Cutis

Flaking/scaling and itching, followed by dry cracked skin that may bleed, pain or soreness, and burning/stinging were noted by psoriasis patients as the symptoms with the most significant impact on daily life in a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.

More than two-thirds of respondents identified flaking/scaling as one of their most significant symptoms of psoriasis, either localized to psoriasis-prone areas such as the elbows and knees or more widespread. Patients reported that this symptom is constant, leaving them to absentmindedly rub certain areas of the skin.

A similar number of respondents indicated that itching was their most significant symptom. One patient called it “an intense subcutaneous itch… deep down in the skin,” a description that resonated with other patients in the room.

Nearly 40% identified dry cracked skin that may bleed as a significant symptom, noting that areas where skin is thinner are affected more, such as the folds of the body. Patients described this symptom as interrelated with other symptoms such as itching. “The thicker the scales get on my skin, the more they itch, and the more they itch, the more I am likely to scratch them, and the more I scratch them, the more they start to crack, and then more come back and it keeps going and going,” one patient said.

More than one-quarter of respondents indicated that pain, soreness, or burning/stinging were the most significant symptoms. Patients indicated that the stinging/burning was more episodic, while the pain was more constant, with the pain being under the skin.

Triggers of these symptoms included stress (primary trigger), changes in weather, hormonal changes, diet, lotions, prolonged exposure to sunlight, sweat, aging, and other medical conditions.

Dermatologists may use these patient insights to prescribe therapies that target these symptoms.

The psoriasis public meeting in March 2016 was the FDA’s 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.

Flaking/scaling and itching, followed by dry cracked skin that may bleed, pain or soreness, and burning/stinging were noted by psoriasis patients as the symptoms with the most significant impact on daily life in a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.

More than two-thirds of respondents identified flaking/scaling as one of their most significant symptoms of psoriasis, either localized to psoriasis-prone areas such as the elbows and knees or more widespread. Patients reported that this symptom is constant, leaving them to absentmindedly rub certain areas of the skin.

A similar number of respondents indicated that itching was their most significant symptom. One patient called it “an intense subcutaneous itch… deep down in the skin,” a description that resonated with other patients in the room.

Nearly 40% identified dry cracked skin that may bleed as a significant symptom, noting that areas where skin is thinner are affected more, such as the folds of the body. Patients described this symptom as interrelated with other symptoms such as itching. “The thicker the scales get on my skin, the more they itch, and the more they itch, the more I am likely to scratch them, and the more I scratch them, the more they start to crack, and then more come back and it keeps going and going,” one patient said.

More than one-quarter of respondents indicated that pain, soreness, or burning/stinging were the most significant symptoms. Patients indicated that the stinging/burning was more episodic, while the pain was more constant, with the pain being under the skin.

Triggers of these symptoms included stress (primary trigger), changes in weather, hormonal changes, diet, lotions, prolonged exposure to sunlight, sweat, aging, and other medical conditions.

Dermatologists may use these patient insights to prescribe therapies that target these symptoms.

The psoriasis public meeting in March 2016 was the FDA’s 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.

Flaking/scaling and itching, followed by dry cracked skin that may bleed, pain or soreness, and burning/stinging were noted by psoriasis patients as the symptoms with the most significant impact on daily life in a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.

More than two-thirds of respondents identified flaking/scaling as one of their most significant symptoms of psoriasis, either localized to psoriasis-prone areas such as the elbows and knees or more widespread. Patients reported that this symptom is constant, leaving them to absentmindedly rub certain areas of the skin.

A similar number of respondents indicated that itching was their most significant symptom. One patient called it “an intense subcutaneous itch… deep down in the skin,” a description that resonated with other patients in the room.

Nearly 40% identified dry cracked skin that may bleed as a significant symptom, noting that areas where skin is thinner are affected more, such as the folds of the body. Patients described this symptom as interrelated with other symptoms such as itching. “The thicker the scales get on my skin, the more they itch, and the more they itch, the more I am likely to scratch them, and the more I scratch them, the more they start to crack, and then more come back and it keeps going and going,” one patient said.

More than one-quarter of respondents indicated that pain, soreness, or burning/stinging were the most significant symptoms. Patients indicated that the stinging/burning was more episodic, while the pain was more constant, with the pain being under the skin.

Triggers of these symptoms included stress (primary trigger), changes in weather, hormonal changes, diet, lotions, prolonged exposure to sunlight, sweat, aging, and other medical conditions.

Dermatologists may use these patient insights to prescribe therapies that target these symptoms.

The psoriasis public meeting in March 2016 was the FDA’s 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.

Metal allergy in patients with orthopedic implants can cause serious problems including dermatitis and implant failure.¹ As life expectancy increases, the general population ages, and more metallic orthopedic implants are placed,² allergy to these implants is expected to be a problem of greater significance. Uncertainty remains regarding best practice for patients with suspected metal implant allergy.¹ The major questions are: Who should be tested? When should they be tested? What are the optimal tests to diagnose metal allergy?^3-8

We report the case of a patient with vanadium allergy who developed a diffuse eczematous dermatitis and implant failure after receiving a vanadium-containing titanium alloy orthopedic implant in the left foot. This case is remarkable because hypersensitivity reactions to titanium-based hardware are rare, as they traditionally have not been thought to provoke allergic reactions.⁹

Case Report

A 62-year-old woman who was otherwise healthy presented with an eruption of more than 80 pruritic, nummular, eczematous plaques on the arms, legs, back, and buttocks of 3 weeks’ duration (Figure 1). She had a history of allergy to metal used in costume jewelry. Six weeks prior, the patient underwent implantation of a titanium alloy plate in the left foot for surgical repair of painful deforming osteoarthritis. A radiograph of the foot showed appropriate placement. According to the manufacturer, the plate was composed of the compound Ti6Al4V, which contained 90% titanium, 6% aluminum, and 4% vanadium. The lesions developed on the skin close to but not directly over the surgical site.

A punch biopsy of one of the lesions on the shoulder showed lymphoeosinophilic spongiosis consistent with a delayed hypersensitivity reaction (Figure 2). There was mild clinical improvement of the eruption with topical steroids. A course of prednisone for systemic effect resulted in clearing of the eruption, but it promptly recurred on cessation of the steroids. The patient was then patch tested using the North American 80 Comprehensive Series, with an additional 59 common textile, shampoo, fragrance, and several metal allergens, all of which were negative.

After the hardware was removed, it was analyzed to determine the elemental composition of the plate and screws, and the patient was then patch tested with the major metal components of the implant: aluminum chloride hexahydrate 2.0% pet, elemental titanium 10.0% pet, titanium dioxide 10.0% pet, titanium (III) nitride 5.0% pet, titanium (III) oxalate decahydrate 5.0% pet, elemental vanadium 5.0% pet, and vanadium (III) chloride 1.0% pet. She demonstrated a 1+ reaction (erythema and induration) to vanadium trichloride at 72 and 96 hours.

The plate and screws removed from the patient were sterilized and submitted for analysis. Electron microprobe analysis confirmed that the major elemental composition of the plate and screws essentially matched the manufacturer’s listing (Table 1). The trace elements were determined using laser ablative inductively coupled mass spectroscopy, which demonstrated that the screws were of different metal composition from the plate (Table 2). Electron microprobe analysis also was used to determine the microstructure of the plate and screws. The plate had 2 distinct phases consisting of a titanium-aluminum phase and a vanadium phase, whereas the screw was much more homogeneous. Basic electrochemical studies were performed in a salt solution replicating the tissue of the foot. These studies showed that galvanic corrosion could have occurred between the plate and screws due to the differences of composition.

Comment

Titanium is an attractive metal to use in orthopedic implants. It has a high strength-to-weight ratio, a low modulus of elasticity, and good resistance to corrosion. Titanium can be categorized as either commercially pure titanium (cp-Ti) or a titanium alloy. Colloquially, both cp-Ti and titanium alloys are often referred to simply as titanium, but the distinction is important when it comes to medical implants and devices. Commercially pure titanium is more than 99% pure titanium, but up to 1% of its volume can be comprised of impurities.¹⁰ In titanium alloys, the alloy elements are intentionally added to create a material with optimal properties. The 2 most common types of titanium that are used for orthopedic implants are cp-Ti and Ti6Al4V, a titanium alloy containing approximately 90% titanium, 6% aluminum, and 4% vanadium. Similar to cp-Ti, titanium alloys also can contain impurities such as aluminum, beryllium, cobalt, chromium, iron, nickel, and palladium, among many others. Although these impurities often are considered negligible from a metallurgy perspective, as they do not change the properties of the material, these trace elements may be present in large enough quantities to cause hypersensitivity reactions.¹¹

Several weeks after implantation of a titanium alloy metal plate in the left foot, a widespread eczematous eruption developed in our patient who had no prior skin disease. The eruption was steroid responsive but did not clear until the plate was removed. Detailed metallurgy analysis confirmed that vanadium was present and was not homogeneously distributed in the plate. The plate also was different in composition from the screws. Additional studies showed that galvanic corrosion between the plate and the chemically different screws might have contributed to the release of vanadium in the tissue.

Vanadium is known to be allergenic, especially in the presence of implant failure.^12,13 In our patient, patch testing with more than 100 allergens was negative, except for vanadium trichloride 1%. Our patient’s presentation strongly suggested that she developed a vanadium allergy manifesting as systemic allergic contact dermatitis. She demonstrated no history of skin disease, a widespread eczematous eruption after exposure, histology consistent with systemic contact allergy, a positive patch test to vanadium, and clearance of the eruption on removal of the antigen, which have been proposed as objective criteria that support a diagnosis of metal implant allergy.¹⁴ She refused our suggestion to reimplant a portion of the remaining plate under the skin without screws and monitor for recurrence of the eruption. She did not have a lesion overlying the surgical site, but she did develop lesions near the surgical scar. The literature indicates that cutaneous manifestations of allergy to metallic implants can be both localized and generalized.¹⁴

Although reports are rare, other researchers have found vanadium allergy in patients with metal orthopedic implants.^5,12,13,15 The scarcity of literature on vanadium allergy seems to suggest that it is a rare entity, but we believe that it may be more common. Vanadium allergy may be underdiagnosed because it is not a standard patch test allergen. Furthermore, many of those who do choose to test for it use what we believe to be ineffective formulas of vanadium when patch testing patients. Our patient demonstrated a positive patch test reaction only to vanadium trichloride and not to pure vanadium, which is consistent with the small number of other studies that investigated vanadium allergy.^5,12,13,15 We believe that vanadium trichloride is more water soluble than elemental vanadium,¹⁶ and thus more likely to identify true vanadium allergy than other test materials.

Although reports of vanadium allergy in patients with metal implants are rare in the medical literature, the material science literature clearly states that vanadium is toxic and that vanadium-containing implants are problematic.^17-20 It has been shown that although Ti6Al4V implants are considered highly resistant to corrosion, they will slowly and continuously corrode in a physiologic environment and release titanium, aluminum, and vanadium ions, both systemically and into the peri-implant space.¹¹ To address these problems with vanadium, vanadium-free titanium alloys such as Ti6Al7Nb have specifically been developed for medical use to address the problems caused by vanadium. Ti6Al7Nb contains 7% niobium rather than vanadium and appears to have some improved qualities in surgical implants.¹⁷

There is still a great deal of uncertainty around metal implant allergy. Allergy to metal implants can be difficult to diagnose for several reasons. Some metals are not conducive to patch testing because of their low bioavailability. Additionally, we lack validated and standardized patch test formulas for metals that can be diagnosed by patch testing. Furthermore, there is uncertainty about what to do after allergy to a metal implant is diagnosed; in some cases (eg, with more extensive procedures such as total joint replacements), removal or replacement of the implant may be associated with increased risk of further complications.^6,21

Conclusion

We suggest that manufacturers consider vanadium-free alloys such as Ti7Al6Nb, which contains niobium instead of vanadium, in their surgical implants,²² and if surgeons have a choice, they should consider using titanium implants with niobium rather than vanadium.¹⁰ We suggest that clinicians consider vanadium allergy in patients with Ti6Al4V surgical implants and signs of a hypersensitivity reaction, and include vanadium trichloride 1% when patch testing.

Acknowledgment

The authors would like to thank Nicholas R. Krasnow, PhD (Tucson, Arizona), for his invaluable help coordinating, performing, and interpreting the metal analyses.

Metal allergy in patients with orthopedic implants can cause serious problems including dermatitis and implant failure.¹ As life expectancy increases, the general population ages, and more metallic orthopedic implants are placed,² allergy to these implants is expected to be a problem of greater significance. Uncertainty remains regarding best practice for patients with suspected metal implant allergy.¹ The major questions are: Who should be tested? When should they be tested? What are the optimal tests to diagnose metal allergy?^3-8

We report the case of a patient with vanadium allergy who developed a diffuse eczematous dermatitis and implant failure after receiving a vanadium-containing titanium alloy orthopedic implant in the left foot. This case is remarkable because hypersensitivity reactions to titanium-based hardware are rare, as they traditionally have not been thought to provoke allergic reactions.⁹

Case Report

A 62-year-old woman who was otherwise healthy presented with an eruption of more than 80 pruritic, nummular, eczematous plaques on the arms, legs, back, and buttocks of 3 weeks’ duration (Figure 1). She had a history of allergy to metal used in costume jewelry. Six weeks prior, the patient underwent implantation of a titanium alloy plate in the left foot for surgical repair of painful deforming osteoarthritis. A radiograph of the foot showed appropriate placement. According to the manufacturer, the plate was composed of the compound Ti6Al4V, which contained 90% titanium, 6% aluminum, and 4% vanadium. The lesions developed on the skin close to but not directly over the surgical site.

A punch biopsy of one of the lesions on the shoulder showed lymphoeosinophilic spongiosis consistent with a delayed hypersensitivity reaction (Figure 2). There was mild clinical improvement of the eruption with topical steroids. A course of prednisone for systemic effect resulted in clearing of the eruption, but it promptly recurred on cessation of the steroids. The patient was then patch tested using the North American 80 Comprehensive Series, with an additional 59 common textile, shampoo, fragrance, and several metal allergens, all of which were negative.

After the hardware was removed, it was analyzed to determine the elemental composition of the plate and screws, and the patient was then patch tested with the major metal components of the implant: aluminum chloride hexahydrate 2.0% pet, elemental titanium 10.0% pet, titanium dioxide 10.0% pet, titanium (III) nitride 5.0% pet, titanium (III) oxalate decahydrate 5.0% pet, elemental vanadium 5.0% pet, and vanadium (III) chloride 1.0% pet. She demonstrated a 1+ reaction (erythema and induration) to vanadium trichloride at 72 and 96 hours.

The plate and screws removed from the patient were sterilized and submitted for analysis. Electron microprobe analysis confirmed that the major elemental composition of the plate and screws essentially matched the manufacturer’s listing (Table 1). The trace elements were determined using laser ablative inductively coupled mass spectroscopy, which demonstrated that the screws were of different metal composition from the plate (Table 2). Electron microprobe analysis also was used to determine the microstructure of the plate and screws. The plate had 2 distinct phases consisting of a titanium-aluminum phase and a vanadium phase, whereas the screw was much more homogeneous. Basic electrochemical studies were performed in a salt solution replicating the tissue of the foot. These studies showed that galvanic corrosion could have occurred between the plate and screws due to the differences of composition.

Comment

Titanium is an attractive metal to use in orthopedic implants. It has a high strength-to-weight ratio, a low modulus of elasticity, and good resistance to corrosion. Titanium can be categorized as either commercially pure titanium (cp-Ti) or a titanium alloy. Colloquially, both cp-Ti and titanium alloys are often referred to simply as titanium, but the distinction is important when it comes to medical implants and devices. Commercially pure titanium is more than 99% pure titanium, but up to 1% of its volume can be comprised of impurities.¹⁰ In titanium alloys, the alloy elements are intentionally added to create a material with optimal properties. The 2 most common types of titanium that are used for orthopedic implants are cp-Ti and Ti6Al4V, a titanium alloy containing approximately 90% titanium, 6% aluminum, and 4% vanadium. Similar to cp-Ti, titanium alloys also can contain impurities such as aluminum, beryllium, cobalt, chromium, iron, nickel, and palladium, among many others. Although these impurities often are considered negligible from a metallurgy perspective, as they do not change the properties of the material, these trace elements may be present in large enough quantities to cause hypersensitivity reactions.¹¹

Several weeks after implantation of a titanium alloy metal plate in the left foot, a widespread eczematous eruption developed in our patient who had no prior skin disease. The eruption was steroid responsive but did not clear until the plate was removed. Detailed metallurgy analysis confirmed that vanadium was present and was not homogeneously distributed in the plate. The plate also was different in composition from the screws. Additional studies showed that galvanic corrosion between the plate and the chemically different screws might have contributed to the release of vanadium in the tissue.

Vanadium is known to be allergenic, especially in the presence of implant failure.^12,13 In our patient, patch testing with more than 100 allergens was negative, except for vanadium trichloride 1%. Our patient’s presentation strongly suggested that she developed a vanadium allergy manifesting as systemic allergic contact dermatitis. She demonstrated no history of skin disease, a widespread eczematous eruption after exposure, histology consistent with systemic contact allergy, a positive patch test to vanadium, and clearance of the eruption on removal of the antigen, which have been proposed as objective criteria that support a diagnosis of metal implant allergy.¹⁴ She refused our suggestion to reimplant a portion of the remaining plate under the skin without screws and monitor for recurrence of the eruption. She did not have a lesion overlying the surgical site, but she did develop lesions near the surgical scar. The literature indicates that cutaneous manifestations of allergy to metallic implants can be both localized and generalized.¹⁴

Although reports are rare, other researchers have found vanadium allergy in patients with metal orthopedic implants.^5,12,13,15 The scarcity of literature on vanadium allergy seems to suggest that it is a rare entity, but we believe that it may be more common. Vanadium allergy may be underdiagnosed because it is not a standard patch test allergen. Furthermore, many of those who do choose to test for it use what we believe to be ineffective formulas of vanadium when patch testing patients. Our patient demonstrated a positive patch test reaction only to vanadium trichloride and not to pure vanadium, which is consistent with the small number of other studies that investigated vanadium allergy.^5,12,13,15 We believe that vanadium trichloride is more water soluble than elemental vanadium,¹⁶ and thus more likely to identify true vanadium allergy than other test materials.

Although reports of vanadium allergy in patients with metal implants are rare in the medical literature, the material science literature clearly states that vanadium is toxic and that vanadium-containing implants are problematic.^17-20 It has been shown that although Ti6Al4V implants are considered highly resistant to corrosion, they will slowly and continuously corrode in a physiologic environment and release titanium, aluminum, and vanadium ions, both systemically and into the peri-implant space.¹¹ To address these problems with vanadium, vanadium-free titanium alloys such as Ti6Al7Nb have specifically been developed for medical use to address the problems caused by vanadium. Ti6Al7Nb contains 7% niobium rather than vanadium and appears to have some improved qualities in surgical implants.¹⁷

There is still a great deal of uncertainty around metal implant allergy. Allergy to metal implants can be difficult to diagnose for several reasons. Some metals are not conducive to patch testing because of their low bioavailability. Additionally, we lack validated and standardized patch test formulas for metals that can be diagnosed by patch testing. Furthermore, there is uncertainty about what to do after allergy to a metal implant is diagnosed; in some cases (eg, with more extensive procedures such as total joint replacements), removal or replacement of the implant may be associated with increased risk of further complications.^6,21

Conclusion

We suggest that manufacturers consider vanadium-free alloys such as Ti7Al6Nb, which contains niobium instead of vanadium, in their surgical implants,²² and if surgeons have a choice, they should consider using titanium implants with niobium rather than vanadium.¹⁰ We suggest that clinicians consider vanadium allergy in patients with Ti6Al4V surgical implants and signs of a hypersensitivity reaction, and include vanadium trichloride 1% when patch testing.

Acknowledgment

The authors would like to thank Nicholas R. Krasnow, PhD (Tucson, Arizona), for his invaluable help coordinating, performing, and interpreting the metal analyses.

Metal allergy in patients with orthopedic implants can cause serious problems including dermatitis and implant failure.¹ As life expectancy increases, the general population ages, and more metallic orthopedic implants are placed,² allergy to these implants is expected to be a problem of greater significance. Uncertainty remains regarding best practice for patients with suspected metal implant allergy.¹ The major questions are: Who should be tested? When should they be tested? What are the optimal tests to diagnose metal allergy?^3-8

We report the case of a patient with vanadium allergy who developed a diffuse eczematous dermatitis and implant failure after receiving a vanadium-containing titanium alloy orthopedic implant in the left foot. This case is remarkable because hypersensitivity reactions to titanium-based hardware are rare, as they traditionally have not been thought to provoke allergic reactions.⁹

Case Report

A 62-year-old woman who was otherwise healthy presented with an eruption of more than 80 pruritic, nummular, eczematous plaques on the arms, legs, back, and buttocks of 3 weeks’ duration (Figure 1). She had a history of allergy to metal used in costume jewelry. Six weeks prior, the patient underwent implantation of a titanium alloy plate in the left foot for surgical repair of painful deforming osteoarthritis. A radiograph of the foot showed appropriate placement. According to the manufacturer, the plate was composed of the compound Ti6Al4V, which contained 90% titanium, 6% aluminum, and 4% vanadium. The lesions developed on the skin close to but not directly over the surgical site.

A punch biopsy of one of the lesions on the shoulder showed lymphoeosinophilic spongiosis consistent with a delayed hypersensitivity reaction (Figure 2). There was mild clinical improvement of the eruption with topical steroids. A course of prednisone for systemic effect resulted in clearing of the eruption, but it promptly recurred on cessation of the steroids. The patient was then patch tested using the North American 80 Comprehensive Series, with an additional 59 common textile, shampoo, fragrance, and several metal allergens, all of which were negative.

After the hardware was removed, it was analyzed to determine the elemental composition of the plate and screws, and the patient was then patch tested with the major metal components of the implant: aluminum chloride hexahydrate 2.0% pet, elemental titanium 10.0% pet, titanium dioxide 10.0% pet, titanium (III) nitride 5.0% pet, titanium (III) oxalate decahydrate 5.0% pet, elemental vanadium 5.0% pet, and vanadium (III) chloride 1.0% pet. She demonstrated a 1+ reaction (erythema and induration) to vanadium trichloride at 72 and 96 hours.

The plate and screws removed from the patient were sterilized and submitted for analysis. Electron microprobe analysis confirmed that the major elemental composition of the plate and screws essentially matched the manufacturer’s listing (Table 1). The trace elements were determined using laser ablative inductively coupled mass spectroscopy, which demonstrated that the screws were of different metal composition from the plate (Table 2). Electron microprobe analysis also was used to determine the microstructure of the plate and screws. The plate had 2 distinct phases consisting of a titanium-aluminum phase and a vanadium phase, whereas the screw was much more homogeneous. Basic electrochemical studies were performed in a salt solution replicating the tissue of the foot. These studies showed that galvanic corrosion could have occurred between the plate and screws due to the differences of composition.

Comment

Titanium is an attractive metal to use in orthopedic implants. It has a high strength-to-weight ratio, a low modulus of elasticity, and good resistance to corrosion. Titanium can be categorized as either commercially pure titanium (cp-Ti) or a titanium alloy. Colloquially, both cp-Ti and titanium alloys are often referred to simply as titanium, but the distinction is important when it comes to medical implants and devices. Commercially pure titanium is more than 99% pure titanium, but up to 1% of its volume can be comprised of impurities.¹⁰ In titanium alloys, the alloy elements are intentionally added to create a material with optimal properties. The 2 most common types of titanium that are used for orthopedic implants are cp-Ti and Ti6Al4V, a titanium alloy containing approximately 90% titanium, 6% aluminum, and 4% vanadium. Similar to cp-Ti, titanium alloys also can contain impurities such as aluminum, beryllium, cobalt, chromium, iron, nickel, and palladium, among many others. Although these impurities often are considered negligible from a metallurgy perspective, as they do not change the properties of the material, these trace elements may be present in large enough quantities to cause hypersensitivity reactions.¹¹

Several weeks after implantation of a titanium alloy metal plate in the left foot, a widespread eczematous eruption developed in our patient who had no prior skin disease. The eruption was steroid responsive but did not clear until the plate was removed. Detailed metallurgy analysis confirmed that vanadium was present and was not homogeneously distributed in the plate. The plate also was different in composition from the screws. Additional studies showed that galvanic corrosion between the plate and the chemically different screws might have contributed to the release of vanadium in the tissue.

Vanadium is known to be allergenic, especially in the presence of implant failure.^12,13 In our patient, patch testing with more than 100 allergens was negative, except for vanadium trichloride 1%. Our patient’s presentation strongly suggested that she developed a vanadium allergy manifesting as systemic allergic contact dermatitis. She demonstrated no history of skin disease, a widespread eczematous eruption after exposure, histology consistent with systemic contact allergy, a positive patch test to vanadium, and clearance of the eruption on removal of the antigen, which have been proposed as objective criteria that support a diagnosis of metal implant allergy.¹⁴ She refused our suggestion to reimplant a portion of the remaining plate under the skin without screws and monitor for recurrence of the eruption. She did not have a lesion overlying the surgical site, but she did develop lesions near the surgical scar. The literature indicates that cutaneous manifestations of allergy to metallic implants can be both localized and generalized.¹⁴

Although reports are rare, other researchers have found vanadium allergy in patients with metal orthopedic implants.^5,12,13,15 The scarcity of literature on vanadium allergy seems to suggest that it is a rare entity, but we believe that it may be more common. Vanadium allergy may be underdiagnosed because it is not a standard patch test allergen. Furthermore, many of those who do choose to test for it use what we believe to be ineffective formulas of vanadium when patch testing patients. Our patient demonstrated a positive patch test reaction only to vanadium trichloride and not to pure vanadium, which is consistent with the small number of other studies that investigated vanadium allergy.^5,12,13,15 We believe that vanadium trichloride is more water soluble than elemental vanadium,¹⁶ and thus more likely to identify true vanadium allergy than other test materials.

Although reports of vanadium allergy in patients with metal implants are rare in the medical literature, the material science literature clearly states that vanadium is toxic and that vanadium-containing implants are problematic.^17-20 It has been shown that although Ti6Al4V implants are considered highly resistant to corrosion, they will slowly and continuously corrode in a physiologic environment and release titanium, aluminum, and vanadium ions, both systemically and into the peri-implant space.¹¹ To address these problems with vanadium, vanadium-free titanium alloys such as Ti6Al7Nb have specifically been developed for medical use to address the problems caused by vanadium. Ti6Al7Nb contains 7% niobium rather than vanadium and appears to have some improved qualities in surgical implants.¹⁷

There is still a great deal of uncertainty around metal implant allergy. Allergy to metal implants can be difficult to diagnose for several reasons. Some metals are not conducive to patch testing because of their low bioavailability. Additionally, we lack validated and standardized patch test formulas for metals that can be diagnosed by patch testing. Furthermore, there is uncertainty about what to do after allergy to a metal implant is diagnosed; in some cases (eg, with more extensive procedures such as total joint replacements), removal or replacement of the implant may be associated with increased risk of further complications.^6,21

Conclusion

We suggest that manufacturers consider vanadium-free alloys such as Ti7Al6Nb, which contains niobium instead of vanadium, in their surgical implants,²² and if surgeons have a choice, they should consider using titanium implants with niobium rather than vanadium.¹⁰ We suggest that clinicians consider vanadium allergy in patients with Ti6Al4V surgical implants and signs of a hypersensitivity reaction, and include vanadium trichloride 1% when patch testing.

Acknowledgment

The authors would like to thank Nicholas R. Krasnow, PhD (Tucson, Arizona), for his invaluable help coordinating, performing, and interpreting the metal analyses.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

Aktipak

Cutanea Life Sciences, Inc, launches Aktipak (erythromycin 3% and benzoyl peroxide 5%) Gel, a prescription combination therapy indicated for acne vulgaris. Aktipak is packaged in a pocket-sized, dual-chamber pouch that contains erythromycin and benzoyl peroxide in separate chambers to enable convenient on-the-go use. Immediately prior to use, the patient cuts or twists open the pouch, squeezes the 2 gels into the palm of the hand, mixes the gels together, and applies the mix to the area affected by acne. Aktipak has an 18-month shelf life and does not require refrigeration. Results can be seen within 8 weeks. For more information, visit www.aktipak.com.

Glytone Acne BPO Clearing Cleanser

Pierre Fabre Group introduces the Glytone Acne BPO Clearing Cleanser (4.5% encapsulated benzoyl peroxide [BPO]) with time-released technology to control the delivery of BPO and enhance penetration. The targeted delivery system adheres to the skin and penetrates the lipid layer while releasing the encapsulated BPO once warmed by the skin, providing optimal efficacy to inhibit the growth of acne-causing bacteria with minimal irritation. Glytone Acne BPO Clearing Cleanser is dispensed by physicians and can be used with other products in the Glytone acne product line for optimal results. For more information, visit www.glytone-usa.com.

Juvéderm Vollure XC

Allergan announces US Food and Drug Administration approval of Juvéderm Vollure XC for correction of moderate to severe facial wrinkles and folds such as the nasolabial folds in adults older than 21 years. It utilizes VYCROSS technology, which blends different weights of hyaluronic acid, contributing to the gel’s duration. Long-lasting results have been demonstrated up to 18 months. For more information, visit www.juvederm.com.

Neutrogena Light Therapy Acne Mask

Johnson & Johnson Consumer Inc presents the Neutrogena Light Therapy Acne Mask, an LED device utilizing red and blue light to treat acne at home. The mask contains 12 blue LED bulbs that kill Propionibacterium acnes bacteria and 9 red LED bulbs to penetrate deep into the skin to calm inflammation. The mask can be used for 10 minutes each night and shuts off automatically. Results have been seen in 1 week for mild to moderate acne. For more information, visit www.neutrogena.com.

3% Retinol Peel ProSystem

NeoStrata Company, Inc, introduces the 3% Retinol Peel ProSystem featuring Retinol Boosting Complex to exfoliate and improve the appearance of fine lines and winkles, help reduce acne, and improve skin laxity, while promoting a bright, even, and clear complexion. This physician-strength peel is applied in the office but is removed at home after 8 hours or overnight. This peel has demonstrated improvement in acne and skin texture as well as diminished pigmentation. For more information, visit www.neostrata.com.

Siliq

Valeant Pharmaceuticals International, Inc, announces US Food and Drug Administration approval of the Biologics License Application for Siliq (brodalumab) injection. Siliq, an IL-17 inhibitor, is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Siliq has a black box warning for patients with a history of suicidal thoughts or behavior and was approved with a Risk Evaluation and Mitigation Strategy involving a one-time enrollment for physicians and one-time informed consent for patients. Sales and marketing in the United States will begin in the second half of 2017. For more information, visit www.valeant.com.

Thermi

Thermi, an Almirall company, announces “The Art of Thermi” campaign focusing on 2 Thermi devices: ThermiRF and Thermi250. ThermiRF is temperature-controlled radiofrequency technology that uses heat to produce aesthetic outcomes for soft tissue applications. Thermi250 is a high-powered, temperature-controlled radiofrequency system emitting at 470 kHz designed with a user-friendly interface to offer versatility for targeting cellulite. For more information, visit www.thermi.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@frontlinemedcom.com.

Aktipak

Cutanea Life Sciences, Inc, launches Aktipak (erythromycin 3% and benzoyl peroxide 5%) Gel, a prescription combination therapy indicated for acne vulgaris. Aktipak is packaged in a pocket-sized, dual-chamber pouch that contains erythromycin and benzoyl peroxide in separate chambers to enable convenient on-the-go use. Immediately prior to use, the patient cuts or twists open the pouch, squeezes the 2 gels into the palm of the hand, mixes the gels together, and applies the mix to the area affected by acne. Aktipak has an 18-month shelf life and does not require refrigeration. Results can be seen within 8 weeks. For more information, visit www.aktipak.com.

Glytone Acne BPO Clearing Cleanser

Pierre Fabre Group introduces the Glytone Acne BPO Clearing Cleanser (4.5% encapsulated benzoyl peroxide [BPO]) with time-released technology to control the delivery of BPO and enhance penetration. The targeted delivery system adheres to the skin and penetrates the lipid layer while releasing the encapsulated BPO once warmed by the skin, providing optimal efficacy to inhibit the growth of acne-causing bacteria with minimal irritation. Glytone Acne BPO Clearing Cleanser is dispensed by physicians and can be used with other products in the Glytone acne product line for optimal results. For more information, visit www.glytone-usa.com.

Juvéderm Vollure XC

Allergan announces US Food and Drug Administration approval of Juvéderm Vollure XC for correction of moderate to severe facial wrinkles and folds such as the nasolabial folds in adults older than 21 years. It utilizes VYCROSS technology, which blends different weights of hyaluronic acid, contributing to the gel’s duration. Long-lasting results have been demonstrated up to 18 months. For more information, visit www.juvederm.com.

Neutrogena Light Therapy Acne Mask

Johnson & Johnson Consumer Inc presents the Neutrogena Light Therapy Acne Mask, an LED device utilizing red and blue light to treat acne at home. The mask contains 12 blue LED bulbs that kill Propionibacterium acnes bacteria and 9 red LED bulbs to penetrate deep into the skin to calm inflammation. The mask can be used for 10 minutes each night and shuts off automatically. Results have been seen in 1 week for mild to moderate acne. For more information, visit www.neutrogena.com.

3% Retinol Peel ProSystem

NeoStrata Company, Inc, introduces the 3% Retinol Peel ProSystem featuring Retinol Boosting Complex to exfoliate and improve the appearance of fine lines and winkles, help reduce acne, and improve skin laxity, while promoting a bright, even, and clear complexion. This physician-strength peel is applied in the office but is removed at home after 8 hours or overnight. This peel has demonstrated improvement in acne and skin texture as well as diminished pigmentation. For more information, visit www.neostrata.com.

Siliq

Valeant Pharmaceuticals International, Inc, announces US Food and Drug Administration approval of the Biologics License Application for Siliq (brodalumab) injection. Siliq, an IL-17 inhibitor, is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Siliq has a black box warning for patients with a history of suicidal thoughts or behavior and was approved with a Risk Evaluation and Mitigation Strategy involving a one-time enrollment for physicians and one-time informed consent for patients. Sales and marketing in the United States will begin in the second half of 2017. For more information, visit www.valeant.com.

Thermi

Thermi, an Almirall company, announces “The Art of Thermi” campaign focusing on 2 Thermi devices: ThermiRF and Thermi250. ThermiRF is temperature-controlled radiofrequency technology that uses heat to produce aesthetic outcomes for soft tissue applications. Thermi250 is a high-powered, temperature-controlled radiofrequency system emitting at 470 kHz designed with a user-friendly interface to offer versatility for targeting cellulite. For more information, visit www.thermi.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@frontlinemedcom.com.

Aktipak

Cutanea Life Sciences, Inc, launches Aktipak (erythromycin 3% and benzoyl peroxide 5%) Gel, a prescription combination therapy indicated for acne vulgaris. Aktipak is packaged in a pocket-sized, dual-chamber pouch that contains erythromycin and benzoyl peroxide in separate chambers to enable convenient on-the-go use. Immediately prior to use, the patient cuts or twists open the pouch, squeezes the 2 gels into the palm of the hand, mixes the gels together, and applies the mix to the area affected by acne. Aktipak has an 18-month shelf life and does not require refrigeration. Results can be seen within 8 weeks. For more information, visit www.aktipak.com.

Glytone Acne BPO Clearing Cleanser

Pierre Fabre Group introduces the Glytone Acne BPO Clearing Cleanser (4.5% encapsulated benzoyl peroxide [BPO]) with time-released technology to control the delivery of BPO and enhance penetration. The targeted delivery system adheres to the skin and penetrates the lipid layer while releasing the encapsulated BPO once warmed by the skin, providing optimal efficacy to inhibit the growth of acne-causing bacteria with minimal irritation. Glytone Acne BPO Clearing Cleanser is dispensed by physicians and can be used with other products in the Glytone acne product line for optimal results. For more information, visit www.glytone-usa.com.

Juvéderm Vollure XC

Allergan announces US Food and Drug Administration approval of Juvéderm Vollure XC for correction of moderate to severe facial wrinkles and folds such as the nasolabial folds in adults older than 21 years. It utilizes VYCROSS technology, which blends different weights of hyaluronic acid, contributing to the gel’s duration. Long-lasting results have been demonstrated up to 18 months. For more information, visit www.juvederm.com.

Neutrogena Light Therapy Acne Mask

Johnson & Johnson Consumer Inc presents the Neutrogena Light Therapy Acne Mask, an LED device utilizing red and blue light to treat acne at home. The mask contains 12 blue LED bulbs that kill Propionibacterium acnes bacteria and 9 red LED bulbs to penetrate deep into the skin to calm inflammation. The mask can be used for 10 minutes each night and shuts off automatically. Results have been seen in 1 week for mild to moderate acne. For more information, visit www.neutrogena.com.

3% Retinol Peel ProSystem

NeoStrata Company, Inc, introduces the 3% Retinol Peel ProSystem featuring Retinol Boosting Complex to exfoliate and improve the appearance of fine lines and winkles, help reduce acne, and improve skin laxity, while promoting a bright, even, and clear complexion. This physician-strength peel is applied in the office but is removed at home after 8 hours or overnight. This peel has demonstrated improvement in acne and skin texture as well as diminished pigmentation. For more information, visit www.neostrata.com.

Siliq

Valeant Pharmaceuticals International, Inc, announces US Food and Drug Administration approval of the Biologics License Application for Siliq (brodalumab) injection. Siliq, an IL-17 inhibitor, is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Siliq has a black box warning for patients with a history of suicidal thoughts or behavior and was approved with a Risk Evaluation and Mitigation Strategy involving a one-time enrollment for physicians and one-time informed consent for patients. Sales and marketing in the United States will begin in the second half of 2017. For more information, visit www.valeant.com.

Thermi

Thermi, an Almirall company, announces “The Art of Thermi” campaign focusing on 2 Thermi devices: ThermiRF and Thermi250. ThermiRF is temperature-controlled radiofrequency technology that uses heat to produce aesthetic outcomes for soft tissue applications. Thermi250 is a high-powered, temperature-controlled radiofrequency system emitting at 470 kHz designed with a user-friendly interface to offer versatility for targeting cellulite. For more information, visit www.thermi.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@frontlinemedcom.com.

What does your patient need to know at the first visit?

Patients with this condition need to avoid friction and excessive moisture. They should be counseled to use gloves for excessive wet work. I recommend they use cotton gloves on the hands, and then cover those with rubber gloves. Patients should use a hand emollient regularly, including after each time they wash their hands or have exposure to water. If the patient lifts weights, I recommend he/she use weight-lifting gloves to reduce friction.

What are your go to treatments? What are the side effects?

The first line of therapy for hand and foot psoriasis is a topical agent. I most often use a combination of topical steroids and a topical vitamin D analogue. If insurance is amenable, I may use a fixed combination of topical steroid and vitamin D analogue.

If topical therapies are not successful, I often consider using excimer laser therapy, which requires the patient to come to the office twice weekly, so it is important to determine if this therapy is compatible with the patient's schedule. Other options include oral and biological therapies. Apremilast is a reasonable first-line systemic therapy given that it is an oral therapy, requires no laboratory monitoring, and has a favorable safety profile. Alternatively, biologic agents can be utilized. There are several analyses available looking at the efficacy of different biologics in hand and foot psoriasis, but at this point there is no consensus first choice for a biologic in this condition. Many available biologics may have a notable impact though.

The side effects of therapies for psoriasis are well established. Topical therapies and excimer laser are relatively safe choices. Apremilast has been associated with early gastrointestinal tract side effects that tend to resolve over time. Each biologic has a unique safety profile, with a rare incidence of side effects that should be reviewed carefully with any prospective patients before starting therapy.

How do you keep patients compliant with treatment?

It is important to reinforce gentle hand care and foot care. Patients need to understand that lack of compliance with treatment will lead to recurrence of disease.

What do you do if patients refuse treatment? 

I try to educate them as best as possible, and ask them to return and reconsider therapy if they find that this condition affects their quality of life.

What does your patient need to know at the first visit?

Patients with this condition need to avoid friction and excessive moisture. They should be counseled to use gloves for excessive wet work. I recommend they use cotton gloves on the hands, and then cover those with rubber gloves. Patients should use a hand emollient regularly, including after each time they wash their hands or have exposure to water. If the patient lifts weights, I recommend he/she use weight-lifting gloves to reduce friction.

What are your go to treatments? What are the side effects?

The first line of therapy for hand and foot psoriasis is a topical agent. I most often use a combination of topical steroids and a topical vitamin D analogue. If insurance is amenable, I may use a fixed combination of topical steroid and vitamin D analogue.

If topical therapies are not successful, I often consider using excimer laser therapy, which requires the patient to come to the office twice weekly, so it is important to determine if this therapy is compatible with the patient's schedule. Other options include oral and biological therapies. Apremilast is a reasonable first-line systemic therapy given that it is an oral therapy, requires no laboratory monitoring, and has a favorable safety profile. Alternatively, biologic agents can be utilized. There are several analyses available looking at the efficacy of different biologics in hand and foot psoriasis, but at this point there is no consensus first choice for a biologic in this condition. Many available biologics may have a notable impact though.

The side effects of therapies for psoriasis are well established. Topical therapies and excimer laser are relatively safe choices. Apremilast has been associated with early gastrointestinal tract side effects that tend to resolve over time. Each biologic has a unique safety profile, with a rare incidence of side effects that should be reviewed carefully with any prospective patients before starting therapy.

How do you keep patients compliant with treatment?

It is important to reinforce gentle hand care and foot care. Patients need to understand that lack of compliance with treatment will lead to recurrence of disease.

What do you do if patients refuse treatment? 

I try to educate them as best as possible, and ask them to return and reconsider therapy if they find that this condition affects their quality of life.

What does your patient need to know at the first visit?

Patients with this condition need to avoid friction and excessive moisture. They should be counseled to use gloves for excessive wet work. I recommend they use cotton gloves on the hands, and then cover those with rubber gloves. Patients should use a hand emollient regularly, including after each time they wash their hands or have exposure to water. If the patient lifts weights, I recommend he/she use weight-lifting gloves to reduce friction.

What are your go to treatments? What are the side effects?

The first line of therapy for hand and foot psoriasis is a topical agent. I most often use a combination of topical steroids and a topical vitamin D analogue. If insurance is amenable, I may use a fixed combination of topical steroid and vitamin D analogue.

If topical therapies are not successful, I often consider using excimer laser therapy, which requires the patient to come to the office twice weekly, so it is important to determine if this therapy is compatible with the patient's schedule. Other options include oral and biological therapies. Apremilast is a reasonable first-line systemic therapy given that it is an oral therapy, requires no laboratory monitoring, and has a favorable safety profile. Alternatively, biologic agents can be utilized. There are several analyses available looking at the efficacy of different biologics in hand and foot psoriasis, but at this point there is no consensus first choice for a biologic in this condition. Many available biologics may have a notable impact though.

The side effects of therapies for psoriasis are well established. Topical therapies and excimer laser are relatively safe choices. Apremilast has been associated with early gastrointestinal tract side effects that tend to resolve over time. Each biologic has a unique safety profile, with a rare incidence of side effects that should be reviewed carefully with any prospective patients before starting therapy.

How do you keep patients compliant with treatment?

It is important to reinforce gentle hand care and foot care. Patients need to understand that lack of compliance with treatment will lead to recurrence of disease.

What do you do if patients refuse treatment? 

I try to educate them as best as possible, and ask them to return and reconsider therapy if they find that this condition affects their quality of life.

Microneedling therapy, also known as collagen induction therapy or percutaneous collagen induction, is an increasingly popular treatment modality for skin rejuvenation. The approach employs small needles to puncture the skin and stimulate local collagen production in a minimally invasive manner. Recently, clinicians have incorporated the use of platelet-rich plasma (PRP) with the aim of augmenting cosmetic outcomes. In this article, we examine the utility of this approach by reviewing comparison studies of microneedling therapy with and without the application of PRP.

Dr. Gary Goldenberg demonstrates microneedling with platelet-rich plasma in a procedural video available here.

Microneedling Therapy

The use of microneedling first gained attention in the 1990s. Initially, Camirand and Doucet¹ described tattooing without pigment for the treatment of achromatic and hypertrophic scars. Fernandes² evolved this concept and developed a drum-shaped device with fine protruding needles to puncture the skin. Microneedling devices have expanded in recent years and now include both cord- and battery-powered pens and rollers, with needles ranging in length from 0.25 to 3.0 mm.

Treatment with microneedling promotes skin rejuvenation by creating small puncture wounds in the epidermis and dermis. This injury triggers the wound healing cascade and alters the modulation of growth factors to promote regenerative effects.^3,4 Following microneedling therapy, increases occur in elastic fiber formation, collagen deposition, and dermal thickness (Figure).⁵ Of interesting histologic note, collagen is deposited in the normal lattice pattern following this treatment rather than in the parallel bundles typical of scars.⁶ Microneedling preserves the overall integrity of the epidermal layers and basement membrane, allowing the epidermis to heal without abnormality, verified on histology by a normal stratum corneum, enhanced stratum granulosum, and normal rete ridges.⁷

Photographs courtesy of Joel L. Cohen, MD (Colorado, USA).

Microneedling has demonstrated several uses beyond general skin rejuvenation. In patients with atrophic acne scars, therapy can lead to improved scar appearance, skin texture, and patient satisfaction.^8,9 Hypertrophic and dyspigmented burn scars on the body, face, arms, and legs have shown to be receptive to repeated treatments.¹⁰ Microneedling also has shown promise in treating androgenic alopecia, increasing hair regrowth in patients who previously showed poor response to conventional therapy with minoxidil and finasteride.^11,12

Platelet-Rich Plasma

Platelet-rich plasma is developed by enriching blood with an autologous concentration of platelets. The preparation of PRP begins with whole blood, commonly obtained peripherally by venipuncture. Samples undergo centrifugation to allow separation of the blood into 3 layers: platelet-poor plasma, PRP, and erythrocytes.¹³ The typical platelet count of whole blood is approximately 200,000/µL; PRP aims to prepare a platelet count of at least 1,000,000/µL in a 5-mL volume.¹⁴

An attractive component of PRP is its high concentration of growth factors, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and epithelial growth factor.¹⁵ Because of the regenerative effects of these proteins, PRP has been investigated as a modality to augment wound healing in a variety of clinical areas, such as maxillofacial surgery, orthopedics, cardiovascular surgery, and treatment of soft tissue ulcers.¹⁶

Combination Use of Microneedling and PRP

Several studies have compared the effects of microneedling with and without the application of PRP (Table).^17-20 In an animal model, Akcal et al¹⁷ examined the effects of microneedling and PRP on skin flap survival. Eight rats were randomly divided into 5 groups: sham, control, microneedling alone, microneedling plus PRP, and microneedling plus platelet-poor plasma. Treatments were applied to skin flaps after 4 hours of induced ischemia. The surviving flap area was measured, with results demonstrating significantly higher viable areas in the microneedling plus PRP group relative to all other groups (P<.01). On histologic examination, the microneedling plus PRP group showed well-organized epidermal layers and a dermal integrity that matched the dermis of the sham group.¹⁷

Asif et al¹⁸ performed a split-face comparison study of 50 patients with atrophic acne scars. On the right side, microneedling was performed followed by intradermal injections and topical application of PRP. On the left side, microneedling was performed followed by intradermal injections of distilled water. The study included 3 treatment sessions with 1 month between each session. Scars were assessed using the Goodman and Baron scale,²¹ which is designed to grade the morphology of postacne scarring. Scars on the right side improved by 62.2% and scars on the left side improved by 45.8%; prior to treatment, both sides demonstrated similar severity scores, but final severity scores were significantly reduced in the microneedling plus PRP group relative to the microneedling plus distilled water group (P<.00001). No residual side effects from treatment were reported.¹⁸

Examining the degree of improvement more carefully, microneedling plus PRP yielded excellent improvement in 40% (20/50) of patients and good improvement in 60% (30/50).¹⁸ Microneedling plus distilled water led to excellent improvement in 10% (5/50) and good improvement in 84% (42/50). Given that microneedling plus distilled water still provided good to excellent results in 94% of patients, the addition of PRP was helpful though not necessary in achieving meaningful benefit.¹⁸

In another split-face study, Fabbrocini et al¹⁹ evaluated 12 adult patients with acne scars. The right side of the face received microneedling plus PRP, while the left side received microneedling alone. Two treatments were performed 8 weeks apart. Severity scores (0=no lesions; 10=maximum severity) were used to assess patient outcomes throughout the study. Acne scars improved on both sides of the face following the treatment period, but the reduction in scar severity with microneedling plus PRP (3.5 points) was significantly greater than with microneedling alone (2.6 points)(P<.05). Patients tended to experience2 to 3 days of mild swelling and erythema after treatment regardless of PRP addition. With only 12 patients, the study was limited by a small sample size. The 10-point grading system differed from the Goodman and Baron scale in that it lacked corresponding qualitative markers, likely decreasing reproducibility.¹⁹

Chawla²⁰ compared the effectiveness of combination therapy with microneedling plus PRP versus microneedling and vitamin C application. In a split-face study of 30 patients with atrophic acne scars, the right side of the face was treated with microneedling plus PRP and the left side was treated with microneedling plus vitamin C. Four sessions were performed with an interval of 1 month in between treatments. The Goodman and Baron Scale was used to assess treatment efficacy. Overall, both treatments led to improved outcomes, but in categorizing patients who demonstrated poor responses, a significantly larger percentage existed in the microneedling plus vitamin C group (37% [10/27]) versus the microneedling plus PRP group (22% [6/27])(P=.021). Additionally, aggregate patient satisfaction scores were higher with microneedling plus PRP relative to microneedling plus vitamin C (P=.01). Of note, assessments of improvement were performed by the treating physician and patient satisfaction reports were completed with knowledge of the therapies and cost factor, which may have influenced results.²⁰

Conclusion

Microneedling therapy continues to evolve with a range of applications now emerging in dermatology. As PRP has gained popularity, there has been increased interest in its utilization to amplify the regenerative effects of microneedling. Although the number of direct comparisons examining microneedling with and without PRP is limited, the available evidence indicates that the addition of PRP may improve cosmetic outcomes. These results have been demonstrated primarily in the management of acne scars, but favorable effects may extend to other indications. Continued study is warranted to further quantify the degree of these benefits and to elucidate optimal treatment schedules.

In addition, it is important to consider a cost-benefit analysis of PRP. The price of PRP varies depending on the clinical site but in certain cases may double the cost of a microneedling treatment session. Although studies have demonstrated a statistically significant benefit to PRP, the clinical significance of this supplementary treatment must be weighed against the increased expense. A discussion should take place with the consideration that microneedling alone can provide a satisfactory result for some patients.

Microneedling therapy, also known as collagen induction therapy or percutaneous collagen induction, is an increasingly popular treatment modality for skin rejuvenation. The approach employs small needles to puncture the skin and stimulate local collagen production in a minimally invasive manner. Recently, clinicians have incorporated the use of platelet-rich plasma (PRP) with the aim of augmenting cosmetic outcomes. In this article, we examine the utility of this approach by reviewing comparison studies of microneedling therapy with and without the application of PRP.

Dr. Gary Goldenberg demonstrates microneedling with platelet-rich plasma in a procedural video available here.

Microneedling Therapy

The use of microneedling first gained attention in the 1990s. Initially, Camirand and Doucet¹ described tattooing without pigment for the treatment of achromatic and hypertrophic scars. Fernandes² evolved this concept and developed a drum-shaped device with fine protruding needles to puncture the skin. Microneedling devices have expanded in recent years and now include both cord- and battery-powered pens and rollers, with needles ranging in length from 0.25 to 3.0 mm.

Treatment with microneedling promotes skin rejuvenation by creating small puncture wounds in the epidermis and dermis. This injury triggers the wound healing cascade and alters the modulation of growth factors to promote regenerative effects.^3,4 Following microneedling therapy, increases occur in elastic fiber formation, collagen deposition, and dermal thickness (Figure).⁵ Of interesting histologic note, collagen is deposited in the normal lattice pattern following this treatment rather than in the parallel bundles typical of scars.⁶ Microneedling preserves the overall integrity of the epidermal layers and basement membrane, allowing the epidermis to heal without abnormality, verified on histology by a normal stratum corneum, enhanced stratum granulosum, and normal rete ridges.⁷

Photographs courtesy of Joel L. Cohen, MD (Colorado, USA).

Microneedling has demonstrated several uses beyond general skin rejuvenation. In patients with atrophic acne scars, therapy can lead to improved scar appearance, skin texture, and patient satisfaction.^8,9 Hypertrophic and dyspigmented burn scars on the body, face, arms, and legs have shown to be receptive to repeated treatments.¹⁰ Microneedling also has shown promise in treating androgenic alopecia, increasing hair regrowth in patients who previously showed poor response to conventional therapy with minoxidil and finasteride.^11,12

Platelet-Rich Plasma

Platelet-rich plasma is developed by enriching blood with an autologous concentration of platelets. The preparation of PRP begins with whole blood, commonly obtained peripherally by venipuncture. Samples undergo centrifugation to allow separation of the blood into 3 layers: platelet-poor plasma, PRP, and erythrocytes.¹³ The typical platelet count of whole blood is approximately 200,000/µL; PRP aims to prepare a platelet count of at least 1,000,000/µL in a 5-mL volume.¹⁴

An attractive component of PRP is its high concentration of growth factors, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and epithelial growth factor.¹⁵ Because of the regenerative effects of these proteins, PRP has been investigated as a modality to augment wound healing in a variety of clinical areas, such as maxillofacial surgery, orthopedics, cardiovascular surgery, and treatment of soft tissue ulcers.¹⁶

Combination Use of Microneedling and PRP

Several studies have compared the effects of microneedling with and without the application of PRP (Table).^17-20 In an animal model, Akcal et al¹⁷ examined the effects of microneedling and PRP on skin flap survival. Eight rats were randomly divided into 5 groups: sham, control, microneedling alone, microneedling plus PRP, and microneedling plus platelet-poor plasma. Treatments were applied to skin flaps after 4 hours of induced ischemia. The surviving flap area was measured, with results demonstrating significantly higher viable areas in the microneedling plus PRP group relative to all other groups (P<.01). On histologic examination, the microneedling plus PRP group showed well-organized epidermal layers and a dermal integrity that matched the dermis of the sham group.¹⁷

Asif et al¹⁸ performed a split-face comparison study of 50 patients with atrophic acne scars. On the right side, microneedling was performed followed by intradermal injections and topical application of PRP. On the left side, microneedling was performed followed by intradermal injections of distilled water. The study included 3 treatment sessions with 1 month between each session. Scars were assessed using the Goodman and Baron scale,²¹ which is designed to grade the morphology of postacne scarring. Scars on the right side improved by 62.2% and scars on the left side improved by 45.8%; prior to treatment, both sides demonstrated similar severity scores, but final severity scores were significantly reduced in the microneedling plus PRP group relative to the microneedling plus distilled water group (P<.00001). No residual side effects from treatment were reported.¹⁸

Examining the degree of improvement more carefully, microneedling plus PRP yielded excellent improvement in 40% (20/50) of patients and good improvement in 60% (30/50).¹⁸ Microneedling plus distilled water led to excellent improvement in 10% (5/50) and good improvement in 84% (42/50). Given that microneedling plus distilled water still provided good to excellent results in 94% of patients, the addition of PRP was helpful though not necessary in achieving meaningful benefit.¹⁸

In another split-face study, Fabbrocini et al¹⁹ evaluated 12 adult patients with acne scars. The right side of the face received microneedling plus PRP, while the left side received microneedling alone. Two treatments were performed 8 weeks apart. Severity scores (0=no lesions; 10=maximum severity) were used to assess patient outcomes throughout the study. Acne scars improved on both sides of the face following the treatment period, but the reduction in scar severity with microneedling plus PRP (3.5 points) was significantly greater than with microneedling alone (2.6 points)(P<.05). Patients tended to experience2 to 3 days of mild swelling and erythema after treatment regardless of PRP addition. With only 12 patients, the study was limited by a small sample size. The 10-point grading system differed from the Goodman and Baron scale in that it lacked corresponding qualitative markers, likely decreasing reproducibility.¹⁹

Chawla²⁰ compared the effectiveness of combination therapy with microneedling plus PRP versus microneedling and vitamin C application. In a split-face study of 30 patients with atrophic acne scars, the right side of the face was treated with microneedling plus PRP and the left side was treated with microneedling plus vitamin C. Four sessions were performed with an interval of 1 month in between treatments. The Goodman and Baron Scale was used to assess treatment efficacy. Overall, both treatments led to improved outcomes, but in categorizing patients who demonstrated poor responses, a significantly larger percentage existed in the microneedling plus vitamin C group (37% [10/27]) versus the microneedling plus PRP group (22% [6/27])(P=.021). Additionally, aggregate patient satisfaction scores were higher with microneedling plus PRP relative to microneedling plus vitamin C (P=.01). Of note, assessments of improvement were performed by the treating physician and patient satisfaction reports were completed with knowledge of the therapies and cost factor, which may have influenced results.²⁰

Conclusion

Microneedling therapy continues to evolve with a range of applications now emerging in dermatology. As PRP has gained popularity, there has been increased interest in its utilization to amplify the regenerative effects of microneedling. Although the number of direct comparisons examining microneedling with and without PRP is limited, the available evidence indicates that the addition of PRP may improve cosmetic outcomes. These results have been demonstrated primarily in the management of acne scars, but favorable effects may extend to other indications. Continued study is warranted to further quantify the degree of these benefits and to elucidate optimal treatment schedules.

In addition, it is important to consider a cost-benefit analysis of PRP. The price of PRP varies depending on the clinical site but in certain cases may double the cost of a microneedling treatment session. Although studies have demonstrated a statistically significant benefit to PRP, the clinical significance of this supplementary treatment must be weighed against the increased expense. A discussion should take place with the consideration that microneedling alone can provide a satisfactory result for some patients.

Microneedling therapy, also known as collagen induction therapy or percutaneous collagen induction, is an increasingly popular treatment modality for skin rejuvenation. The approach employs small needles to puncture the skin and stimulate local collagen production in a minimally invasive manner. Recently, clinicians have incorporated the use of platelet-rich plasma (PRP) with the aim of augmenting cosmetic outcomes. In this article, we examine the utility of this approach by reviewing comparison studies of microneedling therapy with and without the application of PRP.

Dr. Gary Goldenberg demonstrates microneedling with platelet-rich plasma in a procedural video available here.

Microneedling Therapy

The use of microneedling first gained attention in the 1990s. Initially, Camirand and Doucet¹ described tattooing without pigment for the treatment of achromatic and hypertrophic scars. Fernandes² evolved this concept and developed a drum-shaped device with fine protruding needles to puncture the skin. Microneedling devices have expanded in recent years and now include both cord- and battery-powered pens and rollers, with needles ranging in length from 0.25 to 3.0 mm.

Treatment with microneedling promotes skin rejuvenation by creating small puncture wounds in the epidermis and dermis. This injury triggers the wound healing cascade and alters the modulation of growth factors to promote regenerative effects.^3,4 Following microneedling therapy, increases occur in elastic fiber formation, collagen deposition, and dermal thickness (Figure).⁵ Of interesting histologic note, collagen is deposited in the normal lattice pattern following this treatment rather than in the parallel bundles typical of scars.⁶ Microneedling preserves the overall integrity of the epidermal layers and basement membrane, allowing the epidermis to heal without abnormality, verified on histology by a normal stratum corneum, enhanced stratum granulosum, and normal rete ridges.⁷

Photographs courtesy of Joel L. Cohen, MD (Colorado, USA).

Microneedling has demonstrated several uses beyond general skin rejuvenation. In patients with atrophic acne scars, therapy can lead to improved scar appearance, skin texture, and patient satisfaction.^8,9 Hypertrophic and dyspigmented burn scars on the body, face, arms, and legs have shown to be receptive to repeated treatments.¹⁰ Microneedling also has shown promise in treating androgenic alopecia, increasing hair regrowth in patients who previously showed poor response to conventional therapy with minoxidil and finasteride.^11,12

Platelet-Rich Plasma

Platelet-rich plasma is developed by enriching blood with an autologous concentration of platelets. The preparation of PRP begins with whole blood, commonly obtained peripherally by venipuncture. Samples undergo centrifugation to allow separation of the blood into 3 layers: platelet-poor plasma, PRP, and erythrocytes.¹³ The typical platelet count of whole blood is approximately 200,000/µL; PRP aims to prepare a platelet count of at least 1,000,000/µL in a 5-mL volume.¹⁴

An attractive component of PRP is its high concentration of growth factors, including platelet-derived growth factor, transforming growth factor, vascular endothelial growth factor, and epithelial growth factor.¹⁵ Because of the regenerative effects of these proteins, PRP has been investigated as a modality to augment wound healing in a variety of clinical areas, such as maxillofacial surgery, orthopedics, cardiovascular surgery, and treatment of soft tissue ulcers.¹⁶

Combination Use of Microneedling and PRP

Several studies have compared the effects of microneedling with and without the application of PRP (Table).^17-20 In an animal model, Akcal et al¹⁷ examined the effects of microneedling and PRP on skin flap survival. Eight rats were randomly divided into 5 groups: sham, control, microneedling alone, microneedling plus PRP, and microneedling plus platelet-poor plasma. Treatments were applied to skin flaps after 4 hours of induced ischemia. The surviving flap area was measured, with results demonstrating significantly higher viable areas in the microneedling plus PRP group relative to all other groups (P<.01). On histologic examination, the microneedling plus PRP group showed well-organized epidermal layers and a dermal integrity that matched the dermis of the sham group.¹⁷

Asif et al¹⁸ performed a split-face comparison study of 50 patients with atrophic acne scars. On the right side, microneedling was performed followed by intradermal injections and topical application of PRP. On the left side, microneedling was performed followed by intradermal injections of distilled water. The study included 3 treatment sessions with 1 month between each session. Scars were assessed using the Goodman and Baron scale,²¹ which is designed to grade the morphology of postacne scarring. Scars on the right side improved by 62.2% and scars on the left side improved by 45.8%; prior to treatment, both sides demonstrated similar severity scores, but final severity scores were significantly reduced in the microneedling plus PRP group relative to the microneedling plus distilled water group (P<.00001). No residual side effects from treatment were reported.¹⁸

Examining the degree of improvement more carefully, microneedling plus PRP yielded excellent improvement in 40% (20/50) of patients and good improvement in 60% (30/50).¹⁸ Microneedling plus distilled water led to excellent improvement in 10% (5/50) and good improvement in 84% (42/50). Given that microneedling plus distilled water still provided good to excellent results in 94% of patients, the addition of PRP was helpful though not necessary in achieving meaningful benefit.¹⁸

In another split-face study, Fabbrocini et al¹⁹ evaluated 12 adult patients with acne scars. The right side of the face received microneedling plus PRP, while the left side received microneedling alone. Two treatments were performed 8 weeks apart. Severity scores (0=no lesions; 10=maximum severity) were used to assess patient outcomes throughout the study. Acne scars improved on both sides of the face following the treatment period, but the reduction in scar severity with microneedling plus PRP (3.5 points) was significantly greater than with microneedling alone (2.6 points)(P<.05). Patients tended to experience2 to 3 days of mild swelling and erythema after treatment regardless of PRP addition. With only 12 patients, the study was limited by a small sample size. The 10-point grading system differed from the Goodman and Baron scale in that it lacked corresponding qualitative markers, likely decreasing reproducibility.¹⁹

Chawla²⁰ compared the effectiveness of combination therapy with microneedling plus PRP versus microneedling and vitamin C application. In a split-face study of 30 patients with atrophic acne scars, the right side of the face was treated with microneedling plus PRP and the left side was treated with microneedling plus vitamin C. Four sessions were performed with an interval of 1 month in between treatments. The Goodman and Baron Scale was used to assess treatment efficacy. Overall, both treatments led to improved outcomes, but in categorizing patients who demonstrated poor responses, a significantly larger percentage existed in the microneedling plus vitamin C group (37% [10/27]) versus the microneedling plus PRP group (22% [6/27])(P=.021). Additionally, aggregate patient satisfaction scores were higher with microneedling plus PRP relative to microneedling plus vitamin C (P=.01). Of note, assessments of improvement were performed by the treating physician and patient satisfaction reports were completed with knowledge of the therapies and cost factor, which may have influenced results.²⁰

Conclusion

Microneedling therapy continues to evolve with a range of applications now emerging in dermatology. As PRP has gained popularity, there has been increased interest in its utilization to amplify the regenerative effects of microneedling. Although the number of direct comparisons examining microneedling with and without PRP is limited, the available evidence indicates that the addition of PRP may improve cosmetic outcomes. These results have been demonstrated primarily in the management of acne scars, but favorable effects may extend to other indications. Continued study is warranted to further quantify the degree of these benefits and to elucidate optimal treatment schedules.

In addition, it is important to consider a cost-benefit analysis of PRP. The price of PRP varies depending on the clinical site but in certain cases may double the cost of a microneedling treatment session. Although studies have demonstrated a statistically significant benefit to PRP, the clinical significance of this supplementary treatment must be weighed against the increased expense. A discussion should take place with the consideration that microneedling alone can provide a satisfactory result for some patients.

The last decade has been a period of advancement for the lesbian, gay, bisexual, and transgender (LGBT) community for legal protections and visibility. Although the journey to acceptance and equality is far from over, this progress has appropriately extended to medical academia as physicians search for ways to become more inclusive and effective care providers for their LGBT patients.¹ In a recent cross-sectional study, Ginsberg et al² examined the role for dermatologists in the care of transgender patients. The investigators concluded that dermatologists should play a larger role in a transgender patient’s physical transformation.² It is our opinion that dermatologists need to be comfortable building rapport with LGBT patients and to become attuned to their specific needs to provide effective care.

When forging a relationship with an LGBT patient, assumptions can damage rapport. Two assumptions that should be avoided include presuming heterosexuality or, on the other hand, assuming risk for disease based on known LGBT status. A dermatologist who takes a cursory sexual history, or none at all, assuming his/her patient is heterosexual creates an environment in which a nonheterosexual patient feels uncomfortable being honest and open. Although there is enough literature to support the claim that some sexual minority groups have increased risk for sexually transmitted infections (STIs),³ it is dangerous to assume a patient’s risk based solely on sexual orientation. An abstinent patient or a patient in a long-term, monogamous, same-sex relationship, for instance, may feel stereotyped by a dermatologist who wants to screen him/her for an STI. The best step in building a therapeutic relationship is to cast out these assumptions and allow LGBT patients to be open about themselves and their sexual practices. Sexual histories should be asked in nonjudgmental ways that are related to the health of the patient, leading to relevant and useful information for their care. For example, ask patients, “Do you have sex with men, women, or both?” This question should be delivered in a matter-of-fact tone, which conveys to the patient that the provider merely wants an answer to guide patient care.

Dermatologists can tailor their encounters to the specific needs of sexual minority patients. The medical literature is rich with examples of conditions that occur at greater frequency in specific sexual minority groups. Sexually transmitted infections, particularly human immunodeficiency virus, are important causes of morbidity and mortality among sexual minorities, especially men who have sex with men (MSM).^3,4 Anal and penile human papillomavirus (HPV) infection and HPV-associated anal carcinoma risk are increased in MSM.^5,6 The literature has remained inconclusive on the use of anal Papanicolaou tests for diagnosis; however, dermatologists have a duty to at least examine the perianal and genital area of any patient at risk for HPV-related disease or STIs.^7,8 For younger patients, the HPV vaccine can help prevent certain types of HPV infection and likely reduce a patient’s risk for condyloma acuminatum and other sequelae of the virus. Guidelines have been expanded to include men aged 13 to 21 years and up to 26 years.⁹ More research is needed to determine if detection and prevention of these types of HPV infection using the vaccine in MSM actually leads to a decreased incidence of anal carcinoma.

Certain LGBT groups may benefit from a dermatologist’s care outside the realm of infectious diseases. One study found that increased indoor tanning use in MSM correlated with increased risk for nonmelanoma skin cancer.¹⁰ Lesbians have been found to be less likely to pursue preventative health examinations in general, including skin checks.¹¹ Finally, transgender patients can utilize dermatologists for help with transformative procedures and side effects of hormonal treatment such as androgenic acne.^1,4

Cutaneous and beyond, the future of LGBT health care in the United States is affected by the institutions that train future physicians. There is a trend toward incorporating formal LGBT curricula into medical schools and academic centers.¹² The Penn Medicine Program for LGBT Health (Philadelphia, Pennsylvania) is a pilot program geared toward both educating future clinicians and providing equal and unbiased care to LGBT patients.¹² Programs such as this one give rise to a new generation of physicians who feel comfortable and aware of the needs of their LGBT patients.

In a time when LGBT patients are becoming more comfortable claiming their sexual and gender identities openly, there is a need for dermatologists to provide individualized unbiased care, which can best be achieved by building rapport through assumption-free history taking, performing thorough physical examinations that include the genital and perianal area, and passing these good practices on to trainees.

The last decade has been a period of advancement for the lesbian, gay, bisexual, and transgender (LGBT) community for legal protections and visibility. Although the journey to acceptance and equality is far from over, this progress has appropriately extended to medical academia as physicians search for ways to become more inclusive and effective care providers for their LGBT patients.¹ In a recent cross-sectional study, Ginsberg et al² examined the role for dermatologists in the care of transgender patients. The investigators concluded that dermatologists should play a larger role in a transgender patient’s physical transformation.² It is our opinion that dermatologists need to be comfortable building rapport with LGBT patients and to become attuned to their specific needs to provide effective care.

When forging a relationship with an LGBT patient, assumptions can damage rapport. Two assumptions that should be avoided include presuming heterosexuality or, on the other hand, assuming risk for disease based on known LGBT status. A dermatologist who takes a cursory sexual history, or none at all, assuming his/her patient is heterosexual creates an environment in which a nonheterosexual patient feels uncomfortable being honest and open. Although there is enough literature to support the claim that some sexual minority groups have increased risk for sexually transmitted infections (STIs),³ it is dangerous to assume a patient’s risk based solely on sexual orientation. An abstinent patient or a patient in a long-term, monogamous, same-sex relationship, for instance, may feel stereotyped by a dermatologist who wants to screen him/her for an STI. The best step in building a therapeutic relationship is to cast out these assumptions and allow LGBT patients to be open about themselves and their sexual practices. Sexual histories should be asked in nonjudgmental ways that are related to the health of the patient, leading to relevant and useful information for their care. For example, ask patients, “Do you have sex with men, women, or both?” This question should be delivered in a matter-of-fact tone, which conveys to the patient that the provider merely wants an answer to guide patient care.

Dermatologists can tailor their encounters to the specific needs of sexual minority patients. The medical literature is rich with examples of conditions that occur at greater frequency in specific sexual minority groups. Sexually transmitted infections, particularly human immunodeficiency virus, are important causes of morbidity and mortality among sexual minorities, especially men who have sex with men (MSM).^3,4 Anal and penile human papillomavirus (HPV) infection and HPV-associated anal carcinoma risk are increased in MSM.^5,6 The literature has remained inconclusive on the use of anal Papanicolaou tests for diagnosis; however, dermatologists have a duty to at least examine the perianal and genital area of any patient at risk for HPV-related disease or STIs.^7,8 For younger patients, the HPV vaccine can help prevent certain types of HPV infection and likely reduce a patient’s risk for condyloma acuminatum and other sequelae of the virus. Guidelines have been expanded to include men aged 13 to 21 years and up to 26 years.⁹ More research is needed to determine if detection and prevention of these types of HPV infection using the vaccine in MSM actually leads to a decreased incidence of anal carcinoma.

Certain LGBT groups may benefit from a dermatologist’s care outside the realm of infectious diseases. One study found that increased indoor tanning use in MSM correlated with increased risk for nonmelanoma skin cancer.¹⁰ Lesbians have been found to be less likely to pursue preventative health examinations in general, including skin checks.¹¹ Finally, transgender patients can utilize dermatologists for help with transformative procedures and side effects of hormonal treatment such as androgenic acne.^1,4

Cutaneous and beyond, the future of LGBT health care in the United States is affected by the institutions that train future physicians. There is a trend toward incorporating formal LGBT curricula into medical schools and academic centers.¹² The Penn Medicine Program for LGBT Health (Philadelphia, Pennsylvania) is a pilot program geared toward both educating future clinicians and providing equal and unbiased care to LGBT patients.¹² Programs such as this one give rise to a new generation of physicians who feel comfortable and aware of the needs of their LGBT patients.

In a time when LGBT patients are becoming more comfortable claiming their sexual and gender identities openly, there is a need for dermatologists to provide individualized unbiased care, which can best be achieved by building rapport through assumption-free history taking, performing thorough physical examinations that include the genital and perianal area, and passing these good practices on to trainees.

The last decade has been a period of advancement for the lesbian, gay, bisexual, and transgender (LGBT) community for legal protections and visibility. Although the journey to acceptance and equality is far from over, this progress has appropriately extended to medical academia as physicians search for ways to become more inclusive and effective care providers for their LGBT patients.¹ In a recent cross-sectional study, Ginsberg et al² examined the role for dermatologists in the care of transgender patients. The investigators concluded that dermatologists should play a larger role in a transgender patient’s physical transformation.² It is our opinion that dermatologists need to be comfortable building rapport with LGBT patients and to become attuned to their specific needs to provide effective care.

When forging a relationship with an LGBT patient, assumptions can damage rapport. Two assumptions that should be avoided include presuming heterosexuality or, on the other hand, assuming risk for disease based on known LGBT status. A dermatologist who takes a cursory sexual history, or none at all, assuming his/her patient is heterosexual creates an environment in which a nonheterosexual patient feels uncomfortable being honest and open. Although there is enough literature to support the claim that some sexual minority groups have increased risk for sexually transmitted infections (STIs),³ it is dangerous to assume a patient’s risk based solely on sexual orientation. An abstinent patient or a patient in a long-term, monogamous, same-sex relationship, for instance, may feel stereotyped by a dermatologist who wants to screen him/her for an STI. The best step in building a therapeutic relationship is to cast out these assumptions and allow LGBT patients to be open about themselves and their sexual practices. Sexual histories should be asked in nonjudgmental ways that are related to the health of the patient, leading to relevant and useful information for their care. For example, ask patients, “Do you have sex with men, women, or both?” This question should be delivered in a matter-of-fact tone, which conveys to the patient that the provider merely wants an answer to guide patient care.

Dermatologists can tailor their encounters to the specific needs of sexual minority patients. The medical literature is rich with examples of conditions that occur at greater frequency in specific sexual minority groups. Sexually transmitted infections, particularly human immunodeficiency virus, are important causes of morbidity and mortality among sexual minorities, especially men who have sex with men (MSM).^3,4 Anal and penile human papillomavirus (HPV) infection and HPV-associated anal carcinoma risk are increased in MSM.^5,6 The literature has remained inconclusive on the use of anal Papanicolaou tests for diagnosis; however, dermatologists have a duty to at least examine the perianal and genital area of any patient at risk for HPV-related disease or STIs.^7,8 For younger patients, the HPV vaccine can help prevent certain types of HPV infection and likely reduce a patient’s risk for condyloma acuminatum and other sequelae of the virus. Guidelines have been expanded to include men aged 13 to 21 years and up to 26 years.⁹ More research is needed to determine if detection and prevention of these types of HPV infection using the vaccine in MSM actually leads to a decreased incidence of anal carcinoma.

Certain LGBT groups may benefit from a dermatologist’s care outside the realm of infectious diseases. One study found that increased indoor tanning use in MSM correlated with increased risk for nonmelanoma skin cancer.¹⁰ Lesbians have been found to be less likely to pursue preventative health examinations in general, including skin checks.¹¹ Finally, transgender patients can utilize dermatologists for help with transformative procedures and side effects of hormonal treatment such as androgenic acne.^1,4

Cutaneous and beyond, the future of LGBT health care in the United States is affected by the institutions that train future physicians. There is a trend toward incorporating formal LGBT curricula into medical schools and academic centers.¹² The Penn Medicine Program for LGBT Health (Philadelphia, Pennsylvania) is a pilot program geared toward both educating future clinicians and providing equal and unbiased care to LGBT patients.¹² Programs such as this one give rise to a new generation of physicians who feel comfortable and aware of the needs of their LGBT patients.

In a time when LGBT patients are becoming more comfortable claiming their sexual and gender identities openly, there is a need for dermatologists to provide individualized unbiased care, which can best be achieved by building rapport through assumption-free history taking, performing thorough physical examinations that include the genital and perianal area, and passing these good practices on to trainees.

Paraneoplastic palmoplantar keratoderma (PPK) is an acquired dermatosis that presents with hyperkeratosis of the palms and soles in association with visceral malignancies, such as esophageal, gastric, pulmonary, and bladder carcinomas. This condition may either be acquired or inherited.¹

Case Report

A 72-year-old woman was referred to our dermatology clinic for evaluation of a nonpruritic hyperkeratotic eruption predominantly on the palms and soles of 2 to 3 months’ duration (Figure 1A). Review of systems was remarkable for chronic anxiety, unintentional weight loss of 10 lb over the last 6 months, and a mild cough of 10 days’ duration. The differential diagnosis included eczematous dermatitis, tinea manuum, new-onset palmoplantar psoriasis, and PPK.

A punch biopsy of the medial hypothenar eminence of the left hand was performed, revealing notable lichenified hyperkeratosis with vascular ectasia (Figure 2). Periodic acid–Schiff staining was negative for fungal elements. Given the suspicion of PPK, multiple carcinoma markers were ordered. Cancer antigen 125 measured at 68 U/mL (reference range upper limit, 21 U/mL). Cancer antigen 27-29 was 50 U/mL (reference range, <38 U/mL) and cancer antigen 19-9 was 24 U/mL (reference range, <37 U/mL). Computed tomography of the chest revealed a large mass in the left lower lung associated with hilar lymphadenopathy. The patient was referred to oncology for further evaluation. Computed tomography–guided biopsy revealed metastatic uterine adenocarcinoma, which prompted subsequent chemotherapy. The combination of visceral malignancy with PPK led to the diagnosis of acquired PPK secondary to uterine cancer. After the completion of chemotherapy, the palmar dermatosis notably decreased (Figure 1B).

Comment

Paraneoplastic PPK is not uncommon. Ninety percent of acquired diffuse PPK is secondary to cancer,² which occurs more frequently in male patients. Associated visceral malignancies include localized esophageal,³ myeloma,⁴ pulmonary, urinary/bladder,⁵ and gastric carcinoma.⁶ Paraneoplastic PPK in women is rare but has been linked to ovarian and breast carcinoma.⁷

The findings under light microscopy include thickening of any or all of the cell layers of the epidermis, which can include hyperkeratosis, acanthosis, and papillomatosis (Figure 2). A moderate amount of mononuclear cell infiltrates also can be visualized.

Palmoplantar keratoderma associated with uterine malignancy is rare. However, many other paraneoplastic dermatoses resulting from uterine cancer have been described as well as nonuterine gynecological malignancies (Table).^8-17

The first step in managing acquired PPK is to determine its etiology via a complete history and a total-body skin examination. If findings are consistent with a hereditary PPK, then genetic workup is advised. Other suspected etiologies should be investigated via imaging and laboratory analysis.¹⁸

The first approach in managing acquired PPK is to treat the underlying cause. In prior cases, complete resolution of skin findings resulted once the malignancy or associated dermatosis had been treated.^8-17 Adjunctive medication includes topical keratolytics (eg, urea, salicylic acid, lactic acid), topical retinoids, topical psoralen plus UVA, and topical corticosteroids.¹⁸ Vitamin A analogues have been found to be an effective treatment of many hyperkeratotic dermatoses.¹⁹ Isotretinoin and etretinate have been used to treat the cutaneous findings and prevent the onset and progression of esophageal malignancy of the inherited forms of PPK. The oral retinoid acitretin has been shown to rapidly resolve lesions, have persistent effects after 5 months of cessation, and have minimal side effects. Thus, it has been suggested as the first-line treatment of chronic PPK.¹⁹ One study found no response to topical keratolytics (urea cream and salicylic acid ointment) and a 2-week course of oral prednisone; however, low-dose oral acitretin 10 mg once daily resulted in notable improvement over several weeks.⁷ Physical debridement also may be necessary.¹⁸

Conclusion

Palmoplantar keratoderma is a condition that presents with hyperkeratosis of the palms and soles. Acquired PPK often occurs as a paraneoplastic response as well as a stigma of other dermatoses. It occurs more frequently in male patients. Reports of PPK secondary to uterine cancer are not common in the literature. Management of PPK includes a complete history and total-body skin examination. After appropriate imaging and laboratory analysis, treatment of the underlying cause is the best approach. Adjunctive medications include topical keratolytics, topical retinoids, topical psoralen plus UVA, and topical corticosteroids. Oral isotretinoin and etretinate have demonstrated promising results.

Paraneoplastic palmoplantar keratoderma (PPK) is an acquired dermatosis that presents with hyperkeratosis of the palms and soles in association with visceral malignancies, such as esophageal, gastric, pulmonary, and bladder carcinomas. This condition may either be acquired or inherited.¹

Case Report

A 72-year-old woman was referred to our dermatology clinic for evaluation of a nonpruritic hyperkeratotic eruption predominantly on the palms and soles of 2 to 3 months’ duration (Figure 1A). Review of systems was remarkable for chronic anxiety, unintentional weight loss of 10 lb over the last 6 months, and a mild cough of 10 days’ duration. The differential diagnosis included eczematous dermatitis, tinea manuum, new-onset palmoplantar psoriasis, and PPK.

A punch biopsy of the medial hypothenar eminence of the left hand was performed, revealing notable lichenified hyperkeratosis with vascular ectasia (Figure 2). Periodic acid–Schiff staining was negative for fungal elements. Given the suspicion of PPK, multiple carcinoma markers were ordered. Cancer antigen 125 measured at 68 U/mL (reference range upper limit, 21 U/mL). Cancer antigen 27-29 was 50 U/mL (reference range, <38 U/mL) and cancer antigen 19-9 was 24 U/mL (reference range, <37 U/mL). Computed tomography of the chest revealed a large mass in the left lower lung associated with hilar lymphadenopathy. The patient was referred to oncology for further evaluation. Computed tomography–guided biopsy revealed metastatic uterine adenocarcinoma, which prompted subsequent chemotherapy. The combination of visceral malignancy with PPK led to the diagnosis of acquired PPK secondary to uterine cancer. After the completion of chemotherapy, the palmar dermatosis notably decreased (Figure 1B).

Comment

Paraneoplastic PPK is not uncommon. Ninety percent of acquired diffuse PPK is secondary to cancer,² which occurs more frequently in male patients. Associated visceral malignancies include localized esophageal,³ myeloma,⁴ pulmonary, urinary/bladder,⁵ and gastric carcinoma.⁶ Paraneoplastic PPK in women is rare but has been linked to ovarian and breast carcinoma.⁷

The findings under light microscopy include thickening of any or all of the cell layers of the epidermis, which can include hyperkeratosis, acanthosis, and papillomatosis (Figure 2). A moderate amount of mononuclear cell infiltrates also can be visualized.

Palmoplantar keratoderma associated with uterine malignancy is rare. However, many other paraneoplastic dermatoses resulting from uterine cancer have been described as well as nonuterine gynecological malignancies (Table).^8-17

The first step in managing acquired PPK is to determine its etiology via a complete history and a total-body skin examination. If findings are consistent with a hereditary PPK, then genetic workup is advised. Other suspected etiologies should be investigated via imaging and laboratory analysis.¹⁸

The first approach in managing acquired PPK is to treat the underlying cause. In prior cases, complete resolution of skin findings resulted once the malignancy or associated dermatosis had been treated.^8-17 Adjunctive medication includes topical keratolytics (eg, urea, salicylic acid, lactic acid), topical retinoids, topical psoralen plus UVA, and topical corticosteroids.¹⁸ Vitamin A analogues have been found to be an effective treatment of many hyperkeratotic dermatoses.¹⁹ Isotretinoin and etretinate have been used to treat the cutaneous findings and prevent the onset and progression of esophageal malignancy of the inherited forms of PPK. The oral retinoid acitretin has been shown to rapidly resolve lesions, have persistent effects after 5 months of cessation, and have minimal side effects. Thus, it has been suggested as the first-line treatment of chronic PPK.¹⁹ One study found no response to topical keratolytics (urea cream and salicylic acid ointment) and a 2-week course of oral prednisone; however, low-dose oral acitretin 10 mg once daily resulted in notable improvement over several weeks.⁷ Physical debridement also may be necessary.¹⁸

Conclusion

Palmoplantar keratoderma is a condition that presents with hyperkeratosis of the palms and soles. Acquired PPK often occurs as a paraneoplastic response as well as a stigma of other dermatoses. It occurs more frequently in male patients. Reports of PPK secondary to uterine cancer are not common in the literature. Management of PPK includes a complete history and total-body skin examination. After appropriate imaging and laboratory analysis, treatment of the underlying cause is the best approach. Adjunctive medications include topical keratolytics, topical retinoids, topical psoralen plus UVA, and topical corticosteroids. Oral isotretinoin and etretinate have demonstrated promising results.

Paraneoplastic palmoplantar keratoderma (PPK) is an acquired dermatosis that presents with hyperkeratosis of the palms and soles in association with visceral malignancies, such as esophageal, gastric, pulmonary, and bladder carcinomas. This condition may either be acquired or inherited.¹

Case Report

A 72-year-old woman was referred to our dermatology clinic for evaluation of a nonpruritic hyperkeratotic eruption predominantly on the palms and soles of 2 to 3 months’ duration (Figure 1A). Review of systems was remarkable for chronic anxiety, unintentional weight loss of 10 lb over the last 6 months, and a mild cough of 10 days’ duration. The differential diagnosis included eczematous dermatitis, tinea manuum, new-onset palmoplantar psoriasis, and PPK.

A punch biopsy of the medial hypothenar eminence of the left hand was performed, revealing notable lichenified hyperkeratosis with vascular ectasia (Figure 2). Periodic acid–Schiff staining was negative for fungal elements. Given the suspicion of PPK, multiple carcinoma markers were ordered. Cancer antigen 125 measured at 68 U/mL (reference range upper limit, 21 U/mL). Cancer antigen 27-29 was 50 U/mL (reference range, <38 U/mL) and cancer antigen 19-9 was 24 U/mL (reference range, <37 U/mL). Computed tomography of the chest revealed a large mass in the left lower lung associated with hilar lymphadenopathy. The patient was referred to oncology for further evaluation. Computed tomography–guided biopsy revealed metastatic uterine adenocarcinoma, which prompted subsequent chemotherapy. The combination of visceral malignancy with PPK led to the diagnosis of acquired PPK secondary to uterine cancer. After the completion of chemotherapy, the palmar dermatosis notably decreased (Figure 1B).

Comment

Paraneoplastic PPK is not uncommon. Ninety percent of acquired diffuse PPK is secondary to cancer,² which occurs more frequently in male patients. Associated visceral malignancies include localized esophageal,³ myeloma,⁴ pulmonary, urinary/bladder,⁵ and gastric carcinoma.⁶ Paraneoplastic PPK in women is rare but has been linked to ovarian and breast carcinoma.⁷

The findings under light microscopy include thickening of any or all of the cell layers of the epidermis, which can include hyperkeratosis, acanthosis, and papillomatosis (Figure 2). A moderate amount of mononuclear cell infiltrates also can be visualized.

Palmoplantar keratoderma associated with uterine malignancy is rare. However, many other paraneoplastic dermatoses resulting from uterine cancer have been described as well as nonuterine gynecological malignancies (Table).^8-17

The first step in managing acquired PPK is to determine its etiology via a complete history and a total-body skin examination. If findings are consistent with a hereditary PPK, then genetic workup is advised. Other suspected etiologies should be investigated via imaging and laboratory analysis.¹⁸

The first approach in managing acquired PPK is to treat the underlying cause. In prior cases, complete resolution of skin findings resulted once the malignancy or associated dermatosis had been treated.^8-17 Adjunctive medication includes topical keratolytics (eg, urea, salicylic acid, lactic acid), topical retinoids, topical psoralen plus UVA, and topical corticosteroids.¹⁸ Vitamin A analogues have been found to be an effective treatment of many hyperkeratotic dermatoses.¹⁹ Isotretinoin and etretinate have been used to treat the cutaneous findings and prevent the onset and progression of esophageal malignancy of the inherited forms of PPK. The oral retinoid acitretin has been shown to rapidly resolve lesions, have persistent effects after 5 months of cessation, and have minimal side effects. Thus, it has been suggested as the first-line treatment of chronic PPK.¹⁹ One study found no response to topical keratolytics (urea cream and salicylic acid ointment) and a 2-week course of oral prednisone; however, low-dose oral acitretin 10 mg once daily resulted in notable improvement over several weeks.⁷ Physical debridement also may be necessary.¹⁸

Conclusion

Palmoplantar keratoderma is a condition that presents with hyperkeratosis of the palms and soles. Acquired PPK often occurs as a paraneoplastic response as well as a stigma of other dermatoses. It occurs more frequently in male patients. Reports of PPK secondary to uterine cancer are not common in the literature. Management of PPK includes a complete history and total-body skin examination. After appropriate imaging and laboratory analysis, treatment of the underlying cause is the best approach. Adjunctive medications include topical keratolytics, topical retinoids, topical psoralen plus UVA, and topical corticosteroids. Oral isotretinoin and etretinate have demonstrated promising results.

[polldaddy:9711250]

[polldaddy:9711250]

[polldaddy:9711250]