AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

New Codes for 2016

In 2016, noninvasive imaging in dermatology finally received recognition at the Current Procedural Terminology (CPT) level with the publication of 6 new Category I codes for reflectance confocal microscopy.¹ These new codes are classified under the “Special Dermatological Procedures” section of CPT where codes do not have technical and professional payment splits, unlike pathology codes (Table). Currently, the new codes for reflectance confocal microscopy can only be implemented when using the VivaScope 1500 (Caliber I.D.) reflectance confocal imaging system and not with any other devices. At present, these codes are priced by each insurer and should be payable, as they are Category I codes that meet all criteria for widely used procedures that are well supported by strong evidence.

Additionally, MelaFind (MELA Sciences) has received 2 Category III CPT codes in 2016: 0400T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [1–5 lesions]; 0401T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [≥6 lesions]).

The CPT Professional Edition notes that Category III codes are a set of temporary codes for emerging technology, services, and procedures that allow data collection for these services and procedures.¹ Inclusion implies nothing about safety, efficacy, frequency of use, or payment. These codes are used to differentiate emerging technology from the widely accepted Category I codes and use of alphanumeric characters instead of 5-digit codes. If reading this paragraph makes you giddy all over, pay a visit to the American Medical Association website to learn more about the process by which CPT codes come to life.²

Policy and Coding Changes

Last year saw much sturm and drang with the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).³ The MACRA repealed the Sustainable Growth Rate formula and established annual positive or flat-fee updates for 10 years. A 2-tracked fee update was instituted afterward. It also established the Merit-Based Incentive Payment System, which consolidates existing Medicare fee-for-service physician incentive programs, establishes a pathway for physicians to participate in alternative payment models including the patient-centered medical home, and makes a bunch of other changes to existing Medicare physician payment statutes. It is too early to say if and how it will work and if it will change dermatology. It could fail miserably or it could be a brave new world; stay tuned.³

On the coding front, MACRA prohibits across-the-board elimination of global periods that the Centers for Medicare & Medicaid Services (CMS) had previously announced.⁴ Instead, the CMS must develop and implement a process to gather data on services furnished during global periods based on a representative sample of physician data. The CMS can delay up to 5% of payments if it does not get the data it asks for and must work through the rulemaking process, which will impact medicine in 2019. Among our codes with nonzero global periods, the premalignant destruction codes 17000 and 17004, each of which contains the value of a 99212 established patient visit, are at the very apex of the hit list. It is not clear if the CMS will retrospectively pull medical records to evaluate the occurrence of the global visit or will prospectively have us use 99024, the code for a “[p]ostoperative follow-up visit, normally included in the surgical package, to indicate that an evaluation and management service was performed during a postoperative period for a reason(s) related to the original procedure.”¹ This code is not used unless your practice needs a “filler” code for nonreportable visits but that may change. Is this another unfunded mandate? Yes.

Clarifications also have been made for reporting superficial radiation therapy.¹ Treatment delivery using energies below 1 MV are to be reported with CPT code 77401 and cannot be combined with radiation treatment delivery codes (77402, 77407, 77412), clinical treatment planning codes (77261–77263), treatment device development codes (77332–77334), isodose planning codes (77306, 77307, 77316–77318), radiation treatment management codes (77427, 77431, 77432, 77435, 77469, 77470, 77499), continuing medical physics consultation code (77336), and special physics consultation code (77370). Evaluation and management services may still be reported separately, when appropriate, in cases in which only superficial radiation therapy services (ie, 77401) are provided.¹

Electronic brachytherapy for skin cancer has a new Category III tracking code (0394T [high-dose-rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed]) that is priced by the insurer. Noridian Healthcare Solutions pulled the plug on what many perceived as astronomical payments, but changes may be afoot, as its URL for their new policy was down at the time of publication, and there is still great variability in how payment is being made for these codes. For those interested in learning about perception, a visit to http://forums.studentdoctor.net/threads/electronic-brachy.1132531/ is in order, as the economic drivers to the utilization of this therapy are discussed in detail from the perspective of students and young physicians.

Although there are new telehealth codes for inpatient services and end-stage renal disease management, there are still none that are relevant to dermatology.

Place of service codes have been updated. Place of service code 19 refers to “off campus outpatient hospital” settings while place of service code 22 has been revised to “on campus outpatient hospital.” If your practice is a facility, consult the Medicare Claims Processing Manual (20.4.2) on the site of service payment differential for further enlightenment.⁵ Do note that CMS is increasingly interested in physicians who use wrong place of service codes.

Incident to billing rules are somewhat clearer. The physician or other practitioner who bills must be the supervising physician or practitioner. Services cannot be provided by individuals who have been excluded from Medicare, Medicaid, or other federal programs, nor can they be provided by an individual who has had Medicare enrollment revoked. State laws that are more restrictive take precedence.

Of course, the Relative Value Scale Update Committee (RUC) process moves on as always and you likely will receive 1 or more surveys in the near future. If you get one of these surveys, do not delete it. The surveys are the currency of the RUC, and if you give your RUC team bad or no data, the specialty will suffer cuts in valuation of what we do. If you have questions about the survey, contact the American Academy of Dermatology staff as listed in the survey. If you want to learn more about RUC, visit the American Medical Association website.⁶ To see the current relative value units for what dermatologists do and the typical time for these procedures, visit the CMS website, which provides resources that supply tremendous amounts of data on code valuation including documents detailing relative value units for every CPT code.⁷ You also can access current time values for preservice work, intraservice work, and postservice work times for all CPT codes in the entire CPT Professional Edition. They are based on typical times and are the major determinants of what you get paid. Happy reading.

New Codes for 2016

In 2016, noninvasive imaging in dermatology finally received recognition at the Current Procedural Terminology (CPT) level with the publication of 6 new Category I codes for reflectance confocal microscopy.¹ These new codes are classified under the “Special Dermatological Procedures” section of CPT where codes do not have technical and professional payment splits, unlike pathology codes (Table). Currently, the new codes for reflectance confocal microscopy can only be implemented when using the VivaScope 1500 (Caliber I.D.) reflectance confocal imaging system and not with any other devices. At present, these codes are priced by each insurer and should be payable, as they are Category I codes that meet all criteria for widely used procedures that are well supported by strong evidence.

Additionally, MelaFind (MELA Sciences) has received 2 Category III CPT codes in 2016: 0400T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [1–5 lesions]; 0401T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [≥6 lesions]).

The CPT Professional Edition notes that Category III codes are a set of temporary codes for emerging technology, services, and procedures that allow data collection for these services and procedures.¹ Inclusion implies nothing about safety, efficacy, frequency of use, or payment. These codes are used to differentiate emerging technology from the widely accepted Category I codes and use of alphanumeric characters instead of 5-digit codes. If reading this paragraph makes you giddy all over, pay a visit to the American Medical Association website to learn more about the process by which CPT codes come to life.²

Policy and Coding Changes

Last year saw much sturm and drang with the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).³ The MACRA repealed the Sustainable Growth Rate formula and established annual positive or flat-fee updates for 10 years. A 2-tracked fee update was instituted afterward. It also established the Merit-Based Incentive Payment System, which consolidates existing Medicare fee-for-service physician incentive programs, establishes a pathway for physicians to participate in alternative payment models including the patient-centered medical home, and makes a bunch of other changes to existing Medicare physician payment statutes. It is too early to say if and how it will work and if it will change dermatology. It could fail miserably or it could be a brave new world; stay tuned.³

On the coding front, MACRA prohibits across-the-board elimination of global periods that the Centers for Medicare & Medicaid Services (CMS) had previously announced.⁴ Instead, the CMS must develop and implement a process to gather data on services furnished during global periods based on a representative sample of physician data. The CMS can delay up to 5% of payments if it does not get the data it asks for and must work through the rulemaking process, which will impact medicine in 2019. Among our codes with nonzero global periods, the premalignant destruction codes 17000 and 17004, each of which contains the value of a 99212 established patient visit, are at the very apex of the hit list. It is not clear if the CMS will retrospectively pull medical records to evaluate the occurrence of the global visit or will prospectively have us use 99024, the code for a “[p]ostoperative follow-up visit, normally included in the surgical package, to indicate that an evaluation and management service was performed during a postoperative period for a reason(s) related to the original procedure.”¹ This code is not used unless your practice needs a “filler” code for nonreportable visits but that may change. Is this another unfunded mandate? Yes.

Clarifications also have been made for reporting superficial radiation therapy.¹ Treatment delivery using energies below 1 MV are to be reported with CPT code 77401 and cannot be combined with radiation treatment delivery codes (77402, 77407, 77412), clinical treatment planning codes (77261–77263), treatment device development codes (77332–77334), isodose planning codes (77306, 77307, 77316–77318), radiation treatment management codes (77427, 77431, 77432, 77435, 77469, 77470, 77499), continuing medical physics consultation code (77336), and special physics consultation code (77370). Evaluation and management services may still be reported separately, when appropriate, in cases in which only superficial radiation therapy services (ie, 77401) are provided.¹

Electronic brachytherapy for skin cancer has a new Category III tracking code (0394T [high-dose-rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed]) that is priced by the insurer. Noridian Healthcare Solutions pulled the plug on what many perceived as astronomical payments, but changes may be afoot, as its URL for their new policy was down at the time of publication, and there is still great variability in how payment is being made for these codes. For those interested in learning about perception, a visit to http://forums.studentdoctor.net/threads/electronic-brachy.1132531/ is in order, as the economic drivers to the utilization of this therapy are discussed in detail from the perspective of students and young physicians.

Although there are new telehealth codes for inpatient services and end-stage renal disease management, there are still none that are relevant to dermatology.

Place of service codes have been updated. Place of service code 19 refers to “off campus outpatient hospital” settings while place of service code 22 has been revised to “on campus outpatient hospital.” If your practice is a facility, consult the Medicare Claims Processing Manual (20.4.2) on the site of service payment differential for further enlightenment.⁵ Do note that CMS is increasingly interested in physicians who use wrong place of service codes.

Incident to billing rules are somewhat clearer. The physician or other practitioner who bills must be the supervising physician or practitioner. Services cannot be provided by individuals who have been excluded from Medicare, Medicaid, or other federal programs, nor can they be provided by an individual who has had Medicare enrollment revoked. State laws that are more restrictive take precedence.

Of course, the Relative Value Scale Update Committee (RUC) process moves on as always and you likely will receive 1 or more surveys in the near future. If you get one of these surveys, do not delete it. The surveys are the currency of the RUC, and if you give your RUC team bad or no data, the specialty will suffer cuts in valuation of what we do. If you have questions about the survey, contact the American Academy of Dermatology staff as listed in the survey. If you want to learn more about RUC, visit the American Medical Association website.⁶ To see the current relative value units for what dermatologists do and the typical time for these procedures, visit the CMS website, which provides resources that supply tremendous amounts of data on code valuation including documents detailing relative value units for every CPT code.⁷ You also can access current time values for preservice work, intraservice work, and postservice work times for all CPT codes in the entire CPT Professional Edition. They are based on typical times and are the major determinants of what you get paid. Happy reading.

New Codes for 2016

In 2016, noninvasive imaging in dermatology finally received recognition at the Current Procedural Terminology (CPT) level with the publication of 6 new Category I codes for reflectance confocal microscopy.¹ These new codes are classified under the “Special Dermatological Procedures” section of CPT where codes do not have technical and professional payment splits, unlike pathology codes (Table). Currently, the new codes for reflectance confocal microscopy can only be implemented when using the VivaScope 1500 (Caliber I.D.) reflectance confocal imaging system and not with any other devices. At present, these codes are priced by each insurer and should be payable, as they are Category I codes that meet all criteria for widely used procedures that are well supported by strong evidence.

Additionally, MelaFind (MELA Sciences) has received 2 Category III CPT codes in 2016: 0400T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [1–5 lesions]; 0401T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [≥6 lesions]).

The CPT Professional Edition notes that Category III codes are a set of temporary codes for emerging technology, services, and procedures that allow data collection for these services and procedures.¹ Inclusion implies nothing about safety, efficacy, frequency of use, or payment. These codes are used to differentiate emerging technology from the widely accepted Category I codes and use of alphanumeric characters instead of 5-digit codes. If reading this paragraph makes you giddy all over, pay a visit to the American Medical Association website to learn more about the process by which CPT codes come to life.²

Policy and Coding Changes

Last year saw much sturm and drang with the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).³ The MACRA repealed the Sustainable Growth Rate formula and established annual positive or flat-fee updates for 10 years. A 2-tracked fee update was instituted afterward. It also established the Merit-Based Incentive Payment System, which consolidates existing Medicare fee-for-service physician incentive programs, establishes a pathway for physicians to participate in alternative payment models including the patient-centered medical home, and makes a bunch of other changes to existing Medicare physician payment statutes. It is too early to say if and how it will work and if it will change dermatology. It could fail miserably or it could be a brave new world; stay tuned.³

On the coding front, MACRA prohibits across-the-board elimination of global periods that the Centers for Medicare & Medicaid Services (CMS) had previously announced.⁴ Instead, the CMS must develop and implement a process to gather data on services furnished during global periods based on a representative sample of physician data. The CMS can delay up to 5% of payments if it does not get the data it asks for and must work through the rulemaking process, which will impact medicine in 2019. Among our codes with nonzero global periods, the premalignant destruction codes 17000 and 17004, each of which contains the value of a 99212 established patient visit, are at the very apex of the hit list. It is not clear if the CMS will retrospectively pull medical records to evaluate the occurrence of the global visit or will prospectively have us use 99024, the code for a “[p]ostoperative follow-up visit, normally included in the surgical package, to indicate that an evaluation and management service was performed during a postoperative period for a reason(s) related to the original procedure.”¹ This code is not used unless your practice needs a “filler” code for nonreportable visits but that may change. Is this another unfunded mandate? Yes.

Clarifications also have been made for reporting superficial radiation therapy.¹ Treatment delivery using energies below 1 MV are to be reported with CPT code 77401 and cannot be combined with radiation treatment delivery codes (77402, 77407, 77412), clinical treatment planning codes (77261–77263), treatment device development codes (77332–77334), isodose planning codes (77306, 77307, 77316–77318), radiation treatment management codes (77427, 77431, 77432, 77435, 77469, 77470, 77499), continuing medical physics consultation code (77336), and special physics consultation code (77370). Evaluation and management services may still be reported separately, when appropriate, in cases in which only superficial radiation therapy services (ie, 77401) are provided.¹

Electronic brachytherapy for skin cancer has a new Category III tracking code (0394T [high-dose-rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed]) that is priced by the insurer. Noridian Healthcare Solutions pulled the plug on what many perceived as astronomical payments, but changes may be afoot, as its URL for their new policy was down at the time of publication, and there is still great variability in how payment is being made for these codes. For those interested in learning about perception, a visit to http://forums.studentdoctor.net/threads/electronic-brachy.1132531/ is in order, as the economic drivers to the utilization of this therapy are discussed in detail from the perspective of students and young physicians.

Although there are new telehealth codes for inpatient services and end-stage renal disease management, there are still none that are relevant to dermatology.

Place of service codes have been updated. Place of service code 19 refers to “off campus outpatient hospital” settings while place of service code 22 has been revised to “on campus outpatient hospital.” If your practice is a facility, consult the Medicare Claims Processing Manual (20.4.2) on the site of service payment differential for further enlightenment.⁵ Do note that CMS is increasingly interested in physicians who use wrong place of service codes.

Incident to billing rules are somewhat clearer. The physician or other practitioner who bills must be the supervising physician or practitioner. Services cannot be provided by individuals who have been excluded from Medicare, Medicaid, or other federal programs, nor can they be provided by an individual who has had Medicare enrollment revoked. State laws that are more restrictive take precedence.

Of course, the Relative Value Scale Update Committee (RUC) process moves on as always and you likely will receive 1 or more surveys in the near future. If you get one of these surveys, do not delete it. The surveys are the currency of the RUC, and if you give your RUC team bad or no data, the specialty will suffer cuts in valuation of what we do. If you have questions about the survey, contact the American Academy of Dermatology staff as listed in the survey. If you want to learn more about RUC, visit the American Medical Association website.⁶ To see the current relative value units for what dermatologists do and the typical time for these procedures, visit the CMS website, which provides resources that supply tremendous amounts of data on code valuation including documents detailing relative value units for every CPT code.⁷ You also can access current time values for preservice work, intraservice work, and postservice work times for all CPT codes in the entire CPT Professional Edition. They are based on typical times and are the major determinants of what you get paid. Happy reading.

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have jointly released evidence-based guidelines for implementing an inpatient antibiotic stewardship program.

The guidelines, published April 13 online in Clinical Infectious Diseases, address the optimal use of antibiotics in inpatient populations, and were prepared by a multidisciplinary expert panel of the IDSA and the SHEA, which included representation from the specialties of internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases.

Antibiotic stewardship has been defined by IDSA, SHEA, and the Pediatric Infectious Diseases Society as “coordinated interventions designed to improve and measure the appropriate use of [antibiotic] agents by promoting the selection of the optimal [antibiotic] drug regimen including dosing, duration of therapy, and route of administration.” The new guidelines discuss a broad range of possible interventions, but the authors emphasize the need “for each site to assess its clinical needs and available resources and individualize its [antibiotic stewardship program] with that assessment in mind.”

The process used in the development of the guidelines included a systematic weighting of the strength of recommendation and quality of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system, according to Dr. Tamar F. Barlam of the section of infectious diseases at Boston University, and her colleagues.

“The benefits of antibiotic stewardship include improved patient outcomes, reduced adverse events including Clostridium difficile infection, improvement in rates of antibiotic susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care,” Dr. Barlam and her coauthors wrote.

A complete list of any potential conflicts of interest for the multiple coauthors is provided with the full stewardship guidelines, which can be reviewed in Clinical Infectious Diseases (doi: 10.1093/cid/ciw118).

[email protected]

On Twitter @richpizzi

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have jointly released evidence-based guidelines for implementing an inpatient antibiotic stewardship program.

The guidelines, published April 13 online in Clinical Infectious Diseases, address the optimal use of antibiotics in inpatient populations, and were prepared by a multidisciplinary expert panel of the IDSA and the SHEA, which included representation from the specialties of internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases.

Antibiotic stewardship has been defined by IDSA, SHEA, and the Pediatric Infectious Diseases Society as “coordinated interventions designed to improve and measure the appropriate use of [antibiotic] agents by promoting the selection of the optimal [antibiotic] drug regimen including dosing, duration of therapy, and route of administration.” The new guidelines discuss a broad range of possible interventions, but the authors emphasize the need “for each site to assess its clinical needs and available resources and individualize its [antibiotic stewardship program] with that assessment in mind.”

The process used in the development of the guidelines included a systematic weighting of the strength of recommendation and quality of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system, according to Dr. Tamar F. Barlam of the section of infectious diseases at Boston University, and her colleagues.

“The benefits of antibiotic stewardship include improved patient outcomes, reduced adverse events including Clostridium difficile infection, improvement in rates of antibiotic susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care,” Dr. Barlam and her coauthors wrote.

A complete list of any potential conflicts of interest for the multiple coauthors is provided with the full stewardship guidelines, which can be reviewed in Clinical Infectious Diseases (doi: 10.1093/cid/ciw118).

[email protected]

On Twitter @richpizzi

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have jointly released evidence-based guidelines for implementing an inpatient antibiotic stewardship program.

The guidelines, published April 13 online in Clinical Infectious Diseases, address the optimal use of antibiotics in inpatient populations, and were prepared by a multidisciplinary expert panel of the IDSA and the SHEA, which included representation from the specialties of internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases.

Antibiotic stewardship has been defined by IDSA, SHEA, and the Pediatric Infectious Diseases Society as “coordinated interventions designed to improve and measure the appropriate use of [antibiotic] agents by promoting the selection of the optimal [antibiotic] drug regimen including dosing, duration of therapy, and route of administration.” The new guidelines discuss a broad range of possible interventions, but the authors emphasize the need “for each site to assess its clinical needs and available resources and individualize its [antibiotic stewardship program] with that assessment in mind.”

The process used in the development of the guidelines included a systematic weighting of the strength of recommendation and quality of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system, according to Dr. Tamar F. Barlam of the section of infectious diseases at Boston University, and her colleagues.

“The benefits of antibiotic stewardship include improved patient outcomes, reduced adverse events including Clostridium difficile infection, improvement in rates of antibiotic susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care,” Dr. Barlam and her coauthors wrote.

A complete list of any potential conflicts of interest for the multiple coauthors is provided with the full stewardship guidelines, which can be reviewed in Clinical Infectious Diseases (doi: 10.1093/cid/ciw118).

[email protected]

On Twitter @richpizzi

Patients with severe psoriasis were nearly 70% more likely to develop abdominal aortic aneurysms compared with the general population, according to a Danish population-based cohort study.

The findings augment existing evidence linking psoriasis and cardiovascular diseases, wrote Dr. Usman Khalid of Copenhagen University Herlev and Gentofte Hospital, Denmark. The report was published online April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology.

While the mechanisms for the link are unclear, “emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” wrote Dr. Khalid and his associates.

Several case series have linked AAA with other autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, they noted. Their study comprised nearly 5.5 million adults in Denmark between 1997 and 2011. The researchers identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis (Arterioscler Thromb Vasc Biol. 2016 April 14. doi: 10.1161/ATVBAHA.116.307449).

The incidence of AAA in the reference population was 3.72 cases per 10,000 person-years, with an average follow-up period of 14.4 years. In contrast, the incidence of AAA in patients with mild psoriasis was 7.30 cases per 10,000 person-years, and the rate in patients with severe psoriasis was 9.87 cases of per 10,000 person-years, with average follow-up periods of 5.7 years. Both mild and severe psoriasis were significantly associated with AAA after the researchers accounted for age, sex, comorbidities, medications, socioeconomic status, and smoking, with adjusted incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32), respectively.

The historical view that AAA is caused mainly by atherosclerosis has largely been upended, the researchers noted. Instead, AAA appears to be a multifactorial process involving inflammation, matrix degradation, thrombosis, and aortic wall stress. Furthermore, inflammation in both AAA and psoriasis is centrally mediated by T-helper-17 cells and interleukin-17. Together, the data suggest that shared inflammatory mechanisms link psoriasis and AAA, especially because the association correlates with psoriatic disease activity, they said. “This finding clearly requires independent replication, and the clinical consequences are unclear at present.”

The LEO Foundation and the Novo Nordisk Foundation funded the study. Dr. Khalid had no disclosures. Four coinvestigators reported financial ties with Abbott, Pfizer, AstraZeneca, Bayer, and several other pharmaceutical companies.

Patients with severe psoriasis were nearly 70% more likely to develop abdominal aortic aneurysms compared with the general population, according to a Danish population-based cohort study.

The findings augment existing evidence linking psoriasis and cardiovascular diseases, wrote Dr. Usman Khalid of Copenhagen University Herlev and Gentofte Hospital, Denmark. The report was published online April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology.

While the mechanisms for the link are unclear, “emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” wrote Dr. Khalid and his associates.

Several case series have linked AAA with other autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, they noted. Their study comprised nearly 5.5 million adults in Denmark between 1997 and 2011. The researchers identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis (Arterioscler Thromb Vasc Biol. 2016 April 14. doi: 10.1161/ATVBAHA.116.307449).

The incidence of AAA in the reference population was 3.72 cases per 10,000 person-years, with an average follow-up period of 14.4 years. In contrast, the incidence of AAA in patients with mild psoriasis was 7.30 cases per 10,000 person-years, and the rate in patients with severe psoriasis was 9.87 cases of per 10,000 person-years, with average follow-up periods of 5.7 years. Both mild and severe psoriasis were significantly associated with AAA after the researchers accounted for age, sex, comorbidities, medications, socioeconomic status, and smoking, with adjusted incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32), respectively.

The historical view that AAA is caused mainly by atherosclerosis has largely been upended, the researchers noted. Instead, AAA appears to be a multifactorial process involving inflammation, matrix degradation, thrombosis, and aortic wall stress. Furthermore, inflammation in both AAA and psoriasis is centrally mediated by T-helper-17 cells and interleukin-17. Together, the data suggest that shared inflammatory mechanisms link psoriasis and AAA, especially because the association correlates with psoriatic disease activity, they said. “This finding clearly requires independent replication, and the clinical consequences are unclear at present.”

The LEO Foundation and the Novo Nordisk Foundation funded the study. Dr. Khalid had no disclosures. Four coinvestigators reported financial ties with Abbott, Pfizer, AstraZeneca, Bayer, and several other pharmaceutical companies.

Patients with severe psoriasis were nearly 70% more likely to develop abdominal aortic aneurysms compared with the general population, according to a Danish population-based cohort study.

The findings augment existing evidence linking psoriasis and cardiovascular diseases, wrote Dr. Usman Khalid of Copenhagen University Herlev and Gentofte Hospital, Denmark. The report was published online April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology.

While the mechanisms for the link are unclear, “emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” wrote Dr. Khalid and his associates.

Several case series have linked AAA with other autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, they noted. Their study comprised nearly 5.5 million adults in Denmark between 1997 and 2011. The researchers identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis (Arterioscler Thromb Vasc Biol. 2016 April 14. doi: 10.1161/ATVBAHA.116.307449).

The incidence of AAA in the reference population was 3.72 cases per 10,000 person-years, with an average follow-up period of 14.4 years. In contrast, the incidence of AAA in patients with mild psoriasis was 7.30 cases per 10,000 person-years, and the rate in patients with severe psoriasis was 9.87 cases of per 10,000 person-years, with average follow-up periods of 5.7 years. Both mild and severe psoriasis were significantly associated with AAA after the researchers accounted for age, sex, comorbidities, medications, socioeconomic status, and smoking, with adjusted incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32), respectively.

The historical view that AAA is caused mainly by atherosclerosis has largely been upended, the researchers noted. Instead, AAA appears to be a multifactorial process involving inflammation, matrix degradation, thrombosis, and aortic wall stress. Furthermore, inflammation in both AAA and psoriasis is centrally mediated by T-helper-17 cells and interleukin-17. Together, the data suggest that shared inflammatory mechanisms link psoriasis and AAA, especially because the association correlates with psoriatic disease activity, they said. “This finding clearly requires independent replication, and the clinical consequences are unclear at present.”

The LEO Foundation and the Novo Nordisk Foundation funded the study. Dr. Khalid had no disclosures. Four coinvestigators reported financial ties with Abbott, Pfizer, AstraZeneca, Bayer, and several other pharmaceutical companies.

The best diagnosis is:

a. bronchogenic cyst
b. dermoid cyst
c. epidermal inclusion cyst
d. hidrocystoma
e. steatocystoma

H&E, original magnification ×40.

H&E, original magnification ×100.

Continue to the next page for the diagnosis >>

Dermoid Cyst

Dermoid cysts often present clinically as firm subcutaneous nodules on the head or neck in young children. They tend to arise along the lateral aspect of the eyebrow but also can occur on the nose, forehead, neck, chest, or scalp.¹ Dermoid cysts are thought to arise from the sequestration of ectodermal tissues along the embryonic fusion planes during development.² As such, they represent congenital defects and often are identified at birth; however, some are not noticed until much later when they enlarge or become inflamed or infected. Midline dermoid cysts may be associated with underlying dysraphism or intracranial extension.^3,4 Thus, any midline lesion warrants evaluation that incorporates imaging with computed tomography or magnetic resonance imaging.^4,5 Histologically, dermoid cysts are lined by a keratinizing stratified squamous epithelium (quiz image A), but the lining may be brightly eosinophilic and wavy resembling shark teeth.^1,3 The wall of a dermoid cyst commonly contains mature adnexal structures such as terminal hair follicles, sebaceous glands, apocrine glands, and/or eccrine glands (quiz image B).¹ Smooth muscle also may be seen within the lining; however, bone and cartilage are not commonly reported in dermoid cysts.² Lamellar keratin is typical of the cyst contents, and terminal hair shafts also are sometimes noted within the cystic space (quiz image B).^1,2 Treatment options include excision at the time of diagnosis or close clinical monitoring with subsequent excision if the lesion grows or becomes symptomatic.^4,5 Many practitioners opt to excise these cysts at diagnosis, as untreated lesions are at risk for infection and/or inflammation or may be cosmetically deforming.^6,7 Surgical resection, including removal of the wall of the cyst, is curative and reoccurrence is rare.⁵

Figure 1. Bronchogenic cyst demonstrating a ciliated pseudostratified epithelial lining encircled by smooth muscle (H&E, original magnification ×200).
Figure 2. Epidermal inclusion cyst containing loose lamellar keratin and a lining that closely resembles the surface epidermis (H&E, original magnification ×40).

Bronchogenic cysts demonstrate an epithelial lining that often is pseudostratified cuboidal or columnar as well as ciliated (Figure 1). Goblet cells are present in the lining in approximately 50% of cases. Smooth muscle may be seen circumferentially surrounding the cyst lining, and rare cases also contain cartilage.¹ In contrast to dermoid cysts, other types of adnexal structures are not found within the lining. Bronchogenic cysts that arise in the skin are extremely rare.² These cysts are thought to arise from respiratory epithelium that has been sequestered during embryologic formation of the tracheobronchial tree. They often are seen overlying the suprasternal notch and occasionally are found on the anterior aspect of the neck or chin. These cysts also are present at birth, similar to dermoid cysts.³

Epidermal inclusion cysts have a lining that histologically bears close resemblance to the surface epidermis. These cysts contain loose lamellar keratin, similar to a dermoid cyst. In contrast, the lining of an epidermal inclusion cyst will lack adnexal structures (Figure 2).¹ Clinically, epidermal inclusion cysts often present as smooth, dome-shaped papules and nodules with a central punctum. They are classically found on the face, neck, and trunk. These cysts are thought to arise after a traumatic insult to the pilosebaceous unit.²

Hidrocystomas can be apocrine or eccrine.³ Eccrine hidrocystomas are unilocular cysts that are lined by 2 layers of flattened to cuboidal epithelial cells (Figure 3). The cysts are filled with clear fluid and often are found adjacent to normal eccrine glands.¹ Apocrine hidrocystomas are unilocular or multilocular cysts that are lined by 1 to several layers of epithelial cells. The lining of an apocrine hidrocystoma will often exhibit luminal decapitation secretion.³ Apocrine and eccrine hidrocystomas are clinically identical and appear as blue translucent papules on the cheeks or eyelids of adults.^1-3 They usually occur periorbitally but also can be seen on the trunk, popliteal fossa, external ears, or vulva. Eccrine hidrocystomas can wax and wane in accordance with the amount of sweat produced; thus, they often expand in size during the summer months.²

Steatocystomas, or simple sebaceous duct cysts, histologically demonstrate a characteristically wavy and eosinophilic cuticle resembling shark teeth (Figure 4) similar to the lining of the sebaceous duct where it enters the follicle.¹ Sebaceous glands are an almost invariable feature, either present within the lining of the cyst (Figure 4) or in the adjacent tissue.² In comparison, dermoid cysts may have a red wavy cuticle but also will usually have terminal hair follicles or eccrine or apocrine glands within the wall of the cyst. Steatocystomas typically are collapsed and empty or only contain sebaceous debris (Figure 4) rather than the lamellar keratin seen in dermoid and epidermoid inclusion cysts. Steatocystomas can occur as solitary (steatocystoma simplex) or multiple (steatocystoma multiplex) lesions.^1,3 They are clinically comprised of small dome-shaped papules that often are translucent and yellow. These cysts are commonly found on the sternum of males and the axillae or groin of females.²

Figure 3. Eccrine hidrocystoma with clear contents and lined by 2 layers of cuboidal epithelial cells (H&E, original magnification ×100).		Figure 4. Steatocystoma with a red wavy cuticle, sparse sebaceous contents, and sebaceous glands within the lining (H&E, original magnification ×100).

The best diagnosis is:

a. bronchogenic cyst
b. dermoid cyst
c. epidermal inclusion cyst
d. hidrocystoma
e. steatocystoma

H&E, original magnification ×40.

H&E, original magnification ×100.

Continue to the next page for the diagnosis >>

Dermoid Cyst

Dermoid cysts often present clinically as firm subcutaneous nodules on the head or neck in young children. They tend to arise along the lateral aspect of the eyebrow but also can occur on the nose, forehead, neck, chest, or scalp.¹ Dermoid cysts are thought to arise from the sequestration of ectodermal tissues along the embryonic fusion planes during development.² As such, they represent congenital defects and often are identified at birth; however, some are not noticed until much later when they enlarge or become inflamed or infected. Midline dermoid cysts may be associated with underlying dysraphism or intracranial extension.^3,4 Thus, any midline lesion warrants evaluation that incorporates imaging with computed tomography or magnetic resonance imaging.^4,5 Histologically, dermoid cysts are lined by a keratinizing stratified squamous epithelium (quiz image A), but the lining may be brightly eosinophilic and wavy resembling shark teeth.^1,3 The wall of a dermoid cyst commonly contains mature adnexal structures such as terminal hair follicles, sebaceous glands, apocrine glands, and/or eccrine glands (quiz image B).¹ Smooth muscle also may be seen within the lining; however, bone and cartilage are not commonly reported in dermoid cysts.² Lamellar keratin is typical of the cyst contents, and terminal hair shafts also are sometimes noted within the cystic space (quiz image B).^1,2 Treatment options include excision at the time of diagnosis or close clinical monitoring with subsequent excision if the lesion grows or becomes symptomatic.^4,5 Many practitioners opt to excise these cysts at diagnosis, as untreated lesions are at risk for infection and/or inflammation or may be cosmetically deforming.^6,7 Surgical resection, including removal of the wall of the cyst, is curative and reoccurrence is rare.⁵

Figure 1. Bronchogenic cyst demonstrating a ciliated pseudostratified epithelial lining encircled by smooth muscle (H&E, original magnification ×200).
Figure 2. Epidermal inclusion cyst containing loose lamellar keratin and a lining that closely resembles the surface epidermis (H&E, original magnification ×40).

Bronchogenic cysts demonstrate an epithelial lining that often is pseudostratified cuboidal or columnar as well as ciliated (Figure 1). Goblet cells are present in the lining in approximately 50% of cases. Smooth muscle may be seen circumferentially surrounding the cyst lining, and rare cases also contain cartilage.¹ In contrast to dermoid cysts, other types of adnexal structures are not found within the lining. Bronchogenic cysts that arise in the skin are extremely rare.² These cysts are thought to arise from respiratory epithelium that has been sequestered during embryologic formation of the tracheobronchial tree. They often are seen overlying the suprasternal notch and occasionally are found on the anterior aspect of the neck or chin. These cysts also are present at birth, similar to dermoid cysts.³

Epidermal inclusion cysts have a lining that histologically bears close resemblance to the surface epidermis. These cysts contain loose lamellar keratin, similar to a dermoid cyst. In contrast, the lining of an epidermal inclusion cyst will lack adnexal structures (Figure 2).¹ Clinically, epidermal inclusion cysts often present as smooth, dome-shaped papules and nodules with a central punctum. They are classically found on the face, neck, and trunk. These cysts are thought to arise after a traumatic insult to the pilosebaceous unit.²

Hidrocystomas can be apocrine or eccrine.³ Eccrine hidrocystomas are unilocular cysts that are lined by 2 layers of flattened to cuboidal epithelial cells (Figure 3). The cysts are filled with clear fluid and often are found adjacent to normal eccrine glands.¹ Apocrine hidrocystomas are unilocular or multilocular cysts that are lined by 1 to several layers of epithelial cells. The lining of an apocrine hidrocystoma will often exhibit luminal decapitation secretion.³ Apocrine and eccrine hidrocystomas are clinically identical and appear as blue translucent papules on the cheeks or eyelids of adults.^1-3 They usually occur periorbitally but also can be seen on the trunk, popliteal fossa, external ears, or vulva. Eccrine hidrocystomas can wax and wane in accordance with the amount of sweat produced; thus, they often expand in size during the summer months.²

Steatocystomas, or simple sebaceous duct cysts, histologically demonstrate a characteristically wavy and eosinophilic cuticle resembling shark teeth (Figure 4) similar to the lining of the sebaceous duct where it enters the follicle.¹ Sebaceous glands are an almost invariable feature, either present within the lining of the cyst (Figure 4) or in the adjacent tissue.² In comparison, dermoid cysts may have a red wavy cuticle but also will usually have terminal hair follicles or eccrine or apocrine glands within the wall of the cyst. Steatocystomas typically are collapsed and empty or only contain sebaceous debris (Figure 4) rather than the lamellar keratin seen in dermoid and epidermoid inclusion cysts. Steatocystomas can occur as solitary (steatocystoma simplex) or multiple (steatocystoma multiplex) lesions.^1,3 They are clinically comprised of small dome-shaped papules that often are translucent and yellow. These cysts are commonly found on the sternum of males and the axillae or groin of females.²

Figure 3. Eccrine hidrocystoma with clear contents and lined by 2 layers of cuboidal epithelial cells (H&E, original magnification ×100).		Figure 4. Steatocystoma with a red wavy cuticle, sparse sebaceous contents, and sebaceous glands within the lining (H&E, original magnification ×100).

The best diagnosis is:

a. bronchogenic cyst
b. dermoid cyst
c. epidermal inclusion cyst
d. hidrocystoma
e. steatocystoma

H&E, original magnification ×40.

H&E, original magnification ×100.

Continue to the next page for the diagnosis >>

Dermoid Cyst

Dermoid cysts often present clinically as firm subcutaneous nodules on the head or neck in young children. They tend to arise along the lateral aspect of the eyebrow but also can occur on the nose, forehead, neck, chest, or scalp.¹ Dermoid cysts are thought to arise from the sequestration of ectodermal tissues along the embryonic fusion planes during development.² As such, they represent congenital defects and often are identified at birth; however, some are not noticed until much later when they enlarge or become inflamed or infected. Midline dermoid cysts may be associated with underlying dysraphism or intracranial extension.^3,4 Thus, any midline lesion warrants evaluation that incorporates imaging with computed tomography or magnetic resonance imaging.^4,5 Histologically, dermoid cysts are lined by a keratinizing stratified squamous epithelium (quiz image A), but the lining may be brightly eosinophilic and wavy resembling shark teeth.^1,3 The wall of a dermoid cyst commonly contains mature adnexal structures such as terminal hair follicles, sebaceous glands, apocrine glands, and/or eccrine glands (quiz image B).¹ Smooth muscle also may be seen within the lining; however, bone and cartilage are not commonly reported in dermoid cysts.² Lamellar keratin is typical of the cyst contents, and terminal hair shafts also are sometimes noted within the cystic space (quiz image B).^1,2 Treatment options include excision at the time of diagnosis or close clinical monitoring with subsequent excision if the lesion grows or becomes symptomatic.^4,5 Many practitioners opt to excise these cysts at diagnosis, as untreated lesions are at risk for infection and/or inflammation or may be cosmetically deforming.^6,7 Surgical resection, including removal of the wall of the cyst, is curative and reoccurrence is rare.⁵

Figure 1. Bronchogenic cyst demonstrating a ciliated pseudostratified epithelial lining encircled by smooth muscle (H&E, original magnification ×200).
Figure 2. Epidermal inclusion cyst containing loose lamellar keratin and a lining that closely resembles the surface epidermis (H&E, original magnification ×40).

Bronchogenic cysts demonstrate an epithelial lining that often is pseudostratified cuboidal or columnar as well as ciliated (Figure 1). Goblet cells are present in the lining in approximately 50% of cases. Smooth muscle may be seen circumferentially surrounding the cyst lining, and rare cases also contain cartilage.¹ In contrast to dermoid cysts, other types of adnexal structures are not found within the lining. Bronchogenic cysts that arise in the skin are extremely rare.² These cysts are thought to arise from respiratory epithelium that has been sequestered during embryologic formation of the tracheobronchial tree. They often are seen overlying the suprasternal notch and occasionally are found on the anterior aspect of the neck or chin. These cysts also are present at birth, similar to dermoid cysts.³

Epidermal inclusion cysts have a lining that histologically bears close resemblance to the surface epidermis. These cysts contain loose lamellar keratin, similar to a dermoid cyst. In contrast, the lining of an epidermal inclusion cyst will lack adnexal structures (Figure 2).¹ Clinically, epidermal inclusion cysts often present as smooth, dome-shaped papules and nodules with a central punctum. They are classically found on the face, neck, and trunk. These cysts are thought to arise after a traumatic insult to the pilosebaceous unit.²

Hidrocystomas can be apocrine or eccrine.³ Eccrine hidrocystomas are unilocular cysts that are lined by 2 layers of flattened to cuboidal epithelial cells (Figure 3). The cysts are filled with clear fluid and often are found adjacent to normal eccrine glands.¹ Apocrine hidrocystomas are unilocular or multilocular cysts that are lined by 1 to several layers of epithelial cells. The lining of an apocrine hidrocystoma will often exhibit luminal decapitation secretion.³ Apocrine and eccrine hidrocystomas are clinically identical and appear as blue translucent papules on the cheeks or eyelids of adults.^1-3 They usually occur periorbitally but also can be seen on the trunk, popliteal fossa, external ears, or vulva. Eccrine hidrocystomas can wax and wane in accordance with the amount of sweat produced; thus, they often expand in size during the summer months.²

Steatocystomas, or simple sebaceous duct cysts, histologically demonstrate a characteristically wavy and eosinophilic cuticle resembling shark teeth (Figure 4) similar to the lining of the sebaceous duct where it enters the follicle.¹ Sebaceous glands are an almost invariable feature, either present within the lining of the cyst (Figure 4) or in the adjacent tissue.² In comparison, dermoid cysts may have a red wavy cuticle but also will usually have terminal hair follicles or eccrine or apocrine glands within the wall of the cyst. Steatocystomas typically are collapsed and empty or only contain sebaceous debris (Figure 4) rather than the lamellar keratin seen in dermoid and epidermoid inclusion cysts. Steatocystomas can occur as solitary (steatocystoma simplex) or multiple (steatocystoma multiplex) lesions.^1,3 They are clinically comprised of small dome-shaped papules that often are translucent and yellow. These cysts are commonly found on the sternum of males and the axillae or groin of females.²

Figure 3. Eccrine hidrocystoma with clear contents and lined by 2 layers of cuboidal epithelial cells (H&E, original magnification ×100).		Figure 4. Steatocystoma with a red wavy cuticle, sparse sebaceous contents, and sebaceous glands within the lining (H&E, original magnification ×100).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

[email protected]

On Twitter @mitchelzoler

Atopic dermatitis (AD), or eczema, is the leading dermatologic diagnosis worldwide and is vexing to patients due to the itchiness of the rash. It is the leading cause of skin disease burden worldwide with a prevalence of 229,761,000 reported cases in 2010, presenting largely in preadolescence but also persisting through adulthood.¹ Using the children’s life quality index, it has been demonstrated that AD has a greater impact on health-related quality of life than renal disease and cystic fibrosis.² The overall burden of AD includes stress on the patient and his/her family as well as financial burdens that have been estimated to be similar to that of type 1 diabetes mellitus.³

Epidemiology of AD

The worldwide prevalence of AD varies by country and age group surveyed, with a higher prevalence in wealthy developed nations (eg, the United States) compared to poorer developing nations.⁴ Efforts to identify prevalence data for AD in the United States have been approached through a variety of strategies. A group in Oregon estimated the prevalence of AD in children aged 5 to 9 years to be 17.2% via a survey of parents (N=1465) and 11.8% with doctor-diagnosed eczema. In the same study, the question “Has a doctor ever said that your child has eczema?” was found to have a 91.3% predictive correlation.⁵ Analysis of the 2003 National Survey of Children’s Health demonstrated the overall US prevalence of pediatric AD to be 10.7% in 102,353 children 17 years or younger, with a range of 8.7% to 18.1% by region.⁶

In its evaluation of the worldwide prevalence of AD, the International Study of Asthma and Allergies in Childhood ranked the United States 17th.^7,8 The prevalence of AD in developed countries such as the United States is fluid and is expected to increase if the trends from the last 20 years remain true. In an assessment of the National Health Interview Survey data from 1997 to 2011 based on responses to the question, “During the past 12 months, has your child had eczema or any kind of skin allergy?”, the Centers for Disease Control and Prevention identified an increase in the prevalence of AD in patients aged 0 to 17 years from 7.4% in 1997-1999 to 12.5% in 2009-2011.⁹ Rising prevalence seems to be paired with rising incidence in the total number of severe intractable cases, reduced clearance at the approach of grade school, or cases persisting into adulthood.

Racial Disparity in AD

Racial disparity worldwide and migration are thought to contribute to the prevalence of and therapeutic need for AD. For example, in the United Kingdom, the prevalence of AD in London-born Afro-Caribbean children versus white children (total cross-section, N=693 [junior school children]) was 16.3% and 8.7%, respectively.¹⁰ In the United States, black children were more likely to have AD than white children (odds ratio, 1.7).⁶ Asian and black children also were more likely to present to a physician for treatment of AD than white children.^6,10-13

Definition and Diagnostic Considerations

According to Hanifin,¹⁴ “Eczema represents a family of inflammatory skin conditions characterized by pruritic, papulovesicular, sometimes weeping dermatitis. All demonstrate the histological hallmark of spongiosis, which helps to distinguish the eczemas from papulosquamous diseases such as psoriasis.”¹⁴ Atopic dermatitis is a variant of eczema; however, most laymen identify eczema and AD as being one and the same.

The Hanifin and Rajka¹⁵ criteria are the major diagnostic criteria for AD but are difficult to use in clinical practice. Three of the following 4 major criteria are needed for diagnosis: (1) pruritus, which is present universally; (2) typical morphology and distribution; (3) chronic or chronically relapsing dermatitis; and (4) personal and/or family history of atopy. Additionally, 3 of the following 23 minor criteria are needed for diagnosis: xerosis; ichthyosis vulgaris, palmar hyperlinearity, or keratosis pilaris; positive skin prick test; elevated serum IgE level; early age of onset; tendency toward cutaneous infections or impaired cell-mediated immunity; tendency toward nonspecific hand or foot dermatitis; nipple eczema; cheilitis; recurrent conjunctivitis; Dennie-Morgan fold (infraorbital fold); keratoconus; anterior subcapsular cataracts; orbital darkening; facial pallor or facial erythema; pityriasis alba; anterior neck folds; itching when sweating; intolerance to wool and lipid solvents; perifollicular accentuation; skin reactions from ingested foods or by food contact; environmental or emotional factors; and lesional/nonlesional white dermographism or delayed blanch.^15-17

More pragmatic streamlined diagnostic criteria were established by Eichenfield et al.¹⁸ According to these guidelines, essential features for AD include pruritus and eczema. Important features seen in most cases and adding support to the diagnosis include early age of onset, atopy, and xerosis.¹⁸ In clinical practice, diagnosis is often made based on a pruritic relapsing condition in typical locations including the face, neck, and extensor surfaces in infants and children.

Age Considerations

Diagnosis of AD is made by 5 years of age in 85% to 90% of children who will develop the disease and by age 1 year in 60% to 65%.^6,19,20 Atopic dermatitis will persist into adulthood in up to one-third of children.^21,22 Infantile AD is characterized by erythematous, oozing, excoriated plaques on the cheeks (sparing the nose), scalp, trunk, and extensor surfaces. Pruritus is always seen in AD and can be a source of morbidity.^16-18 Seborrheic dermatitis may complicate or overlap with AD in infancy.²²

By 2 years of age, most children who are going to develop AD begin to show disease signs of childhood AD characterized by flexural lesions and lesions on the neck and in the postauricular area with sparing of the diaper area.²³ Adult AD often presents as eczema of the hands and/or feet. Hand eczema in adulthood is correlated with a prior history of childhood hand eczema and/or childhood AD as well as wet work and caring for small children.²⁴ Children with skin of color may manifest with follicular eczema as their primary disease phenotype. Facial and eyelid dermatitis are more common in Asian females, infants, and teenagers.^12,25 Other disease phenotypes that are common in patients with skin of color include lichenoid AD and postinflammatory hypopigmentation.¹²

Pathogenesis of AD

There are 2 theories on the pathogenesis of AD known as the inside-out and outside-in hypotheses.²⁶ The inside-out hypothesis suggests that allergic triggering leads to a weakened skin barrier that furthers allergen introduction and presentation, while the outside-in hypothesis suggests that the skin barrier is weakened in AD and allows for the presentation of allergens. Both theories have validity and biologic basis, and both may in fact be true in certain individuals.²⁶

The Skin Barrier: An Overview

The skin barrier is a complex set of factors present and functional at birth that seal the keratinocytes and the interkeratinocyte space so that the skin can perform key processes and functions including retention of fluid, exclusion of allergens, protection from UV light and solvents, and prevention of pathogen entry (eg, infections).^27-29 The superficial stratum corneum or the cornified envelope consists of keratinocytes with intercellular stripes of hydrophobic and hydrophilic substances formed by various intercellular lipids, largely ceramides, cholesterol, and free fatty acids.^30,31 Keratinocytes are the first responders to a variety of environmental insults with the production of IL-18, RANTES (regulated on activation, normal T-expressed, and presumably secreted), granulocyte-macrophage colony-stimulating factor, and thymic stromal lymphopoietin. These inflammatory substances produce acute and chronic inflammation, mast cell reactivity, and T-cell activation.¹⁴ Corneodesmosins link the keratinocytes. Peptidases released will cleave the corneodesmosins and allow normal desquamation or shedding of surface skin, which is replaced by division of stem cells in the basal layer.²⁹

The stratum granulosum is the layer beneath the stratum corneum that co-contributes to barrier activity. The stratum granulosum is absent or reduced histologically in ichthyosis vulgaris,³² a form of skin dryness linked to filaggrin mutations and AD. Filaggrin breakdown creates natural moisturizing factor, a series of hygroscopic compounds that attract water into the skin.³³ Histidine, a filaggrin breakdown product, is used by urocanic acid to process UV light insults.³⁴ Filaggrin also contributes to other barrier functions including pH and stratum corneum cohesion as well as paracellular permeability of the stratum corneum. Tight junctions in the stratum granulosum include claudin-1 and claudin-6 and provide another barrier feature.²⁹

The skin barrier is composed of lipids and keratinocytes. Ceramides, which represent one type of lipids, are reduced in AD, causing alteration in the lamellar pattern³⁵ and increased transepidermal water loss. Furthermore, the stratum corneum is thickened in AD, possibly in response to trauma, and hydration is reduced.³⁶ Filaggrin (chromosome arm 1q21.3) is formed from the 400-kDa⁺ precursor profilaggrin through dephosphorylation and cleavage, and it performs an essential function in the skin barrier through its differential cleavage and breakdown as well as release of natural moisturizing factor and other compounds.³⁷ Filaggrin mutations are linked to AD and ichthyosis vulgaris; however, barrier defects as evidenced by transepidermal water loss in the absence of filaggrin mutation are sufficient to allow for sensitization to allergens through the skin.²⁹ Filaggrin mutations have been associated with AD development and vary in prevalence worldwide. In the United Kingdom, a prevalence study of filaggrin mutations in patients aged 7 to 9 years (N=792) demonstrated an 18.4% carrier rate in AD patients versus 12.9% in controls.³⁴ A similar study in Sweden (N=3301) showed carrier rates of 13.5% versus 6.5%, respectively.³⁸ Although filaggrin mutations are lower in black patients,³⁹ ceramide content may be reduced in this population, demonstrating that a variety of skin barrier defects can result in AD. Carriers of filaggrin mutations are more likely to have eczema on skin exposed to environmental factors (eg, face, hands).⁴⁰

Barrier Defects Contributing to AD

The breakdown of the stratum corneum allows for antigen presentation to Langerhans cells, the dendritic antigen-presenting cells of the skin. Breaks in the stratum corneum may occur from scratching. These macroscopic breaks are large, whereas the breaks that otherwise occur due to barrier breakdown may be more microscopic in nature. Scratching causes aggravation of the helper T cell (T_H2) response.²⁹ For example, it allows the dendritic ends of Langerhans cells to be exposed to antigens. The dendritic ends capture allergens through IgE (may be elevated in AD²⁹), which is bound to the high-affinity FCER1 receptors on Langerhans cells. Rather than causing a type I hypersensitivity reaction, these Langerhans cells are activated and move to the lymph nodes where they present antigen and initiate a cascade of proinflammatory activity. This T_H2 cascade includes release of cytokines such as IL-2, IL-4, IL-8, IL-10, tumor necrosis factor α, and IFN-γ.^26,29

Transepidermal water loss and barrier dysfunction contribute to disease activity and facilitate food/environmental allergen sensitization by allowing increased penetration of allergens through the skin to be presented by Langerhans cells to T_H1 cells (sensitization phase). The Langerhans cells can reach their dendritic ends through tight junctions and into the stratum corneum, allowing them to reach surface allergens when the barrier is impaired. Ultimate expansion to systemic allergy (effector phase) occurs when dendritic cells move to draining lymph nodes, causing antigen presentation to CD4 and/or CD8 cells. Langerhans cells and dendritic cell sensitization through the weakened skin is believed to be the basis or role of barrier disruption as a trigger of atopic diseases, including AD and food and environmental allergies.

Many different forms of barrier disruption can cause a T_H2 response in AD. The T_H2 response triggers a constellation of proinflammatory activities including release of IL-4, associated with eosinophilia and elevated IgE levels, the latter being minor criterion in the diagnosis of AD.¹⁵ One mechanism by which the T_H2 response is elicited may be the release of molecules such as danger-associated molecule patterns that may elicit recruitment of other inflammatory cells. Helper T cell (T_H2) activity also can worsen barrier defects through IL-4 and IL-13 release, which can reduce filaggrin expression,^29,41 and can aggravate barrier dysfunction in AD.

Inflammatory activation in AD also may involve inflammatory dendritic epidermal cells (IDECs). The IDECs can be tolerogenic or immunogenic mature phenotypes. The IDECs activate helper T cells (T_H1), which may contribute to long-term AD activity.

Conclusion

Atopic dermatitis is a common skin condition worldwide and is characterized by the hallmark of pruritus and features that include a typical pattern, history of atopy (personal or family), and usually xerosis and early disease onset. Barrier dysfunction and immune dysregulation are prominent in AD, both of which aggravate the other and may encourage increased development of allergies and other forms of atopy over time.

Atopic dermatitis (AD), or eczema, is the leading dermatologic diagnosis worldwide and is vexing to patients due to the itchiness of the rash. It is the leading cause of skin disease burden worldwide with a prevalence of 229,761,000 reported cases in 2010, presenting largely in preadolescence but also persisting through adulthood.¹ Using the children’s life quality index, it has been demonstrated that AD has a greater impact on health-related quality of life than renal disease and cystic fibrosis.² The overall burden of AD includes stress on the patient and his/her family as well as financial burdens that have been estimated to be similar to that of type 1 diabetes mellitus.³

Epidemiology of AD

The worldwide prevalence of AD varies by country and age group surveyed, with a higher prevalence in wealthy developed nations (eg, the United States) compared to poorer developing nations.⁴ Efforts to identify prevalence data for AD in the United States have been approached through a variety of strategies. A group in Oregon estimated the prevalence of AD in children aged 5 to 9 years to be 17.2% via a survey of parents (N=1465) and 11.8% with doctor-diagnosed eczema. In the same study, the question “Has a doctor ever said that your child has eczema?” was found to have a 91.3% predictive correlation.⁵ Analysis of the 2003 National Survey of Children’s Health demonstrated the overall US prevalence of pediatric AD to be 10.7% in 102,353 children 17 years or younger, with a range of 8.7% to 18.1% by region.⁶

In its evaluation of the worldwide prevalence of AD, the International Study of Asthma and Allergies in Childhood ranked the United States 17th.^7,8 The prevalence of AD in developed countries such as the United States is fluid and is expected to increase if the trends from the last 20 years remain true. In an assessment of the National Health Interview Survey data from 1997 to 2011 based on responses to the question, “During the past 12 months, has your child had eczema or any kind of skin allergy?”, the Centers for Disease Control and Prevention identified an increase in the prevalence of AD in patients aged 0 to 17 years from 7.4% in 1997-1999 to 12.5% in 2009-2011.⁹ Rising prevalence seems to be paired with rising incidence in the total number of severe intractable cases, reduced clearance at the approach of grade school, or cases persisting into adulthood.

Racial Disparity in AD

Racial disparity worldwide and migration are thought to contribute to the prevalence of and therapeutic need for AD. For example, in the United Kingdom, the prevalence of AD in London-born Afro-Caribbean children versus white children (total cross-section, N=693 [junior school children]) was 16.3% and 8.7%, respectively.¹⁰ In the United States, black children were more likely to have AD than white children (odds ratio, 1.7).⁶ Asian and black children also were more likely to present to a physician for treatment of AD than white children.^6,10-13

Definition and Diagnostic Considerations

According to Hanifin,¹⁴ “Eczema represents a family of inflammatory skin conditions characterized by pruritic, papulovesicular, sometimes weeping dermatitis. All demonstrate the histological hallmark of spongiosis, which helps to distinguish the eczemas from papulosquamous diseases such as psoriasis.”¹⁴ Atopic dermatitis is a variant of eczema; however, most laymen identify eczema and AD as being one and the same.

The Hanifin and Rajka¹⁵ criteria are the major diagnostic criteria for AD but are difficult to use in clinical practice. Three of the following 4 major criteria are needed for diagnosis: (1) pruritus, which is present universally; (2) typical morphology and distribution; (3) chronic or chronically relapsing dermatitis; and (4) personal and/or family history of atopy. Additionally, 3 of the following 23 minor criteria are needed for diagnosis: xerosis; ichthyosis vulgaris, palmar hyperlinearity, or keratosis pilaris; positive skin prick test; elevated serum IgE level; early age of onset; tendency toward cutaneous infections or impaired cell-mediated immunity; tendency toward nonspecific hand or foot dermatitis; nipple eczema; cheilitis; recurrent conjunctivitis; Dennie-Morgan fold (infraorbital fold); keratoconus; anterior subcapsular cataracts; orbital darkening; facial pallor or facial erythema; pityriasis alba; anterior neck folds; itching when sweating; intolerance to wool and lipid solvents; perifollicular accentuation; skin reactions from ingested foods or by food contact; environmental or emotional factors; and lesional/nonlesional white dermographism or delayed blanch.^15-17

More pragmatic streamlined diagnostic criteria were established by Eichenfield et al.¹⁸ According to these guidelines, essential features for AD include pruritus and eczema. Important features seen in most cases and adding support to the diagnosis include early age of onset, atopy, and xerosis.¹⁸ In clinical practice, diagnosis is often made based on a pruritic relapsing condition in typical locations including the face, neck, and extensor surfaces in infants and children.

Age Considerations

Diagnosis of AD is made by 5 years of age in 85% to 90% of children who will develop the disease and by age 1 year in 60% to 65%.^6,19,20 Atopic dermatitis will persist into adulthood in up to one-third of children.^21,22 Infantile AD is characterized by erythematous, oozing, excoriated plaques on the cheeks (sparing the nose), scalp, trunk, and extensor surfaces. Pruritus is always seen in AD and can be a source of morbidity.^16-18 Seborrheic dermatitis may complicate or overlap with AD in infancy.²²

By 2 years of age, most children who are going to develop AD begin to show disease signs of childhood AD characterized by flexural lesions and lesions on the neck and in the postauricular area with sparing of the diaper area.²³ Adult AD often presents as eczema of the hands and/or feet. Hand eczema in adulthood is correlated with a prior history of childhood hand eczema and/or childhood AD as well as wet work and caring for small children.²⁴ Children with skin of color may manifest with follicular eczema as their primary disease phenotype. Facial and eyelid dermatitis are more common in Asian females, infants, and teenagers.^12,25 Other disease phenotypes that are common in patients with skin of color include lichenoid AD and postinflammatory hypopigmentation.¹²

Pathogenesis of AD

There are 2 theories on the pathogenesis of AD known as the inside-out and outside-in hypotheses.²⁶ The inside-out hypothesis suggests that allergic triggering leads to a weakened skin barrier that furthers allergen introduction and presentation, while the outside-in hypothesis suggests that the skin barrier is weakened in AD and allows for the presentation of allergens. Both theories have validity and biologic basis, and both may in fact be true in certain individuals.²⁶

The Skin Barrier: An Overview

The skin barrier is a complex set of factors present and functional at birth that seal the keratinocytes and the interkeratinocyte space so that the skin can perform key processes and functions including retention of fluid, exclusion of allergens, protection from UV light and solvents, and prevention of pathogen entry (eg, infections).^27-29 The superficial stratum corneum or the cornified envelope consists of keratinocytes with intercellular stripes of hydrophobic and hydrophilic substances formed by various intercellular lipids, largely ceramides, cholesterol, and free fatty acids.^30,31 Keratinocytes are the first responders to a variety of environmental insults with the production of IL-18, RANTES (regulated on activation, normal T-expressed, and presumably secreted), granulocyte-macrophage colony-stimulating factor, and thymic stromal lymphopoietin. These inflammatory substances produce acute and chronic inflammation, mast cell reactivity, and T-cell activation.¹⁴ Corneodesmosins link the keratinocytes. Peptidases released will cleave the corneodesmosins and allow normal desquamation or shedding of surface skin, which is replaced by division of stem cells in the basal layer.²⁹

The stratum granulosum is the layer beneath the stratum corneum that co-contributes to barrier activity. The stratum granulosum is absent or reduced histologically in ichthyosis vulgaris,³² a form of skin dryness linked to filaggrin mutations and AD. Filaggrin breakdown creates natural moisturizing factor, a series of hygroscopic compounds that attract water into the skin.³³ Histidine, a filaggrin breakdown product, is used by urocanic acid to process UV light insults.³⁴ Filaggrin also contributes to other barrier functions including pH and stratum corneum cohesion as well as paracellular permeability of the stratum corneum. Tight junctions in the stratum granulosum include claudin-1 and claudin-6 and provide another barrier feature.²⁹

The skin barrier is composed of lipids and keratinocytes. Ceramides, which represent one type of lipids, are reduced in AD, causing alteration in the lamellar pattern³⁵ and increased transepidermal water loss. Furthermore, the stratum corneum is thickened in AD, possibly in response to trauma, and hydration is reduced.³⁶ Filaggrin (chromosome arm 1q21.3) is formed from the 400-kDa⁺ precursor profilaggrin through dephosphorylation and cleavage, and it performs an essential function in the skin barrier through its differential cleavage and breakdown as well as release of natural moisturizing factor and other compounds.³⁷ Filaggrin mutations are linked to AD and ichthyosis vulgaris; however, barrier defects as evidenced by transepidermal water loss in the absence of filaggrin mutation are sufficient to allow for sensitization to allergens through the skin.²⁹ Filaggrin mutations have been associated with AD development and vary in prevalence worldwide. In the United Kingdom, a prevalence study of filaggrin mutations in patients aged 7 to 9 years (N=792) demonstrated an 18.4% carrier rate in AD patients versus 12.9% in controls.³⁴ A similar study in Sweden (N=3301) showed carrier rates of 13.5% versus 6.5%, respectively.³⁸ Although filaggrin mutations are lower in black patients,³⁹ ceramide content may be reduced in this population, demonstrating that a variety of skin barrier defects can result in AD. Carriers of filaggrin mutations are more likely to have eczema on skin exposed to environmental factors (eg, face, hands).⁴⁰

Barrier Defects Contributing to AD

The breakdown of the stratum corneum allows for antigen presentation to Langerhans cells, the dendritic antigen-presenting cells of the skin. Breaks in the stratum corneum may occur from scratching. These macroscopic breaks are large, whereas the breaks that otherwise occur due to barrier breakdown may be more microscopic in nature. Scratching causes aggravation of the helper T cell (T_H2) response.²⁹ For example, it allows the dendritic ends of Langerhans cells to be exposed to antigens. The dendritic ends capture allergens through IgE (may be elevated in AD²⁹), which is bound to the high-affinity FCER1 receptors on Langerhans cells. Rather than causing a type I hypersensitivity reaction, these Langerhans cells are activated and move to the lymph nodes where they present antigen and initiate a cascade of proinflammatory activity. This T_H2 cascade includes release of cytokines such as IL-2, IL-4, IL-8, IL-10, tumor necrosis factor α, and IFN-γ.^26,29

Transepidermal water loss and barrier dysfunction contribute to disease activity and facilitate food/environmental allergen sensitization by allowing increased penetration of allergens through the skin to be presented by Langerhans cells to T_H1 cells (sensitization phase). The Langerhans cells can reach their dendritic ends through tight junctions and into the stratum corneum, allowing them to reach surface allergens when the barrier is impaired. Ultimate expansion to systemic allergy (effector phase) occurs when dendritic cells move to draining lymph nodes, causing antigen presentation to CD4 and/or CD8 cells. Langerhans cells and dendritic cell sensitization through the weakened skin is believed to be the basis or role of barrier disruption as a trigger of atopic diseases, including AD and food and environmental allergies.

Many different forms of barrier disruption can cause a T_H2 response in AD. The T_H2 response triggers a constellation of proinflammatory activities including release of IL-4, associated with eosinophilia and elevated IgE levels, the latter being minor criterion in the diagnosis of AD.¹⁵ One mechanism by which the T_H2 response is elicited may be the release of molecules such as danger-associated molecule patterns that may elicit recruitment of other inflammatory cells. Helper T cell (T_H2) activity also can worsen barrier defects through IL-4 and IL-13 release, which can reduce filaggrin expression,^29,41 and can aggravate barrier dysfunction in AD.

Inflammatory activation in AD also may involve inflammatory dendritic epidermal cells (IDECs). The IDECs can be tolerogenic or immunogenic mature phenotypes. The IDECs activate helper T cells (T_H1), which may contribute to long-term AD activity.

Conclusion

Atopic dermatitis is a common skin condition worldwide and is characterized by the hallmark of pruritus and features that include a typical pattern, history of atopy (personal or family), and usually xerosis and early disease onset. Barrier dysfunction and immune dysregulation are prominent in AD, both of which aggravate the other and may encourage increased development of allergies and other forms of atopy over time.

Atopic dermatitis (AD), or eczema, is the leading dermatologic diagnosis worldwide and is vexing to patients due to the itchiness of the rash. It is the leading cause of skin disease burden worldwide with a prevalence of 229,761,000 reported cases in 2010, presenting largely in preadolescence but also persisting through adulthood.¹ Using the children’s life quality index, it has been demonstrated that AD has a greater impact on health-related quality of life than renal disease and cystic fibrosis.² The overall burden of AD includes stress on the patient and his/her family as well as financial burdens that have been estimated to be similar to that of type 1 diabetes mellitus.³

Epidemiology of AD

The worldwide prevalence of AD varies by country and age group surveyed, with a higher prevalence in wealthy developed nations (eg, the United States) compared to poorer developing nations.⁴ Efforts to identify prevalence data for AD in the United States have been approached through a variety of strategies. A group in Oregon estimated the prevalence of AD in children aged 5 to 9 years to be 17.2% via a survey of parents (N=1465) and 11.8% with doctor-diagnosed eczema. In the same study, the question “Has a doctor ever said that your child has eczema?” was found to have a 91.3% predictive correlation.⁵ Analysis of the 2003 National Survey of Children’s Health demonstrated the overall US prevalence of pediatric AD to be 10.7% in 102,353 children 17 years or younger, with a range of 8.7% to 18.1% by region.⁶

In its evaluation of the worldwide prevalence of AD, the International Study of Asthma and Allergies in Childhood ranked the United States 17th.^7,8 The prevalence of AD in developed countries such as the United States is fluid and is expected to increase if the trends from the last 20 years remain true. In an assessment of the National Health Interview Survey data from 1997 to 2011 based on responses to the question, “During the past 12 months, has your child had eczema or any kind of skin allergy?”, the Centers for Disease Control and Prevention identified an increase in the prevalence of AD in patients aged 0 to 17 years from 7.4% in 1997-1999 to 12.5% in 2009-2011.⁹ Rising prevalence seems to be paired with rising incidence in the total number of severe intractable cases, reduced clearance at the approach of grade school, or cases persisting into adulthood.

Racial Disparity in AD

Racial disparity worldwide and migration are thought to contribute to the prevalence of and therapeutic need for AD. For example, in the United Kingdom, the prevalence of AD in London-born Afro-Caribbean children versus white children (total cross-section, N=693 [junior school children]) was 16.3% and 8.7%, respectively.¹⁰ In the United States, black children were more likely to have AD than white children (odds ratio, 1.7).⁶ Asian and black children also were more likely to present to a physician for treatment of AD than white children.^6,10-13

Definition and Diagnostic Considerations

According to Hanifin,¹⁴ “Eczema represents a family of inflammatory skin conditions characterized by pruritic, papulovesicular, sometimes weeping dermatitis. All demonstrate the histological hallmark of spongiosis, which helps to distinguish the eczemas from papulosquamous diseases such as psoriasis.”¹⁴ Atopic dermatitis is a variant of eczema; however, most laymen identify eczema and AD as being one and the same.

The Hanifin and Rajka¹⁵ criteria are the major diagnostic criteria for AD but are difficult to use in clinical practice. Three of the following 4 major criteria are needed for diagnosis: (1) pruritus, which is present universally; (2) typical morphology and distribution; (3) chronic or chronically relapsing dermatitis; and (4) personal and/or family history of atopy. Additionally, 3 of the following 23 minor criteria are needed for diagnosis: xerosis; ichthyosis vulgaris, palmar hyperlinearity, or keratosis pilaris; positive skin prick test; elevated serum IgE level; early age of onset; tendency toward cutaneous infections or impaired cell-mediated immunity; tendency toward nonspecific hand or foot dermatitis; nipple eczema; cheilitis; recurrent conjunctivitis; Dennie-Morgan fold (infraorbital fold); keratoconus; anterior subcapsular cataracts; orbital darkening; facial pallor or facial erythema; pityriasis alba; anterior neck folds; itching when sweating; intolerance to wool and lipid solvents; perifollicular accentuation; skin reactions from ingested foods or by food contact; environmental or emotional factors; and lesional/nonlesional white dermographism or delayed blanch.^15-17

More pragmatic streamlined diagnostic criteria were established by Eichenfield et al.¹⁸ According to these guidelines, essential features for AD include pruritus and eczema. Important features seen in most cases and adding support to the diagnosis include early age of onset, atopy, and xerosis.¹⁸ In clinical practice, diagnosis is often made based on a pruritic relapsing condition in typical locations including the face, neck, and extensor surfaces in infants and children.

Age Considerations

Diagnosis of AD is made by 5 years of age in 85% to 90% of children who will develop the disease and by age 1 year in 60% to 65%.^6,19,20 Atopic dermatitis will persist into adulthood in up to one-third of children.^21,22 Infantile AD is characterized by erythematous, oozing, excoriated plaques on the cheeks (sparing the nose), scalp, trunk, and extensor surfaces. Pruritus is always seen in AD and can be a source of morbidity.^16-18 Seborrheic dermatitis may complicate or overlap with AD in infancy.²²

By 2 years of age, most children who are going to develop AD begin to show disease signs of childhood AD characterized by flexural lesions and lesions on the neck and in the postauricular area with sparing of the diaper area.²³ Adult AD often presents as eczema of the hands and/or feet. Hand eczema in adulthood is correlated with a prior history of childhood hand eczema and/or childhood AD as well as wet work and caring for small children.²⁴ Children with skin of color may manifest with follicular eczema as their primary disease phenotype. Facial and eyelid dermatitis are more common in Asian females, infants, and teenagers.^12,25 Other disease phenotypes that are common in patients with skin of color include lichenoid AD and postinflammatory hypopigmentation.¹²

Pathogenesis of AD

There are 2 theories on the pathogenesis of AD known as the inside-out and outside-in hypotheses.²⁶ The inside-out hypothesis suggests that allergic triggering leads to a weakened skin barrier that furthers allergen introduction and presentation, while the outside-in hypothesis suggests that the skin barrier is weakened in AD and allows for the presentation of allergens. Both theories have validity and biologic basis, and both may in fact be true in certain individuals.²⁶

The Skin Barrier: An Overview

The skin barrier is a complex set of factors present and functional at birth that seal the keratinocytes and the interkeratinocyte space so that the skin can perform key processes and functions including retention of fluid, exclusion of allergens, protection from UV light and solvents, and prevention of pathogen entry (eg, infections).^27-29 The superficial stratum corneum or the cornified envelope consists of keratinocytes with intercellular stripes of hydrophobic and hydrophilic substances formed by various intercellular lipids, largely ceramides, cholesterol, and free fatty acids.^30,31 Keratinocytes are the first responders to a variety of environmental insults with the production of IL-18, RANTES (regulated on activation, normal T-expressed, and presumably secreted), granulocyte-macrophage colony-stimulating factor, and thymic stromal lymphopoietin. These inflammatory substances produce acute and chronic inflammation, mast cell reactivity, and T-cell activation.¹⁴ Corneodesmosins link the keratinocytes. Peptidases released will cleave the corneodesmosins and allow normal desquamation or shedding of surface skin, which is replaced by division of stem cells in the basal layer.²⁹

The stratum granulosum is the layer beneath the stratum corneum that co-contributes to barrier activity. The stratum granulosum is absent or reduced histologically in ichthyosis vulgaris,³² a form of skin dryness linked to filaggrin mutations and AD. Filaggrin breakdown creates natural moisturizing factor, a series of hygroscopic compounds that attract water into the skin.³³ Histidine, a filaggrin breakdown product, is used by urocanic acid to process UV light insults.³⁴ Filaggrin also contributes to other barrier functions including pH and stratum corneum cohesion as well as paracellular permeability of the stratum corneum. Tight junctions in the stratum granulosum include claudin-1 and claudin-6 and provide another barrier feature.²⁹

The skin barrier is composed of lipids and keratinocytes. Ceramides, which represent one type of lipids, are reduced in AD, causing alteration in the lamellar pattern³⁵ and increased transepidermal water loss. Furthermore, the stratum corneum is thickened in AD, possibly in response to trauma, and hydration is reduced.³⁶ Filaggrin (chromosome arm 1q21.3) is formed from the 400-kDa⁺ precursor profilaggrin through dephosphorylation and cleavage, and it performs an essential function in the skin barrier through its differential cleavage and breakdown as well as release of natural moisturizing factor and other compounds.³⁷ Filaggrin mutations are linked to AD and ichthyosis vulgaris; however, barrier defects as evidenced by transepidermal water loss in the absence of filaggrin mutation are sufficient to allow for sensitization to allergens through the skin.²⁹ Filaggrin mutations have been associated with AD development and vary in prevalence worldwide. In the United Kingdom, a prevalence study of filaggrin mutations in patients aged 7 to 9 years (N=792) demonstrated an 18.4% carrier rate in AD patients versus 12.9% in controls.³⁴ A similar study in Sweden (N=3301) showed carrier rates of 13.5% versus 6.5%, respectively.³⁸ Although filaggrin mutations are lower in black patients,³⁹ ceramide content may be reduced in this population, demonstrating that a variety of skin barrier defects can result in AD. Carriers of filaggrin mutations are more likely to have eczema on skin exposed to environmental factors (eg, face, hands).⁴⁰

Barrier Defects Contributing to AD

The breakdown of the stratum corneum allows for antigen presentation to Langerhans cells, the dendritic antigen-presenting cells of the skin. Breaks in the stratum corneum may occur from scratching. These macroscopic breaks are large, whereas the breaks that otherwise occur due to barrier breakdown may be more microscopic in nature. Scratching causes aggravation of the helper T cell (T_H2) response.²⁹ For example, it allows the dendritic ends of Langerhans cells to be exposed to antigens. The dendritic ends capture allergens through IgE (may be elevated in AD²⁹), which is bound to the high-affinity FCER1 receptors on Langerhans cells. Rather than causing a type I hypersensitivity reaction, these Langerhans cells are activated and move to the lymph nodes where they present antigen and initiate a cascade of proinflammatory activity. This T_H2 cascade includes release of cytokines such as IL-2, IL-4, IL-8, IL-10, tumor necrosis factor α, and IFN-γ.^26,29

Transepidermal water loss and barrier dysfunction contribute to disease activity and facilitate food/environmental allergen sensitization by allowing increased penetration of allergens through the skin to be presented by Langerhans cells to T_H1 cells (sensitization phase). The Langerhans cells can reach their dendritic ends through tight junctions and into the stratum corneum, allowing them to reach surface allergens when the barrier is impaired. Ultimate expansion to systemic allergy (effector phase) occurs when dendritic cells move to draining lymph nodes, causing antigen presentation to CD4 and/or CD8 cells. Langerhans cells and dendritic cell sensitization through the weakened skin is believed to be the basis or role of barrier disruption as a trigger of atopic diseases, including AD and food and environmental allergies.

Many different forms of barrier disruption can cause a T_H2 response in AD. The T_H2 response triggers a constellation of proinflammatory activities including release of IL-4, associated with eosinophilia and elevated IgE levels, the latter being minor criterion in the diagnosis of AD.¹⁵ One mechanism by which the T_H2 response is elicited may be the release of molecules such as danger-associated molecule patterns that may elicit recruitment of other inflammatory cells. Helper T cell (T_H2) activity also can worsen barrier defects through IL-4 and IL-13 release, which can reduce filaggrin expression,^29,41 and can aggravate barrier dysfunction in AD.

Inflammatory activation in AD also may involve inflammatory dendritic epidermal cells (IDECs). The IDECs can be tolerogenic or immunogenic mature phenotypes. The IDECs activate helper T cells (T_H1), which may contribute to long-term AD activity.

Conclusion

Atopic dermatitis is a common skin condition worldwide and is characterized by the hallmark of pruritus and features that include a typical pattern, history of atopy (personal or family), and usually xerosis and early disease onset. Barrier dysfunction and immune dysregulation are prominent in AD, both of which aggravate the other and may encourage increased development of allergies and other forms of atopy over time.

The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.

The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.

“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”

The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:

• Make consumer warnings more prominent and easier to read on tanning devices.

• Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.

• Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.

• Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.

• Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.

The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.

In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.

Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.

The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.

The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.

“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”

The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:

• Make consumer warnings more prominent and easier to read on tanning devices.

• Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.

• Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.

• Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.

• Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.

The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.

In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.

Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.

The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.

The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.

“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”

The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:

• Make consumer warnings more prominent and easier to read on tanning devices.

• Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.

• Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.

• Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.

• Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.

The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.

In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.

Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

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An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”