The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

 A version of this article first appeared on Medscape.com.

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

 A version of this article first appeared on Medscape.com.

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

 A version of this article first appeared on Medscape.com.

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease that typically affects the elderly, with an incidence of approximately 7 new cases per million.¹ The pathogenesis of BP involves autoantibodies to BP antigens 180 and 230 at the dermoepidermal junction. Bullous pemphigoid has been associated with the use of multiple medications; vaccines; and physical damage to the skin, including trauma, radiation, and surgery.²

Several classes of medications may cause BP; one study described an association of BP with loop diuretics,³ while others found higher incidences of BP in patients taking aldosterone antagonists and neuroleptics.⁴ We describe a case of drug-triggered BP to liraglutide, a glucagonlike peptide 1 (GLP-1) receptor agonist.

A 75-year-old man presented to dermatology for evaluation of a vesicular eruption on the head, neck, trunk, and arms of 6 months’ duration. The eruption developed 2 weeks after starting liraglutide 1.2 mg subcutaneously daily for diabetes mellitus. The patient had a medical history of type 2 diabetes mellitus, hypertension, stroke, and prostate cancer treated with prostatectomy, and he also was taking insulin. Liraglutide was discontinued shortly after the onset of the eruption.

Physical examination revealed annular plaques on the head, neck, trunk, and arms with central hypopigmentation and hyperpigmented borders (Figure 1). Two tense bullae were evident on the left flank (Figure 2). Histopathology revealed a subepidermal blister, mixed perivascular infiltrate with numerous eosinophils, and pigment incontinence (Figure 3). Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone that was localized to the roof of the blister on salt-split analysis. No microorganisms were identified on periodic acid–Schiff, Grocott-Gomori methenamine-silver, acid-fast bacilli, and Fite stains. The patient initially was treated with clobetasol ointment 0.05%, leading to marginal improvement. He declined treatment with prednisone or dapsone, and he was started on doxycycline. Seven months after stopping liraglutide and starting doxycycline, the patient had no blisters, but residual pigmentary changes remained.

Two types of BP have been described in response to medications: drug-induced BP and drug-triggered BP. Drug-induced BP presents as an acute, self-limited eruption that typically resolves after withdrawal of the offending agent. It tends to involve a younger population and may present with mucosal involvement and target lesions on the palms and soles. Direct immunofluorescence shows linear IgG and C3 deposition at the basement membrane zone. Patients tend to respond quickly to systemic corticosteroids and have low recurrence rates. Drug-triggered BP is a chronic form of BP that is caused by a medication and is not resolved with removal of the offending agent.⁵ Therefore, drug-triggered BP is more difficult to detect, especially in patients taking multiple medications.

Our patient represents a case of drug-triggered BP to liraglutide. Liraglutide is a GLP-1 receptor agonist that is US Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. Glucagonlike peptide 1 is an incretin hormone that is secreted by the intestine during digestion. It binds to the GLP-1 receptor leading to an increase in glucose-dependent insulin secretion and a decrease in glucagon secretion.⁶ Glucagonlike peptide 1 agonists also affect the immune system; liraglutide has been shown to modestly improve psoriasis, reduce the number of dermal gamma delta T cells, and decrease IL-17 expression.⁷ Glucagonlike peptide 1 agonists also produce anti-inflammatory effects on multiple organs including the liver, brain, vasculature, kidney, and skin.⁸

Dipeptidyl peptidase 4 (DPP-4) inhibitors that function to inhibit the degradation of GLP-1 and other peptides also have been reported to cause BP. In several patients, the DPP-4 inhibitors vildagliptin and sitagliptin caused drug-induced BP that resolved with discontinuation of the medication.⁹ Dipeptidyl peptidase 4 is expressed in various organ systems including the skin, and inhibition of DPP-4 enhances eosinophil mobilization in the blood and recruitment to the skin in animal models.¹⁰

Although the pathogenesis of BP involves autoantibodies to BP antigens 180 and 230, these antibodies are not sufficient to cause disease, as antibasement antibodies have been detected in patients without clinically evident BP. These patients, however, may be more susceptible to developing medication-induced BP. Several hypotheses regarding the pathogenesis of medication-induced BP have been proposed, including immune dysregulation, molecular mimicry, and cross-reactivity to a prior sensitizing agent.⁵ Liraglutide and the DPP-4 inhibitors affect the immune system, supporting the hypothesis of immune dysregulation; however, the exact mechanism of how immune modulating medications such as GLP-1 agonists and DPP-4 inhibitors cause BP remains unclear.

The effects of liraglutide and the DPP-4 inhibitors on the immune system may play a role in the pathogenesis of drug-triggered BP and drug-induced BP, respectively. Additional studies of the immunomodulatory effects of GLP-1 agonists and DPP-4 inhibitors may help elucidate the pathogenesis of drug-triggered or drug-induced BP.

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease that typically affects the elderly, with an incidence of approximately 7 new cases per million.¹ The pathogenesis of BP involves autoantibodies to BP antigens 180 and 230 at the dermoepidermal junction. Bullous pemphigoid has been associated with the use of multiple medications; vaccines; and physical damage to the skin, including trauma, radiation, and surgery.²

Several classes of medications may cause BP; one study described an association of BP with loop diuretics,³ while others found higher incidences of BP in patients taking aldosterone antagonists and neuroleptics.⁴ We describe a case of drug-triggered BP to liraglutide, a glucagonlike peptide 1 (GLP-1) receptor agonist.

A 75-year-old man presented to dermatology for evaluation of a vesicular eruption on the head, neck, trunk, and arms of 6 months’ duration. The eruption developed 2 weeks after starting liraglutide 1.2 mg subcutaneously daily for diabetes mellitus. The patient had a medical history of type 2 diabetes mellitus, hypertension, stroke, and prostate cancer treated with prostatectomy, and he also was taking insulin. Liraglutide was discontinued shortly after the onset of the eruption.

Physical examination revealed annular plaques on the head, neck, trunk, and arms with central hypopigmentation and hyperpigmented borders (Figure 1). Two tense bullae were evident on the left flank (Figure 2). Histopathology revealed a subepidermal blister, mixed perivascular infiltrate with numerous eosinophils, and pigment incontinence (Figure 3). Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone that was localized to the roof of the blister on salt-split analysis. No microorganisms were identified on periodic acid–Schiff, Grocott-Gomori methenamine-silver, acid-fast bacilli, and Fite stains. The patient initially was treated with clobetasol ointment 0.05%, leading to marginal improvement. He declined treatment with prednisone or dapsone, and he was started on doxycycline. Seven months after stopping liraglutide and starting doxycycline, the patient had no blisters, but residual pigmentary changes remained.

Two types of BP have been described in response to medications: drug-induced BP and drug-triggered BP. Drug-induced BP presents as an acute, self-limited eruption that typically resolves after withdrawal of the offending agent. It tends to involve a younger population and may present with mucosal involvement and target lesions on the palms and soles. Direct immunofluorescence shows linear IgG and C3 deposition at the basement membrane zone. Patients tend to respond quickly to systemic corticosteroids and have low recurrence rates. Drug-triggered BP is a chronic form of BP that is caused by a medication and is not resolved with removal of the offending agent.⁵ Therefore, drug-triggered BP is more difficult to detect, especially in patients taking multiple medications.

Our patient represents a case of drug-triggered BP to liraglutide. Liraglutide is a GLP-1 receptor agonist that is US Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. Glucagonlike peptide 1 is an incretin hormone that is secreted by the intestine during digestion. It binds to the GLP-1 receptor leading to an increase in glucose-dependent insulin secretion and a decrease in glucagon secretion.⁶ Glucagonlike peptide 1 agonists also affect the immune system; liraglutide has been shown to modestly improve psoriasis, reduce the number of dermal gamma delta T cells, and decrease IL-17 expression.⁷ Glucagonlike peptide 1 agonists also produce anti-inflammatory effects on multiple organs including the liver, brain, vasculature, kidney, and skin.⁸

Dipeptidyl peptidase 4 (DPP-4) inhibitors that function to inhibit the degradation of GLP-1 and other peptides also have been reported to cause BP. In several patients, the DPP-4 inhibitors vildagliptin and sitagliptin caused drug-induced BP that resolved with discontinuation of the medication.⁹ Dipeptidyl peptidase 4 is expressed in various organ systems including the skin, and inhibition of DPP-4 enhances eosinophil mobilization in the blood and recruitment to the skin in animal models.¹⁰

Although the pathogenesis of BP involves autoantibodies to BP antigens 180 and 230, these antibodies are not sufficient to cause disease, as antibasement antibodies have been detected in patients without clinically evident BP. These patients, however, may be more susceptible to developing medication-induced BP. Several hypotheses regarding the pathogenesis of medication-induced BP have been proposed, including immune dysregulation, molecular mimicry, and cross-reactivity to a prior sensitizing agent.⁵ Liraglutide and the DPP-4 inhibitors affect the immune system, supporting the hypothesis of immune dysregulation; however, the exact mechanism of how immune modulating medications such as GLP-1 agonists and DPP-4 inhibitors cause BP remains unclear.

The effects of liraglutide and the DPP-4 inhibitors on the immune system may play a role in the pathogenesis of drug-triggered BP and drug-induced BP, respectively. Additional studies of the immunomodulatory effects of GLP-1 agonists and DPP-4 inhibitors may help elucidate the pathogenesis of drug-triggered or drug-induced BP.

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease that typically affects the elderly, with an incidence of approximately 7 new cases per million.¹ The pathogenesis of BP involves autoantibodies to BP antigens 180 and 230 at the dermoepidermal junction. Bullous pemphigoid has been associated with the use of multiple medications; vaccines; and physical damage to the skin, including trauma, radiation, and surgery.²

Several classes of medications may cause BP; one study described an association of BP with loop diuretics,³ while others found higher incidences of BP in patients taking aldosterone antagonists and neuroleptics.⁴ We describe a case of drug-triggered BP to liraglutide, a glucagonlike peptide 1 (GLP-1) receptor agonist.

A 75-year-old man presented to dermatology for evaluation of a vesicular eruption on the head, neck, trunk, and arms of 6 months’ duration. The eruption developed 2 weeks after starting liraglutide 1.2 mg subcutaneously daily for diabetes mellitus. The patient had a medical history of type 2 diabetes mellitus, hypertension, stroke, and prostate cancer treated with prostatectomy, and he also was taking insulin. Liraglutide was discontinued shortly after the onset of the eruption.

Physical examination revealed annular plaques on the head, neck, trunk, and arms with central hypopigmentation and hyperpigmented borders (Figure 1). Two tense bullae were evident on the left flank (Figure 2). Histopathology revealed a subepidermal blister, mixed perivascular infiltrate with numerous eosinophils, and pigment incontinence (Figure 3). Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone that was localized to the roof of the blister on salt-split analysis. No microorganisms were identified on periodic acid–Schiff, Grocott-Gomori methenamine-silver, acid-fast bacilli, and Fite stains. The patient initially was treated with clobetasol ointment 0.05%, leading to marginal improvement. He declined treatment with prednisone or dapsone, and he was started on doxycycline. Seven months after stopping liraglutide and starting doxycycline, the patient had no blisters, but residual pigmentary changes remained.

Two types of BP have been described in response to medications: drug-induced BP and drug-triggered BP. Drug-induced BP presents as an acute, self-limited eruption that typically resolves after withdrawal of the offending agent. It tends to involve a younger population and may present with mucosal involvement and target lesions on the palms and soles. Direct immunofluorescence shows linear IgG and C3 deposition at the basement membrane zone. Patients tend to respond quickly to systemic corticosteroids and have low recurrence rates. Drug-triggered BP is a chronic form of BP that is caused by a medication and is not resolved with removal of the offending agent.⁵ Therefore, drug-triggered BP is more difficult to detect, especially in patients taking multiple medications.

Our patient represents a case of drug-triggered BP to liraglutide. Liraglutide is a GLP-1 receptor agonist that is US Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. Glucagonlike peptide 1 is an incretin hormone that is secreted by the intestine during digestion. It binds to the GLP-1 receptor leading to an increase in glucose-dependent insulin secretion and a decrease in glucagon secretion.⁶ Glucagonlike peptide 1 agonists also affect the immune system; liraglutide has been shown to modestly improve psoriasis, reduce the number of dermal gamma delta T cells, and decrease IL-17 expression.⁷ Glucagonlike peptide 1 agonists also produce anti-inflammatory effects on multiple organs including the liver, brain, vasculature, kidney, and skin.⁸

Dipeptidyl peptidase 4 (DPP-4) inhibitors that function to inhibit the degradation of GLP-1 and other peptides also have been reported to cause BP. In several patients, the DPP-4 inhibitors vildagliptin and sitagliptin caused drug-induced BP that resolved with discontinuation of the medication.⁹ Dipeptidyl peptidase 4 is expressed in various organ systems including the skin, and inhibition of DPP-4 enhances eosinophil mobilization in the blood and recruitment to the skin in animal models.¹⁰

Although the pathogenesis of BP involves autoantibodies to BP antigens 180 and 230, these antibodies are not sufficient to cause disease, as antibasement antibodies have been detected in patients without clinically evident BP. These patients, however, may be more susceptible to developing medication-induced BP. Several hypotheses regarding the pathogenesis of medication-induced BP have been proposed, including immune dysregulation, molecular mimicry, and cross-reactivity to a prior sensitizing agent.⁵ Liraglutide and the DPP-4 inhibitors affect the immune system, supporting the hypothesis of immune dysregulation; however, the exact mechanism of how immune modulating medications such as GLP-1 agonists and DPP-4 inhibitors cause BP remains unclear.

The effects of liraglutide and the DPP-4 inhibitors on the immune system may play a role in the pathogenesis of drug-triggered BP and drug-induced BP, respectively. Additional studies of the immunomodulatory effects of GLP-1 agonists and DPP-4 inhibitors may help elucidate the pathogenesis of drug-triggered or drug-induced BP.

To the Editor:

Lymphomatoid papulosis (LyP) is a chronic, recurring, self-healing, primary cutaneous lymphoproliferative disorder. This disease affects patients of all ages but most commonly presents in the fifth decade with a slight male predominance.¹ The estimated worldwide incidence is 1.2 to 1.9 cases per 1,000,000 individuals, and the 10-year survival rate is close to 100%.¹ Clinically, LyP presents as a few to more than 100 red-brown papules or nodules, some with hemorrhagic crust or central necrosis, often occurring in crops and in various stages of evolution. They most commonly are distributed on the trunk and extremities; however, the face, scalp, and oral mucosa rarely may be involved. Each lesion may last on average 3 to 8 weeks, with residual hyperpigmentation or hypopigmentation of the skin or superficial varioliform scars. The clinical characteristic of spontaneous regression is crucial for distinguishing LyP from other forms of cutaneous lymphoma.² The disease course is variable, lasting anywhere from a few months to decades. Histopathologically, LyP consists of a frequently CD30⁺ lymphocytic proliferation in multiple described patterns.¹ We report a case of LyP in a patient who initially presented with pink edematous papules and vesicles that progressed to crusted ulcerations, nodules, and deep necrotic eschars on the scalp, neck, and upper trunk. Multiple biopsies and T-cell gene rearrangement studies were necessary to make the diagnosis.

A 73-year-old man presented with edematous crusted papules and nodules as well as scarring with serous drainage on the scalp and upper trunk of several months’ duration. He also reported pain and pruritus. He had a medical history of B-cell CD20⁻ chronic lymphocytic leukemia (CLL) that was treated with fludarabine, cyclophosphamide, rituximab, and intravenous immunoglobulin approximately one year prior and currently was in remission; prostate cancer treated with prostatectomy; hypertension; and type 2 diabetes mellitus. His medications included metoprolol, valsartan, and glipizide.

Histopathology revealed a hypersensitivity reaction, and the clinicopathologic correlation was believed to represent an exuberant arthropod bite reaction in the setting of CLL. The eruption responded well to oral prednisone and topical corticosteroids but recurred when the medications were withdrawn. A repeat biopsy resulted in a diagnosis of atypical eosinophil-predominant Sweet syndrome. The condition resolved.

Three years later he developed multiple honey-crusted, superficial ulcers as well as serous, fluid-filled vesiculobullae on the head. A tissue culture revealed Proteus mirabilis, Staphylococcus aureus, and Enterococcus faecalis, and was negative for acid-fast bacteria and fungus. Biopsy of these lesions revealed dermal ulceration with a mixed inflammatory infiltrate and numerous eosinophils as well as a few clustered CD30⁺ cells; direct immunofluorescence was negative. An extensive laboratory workup including bullous pemphigoid antigens, C-reactive protein, antinuclear antibodies comprehensive profile, antineutrophil cytoplasmic antibodies, rheumatoid factor, anticyclic citrullinated peptide antibodies, serum protein electrophoresis, lactate dehydrogenase, complete blood cell count with differential, complete metabolic profile, thyroid-stimulating hormone, uric acid, C3, C4, immunoglobulin profile, angiotensin-converting enzyme level, and urinalysis was unremarkable. He improved with courses of minocycline, prednisone, and topical clobetasol, but he had periodic and progressive flares over several months with punched-out crusted ulcerations developing on the scalp (Figure 1A) and neck (Figure 1B). The oral and ocular mucosae were uninvolved, but the nasal mucosa had some involvement.

There is no cure for LyP and data regarding the potential of aggressive therapy on the prevention of secondary lymphomas is lacking. Wieser et al¹ reported that treatment did not prevent the progression to lymphoma in their retrospective analysis of 180 patients. The number of lesions, frequency of outbreaks, and extent of the scarring can dictate the treatment approach for LyP. Conservative topical therapies include corticosteroids, bexarotene, and imiquimod. Mupirocin may help to prevent infection of ulcerated lesions.^1,2 Low-dose methotrexate has been shown to be the most efficacious treatment in reducing the number of lesions, particularly for scarring or cosmetically sensitive areas. Oral methotrexate at a dosage of 10 mg to 25 mg weekly tapered to the lowest effective dose may suppress outbreaks of LyP lesions.^1,2 Other therapies include psoralen plus UVA, UVB, interferon alfa-2a, oral bexarotene, oral acyclovir or valacyclovir, etretinate, mycophenolic acid, photodynamic therapy, oral antibiotics, excision, and radiotherapy.^1,2 Systemic chemotherapy and total-skin electron beam therapy have shown efficacy in clearing the lesions; however, the disease recurs after discontinuation of therapy.² Systemic chemotherapy is not recommended for the treatment of LyP, as risks outweigh the benefits and it does not reduce the risk for developing lymphoma.¹ The prognosis generally is good, though long-term follow-up is imperative to monitor for the development of other lymphomas.

Our patient presented with LyP a few months after completing chemotherapy for his CLL. It is unknown if he developed LyP just before the time of presentation, or if he may have developed it at the same time as his CLL by a common inciting event. In the latter case, it is speculative that the LyP may have been controlled by chemotherapy for his CLL, only to become clinically apparent after discontinuation, then naturally remit for a longer period. Case reports such as ours with unusual clinical presentations, B-cell lymphoma associations, and unique timing of lymphoma onset may help to provide insight into the pathogenesis of this disease.

We highlighted an unusual case of LyP that presented clinically with crusted ulcerations as well as vesiculobullous and edematous papules that progressed into deep punched-out ulcers with eschars, nodules, and scarring on the head and upper trunk. Lymphomatoid papulosis can be difficult to diagnose histopathologically at the early stages, and multiple repeat biopsies may be necessary to confirm the diagnosis. T-cell gene rearrangement and immunohistochemistry studies are helpful along with clinical correlation to establish a diagnosis in these cases. We recommend that physicians keep LyP on the differential diagnosis for patients with similar clinical presentations and remain vigilant in monitoring for the development of secondary lymphoma.

To the Editor:

Lymphomatoid papulosis (LyP) is a chronic, recurring, self-healing, primary cutaneous lymphoproliferative disorder. This disease affects patients of all ages but most commonly presents in the fifth decade with a slight male predominance.¹ The estimated worldwide incidence is 1.2 to 1.9 cases per 1,000,000 individuals, and the 10-year survival rate is close to 100%.¹ Clinically, LyP presents as a few to more than 100 red-brown papules or nodules, some with hemorrhagic crust or central necrosis, often occurring in crops and in various stages of evolution. They most commonly are distributed on the trunk and extremities; however, the face, scalp, and oral mucosa rarely may be involved. Each lesion may last on average 3 to 8 weeks, with residual hyperpigmentation or hypopigmentation of the skin or superficial varioliform scars. The clinical characteristic of spontaneous regression is crucial for distinguishing LyP from other forms of cutaneous lymphoma.² The disease course is variable, lasting anywhere from a few months to decades. Histopathologically, LyP consists of a frequently CD30⁺ lymphocytic proliferation in multiple described patterns.¹ We report a case of LyP in a patient who initially presented with pink edematous papules and vesicles that progressed to crusted ulcerations, nodules, and deep necrotic eschars on the scalp, neck, and upper trunk. Multiple biopsies and T-cell gene rearrangement studies were necessary to make the diagnosis.

A 73-year-old man presented with edematous crusted papules and nodules as well as scarring with serous drainage on the scalp and upper trunk of several months’ duration. He also reported pain and pruritus. He had a medical history of B-cell CD20⁻ chronic lymphocytic leukemia (CLL) that was treated with fludarabine, cyclophosphamide, rituximab, and intravenous immunoglobulin approximately one year prior and currently was in remission; prostate cancer treated with prostatectomy; hypertension; and type 2 diabetes mellitus. His medications included metoprolol, valsartan, and glipizide.

Histopathology revealed a hypersensitivity reaction, and the clinicopathologic correlation was believed to represent an exuberant arthropod bite reaction in the setting of CLL. The eruption responded well to oral prednisone and topical corticosteroids but recurred when the medications were withdrawn. A repeat biopsy resulted in a diagnosis of atypical eosinophil-predominant Sweet syndrome. The condition resolved.

Three years later he developed multiple honey-crusted, superficial ulcers as well as serous, fluid-filled vesiculobullae on the head. A tissue culture revealed Proteus mirabilis, Staphylococcus aureus, and Enterococcus faecalis, and was negative for acid-fast bacteria and fungus. Biopsy of these lesions revealed dermal ulceration with a mixed inflammatory infiltrate and numerous eosinophils as well as a few clustered CD30⁺ cells; direct immunofluorescence was negative. An extensive laboratory workup including bullous pemphigoid antigens, C-reactive protein, antinuclear antibodies comprehensive profile, antineutrophil cytoplasmic antibodies, rheumatoid factor, anticyclic citrullinated peptide antibodies, serum protein electrophoresis, lactate dehydrogenase, complete blood cell count with differential, complete metabolic profile, thyroid-stimulating hormone, uric acid, C3, C4, immunoglobulin profile, angiotensin-converting enzyme level, and urinalysis was unremarkable. He improved with courses of minocycline, prednisone, and topical clobetasol, but he had periodic and progressive flares over several months with punched-out crusted ulcerations developing on the scalp (Figure 1A) and neck (Figure 1B). The oral and ocular mucosae were uninvolved, but the nasal mucosa had some involvement.

There is no cure for LyP and data regarding the potential of aggressive therapy on the prevention of secondary lymphomas is lacking. Wieser et al¹ reported that treatment did not prevent the progression to lymphoma in their retrospective analysis of 180 patients. The number of lesions, frequency of outbreaks, and extent of the scarring can dictate the treatment approach for LyP. Conservative topical therapies include corticosteroids, bexarotene, and imiquimod. Mupirocin may help to prevent infection of ulcerated lesions.^1,2 Low-dose methotrexate has been shown to be the most efficacious treatment in reducing the number of lesions, particularly for scarring or cosmetically sensitive areas. Oral methotrexate at a dosage of 10 mg to 25 mg weekly tapered to the lowest effective dose may suppress outbreaks of LyP lesions.^1,2 Other therapies include psoralen plus UVA, UVB, interferon alfa-2a, oral bexarotene, oral acyclovir or valacyclovir, etretinate, mycophenolic acid, photodynamic therapy, oral antibiotics, excision, and radiotherapy.^1,2 Systemic chemotherapy and total-skin electron beam therapy have shown efficacy in clearing the lesions; however, the disease recurs after discontinuation of therapy.² Systemic chemotherapy is not recommended for the treatment of LyP, as risks outweigh the benefits and it does not reduce the risk for developing lymphoma.¹ The prognosis generally is good, though long-term follow-up is imperative to monitor for the development of other lymphomas.

Our patient presented with LyP a few months after completing chemotherapy for his CLL. It is unknown if he developed LyP just before the time of presentation, or if he may have developed it at the same time as his CLL by a common inciting event. In the latter case, it is speculative that the LyP may have been controlled by chemotherapy for his CLL, only to become clinically apparent after discontinuation, then naturally remit for a longer period. Case reports such as ours with unusual clinical presentations, B-cell lymphoma associations, and unique timing of lymphoma onset may help to provide insight into the pathogenesis of this disease.

We highlighted an unusual case of LyP that presented clinically with crusted ulcerations as well as vesiculobullous and edematous papules that progressed into deep punched-out ulcers with eschars, nodules, and scarring on the head and upper trunk. Lymphomatoid papulosis can be difficult to diagnose histopathologically at the early stages, and multiple repeat biopsies may be necessary to confirm the diagnosis. T-cell gene rearrangement and immunohistochemistry studies are helpful along with clinical correlation to establish a diagnosis in these cases. We recommend that physicians keep LyP on the differential diagnosis for patients with similar clinical presentations and remain vigilant in monitoring for the development of secondary lymphoma.

To the Editor:

Lymphomatoid papulosis (LyP) is a chronic, recurring, self-healing, primary cutaneous lymphoproliferative disorder. This disease affects patients of all ages but most commonly presents in the fifth decade with a slight male predominance.¹ The estimated worldwide incidence is 1.2 to 1.9 cases per 1,000,000 individuals, and the 10-year survival rate is close to 100%.¹ Clinically, LyP presents as a few to more than 100 red-brown papules or nodules, some with hemorrhagic crust or central necrosis, often occurring in crops and in various stages of evolution. They most commonly are distributed on the trunk and extremities; however, the face, scalp, and oral mucosa rarely may be involved. Each lesion may last on average 3 to 8 weeks, with residual hyperpigmentation or hypopigmentation of the skin or superficial varioliform scars. The clinical characteristic of spontaneous regression is crucial for distinguishing LyP from other forms of cutaneous lymphoma.² The disease course is variable, lasting anywhere from a few months to decades. Histopathologically, LyP consists of a frequently CD30⁺ lymphocytic proliferation in multiple described patterns.¹ We report a case of LyP in a patient who initially presented with pink edematous papules and vesicles that progressed to crusted ulcerations, nodules, and deep necrotic eschars on the scalp, neck, and upper trunk. Multiple biopsies and T-cell gene rearrangement studies were necessary to make the diagnosis.

A 73-year-old man presented with edematous crusted papules and nodules as well as scarring with serous drainage on the scalp and upper trunk of several months’ duration. He also reported pain and pruritus. He had a medical history of B-cell CD20⁻ chronic lymphocytic leukemia (CLL) that was treated with fludarabine, cyclophosphamide, rituximab, and intravenous immunoglobulin approximately one year prior and currently was in remission; prostate cancer treated with prostatectomy; hypertension; and type 2 diabetes mellitus. His medications included metoprolol, valsartan, and glipizide.

Histopathology revealed a hypersensitivity reaction, and the clinicopathologic correlation was believed to represent an exuberant arthropod bite reaction in the setting of CLL. The eruption responded well to oral prednisone and topical corticosteroids but recurred when the medications were withdrawn. A repeat biopsy resulted in a diagnosis of atypical eosinophil-predominant Sweet syndrome. The condition resolved.

Three years later he developed multiple honey-crusted, superficial ulcers as well as serous, fluid-filled vesiculobullae on the head. A tissue culture revealed Proteus mirabilis, Staphylococcus aureus, and Enterococcus faecalis, and was negative for acid-fast bacteria and fungus. Biopsy of these lesions revealed dermal ulceration with a mixed inflammatory infiltrate and numerous eosinophils as well as a few clustered CD30⁺ cells; direct immunofluorescence was negative. An extensive laboratory workup including bullous pemphigoid antigens, C-reactive protein, antinuclear antibodies comprehensive profile, antineutrophil cytoplasmic antibodies, rheumatoid factor, anticyclic citrullinated peptide antibodies, serum protein electrophoresis, lactate dehydrogenase, complete blood cell count with differential, complete metabolic profile, thyroid-stimulating hormone, uric acid, C3, C4, immunoglobulin profile, angiotensin-converting enzyme level, and urinalysis was unremarkable. He improved with courses of minocycline, prednisone, and topical clobetasol, but he had periodic and progressive flares over several months with punched-out crusted ulcerations developing on the scalp (Figure 1A) and neck (Figure 1B). The oral and ocular mucosae were uninvolved, but the nasal mucosa had some involvement.

There is no cure for LyP and data regarding the potential of aggressive therapy on the prevention of secondary lymphomas is lacking. Wieser et al¹ reported that treatment did not prevent the progression to lymphoma in their retrospective analysis of 180 patients. The number of lesions, frequency of outbreaks, and extent of the scarring can dictate the treatment approach for LyP. Conservative topical therapies include corticosteroids, bexarotene, and imiquimod. Mupirocin may help to prevent infection of ulcerated lesions.^1,2 Low-dose methotrexate has been shown to be the most efficacious treatment in reducing the number of lesions, particularly for scarring or cosmetically sensitive areas. Oral methotrexate at a dosage of 10 mg to 25 mg weekly tapered to the lowest effective dose may suppress outbreaks of LyP lesions.^1,2 Other therapies include psoralen plus UVA, UVB, interferon alfa-2a, oral bexarotene, oral acyclovir or valacyclovir, etretinate, mycophenolic acid, photodynamic therapy, oral antibiotics, excision, and radiotherapy.^1,2 Systemic chemotherapy and total-skin electron beam therapy have shown efficacy in clearing the lesions; however, the disease recurs after discontinuation of therapy.² Systemic chemotherapy is not recommended for the treatment of LyP, as risks outweigh the benefits and it does not reduce the risk for developing lymphoma.¹ The prognosis generally is good, though long-term follow-up is imperative to monitor for the development of other lymphomas.

Our patient presented with LyP a few months after completing chemotherapy for his CLL. It is unknown if he developed LyP just before the time of presentation, or if he may have developed it at the same time as his CLL by a common inciting event. In the latter case, it is speculative that the LyP may have been controlled by chemotherapy for his CLL, only to become clinically apparent after discontinuation, then naturally remit for a longer period. Case reports such as ours with unusual clinical presentations, B-cell lymphoma associations, and unique timing of lymphoma onset may help to provide insight into the pathogenesis of this disease.

We highlighted an unusual case of LyP that presented clinically with crusted ulcerations as well as vesiculobullous and edematous papules that progressed into deep punched-out ulcers with eschars, nodules, and scarring on the head and upper trunk. Lymphomatoid papulosis can be difficult to diagnose histopathologically at the early stages, and multiple repeat biopsies may be necessary to confirm the diagnosis. T-cell gene rearrangement and immunohistochemistry studies are helpful along with clinical correlation to establish a diagnosis in these cases. We recommend that physicians keep LyP on the differential diagnosis for patients with similar clinical presentations and remain vigilant in monitoring for the development of secondary lymphoma.

VIDEO 1A Liberal use of your nonscanning hand on dynamic scanning shows “wiggling” of debris classic of a hemorrhagic corpus luteum

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VIDEO 1B Liberal use of your nonscanning hand helps identify a small postmenopausal ovary

--

VIDEO 2A Dynamic scanning can give the correct diagnosis even though clips were used! This clip appears to show a relatively normal uterus

--

VIDEO 2B Dynamic scanning can give the correct diagnosis even though clips were used! Same patient as in Video 2A showing what appears to be a solid adnexal mass

--

VIDEO 2C Dynamic scan clearly shows the “mass” to be a pedunculated fibroid

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VIDEO 3A Video clip of a classic endometrioma

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VIDEO 3B Classic endometrioma showing no Doppler flow internally

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VIDEO 4A Video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

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VIDEO 4B Another example of video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

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VIDEO 4C Another example of video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

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VIDEO 5A Sliding organ sign with normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

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VIDEO 5B  Sliding sign showing adherent ovary (Courtesy of Dr. Ilan Timor-Tritsch)

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VIDEO 5C Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

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VIDEO 5D Left ovary: Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

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VIDEO 5E Right ovary: Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

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VIDEO 5F Normal mobility even with a classic endometrioma (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5G Adherent ovary (Courtesy of Dr. Ilan Timor-Tritsch)

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VIDEO 6A Dynamic scanning shows the ovary to be “stuck” in the cul-de-sac in a patient with endometriosis

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VIDEO 6B Dynamic scanning in another patient with endometriosis showing markedly retroverted uterus with adherent bowel posteriorly

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VIDEO 6C Dynamic scanning in another patient with endometriosis showing markedly retroverted uterus with adherent bowel posteriorly

--

VIDEO 7 Cystocele or urethral lengthening are key elements for the diagnosis of incontinence with or without pelvic relaxation

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VIDEO 8 Urethral lengthening is a key element for the diagnosis of incontinence with or without pelvic relaxation

VIDEO 1A Liberal use of your nonscanning hand on dynamic scanning shows “wiggling” of debris classic of a hemorrhagic corpus luteum

--

VIDEO 1B Liberal use of your nonscanning hand helps identify a small postmenopausal ovary

--

VIDEO 2A Dynamic scanning can give the correct diagnosis even though clips were used! This clip appears to show a relatively normal uterus

--

VIDEO 2B Dynamic scanning can give the correct diagnosis even though clips were used! Same patient as in Video 2A showing what appears to be a solid adnexal mass

--

VIDEO 2C Dynamic scan clearly shows the “mass” to be a pedunculated fibroid

--

VIDEO 3A Video clip of a classic endometrioma

--

VIDEO 3B Classic endometrioma showing no Doppler flow internally

--

VIDEO 4A Video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

--

VIDEO 4B Another example of video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

--

VIDEO 4C Another example of video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

--

VIDEO 5A Sliding organ sign with normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5B  Sliding sign showing adherent ovary (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5C Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5D Left ovary: Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5E Right ovary: Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5F Normal mobility even with a classic endometrioma (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5G Adherent ovary (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 6A Dynamic scanning shows the ovary to be “stuck” in the cul-de-sac in a patient with endometriosis

--

VIDEO 6B Dynamic scanning in another patient with endometriosis showing markedly retroverted uterus with adherent bowel posteriorly

--

VIDEO 6C Dynamic scanning in another patient with endometriosis showing markedly retroverted uterus with adherent bowel posteriorly

--

VIDEO 7 Cystocele or urethral lengthening are key elements for the diagnosis of incontinence with or without pelvic relaxation

--

VIDEO 8 Urethral lengthening is a key element for the diagnosis of incontinence with or without pelvic relaxation

VIDEO 1A Liberal use of your nonscanning hand on dynamic scanning shows “wiggling” of debris classic of a hemorrhagic corpus luteum

--

VIDEO 1B Liberal use of your nonscanning hand helps identify a small postmenopausal ovary

--

VIDEO 2A Dynamic scanning can give the correct diagnosis even though clips were used! This clip appears to show a relatively normal uterus

--

VIDEO 2B Dynamic scanning can give the correct diagnosis even though clips were used! Same patient as in Video 2A showing what appears to be a solid adnexal mass

--

VIDEO 2C Dynamic scan clearly shows the “mass” to be a pedunculated fibroid

--

VIDEO 3A Video clip of a classic endometrioma

--

VIDEO 3B Classic endometrioma showing no Doppler flow internally

--

VIDEO 4A Video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

--

VIDEO 4B Another example of video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

--

VIDEO 4C Another example of video of dynamic assessment in a patient with pain symptoms with a hydrosalpinx

--

VIDEO 5A Sliding organ sign with normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5B  Sliding sign showing adherent ovary (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5C Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5D Left ovary: Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5E Right ovary: Normal mobility (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5F Normal mobility even with a classic endometrioma (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 5G Adherent ovary (Courtesy of Dr. Ilan Timor-Tritsch)

--

VIDEO 6A Dynamic scanning shows the ovary to be “stuck” in the cul-de-sac in a patient with endometriosis

--

VIDEO 6B Dynamic scanning in another patient with endometriosis showing markedly retroverted uterus with adherent bowel posteriorly

--

VIDEO 6C Dynamic scanning in another patient with endometriosis showing markedly retroverted uterus with adherent bowel posteriorly

--

VIDEO 7 Cystocele or urethral lengthening are key elements for the diagnosis of incontinence with or without pelvic relaxation

--

VIDEO 8 Urethral lengthening is a key element for the diagnosis of incontinence with or without pelvic relaxation

The prevalence of inflammatory bowel disease increased significantly among Americans aged 67 years and older from 2001 to 2018, based on data from more than 25 million Medicare beneficiaries.

FatCamera/Getty Images

The worldwide prevalence – or rate of existing cases – of inflammatory bowel disease (IBD) increased from 3.7 million in 1990 to 6.8 million in 2017, wrote Fang Xu, PhD, of the Centers for Disease Control and Prevention, and colleagues. “As the prevalence increases with age group, it is important to understand the disease epidemiology among the older population,” they said.

In a study published in the Morbidity and Mortality Weekly Report, the researchers reviewed 2018 Medicare data for 25.1 million beneficiaries aged 67 years and older to assess prevalence trends overall and by race and ethnicity. Over the study period, the study population ranged from 23.7 million persons in 2009 to 25.6 million persons in 2018. The incidence – or rate of new cases – of IBD peaks at 15-29 years of age, but approximately 10%-15% of new cases develop in adults aged 60 years and older, so the prevalence of IBD overall is expected to increase over time with the aging of the U.S. population, the researchers said.

In this population of beneficiaries, 0.40% overall had a Crohn’s disease diagnosis and 0.64% had an ulcerative colitis diagnosis. The prevalence for both diseases was consistently highest among non-Hispanic Whites, the researchers noted. In addition, the prevalence of Crohn’s disease was highest among younger beneficiaries, while the prevalence of ulcerative colitis was highest among those aged 75-84 years. Other factors associated with higher IBD prevalence were female gender and residence in large fringe metropolitan counties.

The overall age-adjusted prevalence of Crohn’s disease increased over time with an annual percentage change (APC) of 3.4%, and the overall age-adjusted prevalence of ulcerative colitis increased with an APC of 2.8%. When the researchers examined subgroups of race and ethnicity, the annual increases were higher for non-Hispanic Blacks for both Crohn’s disease and ulcerative colitis, with APCs of 5.0% and 3.5%, respectively. “The potential rapid increase of disease prevalence in certain racial and ethnic minority groups indicates the need for tailored disease management strategies in these populations,” the researchers noted.

The study findings were limited by several factors including the lack of socioeconomic data, the potential for coding errors related to Crohn’s disease or ulcerative colitis, and the lack of generalizability to all older adults in the United States, the researchers noted. However, “Medicare data are a useful resource to monitor prevalence of IBD over time, understand its prevalence among older adults, assess differences by demographic and geographic characteristics, and have rich information to study health care use,” they concluded.
 

Consider the younger population

The data from the study need to be considered in the context of an accumulation of patients with IBD, and the distinction between incidence and prevalence, Stephen B. Hanauer, MD, of Northwestern University, Chicago, said in an interview.

The overall incidence of IBD is much greater in younger individuals (approximately ages 15-29 years) compared with older adults, he said. Patients with IBD don’t die of it; they grow old with it. Consequently, the prevalence in the Medicare population increases over time, he explained.

The data may be of interest to the practicing clinician, but would be most useful to hospital and Medicare administrators in terms of planning for an increase in the number of older adults surviving into older adulthood with IBD who will require care, he noted.

The researchers and Dr. Hanauer had no financial conflicts to disclose.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD.

The prevalence of inflammatory bowel disease increased significantly among Americans aged 67 years and older from 2001 to 2018, based on data from more than 25 million Medicare beneficiaries.

FatCamera/Getty Images

The worldwide prevalence – or rate of existing cases – of inflammatory bowel disease (IBD) increased from 3.7 million in 1990 to 6.8 million in 2017, wrote Fang Xu, PhD, of the Centers for Disease Control and Prevention, and colleagues. “As the prevalence increases with age group, it is important to understand the disease epidemiology among the older population,” they said.

In a study published in the Morbidity and Mortality Weekly Report, the researchers reviewed 2018 Medicare data for 25.1 million beneficiaries aged 67 years and older to assess prevalence trends overall and by race and ethnicity. Over the study period, the study population ranged from 23.7 million persons in 2009 to 25.6 million persons in 2018. The incidence – or rate of new cases – of IBD peaks at 15-29 years of age, but approximately 10%-15% of new cases develop in adults aged 60 years and older, so the prevalence of IBD overall is expected to increase over time with the aging of the U.S. population, the researchers said.

In this population of beneficiaries, 0.40% overall had a Crohn’s disease diagnosis and 0.64% had an ulcerative colitis diagnosis. The prevalence for both diseases was consistently highest among non-Hispanic Whites, the researchers noted. In addition, the prevalence of Crohn’s disease was highest among younger beneficiaries, while the prevalence of ulcerative colitis was highest among those aged 75-84 years. Other factors associated with higher IBD prevalence were female gender and residence in large fringe metropolitan counties.

The overall age-adjusted prevalence of Crohn’s disease increased over time with an annual percentage change (APC) of 3.4%, and the overall age-adjusted prevalence of ulcerative colitis increased with an APC of 2.8%. When the researchers examined subgroups of race and ethnicity, the annual increases were higher for non-Hispanic Blacks for both Crohn’s disease and ulcerative colitis, with APCs of 5.0% and 3.5%, respectively. “The potential rapid increase of disease prevalence in certain racial and ethnic minority groups indicates the need for tailored disease management strategies in these populations,” the researchers noted.

The study findings were limited by several factors including the lack of socioeconomic data, the potential for coding errors related to Crohn’s disease or ulcerative colitis, and the lack of generalizability to all older adults in the United States, the researchers noted. However, “Medicare data are a useful resource to monitor prevalence of IBD over time, understand its prevalence among older adults, assess differences by demographic and geographic characteristics, and have rich information to study health care use,” they concluded.
 

Consider the younger population

The data from the study need to be considered in the context of an accumulation of patients with IBD, and the distinction between incidence and prevalence, Stephen B. Hanauer, MD, of Northwestern University, Chicago, said in an interview.

The overall incidence of IBD is much greater in younger individuals (approximately ages 15-29 years) compared with older adults, he said. Patients with IBD don’t die of it; they grow old with it. Consequently, the prevalence in the Medicare population increases over time, he explained.

The data may be of interest to the practicing clinician, but would be most useful to hospital and Medicare administrators in terms of planning for an increase in the number of older adults surviving into older adulthood with IBD who will require care, he noted.

The researchers and Dr. Hanauer had no financial conflicts to disclose.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD.

The prevalence of inflammatory bowel disease increased significantly among Americans aged 67 years and older from 2001 to 2018, based on data from more than 25 million Medicare beneficiaries.

FatCamera/Getty Images

The worldwide prevalence – or rate of existing cases – of inflammatory bowel disease (IBD) increased from 3.7 million in 1990 to 6.8 million in 2017, wrote Fang Xu, PhD, of the Centers for Disease Control and Prevention, and colleagues. “As the prevalence increases with age group, it is important to understand the disease epidemiology among the older population,” they said.

In a study published in the Morbidity and Mortality Weekly Report, the researchers reviewed 2018 Medicare data for 25.1 million beneficiaries aged 67 years and older to assess prevalence trends overall and by race and ethnicity. Over the study period, the study population ranged from 23.7 million persons in 2009 to 25.6 million persons in 2018. The incidence – or rate of new cases – of IBD peaks at 15-29 years of age, but approximately 10%-15% of new cases develop in adults aged 60 years and older, so the prevalence of IBD overall is expected to increase over time with the aging of the U.S. population, the researchers said.

In this population of beneficiaries, 0.40% overall had a Crohn’s disease diagnosis and 0.64% had an ulcerative colitis diagnosis. The prevalence for both diseases was consistently highest among non-Hispanic Whites, the researchers noted. In addition, the prevalence of Crohn’s disease was highest among younger beneficiaries, while the prevalence of ulcerative colitis was highest among those aged 75-84 years. Other factors associated with higher IBD prevalence were female gender and residence in large fringe metropolitan counties.

The overall age-adjusted prevalence of Crohn’s disease increased over time with an annual percentage change (APC) of 3.4%, and the overall age-adjusted prevalence of ulcerative colitis increased with an APC of 2.8%. When the researchers examined subgroups of race and ethnicity, the annual increases were higher for non-Hispanic Blacks for both Crohn’s disease and ulcerative colitis, with APCs of 5.0% and 3.5%, respectively. “The potential rapid increase of disease prevalence in certain racial and ethnic minority groups indicates the need for tailored disease management strategies in these populations,” the researchers noted.

The study findings were limited by several factors including the lack of socioeconomic data, the potential for coding errors related to Crohn’s disease or ulcerative colitis, and the lack of generalizability to all older adults in the United States, the researchers noted. However, “Medicare data are a useful resource to monitor prevalence of IBD over time, understand its prevalence among older adults, assess differences by demographic and geographic characteristics, and have rich information to study health care use,” they concluded.
 

Consider the younger population

The data from the study need to be considered in the context of an accumulation of patients with IBD, and the distinction between incidence and prevalence, Stephen B. Hanauer, MD, of Northwestern University, Chicago, said in an interview.

The overall incidence of IBD is much greater in younger individuals (approximately ages 15-29 years) compared with older adults, he said. Patients with IBD don’t die of it; they grow old with it. Consequently, the prevalence in the Medicare population increases over time, he explained.

The data may be of interest to the practicing clinician, but would be most useful to hospital and Medicare administrators in terms of planning for an increase in the number of older adults surviving into older adulthood with IBD who will require care, he noted.

The researchers and Dr. Hanauer had no financial conflicts to disclose.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD.

Key clinical point: Increased levels of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) identified patients with hepatocellular carcinoma (HCC).

Major finding: Median PIVKA-II serum levels were significantly higher in patients with hepatocellular carcinoma (181.50 mAU/mL) vs patients with benign (noncancerous) liver disease (28.60 mAU/mL) or healthy controls (21.82 mAU/mL; both P less than .0001). When comparing HCC patients and healthy controls, PIVKA-II was markedly more sensitive than AFP (83.9% vs 64.3%, respectively), and somewhat more specific (91.5% vs 84.7%). Compared with measuring AFP alone, measuring both PIVKA-II and AFP demonstrated much greater sensitivity (81.95%) and slightly greater specificity (89.3%).

Study details: The researchers used enzyme-linked immunosorbent assays (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls.

Disclosures: Funding sources were described as inapplicable. The researchers reported having no conflicts of interest.

Source: Feng H et al. BMC Cancer. 2021 Apr 13. doi: 10.1186/s12885-021-08138-3

Key clinical point: Increased levels of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) identified patients with hepatocellular carcinoma (HCC).

Major finding: Median PIVKA-II serum levels were significantly higher in patients with hepatocellular carcinoma (181.50 mAU/mL) vs patients with benign (noncancerous) liver disease (28.60 mAU/mL) or healthy controls (21.82 mAU/mL; both P less than .0001). When comparing HCC patients and healthy controls, PIVKA-II was markedly more sensitive than AFP (83.9% vs 64.3%, respectively), and somewhat more specific (91.5% vs 84.7%). Compared with measuring AFP alone, measuring both PIVKA-II and AFP demonstrated much greater sensitivity (81.95%) and slightly greater specificity (89.3%).

Study details: The researchers used enzyme-linked immunosorbent assays (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls.

Disclosures: Funding sources were described as inapplicable. The researchers reported having no conflicts of interest.

Source: Feng H et al. BMC Cancer. 2021 Apr 13. doi: 10.1186/s12885-021-08138-3

Key clinical point: Increased levels of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) identified patients with hepatocellular carcinoma (HCC).

Major finding: Median PIVKA-II serum levels were significantly higher in patients with hepatocellular carcinoma (181.50 mAU/mL) vs patients with benign (noncancerous) liver disease (28.60 mAU/mL) or healthy controls (21.82 mAU/mL; both P less than .0001). When comparing HCC patients and healthy controls, PIVKA-II was markedly more sensitive than AFP (83.9% vs 64.3%, respectively), and somewhat more specific (91.5% vs 84.7%). Compared with measuring AFP alone, measuring both PIVKA-II and AFP demonstrated much greater sensitivity (81.95%) and slightly greater specificity (89.3%).

Study details: The researchers used enzyme-linked immunosorbent assays (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls.

Disclosures: Funding sources were described as inapplicable. The researchers reported having no conflicts of interest.

Source: Feng H et al. BMC Cancer. 2021 Apr 13. doi: 10.1186/s12885-021-08138-3

Key clinical point: Spleen stiffness, a measure of portal hypertension, was a risk factor for hepatocellular carcinoma (HCC) among patients with advanced liver disease whose chronic hepatitis C virus infection (HCV) was successfully treated with direct-acting antivirals (DAA).

Major finding: The incidence of HCC was 14% over a median of 41.5 months of follow-up. Six months after successful DAA treatment, spleen stiffness greater than 42 kPa was associated with a small but statistically significant increase in risk for HCC (hazard ratio, 1.025). Among patients whose liver stiffness exceeded 10 kPa, increased spleen stiffness was a risk factor for HCC, but any additional increase in liver stiffness (10-20 kPa vs >20 kPa) was not.

Study details: This was a single-center retrospective study of 140 patients with advanced chronic liver disease whose HCV was successfully treated with DAA. Liver and spleen stiffness were measured at baseline and 6 months after end of treatment.

Disclosures: The researchers reported receiving no funding for the study and stated that they had no conflicts of interest.

Source: Dajti E et al. JHEP Rep. 2021 Apr 14. doi: 10.1016/j.jhepr.2021.100289

Key clinical point: Spleen stiffness, a measure of portal hypertension, was a risk factor for hepatocellular carcinoma (HCC) among patients with advanced liver disease whose chronic hepatitis C virus infection (HCV) was successfully treated with direct-acting antivirals (DAA).

Major finding: The incidence of HCC was 14% over a median of 41.5 months of follow-up. Six months after successful DAA treatment, spleen stiffness greater than 42 kPa was associated with a small but statistically significant increase in risk for HCC (hazard ratio, 1.025). Among patients whose liver stiffness exceeded 10 kPa, increased spleen stiffness was a risk factor for HCC, but any additional increase in liver stiffness (10-20 kPa vs >20 kPa) was not.

Study details: This was a single-center retrospective study of 140 patients with advanced chronic liver disease whose HCV was successfully treated with DAA. Liver and spleen stiffness were measured at baseline and 6 months after end of treatment.

Disclosures: The researchers reported receiving no funding for the study and stated that they had no conflicts of interest.

Source: Dajti E et al. JHEP Rep. 2021 Apr 14. doi: 10.1016/j.jhepr.2021.100289

Key clinical point: Spleen stiffness, a measure of portal hypertension, was a risk factor for hepatocellular carcinoma (HCC) among patients with advanced liver disease whose chronic hepatitis C virus infection (HCV) was successfully treated with direct-acting antivirals (DAA).

Major finding: The incidence of HCC was 14% over a median of 41.5 months of follow-up. Six months after successful DAA treatment, spleen stiffness greater than 42 kPa was associated with a small but statistically significant increase in risk for HCC (hazard ratio, 1.025). Among patients whose liver stiffness exceeded 10 kPa, increased spleen stiffness was a risk factor for HCC, but any additional increase in liver stiffness (10-20 kPa vs >20 kPa) was not.

Study details: This was a single-center retrospective study of 140 patients with advanced chronic liver disease whose HCV was successfully treated with DAA. Liver and spleen stiffness were measured at baseline and 6 months after end of treatment.

Disclosures: The researchers reported receiving no funding for the study and stated that they had no conflicts of interest.

Source: Dajti E et al. JHEP Rep. 2021 Apr 14. doi: 10.1016/j.jhepr.2021.100289

Key clinical point: Consider testing for hepatitis D virus in patients receiving nucleoside/nucleotide analogues (NA) for chronic hepatitis B virus infection (HBV).

Major finding: Prevalences of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. Five-year cumulative rates of hepatocellular carcinoma (HCC) were 22.2% among patients with detectable HDV RNA vs 7.3% among patients with undetectable HDV RNA (P = .01).

Study details: This was a single-center retrospective study of 1,349 patients receiving NA for chronic HBV.

Disclosures: The Center for Liquid Biopsy, Center for Cancer Research, Cohort Research Center, Kaohsiung Medical University, and Kaohsiung Medical University Hospital provided funding. Two coinvestigators disclosed ties to Abbott, BMS, Gilead, Merck, AbbVie, Roche, and IPSEN. The other investigators reported having no conflicts of interest.

Source: Jang T-Y et al. Sci Rep. 2021 Apr 14. doi: 10.1038/s41598-021-87679-w

Key clinical point: Consider testing for hepatitis D virus in patients receiving nucleoside/nucleotide analogues (NA) for chronic hepatitis B virus infection (HBV).

Major finding: Prevalences of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. Five-year cumulative rates of hepatocellular carcinoma (HCC) were 22.2% among patients with detectable HDV RNA vs 7.3% among patients with undetectable HDV RNA (P = .01).

Study details: This was a single-center retrospective study of 1,349 patients receiving NA for chronic HBV.

Disclosures: The Center for Liquid Biopsy, Center for Cancer Research, Cohort Research Center, Kaohsiung Medical University, and Kaohsiung Medical University Hospital provided funding. Two coinvestigators disclosed ties to Abbott, BMS, Gilead, Merck, AbbVie, Roche, and IPSEN. The other investigators reported having no conflicts of interest.

Source: Jang T-Y et al. Sci Rep. 2021 Apr 14. doi: 10.1038/s41598-021-87679-w

Key clinical point: Consider testing for hepatitis D virus in patients receiving nucleoside/nucleotide analogues (NA) for chronic hepatitis B virus infection (HBV).

Major finding: Prevalences of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. Five-year cumulative rates of hepatocellular carcinoma (HCC) were 22.2% among patients with detectable HDV RNA vs 7.3% among patients with undetectable HDV RNA (P = .01).

Study details: This was a single-center retrospective study of 1,349 patients receiving NA for chronic HBV.

Disclosures: The Center for Liquid Biopsy, Center for Cancer Research, Cohort Research Center, Kaohsiung Medical University, and Kaohsiung Medical University Hospital provided funding. Two coinvestigators disclosed ties to Abbott, BMS, Gilead, Merck, AbbVie, Roche, and IPSEN. The other investigators reported having no conflicts of interest.

Source: Jang T-Y et al. Sci Rep. 2021 Apr 14. doi: 10.1038/s41598-021-87679-w

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185