Consuming caffeinated energy drinks leads to a prolonged QT interval and an increase in blood pressure, according to a study of young volunteers who had their hearts tested after drinking either energy drinks or placebo.

mipan/thinkstockphotos.

“Further investigation is warranted on whether an individual ingredient or a unique combination leads to the observed electrophysiological and hemodynamic changes,” wrote Sachin A. Shah of the University of the Pacific, Stockton, Calif., and coinvestigators. The study was published in the Journal of the American Heart Association.

To analyze electrocardiographic changes in the heart after consumption of 300 mg of caffeine plus other energy drink ingredients, the researchers assigned 34 healthy volunteers with an average age of 22 years to consume two 16-ounce bottles of either Drink A, a commercially available energy drink, Drink B, a different brand of energy drink, or a placebo drink for 3 days, followed by a 6-day washout period. Before and for 4 hours after consuming the beverages, volunteers had their hearts measured via ECG to test for differences in QT interval. Their blood pressures also were recorded.

Compared with placebo, the Drink A group had a 6.1 ms increase in QT interval and the Drink B group had a 7.7 ms rise. The maximum changes from baseline in corrected QT interval for Drink A, Drink B, and placebo were 17.9 ms, 19.6 ms, and 11.9 ms, respectively; both differences were statistically significant. Volunteers in Drink A and Drink B groups also had statistically significant increases of 5 mm Hg in systolic and 4 mm Hg in diastolic blood pressure after energy drink consumption, compared with placebo.

Both energy drinks used in the study contained caffeine (about 300 mg), taurine, glucuronolactone, and B vitamins. The investigators said that caffeine at doses under 400 mg is not expected to induce any electrocardiographic changes.

The coauthors noted their study’s limitations, including not investigating the effects of different doses and the possibility that consuming two 16-ounce bottles is an unrealistic real-world volume. That said, they noted that 16% of respondents to a 2,040-person survey admitted to consuming more than two energy drinks a day. In addition, though not every brand was tested, the researchers stated that, “the class of energy drinks, rather than one particular product, warrants use with caution.”

Dr. Shah reported serving as an expert witness in legal cases related to caffeinated energy drinks. The other authors reported no conflicts of interest.
 

SOURCE: Shah SA et al. J Am Heart Assoc. 2019 May 29.

Consuming caffeinated energy drinks leads to a prolonged QT interval and an increase in blood pressure, according to a study of young volunteers who had their hearts tested after drinking either energy drinks or placebo.

mipan/thinkstockphotos.

“Further investigation is warranted on whether an individual ingredient or a unique combination leads to the observed electrophysiological and hemodynamic changes,” wrote Sachin A. Shah of the University of the Pacific, Stockton, Calif., and coinvestigators. The study was published in the Journal of the American Heart Association.

To analyze electrocardiographic changes in the heart after consumption of 300 mg of caffeine plus other energy drink ingredients, the researchers assigned 34 healthy volunteers with an average age of 22 years to consume two 16-ounce bottles of either Drink A, a commercially available energy drink, Drink B, a different brand of energy drink, or a placebo drink for 3 days, followed by a 6-day washout period. Before and for 4 hours after consuming the beverages, volunteers had their hearts measured via ECG to test for differences in QT interval. Their blood pressures also were recorded.

Compared with placebo, the Drink A group had a 6.1 ms increase in QT interval and the Drink B group had a 7.7 ms rise. The maximum changes from baseline in corrected QT interval for Drink A, Drink B, and placebo were 17.9 ms, 19.6 ms, and 11.9 ms, respectively; both differences were statistically significant. Volunteers in Drink A and Drink B groups also had statistically significant increases of 5 mm Hg in systolic and 4 mm Hg in diastolic blood pressure after energy drink consumption, compared with placebo.

Both energy drinks used in the study contained caffeine (about 300 mg), taurine, glucuronolactone, and B vitamins. The investigators said that caffeine at doses under 400 mg is not expected to induce any electrocardiographic changes.

The coauthors noted their study’s limitations, including not investigating the effects of different doses and the possibility that consuming two 16-ounce bottles is an unrealistic real-world volume. That said, they noted that 16% of respondents to a 2,040-person survey admitted to consuming more than two energy drinks a day. In addition, though not every brand was tested, the researchers stated that, “the class of energy drinks, rather than one particular product, warrants use with caution.”

Dr. Shah reported serving as an expert witness in legal cases related to caffeinated energy drinks. The other authors reported no conflicts of interest.
 

SOURCE: Shah SA et al. J Am Heart Assoc. 2019 May 29.

Consuming caffeinated energy drinks leads to a prolonged QT interval and an increase in blood pressure, according to a study of young volunteers who had their hearts tested after drinking either energy drinks or placebo.

mipan/thinkstockphotos.

“Further investigation is warranted on whether an individual ingredient or a unique combination leads to the observed electrophysiological and hemodynamic changes,” wrote Sachin A. Shah of the University of the Pacific, Stockton, Calif., and coinvestigators. The study was published in the Journal of the American Heart Association.

To analyze electrocardiographic changes in the heart after consumption of 300 mg of caffeine plus other energy drink ingredients, the researchers assigned 34 healthy volunteers with an average age of 22 years to consume two 16-ounce bottles of either Drink A, a commercially available energy drink, Drink B, a different brand of energy drink, or a placebo drink for 3 days, followed by a 6-day washout period. Before and for 4 hours after consuming the beverages, volunteers had their hearts measured via ECG to test for differences in QT interval. Their blood pressures also were recorded.

Compared with placebo, the Drink A group had a 6.1 ms increase in QT interval and the Drink B group had a 7.7 ms rise. The maximum changes from baseline in corrected QT interval for Drink A, Drink B, and placebo were 17.9 ms, 19.6 ms, and 11.9 ms, respectively; both differences were statistically significant. Volunteers in Drink A and Drink B groups also had statistically significant increases of 5 mm Hg in systolic and 4 mm Hg in diastolic blood pressure after energy drink consumption, compared with placebo.

Both energy drinks used in the study contained caffeine (about 300 mg), taurine, glucuronolactone, and B vitamins. The investigators said that caffeine at doses under 400 mg is not expected to induce any electrocardiographic changes.

The coauthors noted their study’s limitations, including not investigating the effects of different doses and the possibility that consuming two 16-ounce bottles is an unrealistic real-world volume. That said, they noted that 16% of respondents to a 2,040-person survey admitted to consuming more than two energy drinks a day. In addition, though not every brand was tested, the researchers stated that, “the class of energy drinks, rather than one particular product, warrants use with caution.”

Dr. Shah reported serving as an expert witness in legal cases related to caffeinated energy drinks. The other authors reported no conflicts of interest.
 

SOURCE: Shah SA et al. J Am Heart Assoc. 2019 May 29.

The U.S. Supreme Court has upheld part of an Indiana law that requires burial or cremation of fetal remains after an abortion, but the justices declined to address the measure’s prohibition on abortions sought because of race, sex, or disability of the fetus.

ETIENJones/thinkstockphotos

In a three-page, unsigned opinion issued May 28, justices wrote that Indiana has a legitimate interest in proper disposition of fetal remains and that the state’s burial/cremation mandate is rational. However, justices said they would not take up the second part of the law regarding abortions based on race, sex, or disability because not enough appeals courts have decided the issue. The court emphasized it was not expressing any view on the merits of the second question.

The opinion stems from an antiabortion measure signed into law by then–Indiana Governor Mike Pence (R) in 2016. According to the law, the health facility where an abortion occurred is required to dispose of fetal remains either by cremation or internment unless the woman or an associated party take possession of the remains. The measure allows the woman or associated party to choose a location of final disposition provided that the parties pay the costs for such arrangements. The second part of the law prohibits an abortion from being performed solely because of the fetus’s expected race, sex, diagnosis, or disability.

Planned Parenthood of Indiana and Kentucky sued over the law, arguing that the measure was unconstitutional. Indiana officials countered the disposal requirements provided fetuses dignity in death and that the law’s abortion restrictions prevented discrimination of particular fetuses in light of technological advances in genetic screening. In 2018, a three-judge panel of the Court of Appeals for the 7th Circuit struck down the entire law. The panel wrote that well-established Supreme Court precedent allows a woman to terminate her pregnancy for any reason and that the Indiana law invaded a woman’s privacy by examining the underlying basis of her decision for an abortion.

In the Supreme Court’s May 28 filing, Justice Ruth Bader Ginsburg and Justice Sonia Sotomayor wrote separately, each stating they would have upheld the lower court’s ban of the entire law. Justice Clarence Thomas, meanwhile, wrote a lengthy separate opinion, agreeing with the court’s decision, but expressing concern over the use of abortion as a “tool of modern-day eugenics.”

“The court will soon need to confront the constitutionality of laws like Indiana’s,” Justice Thomas wrote. “Enshrining a constitutional right to an abortion based solely on the race, sex or disability of an unborn child, as Planned Parenthood advocates, would constitutionalize the views of the 20th-century eugenics movement.”

The Supreme Court’s decision on the Indiana law comes just weeks after two other stringent state abortion measures were signed into law. On May 7, 2019, Georgia Gov. Brian Kemp (R) signed into law a statute that bars physicians from performing an abortion after a heartbeat is detected – usually at about 6 weeks of pregnancy. On May 15, Alabama Gov. Kay Ivey (R) signed a law that would ban abortion at every pregnancy stage and penalize physicians with a Class A felony for performing an abortion and charge them with a Class C felony for attempting to perform an abortion.

Analysts say the Alabama law, in particular, could land in front of the Supreme Court as a direct challenge to Roe v. Wade. Abortion critics have been encouraged by the Supreme Court appointment of right-leaning Justice Brett M. Kavanaugh and hope the Alabama measure will drive the Supreme Court to reconsider its central holding in Roe, court watchers said.

agallegos@mdedge.com

The U.S. Supreme Court has upheld part of an Indiana law that requires burial or cremation of fetal remains after an abortion, but the justices declined to address the measure’s prohibition on abortions sought because of race, sex, or disability of the fetus.

ETIENJones/thinkstockphotos

In a three-page, unsigned opinion issued May 28, justices wrote that Indiana has a legitimate interest in proper disposition of fetal remains and that the state’s burial/cremation mandate is rational. However, justices said they would not take up the second part of the law regarding abortions based on race, sex, or disability because not enough appeals courts have decided the issue. The court emphasized it was not expressing any view on the merits of the second question.

The opinion stems from an antiabortion measure signed into law by then–Indiana Governor Mike Pence (R) in 2016. According to the law, the health facility where an abortion occurred is required to dispose of fetal remains either by cremation or internment unless the woman or an associated party take possession of the remains. The measure allows the woman or associated party to choose a location of final disposition provided that the parties pay the costs for such arrangements. The second part of the law prohibits an abortion from being performed solely because of the fetus’s expected race, sex, diagnosis, or disability.

Planned Parenthood of Indiana and Kentucky sued over the law, arguing that the measure was unconstitutional. Indiana officials countered the disposal requirements provided fetuses dignity in death and that the law’s abortion restrictions prevented discrimination of particular fetuses in light of technological advances in genetic screening. In 2018, a three-judge panel of the Court of Appeals for the 7th Circuit struck down the entire law. The panel wrote that well-established Supreme Court precedent allows a woman to terminate her pregnancy for any reason and that the Indiana law invaded a woman’s privacy by examining the underlying basis of her decision for an abortion.

In the Supreme Court’s May 28 filing, Justice Ruth Bader Ginsburg and Justice Sonia Sotomayor wrote separately, each stating they would have upheld the lower court’s ban of the entire law. Justice Clarence Thomas, meanwhile, wrote a lengthy separate opinion, agreeing with the court’s decision, but expressing concern over the use of abortion as a “tool of modern-day eugenics.”

“The court will soon need to confront the constitutionality of laws like Indiana’s,” Justice Thomas wrote. “Enshrining a constitutional right to an abortion based solely on the race, sex or disability of an unborn child, as Planned Parenthood advocates, would constitutionalize the views of the 20th-century eugenics movement.”

The Supreme Court’s decision on the Indiana law comes just weeks after two other stringent state abortion measures were signed into law. On May 7, 2019, Georgia Gov. Brian Kemp (R) signed into law a statute that bars physicians from performing an abortion after a heartbeat is detected – usually at about 6 weeks of pregnancy. On May 15, Alabama Gov. Kay Ivey (R) signed a law that would ban abortion at every pregnancy stage and penalize physicians with a Class A felony for performing an abortion and charge them with a Class C felony for attempting to perform an abortion.

Analysts say the Alabama law, in particular, could land in front of the Supreme Court as a direct challenge to Roe v. Wade. Abortion critics have been encouraged by the Supreme Court appointment of right-leaning Justice Brett M. Kavanaugh and hope the Alabama measure will drive the Supreme Court to reconsider its central holding in Roe, court watchers said.

agallegos@mdedge.com

The U.S. Supreme Court has upheld part of an Indiana law that requires burial or cremation of fetal remains after an abortion, but the justices declined to address the measure’s prohibition on abortions sought because of race, sex, or disability of the fetus.

ETIENJones/thinkstockphotos

In a three-page, unsigned opinion issued May 28, justices wrote that Indiana has a legitimate interest in proper disposition of fetal remains and that the state’s burial/cremation mandate is rational. However, justices said they would not take up the second part of the law regarding abortions based on race, sex, or disability because not enough appeals courts have decided the issue. The court emphasized it was not expressing any view on the merits of the second question.

The opinion stems from an antiabortion measure signed into law by then–Indiana Governor Mike Pence (R) in 2016. According to the law, the health facility where an abortion occurred is required to dispose of fetal remains either by cremation or internment unless the woman or an associated party take possession of the remains. The measure allows the woman or associated party to choose a location of final disposition provided that the parties pay the costs for such arrangements. The second part of the law prohibits an abortion from being performed solely because of the fetus’s expected race, sex, diagnosis, or disability.

Planned Parenthood of Indiana and Kentucky sued over the law, arguing that the measure was unconstitutional. Indiana officials countered the disposal requirements provided fetuses dignity in death and that the law’s abortion restrictions prevented discrimination of particular fetuses in light of technological advances in genetic screening. In 2018, a three-judge panel of the Court of Appeals for the 7th Circuit struck down the entire law. The panel wrote that well-established Supreme Court precedent allows a woman to terminate her pregnancy for any reason and that the Indiana law invaded a woman’s privacy by examining the underlying basis of her decision for an abortion.

In the Supreme Court’s May 28 filing, Justice Ruth Bader Ginsburg and Justice Sonia Sotomayor wrote separately, each stating they would have upheld the lower court’s ban of the entire law. Justice Clarence Thomas, meanwhile, wrote a lengthy separate opinion, agreeing with the court’s decision, but expressing concern over the use of abortion as a “tool of modern-day eugenics.”

“The court will soon need to confront the constitutionality of laws like Indiana’s,” Justice Thomas wrote. “Enshrining a constitutional right to an abortion based solely on the race, sex or disability of an unborn child, as Planned Parenthood advocates, would constitutionalize the views of the 20th-century eugenics movement.”

The Supreme Court’s decision on the Indiana law comes just weeks after two other stringent state abortion measures were signed into law. On May 7, 2019, Georgia Gov. Brian Kemp (R) signed into law a statute that bars physicians from performing an abortion after a heartbeat is detected – usually at about 6 weeks of pregnancy. On May 15, Alabama Gov. Kay Ivey (R) signed a law that would ban abortion at every pregnancy stage and penalize physicians with a Class A felony for performing an abortion and charge them with a Class C felony for attempting to perform an abortion.

Analysts say the Alabama law, in particular, could land in front of the Supreme Court as a direct challenge to Roe v. Wade. Abortion critics have been encouraged by the Supreme Court appointment of right-leaning Justice Brett M. Kavanaugh and hope the Alabama measure will drive the Supreme Court to reconsider its central holding in Roe, court watchers said.

agallegos@mdedge.com

The contribution of joint and skin improvements to the health-related quality of life of patients with psoriatic arthritis: a post hoc analysis of two randomised controlled studies.

Kavanaugh A, Gottlieb A, Morita A, et al. Ann Rheum Dis. 2019 May 21. 

An integrated analysis to determine the contribution of joint and skin improvements to health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Optimal improvements in patients' HRQoL were dependent on successful treatment of both joint and skin symptoms.

Content validity and psychometric evaluation of Functional Assessment of Chronic Illness Therapy-Fatigue in patients with psoriatic arthritis.

Cella D, Wilson H, Shalhoub H, et al. J Patient Rep Outcomes. 2019 May 20;3(1):30.

One-on-one semi-structured qualitative interviews with adult patients evaluated the measurement properties (e.g., content validity, reliability, and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA). Fatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population.

Birth Outcomes and Disease Activity during Pregnancy in a Prospective Cohort of Women with Psoriatic Arthritis and Ankylosing Spondylitis.

Smith CJF, Bandoli G, Kavanaugh A, Chambers CD. Arthritis Care Res (Hoboken). 2019 May 10.

Women with PsA and AS have increased risk for selected adverse pregnancy outcomes. Compared to healthy controls (n=717), PsA (n = 117) was associated with increased risk for moderate preterm delivery (32-36 weeks' gestation), oligohydramnios, and Caesarean delivery. Active disease and corticosteroid use may increase the risk for some adverse pregnancy outcomes in women with these conditions.

Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis.

Alivernini S, Bruno D, Tolusso B, et al. Arthritis Res Ther. 2019 May 9;21(1):116.

The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and seronegative rheumatoid arthritis and test their predictive value of therapeutic response. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.

Psoriatic arthritis - new perspectives.

Krakowski P, Gerkowicz A, Piertrzak A, et al. Arch Med Sci. 2019 May;15(3):580-589.

The management of PsA requires the care of a multidisciplinary team, which should include dermatologists, rheumatologists, physiotherapists, and orthopedic surgeons. PsA should be diagnosed as early as possible to slow down joint damage and progression of disability.

The contribution of joint and skin improvements to the health-related quality of life of patients with psoriatic arthritis: a post hoc analysis of two randomised controlled studies.

Kavanaugh A, Gottlieb A, Morita A, et al. Ann Rheum Dis. 2019 May 21. 

An integrated analysis to determine the contribution of joint and skin improvements to health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Optimal improvements in patients' HRQoL were dependent on successful treatment of both joint and skin symptoms.

Content validity and psychometric evaluation of Functional Assessment of Chronic Illness Therapy-Fatigue in patients with psoriatic arthritis.

Cella D, Wilson H, Shalhoub H, et al. J Patient Rep Outcomes. 2019 May 20;3(1):30.

One-on-one semi-structured qualitative interviews with adult patients evaluated the measurement properties (e.g., content validity, reliability, and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA). Fatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population.

Birth Outcomes and Disease Activity during Pregnancy in a Prospective Cohort of Women with Psoriatic Arthritis and Ankylosing Spondylitis.

Smith CJF, Bandoli G, Kavanaugh A, Chambers CD. Arthritis Care Res (Hoboken). 2019 May 10.

Women with PsA and AS have increased risk for selected adverse pregnancy outcomes. Compared to healthy controls (n=717), PsA (n = 117) was associated with increased risk for moderate preterm delivery (32-36 weeks' gestation), oligohydramnios, and Caesarean delivery. Active disease and corticosteroid use may increase the risk for some adverse pregnancy outcomes in women with these conditions.

Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis.

Alivernini S, Bruno D, Tolusso B, et al. Arthritis Res Ther. 2019 May 9;21(1):116.

The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and seronegative rheumatoid arthritis and test their predictive value of therapeutic response. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.

Psoriatic arthritis - new perspectives.

Krakowski P, Gerkowicz A, Piertrzak A, et al. Arch Med Sci. 2019 May;15(3):580-589.

The management of PsA requires the care of a multidisciplinary team, which should include dermatologists, rheumatologists, physiotherapists, and orthopedic surgeons. PsA should be diagnosed as early as possible to slow down joint damage and progression of disability.

The contribution of joint and skin improvements to the health-related quality of life of patients with psoriatic arthritis: a post hoc analysis of two randomised controlled studies.

Kavanaugh A, Gottlieb A, Morita A, et al. Ann Rheum Dis. 2019 May 21. 

An integrated analysis to determine the contribution of joint and skin improvements to health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Optimal improvements in patients' HRQoL were dependent on successful treatment of both joint and skin symptoms.

Content validity and psychometric evaluation of Functional Assessment of Chronic Illness Therapy-Fatigue in patients with psoriatic arthritis.

Cella D, Wilson H, Shalhoub H, et al. J Patient Rep Outcomes. 2019 May 20;3(1):30.

One-on-one semi-structured qualitative interviews with adult patients evaluated the measurement properties (e.g., content validity, reliability, and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA). Fatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population.

Birth Outcomes and Disease Activity during Pregnancy in a Prospective Cohort of Women with Psoriatic Arthritis and Ankylosing Spondylitis.

Smith CJF, Bandoli G, Kavanaugh A, Chambers CD. Arthritis Care Res (Hoboken). 2019 May 10.

Women with PsA and AS have increased risk for selected adverse pregnancy outcomes. Compared to healthy controls (n=717), PsA (n = 117) was associated with increased risk for moderate preterm delivery (32-36 weeks' gestation), oligohydramnios, and Caesarean delivery. Active disease and corticosteroid use may increase the risk for some adverse pregnancy outcomes in women with these conditions.

Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis.

Alivernini S, Bruno D, Tolusso B, et al. Arthritis Res Ther. 2019 May 9;21(1):116.

The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and seronegative rheumatoid arthritis and test their predictive value of therapeutic response. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.

Psoriatic arthritis - new perspectives.

Krakowski P, Gerkowicz A, Piertrzak A, et al. Arch Med Sci. 2019 May;15(3):580-589.

The management of PsA requires the care of a multidisciplinary team, which should include dermatologists, rheumatologists, physiotherapists, and orthopedic surgeons. PsA should be diagnosed as early as possible to slow down joint damage and progression of disability.

The Diagnosis: Erosive Adenomatosis of the Nipple 

Biopsy of the lesion revealed proliferative sections of glandular epithelium demonstrating apocrine differentiation, connecting to the epidermis and traversing throughout the entire dermis of the specimen (Figure). There were papillary projections of dilated ducts with a retained layer of myoepithelial cells surrounding the epithelial layers. Cytologic atypia was not appreciated. The patient was diagnosed with erosive adenomatosis of the nipple (EAN), also known as nipple adenoma. The lesion subsequently was treated and cleared with Mohs micrographic surgery (MMS). At 8-month follow-up there was no clinical recurrence of the lesion, and the patient was satisfied with the overall cosmetic appearance and conservation of the areola. The patient was followed clinically with annual breast examinations and mammography to monitor future recurrence. 

Erosive adenomatosis of the nipple is an uncommon benign proliferative process of the lactiferous ducts of the nipple. Recognizing EAN is important because it resembles malignant breast diseases such as Paget disease of the nipple and invasive breast carcinoma. Due to these similarities, early cases of EAN have resulted in unnecessary mastectomies before the benignity of the condition was established.¹ Accurate diagnosis is important to both the patient and the clinician for treatment planning as well as psychosocial consequences associated with the potential removal of this anatomically and cosmetically sensitive area. 

Reviewing the literature on EAN is complicated by the variety of terms used to describe this condition, including but not limited to nipple adenoma, nipple duct adenoma, papillary adenoma of the nipple, and florid papillomatosis of the nipple. In 1955, Jones² described EAN using the term florid papillomatosis of the nipple ducts. In 1962, Handley and Thackray¹ argued that adenoma of the nipple was a more descriptive term because it more closely described the appearance of a sweat gland adenoma. They reasoned that adenoma of the nipple is a separate process from ductal papilloma due to the adenomatous proliferation into the nipple stroma rather than the lumen of the nipple ducts.¹ The term adenoma of the nipple was further supported in 1965 by Taylor and Robertson.³ In 1959, Le Gal et al⁴ used the term erosive adenomatosis of the nipple to describe the erosive nature of nipple adenoma. The term nipple adenoma was published in the 2012 WHO Classification of Tumors of the Breast with 4 common histologic subtypes.^5,6  

Erosive adenomatosis of the nipple is clinically indistinguishable from Paget disease of the nipple, thus biopsy is essential for accurate diagnosis. In contrast to Paget disease, EAN tends to present in younger patients and progresses more slowly, and symptoms may be exacerbated around menstruation.¹ Case reports demonstrate that patients may wait years before seeking medical attention for EAN.^1,3,7,8 Presenting symptoms may include inflammation, crusting, nipple skin erosion, itching, and pain. Serous or sanguineous discharge from the lesions also is commonly reported. Palpation may reveal a small, hard, or elastic nodule within or underlying the nipple. In addition to Paget disease, EAN may resemble squamous cell carcinoma of the nipple, eczema, psoriasis, or a skin infection.⁶ Axillary lymphadenopathy is not present in the absence of a concomitant breast malignancy.⁸ On biopsy, nipple adenoma represents ductal proliferation of glandular structures within the stroma of the nipple that is well circumscribed but without borders. The erosive appearance of the lesion is produced by extensions of the glandular epithelium on the surface of the nipple.^1,6 Specific to EAN is the presence of 2 cell types: an inner columnar epithelium and an outer cuboidal myoepithelium. These 2 cell types are present in normal lactiferous ducts; however, normal ducts are highly organized compared to EAN.⁹  

After confirmation of EAN by nipple biopsy, complete surgical excision has been the gold standard for treatment, followed by reconstructive surgery.⁶ Handley and Thackray¹ advocated for total excision of the nipple and areola with an underlying wedge of breast tissue to facilitate wound closure. More recently, successful alternative forms of treatment have been utilized to minimize disfiguring surgery. Alternative treatments include MMS,⁸ cryotherapy,¹⁰ and nipple splitting enucleation.⁶ Treatment with MMS has resulted in nipple sparing with the least amount of surface area sacrificed (1.1 cm2).⁹ Our case and prior case reports demonstrate that the tissue sparing potential of MMS is appropriate for the treatment of EAN, though traditionally it has been reserved for more malignant tumors. Preserving this sensitive area is both cosmetically and psychologically advantageous for the patient and thus should be considered when reviewing treatment options for EAN. 

The Diagnosis: Erosive Adenomatosis of the Nipple 

Biopsy of the lesion revealed proliferative sections of glandular epithelium demonstrating apocrine differentiation, connecting to the epidermis and traversing throughout the entire dermis of the specimen (Figure). There were papillary projections of dilated ducts with a retained layer of myoepithelial cells surrounding the epithelial layers. Cytologic atypia was not appreciated. The patient was diagnosed with erosive adenomatosis of the nipple (EAN), also known as nipple adenoma. The lesion subsequently was treated and cleared with Mohs micrographic surgery (MMS). At 8-month follow-up there was no clinical recurrence of the lesion, and the patient was satisfied with the overall cosmetic appearance and conservation of the areola. The patient was followed clinically with annual breast examinations and mammography to monitor future recurrence. 

Erosive adenomatosis of the nipple is an uncommon benign proliferative process of the lactiferous ducts of the nipple. Recognizing EAN is important because it resembles malignant breast diseases such as Paget disease of the nipple and invasive breast carcinoma. Due to these similarities, early cases of EAN have resulted in unnecessary mastectomies before the benignity of the condition was established.¹ Accurate diagnosis is important to both the patient and the clinician for treatment planning as well as psychosocial consequences associated with the potential removal of this anatomically and cosmetically sensitive area. 

Reviewing the literature on EAN is complicated by the variety of terms used to describe this condition, including but not limited to nipple adenoma, nipple duct adenoma, papillary adenoma of the nipple, and florid papillomatosis of the nipple. In 1955, Jones² described EAN using the term florid papillomatosis of the nipple ducts. In 1962, Handley and Thackray¹ argued that adenoma of the nipple was a more descriptive term because it more closely described the appearance of a sweat gland adenoma. They reasoned that adenoma of the nipple is a separate process from ductal papilloma due to the adenomatous proliferation into the nipple stroma rather than the lumen of the nipple ducts.¹ The term adenoma of the nipple was further supported in 1965 by Taylor and Robertson.³ In 1959, Le Gal et al⁴ used the term erosive adenomatosis of the nipple to describe the erosive nature of nipple adenoma. The term nipple adenoma was published in the 2012 WHO Classification of Tumors of the Breast with 4 common histologic subtypes.^5,6  

Erosive adenomatosis of the nipple is clinically indistinguishable from Paget disease of the nipple, thus biopsy is essential for accurate diagnosis. In contrast to Paget disease, EAN tends to present in younger patients and progresses more slowly, and symptoms may be exacerbated around menstruation.¹ Case reports demonstrate that patients may wait years before seeking medical attention for EAN.^1,3,7,8 Presenting symptoms may include inflammation, crusting, nipple skin erosion, itching, and pain. Serous or sanguineous discharge from the lesions also is commonly reported. Palpation may reveal a small, hard, or elastic nodule within or underlying the nipple. In addition to Paget disease, EAN may resemble squamous cell carcinoma of the nipple, eczema, psoriasis, or a skin infection.⁶ Axillary lymphadenopathy is not present in the absence of a concomitant breast malignancy.⁸ On biopsy, nipple adenoma represents ductal proliferation of glandular structures within the stroma of the nipple that is well circumscribed but without borders. The erosive appearance of the lesion is produced by extensions of the glandular epithelium on the surface of the nipple.^1,6 Specific to EAN is the presence of 2 cell types: an inner columnar epithelium and an outer cuboidal myoepithelium. These 2 cell types are present in normal lactiferous ducts; however, normal ducts are highly organized compared to EAN.⁹  

After confirmation of EAN by nipple biopsy, complete surgical excision has been the gold standard for treatment, followed by reconstructive surgery.⁶ Handley and Thackray¹ advocated for total excision of the nipple and areola with an underlying wedge of breast tissue to facilitate wound closure. More recently, successful alternative forms of treatment have been utilized to minimize disfiguring surgery. Alternative treatments include MMS,⁸ cryotherapy,¹⁰ and nipple splitting enucleation.⁶ Treatment with MMS has resulted in nipple sparing with the least amount of surface area sacrificed (1.1 cm2).⁹ Our case and prior case reports demonstrate that the tissue sparing potential of MMS is appropriate for the treatment of EAN, though traditionally it has been reserved for more malignant tumors. Preserving this sensitive area is both cosmetically and psychologically advantageous for the patient and thus should be considered when reviewing treatment options for EAN. 

The Diagnosis: Erosive Adenomatosis of the Nipple 

Biopsy of the lesion revealed proliferative sections of glandular epithelium demonstrating apocrine differentiation, connecting to the epidermis and traversing throughout the entire dermis of the specimen (Figure). There were papillary projections of dilated ducts with a retained layer of myoepithelial cells surrounding the epithelial layers. Cytologic atypia was not appreciated. The patient was diagnosed with erosive adenomatosis of the nipple (EAN), also known as nipple adenoma. The lesion subsequently was treated and cleared with Mohs micrographic surgery (MMS). At 8-month follow-up there was no clinical recurrence of the lesion, and the patient was satisfied with the overall cosmetic appearance and conservation of the areola. The patient was followed clinically with annual breast examinations and mammography to monitor future recurrence. 

Erosive adenomatosis of the nipple is an uncommon benign proliferative process of the lactiferous ducts of the nipple. Recognizing EAN is important because it resembles malignant breast diseases such as Paget disease of the nipple and invasive breast carcinoma. Due to these similarities, early cases of EAN have resulted in unnecessary mastectomies before the benignity of the condition was established.¹ Accurate diagnosis is important to both the patient and the clinician for treatment planning as well as psychosocial consequences associated with the potential removal of this anatomically and cosmetically sensitive area. 

Reviewing the literature on EAN is complicated by the variety of terms used to describe this condition, including but not limited to nipple adenoma, nipple duct adenoma, papillary adenoma of the nipple, and florid papillomatosis of the nipple. In 1955, Jones² described EAN using the term florid papillomatosis of the nipple ducts. In 1962, Handley and Thackray¹ argued that adenoma of the nipple was a more descriptive term because it more closely described the appearance of a sweat gland adenoma. They reasoned that adenoma of the nipple is a separate process from ductal papilloma due to the adenomatous proliferation into the nipple stroma rather than the lumen of the nipple ducts.¹ The term adenoma of the nipple was further supported in 1965 by Taylor and Robertson.³ In 1959, Le Gal et al⁴ used the term erosive adenomatosis of the nipple to describe the erosive nature of nipple adenoma. The term nipple adenoma was published in the 2012 WHO Classification of Tumors of the Breast with 4 common histologic subtypes.^5,6  

Erosive adenomatosis of the nipple is clinically indistinguishable from Paget disease of the nipple, thus biopsy is essential for accurate diagnosis. In contrast to Paget disease, EAN tends to present in younger patients and progresses more slowly, and symptoms may be exacerbated around menstruation.¹ Case reports demonstrate that patients may wait years before seeking medical attention for EAN.^1,3,7,8 Presenting symptoms may include inflammation, crusting, nipple skin erosion, itching, and pain. Serous or sanguineous discharge from the lesions also is commonly reported. Palpation may reveal a small, hard, or elastic nodule within or underlying the nipple. In addition to Paget disease, EAN may resemble squamous cell carcinoma of the nipple, eczema, psoriasis, or a skin infection.⁶ Axillary lymphadenopathy is not present in the absence of a concomitant breast malignancy.⁸ On biopsy, nipple adenoma represents ductal proliferation of glandular structures within the stroma of the nipple that is well circumscribed but without borders. The erosive appearance of the lesion is produced by extensions of the glandular epithelium on the surface of the nipple.^1,6 Specific to EAN is the presence of 2 cell types: an inner columnar epithelium and an outer cuboidal myoepithelium. These 2 cell types are present in normal lactiferous ducts; however, normal ducts are highly organized compared to EAN.⁹  

After confirmation of EAN by nipple biopsy, complete surgical excision has been the gold standard for treatment, followed by reconstructive surgery.⁶ Handley and Thackray¹ advocated for total excision of the nipple and areola with an underlying wedge of breast tissue to facilitate wound closure. More recently, successful alternative forms of treatment have been utilized to minimize disfiguring surgery. Alternative treatments include MMS,⁸ cryotherapy,¹⁰ and nipple splitting enucleation.⁶ Treatment with MMS has resulted in nipple sparing with the least amount of surface area sacrificed (1.1 cm2).⁹ Our case and prior case reports demonstrate that the tissue sparing potential of MMS is appropriate for the treatment of EAN, though traditionally it has been reserved for more malignant tumors. Preserving this sensitive area is both cosmetically and psychologically advantageous for the patient and thus should be considered when reviewing treatment options for EAN. 

The Food and Drug Administration on May 28 approved a supplemental New Drug Application for cariprazine (Vraylar) for the treatment of depressive episodes associated with bipolar I disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval for the expanded label was based on results of the RGH-MD-53, RGH-MD-54, and RGH-MD-56 clinical trials, in which cariprazine was compared with placebo over a 6-week period in patients with bipolar I disorder. In all three trials, patients receiving 1.5 mg cariprazine had significantly greater improvement in their Montgomery-Åsberg Depression Rating scale after 6 weeks, compared with patients receiving placebo.

Cariprazine previously was indicated for the treatment of manic or mixed episodes associated with bipolar I disorder in adults. The most common adverse reactions reported in the clinical trials were nausea, akathisia, restlessness, and extrapyramidal symptoms; these symptoms are similar to those on the Vraylar label.

“Treating bipolar disorder can be very difficult, because people living with the illness experience a range of depressive and manic symptoms, sometimes both at the same time, and this FDA approval gives health care providers a new option to treat the full spectrum of bipolar I disorder symptoms, specifically manic, mixed, and depressive episodes, with just one medication,” Stephen M. Stahl, MD, PhD, professor of psychiatry at the University of California, San Diego, said in the press release.

Find the full press release on the Allergan website.

lfranki@mdedge.com

The Food and Drug Administration on May 28 approved a supplemental New Drug Application for cariprazine (Vraylar) for the treatment of depressive episodes associated with bipolar I disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval for the expanded label was based on results of the RGH-MD-53, RGH-MD-54, and RGH-MD-56 clinical trials, in which cariprazine was compared with placebo over a 6-week period in patients with bipolar I disorder. In all three trials, patients receiving 1.5 mg cariprazine had significantly greater improvement in their Montgomery-Åsberg Depression Rating scale after 6 weeks, compared with patients receiving placebo.

Cariprazine previously was indicated for the treatment of manic or mixed episodes associated with bipolar I disorder in adults. The most common adverse reactions reported in the clinical trials were nausea, akathisia, restlessness, and extrapyramidal symptoms; these symptoms are similar to those on the Vraylar label.

“Treating bipolar disorder can be very difficult, because people living with the illness experience a range of depressive and manic symptoms, sometimes both at the same time, and this FDA approval gives health care providers a new option to treat the full spectrum of bipolar I disorder symptoms, specifically manic, mixed, and depressive episodes, with just one medication,” Stephen M. Stahl, MD, PhD, professor of psychiatry at the University of California, San Diego, said in the press release.

Find the full press release on the Allergan website.

lfranki@mdedge.com

The Food and Drug Administration on May 28 approved a supplemental New Drug Application for cariprazine (Vraylar) for the treatment of depressive episodes associated with bipolar I disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval for the expanded label was based on results of the RGH-MD-53, RGH-MD-54, and RGH-MD-56 clinical trials, in which cariprazine was compared with placebo over a 6-week period in patients with bipolar I disorder. In all three trials, patients receiving 1.5 mg cariprazine had significantly greater improvement in their Montgomery-Åsberg Depression Rating scale after 6 weeks, compared with patients receiving placebo.

Cariprazine previously was indicated for the treatment of manic or mixed episodes associated with bipolar I disorder in adults. The most common adverse reactions reported in the clinical trials were nausea, akathisia, restlessness, and extrapyramidal symptoms; these symptoms are similar to those on the Vraylar label.

“Treating bipolar disorder can be very difficult, because people living with the illness experience a range of depressive and manic symptoms, sometimes both at the same time, and this FDA approval gives health care providers a new option to treat the full spectrum of bipolar I disorder symptoms, specifically manic, mixed, and depressive episodes, with just one medication,” Stephen M. Stahl, MD, PhD, professor of psychiatry at the University of California, San Diego, said in the press release.

Find the full press release on the Allergan website.

lfranki@mdedge.com

LJUBLJANA, SLOVENIA – Don’t hold your breath waiting for a substantially better, more reliably effective influenza vaccine.

Bruce Jancin/MDedge News

That was a key cautionary message provided by vaccine expert Edward A. Belongia, MD, at the annual meeting of the European Society for Paediatric Infectious Diseases.

The effectiveness of seasonal influenza vaccine varies from 10% to 60% year by year, leaving enormous room for improvement. But many obstacles exist to developing a more consistent and reliably effective version of the seasonal influenza vaccine. And the lofty goal of creating a universal vaccine is even more ambitious, although the National Institute of Allergy and Infectious Diseases has declared it to be a top priority and mapped out a strategic plan for getting there (J Infect Dis. 2018 Jul 2;218[3]:347-54).

“Ultimately the Holy Grail is a universal flu vaccine that would provide pan-A and pan-B protection that would last for more than 1 year, with protection against avian and pandemic viruses, and would work for both children and adults. We are nowhere near that. Every 5 years someone says we’re 5 years away, and then 5 years go by and we’re still 5 years away. So I’m not making any predictions on that,” said Dr. Belongia, director of the Center for Clinical Epidemiology and Population Health at the Marshfield (Wisc.) Clinic Research Institute, which is part of the U.S. Influenza Vaccine Effectiveness Network.

One of the big problems in creating a more effective flu vaccine, particularly for children, is the H3N2 virus subtype. Dr. Belongia was first author of a systematic review and meta-analysis of studies of more than a dozen recent flu seasons showing that although vaccine effectiveness against H3N2 varied widely from year to year, it was consistently lower than against influenza type B and H1N1 (Lancet Infect Dis. 2016 Aug;16[8]:942-51).

And that’s especially true in children and adolescents. Notably, in the 2014-2015 U.S. flu season, vaccine effectiveness against H3N2 in children aged 6 months to 8 years was low at 23%, but shockingly lower at a mere 7% in the 9- to 17-year-olds. Whereas in the 2017-2018 season, vaccine effectiveness against H3N2 in the 9- to 17-year-olds jumped to 46% while remaining low but consistent at 22% in the younger children.

“We see a very different age pattern here for the older children compared to the younger children, and quite frankly we don’t really understand what’s doing this,” said Dr. Belongia.

What is well understood, however, is that the problematic performance of influenza vaccines when it comes to protecting against H3N2 is a complicated matter stemming from three sources: the virus itself; the current egg-based vaccine manufacturing methodology, which is now 7 decades old; and host factors.


 

That troublesome H3N2 virus

Antigenic evolution of the H3N2 virus occurs at a 5- to 6-fold higher rate than for influenza B virus and roughly 17-fold faster than for H1N1. That high mutation rate makes for a moving target that’s a real problem when trying to keep a vaccine current. Also, the globular head of the virus is prone to glycosylation, which enables the virus to evade immune detection.

Vaccine-related factors

It’s likely that the availability of the flu vaccine for the upcoming 2019-2020 season is going to be delayed because of late selection of the strains for inclusion. The World Health Organization ordinarily selects strains for vaccines for the Northern Hemisphere in February, giving vaccine manufacturers 6-8 months to produce their vaccines and ship them in time for administration from September through November. This year, however, the WHO delayed selection of the H3N2 component until March because of the high level of antigenic and genetic diversity of circulating strains.

“This hasn’t happened since 2003 – it’s a very rare occurrence – but it does increase the potential that there’s going to be a delay in the availability of the vaccine in the fall,” he explained.

Eventually, the WHO selected a new clade 3C.3a virus called A/Kansas/14/2017 for the 2019-2020 vaccine. It should cover the circulating strains of H3N2 “reasonably well,” according to the physician.

Another issue: H3N2 has become adapted to the mammalian environment, so growing the virus in eggs introduces strong selection pressure for mutations leading to reduced vaccine effectiveness. Yet only two flu vaccines licensed in the United States are manufactured without eggs: Flucelvax, marketed by Seqirus for patients aged 4 years and up, and Sanofi’s Flublok, which is licensed for individuals who are 18 years of age or older. Studies are underway looking at the relative effectiveness of egg-based versus cell culture-manufactured flu vaccines in real-world settings.
 

Host factors

Hemagglutinin imprinting, sometimes referred to as “original antigenic sin,” is a decades-old concept whereby early childhood exposure to influenza viruses shapes future vaccine response.

“It suggests there could be some birth cohort effects in vaccine responsiveness, depending on what was circulating in the first 2-3 years after birth. It would complicate vaccine strategy quite a bit if you had to have different strategies for different birth cohorts,” Dr. Belongia observed.

Another host factor issue is the controversial topic of negative interference stemming from repeated vaccinations. It’s unclear how important this is in the real world, because studies have been inconsistent. Reassuringly, Dr. Belongia and coworkers found no association between prior-season influenza vaccination and diminished vaccine effectiveness in 3,369 U.S. children aged 2-17 years studied during the 2013-14 through 2015-16 flu seasons (JAMA Netw Open. 2018 Oct 5;1[6]:e183742. doi: 10.1001/jamanetworkopen.2018.3742).

“We found no suggestion at all of a problem with being vaccinated two seasons in a row,” according to Dr. Belongia.


 

How to build a better influenza vaccine for children

“I would say that even before we get to a universal vaccine, the next generation of flu vaccines that are more effective are not going to be manufactured using eggs, although we’re not real close to that. But I think that’s eventually where we’re going,” he said.

“I think it’s going to take a systems biology approach in order to really understand the adaptive immune response to infection and vaccination in early life. That means a much more detailed understanding of what is underlying the imprinting mechanisms and what is the adaptive response to repeated vaccination and infection. I think this is going to take prospective infant cohort studies; the National Institutes of Health is funding some that will begin within the next year,” Dr. Belongia added.

Many investigational approaches to improving influenza virus subtype-level protection are being explored. These include novel adjuvants, nanoparticle vaccines, computationally optimized broadly reactive antigens, and standardization of neuraminidase content.

And as for the much-desired universal flu vaccine?

“I will say that if a universal vaccine is going to work it’s probably going to work first in children. They have a much shorter immune history and their antibody landscape is a lot smaller, so you have a much better opportunity, I think, to generate a broad response to a universal vaccine compared to adults, who have much more complex immune landscapes,” he said.

Dr. Belongia reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Don’t hold your breath waiting for a substantially better, more reliably effective influenza vaccine.

Bruce Jancin/MDedge News

That was a key cautionary message provided by vaccine expert Edward A. Belongia, MD, at the annual meeting of the European Society for Paediatric Infectious Diseases.

The effectiveness of seasonal influenza vaccine varies from 10% to 60% year by year, leaving enormous room for improvement. But many obstacles exist to developing a more consistent and reliably effective version of the seasonal influenza vaccine. And the lofty goal of creating a universal vaccine is even more ambitious, although the National Institute of Allergy and Infectious Diseases has declared it to be a top priority and mapped out a strategic plan for getting there (J Infect Dis. 2018 Jul 2;218[3]:347-54).

“Ultimately the Holy Grail is a universal flu vaccine that would provide pan-A and pan-B protection that would last for more than 1 year, with protection against avian and pandemic viruses, and would work for both children and adults. We are nowhere near that. Every 5 years someone says we’re 5 years away, and then 5 years go by and we’re still 5 years away. So I’m not making any predictions on that,” said Dr. Belongia, director of the Center for Clinical Epidemiology and Population Health at the Marshfield (Wisc.) Clinic Research Institute, which is part of the U.S. Influenza Vaccine Effectiveness Network.

One of the big problems in creating a more effective flu vaccine, particularly for children, is the H3N2 virus subtype. Dr. Belongia was first author of a systematic review and meta-analysis of studies of more than a dozen recent flu seasons showing that although vaccine effectiveness against H3N2 varied widely from year to year, it was consistently lower than against influenza type B and H1N1 (Lancet Infect Dis. 2016 Aug;16[8]:942-51).

And that’s especially true in children and adolescents. Notably, in the 2014-2015 U.S. flu season, vaccine effectiveness against H3N2 in children aged 6 months to 8 years was low at 23%, but shockingly lower at a mere 7% in the 9- to 17-year-olds. Whereas in the 2017-2018 season, vaccine effectiveness against H3N2 in the 9- to 17-year-olds jumped to 46% while remaining low but consistent at 22% in the younger children.

“We see a very different age pattern here for the older children compared to the younger children, and quite frankly we don’t really understand what’s doing this,” said Dr. Belongia.

What is well understood, however, is that the problematic performance of influenza vaccines when it comes to protecting against H3N2 is a complicated matter stemming from three sources: the virus itself; the current egg-based vaccine manufacturing methodology, which is now 7 decades old; and host factors.


 

That troublesome H3N2 virus

Antigenic evolution of the H3N2 virus occurs at a 5- to 6-fold higher rate than for influenza B virus and roughly 17-fold faster than for H1N1. That high mutation rate makes for a moving target that’s a real problem when trying to keep a vaccine current. Also, the globular head of the virus is prone to glycosylation, which enables the virus to evade immune detection.

Vaccine-related factors

It’s likely that the availability of the flu vaccine for the upcoming 2019-2020 season is going to be delayed because of late selection of the strains for inclusion. The World Health Organization ordinarily selects strains for vaccines for the Northern Hemisphere in February, giving vaccine manufacturers 6-8 months to produce their vaccines and ship them in time for administration from September through November. This year, however, the WHO delayed selection of the H3N2 component until March because of the high level of antigenic and genetic diversity of circulating strains.

“This hasn’t happened since 2003 – it’s a very rare occurrence – but it does increase the potential that there’s going to be a delay in the availability of the vaccine in the fall,” he explained.

Eventually, the WHO selected a new clade 3C.3a virus called A/Kansas/14/2017 for the 2019-2020 vaccine. It should cover the circulating strains of H3N2 “reasonably well,” according to the physician.

Another issue: H3N2 has become adapted to the mammalian environment, so growing the virus in eggs introduces strong selection pressure for mutations leading to reduced vaccine effectiveness. Yet only two flu vaccines licensed in the United States are manufactured without eggs: Flucelvax, marketed by Seqirus for patients aged 4 years and up, and Sanofi’s Flublok, which is licensed for individuals who are 18 years of age or older. Studies are underway looking at the relative effectiveness of egg-based versus cell culture-manufactured flu vaccines in real-world settings.
 

Host factors

Hemagglutinin imprinting, sometimes referred to as “original antigenic sin,” is a decades-old concept whereby early childhood exposure to influenza viruses shapes future vaccine response.

“It suggests there could be some birth cohort effects in vaccine responsiveness, depending on what was circulating in the first 2-3 years after birth. It would complicate vaccine strategy quite a bit if you had to have different strategies for different birth cohorts,” Dr. Belongia observed.

Another host factor issue is the controversial topic of negative interference stemming from repeated vaccinations. It’s unclear how important this is in the real world, because studies have been inconsistent. Reassuringly, Dr. Belongia and coworkers found no association between prior-season influenza vaccination and diminished vaccine effectiveness in 3,369 U.S. children aged 2-17 years studied during the 2013-14 through 2015-16 flu seasons (JAMA Netw Open. 2018 Oct 5;1[6]:e183742. doi: 10.1001/jamanetworkopen.2018.3742).

“We found no suggestion at all of a problem with being vaccinated two seasons in a row,” according to Dr. Belongia.


 

How to build a better influenza vaccine for children

“I would say that even before we get to a universal vaccine, the next generation of flu vaccines that are more effective are not going to be manufactured using eggs, although we’re not real close to that. But I think that’s eventually where we’re going,” he said.

“I think it’s going to take a systems biology approach in order to really understand the adaptive immune response to infection and vaccination in early life. That means a much more detailed understanding of what is underlying the imprinting mechanisms and what is the adaptive response to repeated vaccination and infection. I think this is going to take prospective infant cohort studies; the National Institutes of Health is funding some that will begin within the next year,” Dr. Belongia added.

Many investigational approaches to improving influenza virus subtype-level protection are being explored. These include novel adjuvants, nanoparticle vaccines, computationally optimized broadly reactive antigens, and standardization of neuraminidase content.

And as for the much-desired universal flu vaccine?

“I will say that if a universal vaccine is going to work it’s probably going to work first in children. They have a much shorter immune history and their antibody landscape is a lot smaller, so you have a much better opportunity, I think, to generate a broad response to a universal vaccine compared to adults, who have much more complex immune landscapes,” he said.

Dr. Belongia reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Don’t hold your breath waiting for a substantially better, more reliably effective influenza vaccine.

Bruce Jancin/MDedge News

That was a key cautionary message provided by vaccine expert Edward A. Belongia, MD, at the annual meeting of the European Society for Paediatric Infectious Diseases.

The effectiveness of seasonal influenza vaccine varies from 10% to 60% year by year, leaving enormous room for improvement. But many obstacles exist to developing a more consistent and reliably effective version of the seasonal influenza vaccine. And the lofty goal of creating a universal vaccine is even more ambitious, although the National Institute of Allergy and Infectious Diseases has declared it to be a top priority and mapped out a strategic plan for getting there (J Infect Dis. 2018 Jul 2;218[3]:347-54).

“Ultimately the Holy Grail is a universal flu vaccine that would provide pan-A and pan-B protection that would last for more than 1 year, with protection against avian and pandemic viruses, and would work for both children and adults. We are nowhere near that. Every 5 years someone says we’re 5 years away, and then 5 years go by and we’re still 5 years away. So I’m not making any predictions on that,” said Dr. Belongia, director of the Center for Clinical Epidemiology and Population Health at the Marshfield (Wisc.) Clinic Research Institute, which is part of the U.S. Influenza Vaccine Effectiveness Network.

One of the big problems in creating a more effective flu vaccine, particularly for children, is the H3N2 virus subtype. Dr. Belongia was first author of a systematic review and meta-analysis of studies of more than a dozen recent flu seasons showing that although vaccine effectiveness against H3N2 varied widely from year to year, it was consistently lower than against influenza type B and H1N1 (Lancet Infect Dis. 2016 Aug;16[8]:942-51).

And that’s especially true in children and adolescents. Notably, in the 2014-2015 U.S. flu season, vaccine effectiveness against H3N2 in children aged 6 months to 8 years was low at 23%, but shockingly lower at a mere 7% in the 9- to 17-year-olds. Whereas in the 2017-2018 season, vaccine effectiveness against H3N2 in the 9- to 17-year-olds jumped to 46% while remaining low but consistent at 22% in the younger children.

“We see a very different age pattern here for the older children compared to the younger children, and quite frankly we don’t really understand what’s doing this,” said Dr. Belongia.

What is well understood, however, is that the problematic performance of influenza vaccines when it comes to protecting against H3N2 is a complicated matter stemming from three sources: the virus itself; the current egg-based vaccine manufacturing methodology, which is now 7 decades old; and host factors.


 

That troublesome H3N2 virus

Antigenic evolution of the H3N2 virus occurs at a 5- to 6-fold higher rate than for influenza B virus and roughly 17-fold faster than for H1N1. That high mutation rate makes for a moving target that’s a real problem when trying to keep a vaccine current. Also, the globular head of the virus is prone to glycosylation, which enables the virus to evade immune detection.

Vaccine-related factors

It’s likely that the availability of the flu vaccine for the upcoming 2019-2020 season is going to be delayed because of late selection of the strains for inclusion. The World Health Organization ordinarily selects strains for vaccines for the Northern Hemisphere in February, giving vaccine manufacturers 6-8 months to produce their vaccines and ship them in time for administration from September through November. This year, however, the WHO delayed selection of the H3N2 component until March because of the high level of antigenic and genetic diversity of circulating strains.

“This hasn’t happened since 2003 – it’s a very rare occurrence – but it does increase the potential that there’s going to be a delay in the availability of the vaccine in the fall,” he explained.

Eventually, the WHO selected a new clade 3C.3a virus called A/Kansas/14/2017 for the 2019-2020 vaccine. It should cover the circulating strains of H3N2 “reasonably well,” according to the physician.

Another issue: H3N2 has become adapted to the mammalian environment, so growing the virus in eggs introduces strong selection pressure for mutations leading to reduced vaccine effectiveness. Yet only two flu vaccines licensed in the United States are manufactured without eggs: Flucelvax, marketed by Seqirus for patients aged 4 years and up, and Sanofi’s Flublok, which is licensed for individuals who are 18 years of age or older. Studies are underway looking at the relative effectiveness of egg-based versus cell culture-manufactured flu vaccines in real-world settings.
 

Host factors

Hemagglutinin imprinting, sometimes referred to as “original antigenic sin,” is a decades-old concept whereby early childhood exposure to influenza viruses shapes future vaccine response.

“It suggests there could be some birth cohort effects in vaccine responsiveness, depending on what was circulating in the first 2-3 years after birth. It would complicate vaccine strategy quite a bit if you had to have different strategies for different birth cohorts,” Dr. Belongia observed.

Another host factor issue is the controversial topic of negative interference stemming from repeated vaccinations. It’s unclear how important this is in the real world, because studies have been inconsistent. Reassuringly, Dr. Belongia and coworkers found no association between prior-season influenza vaccination and diminished vaccine effectiveness in 3,369 U.S. children aged 2-17 years studied during the 2013-14 through 2015-16 flu seasons (JAMA Netw Open. 2018 Oct 5;1[6]:e183742. doi: 10.1001/jamanetworkopen.2018.3742).

“We found no suggestion at all of a problem with being vaccinated two seasons in a row,” according to Dr. Belongia.


 

How to build a better influenza vaccine for children

“I would say that even before we get to a universal vaccine, the next generation of flu vaccines that are more effective are not going to be manufactured using eggs, although we’re not real close to that. But I think that’s eventually where we’re going,” he said.

“I think it’s going to take a systems biology approach in order to really understand the adaptive immune response to infection and vaccination in early life. That means a much more detailed understanding of what is underlying the imprinting mechanisms and what is the adaptive response to repeated vaccination and infection. I think this is going to take prospective infant cohort studies; the National Institutes of Health is funding some that will begin within the next year,” Dr. Belongia added.

Many investigational approaches to improving influenza virus subtype-level protection are being explored. These include novel adjuvants, nanoparticle vaccines, computationally optimized broadly reactive antigens, and standardization of neuraminidase content.

And as for the much-desired universal flu vaccine?

“I will say that if a universal vaccine is going to work it’s probably going to work first in children. They have a much shorter immune history and their antibody landscape is a lot smaller, so you have a much better opportunity, I think, to generate a broad response to a universal vaccine compared to adults, who have much more complex immune landscapes,” he said.

Dr. Belongia reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) should include risk assessment and clinician-patient discussion that varies by the level of risk involved, according to the 2018 update to U.S. guidelines for cholesterol management from the American Heart Association and the American College of Cardiology.

The guideline also emphasizes “careful adherence to lifestyle recommendations at an early age [to] reduce risk factor burden over the lifespan and decrease the need for preventive drug therapies later in life,” Scott M. Grundy, MD, PhD, and Neil J. Stone, MD, said in a synopsis of the document in the Annals of Internal Medicine.

For primary prevention in patients aged 40-75 years, estimation of 10-year ASCVD risk – introduced in the 2013 guidelines – and stratification into one of four categories should set the stage for clinician-patient discussion. A score of less than 5% indicates low risk and should prompt a risk discussion that emphasizes lifestyle recommendations. “Statins are clinically efficacious in the latter three categories, but the higher the risk, the stronger the statin indication,” said Dr. Grundy of the University of Texas, Dallas, and Dr. Stone of Northwestern University, Chicago.


When risk status is uncertain, measurement of coronary artery calcium should be considered in patients aged 40-75 years with LDL cholesterol levels of 70-189 mg/dL who do no not have diabetes, they noted.

The guideline emphasizes secondary prevention with “maximally tolerated doses of statins” and the use of nonstatin drugs such as ezetimibe and PCSK9 inhibitors for patients with very high ASCVD risk – defined as a history of multiple major events or one event and other high-risk conditions, Dr. Grundy and Dr. Stone wrote.

Financial support for the Guideline Writing Committee for the 2018 Cholesterol Guidelines came from the AHA and the ACC. Dr. Grundy and Dr. Stone said that they had no relevant conflicts of interest.

rfranki@mdedge.com

SOURCE: Grundy SM and Stone NJ. Ann Intern Med. 2019 May 28. doi: 10.7326/M19-0365.

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) should include risk assessment and clinician-patient discussion that varies by the level of risk involved, according to the 2018 update to U.S. guidelines for cholesterol management from the American Heart Association and the American College of Cardiology.

The guideline also emphasizes “careful adherence to lifestyle recommendations at an early age [to] reduce risk factor burden over the lifespan and decrease the need for preventive drug therapies later in life,” Scott M. Grundy, MD, PhD, and Neil J. Stone, MD, said in a synopsis of the document in the Annals of Internal Medicine.

For primary prevention in patients aged 40-75 years, estimation of 10-year ASCVD risk – introduced in the 2013 guidelines – and stratification into one of four categories should set the stage for clinician-patient discussion. A score of less than 5% indicates low risk and should prompt a risk discussion that emphasizes lifestyle recommendations. “Statins are clinically efficacious in the latter three categories, but the higher the risk, the stronger the statin indication,” said Dr. Grundy of the University of Texas, Dallas, and Dr. Stone of Northwestern University, Chicago.


When risk status is uncertain, measurement of coronary artery calcium should be considered in patients aged 40-75 years with LDL cholesterol levels of 70-189 mg/dL who do no not have diabetes, they noted.

The guideline emphasizes secondary prevention with “maximally tolerated doses of statins” and the use of nonstatin drugs such as ezetimibe and PCSK9 inhibitors for patients with very high ASCVD risk – defined as a history of multiple major events or one event and other high-risk conditions, Dr. Grundy and Dr. Stone wrote.

Financial support for the Guideline Writing Committee for the 2018 Cholesterol Guidelines came from the AHA and the ACC. Dr. Grundy and Dr. Stone said that they had no relevant conflicts of interest.

rfranki@mdedge.com

SOURCE: Grundy SM and Stone NJ. Ann Intern Med. 2019 May 28. doi: 10.7326/M19-0365.

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) should include risk assessment and clinician-patient discussion that varies by the level of risk involved, according to the 2018 update to U.S. guidelines for cholesterol management from the American Heart Association and the American College of Cardiology.

The guideline also emphasizes “careful adherence to lifestyle recommendations at an early age [to] reduce risk factor burden over the lifespan and decrease the need for preventive drug therapies later in life,” Scott M. Grundy, MD, PhD, and Neil J. Stone, MD, said in a synopsis of the document in the Annals of Internal Medicine.

For primary prevention in patients aged 40-75 years, estimation of 10-year ASCVD risk – introduced in the 2013 guidelines – and stratification into one of four categories should set the stage for clinician-patient discussion. A score of less than 5% indicates low risk and should prompt a risk discussion that emphasizes lifestyle recommendations. “Statins are clinically efficacious in the latter three categories, but the higher the risk, the stronger the statin indication,” said Dr. Grundy of the University of Texas, Dallas, and Dr. Stone of Northwestern University, Chicago.


When risk status is uncertain, measurement of coronary artery calcium should be considered in patients aged 40-75 years with LDL cholesterol levels of 70-189 mg/dL who do no not have diabetes, they noted.

The guideline emphasizes secondary prevention with “maximally tolerated doses of statins” and the use of nonstatin drugs such as ezetimibe and PCSK9 inhibitors for patients with very high ASCVD risk – defined as a history of multiple major events or one event and other high-risk conditions, Dr. Grundy and Dr. Stone wrote.

Financial support for the Guideline Writing Committee for the 2018 Cholesterol Guidelines came from the AHA and the ACC. Dr. Grundy and Dr. Stone said that they had no relevant conflicts of interest.

rfranki@mdedge.com

SOURCE: Grundy SM and Stone NJ. Ann Intern Med. 2019 May 28. doi: 10.7326/M19-0365.

Endometriosis, defined by the ectopic growth of functioning endometrial glands and stroma,^1,2 usually affects the peritoneal cavity. However, endometriosis has been identified in the pneumothorax, brain, and within the extraperitoneum, such as the abdominal wall.^1-3 Incidence of abdominal wall endometriosis can be up to 12%.^3-5 If patients report symptoms, they can include abdominal pain, a palpable mass, pelvic pain consistent with endometriosis, and bleeding from involvement of the overlying skin. Abdominal wall endometriosis can be surgically resected, with complete resolution and a low rate of recurrence.

In the following video, we review the diagnosis of abdominal wall endometriosis, including our imaging of choice, and treatment options. In addition, we illustrate a surgical technique for the excision of abdominal wall endometriosis in a 38-year-old patient with symptomatic disease. We conclude with a review of key surgical steps.

We hope that you find this video useful to your clinical practice.
>> Dr. Arnold P. Advincula, and colleagues

Vidyard Video

Endometriosis, defined by the ectopic growth of functioning endometrial glands and stroma,^1,2 usually affects the peritoneal cavity. However, endometriosis has been identified in the pneumothorax, brain, and within the extraperitoneum, such as the abdominal wall.^1-3 Incidence of abdominal wall endometriosis can be up to 12%.^3-5 If patients report symptoms, they can include abdominal pain, a palpable mass, pelvic pain consistent with endometriosis, and bleeding from involvement of the overlying skin. Abdominal wall endometriosis can be surgically resected, with complete resolution and a low rate of recurrence.

In the following video, we review the diagnosis of abdominal wall endometriosis, including our imaging of choice, and treatment options. In addition, we illustrate a surgical technique for the excision of abdominal wall endometriosis in a 38-year-old patient with symptomatic disease. We conclude with a review of key surgical steps.

We hope that you find this video useful to your clinical practice.
>> Dr. Arnold P. Advincula, and colleagues

Vidyard Video

Endometriosis, defined by the ectopic growth of functioning endometrial glands and stroma,^1,2 usually affects the peritoneal cavity. However, endometriosis has been identified in the pneumothorax, brain, and within the extraperitoneum, such as the abdominal wall.^1-3 Incidence of abdominal wall endometriosis can be up to 12%.^3-5 If patients report symptoms, they can include abdominal pain, a palpable mass, pelvic pain consistent with endometriosis, and bleeding from involvement of the overlying skin. Abdominal wall endometriosis can be surgically resected, with complete resolution and a low rate of recurrence.

In the following video, we review the diagnosis of abdominal wall endometriosis, including our imaging of choice, and treatment options. In addition, we illustrate a surgical technique for the excision of abdominal wall endometriosis in a 38-year-old patient with symptomatic disease. We conclude with a review of key surgical steps.

We hope that you find this video useful to your clinical practice.
>> Dr. Arnold P. Advincula, and colleagues

Vidyard Video

The year’s first cases of measles in Maine and New Mexico bring the total number of states with the virus to 26 in 2019, according to the Centers for Disease Control and Prevention.

The CDC received reports of 60 new measles cases last week – up from 41 the previous week – bringing the U.S. total to 940 for the year as of May 24. The CDC is currently tracking 10 outbreaks in seven states: California (3), Georgia, Maryland, Michigan, New York (2), Pennsylvania, and Washington.


The Maine Center for Disease Control and Prevention confirmed the state’s first case on May 20. The school-aged child from Somerset County had been vaccinated and is fully recovered from the disease. It’s not yet known where the child was exposed to measles, but sporadic cases are not unexpected, the Maine CDC said.

New Mexico’s first measles case of the year, a 1-year-old in Sierra County, has at least one state lawmaker considering changes to the state’s immunization exemption laws, the Farmington Daily Times reported.

rfranki@mdedge.com

The year’s first cases of measles in Maine and New Mexico bring the total number of states with the virus to 26 in 2019, according to the Centers for Disease Control and Prevention.

The CDC received reports of 60 new measles cases last week – up from 41 the previous week – bringing the U.S. total to 940 for the year as of May 24. The CDC is currently tracking 10 outbreaks in seven states: California (3), Georgia, Maryland, Michigan, New York (2), Pennsylvania, and Washington.


The Maine Center for Disease Control and Prevention confirmed the state’s first case on May 20. The school-aged child from Somerset County had been vaccinated and is fully recovered from the disease. It’s not yet known where the child was exposed to measles, but sporadic cases are not unexpected, the Maine CDC said.

New Mexico’s first measles case of the year, a 1-year-old in Sierra County, has at least one state lawmaker considering changes to the state’s immunization exemption laws, the Farmington Daily Times reported.

rfranki@mdedge.com

The year’s first cases of measles in Maine and New Mexico bring the total number of states with the virus to 26 in 2019, according to the Centers for Disease Control and Prevention.

The CDC received reports of 60 new measles cases last week – up from 41 the previous week – bringing the U.S. total to 940 for the year as of May 24. The CDC is currently tracking 10 outbreaks in seven states: California (3), Georgia, Maryland, Michigan, New York (2), Pennsylvania, and Washington.


The Maine Center for Disease Control and Prevention confirmed the state’s first case on May 20. The school-aged child from Somerset County had been vaccinated and is fully recovered from the disease. It’s not yet known where the child was exposed to measles, but sporadic cases are not unexpected, the Maine CDC said.

New Mexico’s first measles case of the year, a 1-year-old in Sierra County, has at least one state lawmaker considering changes to the state’s immunization exemption laws, the Farmington Daily Times reported.

rfranki@mdedge.com

TORONTO – Patients with osteoarthritis often want to know if their debilitating disease is likely to be passed on to their children. Karin Magnusson, PhD, believes she can answer that question based upon an analysis of two large Nordic studies.

Bruce Jancin/MDedge News

“OA in the mother, but not in the father, increases the risk of surgical and clinically defined hip, knee, and hand OA in the offspring, and particularly in daughters,” she reported at the OARSI 2019 World Congress.

Dr. Magnusson, an epidemiologist at Lund (Sweden) University, and her coinvestigators, turned to the Musculoskeletal Pain in Ullensaker Study (MUST) of 630 individuals aged 40-79 with rheumatologist-diagnosed hand, hip, or knee OA by American College of Rheumatology clinical criteria and their offspring, as well as the Nor-Twin OA Study of 7,184 twins, aged 30-75, and their children. Linkage with a national registry that records virtually all joint arthroplasties performed in Norway enabled the investigators to identify which subjects in the two studies had joint surgery for OA, she explained at the meeting, sponsored by the Osteoarthritis Research Society International.

The main outcome in this analysis was the relative risk of hip, knee, or hand OA in the sons and daughters of families in which a parent had OA at those sites, compared with the rate when neither parent had OA. The key finding: If the mother had OA, her daughters had a 13% increased risk of OA in MUST and a 44% increased risk in the Nor-Twin OA Study when compared with daughters of women without OA. In contrast, the sons of a mother with OA had no significant increase in risk of OA. And when OA was present in the father, there was no increased risk of OA at any site in his daughters or sons.

“The implication is the heredity of OA is linked to maternal genes and/or maternal-specific factors, such as the fetal environment,” according to Dr. Magnusson.

And for clinical practice, the implication is that it’s important to ask about family history of OA, and in which parent, to better predict future risk of disease transmission to the children, she added.

These Norwegian study results open the door to exploration of the possible role of mitochondrial DNA in familial clustering of OA, since mitochondrial DNA is inherited only from the mother, Dr. Magnusson noted.

David T. Felson, MD, rose from the audience to say, “I’m a little bit worried” about the fact that when he and other Framingham Heart Study investigators looked specifically for possible mother/daughter, mother/son, father/daughter, and father/son associations for knee and hip OA, “we really didn’t find any.

“You can go through all of the explanations that you want about maternal inheritance, but I’m not sure that’s the best explanation. It might just be that what’s going on here is you’re seeing guys who are relatively young and who got their OA through injury or sports, which is fairly common in young men, and not through inheritance,” said Dr. Felson, professor of medicine and epidemiology at Boston University.

So a third observational study in an independent cohort might be needed as a tie breaker regarding the issue of OA inheritance.

Dr. Magnusson reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Magnusson K et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S47, Abstract 33

TORONTO – Patients with osteoarthritis often want to know if their debilitating disease is likely to be passed on to their children. Karin Magnusson, PhD, believes she can answer that question based upon an analysis of two large Nordic studies.

Bruce Jancin/MDedge News

“OA in the mother, but not in the father, increases the risk of surgical and clinically defined hip, knee, and hand OA in the offspring, and particularly in daughters,” she reported at the OARSI 2019 World Congress.

Dr. Magnusson, an epidemiologist at Lund (Sweden) University, and her coinvestigators, turned to the Musculoskeletal Pain in Ullensaker Study (MUST) of 630 individuals aged 40-79 with rheumatologist-diagnosed hand, hip, or knee OA by American College of Rheumatology clinical criteria and their offspring, as well as the Nor-Twin OA Study of 7,184 twins, aged 30-75, and their children. Linkage with a national registry that records virtually all joint arthroplasties performed in Norway enabled the investigators to identify which subjects in the two studies had joint surgery for OA, she explained at the meeting, sponsored by the Osteoarthritis Research Society International.

The main outcome in this analysis was the relative risk of hip, knee, or hand OA in the sons and daughters of families in which a parent had OA at those sites, compared with the rate when neither parent had OA. The key finding: If the mother had OA, her daughters had a 13% increased risk of OA in MUST and a 44% increased risk in the Nor-Twin OA Study when compared with daughters of women without OA. In contrast, the sons of a mother with OA had no significant increase in risk of OA. And when OA was present in the father, there was no increased risk of OA at any site in his daughters or sons.

“The implication is the heredity of OA is linked to maternal genes and/or maternal-specific factors, such as the fetal environment,” according to Dr. Magnusson.

And for clinical practice, the implication is that it’s important to ask about family history of OA, and in which parent, to better predict future risk of disease transmission to the children, she added.

These Norwegian study results open the door to exploration of the possible role of mitochondrial DNA in familial clustering of OA, since mitochondrial DNA is inherited only from the mother, Dr. Magnusson noted.

David T. Felson, MD, rose from the audience to say, “I’m a little bit worried” about the fact that when he and other Framingham Heart Study investigators looked specifically for possible mother/daughter, mother/son, father/daughter, and father/son associations for knee and hip OA, “we really didn’t find any.

“You can go through all of the explanations that you want about maternal inheritance, but I’m not sure that’s the best explanation. It might just be that what’s going on here is you’re seeing guys who are relatively young and who got their OA through injury or sports, which is fairly common in young men, and not through inheritance,” said Dr. Felson, professor of medicine and epidemiology at Boston University.

So a third observational study in an independent cohort might be needed as a tie breaker regarding the issue of OA inheritance.

Dr. Magnusson reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Magnusson K et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S47, Abstract 33

TORONTO – Patients with osteoarthritis often want to know if their debilitating disease is likely to be passed on to their children. Karin Magnusson, PhD, believes she can answer that question based upon an analysis of two large Nordic studies.

Bruce Jancin/MDedge News

“OA in the mother, but not in the father, increases the risk of surgical and clinically defined hip, knee, and hand OA in the offspring, and particularly in daughters,” she reported at the OARSI 2019 World Congress.

Dr. Magnusson, an epidemiologist at Lund (Sweden) University, and her coinvestigators, turned to the Musculoskeletal Pain in Ullensaker Study (MUST) of 630 individuals aged 40-79 with rheumatologist-diagnosed hand, hip, or knee OA by American College of Rheumatology clinical criteria and their offspring, as well as the Nor-Twin OA Study of 7,184 twins, aged 30-75, and their children. Linkage with a national registry that records virtually all joint arthroplasties performed in Norway enabled the investigators to identify which subjects in the two studies had joint surgery for OA, she explained at the meeting, sponsored by the Osteoarthritis Research Society International.

The main outcome in this analysis was the relative risk of hip, knee, or hand OA in the sons and daughters of families in which a parent had OA at those sites, compared with the rate when neither parent had OA. The key finding: If the mother had OA, her daughters had a 13% increased risk of OA in MUST and a 44% increased risk in the Nor-Twin OA Study when compared with daughters of women without OA. In contrast, the sons of a mother with OA had no significant increase in risk of OA. And when OA was present in the father, there was no increased risk of OA at any site in his daughters or sons.

“The implication is the heredity of OA is linked to maternal genes and/or maternal-specific factors, such as the fetal environment,” according to Dr. Magnusson.

And for clinical practice, the implication is that it’s important to ask about family history of OA, and in which parent, to better predict future risk of disease transmission to the children, she added.

These Norwegian study results open the door to exploration of the possible role of mitochondrial DNA in familial clustering of OA, since mitochondrial DNA is inherited only from the mother, Dr. Magnusson noted.

David T. Felson, MD, rose from the audience to say, “I’m a little bit worried” about the fact that when he and other Framingham Heart Study investigators looked specifically for possible mother/daughter, mother/son, father/daughter, and father/son associations for knee and hip OA, “we really didn’t find any.

“You can go through all of the explanations that you want about maternal inheritance, but I’m not sure that’s the best explanation. It might just be that what’s going on here is you’re seeing guys who are relatively young and who got their OA through injury or sports, which is fairly common in young men, and not through inheritance,” said Dr. Felson, professor of medicine and epidemiology at Boston University.

So a third observational study in an independent cohort might be needed as a tie breaker regarding the issue of OA inheritance.

Dr. Magnusson reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Magnusson K et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S47, Abstract 33