with moderate (approximately 80% of participants) or severe AV (approximately 20% of participants) at baseline. The entry criteria for lesion types and number of lesions were 17 to 40 inflammatory lesions (ie, papules, pustules, <2 nodules)(range of mean number of lesions, 25.8–26.4) and 20 to 100 noninflammatory lesions (ie, closed comedones, open comedones)(range of mean number of lesions, 44.0–47.4). Participant demographics included white (73.9%–77.5%), black/African American (16.1%–20.4%), and Asian (2.1%–3.3%), with the remaining participants distributed among a variety of other ethnic groups such as Native Hawaiian/Native Pacific Islander and Native American Indian/Native Alaskan (collectively <5% in each study arm). Therefore, approximately 1 of every 4 patients had skin of color, which provided good diversity of patients considering the large study size (N=2813). Data analysis included dichotomization of participants by severity rating (moderate or severe based on evaluator global severity score) and skin phototype (Fitzpatrick skin types I–III or IV–VI).²²

The pooled results from both studies completed at 68 investigative sites demonstrated that CP 1.2%–BP 2.5% gel was superior in efficacy to each individual monad and to the vehicle in inflammatory, noninflammatory, and total lesion reductions as early as week 4 (P<.001) and at week 12, which was the study end point (P<.001), with superiority also demonstrated in achieving treatment success (defined as a >2 grade improvement according to the evaluator global severity score) compared to the 3 other study arms (P<.001).²² Subject assessments also were consistent with outcomes noted by the investigators. Cutaneous tolerability was favorable and comparable in all 4 study arms with less than 1% of participants discontinuing treatment due to adverse events.²²

A subset analysis of the data from the phase 3 pivotal trials with CP 1.2%–BP 2.5% gel was completed to compare reductions in both inflammatory and noninflammatory lesions in female participants who were younger than 25 years and 25 years of age or older in all 4 study arms. This information has been presented^14,17 but has not been previously published. Based on the overall results reported in the phase 3 studies, there were no differentiations in skin tolerability or safety based on participant age, gender, or skin type.²² The subanalysis included a total of 1080 females who were younger than 25 years and 395 females who were 25 years of age or older. The lesion reduction outcomes of this subanalysis are presented in the Table. Statistical analyses of the results among these age groups in the 4 study arms were not completed because the objective was to determine if there were any major or obvious differences in reduction of AV lesions based on the conventional dividing line of 25 years of age in adult women as compared to adolescent females treated with CP 1.2%–BP 2.5% gel. In addition, the large difference in numbers of female participants between the 2 age groups (>25 years of age, n=395; <25 years of age, n=1080) at least partially confounds both statistical and observational analysis. Among the women who were 25 years of age or older who were included in the subanalysis, 67.0% and 25.8% were between the ages of 25 to 35 years and 36 to 45 years, respectively. Based on the outcomes reported in the phase 3 trials and in this subgroup analysis, CP 1.2%–BP 2.5% gel applied once daily over a 12-week period appeared overall to be comparably effective in females regardless of age and with no apparent adverse events regarding differences in skin tolerability or safety.^14,22 One observation that was noted was the possible trend of greater reduction in both lesion types in women older than 35 years versus younger females with the use of the combination gel or BP alone; however, the number of female participants who were older than 35 years of age was substantially less (n=102) than those who were 35 years of age or younger (n=1345), thus precluding support for any definitive conclusions about this possible trend.²²

How can CP 1.2%–BP 2.5% gel be incorporated into a treatment regimen for women with facial AV?

The incorporation of CP 1.2%–BP 2.5% gel into a treatment regimen for women with facial AV is similar to the general use of BP-containing formulations in the overall management of AV.^9,14,27,28 Because women with AV commonly present with facial inflammatory lesions and many also with facial comedones, CP 1.2%–BP 2.5% gel is best used once daily in the morning in combination with a topical retinoid in the evening,^9,27 which can be achieved with use of CP 1.2%–BP 2.5% gel in the morning and a topical retinoid (ie, tretinoin, adapalene, tazarotene) in the evening or CP 1.2%–tretinoin 0.025% gel in the evening. It is important to note that cutaneous irritation may be more likely if neck lesions are present; the potential for bleaching of colored fabric by BP also is a practical concern.²⁸ In addition, CP 1.2%–BP 2.5% gel may also be used in combination with topical dapsone, but both products should be applied separately at different times of the day to avoid temporary orange discoloration of the skin, which appears to be an uncommon side effect but remains a possibility based on the product information for dapsone gel 5% with regard to its concomitant use with BP.^29,30

The management of acne vulgaris (AV) in women has been the subject of considerable attention over the last few years. It has become increasingly recognized that a greater number of patient encounters in dermatology offices involve women with AV who are beyond their adolescent years. Overall, it is estimated that up to approximately 22% of women in the United States are affected by AV, with approximately half of women in their 20s and one-third of women in their 30s reporting some degree of AV.^1-4 Among women, the disease shows no predilection for certain skin types or ethnicities, can start during the preteenaged or adolescent years, can persist or recur in adulthood (persistent acne, 75%), or can start in adulthood (late-onset acne, 25%) in females with minimal or no history of AV occurring earlier in life.^3,5-7 In the subpopulation of adult women, AV occurs at a time when many expect to be far beyond this “teenage affliction.” Women who are affected commonly express feeling embarrassed and frustrated.^5-8

Most of the emphasis in the literature and in presentations at dermatology meetings regarding the management of AV in adult women has focused on excluding underlying disorders that cause excess androgens (eg, polycystic ovary syndrome, congenital adrenal hyperplasia, tumors, exogenous sources) as well as the use of systemic therapies such as oral contraceptives (OCs) and spironolactone.^5-7,9,10 Little attention has been given to the selection of topical therapies in this patient population, especially with regard to evidence from clinical studies. To date, results from published study analyses using topical agents specifically for adult females with facial AV have only included adapalene gel 0.3% applied once daily and dapsone gel 5% applied twice daily.^11-13 Both agents have been evaluated in subset analysis comparisons of outcomes in women aged 18 years and older versus adolescents aged 12 to 17 years based on data from 12-week phase 3 pivotal trials.^14-16

Are there clinically relevant differences between AV in adult versus adolescent females?

Although much has been written about AV in women, epidemiology, demographics, assessment of clinical presentation, and correlation of clinical presentation with excess androgens have not been emphasized,^1-3,5-10,17 likely due to marketing campaigns that emphasize AV as a disorder that predominantly affects teenagers as well as the focus on optimal use of oral spironolactone and/or OCs in the management of AV in the adult female population. Attention to spironolactone use is important because it is not approved by the US Food and Drug Administration for the treatment of AV. Spironolactone carries certain black-box warnings that may not be clinically relevant in all patients but still require attention. It also is associated with risks if taken during pregnancy, and it is a potassium-sparing diuretic with potential for hyperkalemia, especially in patients with reduced renal function or those who are taking potassium supplements or certain other medications.^6,9,11,17 Use of OCs to treat AV also is not without potential risks, with specific warnings and relative contraindications reported, especially in relation to increased risks for cardiac complications, stroke, and thromboembolism.^6,9,11,12 Because adult females are in a different stage of life than teenagers, there are defined psychosocial and medical considerations in managing AV in these patients compared with adolescents.^5-8,17 Importantly for both clinicians and patients, addressing these differences and considerations can have a major impact on whether or not women with AV experience successful treatment outcomes.^{1-3,5,6,8,10,13} Skin color and ethnicity also can affect the psychosocial and physical factors that influence the overall management of adult female patients with AV, including selection of therapies and handling long-term visible sequelae that occur in some AV patients, such as dyschromia (eg, persistent or postinflammatory erythema or hyperpigmentation) and acne scarring.^5-8,13,17-20

Psychosocial Considerations

With regard to psychosocial, emotional, and attitudinal considerations in women with AV, common findings include concern or frustration regarding the presence of AV beyond adolescence; anxiety; symptoms of depression; decreased self-confidence; increased self-consciousness, especially during public interactions or intimate situations; and interference with steady concentration at work or school.^5,6,8,13 Long-term complications of AV, such as dyschromia and acne scarring, are more likely to be encountered in adult patients, especially if they had AV as a teenager, with women reporting that they remain conscious of these adverse sequelae.⁸ It is estimated that approximately three-fourths of women with AV also had AV as teenagers; therefore, most of them have already used many over-the-counter and prescription therapies and are likely to want treatments that are newer, well-tolerated, safe, and known to be effective in adult women.^8,16,17 Convenience and simplicity are vital components of treatment selection and regimen design, as many women with AV frequently face time constraints in their daily routines due to family, social, employment, and home-related demands and responsibilities.^6-8,17

Medical Considerations

It is apparent from reports in the literature as well as from clinical experience that some women with AV present with a U-shaped pattern of involvement on the face,^5-7,10,13,17 which refers to the presence of predominantly inflammatory papules (many of them deep) and some nodules on the lower face, jawline, and anterolateral neck region, with comedones often sparse or absent.^5-7 It often is perceived and may be true that women who present with this pattern of distribution are more androgen sensitive despite having normal serum androgen levels or in some cases exhibit detectable excess androgens (eg, in the setting of polycystic ovary syndrome) and may be more likely to respond to hormonal therapies (eg, spironolactone, OCs) than those with mixed facial AV (ie, multiple comedonal and inflammatory acne lesions, not limited to a U-shaped pattern, similar to adolescent AV), but data are limited to support differentiation between the U-shaped pattern group and the conventional mixed facial AV group.^5-7,17 Adult and adolescent females in both groups sometimes report perimenstrual flares and frequent persistent papular AV that tends to concentrate on the perioral and chin area.

It is also important to consider that the current literature suggests approximately three-fourths of women with AV report that they also had AV as a teenager, with many indicating the same clinical pattern of AV and approximately one-third reporting AV that is more severe in adulthood than adolescence.^5-8,17 The available literature on topical and oral therapies used to treat AV in both adolescent and adult females predominantly focuses on inclusion of both inflammatory and noninflammatory (comedonal) facial AV lesions, does not specifically address or include the U-shaped pattern of AV in adult women for inclusion in studies that evaluate efficacy in this subgroup, and does not include AV involving the neck region and below the jawline margin as part of any study protocols and/or discussions about therapy.^{5-7,9-12,17,21-26} Involvement of the neck and lower jawline is common in women presenting with the U-shaped pattern of AV, and available studies only evaluate AV involving the face and do not include AV lesions present below the jawline margin. As a result, there is a considerable need for well-designed studies with laboratory assessments to include or exclude underlying detectable excess androgens and to assess the efficacy, tolerability, and safety of specific therapeutic agents both alone and in combination in adult women who present with a U-shaped pattern of AV.¹⁷

Other medical considerations that can influence treatment selection and are more likely to be present in adult versus adolescent females include underlying chronic medical disorders; concomitant medications that may interact with other oral agents; potential for pregnancy; age, particularly when prescribing OCs; and the  potential desire to stop taking OCs if already used over a prolonged period.^6,7

Age-Related Differentiation of Female Subgroups With AV

The age-based dividing line that defines AV in adults versus adolescent females has been described in the literature; however, the basis for published definitions of female subgroups with AV is not well-supported by strong scientific evidence.^1-3,5-7,17 The conventional dividing line that was originally selected to define adult females with AV was 25 years of age or older; persistent acne is present both during adolescence and at or after 25 years of age, while late-onset acne is described as AV that first presents at 25 years of age or older.^3,5-7

More recently, a range of 18 years or older has been used to classify adult female AV and a range of 12 to 17 years for adolescent female AV in subset analyses that evaluated treatment outcomes in both patient populations from phase 3 pivotal trials completed with adapalene gel 0.3% applied once daily and dapsone gel 5% applied twice daily.^14-16 These subanalyses included participants with facial AV that was predominantly moderate in severity, mandated specific lesion count ranges for both comedonal and inflammatory lesions, and included only facial AV that was above the mandibular (jawline) margin.^15,16,21,26 Therefore, patients with AV presenting in a U-shaped pattern with involvement below the jawline and on the neck were not included in these study analyses, as these patients were excluded from the phase 3 trials on which the analyses were based. The outcomes of these analyses apply to treatment in women who present with both inflammatory and noninflammatory facial AV lesions, which supports the observation that AV in this patient population is not always predominantly inflammatory and does not always present in a U-shaped distribution.^14-16 In fact, a U-shaped pattern of distribution appears to be less common in women with AV than a mixed inflammatory and comedonal distribution that involves the face more diffusely, though more data are needed from well-designed and large-scale epidemiologic and demographic studies.^5,14,17

Are there data available on the use of benzoyl peroxide with or without a topical antibiotic in women with AV?

There is a conspicuous absence of prospective clinical trials and retrospective analyses evaluating the specific use of individual AV therapies in adult females, with a particular lack of studies with topical agents (eg, benzoyl peroxide [BP]).¹⁴ Subset analyses have been completed for adapalene gel 0.3% and dapsone gel 5%.^15,16 Additionally, an age-based subset analysis in females with facial AV also has been completed with clindamycin phosphate (CP) 1.2%–BP 2.5% gel once daily, with data presented but not yet fully published.¹⁴

Two identical phase 3, double-blind, randomized, 12-week, 4-arm trials compared treatment outcomes in groups treated with an aqueous-based combination gel formulation containing BP 2.5% and CP 1.2% (n=797), active monad gels (BP [n=809] or CP [n=812]), or vehicle gel (n=395), all applied once daily in patients with facial AV.²² Participants were 12 years or older (mean age range, 19.1–19.6 years; age range, 12.1–70.2 years), were of either gender (approximately 50% split in each study arm), and presented with moderate (approximately 80% of participants) or severe AV (approximately 20% of participants) at baseline. The entry criteria for lesion types and number of lesions were 17 to 40 inflammatory lesions (ie, papules, pustules, <2 nodules)(range of mean number of lesions, 25.8–26.4) and 20 to 100 noninflammatory lesions (ie, closed comedones, open comedones)(range of mean number of lesions, 44.0–47.4). Participant demographics included white (73.9%–77.5%), black/African American (16.1%–20.4%), and Asian (2.1%–3.3%), with the remaining participants distributed among a variety of other ethnic groups such as Native Hawaiian/Native Pacific Islander and Native American Indian/Native Alaskan (collectively <5% in each study arm). Therefore, approximately 1 of every 4 patients had skin of color, which provided good diversity of patients considering the large study size (N=2813). Data analysis included dichotomization of participants by severity rating (moderate or severe based on evaluator global severity score) and skin phototype (Fitzpatrick skin types I–III or IV–VI).²²

The pooled results from both studies completed at 68 investigative sites demonstrated that CP 1.2%–BP 2.5% gel was superior in efficacy to each individual monad and to the vehicle in inflammatory, noninflammatory, and total lesion reductions as early as week 4 (P<.001) and at week 12, which was the study end point (P<.001), with superiority also demonstrated in achieving treatment success (defined as a >2 grade improvement according to the evaluator global severity score) compared to the 3 other study arms (P<.001).²² Subject assessments also were consistent with outcomes noted by the investigators. Cutaneous tolerability was favorable and comparable in all 4 study arms with less than 1% of participants discontinuing treatment due to adverse events.²²

A subset analysis of the data from the phase 3 pivotal trials with CP 1.2%–BP 2.5% gel was completed to compare reductions in both inflammatory and noninflammatory lesions in female participants who were younger than 25 years and 25 years of age or older in all 4 study arms. This information has been presented^14,17 but has not been previously published. Based on the overall results reported in the phase 3 studies, there were no differentiations in skin tolerability or safety based on participant age, gender, or skin type.²² The subanalysis included a total of 1080 females who were younger than 25 years and 395 females who were 25 years of age or older. The lesion reduction outcomes of this subanalysis are presented in the Table. Statistical analyses of the results among these age groups in the 4 study arms were not completed because the objective was to determine if there were any major or obvious differences in reduction of AV lesions based on the conventional dividing line of 25 years of age in adult women as compared to adolescent females treated with CP 1.2%–BP 2.5% gel. In addition, the large difference in numbers of female participants between the 2 age groups (>25 years of age, n=395; <25 years of age, n=1080) at least partially confounds both statistical and observational analysis. Among the women who were 25 years of age or older who were included in the subanalysis, 67.0% and 25.8% were between the ages of 25 to 35 years and 36 to 45 years, respectively. Based on the outcomes reported in the phase 3 trials and in this subgroup analysis, CP 1.2%–BP 2.5% gel applied once daily over a 12-week period appeared overall to be comparably effective in females regardless of age and with no apparent adverse events regarding differences in skin tolerability or safety.^14,22 One observation that was noted was the possible trend of greater reduction in both lesion types in women older than 35 years versus younger females with the use of the combination gel or BP alone; however, the number of female participants who were older than 35 years of age was substantially less (n=102) than those who were 35 years of age or younger (n=1345), thus precluding support for any definitive conclusions about this possible trend.²²

How can CP 1.2%–BP 2.5% gel be incorporated into a treatment regimen for women with facial AV?

The incorporation of CP 1.2%–BP 2.5% gel into a treatment regimen for women with facial AV is similar to the general use of BP-containing formulations in the overall management of AV.^9,14,27,28 Because women with AV commonly present with facial inflammatory lesions and many also with facial comedones, CP 1.2%–BP 2.5% gel is best used once daily in the morning in combination with a topical retinoid in the evening,^9,27 which can be achieved with use of CP 1.2%–BP 2.5% gel in the morning and a topical retinoid (ie, tretinoin, adapalene, tazarotene) in the evening or CP 1.2%–tretinoin 0.025% gel in the evening. It is important to note that cutaneous irritation may be more likely if neck lesions are present; the potential for bleaching of colored fabric by BP also is a practical concern.²⁸ In addition, CP 1.2%–BP 2.5% gel may also be used in combination with topical dapsone, but both products should be applied separately at different times of the day to avoid temporary orange discoloration of the skin, which appears to be an uncommon side effect but remains a possibility based on the product information for dapsone gel 5% with regard to its concomitant use with BP.^29,30

The management of acne vulgaris (AV) in women has been the subject of considerable attention over the last few years. It has become increasingly recognized that a greater number of patient encounters in dermatology offices involve women with AV who are beyond their adolescent years. Overall, it is estimated that up to approximately 22% of women in the United States are affected by AV, with approximately half of women in their 20s and one-third of women in their 30s reporting some degree of AV.^1-4 Among women, the disease shows no predilection for certain skin types or ethnicities, can start during the preteenaged or adolescent years, can persist or recur in adulthood (persistent acne, 75%), or can start in adulthood (late-onset acne, 25%) in females with minimal or no history of AV occurring earlier in life.^3,5-7 In the subpopulation of adult women, AV occurs at a time when many expect to be far beyond this “teenage affliction.” Women who are affected commonly express feeling embarrassed and frustrated.^5-8

Most of the emphasis in the literature and in presentations at dermatology meetings regarding the management of AV in adult women has focused on excluding underlying disorders that cause excess androgens (eg, polycystic ovary syndrome, congenital adrenal hyperplasia, tumors, exogenous sources) as well as the use of systemic therapies such as oral contraceptives (OCs) and spironolactone.^5-7,9,10 Little attention has been given to the selection of topical therapies in this patient population, especially with regard to evidence from clinical studies. To date, results from published study analyses using topical agents specifically for adult females with facial AV have only included adapalene gel 0.3% applied once daily and dapsone gel 5% applied twice daily.^11-13 Both agents have been evaluated in subset analysis comparisons of outcomes in women aged 18 years and older versus adolescents aged 12 to 17 years based on data from 12-week phase 3 pivotal trials.^14-16

Are there clinically relevant differences between AV in adult versus adolescent females?

Although much has been written about AV in women, epidemiology, demographics, assessment of clinical presentation, and correlation of clinical presentation with excess androgens have not been emphasized,^1-3,5-10,17 likely due to marketing campaigns that emphasize AV as a disorder that predominantly affects teenagers as well as the focus on optimal use of oral spironolactone and/or OCs in the management of AV in the adult female population. Attention to spironolactone use is important because it is not approved by the US Food and Drug Administration for the treatment of AV. Spironolactone carries certain black-box warnings that may not be clinically relevant in all patients but still require attention. It also is associated with risks if taken during pregnancy, and it is a potassium-sparing diuretic with potential for hyperkalemia, especially in patients with reduced renal function or those who are taking potassium supplements or certain other medications.^6,9,11,17 Use of OCs to treat AV also is not without potential risks, with specific warnings and relative contraindications reported, especially in relation to increased risks for cardiac complications, stroke, and thromboembolism.^6,9,11,12 Because adult females are in a different stage of life than teenagers, there are defined psychosocial and medical considerations in managing AV in these patients compared with adolescents.^5-8,17 Importantly for both clinicians and patients, addressing these differences and considerations can have a major impact on whether or not women with AV experience successful treatment outcomes.^{1-3,5,6,8,10,13} Skin color and ethnicity also can affect the psychosocial and physical factors that influence the overall management of adult female patients with AV, including selection of therapies and handling long-term visible sequelae that occur in some AV patients, such as dyschromia (eg, persistent or postinflammatory erythema or hyperpigmentation) and acne scarring.^5-8,13,17-20

Psychosocial Considerations

With regard to psychosocial, emotional, and attitudinal considerations in women with AV, common findings include concern or frustration regarding the presence of AV beyond adolescence; anxiety; symptoms of depression; decreased self-confidence; increased self-consciousness, especially during public interactions or intimate situations; and interference with steady concentration at work or school.^5,6,8,13 Long-term complications of AV, such as dyschromia and acne scarring, are more likely to be encountered in adult patients, especially if they had AV as a teenager, with women reporting that they remain conscious of these adverse sequelae.⁸ It is estimated that approximately three-fourths of women with AV also had AV as teenagers; therefore, most of them have already used many over-the-counter and prescription therapies and are likely to want treatments that are newer, well-tolerated, safe, and known to be effective in adult women.^8,16,17 Convenience and simplicity are vital components of treatment selection and regimen design, as many women with AV frequently face time constraints in their daily routines due to family, social, employment, and home-related demands and responsibilities.^6-8,17

Medical Considerations

It is apparent from reports in the literature as well as from clinical experience that some women with AV present with a U-shaped pattern of involvement on the face,^5-7,10,13,17 which refers to the presence of predominantly inflammatory papules (many of them deep) and some nodules on the lower face, jawline, and anterolateral neck region, with comedones often sparse or absent.^5-7 It often is perceived and may be true that women who present with this pattern of distribution are more androgen sensitive despite having normal serum androgen levels or in some cases exhibit detectable excess androgens (eg, in the setting of polycystic ovary syndrome) and may be more likely to respond to hormonal therapies (eg, spironolactone, OCs) than those with mixed facial AV (ie, multiple comedonal and inflammatory acne lesions, not limited to a U-shaped pattern, similar to adolescent AV), but data are limited to support differentiation between the U-shaped pattern group and the conventional mixed facial AV group.^5-7,17 Adult and adolescent females in both groups sometimes report perimenstrual flares and frequent persistent papular AV that tends to concentrate on the perioral and chin area.

It is also important to consider that the current literature suggests approximately three-fourths of women with AV report that they also had AV as a teenager, with many indicating the same clinical pattern of AV and approximately one-third reporting AV that is more severe in adulthood than adolescence.^5-8,17 The available literature on topical and oral therapies used to treat AV in both adolescent and adult females predominantly focuses on inclusion of both inflammatory and noninflammatory (comedonal) facial AV lesions, does not specifically address or include the U-shaped pattern of AV in adult women for inclusion in studies that evaluate efficacy in this subgroup, and does not include AV involving the neck region and below the jawline margin as part of any study protocols and/or discussions about therapy.^{5-7,9-12,17,21-26} Involvement of the neck and lower jawline is common in women presenting with the U-shaped pattern of AV, and available studies only evaluate AV involving the face and do not include AV lesions present below the jawline margin. As a result, there is a considerable need for well-designed studies with laboratory assessments to include or exclude underlying detectable excess androgens and to assess the efficacy, tolerability, and safety of specific therapeutic agents both alone and in combination in adult women who present with a U-shaped pattern of AV.¹⁷

Other medical considerations that can influence treatment selection and are more likely to be present in adult versus adolescent females include underlying chronic medical disorders; concomitant medications that may interact with other oral agents; potential for pregnancy; age, particularly when prescribing OCs; and the  potential desire to stop taking OCs if already used over a prolonged period.^6,7

Age-Related Differentiation of Female Subgroups With AV

The age-based dividing line that defines AV in adults versus adolescent females has been described in the literature; however, the basis for published definitions of female subgroups with AV is not well-supported by strong scientific evidence.^1-3,5-7,17 The conventional dividing line that was originally selected to define adult females with AV was 25 years of age or older; persistent acne is present both during adolescence and at or after 25 years of age, while late-onset acne is described as AV that first presents at 25 years of age or older.^3,5-7

More recently, a range of 18 years or older has been used to classify adult female AV and a range of 12 to 17 years for adolescent female AV in subset analyses that evaluated treatment outcomes in both patient populations from phase 3 pivotal trials completed with adapalene gel 0.3% applied once daily and dapsone gel 5% applied twice daily.^14-16 These subanalyses included participants with facial AV that was predominantly moderate in severity, mandated specific lesion count ranges for both comedonal and inflammatory lesions, and included only facial AV that was above the mandibular (jawline) margin.^15,16,21,26 Therefore, patients with AV presenting in a U-shaped pattern with involvement below the jawline and on the neck were not included in these study analyses, as these patients were excluded from the phase 3 trials on which the analyses were based. The outcomes of these analyses apply to treatment in women who present with both inflammatory and noninflammatory facial AV lesions, which supports the observation that AV in this patient population is not always predominantly inflammatory and does not always present in a U-shaped distribution.^14-16 In fact, a U-shaped pattern of distribution appears to be less common in women with AV than a mixed inflammatory and comedonal distribution that involves the face more diffusely, though more data are needed from well-designed and large-scale epidemiologic and demographic studies.^5,14,17

Are there data available on the use of benzoyl peroxide with or without a topical antibiotic in women with AV?

There is a conspicuous absence of prospective clinical trials and retrospective analyses evaluating the specific use of individual AV therapies in adult females, with a particular lack of studies with topical agents (eg, benzoyl peroxide [BP]).¹⁴ Subset analyses have been completed for adapalene gel 0.3% and dapsone gel 5%.^15,16 Additionally, an age-based subset analysis in females with facial AV also has been completed with clindamycin phosphate (CP) 1.2%–BP 2.5% gel once daily, with data presented but not yet fully published.¹⁴

Two identical phase 3, double-blind, randomized, 12-week, 4-arm trials compared treatment outcomes in groups treated with an aqueous-based combination gel formulation containing BP 2.5% and CP 1.2% (n=797), active monad gels (BP [n=809] or CP [n=812]), or vehicle gel (n=395), all applied once daily in patients with facial AV.²² Participants were 12 years or older (mean age range, 19.1–19.6 years; age range, 12.1–70.2 years), were of either gender (approximately 50% split in each study arm), and presented with moderate (approximately 80% of participants) or severe AV (approximately 20% of participants) at baseline. The entry criteria for lesion types and number of lesions were 17 to 40 inflammatory lesions (ie, papules, pustules, <2 nodules)(range of mean number of lesions, 25.8–26.4) and 20 to 100 noninflammatory lesions (ie, closed comedones, open comedones)(range of mean number of lesions, 44.0–47.4). Participant demographics included white (73.9%–77.5%), black/African American (16.1%–20.4%), and Asian (2.1%–3.3%), with the remaining participants distributed among a variety of other ethnic groups such as Native Hawaiian/Native Pacific Islander and Native American Indian/Native Alaskan (collectively <5% in each study arm). Therefore, approximately 1 of every 4 patients had skin of color, which provided good diversity of patients considering the large study size (N=2813). Data analysis included dichotomization of participants by severity rating (moderate or severe based on evaluator global severity score) and skin phototype (Fitzpatrick skin types I–III or IV–VI).²²

The pooled results from both studies completed at 68 investigative sites demonstrated that CP 1.2%–BP 2.5% gel was superior in efficacy to each individual monad and to the vehicle in inflammatory, noninflammatory, and total lesion reductions as early as week 4 (P<.001) and at week 12, which was the study end point (P<.001), with superiority also demonstrated in achieving treatment success (defined as a >2 grade improvement according to the evaluator global severity score) compared to the 3 other study arms (P<.001).²² Subject assessments also were consistent with outcomes noted by the investigators. Cutaneous tolerability was favorable and comparable in all 4 study arms with less than 1% of participants discontinuing treatment due to adverse events.²²

A subset analysis of the data from the phase 3 pivotal trials with CP 1.2%–BP 2.5% gel was completed to compare reductions in both inflammatory and noninflammatory lesions in female participants who were younger than 25 years and 25 years of age or older in all 4 study arms. This information has been presented^14,17 but has not been previously published. Based on the overall results reported in the phase 3 studies, there were no differentiations in skin tolerability or safety based on participant age, gender, or skin type.²² The subanalysis included a total of 1080 females who were younger than 25 years and 395 females who were 25 years of age or older. The lesion reduction outcomes of this subanalysis are presented in the Table. Statistical analyses of the results among these age groups in the 4 study arms were not completed because the objective was to determine if there were any major or obvious differences in reduction of AV lesions based on the conventional dividing line of 25 years of age in adult women as compared to adolescent females treated with CP 1.2%–BP 2.5% gel. In addition, the large difference in numbers of female participants between the 2 age groups (>25 years of age, n=395; <25 years of age, n=1080) at least partially confounds both statistical and observational analysis. Among the women who were 25 years of age or older who were included in the subanalysis, 67.0% and 25.8% were between the ages of 25 to 35 years and 36 to 45 years, respectively. Based on the outcomes reported in the phase 3 trials and in this subgroup analysis, CP 1.2%–BP 2.5% gel applied once daily over a 12-week period appeared overall to be comparably effective in females regardless of age and with no apparent adverse events regarding differences in skin tolerability or safety.^14,22 One observation that was noted was the possible trend of greater reduction in both lesion types in women older than 35 years versus younger females with the use of the combination gel or BP alone; however, the number of female participants who were older than 35 years of age was substantially less (n=102) than those who were 35 years of age or younger (n=1345), thus precluding support for any definitive conclusions about this possible trend.²²

How can CP 1.2%–BP 2.5% gel be incorporated into a treatment regimen for women with facial AV?

The incorporation of CP 1.2%–BP 2.5% gel into a treatment regimen for women with facial AV is similar to the general use of BP-containing formulations in the overall management of AV.^9,14,27,28 Because women with AV commonly present with facial inflammatory lesions and many also with facial comedones, CP 1.2%–BP 2.5% gel is best used once daily in the morning in combination with a topical retinoid in the evening,^9,27 which can be achieved with use of CP 1.2%–BP 2.5% gel in the morning and a topical retinoid (ie, tretinoin, adapalene, tazarotene) in the evening or CP 1.2%–tretinoin 0.025% gel in the evening. It is important to note that cutaneous irritation may be more likely if neck lesions are present; the potential for bleaching of colored fabric by BP also is a practical concern.²⁸ In addition, CP 1.2%–BP 2.5% gel may also be used in combination with topical dapsone, but both products should be applied separately at different times of the day to avoid temporary orange discoloration of the skin, which appears to be an uncommon side effect but remains a possibility based on the product information for dapsone gel 5% with regard to its concomitant use with BP.^29,30

Lipidized dermatofibromas most commonly are found on the ankles, which has led some authors to refer to these lesions as ankle-type fibrous histiocytomas.¹ Compared to ordinary dermatofibromas, patients with lipidized dermatofibromas tend to be older, most commonly presenting in the fifth or sixth decades of life, and are predominantly male. Lipidized dermatofibromas typically present as well-circumscribed solitary nodules in the dermis. Characteristic features include numerous xanthomatous cells dissected by distinctive hyalinized wiry collagen fibers (Figures 1 and 2).¹ Xanthomatous cells can be round, polygonal, or stellate in shape. These characteristic features in combination with others of dermatofibromas (eg, epidermal acanthosis [Figure 1]) fulfill the criteria for diagnosis of a lipidized dermatofibroma. Additionally, lipidized dermatofibromas tend to be larger than ordinary dermatofibromas, which typically are less than 2 cm in diameter.¹

Figure 1. Lipidized dermatofibromas are characterized by classic epidermal features of dermatofibromas, such as acanthosis, along with numerous foam cells and extensive stromal hyalinization (H&E, original magnification ×1.5).

Figure 2. Higher-power view of a lipidized dermatofibroma shows the characteristic irregular dissection of hyalinized wiry collagen fibers between the xanthomatous cells (H&E, original magnification ×20).

Eruptive xanthomas are characterized by a lacelike infiltrate of extravascular lipid deposits between collagen bundles (Figure 3).² Granular cell tumors are composed of sheets and/or nests of large cells with abundant eosinophilic cytoplasm and may be confused with lipidized dermatofibromas, as they also may induce overlying pseudoepitheliomatous hyperplasia³; however, on closer examination of the cells, the cytoplasm is found to be granular (Figure 4), which contrasts the finely vacuolated cytoplasm of xanthomatous cells found in lipidized dermatofibromas. Giant lysosomal granules (eg, pustulo-ovoid bodies of Milian) are present in some cases.² Of note, an unusual variant of dermatofibroma exists that features prominent granular cells.⁴

Figure 3. Lacelike deposition of extravascular lipid deposits is seen infiltrating between collagen bundles in an eruptive xanthoma (H&E, original magnification ×20).

Figure 4. An abundant eosinophilic, finely granular cytoplasm is characteristic of granular cell tumor (H&E, original magnification ×40).

Tuberous xanthomas most commonly occur around the pressure areas, such as the knees, elbows, and buttocks. Foam cells are a main feature of tuberous xanthomas and are arranged in large aggregates throughout the dermis.² Tuberous xanthomas lack Touton giant cells or inflammatory cells. Older lesions tend to develop substantial fibrosis (Figure 5). Although foam cells can be present in older lesions, they are never as conspicuous as those found in other xanthomas.

Xanthogranulomas commonly occur on the head and neck. Findings noted on low magnification include a well-circumscribed exophytic nodule and an epidermal collarette, which help to easily distinguish xanthogranulomas from lipidized dermatofibromas. Additionally, the presence of a more prominent inflammatory infiltrate, which often includes eosinophils, as well as multinucleated Touton giant cells (Figure 6) and histiocytes with more eosinophilic and less xanthomatous cytoplasm can help distinguish between the lesions.^1,5 Notably, Touton giant cells also can be seen in lipidized dermatofibromas,¹ but the presence of unique features such as distinctive stromal hyalinization are clues to the correct diagnosis of a lipidized dermatofibroma.

Lipidized dermatofibromas most commonly are found on the ankles, which has led some authors to refer to these lesions as ankle-type fibrous histiocytomas.¹ Compared to ordinary dermatofibromas, patients with lipidized dermatofibromas tend to be older, most commonly presenting in the fifth or sixth decades of life, and are predominantly male. Lipidized dermatofibromas typically present as well-circumscribed solitary nodules in the dermis. Characteristic features include numerous xanthomatous cells dissected by distinctive hyalinized wiry collagen fibers (Figures 1 and 2).¹ Xanthomatous cells can be round, polygonal, or stellate in shape. These characteristic features in combination with others of dermatofibromas (eg, epidermal acanthosis [Figure 1]) fulfill the criteria for diagnosis of a lipidized dermatofibroma. Additionally, lipidized dermatofibromas tend to be larger than ordinary dermatofibromas, which typically are less than 2 cm in diameter.¹

Figure 1. Lipidized dermatofibromas are characterized by classic epidermal features of dermatofibromas, such as acanthosis, along with numerous foam cells and extensive stromal hyalinization (H&E, original magnification ×1.5).

Figure 2. Higher-power view of a lipidized dermatofibroma shows the characteristic irregular dissection of hyalinized wiry collagen fibers between the xanthomatous cells (H&E, original magnification ×20).

Eruptive xanthomas are characterized by a lacelike infiltrate of extravascular lipid deposits between collagen bundles (Figure 3).² Granular cell tumors are composed of sheets and/or nests of large cells with abundant eosinophilic cytoplasm and may be confused with lipidized dermatofibromas, as they also may induce overlying pseudoepitheliomatous hyperplasia³; however, on closer examination of the cells, the cytoplasm is found to be granular (Figure 4), which contrasts the finely vacuolated cytoplasm of xanthomatous cells found in lipidized dermatofibromas. Giant lysosomal granules (eg, pustulo-ovoid bodies of Milian) are present in some cases.² Of note, an unusual variant of dermatofibroma exists that features prominent granular cells.⁴

Figure 3. Lacelike deposition of extravascular lipid deposits is seen infiltrating between collagen bundles in an eruptive xanthoma (H&E, original magnification ×20).

Figure 4. An abundant eosinophilic, finely granular cytoplasm is characteristic of granular cell tumor (H&E, original magnification ×40).

Tuberous xanthomas most commonly occur around the pressure areas, such as the knees, elbows, and buttocks. Foam cells are a main feature of tuberous xanthomas and are arranged in large aggregates throughout the dermis.² Tuberous xanthomas lack Touton giant cells or inflammatory cells. Older lesions tend to develop substantial fibrosis (Figure 5). Although foam cells can be present in older lesions, they are never as conspicuous as those found in other xanthomas.

Xanthogranulomas commonly occur on the head and neck. Findings noted on low magnification include a well-circumscribed exophytic nodule and an epidermal collarette, which help to easily distinguish xanthogranulomas from lipidized dermatofibromas. Additionally, the presence of a more prominent inflammatory infiltrate, which often includes eosinophils, as well as multinucleated Touton giant cells (Figure 6) and histiocytes with more eosinophilic and less xanthomatous cytoplasm can help distinguish between the lesions.^1,5 Notably, Touton giant cells also can be seen in lipidized dermatofibromas,¹ but the presence of unique features such as distinctive stromal hyalinization are clues to the correct diagnosis of a lipidized dermatofibroma.

Lipidized dermatofibromas most commonly are found on the ankles, which has led some authors to refer to these lesions as ankle-type fibrous histiocytomas.¹ Compared to ordinary dermatofibromas, patients with lipidized dermatofibromas tend to be older, most commonly presenting in the fifth or sixth decades of life, and are predominantly male. Lipidized dermatofibromas typically present as well-circumscribed solitary nodules in the dermis. Characteristic features include numerous xanthomatous cells dissected by distinctive hyalinized wiry collagen fibers (Figures 1 and 2).¹ Xanthomatous cells can be round, polygonal, or stellate in shape. These characteristic features in combination with others of dermatofibromas (eg, epidermal acanthosis [Figure 1]) fulfill the criteria for diagnosis of a lipidized dermatofibroma. Additionally, lipidized dermatofibromas tend to be larger than ordinary dermatofibromas, which typically are less than 2 cm in diameter.¹

Figure 1. Lipidized dermatofibromas are characterized by classic epidermal features of dermatofibromas, such as acanthosis, along with numerous foam cells and extensive stromal hyalinization (H&E, original magnification ×1.5).

Figure 2. Higher-power view of a lipidized dermatofibroma shows the characteristic irregular dissection of hyalinized wiry collagen fibers between the xanthomatous cells (H&E, original magnification ×20).

Eruptive xanthomas are characterized by a lacelike infiltrate of extravascular lipid deposits between collagen bundles (Figure 3).² Granular cell tumors are composed of sheets and/or nests of large cells with abundant eosinophilic cytoplasm and may be confused with lipidized dermatofibromas, as they also may induce overlying pseudoepitheliomatous hyperplasia³; however, on closer examination of the cells, the cytoplasm is found to be granular (Figure 4), which contrasts the finely vacuolated cytoplasm of xanthomatous cells found in lipidized dermatofibromas. Giant lysosomal granules (eg, pustulo-ovoid bodies of Milian) are present in some cases.² Of note, an unusual variant of dermatofibroma exists that features prominent granular cells.⁴

Figure 3. Lacelike deposition of extravascular lipid deposits is seen infiltrating between collagen bundles in an eruptive xanthoma (H&E, original magnification ×20).

Figure 4. An abundant eosinophilic, finely granular cytoplasm is characteristic of granular cell tumor (H&E, original magnification ×40).

Tuberous xanthomas most commonly occur around the pressure areas, such as the knees, elbows, and buttocks. Foam cells are a main feature of tuberous xanthomas and are arranged in large aggregates throughout the dermis.² Tuberous xanthomas lack Touton giant cells or inflammatory cells. Older lesions tend to develop substantial fibrosis (Figure 5). Although foam cells can be present in older lesions, they are never as conspicuous as those found in other xanthomas.

Xanthogranulomas commonly occur on the head and neck. Findings noted on low magnification include a well-circumscribed exophytic nodule and an epidermal collarette, which help to easily distinguish xanthogranulomas from lipidized dermatofibromas. Additionally, the presence of a more prominent inflammatory infiltrate, which often includes eosinophils, as well as multinucleated Touton giant cells (Figure 6) and histiocytes with more eosinophilic and less xanthomatous cytoplasm can help distinguish between the lesions.^1,5 Notably, Touton giant cells also can be seen in lipidized dermatofibromas,¹ but the presence of unique features such as distinctive stromal hyalinization are clues to the correct diagnosis of a lipidized dermatofibroma.

The first year of residency can be overwhelming. Just ask Dr. Anneliese Beaubrun, an intern at the University of Central Florida College of Medicine’s internal medicine residency program in Orlando.

You’re suddenly responsible for patients, and you definitely don’t want to be the one asking what you think is the wrong question, she says.

But the professors and program directors have a different view.

In a video interview, Dr. Abdo Asmar, associate director of the internal medicine residency program at UCF, shares his advice to first-year residents. Chief resident Olga Karasik, too, looks back at her first year and shares what she’s learned.

And there’s more.

In her blog, Wellness Rounds, Dr. Mary L. Brandt, professor of surgery, pediatrics and medical ethics and interim senior associate dean of Medical Education at Baylor College of Medicine, Houston, takes a holistic approach to medical school and residency. Her posts cover a wide range of topics, from the type of shoes to wear at the hospital, to advice on preparing for residency interviews.

Being a good intern is among the popular posts on her blog, and in a phone interview she shared some of her top tips and advice for first-year residents.

What are your tips and advice for interns? Leave us a comment.

[email protected]

On Twitter @naseemmiller

The first year of residency can be overwhelming. Just ask Dr. Anneliese Beaubrun, an intern at the University of Central Florida College of Medicine’s internal medicine residency program in Orlando.

You’re suddenly responsible for patients, and you definitely don’t want to be the one asking what you think is the wrong question, she says.

But the professors and program directors have a different view.

In a video interview, Dr. Abdo Asmar, associate director of the internal medicine residency program at UCF, shares his advice to first-year residents. Chief resident Olga Karasik, too, looks back at her first year and shares what she’s learned.

And there’s more.

In her blog, Wellness Rounds, Dr. Mary L. Brandt, professor of surgery, pediatrics and medical ethics and interim senior associate dean of Medical Education at Baylor College of Medicine, Houston, takes a holistic approach to medical school and residency. Her posts cover a wide range of topics, from the type of shoes to wear at the hospital, to advice on preparing for residency interviews.

Being a good intern is among the popular posts on her blog, and in a phone interview she shared some of her top tips and advice for first-year residents.

What are your tips and advice for interns? Leave us a comment.

[email protected]

On Twitter @naseemmiller

The first year of residency can be overwhelming. Just ask Dr. Anneliese Beaubrun, an intern at the University of Central Florida College of Medicine’s internal medicine residency program in Orlando.

You’re suddenly responsible for patients, and you definitely don’t want to be the one asking what you think is the wrong question, she says.

But the professors and program directors have a different view.

In a video interview, Dr. Abdo Asmar, associate director of the internal medicine residency program at UCF, shares his advice to first-year residents. Chief resident Olga Karasik, too, looks back at her first year and shares what she’s learned.

And there’s more.

In her blog, Wellness Rounds, Dr. Mary L. Brandt, professor of surgery, pediatrics and medical ethics and interim senior associate dean of Medical Education at Baylor College of Medicine, Houston, takes a holistic approach to medical school and residency. Her posts cover a wide range of topics, from the type of shoes to wear at the hospital, to advice on preparing for residency interviews.

Being a good intern is among the popular posts on her blog, and in a phone interview she shared some of her top tips and advice for first-year residents.

What are your tips and advice for interns? Leave us a comment.

[email protected]

On Twitter @naseemmiller

As I have mentioned in prior columns, the key to success with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding will be additional specificity, which will come in the form of more characters to communicate with payors and statisticians regarding the services that have been provided during the office visit. The addition of characters will permit more information about the visit to be delivered in the code.

Some of these additional characters will be required to submit the code for processing. Specifically look out for codes that communicate accidents or injury. Some common circumstances for dermatologists will be lacerations, abrasions, laceration repairs, and burns. The structure of the ICD-10-CM codes is outlined below to explain circumstances in which the increased number of characters will be most important for dermatologists.

The ICD-10-CM codes will be 3 to 7 characters long.¹ The first 3 characters are the general categories. For example, L70 is the 3-character category for acne and L40 is the category for psoriasis. The next 3 characters (ie, characters 4–6) correspond to the related etiology (ie, the cause, set of causes, manner of causation of a disease or condition), anatomic site, severity, and other vital clinical details.¹

Take the case of a burn on the hand. With the International Classification of Diseases, Ninth Revision, a first-degree burn on the back of the hand is coded with 5 characters (944.16).² According to the ICD-10-CM coding system, the code for an initial visit for a first-degree burn on the back of the hand would include 7 characters (T23.169A).¹ There will be times when the sixth character may not be necessary; in these instances, an X must be placed in this position as a placeholder, but the absence of a sixth character does not negate the need for a seventh. Thankfully, the seventh character can only be 1 of 3 letters. As illustrated above in the code for a first-degree burn on the back of the hand, the A designates an initial encounter; a D would designate a follow-up visit for this burn, and an S would represent a sequela from the initial burn, such as a postinflammatory change, which would have its own code.¹

Conclusion

To be reimbursed, appropriate ICD-10-CM codes must be used. Be sure to master the structure of these codes before the October 1, 2015, compliance deadline; plan now for a training and testing period.

As I have mentioned in prior columns, the key to success with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding will be additional specificity, which will come in the form of more characters to communicate with payors and statisticians regarding the services that have been provided during the office visit. The addition of characters will permit more information about the visit to be delivered in the code.

Some of these additional characters will be required to submit the code for processing. Specifically look out for codes that communicate accidents or injury. Some common circumstances for dermatologists will be lacerations, abrasions, laceration repairs, and burns. The structure of the ICD-10-CM codes is outlined below to explain circumstances in which the increased number of characters will be most important for dermatologists.

The ICD-10-CM codes will be 3 to 7 characters long.¹ The first 3 characters are the general categories. For example, L70 is the 3-character category for acne and L40 is the category for psoriasis. The next 3 characters (ie, characters 4–6) correspond to the related etiology (ie, the cause, set of causes, manner of causation of a disease or condition), anatomic site, severity, and other vital clinical details.¹

Take the case of a burn on the hand. With the International Classification of Diseases, Ninth Revision, a first-degree burn on the back of the hand is coded with 5 characters (944.16).² According to the ICD-10-CM coding system, the code for an initial visit for a first-degree burn on the back of the hand would include 7 characters (T23.169A).¹ There will be times when the sixth character may not be necessary; in these instances, an X must be placed in this position as a placeholder, but the absence of a sixth character does not negate the need for a seventh. Thankfully, the seventh character can only be 1 of 3 letters. As illustrated above in the code for a first-degree burn on the back of the hand, the A designates an initial encounter; a D would designate a follow-up visit for this burn, and an S would represent a sequela from the initial burn, such as a postinflammatory change, which would have its own code.¹

Conclusion

To be reimbursed, appropriate ICD-10-CM codes must be used. Be sure to master the structure of these codes before the October 1, 2015, compliance deadline; plan now for a training and testing period.

As I have mentioned in prior columns, the key to success with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding will be additional specificity, which will come in the form of more characters to communicate with payors and statisticians regarding the services that have been provided during the office visit. The addition of characters will permit more information about the visit to be delivered in the code.

Some of these additional characters will be required to submit the code for processing. Specifically look out for codes that communicate accidents or injury. Some common circumstances for dermatologists will be lacerations, abrasions, laceration repairs, and burns. The structure of the ICD-10-CM codes is outlined below to explain circumstances in which the increased number of characters will be most important for dermatologists.

The ICD-10-CM codes will be 3 to 7 characters long.¹ The first 3 characters are the general categories. For example, L70 is the 3-character category for acne and L40 is the category for psoriasis. The next 3 characters (ie, characters 4–6) correspond to the related etiology (ie, the cause, set of causes, manner of causation of a disease or condition), anatomic site, severity, and other vital clinical details.¹

Take the case of a burn on the hand. With the International Classification of Diseases, Ninth Revision, a first-degree burn on the back of the hand is coded with 5 characters (944.16).² According to the ICD-10-CM coding system, the code for an initial visit for a first-degree burn on the back of the hand would include 7 characters (T23.169A).¹ There will be times when the sixth character may not be necessary; in these instances, an X must be placed in this position as a placeholder, but the absence of a sixth character does not negate the need for a seventh. Thankfully, the seventh character can only be 1 of 3 letters. As illustrated above in the code for a first-degree burn on the back of the hand, the A designates an initial encounter; a D would designate a follow-up visit for this burn, and an S would represent a sequela from the initial burn, such as a postinflammatory change, which would have its own code.¹

Conclusion

To be reimbursed, appropriate ICD-10-CM codes must be used. Be sure to master the structure of these codes before the October 1, 2015, compliance deadline; plan now for a training and testing period.

Thrombosis occurs in up to 15% of pediatric patients following cardiac surgery, and is associated with increased mortality. Although aspirin is commonly administered to pediatric patients after high-risk congenital cardiac surgery to reduce thrombosis risk, aspirin responsiveness is rarely assessed, according to Dr. Sirisha Emani and colleagues .

“In our observational study, aspirin unresponsiveness occurred in approximately 11% of patients undergoing specific high-risk cardiac procedures, and postoperative thrombosis was associated with aspirin unresponsiveness in this patient population,” said Dr. Emani.

In order to determine whether inadequate response to aspirin was associated with increased risk of thrombosis following high-risk procedures, the researchers performed a prospective analysis of 62 patients undergoing congenital cardiac surgical procedures involving placement of prosthetic material into the circulation or coronary artery manipulation who received aspirin.

Response to aspirin was determined using the Verify Now system at least 48 hours following administration. Patients were prospectively monitored for development of thrombosis events by imaging (echocardiogram, cardiac catheterization, MRI) and review of clinical events (shunt thrombosis, stroke, or limb ischemia) until the time of hospital discharge.

Aspirin responsiveness was tested a median of 2 days after initiation of therapy. The rate of aspirin unresponsiveness (Aspirin Responsive Unit, ARU greater than 550) was 7/62 (11.3%) in all patients and was highest in patients less than 5 kg who received 20.25 mg aspirin. Thrombosis events were demonstrated in 7 patients (11.3%). Thrombosis was observed in 6 (86%) of 7 patients who were unresponsive to aspirin as opposed to 1 (2%) of 54 patients who were responsive to aspirin, a significant difference. In two neonates who were unresponsive at 20.25 and 40.5 mg of aspirin, increase in dosage to 40.5 and 81 mg, respectively, resulted in an aspirin response, suggesting insufficiency rather than true unresponsiveness.

“Monitoring of aspirin therapy and consideration of dose adjustment or alternative agents for unresponsive patients may be justified and warrants further investigation in a prospective trial,” concluded Dr. Emani.

[email protected]

Thrombosis occurs in up to 15% of pediatric patients following cardiac surgery, and is associated with increased mortality. Although aspirin is commonly administered to pediatric patients after high-risk congenital cardiac surgery to reduce thrombosis risk, aspirin responsiveness is rarely assessed, according to Dr. Sirisha Emani and colleagues .

“In our observational study, aspirin unresponsiveness occurred in approximately 11% of patients undergoing specific high-risk cardiac procedures, and postoperative thrombosis was associated with aspirin unresponsiveness in this patient population,” said Dr. Emani.

In order to determine whether inadequate response to aspirin was associated with increased risk of thrombosis following high-risk procedures, the researchers performed a prospective analysis of 62 patients undergoing congenital cardiac surgical procedures involving placement of prosthetic material into the circulation or coronary artery manipulation who received aspirin.

Response to aspirin was determined using the Verify Now system at least 48 hours following administration. Patients were prospectively monitored for development of thrombosis events by imaging (echocardiogram, cardiac catheterization, MRI) and review of clinical events (shunt thrombosis, stroke, or limb ischemia) until the time of hospital discharge.

Aspirin responsiveness was tested a median of 2 days after initiation of therapy. The rate of aspirin unresponsiveness (Aspirin Responsive Unit, ARU greater than 550) was 7/62 (11.3%) in all patients and was highest in patients less than 5 kg who received 20.25 mg aspirin. Thrombosis events were demonstrated in 7 patients (11.3%). Thrombosis was observed in 6 (86%) of 7 patients who were unresponsive to aspirin as opposed to 1 (2%) of 54 patients who were responsive to aspirin, a significant difference. In two neonates who were unresponsive at 20.25 and 40.5 mg of aspirin, increase in dosage to 40.5 and 81 mg, respectively, resulted in an aspirin response, suggesting insufficiency rather than true unresponsiveness.

“Monitoring of aspirin therapy and consideration of dose adjustment or alternative agents for unresponsive patients may be justified and warrants further investigation in a prospective trial,” concluded Dr. Emani.

[email protected]

Thrombosis occurs in up to 15% of pediatric patients following cardiac surgery, and is associated with increased mortality. Although aspirin is commonly administered to pediatric patients after high-risk congenital cardiac surgery to reduce thrombosis risk, aspirin responsiveness is rarely assessed, according to Dr. Sirisha Emani and colleagues .

“In our observational study, aspirin unresponsiveness occurred in approximately 11% of patients undergoing specific high-risk cardiac procedures, and postoperative thrombosis was associated with aspirin unresponsiveness in this patient population,” said Dr. Emani.

In order to determine whether inadequate response to aspirin was associated with increased risk of thrombosis following high-risk procedures, the researchers performed a prospective analysis of 62 patients undergoing congenital cardiac surgical procedures involving placement of prosthetic material into the circulation or coronary artery manipulation who received aspirin.

Response to aspirin was determined using the Verify Now system at least 48 hours following administration. Patients were prospectively monitored for development of thrombosis events by imaging (echocardiogram, cardiac catheterization, MRI) and review of clinical events (shunt thrombosis, stroke, or limb ischemia) until the time of hospital discharge.

Aspirin responsiveness was tested a median of 2 days after initiation of therapy. The rate of aspirin unresponsiveness (Aspirin Responsive Unit, ARU greater than 550) was 7/62 (11.3%) in all patients and was highest in patients less than 5 kg who received 20.25 mg aspirin. Thrombosis events were demonstrated in 7 patients (11.3%). Thrombosis was observed in 6 (86%) of 7 patients who were unresponsive to aspirin as opposed to 1 (2%) of 54 patients who were responsive to aspirin, a significant difference. In two neonates who were unresponsive at 20.25 and 40.5 mg of aspirin, increase in dosage to 40.5 and 81 mg, respectively, resulted in an aspirin response, suggesting insufficiency rather than true unresponsiveness.

“Monitoring of aspirin therapy and consideration of dose adjustment or alternative agents for unresponsive patients may be justified and warrants further investigation in a prospective trial,” concluded Dr. Emani.

[email protected]

For many years I have advised physicians that aggressive management of accounts receivable is the key to financial health for any private practice. In the current health care reform climate, it has become more important than ever. A crucial step toward proper management of accounts receivable in the age of the Patient Protection and Affordable Care Act is minimization, if not outright elimination, of patient billing, which is a hallowed yet obsolete tradition in private practice. Billing, in effect, is extending free credit to patients, and independent physicians can no longer afford it.

Some physicians of a traditional bent cling to the idea that accepting credit cards or even asking for payment at the time of service smacks of “storekeeping.” They feel more comfortable billing patients for outstanding balances but complain that their bills often are ignored; with each passing day following treatment in your office, the likelihood decreases that a patient will pay the bill.

Patient billing also is expensive. When you total the costs of materials, postage, and staff labor, each bill can cost anywhere from $2 to $10 or more. Every minute the office staff spends producing and mailing bills is time not spent on more productive work. Billing services are an alternative, but they also are expensive, and those bills get ignored too. Requiring immediate payment may seem distasteful to some physicians, but for physicians who wish to keep their office private and independent, it is rapidly becoming the only viable option.

Health Savings Accounts

Private practices will need to become increasingly flexible in how they accept payments as the population continues to age. This flexibility becomes increasingly important as more and more patients rely on health savings accounts (HSAs). Enrollment in these specialized, tax-deductible, tax-free accounts has increased 10-fold over the last decade.¹ Private practice physicians will want to accommodate for HSAs as much as possible.

A few credit companies are already promoting cards to finance HSAs and other private-pay portions of health care expenses, such as The HELPcard (www.helpcard.com). Major credit card companies also have begun to appreciate this largely untapped segment of potential business for them. Soon you may begin receiving help from them in setting up creative payment plans for your patients. Some financial institutions have even begun creating medical credit and debit cards called health benefit cards that are designed specifically for use at physicians’ offices.²

Credit and Debit Cards

Credit and debit cards eliminate many of the problems associated with patient billing. They allow you to collect more fees at the time of service while you still have the patient’s attention and the service you provided is still appreciated.

Charging to a credit or debit card also reduces the chances of a balance owed falling through the cracks, getting lost in the mail, or getting embezzled, and it cannot bounce so it is better than a check. Card payments also can improve your practice’s cash flow, which is always a welcome benefit. Additionally, if a patient is delinquent in paying a credit card bill, it is the credit card company’s problem, not yours.

Credit cards also offer more payment flexibility for patients. In the case of a large balance, offer your patient the option of charging all of the services to a credit card, which he/she can then pay off in affordable monthly installments. Your practice will get reimbursed in full, even as the patient is paying it off slowly, and the patient is able to pay off the debt at a pace that makes sense for his/her finances.

Payment Policies

Beyond simply accepting credit cards, the next step is one that every hotel, rental car agency, and many other businesses have used for years: Retain a card number in each patient’s file, and bill balances as they come in.

Every new patient in my office receives a letter at his/her first visit explaining our policy: We will keep a credit card number on file and use it to bill any outstanding balances after third parties pay their portion. At the bottom of the letter is a brief statement of consent for the patient to sign, along with a place to write the credit card number and expiration date. This policy also comes in handy for patients who claim to have come to the office without cash, a checkbook, credit cards, or any other method of payment. In such situations, my office manager can say, “No problem, we have your credit card information on file!”

Do patients object to this policy? Some do, mostly older patients. But when we explain that we are doing nothing different than hotels do at check-in and that this policy also will work to their advantage by decreasing the number of bills they receive and checks they must write, most come around. Make it an option at first if you wish; then, when everyone is accustomed, you can make it a mandatory policy. My office manager has the authority to make exceptions on a case-by-case basis when necessary.

Do patients worry about confidentiality or unauthorized use? Most individuals do not worry when they use a credit card at a restaurant, hotel, or the Internet. Guard your patients’ financial information as carefully as their medical information. If you have electronic health records, the patient’s credit card number can go in the medical chart. Otherwise use a separate portable filing system that can be locked up each night.

Does this policy work? In only 1 year, my total accounts receivable dropped by nearly 50%; after another year they stabilized at 30% to 35% of prior levels and have remained there ever since, which was a source of consternation for our new accountant who we hired shortly thereafter. “Something must be wrong,” he said nervously after his first look at our books. “Accounts receivable totals are never that low in a medical office with your level of volume.” His eyes widened as I explained our system. “Why doesn’t every private practice do that?” he asked. Why, indeed.

Final Thoughts

The business of health care delivery is currently being rocked at its foundations, as I have been detailing in this column. Without considerable adaptation to these fundamental changes, a private practice can do little more than survive, and even that will take luck. A crucial component of adaptation involves doing more of what we do best, treating patients. Leave the business of extending credit to the banks and credit card companies.

For many years I have advised physicians that aggressive management of accounts receivable is the key to financial health for any private practice. In the current health care reform climate, it has become more important than ever. A crucial step toward proper management of accounts receivable in the age of the Patient Protection and Affordable Care Act is minimization, if not outright elimination, of patient billing, which is a hallowed yet obsolete tradition in private practice. Billing, in effect, is extending free credit to patients, and independent physicians can no longer afford it.

Some physicians of a traditional bent cling to the idea that accepting credit cards or even asking for payment at the time of service smacks of “storekeeping.” They feel more comfortable billing patients for outstanding balances but complain that their bills often are ignored; with each passing day following treatment in your office, the likelihood decreases that a patient will pay the bill.

Patient billing also is expensive. When you total the costs of materials, postage, and staff labor, each bill can cost anywhere from $2 to $10 or more. Every minute the office staff spends producing and mailing bills is time not spent on more productive work. Billing services are an alternative, but they also are expensive, and those bills get ignored too. Requiring immediate payment may seem distasteful to some physicians, but for physicians who wish to keep their office private and independent, it is rapidly becoming the only viable option.

Health Savings Accounts

Private practices will need to become increasingly flexible in how they accept payments as the population continues to age. This flexibility becomes increasingly important as more and more patients rely on health savings accounts (HSAs). Enrollment in these specialized, tax-deductible, tax-free accounts has increased 10-fold over the last decade.¹ Private practice physicians will want to accommodate for HSAs as much as possible.

A few credit companies are already promoting cards to finance HSAs and other private-pay portions of health care expenses, such as The HELPcard (www.helpcard.com). Major credit card companies also have begun to appreciate this largely untapped segment of potential business for them. Soon you may begin receiving help from them in setting up creative payment plans for your patients. Some financial institutions have even begun creating medical credit and debit cards called health benefit cards that are designed specifically for use at physicians’ offices.²

Credit and Debit Cards

Credit and debit cards eliminate many of the problems associated with patient billing. They allow you to collect more fees at the time of service while you still have the patient’s attention and the service you provided is still appreciated.

Charging to a credit or debit card also reduces the chances of a balance owed falling through the cracks, getting lost in the mail, or getting embezzled, and it cannot bounce so it is better than a check. Card payments also can improve your practice’s cash flow, which is always a welcome benefit. Additionally, if a patient is delinquent in paying a credit card bill, it is the credit card company’s problem, not yours.

Credit cards also offer more payment flexibility for patients. In the case of a large balance, offer your patient the option of charging all of the services to a credit card, which he/she can then pay off in affordable monthly installments. Your practice will get reimbursed in full, even as the patient is paying it off slowly, and the patient is able to pay off the debt at a pace that makes sense for his/her finances.

Payment Policies

Beyond simply accepting credit cards, the next step is one that every hotel, rental car agency, and many other businesses have used for years: Retain a card number in each patient’s file, and bill balances as they come in.

Every new patient in my office receives a letter at his/her first visit explaining our policy: We will keep a credit card number on file and use it to bill any outstanding balances after third parties pay their portion. At the bottom of the letter is a brief statement of consent for the patient to sign, along with a place to write the credit card number and expiration date. This policy also comes in handy for patients who claim to have come to the office without cash, a checkbook, credit cards, or any other method of payment. In such situations, my office manager can say, “No problem, we have your credit card information on file!”

Do patients object to this policy? Some do, mostly older patients. But when we explain that we are doing nothing different than hotels do at check-in and that this policy also will work to their advantage by decreasing the number of bills they receive and checks they must write, most come around. Make it an option at first if you wish; then, when everyone is accustomed, you can make it a mandatory policy. My office manager has the authority to make exceptions on a case-by-case basis when necessary.

Do patients worry about confidentiality or unauthorized use? Most individuals do not worry when they use a credit card at a restaurant, hotel, or the Internet. Guard your patients’ financial information as carefully as their medical information. If you have electronic health records, the patient’s credit card number can go in the medical chart. Otherwise use a separate portable filing system that can be locked up each night.

Does this policy work? In only 1 year, my total accounts receivable dropped by nearly 50%; after another year they stabilized at 30% to 35% of prior levels and have remained there ever since, which was a source of consternation for our new accountant who we hired shortly thereafter. “Something must be wrong,” he said nervously after his first look at our books. “Accounts receivable totals are never that low in a medical office with your level of volume.” His eyes widened as I explained our system. “Why doesn’t every private practice do that?” he asked. Why, indeed.

Final Thoughts

The business of health care delivery is currently being rocked at its foundations, as I have been detailing in this column. Without considerable adaptation to these fundamental changes, a private practice can do little more than survive, and even that will take luck. A crucial component of adaptation involves doing more of what we do best, treating patients. Leave the business of extending credit to the banks and credit card companies.

For many years I have advised physicians that aggressive management of accounts receivable is the key to financial health for any private practice. In the current health care reform climate, it has become more important than ever. A crucial step toward proper management of accounts receivable in the age of the Patient Protection and Affordable Care Act is minimization, if not outright elimination, of patient billing, which is a hallowed yet obsolete tradition in private practice. Billing, in effect, is extending free credit to patients, and independent physicians can no longer afford it.

Some physicians of a traditional bent cling to the idea that accepting credit cards or even asking for payment at the time of service smacks of “storekeeping.” They feel more comfortable billing patients for outstanding balances but complain that their bills often are ignored; with each passing day following treatment in your office, the likelihood decreases that a patient will pay the bill.

Patient billing also is expensive. When you total the costs of materials, postage, and staff labor, each bill can cost anywhere from $2 to $10 or more. Every minute the office staff spends producing and mailing bills is time not spent on more productive work. Billing services are an alternative, but they also are expensive, and those bills get ignored too. Requiring immediate payment may seem distasteful to some physicians, but for physicians who wish to keep their office private and independent, it is rapidly becoming the only viable option.

Health Savings Accounts

Private practices will need to become increasingly flexible in how they accept payments as the population continues to age. This flexibility becomes increasingly important as more and more patients rely on health savings accounts (HSAs). Enrollment in these specialized, tax-deductible, tax-free accounts has increased 10-fold over the last decade.¹ Private practice physicians will want to accommodate for HSAs as much as possible.

A few credit companies are already promoting cards to finance HSAs and other private-pay portions of health care expenses, such as The HELPcard (www.helpcard.com). Major credit card companies also have begun to appreciate this largely untapped segment of potential business for them. Soon you may begin receiving help from them in setting up creative payment plans for your patients. Some financial institutions have even begun creating medical credit and debit cards called health benefit cards that are designed specifically for use at physicians’ offices.²

Credit and Debit Cards

Credit and debit cards eliminate many of the problems associated with patient billing. They allow you to collect more fees at the time of service while you still have the patient’s attention and the service you provided is still appreciated.

Charging to a credit or debit card also reduces the chances of a balance owed falling through the cracks, getting lost in the mail, or getting embezzled, and it cannot bounce so it is better than a check. Card payments also can improve your practice’s cash flow, which is always a welcome benefit. Additionally, if a patient is delinquent in paying a credit card bill, it is the credit card company’s problem, not yours.

Credit cards also offer more payment flexibility for patients. In the case of a large balance, offer your patient the option of charging all of the services to a credit card, which he/she can then pay off in affordable monthly installments. Your practice will get reimbursed in full, even as the patient is paying it off slowly, and the patient is able to pay off the debt at a pace that makes sense for his/her finances.

Payment Policies

Beyond simply accepting credit cards, the next step is one that every hotel, rental car agency, and many other businesses have used for years: Retain a card number in each patient’s file, and bill balances as they come in.

Every new patient in my office receives a letter at his/her first visit explaining our policy: We will keep a credit card number on file and use it to bill any outstanding balances after third parties pay their portion. At the bottom of the letter is a brief statement of consent for the patient to sign, along with a place to write the credit card number and expiration date. This policy also comes in handy for patients who claim to have come to the office without cash, a checkbook, credit cards, or any other method of payment. In such situations, my office manager can say, “No problem, we have your credit card information on file!”

Do patients object to this policy? Some do, mostly older patients. But when we explain that we are doing nothing different than hotels do at check-in and that this policy also will work to their advantage by decreasing the number of bills they receive and checks they must write, most come around. Make it an option at first if you wish; then, when everyone is accustomed, you can make it a mandatory policy. My office manager has the authority to make exceptions on a case-by-case basis when necessary.

Do patients worry about confidentiality or unauthorized use? Most individuals do not worry when they use a credit card at a restaurant, hotel, or the Internet. Guard your patients’ financial information as carefully as their medical information. If you have electronic health records, the patient’s credit card number can go in the medical chart. Otherwise use a separate portable filing system that can be locked up each night.

Does this policy work? In only 1 year, my total accounts receivable dropped by nearly 50%; after another year they stabilized at 30% to 35% of prior levels and have remained there ever since, which was a source of consternation for our new accountant who we hired shortly thereafter. “Something must be wrong,” he said nervously after his first look at our books. “Accounts receivable totals are never that low in a medical office with your level of volume.” His eyes widened as I explained our system. “Why doesn’t every private practice do that?” he asked. Why, indeed.

Final Thoughts

The business of health care delivery is currently being rocked at its foundations, as I have been detailing in this column. Without considerable adaptation to these fundamental changes, a private practice can do little more than survive, and even that will take luck. A crucial component of adaptation involves doing more of what we do best, treating patients. Leave the business of extending credit to the banks and credit card companies.

Decades of experience have narrowed the most effective dose of methotrexate (MTX) for rheumatoid arthritis to somewhere between 15 mg and 25 mg per week. However, experience has also suggested that early and rapid control of the disease activity minimizes damage. The result has been a quicker escalation of MTX dosing, with a starting dose of 10 mg to 15 mg per week and escalating by 5 mg every month, rather than the more traditional 5 mg every 3 months.

But researchers from Post Graduate Institute of Medical Education and Research in Chandigarh, India, point out that the recommendation to start with the higher dose of 15 mg is based on “weak evidence.” What’s more, they say, only a limited number of studies had compared fixed MTX doses head-to-head, and of those studies, many are 20 to 30 years old. No study had compared starting doses of 7.5 mg and 15 mg MTX, the researchers say.

Starting higher may have some benefits of efficacy, but that higher dose can also lead to adverse effects (AEs), intolerance, and withdrawal from therapy, say the researchers. They decided to find a balance between efficacy, speed, and tolerability by comparing 2 dosage regimens of oral MTX, starting at either 7.5 mgor 15 mg per week and escalating 2.5 mg every 2 weeks over 12 weeks, to a possible maximum of 25 mg per week. In group one, 47 patients were started on the lower dose, reaching a mean dose at 12 weeks of 17.3 mg per week. In group two, 53 patients were started on the higher dose and reached a mean dose of 23.6 mg per week. In patients who completed the study, the mean doses were 19.2 mg per week and 24.5 mg per week, respectively (P < .001).

Nine patients withdrew from group 1, and 7 patients withdrew from group 2. The numbers withdrawing from each group due to AEs were not statistically significant (P = .9). However, group 2 had a higher incidence of nausea and vomiting (42%, vs 19% in group 1), although the severity and duration of nausea were similar in both groups. There were no significant differences in frequency of cytopenia (P = .09) or transaminitis (P = .08). There was no difference in disease activity at weeks 4, 8, or 12.

The researchers say one limitation of their study is the short duration. They chose 12 weeks, because guidelines had suggested 3 months as a decision point, when other drugs could be added if the patient did not respond to MTX. However, they note that the European League Against Rheumatism 2013 update now specifies that the 3-month period relates “solely to assessing improvements” and says it takes 6 months to see maximal efficacy. The researchers, agreeing with this, say they found “a relatively poor response” by week 12. Indeed, they say, in view of the relatively slow decline in disease activity, future studies might benefit from extending the follow-up period to 24 weeks.

Source
Dhir V, Singla M, Gupta N, et al. Clin Ther. 2014;36(7):1005-1015.
doi: 10.1016/j.clinthera.2014.05.063.

Decades of experience have narrowed the most effective dose of methotrexate (MTX) for rheumatoid arthritis to somewhere between 15 mg and 25 mg per week. However, experience has also suggested that early and rapid control of the disease activity minimizes damage. The result has been a quicker escalation of MTX dosing, with a starting dose of 10 mg to 15 mg per week and escalating by 5 mg every month, rather than the more traditional 5 mg every 3 months.

But researchers from Post Graduate Institute of Medical Education and Research in Chandigarh, India, point out that the recommendation to start with the higher dose of 15 mg is based on “weak evidence.” What’s more, they say, only a limited number of studies had compared fixed MTX doses head-to-head, and of those studies, many are 20 to 30 years old. No study had compared starting doses of 7.5 mg and 15 mg MTX, the researchers say.

Starting higher may have some benefits of efficacy, but that higher dose can also lead to adverse effects (AEs), intolerance, and withdrawal from therapy, say the researchers. They decided to find a balance between efficacy, speed, and tolerability by comparing 2 dosage regimens of oral MTX, starting at either 7.5 mgor 15 mg per week and escalating 2.5 mg every 2 weeks over 12 weeks, to a possible maximum of 25 mg per week. In group one, 47 patients were started on the lower dose, reaching a mean dose at 12 weeks of 17.3 mg per week. In group two, 53 patients were started on the higher dose and reached a mean dose of 23.6 mg per week. In patients who completed the study, the mean doses were 19.2 mg per week and 24.5 mg per week, respectively (P < .001).

Nine patients withdrew from group 1, and 7 patients withdrew from group 2. The numbers withdrawing from each group due to AEs were not statistically significant (P = .9). However, group 2 had a higher incidence of nausea and vomiting (42%, vs 19% in group 1), although the severity and duration of nausea were similar in both groups. There were no significant differences in frequency of cytopenia (P = .09) or transaminitis (P = .08). There was no difference in disease activity at weeks 4, 8, or 12.

The researchers say one limitation of their study is the short duration. They chose 12 weeks, because guidelines had suggested 3 months as a decision point, when other drugs could be added if the patient did not respond to MTX. However, they note that the European League Against Rheumatism 2013 update now specifies that the 3-month period relates “solely to assessing improvements” and says it takes 6 months to see maximal efficacy. The researchers, agreeing with this, say they found “a relatively poor response” by week 12. Indeed, they say, in view of the relatively slow decline in disease activity, future studies might benefit from extending the follow-up period to 24 weeks.

Source
Dhir V, Singla M, Gupta N, et al. Clin Ther. 2014;36(7):1005-1015.
doi: 10.1016/j.clinthera.2014.05.063.

Decades of experience have narrowed the most effective dose of methotrexate (MTX) for rheumatoid arthritis to somewhere between 15 mg and 25 mg per week. However, experience has also suggested that early and rapid control of the disease activity minimizes damage. The result has been a quicker escalation of MTX dosing, with a starting dose of 10 mg to 15 mg per week and escalating by 5 mg every month, rather than the more traditional 5 mg every 3 months.

But researchers from Post Graduate Institute of Medical Education and Research in Chandigarh, India, point out that the recommendation to start with the higher dose of 15 mg is based on “weak evidence.” What’s more, they say, only a limited number of studies had compared fixed MTX doses head-to-head, and of those studies, many are 20 to 30 years old. No study had compared starting doses of 7.5 mg and 15 mg MTX, the researchers say.

Starting higher may have some benefits of efficacy, but that higher dose can also lead to adverse effects (AEs), intolerance, and withdrawal from therapy, say the researchers. They decided to find a balance between efficacy, speed, and tolerability by comparing 2 dosage regimens of oral MTX, starting at either 7.5 mgor 15 mg per week and escalating 2.5 mg every 2 weeks over 12 weeks, to a possible maximum of 25 mg per week. In group one, 47 patients were started on the lower dose, reaching a mean dose at 12 weeks of 17.3 mg per week. In group two, 53 patients were started on the higher dose and reached a mean dose of 23.6 mg per week. In patients who completed the study, the mean doses were 19.2 mg per week and 24.5 mg per week, respectively (P < .001).

Nine patients withdrew from group 1, and 7 patients withdrew from group 2. The numbers withdrawing from each group due to AEs were not statistically significant (P = .9). However, group 2 had a higher incidence of nausea and vomiting (42%, vs 19% in group 1), although the severity and duration of nausea were similar in both groups. There were no significant differences in frequency of cytopenia (P = .09) or transaminitis (P = .08). There was no difference in disease activity at weeks 4, 8, or 12.

The researchers say one limitation of their study is the short duration. They chose 12 weeks, because guidelines had suggested 3 months as a decision point, when other drugs could be added if the patient did not respond to MTX. However, they note that the European League Against Rheumatism 2013 update now specifies that the 3-month period relates “solely to assessing improvements” and says it takes 6 months to see maximal efficacy. The researchers, agreeing with this, say they found “a relatively poor response” by week 12. Indeed, they say, in view of the relatively slow decline in disease activity, future studies might benefit from extending the follow-up period to 24 weeks.

Source
Dhir V, Singla M, Gupta N, et al. Clin Ther. 2014;36(7):1005-1015.
doi: 10.1016/j.clinthera.2014.05.063.