Infectious Diseases

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most recently identified member of the zoonotic pathogens of coronaviruses. It caused an outbreak of pneumonia in December 2019 in Wuhan, China.¹ Among all related acute respiratory syndromes (SARS-CoV, Middle East respiratory syndrome coronavirus), SARS-CoV-2 remains to be the most infectious, has the highest potential for human transmission, and can eventually result in acute respiratory distress syndrome.^2,3

Only 15% of coronavirus disease 2019 (COVID-19) cases progress to pneumonia, and approximately 5% of these cases develop acute respiratory distress syndrome, septic shock, and/or multiple organ failure. The majority of cases only exhibit mild to moderate symptoms.^4,5 A wide array of skin manifestations in COVID-19 infection have been reported, including maculopapular eruptions, morbilliform rashes, urticaria, chickenpoxlike lesions, livedo reticularis, COVID toes, erythema multiforme, pityriasis rosea, and several other patterns.⁶ We report a case of herpes zoster (HZ) complication in a COVID-19–positive woman who was 27 weeks pregnant.

Case Report

A 36-year-old woman who was 27 weeks pregnant was referred by her obstetrician to the dermatology clinic. She presented with a low-grade fever and a vesicular painful rash. Physical examination revealed painful, itchy, dysesthetic papules and vesicles on the left side of the forehead along with mild edema of the left upper eyelid but no watering of the eye or photophobia. She reported episodes of fever (temperature, 38.9°C), fatigue, and myalgia over the last week. She had bouts of dyspnea and tachycardia that she thought were related to being in the late second trimester of pregnancy. The area surrounding the vesicular eruption was tender to touch. No dry cough or any gastrointestinal or urinary tract symptoms were noted. She reported a burning sensation when splashing water on the face or when exposed to air currents. One week following the initial symptoms, she experienced a painful vesicular rash along the upper left forehead (Figure) associated with eyelid edema. Oral and ocular mucosae were free of any presentations. She had no relevant history and had not experienced any complications during pregnancy. A diagnosis of HZ was made, and she was prescribed valacyclovir 1 g 3 times daily for 7 days, acetaminophen for the fever, and calamine lotion. We recommended COVID-19 testing based on her symptoms. A chest radiograph and a positive nasopharyngeal smear were consistent with COVID-19 infection. She reported via telephone follow-up 1 week after presentation that her skin condition had improved following the treatment course and that the vesicles eventually dried, leaving a crusting appearance after 5 to 7 days. Regarding her SARS-CoV-2 condition, her oxygen saturation was 95% at presentation; she self-quarantined at home; and she was treated with oseltamivir 75 mg orally every 12 hours for 5 days, azithromycin 500 mg orally daily, acetaminophen, and vitamin C. Electronic fetal heart rate monitoring and ultrasound examinations were performed to assess the condition of the fetus and were reported normal. At the time of writing this article, she was 32 weeks pregnant and tested negative to 2 consecutive nasopharyngeal swabs for COVID-19 and was in good general condition. She continued her pregnancy according to her obstetrician’s recommendations.

Comment

The incubation time of COVID-19 can be up to 14 days. Fever, dry cough, fatigue, and diarrhea have been speculated to be clinical symptoms; however, many cases may be asymptomatic. Aside from a medical or travel history at risk for COVID-19, diagnosis can be confirmed by detection of viral RNA by reverse transcriptase–polymerase chain reaction for nasopharyngeal swabs or bronchoalveolar fluid. Patients who are immunocompromised, older, or male or who have a history of cardiovascular conditions or debilitating chronic conditions are at an increased risk for severe disease and poor outcome compared to younger healthy individuals.⁷

The vesicular rash of COVID-19 has been reported to have different forms of presentation. A diffuse widespread pattern resembling hand-foot-and-mouth disease and a localized monomorphic pattern resembling chickenpox but with predilection to the trunk has been described.⁸

Physiologic changes in the immune and cardiopulmonary systems during pregnancy (eg, diaphragm elevation, increased oxygen consumption, edema of the respiratory tract mucosae) make pregnant women intolerant to hypoxia. The mortality rate of the 1918 influenza pandemic was 2.6% in the overall population but 37% among pregnant women.⁹ In 2009, pregnant women were reported to be at an increased risk for complications from the H1N1 influenza virus pandemic, with a higher estimated rate of hospital admission than the general population.¹⁰ In 2003, approximately 50% of pregnant women who received a diagnosis of SARS-CoV were admitted to the intensive care unit, approximately 33% of pregnant women with SARS-CoV required mechanical ventilation, and the mortality rate was as high as 25% for these women.¹¹ To date, data on the effects of COVID-19 in pregnancy are limited to small case series.^12-15

It was confirmed that COVID-19 infection is accompanied by a reduction in lymphocytes, monocytes, and eosinophils, along with a notable reduction of CD4/CD8 T cells, B cells, and natural killer cells. It was further revealed that nonsurvivor COVID-19 patients continued to show a decrease in lymphocyte counts along the course of their disease until death.^16-18

Different mechanisms for lymphocyte depletion and deficiency were speculated among COVID-19 patients and include direct lymphocyte death through coronavirus angiotensin-converting enzyme 2–lymphocyte-expressed receptors; direct damage to lymphatic organs, such as the thymus and spleen, but this theory needs to be further investigated; direct lymphocyte apoptosis mediated by tumor necrosis factor α, IL-6, and other proinflammatory cytokines; and direct inhibition of lymphocytes by metabolic upset, such as acidosis.^19,20

These causes may precipitate lymphopenia and impaired antiviral responses.²¹ It also has been postulated that the functional damage of CD4⁺ T cells may predispose patients with COVID-19 to severe disease.²² Such immune changes can render a patient more susceptible to developing shingles by reactivating varicella-zoster virus, which could be a sign of undiagnosed COVID-19 infection in younger age groups.

Two earlier reports discussed HZ among COVID-19–diagnosed patients. Shors²³ presented a case of a patient who developed varicella-zoster virus reactivation of the V2 dermatome during the course of COVID-19 infection. In addition, the patient developed severe acute herpetic neuralgia despite the early initiation of antiviral therapy.²³ Elsaie et al²⁴ described 2 cases of patients during the pandemic who first presented with HZ before later being diagnosed with COVID-19 infection.

New information and cutaneous manifestations possibly related to COVID-19 are emerging every day. We report a pregnant female presenting with HZ during the course of COVID-19 infection, which suggests that the clinical presentation of HZ at the time of the current pandemic, especially if associated with other signs of COVID-19 infection, should be carefully monitored and reported for further assessment.

Acknowledgment
The authors would like to thank all the health care workers who have been fighting COVID-19 in Egypt and worldwide.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most recently identified member of the zoonotic pathogens of coronaviruses. It caused an outbreak of pneumonia in December 2019 in Wuhan, China.¹ Among all related acute respiratory syndromes (SARS-CoV, Middle East respiratory syndrome coronavirus), SARS-CoV-2 remains to be the most infectious, has the highest potential for human transmission, and can eventually result in acute respiratory distress syndrome.^2,3

Only 15% of coronavirus disease 2019 (COVID-19) cases progress to pneumonia, and approximately 5% of these cases develop acute respiratory distress syndrome, septic shock, and/or multiple organ failure. The majority of cases only exhibit mild to moderate symptoms.^4,5 A wide array of skin manifestations in COVID-19 infection have been reported, including maculopapular eruptions, morbilliform rashes, urticaria, chickenpoxlike lesions, livedo reticularis, COVID toes, erythema multiforme, pityriasis rosea, and several other patterns.⁶ We report a case of herpes zoster (HZ) complication in a COVID-19–positive woman who was 27 weeks pregnant.

Case Report

A 36-year-old woman who was 27 weeks pregnant was referred by her obstetrician to the dermatology clinic. She presented with a low-grade fever and a vesicular painful rash. Physical examination revealed painful, itchy, dysesthetic papules and vesicles on the left side of the forehead along with mild edema of the left upper eyelid but no watering of the eye or photophobia. She reported episodes of fever (temperature, 38.9°C), fatigue, and myalgia over the last week. She had bouts of dyspnea and tachycardia that she thought were related to being in the late second trimester of pregnancy. The area surrounding the vesicular eruption was tender to touch. No dry cough or any gastrointestinal or urinary tract symptoms were noted. She reported a burning sensation when splashing water on the face or when exposed to air currents. One week following the initial symptoms, she experienced a painful vesicular rash along the upper left forehead (Figure) associated with eyelid edema. Oral and ocular mucosae were free of any presentations. She had no relevant history and had not experienced any complications during pregnancy. A diagnosis of HZ was made, and she was prescribed valacyclovir 1 g 3 times daily for 7 days, acetaminophen for the fever, and calamine lotion. We recommended COVID-19 testing based on her symptoms. A chest radiograph and a positive nasopharyngeal smear were consistent with COVID-19 infection. She reported via telephone follow-up 1 week after presentation that her skin condition had improved following the treatment course and that the vesicles eventually dried, leaving a crusting appearance after 5 to 7 days. Regarding her SARS-CoV-2 condition, her oxygen saturation was 95% at presentation; she self-quarantined at home; and she was treated with oseltamivir 75 mg orally every 12 hours for 5 days, azithromycin 500 mg orally daily, acetaminophen, and vitamin C. Electronic fetal heart rate monitoring and ultrasound examinations were performed to assess the condition of the fetus and were reported normal. At the time of writing this article, she was 32 weeks pregnant and tested negative to 2 consecutive nasopharyngeal swabs for COVID-19 and was in good general condition. She continued her pregnancy according to her obstetrician’s recommendations.

Comment

The incubation time of COVID-19 can be up to 14 days. Fever, dry cough, fatigue, and diarrhea have been speculated to be clinical symptoms; however, many cases may be asymptomatic. Aside from a medical or travel history at risk for COVID-19, diagnosis can be confirmed by detection of viral RNA by reverse transcriptase–polymerase chain reaction for nasopharyngeal swabs or bronchoalveolar fluid. Patients who are immunocompromised, older, or male or who have a history of cardiovascular conditions or debilitating chronic conditions are at an increased risk for severe disease and poor outcome compared to younger healthy individuals.⁷

The vesicular rash of COVID-19 has been reported to have different forms of presentation. A diffuse widespread pattern resembling hand-foot-and-mouth disease and a localized monomorphic pattern resembling chickenpox but with predilection to the trunk has been described.⁸

Physiologic changes in the immune and cardiopulmonary systems during pregnancy (eg, diaphragm elevation, increased oxygen consumption, edema of the respiratory tract mucosae) make pregnant women intolerant to hypoxia. The mortality rate of the 1918 influenza pandemic was 2.6% in the overall population but 37% among pregnant women.⁹ In 2009, pregnant women were reported to be at an increased risk for complications from the H1N1 influenza virus pandemic, with a higher estimated rate of hospital admission than the general population.¹⁰ In 2003, approximately 50% of pregnant women who received a diagnosis of SARS-CoV were admitted to the intensive care unit, approximately 33% of pregnant women with SARS-CoV required mechanical ventilation, and the mortality rate was as high as 25% for these women.¹¹ To date, data on the effects of COVID-19 in pregnancy are limited to small case series.^12-15

It was confirmed that COVID-19 infection is accompanied by a reduction in lymphocytes, monocytes, and eosinophils, along with a notable reduction of CD4/CD8 T cells, B cells, and natural killer cells. It was further revealed that nonsurvivor COVID-19 patients continued to show a decrease in lymphocyte counts along the course of their disease until death.^16-18

Different mechanisms for lymphocyte depletion and deficiency were speculated among COVID-19 patients and include direct lymphocyte death through coronavirus angiotensin-converting enzyme 2–lymphocyte-expressed receptors; direct damage to lymphatic organs, such as the thymus and spleen, but this theory needs to be further investigated; direct lymphocyte apoptosis mediated by tumor necrosis factor α, IL-6, and other proinflammatory cytokines; and direct inhibition of lymphocytes by metabolic upset, such as acidosis.^19,20

These causes may precipitate lymphopenia and impaired antiviral responses.²¹ It also has been postulated that the functional damage of CD4⁺ T cells may predispose patients with COVID-19 to severe disease.²² Such immune changes can render a patient more susceptible to developing shingles by reactivating varicella-zoster virus, which could be a sign of undiagnosed COVID-19 infection in younger age groups.

Two earlier reports discussed HZ among COVID-19–diagnosed patients. Shors²³ presented a case of a patient who developed varicella-zoster virus reactivation of the V2 dermatome during the course of COVID-19 infection. In addition, the patient developed severe acute herpetic neuralgia despite the early initiation of antiviral therapy.²³ Elsaie et al²⁴ described 2 cases of patients during the pandemic who first presented with HZ before later being diagnosed with COVID-19 infection.

New information and cutaneous manifestations possibly related to COVID-19 are emerging every day. We report a pregnant female presenting with HZ during the course of COVID-19 infection, which suggests that the clinical presentation of HZ at the time of the current pandemic, especially if associated with other signs of COVID-19 infection, should be carefully monitored and reported for further assessment.

Acknowledgment
The authors would like to thank all the health care workers who have been fighting COVID-19 in Egypt and worldwide.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most recently identified member of the zoonotic pathogens of coronaviruses. It caused an outbreak of pneumonia in December 2019 in Wuhan, China.¹ Among all related acute respiratory syndromes (SARS-CoV, Middle East respiratory syndrome coronavirus), SARS-CoV-2 remains to be the most infectious, has the highest potential for human transmission, and can eventually result in acute respiratory distress syndrome.^2,3

Only 15% of coronavirus disease 2019 (COVID-19) cases progress to pneumonia, and approximately 5% of these cases develop acute respiratory distress syndrome, septic shock, and/or multiple organ failure. The majority of cases only exhibit mild to moderate symptoms.^4,5 A wide array of skin manifestations in COVID-19 infection have been reported, including maculopapular eruptions, morbilliform rashes, urticaria, chickenpoxlike lesions, livedo reticularis, COVID toes, erythema multiforme, pityriasis rosea, and several other patterns.⁶ We report a case of herpes zoster (HZ) complication in a COVID-19–positive woman who was 27 weeks pregnant.

Case Report

A 36-year-old woman who was 27 weeks pregnant was referred by her obstetrician to the dermatology clinic. She presented with a low-grade fever and a vesicular painful rash. Physical examination revealed painful, itchy, dysesthetic papules and vesicles on the left side of the forehead along with mild edema of the left upper eyelid but no watering of the eye or photophobia. She reported episodes of fever (temperature, 38.9°C), fatigue, and myalgia over the last week. She had bouts of dyspnea and tachycardia that she thought were related to being in the late second trimester of pregnancy. The area surrounding the vesicular eruption was tender to touch. No dry cough or any gastrointestinal or urinary tract symptoms were noted. She reported a burning sensation when splashing water on the face or when exposed to air currents. One week following the initial symptoms, she experienced a painful vesicular rash along the upper left forehead (Figure) associated with eyelid edema. Oral and ocular mucosae were free of any presentations. She had no relevant history and had not experienced any complications during pregnancy. A diagnosis of HZ was made, and she was prescribed valacyclovir 1 g 3 times daily for 7 days, acetaminophen for the fever, and calamine lotion. We recommended COVID-19 testing based on her symptoms. A chest radiograph and a positive nasopharyngeal smear were consistent with COVID-19 infection. She reported via telephone follow-up 1 week after presentation that her skin condition had improved following the treatment course and that the vesicles eventually dried, leaving a crusting appearance after 5 to 7 days. Regarding her SARS-CoV-2 condition, her oxygen saturation was 95% at presentation; she self-quarantined at home; and she was treated with oseltamivir 75 mg orally every 12 hours for 5 days, azithromycin 500 mg orally daily, acetaminophen, and vitamin C. Electronic fetal heart rate monitoring and ultrasound examinations were performed to assess the condition of the fetus and were reported normal. At the time of writing this article, she was 32 weeks pregnant and tested negative to 2 consecutive nasopharyngeal swabs for COVID-19 and was in good general condition. She continued her pregnancy according to her obstetrician’s recommendations.

Comment

The incubation time of COVID-19 can be up to 14 days. Fever, dry cough, fatigue, and diarrhea have been speculated to be clinical symptoms; however, many cases may be asymptomatic. Aside from a medical or travel history at risk for COVID-19, diagnosis can be confirmed by detection of viral RNA by reverse transcriptase–polymerase chain reaction for nasopharyngeal swabs or bronchoalveolar fluid. Patients who are immunocompromised, older, or male or who have a history of cardiovascular conditions or debilitating chronic conditions are at an increased risk for severe disease and poor outcome compared to younger healthy individuals.⁷

The vesicular rash of COVID-19 has been reported to have different forms of presentation. A diffuse widespread pattern resembling hand-foot-and-mouth disease and a localized monomorphic pattern resembling chickenpox but with predilection to the trunk has been described.⁸

Physiologic changes in the immune and cardiopulmonary systems during pregnancy (eg, diaphragm elevation, increased oxygen consumption, edema of the respiratory tract mucosae) make pregnant women intolerant to hypoxia. The mortality rate of the 1918 influenza pandemic was 2.6% in the overall population but 37% among pregnant women.⁹ In 2009, pregnant women were reported to be at an increased risk for complications from the H1N1 influenza virus pandemic, with a higher estimated rate of hospital admission than the general population.¹⁰ In 2003, approximately 50% of pregnant women who received a diagnosis of SARS-CoV were admitted to the intensive care unit, approximately 33% of pregnant women with SARS-CoV required mechanical ventilation, and the mortality rate was as high as 25% for these women.¹¹ To date, data on the effects of COVID-19 in pregnancy are limited to small case series.^12-15

It was confirmed that COVID-19 infection is accompanied by a reduction in lymphocytes, monocytes, and eosinophils, along with a notable reduction of CD4/CD8 T cells, B cells, and natural killer cells. It was further revealed that nonsurvivor COVID-19 patients continued to show a decrease in lymphocyte counts along the course of their disease until death.^16-18

Different mechanisms for lymphocyte depletion and deficiency were speculated among COVID-19 patients and include direct lymphocyte death through coronavirus angiotensin-converting enzyme 2–lymphocyte-expressed receptors; direct damage to lymphatic organs, such as the thymus and spleen, but this theory needs to be further investigated; direct lymphocyte apoptosis mediated by tumor necrosis factor α, IL-6, and other proinflammatory cytokines; and direct inhibition of lymphocytes by metabolic upset, such as acidosis.^19,20

These causes may precipitate lymphopenia and impaired antiviral responses.²¹ It also has been postulated that the functional damage of CD4⁺ T cells may predispose patients with COVID-19 to severe disease.²² Such immune changes can render a patient more susceptible to developing shingles by reactivating varicella-zoster virus, which could be a sign of undiagnosed COVID-19 infection in younger age groups.

Two earlier reports discussed HZ among COVID-19–diagnosed patients. Shors²³ presented a case of a patient who developed varicella-zoster virus reactivation of the V2 dermatome during the course of COVID-19 infection. In addition, the patient developed severe acute herpetic neuralgia despite the early initiation of antiviral therapy.²³ Elsaie et al²⁴ described 2 cases of patients during the pandemic who first presented with HZ before later being diagnosed with COVID-19 infection.

New information and cutaneous manifestations possibly related to COVID-19 are emerging every day. We report a pregnant female presenting with HZ during the course of COVID-19 infection, which suggests that the clinical presentation of HZ at the time of the current pandemic, especially if associated with other signs of COVID-19 infection, should be carefully monitored and reported for further assessment.

Acknowledgment
The authors would like to thank all the health care workers who have been fighting COVID-19 in Egypt and worldwide.

We are in unprecedented times. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is attacking our communities and, as with any battle, we face unexpected challenges from the global pandemic. What can dermatologists, as highly skilled health care experts, do to support the fight against coronavirus disease 2019 (COVID-19)?

In early 2020, I became involved in a fulfilling and stimulating opportunity to contribute as a US Navy reservist, having just returned from a 3-month deployment. I served in the Medical Operations Center aboard the hospital ship USNS Comfort, which was docked in New York Harbor, as liaison to surrounding New York City hospitals. I also served as sole dermatologist on the ship, caring for the dermatologic needs of our team and consulting on numerous COVID-19 inpatients.

In May 2020, upon return to Virginia from New York City, I served as senior medical officer to medically clear other Navy Reserve health care workers returning from the field hospital at the Jacob K. Javits Convention Center of New York and from serving as embedded caregivers in existing New York City hospitals. I share 2 very important observations from my work there: First, COVID-19 is devastatingly real; second, we dermatologists can be valuable team members in the fight against this disease.

It is normal for us to feel scared, confused, and helpless; as 1% of the physician population, dermatologists represent a small focused fraction of the health care force. Nevertheless, we are all well-trained medical professionals who have taken the same Hippocratic Oath as other physicians. As members of the global health care team, we can each play a role in defeating COVID-19: We can be a trusted voice of reason, set an example, implement safe and effective distancing and hygiene precautions, and assist our local overburdened medical teams.

The magnitude and severity of COVID-19 can create a mass casualty–type phenomenon, overwhelming health care systems if the disease curve is not flattened. We can help flatten that curve by lengthening the pulse duration (to use dermatology jargon): that is, slowing the abrupt impact of cases to allow health care systems to triage, treat, and discharge in a more controlled manner.

How We Can Make a Difference

Despite representing a fraction of the health care team, we see a larger percentage of the population. On the Comfort, for example, dermatology visits accounted for approximately 20% of outpatient crew visits. We have an opportunity and a voice to reach a large percentage of the population directly. Whether we are now seeing patients face-to-face or virtually, we can spread the public health message and set an example. Wearing masks and social distancing do help to slow and markedly decrease the spread of SARS-CoV-2.

When you see patients in your office, consider the following:

• Have patients wait outside the office in their car and call the receptionist upon arrival.

• Have the receptionist call back the patient when the office is ready.

• Prescreen the patient before having him/her enter the clinic.

• Do not allow handshaking.

• Require everyone to wear a mask.

• Wear gloves.

• Have ample hand sanitizer openly available for all.

• Thoroughly clean or disinfect surfaces between patients.

Recalling the Difficult Experience of a Colleague-Patient

I think back to a crew member of Comfort who presented with new-onset pruritus and erythematous papules on the arms, legs, and torso. She was an intensive care unit nurse working 13-hour days, every day, for weeks on a COVID-positive unit—double-masked, gowned, wearing eye protection, in a warmer than usual intensive care unit, managing the most critically ill patients she’s ever cared for. Outside work, her life consisted of a commute on a government-chartered bus between Comfort and a contracted hotel while eating boxed meals. For 6 hours daily, she would—unsuccessfully—attempt to sleep with raging pruritus. Treating this routine case of eczema had a domino effect, improving her quality of life and thus allowing her to provide better care for the critically ill.

Let Us All Join in the Fight

As well-educated medical experts, we have the ability and the opportunity to reach outside our comfort zone and assist our medical colleagues. As I saw in New York City, the spectrum of specialists bravely worked together to meet overwhelming demand on the health care system and care for thousands of critically ill and dying patients. Dermatologists treated extensive eczema, ulcers, and other dermatoses on caretakers; triaged patients for appropriate allocation of care; and delivered care outside their comfort zone as physician extenders on inpatient and critical care units.

We are all in this together. I encourage all dermatologists who are in an area of need to ask your health care system how you can join the fight against SARS-CoV-2. Let’s step forward to help, in recognition of the oath we took to “prevent disease whenever we can.”

We are in unprecedented times. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is attacking our communities and, as with any battle, we face unexpected challenges from the global pandemic. What can dermatologists, as highly skilled health care experts, do to support the fight against coronavirus disease 2019 (COVID-19)?

In early 2020, I became involved in a fulfilling and stimulating opportunity to contribute as a US Navy reservist, having just returned from a 3-month deployment. I served in the Medical Operations Center aboard the hospital ship USNS Comfort, which was docked in New York Harbor, as liaison to surrounding New York City hospitals. I also served as sole dermatologist on the ship, caring for the dermatologic needs of our team and consulting on numerous COVID-19 inpatients.

In May 2020, upon return to Virginia from New York City, I served as senior medical officer to medically clear other Navy Reserve health care workers returning from the field hospital at the Jacob K. Javits Convention Center of New York and from serving as embedded caregivers in existing New York City hospitals. I share 2 very important observations from my work there: First, COVID-19 is devastatingly real; second, we dermatologists can be valuable team members in the fight against this disease.

It is normal for us to feel scared, confused, and helpless; as 1% of the physician population, dermatologists represent a small focused fraction of the health care force. Nevertheless, we are all well-trained medical professionals who have taken the same Hippocratic Oath as other physicians. As members of the global health care team, we can each play a role in defeating COVID-19: We can be a trusted voice of reason, set an example, implement safe and effective distancing and hygiene precautions, and assist our local overburdened medical teams.

The magnitude and severity of COVID-19 can create a mass casualty–type phenomenon, overwhelming health care systems if the disease curve is not flattened. We can help flatten that curve by lengthening the pulse duration (to use dermatology jargon): that is, slowing the abrupt impact of cases to allow health care systems to triage, treat, and discharge in a more controlled manner.

How We Can Make a Difference

Despite representing a fraction of the health care team, we see a larger percentage of the population. On the Comfort, for example, dermatology visits accounted for approximately 20% of outpatient crew visits. We have an opportunity and a voice to reach a large percentage of the population directly. Whether we are now seeing patients face-to-face or virtually, we can spread the public health message and set an example. Wearing masks and social distancing do help to slow and markedly decrease the spread of SARS-CoV-2.

When you see patients in your office, consider the following:

• Have patients wait outside the office in their car and call the receptionist upon arrival.

• Have the receptionist call back the patient when the office is ready.

• Prescreen the patient before having him/her enter the clinic.

• Do not allow handshaking.

• Require everyone to wear a mask.

• Wear gloves.

• Have ample hand sanitizer openly available for all.

• Thoroughly clean or disinfect surfaces between patients.

Recalling the Difficult Experience of a Colleague-Patient

I think back to a crew member of Comfort who presented with new-onset pruritus and erythematous papules on the arms, legs, and torso. She was an intensive care unit nurse working 13-hour days, every day, for weeks on a COVID-positive unit—double-masked, gowned, wearing eye protection, in a warmer than usual intensive care unit, managing the most critically ill patients she’s ever cared for. Outside work, her life consisted of a commute on a government-chartered bus between Comfort and a contracted hotel while eating boxed meals. For 6 hours daily, she would—unsuccessfully—attempt to sleep with raging pruritus. Treating this routine case of eczema had a domino effect, improving her quality of life and thus allowing her to provide better care for the critically ill.

Let Us All Join in the Fight

As well-educated medical experts, we have the ability and the opportunity to reach outside our comfort zone and assist our medical colleagues. As I saw in New York City, the spectrum of specialists bravely worked together to meet overwhelming demand on the health care system and care for thousands of critically ill and dying patients. Dermatologists treated extensive eczema, ulcers, and other dermatoses on caretakers; triaged patients for appropriate allocation of care; and delivered care outside their comfort zone as physician extenders on inpatient and critical care units.

We are all in this together. I encourage all dermatologists who are in an area of need to ask your health care system how you can join the fight against SARS-CoV-2. Let’s step forward to help, in recognition of the oath we took to “prevent disease whenever we can.”

We are in unprecedented times. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is attacking our communities and, as with any battle, we face unexpected challenges from the global pandemic. What can dermatologists, as highly skilled health care experts, do to support the fight against coronavirus disease 2019 (COVID-19)?

In early 2020, I became involved in a fulfilling and stimulating opportunity to contribute as a US Navy reservist, having just returned from a 3-month deployment. I served in the Medical Operations Center aboard the hospital ship USNS Comfort, which was docked in New York Harbor, as liaison to surrounding New York City hospitals. I also served as sole dermatologist on the ship, caring for the dermatologic needs of our team and consulting on numerous COVID-19 inpatients.

In May 2020, upon return to Virginia from New York City, I served as senior medical officer to medically clear other Navy Reserve health care workers returning from the field hospital at the Jacob K. Javits Convention Center of New York and from serving as embedded caregivers in existing New York City hospitals. I share 2 very important observations from my work there: First, COVID-19 is devastatingly real; second, we dermatologists can be valuable team members in the fight against this disease.

It is normal for us to feel scared, confused, and helpless; as 1% of the physician population, dermatologists represent a small focused fraction of the health care force. Nevertheless, we are all well-trained medical professionals who have taken the same Hippocratic Oath as other physicians. As members of the global health care team, we can each play a role in defeating COVID-19: We can be a trusted voice of reason, set an example, implement safe and effective distancing and hygiene precautions, and assist our local overburdened medical teams.

The magnitude and severity of COVID-19 can create a mass casualty–type phenomenon, overwhelming health care systems if the disease curve is not flattened. We can help flatten that curve by lengthening the pulse duration (to use dermatology jargon): that is, slowing the abrupt impact of cases to allow health care systems to triage, treat, and discharge in a more controlled manner.

How We Can Make a Difference

Despite representing a fraction of the health care team, we see a larger percentage of the population. On the Comfort, for example, dermatology visits accounted for approximately 20% of outpatient crew visits. We have an opportunity and a voice to reach a large percentage of the population directly. Whether we are now seeing patients face-to-face or virtually, we can spread the public health message and set an example. Wearing masks and social distancing do help to slow and markedly decrease the spread of SARS-CoV-2.

When you see patients in your office, consider the following:

• Have patients wait outside the office in their car and call the receptionist upon arrival.

• Have the receptionist call back the patient when the office is ready.

• Prescreen the patient before having him/her enter the clinic.

• Do not allow handshaking.

• Require everyone to wear a mask.

• Wear gloves.

• Have ample hand sanitizer openly available for all.

• Thoroughly clean or disinfect surfaces between patients.

Recalling the Difficult Experience of a Colleague-Patient

I think back to a crew member of Comfort who presented with new-onset pruritus and erythematous papules on the arms, legs, and torso. She was an intensive care unit nurse working 13-hour days, every day, for weeks on a COVID-positive unit—double-masked, gowned, wearing eye protection, in a warmer than usual intensive care unit, managing the most critically ill patients she’s ever cared for. Outside work, her life consisted of a commute on a government-chartered bus between Comfort and a contracted hotel while eating boxed meals. For 6 hours daily, she would—unsuccessfully—attempt to sleep with raging pruritus. Treating this routine case of eczema had a domino effect, improving her quality of life and thus allowing her to provide better care for the critically ill.

Let Us All Join in the Fight

As well-educated medical experts, we have the ability and the opportunity to reach outside our comfort zone and assist our medical colleagues. As I saw in New York City, the spectrum of specialists bravely worked together to meet overwhelming demand on the health care system and care for thousands of critically ill and dying patients. Dermatologists treated extensive eczema, ulcers, and other dermatoses on caretakers; triaged patients for appropriate allocation of care; and delivered care outside their comfort zone as physician extenders on inpatient and critical care units.

We are all in this together. I encourage all dermatologists who are in an area of need to ask your health care system how you can join the fight against SARS-CoV-2. Let’s step forward to help, in recognition of the oath we took to “prevent disease whenever we can.”

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started an outbreak of respiratory illnesses in Wuhan, China. The respiratory disease was termed coronavirus disease 2019 (COVID-19) and rapidly spread worldwide, resulting in a pandemic classification on March 11, 2020. ¹ Recently, several cutaneous manifestations of COVID-19 have been reported. Skin manifestations have been reported to be similar to other common viral infections. ² However, there is a paucity of published clinical images of more atypical presentations.

Case Report

A 52-year-old black man presented via urgent store-and-forward teledermatology consultation from his primary care provider with a self-described “vesicular,” highly pruritic rash of both arms and legs of 1 week’s duration without involvement of the trunk, axillae, groin, face, genitalia, or any mucous membranes. He noted nausea, loss of appetite, and nonbloody diarrhea 4 days later. He denied fever, chills, dry cough, shortness of breath, or dyspnea. He had a history of hypertension and type 2 diabetes mellitus. There were no changes in medications; no outdoor activities, gardening, or yard work; no exposure to plants or metals; and no use of new personal care products.

The digital images showed zones of flesh-colored to slightly erythematous, somewhat “juicy” papules with some coalescence into ill-defined plaques. There were scattered foci of scale and hemorrhagic crust that involved both palms, forearms (Figure, A), and legs (Figure, B). There were no intact vesicles, and a herald patch was not identified. Vital signs at the time of imaging were normal, with the exception of a low-grade fever (temperature, 37.3°C). Basic laboratory testing showed only mild leukocytosis with mild neutropenia and mild aspartate aminotransaminase elevation. A skin biopsy was not performed. Pulmonary imaging and workup were not performed because of the lack of respiratory symptoms.

Comment

Coronavirus disease 2019 is caused by SARS-CoV2, an enveloped, nonsegmented, positive-sense RNA virus of the coronavirus family. It is currently believed that SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to gain entry into human cells, leading to infection primarily affecting the lower respiratory tract.³ Patients suspected of COVID-19 infection most often present with fever, dry cough, dyspnea, and fatigue, while GI symptoms such as nausea, vomiting, and diarrhea are uncommon.⁴ More recently, several reports describe a variety of skin findings associated with COVID-19. A current theory suggests that the virus does not directly target keratinocytes but triggers a systemic immune response, leading to a diversity of skin morphologies.⁵ The main types of described cutaneous findings include pseudochilblains, overtly vesicular, urticarial, maculopapular, and livedo/necrosis.⁶ Others have described petechial⁷ and papulosquamous eruptions.⁸ Most of these patients initially presented with typical COVID-19 symptoms and frequently represented more severe cases of the disease. Additionally, the vesicular and papulosquamous eruptions reportedly occurred on the trunk and not the limbs, as in our case.

This confirmed COVID-19–positive patient presented with an ill-defined vesicular and papulosquamous-type eruption on the arms and legs and later developed only mild GI symptoms. By sharing this case, we report yet another skin manifestation of COVID-19 and propose the possible expansion of testing for SARS-CoV-2 in patients presenting with rash and GI symptoms, which holds the potential to increase the identification of COVID-19 in the population, thereby increasing strict contact tracing and slowing the spread of this pandemic.

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started an outbreak of respiratory illnesses in Wuhan, China. The respiratory disease was termed coronavirus disease 2019 (COVID-19) and rapidly spread worldwide, resulting in a pandemic classification on March 11, 2020. ¹ Recently, several cutaneous manifestations of COVID-19 have been reported. Skin manifestations have been reported to be similar to other common viral infections. ² However, there is a paucity of published clinical images of more atypical presentations.

Case Report

A 52-year-old black man presented via urgent store-and-forward teledermatology consultation from his primary care provider with a self-described “vesicular,” highly pruritic rash of both arms and legs of 1 week’s duration without involvement of the trunk, axillae, groin, face, genitalia, or any mucous membranes. He noted nausea, loss of appetite, and nonbloody diarrhea 4 days later. He denied fever, chills, dry cough, shortness of breath, or dyspnea. He had a history of hypertension and type 2 diabetes mellitus. There were no changes in medications; no outdoor activities, gardening, or yard work; no exposure to plants or metals; and no use of new personal care products.

The digital images showed zones of flesh-colored to slightly erythematous, somewhat “juicy” papules with some coalescence into ill-defined plaques. There were scattered foci of scale and hemorrhagic crust that involved both palms, forearms (Figure, A), and legs (Figure, B). There were no intact vesicles, and a herald patch was not identified. Vital signs at the time of imaging were normal, with the exception of a low-grade fever (temperature, 37.3°C). Basic laboratory testing showed only mild leukocytosis with mild neutropenia and mild aspartate aminotransaminase elevation. A skin biopsy was not performed. Pulmonary imaging and workup were not performed because of the lack of respiratory symptoms.

Comment

Coronavirus disease 2019 is caused by SARS-CoV2, an enveloped, nonsegmented, positive-sense RNA virus of the coronavirus family. It is currently believed that SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to gain entry into human cells, leading to infection primarily affecting the lower respiratory tract.³ Patients suspected of COVID-19 infection most often present with fever, dry cough, dyspnea, and fatigue, while GI symptoms such as nausea, vomiting, and diarrhea are uncommon.⁴ More recently, several reports describe a variety of skin findings associated with COVID-19. A current theory suggests that the virus does not directly target keratinocytes but triggers a systemic immune response, leading to a diversity of skin morphologies.⁵ The main types of described cutaneous findings include pseudochilblains, overtly vesicular, urticarial, maculopapular, and livedo/necrosis.⁶ Others have described petechial⁷ and papulosquamous eruptions.⁸ Most of these patients initially presented with typical COVID-19 symptoms and frequently represented more severe cases of the disease. Additionally, the vesicular and papulosquamous eruptions reportedly occurred on the trunk and not the limbs, as in our case.

This confirmed COVID-19–positive patient presented with an ill-defined vesicular and papulosquamous-type eruption on the arms and legs and later developed only mild GI symptoms. By sharing this case, we report yet another skin manifestation of COVID-19 and propose the possible expansion of testing for SARS-CoV-2 in patients presenting with rash and GI symptoms, which holds the potential to increase the identification of COVID-19 in the population, thereby increasing strict contact tracing and slowing the spread of this pandemic.

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started an outbreak of respiratory illnesses in Wuhan, China. The respiratory disease was termed coronavirus disease 2019 (COVID-19) and rapidly spread worldwide, resulting in a pandemic classification on March 11, 2020. ¹ Recently, several cutaneous manifestations of COVID-19 have been reported. Skin manifestations have been reported to be similar to other common viral infections. ² However, there is a paucity of published clinical images of more atypical presentations.

Case Report

A 52-year-old black man presented via urgent store-and-forward teledermatology consultation from his primary care provider with a self-described “vesicular,” highly pruritic rash of both arms and legs of 1 week’s duration without involvement of the trunk, axillae, groin, face, genitalia, or any mucous membranes. He noted nausea, loss of appetite, and nonbloody diarrhea 4 days later. He denied fever, chills, dry cough, shortness of breath, or dyspnea. He had a history of hypertension and type 2 diabetes mellitus. There were no changes in medications; no outdoor activities, gardening, or yard work; no exposure to plants or metals; and no use of new personal care products.

The digital images showed zones of flesh-colored to slightly erythematous, somewhat “juicy” papules with some coalescence into ill-defined plaques. There were scattered foci of scale and hemorrhagic crust that involved both palms, forearms (Figure, A), and legs (Figure, B). There were no intact vesicles, and a herald patch was not identified. Vital signs at the time of imaging were normal, with the exception of a low-grade fever (temperature, 37.3°C). Basic laboratory testing showed only mild leukocytosis with mild neutropenia and mild aspartate aminotransaminase elevation. A skin biopsy was not performed. Pulmonary imaging and workup were not performed because of the lack of respiratory symptoms.

Comment

Coronavirus disease 2019 is caused by SARS-CoV2, an enveloped, nonsegmented, positive-sense RNA virus of the coronavirus family. It is currently believed that SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to gain entry into human cells, leading to infection primarily affecting the lower respiratory tract.³ Patients suspected of COVID-19 infection most often present with fever, dry cough, dyspnea, and fatigue, while GI symptoms such as nausea, vomiting, and diarrhea are uncommon.⁴ More recently, several reports describe a variety of skin findings associated with COVID-19. A current theory suggests that the virus does not directly target keratinocytes but triggers a systemic immune response, leading to a diversity of skin morphologies.⁵ The main types of described cutaneous findings include pseudochilblains, overtly vesicular, urticarial, maculopapular, and livedo/necrosis.⁶ Others have described petechial⁷ and papulosquamous eruptions.⁸ Most of these patients initially presented with typical COVID-19 symptoms and frequently represented more severe cases of the disease. Additionally, the vesicular and papulosquamous eruptions reportedly occurred on the trunk and not the limbs, as in our case.

This confirmed COVID-19–positive patient presented with an ill-defined vesicular and papulosquamous-type eruption on the arms and legs and later developed only mild GI symptoms. By sharing this case, we report yet another skin manifestation of COVID-19 and propose the possible expansion of testing for SARS-CoV-2 in patients presenting with rash and GI symptoms, which holds the potential to increase the identification of COVID-19 in the population, thereby increasing strict contact tracing and slowing the spread of this pandemic.

What Are Essential Oils?

Essential oils are aromatic volatile oils produced by medicinal plants that give them their distinct flavors and aromas. They are extracted using a variety of different techniques, such as microwave-assisted extraction, headspace extraction, and the most commonly employed hydrodistillation.¹ Different parts of the plant are used for the specific oils; the shoots and leaves of Origanum vulgare are used for oregano oil, whereas the skins of Citrus limonum are used for lemon oil.² Historically, essential oils have been used for cooking, food preservation, perfume, and medicine.^3,4

Historical Uses for Essential Oils

Essential oils and their intact medicinal plants were among the first medicines widely available to the ancient world. The Ancient Greeks used topical and oral oregano as a cure-all for ailments including wounds, sore muscles, and diarrhea. Because of its use as a cure-all medicine, it remains a popular folk remedy in parts of Europe today.³ Lavender also has a long history of being a cure-all plant and oil. Some of the many claims behind this flower include treatment of burns, insect bites, parasites, muscle spasms, nausea, and anxiety/depression.⁵ With an extensive list of historical uses, many essential oils are being researched to determine if their acclaimed qualities have quantifiable properties.

Science Behind the Belief

In vitro experiments with oregano (O vulgare) have demonstrated notable antifungal and antimicrobial effects.⁶ Gas chromatographic analysis of the oil shows much of it is composed of phenolic monoterpenes, such as thymol and carvacrol. They exhibit strong antifungal effects with a slightly stronger effect on the dermatophyte Trichophyton rubrum over other yeast species such as Candida.^7,8 The full effect of the monoterpenes on fungi is not completely understood, but early data show it has a strong affinity for the ergosterol used in the cell-wall synthesis. Other effects demonstrated in in vitro studies include the ability to block drug efflux pumps, biofilm formation, cellular communication among bacteria, and mycotoxin production.⁹

A double-blind, randomized trial by Akhondzadeh et al¹⁰ demonstrated lavender (Lavandula officinalis) to have a mild antidepressant quality but a noticeably more potent effect when combined with imipramine. The effects of the lavender with imipramine were stronger and provided earlier improvement than imipramine alone for treatment of mild to moderate depression. The team concluded that lavender may be an effective adjunct therapy in treating depression.¹⁰

In a study by Mori et al,¹¹ full-thickness circular wounds were made in rats and treated with either lavender oil (L officinalis), nothing, or a control oil. With the lavender oil being at only 1% solution, the wounds treated with lavender oil demonstrated earlier closure than the other 2 groups of wounds, where no major difference was noted. On cellular analysis, it was seen that the lavender had increased the rate of granulation as well as expression of types I and III collagen. The most striking result was the large expression of transforming growth factor β seen in the lavender group compared to the others. The final thoughts on this experiment were that lavender may provide new approaches to wound care in the future.¹¹

Potential Problems With Purity

One major concern raised about essential oils is their purity and the fidelity of their chemical composition. The specific aromatic chemicals in each essential oil are maintained for each species, but the proportions of each change even with the time of year.¹² Gas chromatograph analysis of the same oil distilled with different techniques showed that the proportions of aromatic chemicals varied with technique. However, the major constituents of the oil remained present in large quantities, just at different percentages.¹ Even using the same distillation technique for different time periods can greatly affect the yield and composition of the oil. Although the percentage of each aromatic compound can be affected by distillation times, the antioxidant and antimicrobial effects of the oil remain constant regardless of these variables.² There is clearly a lack in standardization in essential oil production, which may not be an issue for its use in complementary medicine if its properties are maintained regardless.

Safety Concerns and Regulations

With essential oils being a natural cure for everyday ailments, some people are turning first to oils for every cut and bruise. The danger in these natural cures is that essential oils can cause several types of dermatitis and allergic reactions. The development of allergies to essential oils is at an even higher risk, considering people frequently put them on wounds and rashes where the skin barrier is already weakened. Many essential oils fall into the fragrance category in patch tests, negating the widely circulating blogger and online reports that essential oils cannot cause allergies.

Some of the oils, although regarded safe by the US Food and Drug Administration for consumption, can cause dermatitis from simple contact or with sun exposure.¹³ Members of the citrus family are notorious for the phytophotodermatitis reaction, which can leave hyperpigmented scarring after exposure of the oils to sunlight.¹⁴ Most companies that sell essential oils are aware of this reaction and include it in the warning labels.

The legal problem with selling and classifying essential oils is that the US Food and Drug Administration requires products intended for treatment to be labeled as drugs, which hinders their sales on the open market.¹³ It all boils down to intended use, so some companies sell the oils under a food or fragrance classification with vague instructions on how to use said oil for medicinal purposes, which leads to lack of supervision, anecdotal cures, and false health claims. One company claims in their safety guide for topical applications of their oils that “[i]f a rash occurs, this may be a sign of detoxification.”¹⁵ If essential oils had only minimal absorption topically, their safety would be less concerning, but this does not appear to be the case.

Absorption and Systemics

The effects of essential oils on the skin is one aspect of their use to be studied; another is the more systemic effects from absorption through the skin. Most essential oils used in small quantities for fragrance in over-the-counter lotions prove only to be an issue for allergens in sensitive patient groups. However, topical applications of essential oils in their pure concentrated form get absorbed into the skin faster than if used with a carrier oil, emulsion, or solvent.¹⁶ For most minor uses of essential oils, the body can detoxify absorbed chemicals the same way it does when a person eats the plants the oils came from (eg, basil essential oils leaching from the leaves into a tomato sauce). A possible danger of the oils’ systemic properties lies in the pregnant patient population who use essential oils thinking that natural is safe.

Many essential oils, such as lavender (L officinalis), exhibit hormonal mimicry with phytoestrogens and can produce emmenagogue (increasing menstrual flow) effects in women. Other oils, such as those of nutmeg (Myristica fragrans) and myrrh (Commiphora myrrha), can have abortifacient effects. These natural essential oils can lead to unintended health risks for mother and baby.¹⁷ With implications this serious, many essential oil companies put pregnancy warnings on most if not all of their products, but pregnant patients may not always note the risk.

Conclusion

Essential oils are not the newest medical fad. They outdate every drug on the market and were used by some of the first physicians in history. It is important to continue research into the antimicrobial effects of essential oils, as they may hold the secret to treatment options with the continued rise of multidrug-resistant organisms. The danger of these oils lies not in their hidden potential but in the belief that natural things are safe. A few animal studies have been performed, but little is known about the full effects of essential oils in humans. Patients need to be educated that these are not panaceas with freedom from side effects and that treatment options backed by the scientific method should be their first choice under the supervision of trained physicians. The Table outlines the uses and side effects of the essential oils discussed here.

What Are Essential Oils?

Essential oils are aromatic volatile oils produced by medicinal plants that give them their distinct flavors and aromas. They are extracted using a variety of different techniques, such as microwave-assisted extraction, headspace extraction, and the most commonly employed hydrodistillation.¹ Different parts of the plant are used for the specific oils; the shoots and leaves of Origanum vulgare are used for oregano oil, whereas the skins of Citrus limonum are used for lemon oil.² Historically, essential oils have been used for cooking, food preservation, perfume, and medicine.^3,4

Historical Uses for Essential Oils

Essential oils and their intact medicinal plants were among the first medicines widely available to the ancient world. The Ancient Greeks used topical and oral oregano as a cure-all for ailments including wounds, sore muscles, and diarrhea. Because of its use as a cure-all medicine, it remains a popular folk remedy in parts of Europe today.³ Lavender also has a long history of being a cure-all plant and oil. Some of the many claims behind this flower include treatment of burns, insect bites, parasites, muscle spasms, nausea, and anxiety/depression.⁵ With an extensive list of historical uses, many essential oils are being researched to determine if their acclaimed qualities have quantifiable properties.

Science Behind the Belief

In vitro experiments with oregano (O vulgare) have demonstrated notable antifungal and antimicrobial effects.⁶ Gas chromatographic analysis of the oil shows much of it is composed of phenolic monoterpenes, such as thymol and carvacrol. They exhibit strong antifungal effects with a slightly stronger effect on the dermatophyte Trichophyton rubrum over other yeast species such as Candida.^7,8 The full effect of the monoterpenes on fungi is not completely understood, but early data show it has a strong affinity for the ergosterol used in the cell-wall synthesis. Other effects demonstrated in in vitro studies include the ability to block drug efflux pumps, biofilm formation, cellular communication among bacteria, and mycotoxin production.⁹

A double-blind, randomized trial by Akhondzadeh et al¹⁰ demonstrated lavender (Lavandula officinalis) to have a mild antidepressant quality but a noticeably more potent effect when combined with imipramine. The effects of the lavender with imipramine were stronger and provided earlier improvement than imipramine alone for treatment of mild to moderate depression. The team concluded that lavender may be an effective adjunct therapy in treating depression.¹⁰

In a study by Mori et al,¹¹ full-thickness circular wounds were made in rats and treated with either lavender oil (L officinalis), nothing, or a control oil. With the lavender oil being at only 1% solution, the wounds treated with lavender oil demonstrated earlier closure than the other 2 groups of wounds, where no major difference was noted. On cellular analysis, it was seen that the lavender had increased the rate of granulation as well as expression of types I and III collagen. The most striking result was the large expression of transforming growth factor β seen in the lavender group compared to the others. The final thoughts on this experiment were that lavender may provide new approaches to wound care in the future.¹¹

Potential Problems With Purity

One major concern raised about essential oils is their purity and the fidelity of their chemical composition. The specific aromatic chemicals in each essential oil are maintained for each species, but the proportions of each change even with the time of year.¹² Gas chromatograph analysis of the same oil distilled with different techniques showed that the proportions of aromatic chemicals varied with technique. However, the major constituents of the oil remained present in large quantities, just at different percentages.¹ Even using the same distillation technique for different time periods can greatly affect the yield and composition of the oil. Although the percentage of each aromatic compound can be affected by distillation times, the antioxidant and antimicrobial effects of the oil remain constant regardless of these variables.² There is clearly a lack in standardization in essential oil production, which may not be an issue for its use in complementary medicine if its properties are maintained regardless.

Safety Concerns and Regulations

With essential oils being a natural cure for everyday ailments, some people are turning first to oils for every cut and bruise. The danger in these natural cures is that essential oils can cause several types of dermatitis and allergic reactions. The development of allergies to essential oils is at an even higher risk, considering people frequently put them on wounds and rashes where the skin barrier is already weakened. Many essential oils fall into the fragrance category in patch tests, negating the widely circulating blogger and online reports that essential oils cannot cause allergies.

Some of the oils, although regarded safe by the US Food and Drug Administration for consumption, can cause dermatitis from simple contact or with sun exposure.¹³ Members of the citrus family are notorious for the phytophotodermatitis reaction, which can leave hyperpigmented scarring after exposure of the oils to sunlight.¹⁴ Most companies that sell essential oils are aware of this reaction and include it in the warning labels.

The legal problem with selling and classifying essential oils is that the US Food and Drug Administration requires products intended for treatment to be labeled as drugs, which hinders their sales on the open market.¹³ It all boils down to intended use, so some companies sell the oils under a food or fragrance classification with vague instructions on how to use said oil for medicinal purposes, which leads to lack of supervision, anecdotal cures, and false health claims. One company claims in their safety guide for topical applications of their oils that “[i]f a rash occurs, this may be a sign of detoxification.”¹⁵ If essential oils had only minimal absorption topically, their safety would be less concerning, but this does not appear to be the case.

Absorption and Systemics

The effects of essential oils on the skin is one aspect of their use to be studied; another is the more systemic effects from absorption through the skin. Most essential oils used in small quantities for fragrance in over-the-counter lotions prove only to be an issue for allergens in sensitive patient groups. However, topical applications of essential oils in their pure concentrated form get absorbed into the skin faster than if used with a carrier oil, emulsion, or solvent.¹⁶ For most minor uses of essential oils, the body can detoxify absorbed chemicals the same way it does when a person eats the plants the oils came from (eg, basil essential oils leaching from the leaves into a tomato sauce). A possible danger of the oils’ systemic properties lies in the pregnant patient population who use essential oils thinking that natural is safe.

Many essential oils, such as lavender (L officinalis), exhibit hormonal mimicry with phytoestrogens and can produce emmenagogue (increasing menstrual flow) effects in women. Other oils, such as those of nutmeg (Myristica fragrans) and myrrh (Commiphora myrrha), can have abortifacient effects. These natural essential oils can lead to unintended health risks for mother and baby.¹⁷ With implications this serious, many essential oil companies put pregnancy warnings on most if not all of their products, but pregnant patients may not always note the risk.

Conclusion

Essential oils are not the newest medical fad. They outdate every drug on the market and were used by some of the first physicians in history. It is important to continue research into the antimicrobial effects of essential oils, as they may hold the secret to treatment options with the continued rise of multidrug-resistant organisms. The danger of these oils lies not in their hidden potential but in the belief that natural things are safe. A few animal studies have been performed, but little is known about the full effects of essential oils in humans. Patients need to be educated that these are not panaceas with freedom from side effects and that treatment options backed by the scientific method should be their first choice under the supervision of trained physicians. The Table outlines the uses and side effects of the essential oils discussed here.

What Are Essential Oils?

Essential oils are aromatic volatile oils produced by medicinal plants that give them their distinct flavors and aromas. They are extracted using a variety of different techniques, such as microwave-assisted extraction, headspace extraction, and the most commonly employed hydrodistillation.¹ Different parts of the plant are used for the specific oils; the shoots and leaves of Origanum vulgare are used for oregano oil, whereas the skins of Citrus limonum are used for lemon oil.² Historically, essential oils have been used for cooking, food preservation, perfume, and medicine.^3,4

Historical Uses for Essential Oils

Essential oils and their intact medicinal plants were among the first medicines widely available to the ancient world. The Ancient Greeks used topical and oral oregano as a cure-all for ailments including wounds, sore muscles, and diarrhea. Because of its use as a cure-all medicine, it remains a popular folk remedy in parts of Europe today.³ Lavender also has a long history of being a cure-all plant and oil. Some of the many claims behind this flower include treatment of burns, insect bites, parasites, muscle spasms, nausea, and anxiety/depression.⁵ With an extensive list of historical uses, many essential oils are being researched to determine if their acclaimed qualities have quantifiable properties.

Science Behind the Belief

In vitro experiments with oregano (O vulgare) have demonstrated notable antifungal and antimicrobial effects.⁶ Gas chromatographic analysis of the oil shows much of it is composed of phenolic monoterpenes, such as thymol and carvacrol. They exhibit strong antifungal effects with a slightly stronger effect on the dermatophyte Trichophyton rubrum over other yeast species such as Candida.^7,8 The full effect of the monoterpenes on fungi is not completely understood, but early data show it has a strong affinity for the ergosterol used in the cell-wall synthesis. Other effects demonstrated in in vitro studies include the ability to block drug efflux pumps, biofilm formation, cellular communication among bacteria, and mycotoxin production.⁹

A double-blind, randomized trial by Akhondzadeh et al¹⁰ demonstrated lavender (Lavandula officinalis) to have a mild antidepressant quality but a noticeably more potent effect when combined with imipramine. The effects of the lavender with imipramine were stronger and provided earlier improvement than imipramine alone for treatment of mild to moderate depression. The team concluded that lavender may be an effective adjunct therapy in treating depression.¹⁰

In a study by Mori et al,¹¹ full-thickness circular wounds were made in rats and treated with either lavender oil (L officinalis), nothing, or a control oil. With the lavender oil being at only 1% solution, the wounds treated with lavender oil demonstrated earlier closure than the other 2 groups of wounds, where no major difference was noted. On cellular analysis, it was seen that the lavender had increased the rate of granulation as well as expression of types I and III collagen. The most striking result was the large expression of transforming growth factor β seen in the lavender group compared to the others. The final thoughts on this experiment were that lavender may provide new approaches to wound care in the future.¹¹

Potential Problems With Purity

One major concern raised about essential oils is their purity and the fidelity of their chemical composition. The specific aromatic chemicals in each essential oil are maintained for each species, but the proportions of each change even with the time of year.¹² Gas chromatograph analysis of the same oil distilled with different techniques showed that the proportions of aromatic chemicals varied with technique. However, the major constituents of the oil remained present in large quantities, just at different percentages.¹ Even using the same distillation technique for different time periods can greatly affect the yield and composition of the oil. Although the percentage of each aromatic compound can be affected by distillation times, the antioxidant and antimicrobial effects of the oil remain constant regardless of these variables.² There is clearly a lack in standardization in essential oil production, which may not be an issue for its use in complementary medicine if its properties are maintained regardless.

Safety Concerns and Regulations

With essential oils being a natural cure for everyday ailments, some people are turning first to oils for every cut and bruise. The danger in these natural cures is that essential oils can cause several types of dermatitis and allergic reactions. The development of allergies to essential oils is at an even higher risk, considering people frequently put them on wounds and rashes where the skin barrier is already weakened. Many essential oils fall into the fragrance category in patch tests, negating the widely circulating blogger and online reports that essential oils cannot cause allergies.

Some of the oils, although regarded safe by the US Food and Drug Administration for consumption, can cause dermatitis from simple contact or with sun exposure.¹³ Members of the citrus family are notorious for the phytophotodermatitis reaction, which can leave hyperpigmented scarring after exposure of the oils to sunlight.¹⁴ Most companies that sell essential oils are aware of this reaction and include it in the warning labels.

The legal problem with selling and classifying essential oils is that the US Food and Drug Administration requires products intended for treatment to be labeled as drugs, which hinders their sales on the open market.¹³ It all boils down to intended use, so some companies sell the oils under a food or fragrance classification with vague instructions on how to use said oil for medicinal purposes, which leads to lack of supervision, anecdotal cures, and false health claims. One company claims in their safety guide for topical applications of their oils that “[i]f a rash occurs, this may be a sign of detoxification.”¹⁵ If essential oils had only minimal absorption topically, their safety would be less concerning, but this does not appear to be the case.

Absorption and Systemics

The effects of essential oils on the skin is one aspect of their use to be studied; another is the more systemic effects from absorption through the skin. Most essential oils used in small quantities for fragrance in over-the-counter lotions prove only to be an issue for allergens in sensitive patient groups. However, topical applications of essential oils in their pure concentrated form get absorbed into the skin faster than if used with a carrier oil, emulsion, or solvent.¹⁶ For most minor uses of essential oils, the body can detoxify absorbed chemicals the same way it does when a person eats the plants the oils came from (eg, basil essential oils leaching from the leaves into a tomato sauce). A possible danger of the oils’ systemic properties lies in the pregnant patient population who use essential oils thinking that natural is safe.

Many essential oils, such as lavender (L officinalis), exhibit hormonal mimicry with phytoestrogens and can produce emmenagogue (increasing menstrual flow) effects in women. Other oils, such as those of nutmeg (Myristica fragrans) and myrrh (Commiphora myrrha), can have abortifacient effects. These natural essential oils can lead to unintended health risks for mother and baby.¹⁷ With implications this serious, many essential oil companies put pregnancy warnings on most if not all of their products, but pregnant patients may not always note the risk.

Conclusion

Essential oils are not the newest medical fad. They outdate every drug on the market and were used by some of the first physicians in history. It is important to continue research into the antimicrobial effects of essential oils, as they may hold the secret to treatment options with the continued rise of multidrug-resistant organisms. The danger of these oils lies not in their hidden potential but in the belief that natural things are safe. A few animal studies have been performed, but little is known about the full effects of essential oils in humans. Patients need to be educated that these are not panaceas with freedom from side effects and that treatment options backed by the scientific method should be their first choice under the supervision of trained physicians. The Table outlines the uses and side effects of the essential oils discussed here.

Vaccines work. They are powerful tools that have saved millions of lives worldwide; however, a robust antivaccine movement has taken hold in the United States and worldwide despite overwhelming data in support of vaccination. In fact, vaccine hesitancy—the reluctance or refusal to vaccinate despite the availability of vaccines—was listed by the World Health Organization as one of the top 10 global health threats in 2019.¹

Several vaccines have a role in dermatology, including the human papillomavirus (HPV) vaccine (Gardasil 9 [Merck Sharp & Dohme Corp]), the herpes zoster vaccines (Zostavax [Merck Sharp & Dohme Corp] and Shingrix [GlaxoSmithKline Biologicals]), and the measles-mumps-rubella vaccine, among others. These vaccinations are necessary for children and many adults alike, and they play a critical role in protecting both healthy and immunosuppressed patients.

Vaccine hesitancy is a growing threat to individual and public health that requires a response from all physicians. In our experience, dermatologists have been somewhat passive in advocating for vaccinations, possibly due to knowledge barriers or time constraints; however, this stance must change. Dermatologists must join the front lines in advocating for vaccinations, which are a proven and effective modality in promoting public health.

Dermatologists can employ the following practical tips to improve vaccination compliance among patients:

• Familiarize yourself with the Centers for Disease Control and Prevention immunization schedules and vaccination information sheets (https://www.cdc.gov/vaccines/hcp/vis/current-vis.html). Printed copies of informational handouts should be readily available to provide to patients in the office. The Centers for Disease Control and Prevention also offers tip sheets to guide conversations with patients (https://www.cdc.gov/vaccines/hcp/conversations/index.html).

• Prior to starting an immunosuppressive medication, confirm the patient’s immunization status. You should know which vaccines are live (containing an attenuated pathogen) and which are inactivated. Live vaccines typically are not administered to immunosuppressed patients.

• Use electronic medical records to help provide reminders to prompt administration of any necessary vaccines.

• Know the facts, especially regarding purported vaccine controversies, and be able to cite data on vaccine safety and efficacy. For example, when having a conversation with a patient you could state that vaccination against HPV, which can cause genital warts and certain cancers, has decreased the number of HPV infections by more than 70% in young women and 80% in teenaged girls.² Cervical precancers were reduced by 40% in women vaccinated against HPV. Twelve years of monitoring data validates the safety and efficacy of the HPV vaccine—it is safe and effective, with benefits that outweigh any potential risks.²

• Tailor counseling based on the patient’s age and focus on benefits that directly impact the patient. For example, consider showing young adults photographs of genital warts while educating them that the HPV vaccine can help prevent this kind of infection in the future.

• Emphasize that vaccines are a routine part of comprehensive patient care and support this point by providing data and specific reasons for recommending vaccines.³ Avoid phrases such as, “Do you want the vaccine?” or “You could consider receiving the vaccine today,” which can imply that the vaccine is not necessary.

• Offer vaccines in your office or provide clear printed informational sheets directing patients to nearby primary care clinics, infectious disease clinics, or pharmacies where vaccinations are offered.

• Consider using social media to promote the benefits of vaccination among patients.

The recent coronavirus disease 2019 pandemic has brought the topic of vaccination into the limelight while highlighting that rampant misinformation can lead to distrust of health care workers. Dermatologists, along with all physicians, should be trusted advisors and advocates for public health. In addition to being knowledgeable, dermatologists must remain open-minded in having conversations with skeptical patients. Physicians must take the time and effort to promote vaccinations—the health of patients and the general public depends on it.

Vaccines work. They are powerful tools that have saved millions of lives worldwide; however, a robust antivaccine movement has taken hold in the United States and worldwide despite overwhelming data in support of vaccination. In fact, vaccine hesitancy—the reluctance or refusal to vaccinate despite the availability of vaccines—was listed by the World Health Organization as one of the top 10 global health threats in 2019.¹

Several vaccines have a role in dermatology, including the human papillomavirus (HPV) vaccine (Gardasil 9 [Merck Sharp & Dohme Corp]), the herpes zoster vaccines (Zostavax [Merck Sharp & Dohme Corp] and Shingrix [GlaxoSmithKline Biologicals]), and the measles-mumps-rubella vaccine, among others. These vaccinations are necessary for children and many adults alike, and they play a critical role in protecting both healthy and immunosuppressed patients.

Vaccine hesitancy is a growing threat to individual and public health that requires a response from all physicians. In our experience, dermatologists have been somewhat passive in advocating for vaccinations, possibly due to knowledge barriers or time constraints; however, this stance must change. Dermatologists must join the front lines in advocating for vaccinations, which are a proven and effective modality in promoting public health.

Dermatologists can employ the following practical tips to improve vaccination compliance among patients:

• Familiarize yourself with the Centers for Disease Control and Prevention immunization schedules and vaccination information sheets (https://www.cdc.gov/vaccines/hcp/vis/current-vis.html). Printed copies of informational handouts should be readily available to provide to patients in the office. The Centers for Disease Control and Prevention also offers tip sheets to guide conversations with patients (https://www.cdc.gov/vaccines/hcp/conversations/index.html).

• Prior to starting an immunosuppressive medication, confirm the patient’s immunization status. You should know which vaccines are live (containing an attenuated pathogen) and which are inactivated. Live vaccines typically are not administered to immunosuppressed patients.

• Use electronic medical records to help provide reminders to prompt administration of any necessary vaccines.

• Know the facts, especially regarding purported vaccine controversies, and be able to cite data on vaccine safety and efficacy. For example, when having a conversation with a patient you could state that vaccination against HPV, which can cause genital warts and certain cancers, has decreased the number of HPV infections by more than 70% in young women and 80% in teenaged girls.² Cervical precancers were reduced by 40% in women vaccinated against HPV. Twelve years of monitoring data validates the safety and efficacy of the HPV vaccine—it is safe and effective, with benefits that outweigh any potential risks.²

• Tailor counseling based on the patient’s age and focus on benefits that directly impact the patient. For example, consider showing young adults photographs of genital warts while educating them that the HPV vaccine can help prevent this kind of infection in the future.

• Emphasize that vaccines are a routine part of comprehensive patient care and support this point by providing data and specific reasons for recommending vaccines.³ Avoid phrases such as, “Do you want the vaccine?” or “You could consider receiving the vaccine today,” which can imply that the vaccine is not necessary.

• Offer vaccines in your office or provide clear printed informational sheets directing patients to nearby primary care clinics, infectious disease clinics, or pharmacies where vaccinations are offered.

• Consider using social media to promote the benefits of vaccination among patients.

The recent coronavirus disease 2019 pandemic has brought the topic of vaccination into the limelight while highlighting that rampant misinformation can lead to distrust of health care workers. Dermatologists, along with all physicians, should be trusted advisors and advocates for public health. In addition to being knowledgeable, dermatologists must remain open-minded in having conversations with skeptical patients. Physicians must take the time and effort to promote vaccinations—the health of patients and the general public depends on it.

Vaccines work. They are powerful tools that have saved millions of lives worldwide; however, a robust antivaccine movement has taken hold in the United States and worldwide despite overwhelming data in support of vaccination. In fact, vaccine hesitancy—the reluctance or refusal to vaccinate despite the availability of vaccines—was listed by the World Health Organization as one of the top 10 global health threats in 2019.¹

Several vaccines have a role in dermatology, including the human papillomavirus (HPV) vaccine (Gardasil 9 [Merck Sharp & Dohme Corp]), the herpes zoster vaccines (Zostavax [Merck Sharp & Dohme Corp] and Shingrix [GlaxoSmithKline Biologicals]), and the measles-mumps-rubella vaccine, among others. These vaccinations are necessary for children and many adults alike, and they play a critical role in protecting both healthy and immunosuppressed patients.

Vaccine hesitancy is a growing threat to individual and public health that requires a response from all physicians. In our experience, dermatologists have been somewhat passive in advocating for vaccinations, possibly due to knowledge barriers or time constraints; however, this stance must change. Dermatologists must join the front lines in advocating for vaccinations, which are a proven and effective modality in promoting public health.

Dermatologists can employ the following practical tips to improve vaccination compliance among patients:

• Familiarize yourself with the Centers for Disease Control and Prevention immunization schedules and vaccination information sheets (https://www.cdc.gov/vaccines/hcp/vis/current-vis.html). Printed copies of informational handouts should be readily available to provide to patients in the office. The Centers for Disease Control and Prevention also offers tip sheets to guide conversations with patients (https://www.cdc.gov/vaccines/hcp/conversations/index.html).

• Prior to starting an immunosuppressive medication, confirm the patient’s immunization status. You should know which vaccines are live (containing an attenuated pathogen) and which are inactivated. Live vaccines typically are not administered to immunosuppressed patients.

• Use electronic medical records to help provide reminders to prompt administration of any necessary vaccines.

• Know the facts, especially regarding purported vaccine controversies, and be able to cite data on vaccine safety and efficacy. For example, when having a conversation with a patient you could state that vaccination against HPV, which can cause genital warts and certain cancers, has decreased the number of HPV infections by more than 70% in young women and 80% in teenaged girls.² Cervical precancers were reduced by 40% in women vaccinated against HPV. Twelve years of monitoring data validates the safety and efficacy of the HPV vaccine—it is safe and effective, with benefits that outweigh any potential risks.²

• Tailor counseling based on the patient’s age and focus on benefits that directly impact the patient. For example, consider showing young adults photographs of genital warts while educating them that the HPV vaccine can help prevent this kind of infection in the future.

• Emphasize that vaccines are a routine part of comprehensive patient care and support this point by providing data and specific reasons for recommending vaccines.³ Avoid phrases such as, “Do you want the vaccine?” or “You could consider receiving the vaccine today,” which can imply that the vaccine is not necessary.

• Offer vaccines in your office or provide clear printed informational sheets directing patients to nearby primary care clinics, infectious disease clinics, or pharmacies where vaccinations are offered.

• Consider using social media to promote the benefits of vaccination among patients.

The recent coronavirus disease 2019 pandemic has brought the topic of vaccination into the limelight while highlighting that rampant misinformation can lead to distrust of health care workers. Dermatologists, along with all physicians, should be trusted advisors and advocates for public health. In addition to being knowledgeable, dermatologists must remain open-minded in having conversations with skeptical patients. Physicians must take the time and effort to promote vaccinations—the health of patients and the general public depends on it.

Reports of signs of heart failure in adults with COVID-19 have been rare – just four such cases have been published since the outbreak started in China – and now a team of pediatric cardiologists in New York have reported a case of acute but reversible myocardial injury in an infant with COVID-19.

Madhu S. et al. J Am Coll Cardiol Case Rep. 2020 doi: 10.1016/j.jaccas.2020.09.031

SOURCE: Sharma M et al. JACC Case Rep. 2020. doi: 10.1016/j.jaccas.2020.09.031.

Reports of signs of heart failure in adults with COVID-19 have been rare – just four such cases have been published since the outbreak started in China – and now a team of pediatric cardiologists in New York have reported a case of acute but reversible myocardial injury in an infant with COVID-19.

Madhu S. et al. J Am Coll Cardiol Case Rep. 2020 doi: 10.1016/j.jaccas.2020.09.031

SOURCE: Sharma M et al. JACC Case Rep. 2020. doi: 10.1016/j.jaccas.2020.09.031.

Reports of signs of heart failure in adults with COVID-19 have been rare – just four such cases have been published since the outbreak started in China – and now a team of pediatric cardiologists in New York have reported a case of acute but reversible myocardial injury in an infant with COVID-19.

Madhu S. et al. J Am Coll Cardiol Case Rep. 2020 doi: 10.1016/j.jaccas.2020.09.031

SOURCE: Sharma M et al. JACC Case Rep. 2020. doi: 10.1016/j.jaccas.2020.09.031.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Additional blood cultures are not needed after two negative follow-up blood culture results in well-appearing patients with Staphylococcus aureus bacteremia, reported Caitlin Cardenas-Comfort, MD, of the section of pediatric infectious diseases at Baylor College of Medicine, Houston, and colleagues.

CDC/Janice Haney Carr

In a retrospective cohort study of 122 pediatric patients with documented Staphylococcus aureus bacteremia (SAB) that were hospitalized at one of three hospitals in the Texas Children’s Hospital network in Houston, Dr. Cardenas-Comfort and colleagues sought to determine whether specific recommendations can be made on the number of follow-up blood cultures (FUBC) needed to document clearance of SAB. Patients included in the study were under 18 years of age and had confirmed diagnosis of SAB between Jan. 1, and Dec. 31, 2018.
 

Most cases of bacteremia resolve in under 48 hours

In the majority of cases, patients had bacteremia for less than 48 hours and few to no complications. Only 16% of patients experienced bacteremia lasting 3 or more days, and they had either central line-associated bloodstream infection, endocarditis, or osteomyelitis. In such cases, “patients with endovascular and closed-space infections are at an increased risk of persistent bacteremia,” warranting more conservative monitoring and follow-up, cautioned the researchers.

Although Dr. Cardenas-Comfort and colleagues did note an association between the duration of bacteremia and a diagnosis of infectious disease, increased risk for persistent SAB did not appear to be tied to an underlying medical condition, including immunosuppression.

Fewer than 5% of patients with SAB had intermittent positive cultures and fewer than 1% had repeat positive cultures following two negative FUBC results. For those patients with intermittent positive cultures, the risk of being diagnosed with endocarditis or osteomyelitis is more than double. The authors suggested that “source control could be a critical variable” increasing the risk for intermittent positive cultures, noting that surgical debridement occurred more than 24 hours following initial blood draw for every patient in the osteomyelitis group. In contrast, of those who had consistently negative FUBC results, only 2 of 33 (6%) had debridement in the same period, and only 6 of 33 (18%) required more than one debridement.
 

Children are less likely to have intermittent positive cultures

Dr. Cardenas-Comfort and colleagues also observed that intermittent positive cultures may appear less frequently in children than adults, consistent with a recent study of adults in which intermittent cultures were found in 13% of 1.071 SAB cases. In just 4% of the cases in that study, more than 2 days of negative blood cultures preceded a repeat positive culture.

The researchers noted several study limitations in their own research. Because more than half (61%) of patients had two or less FUBCs collected, and 21% one or less, they acknowledged that their conclusions are based on the presumption that the 61% of patients would not have any further positive cultures if they had been drawn. Relying on provider documentation also suggested that cases of bacteremia without an identified source also likely were overrepresented. The retrospective nature of the study only allowed for limited collection of standardized follow-up metrics with the limited patient sample available. Patient characteristics also may have affected the quality of study results because a large number of patients had underlying medical conditions or were premature infants.
 

Look for ongoing hemodynamic instability before third FUBC

Dr. Cardenas-Comfort and colleagues only recommend a third FUBC in cases where patients demonstrate ongoing hemodynamic instability. Applying this to their study population, in retrospect, the authors noted that unnecessary FUBCs could have been prevented in 26% of patients included in the study. They further recommend a thorough clinical evaluation for any patients with SAB lasting 3 or more days with an unidentified infection source. Further research could be beneficial in evaluating cost savings that come from eliminating unnecessary cultures. Additionally, performing a powered analysis would help to determine the probability of an increase in complications based on implementation of these recommendations.

In a separate interview, Tina Q. Tan, MD, infectious disease specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago noted: “This study provides some importance evidence-based guidance on deciding how many blood cultures are needed to demonstrate clearance of S. aureus bacteremia, even in children who have intermittent positive cultures after having negative FUBCs. The recommendation that additional blood cultures to document sterility are not needed after 2 FUBC results are negative in well-appearing children is one that has the potential to decrease cost and unnecessary discomfort in patients. The recommendation currently is for well-appearing children; children who are ill appearing may require further blood cultures to document sterility. Even though this is a single-center study with a relatively small number of patients (n = 122), the information provided is a very useful guide to all clinicians who deal with this issue. Further studies are needed to determine the impact on cost reduction by the elimination of unnecessary blood cultures and whether the rate of complications would increase as a result of not obtaining further cultures in well-appearing children who have two negative follow up blood cultures.”

Dr. Cardenas-Comfort and colleagues as well as Dr. Tan had no conflicts of interest and no relevant financial disclosures. There was no external funding for the study.

SOURCE: Cardenas-Comfort C et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1821.

Additional blood cultures are not needed after two negative follow-up blood culture results in well-appearing patients with Staphylococcus aureus bacteremia, reported Caitlin Cardenas-Comfort, MD, of the section of pediatric infectious diseases at Baylor College of Medicine, Houston, and colleagues.

CDC/Janice Haney Carr

In a retrospective cohort study of 122 pediatric patients with documented Staphylococcus aureus bacteremia (SAB) that were hospitalized at one of three hospitals in the Texas Children’s Hospital network in Houston, Dr. Cardenas-Comfort and colleagues sought to determine whether specific recommendations can be made on the number of follow-up blood cultures (FUBC) needed to document clearance of SAB. Patients included in the study were under 18 years of age and had confirmed diagnosis of SAB between Jan. 1, and Dec. 31, 2018.
 

Most cases of bacteremia resolve in under 48 hours

In the majority of cases, patients had bacteremia for less than 48 hours and few to no complications. Only 16% of patients experienced bacteremia lasting 3 or more days, and they had either central line-associated bloodstream infection, endocarditis, or osteomyelitis. In such cases, “patients with endovascular and closed-space infections are at an increased risk of persistent bacteremia,” warranting more conservative monitoring and follow-up, cautioned the researchers.

Although Dr. Cardenas-Comfort and colleagues did note an association between the duration of bacteremia and a diagnosis of infectious disease, increased risk for persistent SAB did not appear to be tied to an underlying medical condition, including immunosuppression.

Fewer than 5% of patients with SAB had intermittent positive cultures and fewer than 1% had repeat positive cultures following two negative FUBC results. For those patients with intermittent positive cultures, the risk of being diagnosed with endocarditis or osteomyelitis is more than double. The authors suggested that “source control could be a critical variable” increasing the risk for intermittent positive cultures, noting that surgical debridement occurred more than 24 hours following initial blood draw for every patient in the osteomyelitis group. In contrast, of those who had consistently negative FUBC results, only 2 of 33 (6%) had debridement in the same period, and only 6 of 33 (18%) required more than one debridement.
 

Children are less likely to have intermittent positive cultures

Dr. Cardenas-Comfort and colleagues also observed that intermittent positive cultures may appear less frequently in children than adults, consistent with a recent study of adults in which intermittent cultures were found in 13% of 1.071 SAB cases. In just 4% of the cases in that study, more than 2 days of negative blood cultures preceded a repeat positive culture.

The researchers noted several study limitations in their own research. Because more than half (61%) of patients had two or less FUBCs collected, and 21% one or less, they acknowledged that their conclusions are based on the presumption that the 61% of patients would not have any further positive cultures if they had been drawn. Relying on provider documentation also suggested that cases of bacteremia without an identified source also likely were overrepresented. The retrospective nature of the study only allowed for limited collection of standardized follow-up metrics with the limited patient sample available. Patient characteristics also may have affected the quality of study results because a large number of patients had underlying medical conditions or were premature infants.
 

Look for ongoing hemodynamic instability before third FUBC

Dr. Cardenas-Comfort and colleagues only recommend a third FUBC in cases where patients demonstrate ongoing hemodynamic instability. Applying this to their study population, in retrospect, the authors noted that unnecessary FUBCs could have been prevented in 26% of patients included in the study. They further recommend a thorough clinical evaluation for any patients with SAB lasting 3 or more days with an unidentified infection source. Further research could be beneficial in evaluating cost savings that come from eliminating unnecessary cultures. Additionally, performing a powered analysis would help to determine the probability of an increase in complications based on implementation of these recommendations.

In a separate interview, Tina Q. Tan, MD, infectious disease specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago noted: “This study provides some importance evidence-based guidance on deciding how many blood cultures are needed to demonstrate clearance of S. aureus bacteremia, even in children who have intermittent positive cultures after having negative FUBCs. The recommendation that additional blood cultures to document sterility are not needed after 2 FUBC results are negative in well-appearing children is one that has the potential to decrease cost and unnecessary discomfort in patients. The recommendation currently is for well-appearing children; children who are ill appearing may require further blood cultures to document sterility. Even though this is a single-center study with a relatively small number of patients (n = 122), the information provided is a very useful guide to all clinicians who deal with this issue. Further studies are needed to determine the impact on cost reduction by the elimination of unnecessary blood cultures and whether the rate of complications would increase as a result of not obtaining further cultures in well-appearing children who have two negative follow up blood cultures.”

Dr. Cardenas-Comfort and colleagues as well as Dr. Tan had no conflicts of interest and no relevant financial disclosures. There was no external funding for the study.

SOURCE: Cardenas-Comfort C et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1821.

Additional blood cultures are not needed after two negative follow-up blood culture results in well-appearing patients with Staphylococcus aureus bacteremia, reported Caitlin Cardenas-Comfort, MD, of the section of pediatric infectious diseases at Baylor College of Medicine, Houston, and colleagues.

CDC/Janice Haney Carr

In a retrospective cohort study of 122 pediatric patients with documented Staphylococcus aureus bacteremia (SAB) that were hospitalized at one of three hospitals in the Texas Children’s Hospital network in Houston, Dr. Cardenas-Comfort and colleagues sought to determine whether specific recommendations can be made on the number of follow-up blood cultures (FUBC) needed to document clearance of SAB. Patients included in the study were under 18 years of age and had confirmed diagnosis of SAB between Jan. 1, and Dec. 31, 2018.
 

Most cases of bacteremia resolve in under 48 hours

In the majority of cases, patients had bacteremia for less than 48 hours and few to no complications. Only 16% of patients experienced bacteremia lasting 3 or more days, and they had either central line-associated bloodstream infection, endocarditis, or osteomyelitis. In such cases, “patients with endovascular and closed-space infections are at an increased risk of persistent bacteremia,” warranting more conservative monitoring and follow-up, cautioned the researchers.

Although Dr. Cardenas-Comfort and colleagues did note an association between the duration of bacteremia and a diagnosis of infectious disease, increased risk for persistent SAB did not appear to be tied to an underlying medical condition, including immunosuppression.

Fewer than 5% of patients with SAB had intermittent positive cultures and fewer than 1% had repeat positive cultures following two negative FUBC results. For those patients with intermittent positive cultures, the risk of being diagnosed with endocarditis or osteomyelitis is more than double. The authors suggested that “source control could be a critical variable” increasing the risk for intermittent positive cultures, noting that surgical debridement occurred more than 24 hours following initial blood draw for every patient in the osteomyelitis group. In contrast, of those who had consistently negative FUBC results, only 2 of 33 (6%) had debridement in the same period, and only 6 of 33 (18%) required more than one debridement.
 

Children are less likely to have intermittent positive cultures

Dr. Cardenas-Comfort and colleagues also observed that intermittent positive cultures may appear less frequently in children than adults, consistent with a recent study of adults in which intermittent cultures were found in 13% of 1.071 SAB cases. In just 4% of the cases in that study, more than 2 days of negative blood cultures preceded a repeat positive culture.

The researchers noted several study limitations in their own research. Because more than half (61%) of patients had two or less FUBCs collected, and 21% one or less, they acknowledged that their conclusions are based on the presumption that the 61% of patients would not have any further positive cultures if they had been drawn. Relying on provider documentation also suggested that cases of bacteremia without an identified source also likely were overrepresented. The retrospective nature of the study only allowed for limited collection of standardized follow-up metrics with the limited patient sample available. Patient characteristics also may have affected the quality of study results because a large number of patients had underlying medical conditions or were premature infants.
 

Look for ongoing hemodynamic instability before third FUBC

Dr. Cardenas-Comfort and colleagues only recommend a third FUBC in cases where patients demonstrate ongoing hemodynamic instability. Applying this to their study population, in retrospect, the authors noted that unnecessary FUBCs could have been prevented in 26% of patients included in the study. They further recommend a thorough clinical evaluation for any patients with SAB lasting 3 or more days with an unidentified infection source. Further research could be beneficial in evaluating cost savings that come from eliminating unnecessary cultures. Additionally, performing a powered analysis would help to determine the probability of an increase in complications based on implementation of these recommendations.

In a separate interview, Tina Q. Tan, MD, infectious disease specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago noted: “This study provides some importance evidence-based guidance on deciding how many blood cultures are needed to demonstrate clearance of S. aureus bacteremia, even in children who have intermittent positive cultures after having negative FUBCs. The recommendation that additional blood cultures to document sterility are not needed after 2 FUBC results are negative in well-appearing children is one that has the potential to decrease cost and unnecessary discomfort in patients. The recommendation currently is for well-appearing children; children who are ill appearing may require further blood cultures to document sterility. Even though this is a single-center study with a relatively small number of patients (n = 122), the information provided is a very useful guide to all clinicians who deal with this issue. Further studies are needed to determine the impact on cost reduction by the elimination of unnecessary blood cultures and whether the rate of complications would increase as a result of not obtaining further cultures in well-appearing children who have two negative follow up blood cultures.”

Dr. Cardenas-Comfort and colleagues as well as Dr. Tan had no conflicts of interest and no relevant financial disclosures. There was no external funding for the study.

SOURCE: Cardenas-Comfort C et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1821.

From the University of Alabama at Birmingham, Birmingham, AL.

Abstract

Objective: To review current challenges in the management of peptic ulcer disease.

Methods: Review of the literature.

Results: Peptic ulcer disease affects 5% to 10% of the population worldwide, with recent decreases in lifetime prevalence in high-income countries. Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use are the most important drivers of peptic ulcer disease. Current management strategies for peptic ulcer disease focus on ulcer healing; management of complications such as bleeding, perforation, and obstruction; and prevention of ulcer recurrence. Proton pump inhibitors (PPIs) are the cornerstone of medical therapy for peptic ulcers, and complement testing for and treatment of H. pylori infection as well as elimination of NSAID use. Although advances have been made in the medical and endoscopic treatment of peptic ulcer disease and the management of ulcer complications, such as bleeding and obstruction, challenges remain.

Conclusion: Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with PPI therapy of adequate frequency and duration, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Keywords: H. pylori; nonsteroidal anti-inflammatory drugs; NSAIDs; proton pump inhibitor; PPI; bleeding; perforation; obstruction; refractory ulcer; salvage endoscopic therapy; transcatheter angiographic embolization.

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1). Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel’s diverticulum.^1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3%¹; both rates are declining.³ The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%.⁴ The lifetime prevalence of peptic ulcers has been decreasing in high-income countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.^1,3

Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, or both. A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers. H. pylori–specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury. The mucosal inflammatory response is at least partially determined by polymorphisms in the host’s cytokine genes.^1,4 NSAIDs inhibit the production of cyclooxygenase-1-derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.^1,5 Less common causes of peptic ulcers include gastrinoma, adenocarcinoma, idiopathic ulcers, use of sympathomimetic drugs (eg, cocaine or methamphetamine), certain anticancer agents, and bariatric surgery.^4,6

This article provides an overview of current management principles for peptic ulcer disease and discusses current challenges in peptic ulcer management, including proton pump inhibitor (PPI) therapy, refractory ulcers, handling of antiplatelet and anticoagulants during and after peptic ulcer bleeding, and ulcer bleeding that continues despite salvage endoscopic therapy.

Methods

We searched MEDLINE using the term peptic ulcer disease in combination with the terms current challenges, epidemiology, bleeding, anticoagulant, antiplatelet, PPI potency, etiology, treatment, management, and refractory. We selected publications from the past 35 years that we judged to be relevant.

Current Management

The goals of peptic ulcer disease management are ulcer healing and prevention of recurrence. The primary interventions used in the management of peptic ulcer disease are medical therapy and implementation of measures that address the underlying etiology of the disease.

Medical Therapy

Introduced in the late 1980s, PPIs are the cornerstone of medical therapy for peptic ulcer disease.⁶ These agents irreversibly inhibit the H+/K+-ATPase pump in the gastric mucosa and thereby inhibit gastric acid secretion, promoting ulcer healing. PPIs improve rates of ulcer healing compared to H2-receptor antagonists.^4,7

Underlying Causes

The underlying cause of peptic ulcer disease should be addressed, in addition to initiating medical therapy. A detailed history of NSAID use should be obtained, and patients with peptic ulcers caused by NSAIDs should be counseled to avoid them, if possible. Patients with peptic ulcer disease who require long-term use of NSAIDs should be placed on long-term PPI therapy.⁶ Any patient with peptic ulcer disease, regardless of any history of H. pylori infection or treatment, should be tested for infection. Tests that identify active infection, such as urea breath test, stool antigen assay, or mucosal biopsy–based testing, are preferred to IgG antibody testing, although the latter is acceptable in the context of peptic ulcer disease with a high pretest probability of infection.⁸ Any evidence of active infection warrants appropriate treatment to allow ulcer healing and prevent recurrence.¹H. pylori infection is most often treated with clarithromycin triple therapy or bismuth quadruple therapy for 14 days, with regimens selected based on the presence or absence of penicillin allergy, prior antibiotic exposure, and local clarithromycin resistance rates, when known.^4,8

Managing Complications

An additional aspect of care in peptic ulcer disease is managing the complications of bleeding, perforation, and gastric outlet obstruction. Acute upper gastrointestinal bleeding (GIB) is the most common complication of peptic ulcer disease, which accounts for 40% to 60% of nonvariceal acute upper GIB.^1,6 The first step in the management of acute GIB from a peptic ulcer is fluid resuscitation to ensure hemodynamic stability. If there is associated anemia with a hemoglobin level < 8 g/dL, blood transfusion should be undertaken to target a hemoglobin level > 8 g/dL. In patients with peptic ulcer disease–related acute upper GIB and comorbid cardiovascular disease, the transfusion threshold is higher, with the specific cutoff depending on clinical status, type and severity of cardiovascular disease, and degree of bleeding. Endoscopic management should generally be undertaken within 24 hours of presentation and should not be delayed in patients taking anticoagulants.⁹ Combination endoscopic treatment with through-the-scope clips plus thermocoagulation or sclerosant injection is recommended for acutely bleeding peptic ulcers with high-risk stigmata.

Pharmacologic management of patients with bleeding peptic ulcers with high-risk stigmata includes PPI therapy, with an 80 mg intravenous (IV) loading dose followed by continuous infusion of 8 mg/hr for 72 hours to reduce rebleeding and mortality. Following completion of IV therapy, oral PPI therapy should be continued twice daily for 14 days, followed by once-daily dosing thereafter.⁹Patients with peptic ulcer perforation present with sudden-onset epigastric abdominal pain and have tenderness to palpation, guarding, and rigidity on examination, often along with tachycardia and hypotension.^1,4 Computed tomography (CT) of the abdomen is 98% sensitive for identifying and localizing a perforation. Most perforations occur in the duodenum or antrum.

Management of a peptic ulcer perforation requires consultation with a surgeon to determine whether a nonoperative approach may be employed (eg, a stable patient with a contained perforation), or if surgery is indicated. The surgical approach to peptic ulcer perforation has been impacted by the clinical success of gastric acid suppression with PPIs and H. pylori eradication, but a range of surgical approaches are still used to repair perforations, from omental patch repair with peritoneal drain placement, to more extensive surgeries such as wedge resection or partial gastrectomy.⁴ Perforation carries a high mortality risk, up to 20% to 30%, and is the leading cause of death in patients with peptic ulcer disease.^1,4

Gastric outlet obstruction, a rare complication of peptic ulcer disease, results from recurrent ulcer formation and scarring. Obstruction often presents with hypovolemia and metabolic alkalosis from prolonged vomiting. CT imaging with oral contrast is often the first diagnostic test employed to demonstrate obstruction. Upper endoscopy should be performed to evaluate the appearance and degree of obstruction as well as to obtain biopsies to evaluate for a malignant etiology of the ulcer disease. Endoscopic balloon dilation has become the cornerstone of initial therapy for obstruction from peptic ulcer disease, especially in the case of ulcers due to reversible causes. Surgery is now typically reserved for cases of refractory obstruction, after repeated endoscopic balloon dilation has failed to remove the obstruction. However, because nearly all patients with gastric outlet obstruction present with malnutrition, nutritional deficiencies should be addressed prior to the patient undergoing surgical intervention. Surgical options include pyloroplasty, antrectomy, and gastrojejunostomy.⁴

Current Challenges

Rapid Metabolism of PPIs

High-dose PPI therapy is a key component of therapy for peptic ulcer healing. PPIs are metabolized by the cytochrome P450 system, which is comprised of multiple isoenzymes. CYP2C19, an isoenzyme involved in PPI metabolism, has 21 polymorphisms, which have variable effects leading to ultra-rapid, extensive, intermediate, or poor metabolism of PPIs.¹⁰ With rapid metabolism of PPIs, standard dosing can result in inadequate suppression of acid secretion. Despite this knowledge, routine testing of CYP2C19 phenotype is not recommended due to the cost of testing. Instead, inadequate ulcer healing should prompt consideration of increased PPI dosing to 80 mg orally twice daily, which may be sufficient to overcome rapid PPI metabolism.¹¹

Relative Potency of PPIs

In addition to variation in PPI metabolism, the relative potency of various PPIs has been questioned. A review of all available clinical studies of the effects of PPIs on mean 24-hour intragastric pH reported a quantitative difference in the potency of 5 PPIs, with omeprazole as the reference standard. Potencies ranged from 0.23 omeprazole equivalents for pantoprazole to 1.82 omeprazole equivalents for rabeprazole.¹² An additional study of data from 56 randomized clinical trials confirmed that PPIs vary in potency, which was measured as time that gastric pH is less than 4. A linear increase in intragastric pH time less than 4 was observed from 9 to 64 mg omeprazole equivalents; higher doses yielded no additional benefit. An increase in PPI dosing from once daily to twice daily also increased the duration of intragastric pH time less than 4 from 15 to 21 hours.¹³ Earlier modeling of the relationship between duodenal ulcer healing and antisecretory therapy showed a strong correlation of ulcer healing with the duration of acid suppression, length of therapy, and the degree of acid suppression. Additional benefit was not observed after intragastric pH rose above 3.¹⁴ Thus, as the frequency and duration of acid suppression therapy are more important than PPI potency, PPIs can be used interchangeably.^13,14

Addressing Underlying Causes

Continued NSAID Use. Refractory peptic ulcers are defined as those that do not heal despite adherence to 8 to 12 weeks of standard acid-suppression therapy. A cause of refractory peptic ulcer disease that must be considered is continued NSAID use.^1,15 In a study of patients with refractory peptic ulcers, 27% of patients continued NSAID use, as determined by eventual disclosure by the patients or platelet cyclooxygenase activity assay, despite extensive counseling to avoid NSAIDs at the time of the diagnosis of their refractory ulcer and at subsequent visits.¹⁶ Pain may make NSAID cessation difficult for some patients, while others do not realize that over-the-counter preparations they take contain NSAIDs.¹⁵

Another group of patients with continued NSAID exposure are those who require long-term NSAID therapy for control of arthritis or the management of cardiovascular conditions. If NSAID therapy cannot be discontinued, the risk of NSAID-related gastrointestinal injury can be assessed based on the presence of multiple risk factors, including age > 65 years, high-dose NSAID therapy, a history of peptic ulcer, and concurrent use of aspirin, corticosteroids, or anticoagulants. Individuals with 3 or more of the preceding risk factors or a history of a peptic ulcer with a complication, especially if recent, are considered to be at high risk of developing an NSAID-related ulcer and possible subsequent complications.¹⁷ In these individuals, NSAID therapy should be continued with agents that have the lowest risk for gastrointestinal toxicity and at the lowest possible dose. A meta-analysis comparing nonselective NSAIDs to placebo demonstrated naproxen to have the highest risk of gastrointestinal complications, including GIB, perforation, and obstruction (adjusted rate ratio, 4.2), while diclofenac demonstrated the lowest risk (adjusted rate ratio, 1.89). High-dose NSAID therapy demonstrated a 2-fold increase in risk of peptic ulcer formation as compared to low-dose therapy.¹⁸

In addition to selecting the NSAID with the least gastrointestinal toxicity at the lowest possible dose, additional strategies to prevent peptic ulcer disease and its complications in chronic NSAID users include co-administration of a PPI and substitution of a COX-2 selective NSAID for nonselective NSAIDs.^1,9 Prior double-blind, placebo-controlled, randomized, multicenter trials with patients requiring daily NSAIDs demonstrated an up to 15% absolute reduction in the risk of developing peptic ulcers over 6 months while taking esomeprazole.¹⁹

Persistent Infection. Persistent H. pylori infection, due either to initial false-negative testing or ongoing infection despite first-line therapy, is another cause of refractory peptic ulcer disease.^1,15 Because antibiotics and PPIs can reduce the number of H. pylori bacteria, use of these medications concurrent with H. pylori testing can lead to false-negative results with several testing modalities. When suspicion for H. pylori is high, 2 or more diagnostic tests may be needed to effectively rule out infection.¹⁵

When H. pylori is detected, successful eradication is becoming more difficult due to an increasing prevalence of antibiotic resistance, leading to persistent infection in many cases and maintained risk of peptic ulcer disease, despite appropriate first-line therapy.⁸ Options for salvage therapy for persistent H. pylori, as well as information on the role and best timing of susceptibility testing, are beyond the scope of this review, but are reviewed by Lanas and Chan¹ and in the American College of Gastroenterology guideline on the treatment of H. pylori infection.⁸

Other Causes. In a meta-analysis of rigorously designed studies from North America, 20% of patients experienced ulcer recurrence at 6 months, despite successful H. pylori eradication and no NSAID use.²⁰ In addition, as H. pylori prevalence is decreasing, idiopathic ulcers are increasingly being diagnosed, and such ulcers may be associated with high rates of GIB and mortality.¹ In this subset of patients with non-H. pylori, non-NSAID ulcers, increased effort is required to further evaluate the differential diagnosis for rarer causes of upper GI tract ulcer disease (Table). Certain malignancies, including adenocarcinoma and lymphoma, can cause ulcer formation and should be considered in refractory cases. Repeat biopsy at follow-up endoscopy for persistent ulcers should always be obtained to further evaluate for malignancy.^1,15 Infectious diseases other than H. pylori infection, such as tuberculosis, syphilis, cytomegalovirus, and herpes simplex virus, are also reported as etiologies of refractory ulcers, and require specific antimicrobial treatment over and above PPI monotherapy. Special attention in biopsy sampling and sample processing is often required when infectious etiologies are being considered, as specific histologic stains and cultures may be needed for identification.¹⁵

Systemic conditions, including sarcoidosis,²¹ Behçet disease,²² and polyarteritis nodosa,^15,23 can also cause refractory ulcers. Approximately 15% of patients with Crohn disease have gastroduodenal involvement, which may include ulcers of variable sizes.^1,15,24 The increased gastric acid production seen in Zollinger-Ellison syndrome commonly presents as refractory peptic ulcers in the duodenum beyond the bulb that do not heal with standard doses of PPIs.^1,15 More rare causes of acid hypersecretion leading to refractory ulcers include idiopathic gastric acid hypersecretion and retained gastric antrum syndrome after partial gastrectomy with Billroth II anastomosis.¹⁵ Smoking is a known risk factor for impaired tissue healing throughout the body, and can contribute to impaired healing of peptic ulcers through decreased prostaglandin synthesis²⁵ and reduced gastric mucosal blood flow.²⁶ Smoking should always be addressed in patients with refractory peptic ulcers, and cessation should be strongly encouraged. Other less common causes of refractory upper GI tract ulcers include radiation therapy, crack cocaine use, and mesenteric ischemia.¹⁵

Managing Antiplatelet and Anticoagulant Medications

Use of antiplatelets and anticoagulants, alone or in combination, increases the risk of peptic ulcer bleeding. In patients who continue to take aspirin after a peptic ulcer bleed, recurrent bleeding occurs in up to 300 cases per 1000 person-years. The rate of GIB associated with aspirin use ranges from 1.1% to 2.5%, depending on the dose. Prior peptic ulcer disease, age greater than 70 years, and concurrent NSAID, steroid, anticoagulant, or dual antiplatelet therapy (DAPT) use increase the risk of bleeding while on aspirin. The rate of GIB while taking a thienopyridine alone is slightly less than that when taking aspirin, ranging from 0.5% to 1.6%. Studies to date have yielded mixed estimates of the effect of DAPT on the risk of GIB. Estimates of the risk of GIB with DAPT range from an odds ratio for serious GIB of 7.4 to an absolute risk increase of only 1.3% when compared to clopidogrel alone.²⁷

Many patients are also on warfarin or a direct oral anticoagulant (DOAC). In a study from the United Kingdom, the adjusted rate ratio of GIB with warfarin alone was 1.94, and this increased to 6.48 when warfarin was used with aspirin.²⁸ The use of warfarin and DAPT, often called triple therapy, further increases the risk of GIB, with a hazard ratio of 5.0 compared to DAPT alone, and 5.38 when compared to warfarin alone. DOACs are increasingly prescribed for the treatment and prevention of thromboembolism, and by 2014 were prescribed as often as warfarin for stroke prevention in atrial fibrillation in the United States. A meta-analysis showed the risk of major GIB did not differ between DOACs and warfarin or low-molecular-weight heparin, but among DOACs factor Xa inhibitors showed a reduced risk of GIB compared with dabigatran, a direct thrombin inhibitor.²⁹

The use of antiplatelets and anticoagulants in the context of peptic ulcer bleeding is a current management challenge. Data to guide decision-making in patients on antiplatelet and/or anticoagulant therapy who experience peptic ulcer bleeding are scarce. Decision-making in this group of patients requires balancing the severity and risk of bleeding with the risk of thromboembolism.^1,27 In patients on antiplatelet therapy for primary prophylaxis of atherothrombosis who develop bleeding from a peptic ulcer, the antiplatelet should generally be held and the indication for the medication reassessed. In patients on antiplatelet therapy for secondary prevention, the agent may be immediately resumed after endoscopy if bleeding is found to be due to an ulcer with low-risk stigmata. With bleeding resulting from an ulcer with high-risk stigmata, antiplatelet agents employed for secondary prevention may be held initially, with consideration given to early reintroduction, as early as day 3 after endoscopy.¹ In patients at high risk for atherothrombotic events, including those on aspirin for secondary prophylaxis, withholding aspirin leads to a 3-fold increase in the risk of a major adverse cardiac event, with events occurring as early as 5 days after aspirin cessation in some cases.²⁷ A randomized controlled trial of continuing low-dose aspirin versus withholding it for 8 weeks in patients on aspirin for secondary prophylaxis of cardiovascular events who experienced peptic ulcer bleeding that required endoscopic therapy demonstrated lower all-cause mortality (1.3% vs 12.9%), including death from cardiovascular or cerebrovascular events, among those who continued aspirin therapy, with a small increased risk of recurrent ulcer bleeding (10.3% vs 5.4%).³⁰ Thus, it is recommended that antiplatelet therapy, when held, be resumed as early as possible when the risk of a cardiovascular or cerebrovascular event is considered to be higher than the risk of bleeding.²⁷

When patients are on DAPT for a history of drug-eluting stent placement, withholding both antiplatelet medications should be avoided, even for a brief period of time, given the risk of in-stent thrombosis. When DAPT is employed for other reasons, it should be continued, if indicated, after bleeding that is found to be due to peptic ulcers with low-risk stigmata. If bleeding is due to a peptic ulcer with high-risk stigmata at endoscopy, then aspirin monotherapy should be continued and consultation should be obtained with a cardiologist to determine optimal timing to resume the second antiplatelet agent.¹ In patients on anticoagulants, anticoagulation should be resumed once hemostasis is achieved when the risk of withholding anticoagulation is thought to be greater than the risk of rebleeding. For example, anticoagulation should be resumed early in a patient with a mechanical heart valve to prevent thrombosis.^1,27 Following upper GIB from peptic ulcer disease, patients who will require long-term aspirin, DAPT, or anticoagulation with either warfarin or DOACs should be maintained on long-term PPI therapy to reduce the risk of recurrent bleeding.^9,27

Failure of Endoscopic Therapy to Control Peptic Ulcer Bleeding

Bleeding recurs in as many as 10% to 20% of patients after initial endoscopic control of peptic ulcer bleeding.^4,31 In this context, repeat upper endoscopy for hemostasis is preferred to surgery, as it leads to less morbidity while providing long-term control of bleeding in more than 70% of cases.^31,32 Two potential endoscopic rescue therapies that may be employed are over-the-scope clips (OTSCs) and hemostatic powder.^32,33

While through-the-scope (TTS) hemostatic clips are often used during endoscopy to control active peptic ulcer bleeding, their use may be limited in large or fibrotic ulcers due to the smaller size of the clips and method of application. OTSCs have several advantages over TTS clips; notably, their larger size allows the endoscopist to achieve deeper mucosal or submucosal clip attachment via suction of the targeted tissue into the endoscopic cap (Figure 2). In a systematic review of OTSCs, successful hemostasis was achieved in 84% of 761 lesions, including 75% of lesions due to peptic ulcer disease.³⁴ Some have argued that OTSCs may be preferred as first-line therapy over epinephrine with TTS clips for hemostasis in bleeding from high-risk peptic ulcers (ie, those with visualized arterial bleeding or a visible vessel) given observed decreases in rebleeding events.³⁵

Despite the advantages of OTSCs, endoscopists should be mindful of the potential complications of OTSC use, including luminal obstruction, particularly in the duodenum, and perforation, which occurs in 0.3% to 2% of cases. Additionally, retrieval of misplaced OTSCs presents a significant challenge. Careful decision-making with consideration of the location, size, and depth of lesions is required when deciding on OTSC placement.^34,36

A newer endoscopic tool developed for refractory bleeding from peptic ulcers and other causes is hemostatic powder. Hemostatic powders accelerate the coagulation cascade, leading to shortened coagulation times and enhanced clot formation.³⁷ A recent meta-analysis showed that immediate hemostasis could be achieved in 95% of cases of bleeding, including in 96% of cases of bleeding from peptic ulcer disease.³⁸ The primary limitation of hemostatic powders is the temporary nature of hemostasis, which requires the underlying etiology of bleeding to be addressed in order to provide long-term hemostasis. In the above meta-analysis, rebleeding occurred in 17% of cases after 30 days.³⁸

Hypotension and ulcer diameter ≥ 2 cm are independent predictors of failure of endoscopic salvage therapy.³¹ When severe bleeding is not controlled with initial endoscopic therapy or bleeding recurs despite salvage endoscopic therapy, transcatheter angiographic embolization (TAE) is the treatment of choice.⁴ Systematic reviews and meta-analyses of studies that compared TAE to surgery have shown that the rate of rebleeding may be higher with TAE, but with less morbidity and either decreased or equivalent rates of mortality, with no increased need for additional interventions.^4,32 In a case series examining 5 years of experience at a single medical center in China, massive GIB from duodenal ulcers was successfully treated with TAE in 27 of 29 cases (93% clinical success rate), with no mucosal ischemic necrosis observed.³⁹

If repeated endoscopic therapy has not led to hemostasis of a bleeding peptic ulcer and TAE is not available, then surgery is the next best option. Bleeding gastric ulcers may be excised, wedge resected, or oversewn after an anterior gastrostomy. Bleeding duodenal ulcers may require use of a Kocher maneuver and linear incision of the anterior duodenum followed by ligation of the gastroduodenal artery. Fortunately, such surgical management is rarely necessary given the availability of TAE at most centers.⁴

Conclusion

Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with adequate frequency and duration of PPI therapy, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Acknowledgment: We thank Dr. Nipun Reddy from our institution for providing the endoscopic images used in this article.

Corresponding author: Adam L. Edwards, MD, MS; aledwards@uabmc.edu.

Financial disclosures: None.

From the University of Alabama at Birmingham, Birmingham, AL.

Abstract

Objective: To review current challenges in the management of peptic ulcer disease.

Methods: Review of the literature.

Results: Peptic ulcer disease affects 5% to 10% of the population worldwide, with recent decreases in lifetime prevalence in high-income countries. Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use are the most important drivers of peptic ulcer disease. Current management strategies for peptic ulcer disease focus on ulcer healing; management of complications such as bleeding, perforation, and obstruction; and prevention of ulcer recurrence. Proton pump inhibitors (PPIs) are the cornerstone of medical therapy for peptic ulcers, and complement testing for and treatment of H. pylori infection as well as elimination of NSAID use. Although advances have been made in the medical and endoscopic treatment of peptic ulcer disease and the management of ulcer complications, such as bleeding and obstruction, challenges remain.

Conclusion: Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with PPI therapy of adequate frequency and duration, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Keywords: H. pylori; nonsteroidal anti-inflammatory drugs; NSAIDs; proton pump inhibitor; PPI; bleeding; perforation; obstruction; refractory ulcer; salvage endoscopic therapy; transcatheter angiographic embolization.

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1). Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel’s diverticulum.^1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3%¹; both rates are declining.³ The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%.⁴ The lifetime prevalence of peptic ulcers has been decreasing in high-income countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.^1,3

Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, or both. A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers. H. pylori–specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury. The mucosal inflammatory response is at least partially determined by polymorphisms in the host’s cytokine genes.^1,4 NSAIDs inhibit the production of cyclooxygenase-1-derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.^1,5 Less common causes of peptic ulcers include gastrinoma, adenocarcinoma, idiopathic ulcers, use of sympathomimetic drugs (eg, cocaine or methamphetamine), certain anticancer agents, and bariatric surgery.^4,6

This article provides an overview of current management principles for peptic ulcer disease and discusses current challenges in peptic ulcer management, including proton pump inhibitor (PPI) therapy, refractory ulcers, handling of antiplatelet and anticoagulants during and after peptic ulcer bleeding, and ulcer bleeding that continues despite salvage endoscopic therapy.

Methods

We searched MEDLINE using the term peptic ulcer disease in combination with the terms current challenges, epidemiology, bleeding, anticoagulant, antiplatelet, PPI potency, etiology, treatment, management, and refractory. We selected publications from the past 35 years that we judged to be relevant.

Current Management

The goals of peptic ulcer disease management are ulcer healing and prevention of recurrence. The primary interventions used in the management of peptic ulcer disease are medical therapy and implementation of measures that address the underlying etiology of the disease.

Medical Therapy

Introduced in the late 1980s, PPIs are the cornerstone of medical therapy for peptic ulcer disease.⁶ These agents irreversibly inhibit the H+/K+-ATPase pump in the gastric mucosa and thereby inhibit gastric acid secretion, promoting ulcer healing. PPIs improve rates of ulcer healing compared to H2-receptor antagonists.^4,7

Underlying Causes

The underlying cause of peptic ulcer disease should be addressed, in addition to initiating medical therapy. A detailed history of NSAID use should be obtained, and patients with peptic ulcers caused by NSAIDs should be counseled to avoid them, if possible. Patients with peptic ulcer disease who require long-term use of NSAIDs should be placed on long-term PPI therapy.⁶ Any patient with peptic ulcer disease, regardless of any history of H. pylori infection or treatment, should be tested for infection. Tests that identify active infection, such as urea breath test, stool antigen assay, or mucosal biopsy–based testing, are preferred to IgG antibody testing, although the latter is acceptable in the context of peptic ulcer disease with a high pretest probability of infection.⁸ Any evidence of active infection warrants appropriate treatment to allow ulcer healing and prevent recurrence.¹H. pylori infection is most often treated with clarithromycin triple therapy or bismuth quadruple therapy for 14 days, with regimens selected based on the presence or absence of penicillin allergy, prior antibiotic exposure, and local clarithromycin resistance rates, when known.^4,8

Managing Complications

An additional aspect of care in peptic ulcer disease is managing the complications of bleeding, perforation, and gastric outlet obstruction. Acute upper gastrointestinal bleeding (GIB) is the most common complication of peptic ulcer disease, which accounts for 40% to 60% of nonvariceal acute upper GIB.^1,6 The first step in the management of acute GIB from a peptic ulcer is fluid resuscitation to ensure hemodynamic stability. If there is associated anemia with a hemoglobin level < 8 g/dL, blood transfusion should be undertaken to target a hemoglobin level > 8 g/dL. In patients with peptic ulcer disease–related acute upper GIB and comorbid cardiovascular disease, the transfusion threshold is higher, with the specific cutoff depending on clinical status, type and severity of cardiovascular disease, and degree of bleeding. Endoscopic management should generally be undertaken within 24 hours of presentation and should not be delayed in patients taking anticoagulants.⁹ Combination endoscopic treatment with through-the-scope clips plus thermocoagulation or sclerosant injection is recommended for acutely bleeding peptic ulcers with high-risk stigmata.

Pharmacologic management of patients with bleeding peptic ulcers with high-risk stigmata includes PPI therapy, with an 80 mg intravenous (IV) loading dose followed by continuous infusion of 8 mg/hr for 72 hours to reduce rebleeding and mortality. Following completion of IV therapy, oral PPI therapy should be continued twice daily for 14 days, followed by once-daily dosing thereafter.⁹Patients with peptic ulcer perforation present with sudden-onset epigastric abdominal pain and have tenderness to palpation, guarding, and rigidity on examination, often along with tachycardia and hypotension.^1,4 Computed tomography (CT) of the abdomen is 98% sensitive for identifying and localizing a perforation. Most perforations occur in the duodenum or antrum.

Management of a peptic ulcer perforation requires consultation with a surgeon to determine whether a nonoperative approach may be employed (eg, a stable patient with a contained perforation), or if surgery is indicated. The surgical approach to peptic ulcer perforation has been impacted by the clinical success of gastric acid suppression with PPIs and H. pylori eradication, but a range of surgical approaches are still used to repair perforations, from omental patch repair with peritoneal drain placement, to more extensive surgeries such as wedge resection or partial gastrectomy.⁴ Perforation carries a high mortality risk, up to 20% to 30%, and is the leading cause of death in patients with peptic ulcer disease.^1,4

Gastric outlet obstruction, a rare complication of peptic ulcer disease, results from recurrent ulcer formation and scarring. Obstruction often presents with hypovolemia and metabolic alkalosis from prolonged vomiting. CT imaging with oral contrast is often the first diagnostic test employed to demonstrate obstruction. Upper endoscopy should be performed to evaluate the appearance and degree of obstruction as well as to obtain biopsies to evaluate for a malignant etiology of the ulcer disease. Endoscopic balloon dilation has become the cornerstone of initial therapy for obstruction from peptic ulcer disease, especially in the case of ulcers due to reversible causes. Surgery is now typically reserved for cases of refractory obstruction, after repeated endoscopic balloon dilation has failed to remove the obstruction. However, because nearly all patients with gastric outlet obstruction present with malnutrition, nutritional deficiencies should be addressed prior to the patient undergoing surgical intervention. Surgical options include pyloroplasty, antrectomy, and gastrojejunostomy.⁴

Current Challenges

Rapid Metabolism of PPIs

High-dose PPI therapy is a key component of therapy for peptic ulcer healing. PPIs are metabolized by the cytochrome P450 system, which is comprised of multiple isoenzymes. CYP2C19, an isoenzyme involved in PPI metabolism, has 21 polymorphisms, which have variable effects leading to ultra-rapid, extensive, intermediate, or poor metabolism of PPIs.¹⁰ With rapid metabolism of PPIs, standard dosing can result in inadequate suppression of acid secretion. Despite this knowledge, routine testing of CYP2C19 phenotype is not recommended due to the cost of testing. Instead, inadequate ulcer healing should prompt consideration of increased PPI dosing to 80 mg orally twice daily, which may be sufficient to overcome rapid PPI metabolism.¹¹

Relative Potency of PPIs

In addition to variation in PPI metabolism, the relative potency of various PPIs has been questioned. A review of all available clinical studies of the effects of PPIs on mean 24-hour intragastric pH reported a quantitative difference in the potency of 5 PPIs, with omeprazole as the reference standard. Potencies ranged from 0.23 omeprazole equivalents for pantoprazole to 1.82 omeprazole equivalents for rabeprazole.¹² An additional study of data from 56 randomized clinical trials confirmed that PPIs vary in potency, which was measured as time that gastric pH is less than 4. A linear increase in intragastric pH time less than 4 was observed from 9 to 64 mg omeprazole equivalents; higher doses yielded no additional benefit. An increase in PPI dosing from once daily to twice daily also increased the duration of intragastric pH time less than 4 from 15 to 21 hours.¹³ Earlier modeling of the relationship between duodenal ulcer healing and antisecretory therapy showed a strong correlation of ulcer healing with the duration of acid suppression, length of therapy, and the degree of acid suppression. Additional benefit was not observed after intragastric pH rose above 3.¹⁴ Thus, as the frequency and duration of acid suppression therapy are more important than PPI potency, PPIs can be used interchangeably.^13,14

Addressing Underlying Causes

Continued NSAID Use. Refractory peptic ulcers are defined as those that do not heal despite adherence to 8 to 12 weeks of standard acid-suppression therapy. A cause of refractory peptic ulcer disease that must be considered is continued NSAID use.^1,15 In a study of patients with refractory peptic ulcers, 27% of patients continued NSAID use, as determined by eventual disclosure by the patients or platelet cyclooxygenase activity assay, despite extensive counseling to avoid NSAIDs at the time of the diagnosis of their refractory ulcer and at subsequent visits.¹⁶ Pain may make NSAID cessation difficult for some patients, while others do not realize that over-the-counter preparations they take contain NSAIDs.¹⁵

Another group of patients with continued NSAID exposure are those who require long-term NSAID therapy for control of arthritis or the management of cardiovascular conditions. If NSAID therapy cannot be discontinued, the risk of NSAID-related gastrointestinal injury can be assessed based on the presence of multiple risk factors, including age > 65 years, high-dose NSAID therapy, a history of peptic ulcer, and concurrent use of aspirin, corticosteroids, or anticoagulants. Individuals with 3 or more of the preceding risk factors or a history of a peptic ulcer with a complication, especially if recent, are considered to be at high risk of developing an NSAID-related ulcer and possible subsequent complications.¹⁷ In these individuals, NSAID therapy should be continued with agents that have the lowest risk for gastrointestinal toxicity and at the lowest possible dose. A meta-analysis comparing nonselective NSAIDs to placebo demonstrated naproxen to have the highest risk of gastrointestinal complications, including GIB, perforation, and obstruction (adjusted rate ratio, 4.2), while diclofenac demonstrated the lowest risk (adjusted rate ratio, 1.89). High-dose NSAID therapy demonstrated a 2-fold increase in risk of peptic ulcer formation as compared to low-dose therapy.¹⁸

In addition to selecting the NSAID with the least gastrointestinal toxicity at the lowest possible dose, additional strategies to prevent peptic ulcer disease and its complications in chronic NSAID users include co-administration of a PPI and substitution of a COX-2 selective NSAID for nonselective NSAIDs.^1,9 Prior double-blind, placebo-controlled, randomized, multicenter trials with patients requiring daily NSAIDs demonstrated an up to 15% absolute reduction in the risk of developing peptic ulcers over 6 months while taking esomeprazole.¹⁹

Persistent Infection. Persistent H. pylori infection, due either to initial false-negative testing or ongoing infection despite first-line therapy, is another cause of refractory peptic ulcer disease.^1,15 Because antibiotics and PPIs can reduce the number of H. pylori bacteria, use of these medications concurrent with H. pylori testing can lead to false-negative results with several testing modalities. When suspicion for H. pylori is high, 2 or more diagnostic tests may be needed to effectively rule out infection.¹⁵

When H. pylori is detected, successful eradication is becoming more difficult due to an increasing prevalence of antibiotic resistance, leading to persistent infection in many cases and maintained risk of peptic ulcer disease, despite appropriate first-line therapy.⁸ Options for salvage therapy for persistent H. pylori, as well as information on the role and best timing of susceptibility testing, are beyond the scope of this review, but are reviewed by Lanas and Chan¹ and in the American College of Gastroenterology guideline on the treatment of H. pylori infection.⁸

Other Causes. In a meta-analysis of rigorously designed studies from North America, 20% of patients experienced ulcer recurrence at 6 months, despite successful H. pylori eradication and no NSAID use.²⁰ In addition, as H. pylori prevalence is decreasing, idiopathic ulcers are increasingly being diagnosed, and such ulcers may be associated with high rates of GIB and mortality.¹ In this subset of patients with non-H. pylori, non-NSAID ulcers, increased effort is required to further evaluate the differential diagnosis for rarer causes of upper GI tract ulcer disease (Table). Certain malignancies, including adenocarcinoma and lymphoma, can cause ulcer formation and should be considered in refractory cases. Repeat biopsy at follow-up endoscopy for persistent ulcers should always be obtained to further evaluate for malignancy.^1,15 Infectious diseases other than H. pylori infection, such as tuberculosis, syphilis, cytomegalovirus, and herpes simplex virus, are also reported as etiologies of refractory ulcers, and require specific antimicrobial treatment over and above PPI monotherapy. Special attention in biopsy sampling and sample processing is often required when infectious etiologies are being considered, as specific histologic stains and cultures may be needed for identification.¹⁵

Systemic conditions, including sarcoidosis,²¹ Behçet disease,²² and polyarteritis nodosa,^15,23 can also cause refractory ulcers. Approximately 15% of patients with Crohn disease have gastroduodenal involvement, which may include ulcers of variable sizes.^1,15,24 The increased gastric acid production seen in Zollinger-Ellison syndrome commonly presents as refractory peptic ulcers in the duodenum beyond the bulb that do not heal with standard doses of PPIs.^1,15 More rare causes of acid hypersecretion leading to refractory ulcers include idiopathic gastric acid hypersecretion and retained gastric antrum syndrome after partial gastrectomy with Billroth II anastomosis.¹⁵ Smoking is a known risk factor for impaired tissue healing throughout the body, and can contribute to impaired healing of peptic ulcers through decreased prostaglandin synthesis²⁵ and reduced gastric mucosal blood flow.²⁶ Smoking should always be addressed in patients with refractory peptic ulcers, and cessation should be strongly encouraged. Other less common causes of refractory upper GI tract ulcers include radiation therapy, crack cocaine use, and mesenteric ischemia.¹⁵

Managing Antiplatelet and Anticoagulant Medications

Use of antiplatelets and anticoagulants, alone or in combination, increases the risk of peptic ulcer bleeding. In patients who continue to take aspirin after a peptic ulcer bleed, recurrent bleeding occurs in up to 300 cases per 1000 person-years. The rate of GIB associated with aspirin use ranges from 1.1% to 2.5%, depending on the dose. Prior peptic ulcer disease, age greater than 70 years, and concurrent NSAID, steroid, anticoagulant, or dual antiplatelet therapy (DAPT) use increase the risk of bleeding while on aspirin. The rate of GIB while taking a thienopyridine alone is slightly less than that when taking aspirin, ranging from 0.5% to 1.6%. Studies to date have yielded mixed estimates of the effect of DAPT on the risk of GIB. Estimates of the risk of GIB with DAPT range from an odds ratio for serious GIB of 7.4 to an absolute risk increase of only 1.3% when compared to clopidogrel alone.²⁷

Many patients are also on warfarin or a direct oral anticoagulant (DOAC). In a study from the United Kingdom, the adjusted rate ratio of GIB with warfarin alone was 1.94, and this increased to 6.48 when warfarin was used with aspirin.²⁸ The use of warfarin and DAPT, often called triple therapy, further increases the risk of GIB, with a hazard ratio of 5.0 compared to DAPT alone, and 5.38 when compared to warfarin alone. DOACs are increasingly prescribed for the treatment and prevention of thromboembolism, and by 2014 were prescribed as often as warfarin for stroke prevention in atrial fibrillation in the United States. A meta-analysis showed the risk of major GIB did not differ between DOACs and warfarin or low-molecular-weight heparin, but among DOACs factor Xa inhibitors showed a reduced risk of GIB compared with dabigatran, a direct thrombin inhibitor.²⁹

The use of antiplatelets and anticoagulants in the context of peptic ulcer bleeding is a current management challenge. Data to guide decision-making in patients on antiplatelet and/or anticoagulant therapy who experience peptic ulcer bleeding are scarce. Decision-making in this group of patients requires balancing the severity and risk of bleeding with the risk of thromboembolism.^1,27 In patients on antiplatelet therapy for primary prophylaxis of atherothrombosis who develop bleeding from a peptic ulcer, the antiplatelet should generally be held and the indication for the medication reassessed. In patients on antiplatelet therapy for secondary prevention, the agent may be immediately resumed after endoscopy if bleeding is found to be due to an ulcer with low-risk stigmata. With bleeding resulting from an ulcer with high-risk stigmata, antiplatelet agents employed for secondary prevention may be held initially, with consideration given to early reintroduction, as early as day 3 after endoscopy.¹ In patients at high risk for atherothrombotic events, including those on aspirin for secondary prophylaxis, withholding aspirin leads to a 3-fold increase in the risk of a major adverse cardiac event, with events occurring as early as 5 days after aspirin cessation in some cases.²⁷ A randomized controlled trial of continuing low-dose aspirin versus withholding it for 8 weeks in patients on aspirin for secondary prophylaxis of cardiovascular events who experienced peptic ulcer bleeding that required endoscopic therapy demonstrated lower all-cause mortality (1.3% vs 12.9%), including death from cardiovascular or cerebrovascular events, among those who continued aspirin therapy, with a small increased risk of recurrent ulcer bleeding (10.3% vs 5.4%).³⁰ Thus, it is recommended that antiplatelet therapy, when held, be resumed as early as possible when the risk of a cardiovascular or cerebrovascular event is considered to be higher than the risk of bleeding.²⁷

When patients are on DAPT for a history of drug-eluting stent placement, withholding both antiplatelet medications should be avoided, even for a brief period of time, given the risk of in-stent thrombosis. When DAPT is employed for other reasons, it should be continued, if indicated, after bleeding that is found to be due to peptic ulcers with low-risk stigmata. If bleeding is due to a peptic ulcer with high-risk stigmata at endoscopy, then aspirin monotherapy should be continued and consultation should be obtained with a cardiologist to determine optimal timing to resume the second antiplatelet agent.¹ In patients on anticoagulants, anticoagulation should be resumed once hemostasis is achieved when the risk of withholding anticoagulation is thought to be greater than the risk of rebleeding. For example, anticoagulation should be resumed early in a patient with a mechanical heart valve to prevent thrombosis.^1,27 Following upper GIB from peptic ulcer disease, patients who will require long-term aspirin, DAPT, or anticoagulation with either warfarin or DOACs should be maintained on long-term PPI therapy to reduce the risk of recurrent bleeding.^9,27

Failure of Endoscopic Therapy to Control Peptic Ulcer Bleeding

Bleeding recurs in as many as 10% to 20% of patients after initial endoscopic control of peptic ulcer bleeding.^4,31 In this context, repeat upper endoscopy for hemostasis is preferred to surgery, as it leads to less morbidity while providing long-term control of bleeding in more than 70% of cases.^31,32 Two potential endoscopic rescue therapies that may be employed are over-the-scope clips (OTSCs) and hemostatic powder.^32,33

While through-the-scope (TTS) hemostatic clips are often used during endoscopy to control active peptic ulcer bleeding, their use may be limited in large or fibrotic ulcers due to the smaller size of the clips and method of application. OTSCs have several advantages over TTS clips; notably, their larger size allows the endoscopist to achieve deeper mucosal or submucosal clip attachment via suction of the targeted tissue into the endoscopic cap (Figure 2). In a systematic review of OTSCs, successful hemostasis was achieved in 84% of 761 lesions, including 75% of lesions due to peptic ulcer disease.³⁴ Some have argued that OTSCs may be preferred as first-line therapy over epinephrine with TTS clips for hemostasis in bleeding from high-risk peptic ulcers (ie, those with visualized arterial bleeding or a visible vessel) given observed decreases in rebleeding events.³⁵

Despite the advantages of OTSCs, endoscopists should be mindful of the potential complications of OTSC use, including luminal obstruction, particularly in the duodenum, and perforation, which occurs in 0.3% to 2% of cases. Additionally, retrieval of misplaced OTSCs presents a significant challenge. Careful decision-making with consideration of the location, size, and depth of lesions is required when deciding on OTSC placement.^34,36

A newer endoscopic tool developed for refractory bleeding from peptic ulcers and other causes is hemostatic powder. Hemostatic powders accelerate the coagulation cascade, leading to shortened coagulation times and enhanced clot formation.³⁷ A recent meta-analysis showed that immediate hemostasis could be achieved in 95% of cases of bleeding, including in 96% of cases of bleeding from peptic ulcer disease.³⁸ The primary limitation of hemostatic powders is the temporary nature of hemostasis, which requires the underlying etiology of bleeding to be addressed in order to provide long-term hemostasis. In the above meta-analysis, rebleeding occurred in 17% of cases after 30 days.³⁸

Hypotension and ulcer diameter ≥ 2 cm are independent predictors of failure of endoscopic salvage therapy.³¹ When severe bleeding is not controlled with initial endoscopic therapy or bleeding recurs despite salvage endoscopic therapy, transcatheter angiographic embolization (TAE) is the treatment of choice.⁴ Systematic reviews and meta-analyses of studies that compared TAE to surgery have shown that the rate of rebleeding may be higher with TAE, but with less morbidity and either decreased or equivalent rates of mortality, with no increased need for additional interventions.^4,32 In a case series examining 5 years of experience at a single medical center in China, massive GIB from duodenal ulcers was successfully treated with TAE in 27 of 29 cases (93% clinical success rate), with no mucosal ischemic necrosis observed.³⁹

If repeated endoscopic therapy has not led to hemostasis of a bleeding peptic ulcer and TAE is not available, then surgery is the next best option. Bleeding gastric ulcers may be excised, wedge resected, or oversewn after an anterior gastrostomy. Bleeding duodenal ulcers may require use of a Kocher maneuver and linear incision of the anterior duodenum followed by ligation of the gastroduodenal artery. Fortunately, such surgical management is rarely necessary given the availability of TAE at most centers.⁴

Conclusion

Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with adequate frequency and duration of PPI therapy, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Acknowledgment: We thank Dr. Nipun Reddy from our institution for providing the endoscopic images used in this article.

Corresponding author: Adam L. Edwards, MD, MS; aledwards@uabmc.edu.

Financial disclosures: None.

From the University of Alabama at Birmingham, Birmingham, AL.

Abstract

Objective: To review current challenges in the management of peptic ulcer disease.

Methods: Review of the literature.

Results: Peptic ulcer disease affects 5% to 10% of the population worldwide, with recent decreases in lifetime prevalence in high-income countries. Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use are the most important drivers of peptic ulcer disease. Current management strategies for peptic ulcer disease focus on ulcer healing; management of complications such as bleeding, perforation, and obstruction; and prevention of ulcer recurrence. Proton pump inhibitors (PPIs) are the cornerstone of medical therapy for peptic ulcers, and complement testing for and treatment of H. pylori infection as well as elimination of NSAID use. Although advances have been made in the medical and endoscopic treatment of peptic ulcer disease and the management of ulcer complications, such as bleeding and obstruction, challenges remain.

Conclusion: Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with PPI therapy of adequate frequency and duration, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Keywords: H. pylori; nonsteroidal anti-inflammatory drugs; NSAIDs; proton pump inhibitor; PPI; bleeding; perforation; obstruction; refractory ulcer; salvage endoscopic therapy; transcatheter angiographic embolization.

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1). Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel’s diverticulum.^1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3%¹; both rates are declining.³ The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%.⁴ The lifetime prevalence of peptic ulcers has been decreasing in high-income countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.^1,3

Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, or both. A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers. H. pylori–specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury. The mucosal inflammatory response is at least partially determined by polymorphisms in the host’s cytokine genes.^1,4 NSAIDs inhibit the production of cyclooxygenase-1-derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.^1,5 Less common causes of peptic ulcers include gastrinoma, adenocarcinoma, idiopathic ulcers, use of sympathomimetic drugs (eg, cocaine or methamphetamine), certain anticancer agents, and bariatric surgery.^4,6

This article provides an overview of current management principles for peptic ulcer disease and discusses current challenges in peptic ulcer management, including proton pump inhibitor (PPI) therapy, refractory ulcers, handling of antiplatelet and anticoagulants during and after peptic ulcer bleeding, and ulcer bleeding that continues despite salvage endoscopic therapy.

Methods

We searched MEDLINE using the term peptic ulcer disease in combination with the terms current challenges, epidemiology, bleeding, anticoagulant, antiplatelet, PPI potency, etiology, treatment, management, and refractory. We selected publications from the past 35 years that we judged to be relevant.

Current Management

The goals of peptic ulcer disease management are ulcer healing and prevention of recurrence. The primary interventions used in the management of peptic ulcer disease are medical therapy and implementation of measures that address the underlying etiology of the disease.

Medical Therapy

Introduced in the late 1980s, PPIs are the cornerstone of medical therapy for peptic ulcer disease.⁶ These agents irreversibly inhibit the H+/K+-ATPase pump in the gastric mucosa and thereby inhibit gastric acid secretion, promoting ulcer healing. PPIs improve rates of ulcer healing compared to H2-receptor antagonists.^4,7

Underlying Causes

The underlying cause of peptic ulcer disease should be addressed, in addition to initiating medical therapy. A detailed history of NSAID use should be obtained, and patients with peptic ulcers caused by NSAIDs should be counseled to avoid them, if possible. Patients with peptic ulcer disease who require long-term use of NSAIDs should be placed on long-term PPI therapy.⁶ Any patient with peptic ulcer disease, regardless of any history of H. pylori infection or treatment, should be tested for infection. Tests that identify active infection, such as urea breath test, stool antigen assay, or mucosal biopsy–based testing, are preferred to IgG antibody testing, although the latter is acceptable in the context of peptic ulcer disease with a high pretest probability of infection.⁸ Any evidence of active infection warrants appropriate treatment to allow ulcer healing and prevent recurrence.¹H. pylori infection is most often treated with clarithromycin triple therapy or bismuth quadruple therapy for 14 days, with regimens selected based on the presence or absence of penicillin allergy, prior antibiotic exposure, and local clarithromycin resistance rates, when known.^4,8

Managing Complications

An additional aspect of care in peptic ulcer disease is managing the complications of bleeding, perforation, and gastric outlet obstruction. Acute upper gastrointestinal bleeding (GIB) is the most common complication of peptic ulcer disease, which accounts for 40% to 60% of nonvariceal acute upper GIB.^1,6 The first step in the management of acute GIB from a peptic ulcer is fluid resuscitation to ensure hemodynamic stability. If there is associated anemia with a hemoglobin level < 8 g/dL, blood transfusion should be undertaken to target a hemoglobin level > 8 g/dL. In patients with peptic ulcer disease–related acute upper GIB and comorbid cardiovascular disease, the transfusion threshold is higher, with the specific cutoff depending on clinical status, type and severity of cardiovascular disease, and degree of bleeding. Endoscopic management should generally be undertaken within 24 hours of presentation and should not be delayed in patients taking anticoagulants.⁹ Combination endoscopic treatment with through-the-scope clips plus thermocoagulation or sclerosant injection is recommended for acutely bleeding peptic ulcers with high-risk stigmata.

Pharmacologic management of patients with bleeding peptic ulcers with high-risk stigmata includes PPI therapy, with an 80 mg intravenous (IV) loading dose followed by continuous infusion of 8 mg/hr for 72 hours to reduce rebleeding and mortality. Following completion of IV therapy, oral PPI therapy should be continued twice daily for 14 days, followed by once-daily dosing thereafter.⁹Patients with peptic ulcer perforation present with sudden-onset epigastric abdominal pain and have tenderness to palpation, guarding, and rigidity on examination, often along with tachycardia and hypotension.^1,4 Computed tomography (CT) of the abdomen is 98% sensitive for identifying and localizing a perforation. Most perforations occur in the duodenum or antrum.

Management of a peptic ulcer perforation requires consultation with a surgeon to determine whether a nonoperative approach may be employed (eg, a stable patient with a contained perforation), or if surgery is indicated. The surgical approach to peptic ulcer perforation has been impacted by the clinical success of gastric acid suppression with PPIs and H. pylori eradication, but a range of surgical approaches are still used to repair perforations, from omental patch repair with peritoneal drain placement, to more extensive surgeries such as wedge resection or partial gastrectomy.⁴ Perforation carries a high mortality risk, up to 20% to 30%, and is the leading cause of death in patients with peptic ulcer disease.^1,4

Gastric outlet obstruction, a rare complication of peptic ulcer disease, results from recurrent ulcer formation and scarring. Obstruction often presents with hypovolemia and metabolic alkalosis from prolonged vomiting. CT imaging with oral contrast is often the first diagnostic test employed to demonstrate obstruction. Upper endoscopy should be performed to evaluate the appearance and degree of obstruction as well as to obtain biopsies to evaluate for a malignant etiology of the ulcer disease. Endoscopic balloon dilation has become the cornerstone of initial therapy for obstruction from peptic ulcer disease, especially in the case of ulcers due to reversible causes. Surgery is now typically reserved for cases of refractory obstruction, after repeated endoscopic balloon dilation has failed to remove the obstruction. However, because nearly all patients with gastric outlet obstruction present with malnutrition, nutritional deficiencies should be addressed prior to the patient undergoing surgical intervention. Surgical options include pyloroplasty, antrectomy, and gastrojejunostomy.⁴

Current Challenges

Rapid Metabolism of PPIs

High-dose PPI therapy is a key component of therapy for peptic ulcer healing. PPIs are metabolized by the cytochrome P450 system, which is comprised of multiple isoenzymes. CYP2C19, an isoenzyme involved in PPI metabolism, has 21 polymorphisms, which have variable effects leading to ultra-rapid, extensive, intermediate, or poor metabolism of PPIs.¹⁰ With rapid metabolism of PPIs, standard dosing can result in inadequate suppression of acid secretion. Despite this knowledge, routine testing of CYP2C19 phenotype is not recommended due to the cost of testing. Instead, inadequate ulcer healing should prompt consideration of increased PPI dosing to 80 mg orally twice daily, which may be sufficient to overcome rapid PPI metabolism.¹¹

Relative Potency of PPIs

In addition to variation in PPI metabolism, the relative potency of various PPIs has been questioned. A review of all available clinical studies of the effects of PPIs on mean 24-hour intragastric pH reported a quantitative difference in the potency of 5 PPIs, with omeprazole as the reference standard. Potencies ranged from 0.23 omeprazole equivalents for pantoprazole to 1.82 omeprazole equivalents for rabeprazole.¹² An additional study of data from 56 randomized clinical trials confirmed that PPIs vary in potency, which was measured as time that gastric pH is less than 4. A linear increase in intragastric pH time less than 4 was observed from 9 to 64 mg omeprazole equivalents; higher doses yielded no additional benefit. An increase in PPI dosing from once daily to twice daily also increased the duration of intragastric pH time less than 4 from 15 to 21 hours.¹³ Earlier modeling of the relationship between duodenal ulcer healing and antisecretory therapy showed a strong correlation of ulcer healing with the duration of acid suppression, length of therapy, and the degree of acid suppression. Additional benefit was not observed after intragastric pH rose above 3.¹⁴ Thus, as the frequency and duration of acid suppression therapy are more important than PPI potency, PPIs can be used interchangeably.^13,14

Addressing Underlying Causes

Continued NSAID Use. Refractory peptic ulcers are defined as those that do not heal despite adherence to 8 to 12 weeks of standard acid-suppression therapy. A cause of refractory peptic ulcer disease that must be considered is continued NSAID use.^1,15 In a study of patients with refractory peptic ulcers, 27% of patients continued NSAID use, as determined by eventual disclosure by the patients or platelet cyclooxygenase activity assay, despite extensive counseling to avoid NSAIDs at the time of the diagnosis of their refractory ulcer and at subsequent visits.¹⁶ Pain may make NSAID cessation difficult for some patients, while others do not realize that over-the-counter preparations they take contain NSAIDs.¹⁵

Another group of patients with continued NSAID exposure are those who require long-term NSAID therapy for control of arthritis or the management of cardiovascular conditions. If NSAID therapy cannot be discontinued, the risk of NSAID-related gastrointestinal injury can be assessed based on the presence of multiple risk factors, including age > 65 years, high-dose NSAID therapy, a history of peptic ulcer, and concurrent use of aspirin, corticosteroids, or anticoagulants. Individuals with 3 or more of the preceding risk factors or a history of a peptic ulcer with a complication, especially if recent, are considered to be at high risk of developing an NSAID-related ulcer and possible subsequent complications.¹⁷ In these individuals, NSAID therapy should be continued with agents that have the lowest risk for gastrointestinal toxicity and at the lowest possible dose. A meta-analysis comparing nonselective NSAIDs to placebo demonstrated naproxen to have the highest risk of gastrointestinal complications, including GIB, perforation, and obstruction (adjusted rate ratio, 4.2), while diclofenac demonstrated the lowest risk (adjusted rate ratio, 1.89). High-dose NSAID therapy demonstrated a 2-fold increase in risk of peptic ulcer formation as compared to low-dose therapy.¹⁸

In addition to selecting the NSAID with the least gastrointestinal toxicity at the lowest possible dose, additional strategies to prevent peptic ulcer disease and its complications in chronic NSAID users include co-administration of a PPI and substitution of a COX-2 selective NSAID for nonselective NSAIDs.^1,9 Prior double-blind, placebo-controlled, randomized, multicenter trials with patients requiring daily NSAIDs demonstrated an up to 15% absolute reduction in the risk of developing peptic ulcers over 6 months while taking esomeprazole.¹⁹

Persistent Infection. Persistent H. pylori infection, due either to initial false-negative testing or ongoing infection despite first-line therapy, is another cause of refractory peptic ulcer disease.^1,15 Because antibiotics and PPIs can reduce the number of H. pylori bacteria, use of these medications concurrent with H. pylori testing can lead to false-negative results with several testing modalities. When suspicion for H. pylori is high, 2 or more diagnostic tests may be needed to effectively rule out infection.¹⁵

When H. pylori is detected, successful eradication is becoming more difficult due to an increasing prevalence of antibiotic resistance, leading to persistent infection in many cases and maintained risk of peptic ulcer disease, despite appropriate first-line therapy.⁸ Options for salvage therapy for persistent H. pylori, as well as information on the role and best timing of susceptibility testing, are beyond the scope of this review, but are reviewed by Lanas and Chan¹ and in the American College of Gastroenterology guideline on the treatment of H. pylori infection.⁸

Other Causes. In a meta-analysis of rigorously designed studies from North America, 20% of patients experienced ulcer recurrence at 6 months, despite successful H. pylori eradication and no NSAID use.²⁰ In addition, as H. pylori prevalence is decreasing, idiopathic ulcers are increasingly being diagnosed, and such ulcers may be associated with high rates of GIB and mortality.¹ In this subset of patients with non-H. pylori, non-NSAID ulcers, increased effort is required to further evaluate the differential diagnosis for rarer causes of upper GI tract ulcer disease (Table). Certain malignancies, including adenocarcinoma and lymphoma, can cause ulcer formation and should be considered in refractory cases. Repeat biopsy at follow-up endoscopy for persistent ulcers should always be obtained to further evaluate for malignancy.^1,15 Infectious diseases other than H. pylori infection, such as tuberculosis, syphilis, cytomegalovirus, and herpes simplex virus, are also reported as etiologies of refractory ulcers, and require specific antimicrobial treatment over and above PPI monotherapy. Special attention in biopsy sampling and sample processing is often required when infectious etiologies are being considered, as specific histologic stains and cultures may be needed for identification.¹⁵

Systemic conditions, including sarcoidosis,²¹ Behçet disease,²² and polyarteritis nodosa,^15,23 can also cause refractory ulcers. Approximately 15% of patients with Crohn disease have gastroduodenal involvement, which may include ulcers of variable sizes.^1,15,24 The increased gastric acid production seen in Zollinger-Ellison syndrome commonly presents as refractory peptic ulcers in the duodenum beyond the bulb that do not heal with standard doses of PPIs.^1,15 More rare causes of acid hypersecretion leading to refractory ulcers include idiopathic gastric acid hypersecretion and retained gastric antrum syndrome after partial gastrectomy with Billroth II anastomosis.¹⁵ Smoking is a known risk factor for impaired tissue healing throughout the body, and can contribute to impaired healing of peptic ulcers through decreased prostaglandin synthesis²⁵ and reduced gastric mucosal blood flow.²⁶ Smoking should always be addressed in patients with refractory peptic ulcers, and cessation should be strongly encouraged. Other less common causes of refractory upper GI tract ulcers include radiation therapy, crack cocaine use, and mesenteric ischemia.¹⁵

Managing Antiplatelet and Anticoagulant Medications

Use of antiplatelets and anticoagulants, alone or in combination, increases the risk of peptic ulcer bleeding. In patients who continue to take aspirin after a peptic ulcer bleed, recurrent bleeding occurs in up to 300 cases per 1000 person-years. The rate of GIB associated with aspirin use ranges from 1.1% to 2.5%, depending on the dose. Prior peptic ulcer disease, age greater than 70 years, and concurrent NSAID, steroid, anticoagulant, or dual antiplatelet therapy (DAPT) use increase the risk of bleeding while on aspirin. The rate of GIB while taking a thienopyridine alone is slightly less than that when taking aspirin, ranging from 0.5% to 1.6%. Studies to date have yielded mixed estimates of the effect of DAPT on the risk of GIB. Estimates of the risk of GIB with DAPT range from an odds ratio for serious GIB of 7.4 to an absolute risk increase of only 1.3% when compared to clopidogrel alone.²⁷

Many patients are also on warfarin or a direct oral anticoagulant (DOAC). In a study from the United Kingdom, the adjusted rate ratio of GIB with warfarin alone was 1.94, and this increased to 6.48 when warfarin was used with aspirin.²⁸ The use of warfarin and DAPT, often called triple therapy, further increases the risk of GIB, with a hazard ratio of 5.0 compared to DAPT alone, and 5.38 when compared to warfarin alone. DOACs are increasingly prescribed for the treatment and prevention of thromboembolism, and by 2014 were prescribed as often as warfarin for stroke prevention in atrial fibrillation in the United States. A meta-analysis showed the risk of major GIB did not differ between DOACs and warfarin or low-molecular-weight heparin, but among DOACs factor Xa inhibitors showed a reduced risk of GIB compared with dabigatran, a direct thrombin inhibitor.²⁹

The use of antiplatelets and anticoagulants in the context of peptic ulcer bleeding is a current management challenge. Data to guide decision-making in patients on antiplatelet and/or anticoagulant therapy who experience peptic ulcer bleeding are scarce. Decision-making in this group of patients requires balancing the severity and risk of bleeding with the risk of thromboembolism.^1,27 In patients on antiplatelet therapy for primary prophylaxis of atherothrombosis who develop bleeding from a peptic ulcer, the antiplatelet should generally be held and the indication for the medication reassessed. In patients on antiplatelet therapy for secondary prevention, the agent may be immediately resumed after endoscopy if bleeding is found to be due to an ulcer with low-risk stigmata. With bleeding resulting from an ulcer with high-risk stigmata, antiplatelet agents employed for secondary prevention may be held initially, with consideration given to early reintroduction, as early as day 3 after endoscopy.¹ In patients at high risk for atherothrombotic events, including those on aspirin for secondary prophylaxis, withholding aspirin leads to a 3-fold increase in the risk of a major adverse cardiac event, with events occurring as early as 5 days after aspirin cessation in some cases.²⁷ A randomized controlled trial of continuing low-dose aspirin versus withholding it for 8 weeks in patients on aspirin for secondary prophylaxis of cardiovascular events who experienced peptic ulcer bleeding that required endoscopic therapy demonstrated lower all-cause mortality (1.3% vs 12.9%), including death from cardiovascular or cerebrovascular events, among those who continued aspirin therapy, with a small increased risk of recurrent ulcer bleeding (10.3% vs 5.4%).³⁰ Thus, it is recommended that antiplatelet therapy, when held, be resumed as early as possible when the risk of a cardiovascular or cerebrovascular event is considered to be higher than the risk of bleeding.²⁷

When patients are on DAPT for a history of drug-eluting stent placement, withholding both antiplatelet medications should be avoided, even for a brief period of time, given the risk of in-stent thrombosis. When DAPT is employed for other reasons, it should be continued, if indicated, after bleeding that is found to be due to peptic ulcers with low-risk stigmata. If bleeding is due to a peptic ulcer with high-risk stigmata at endoscopy, then aspirin monotherapy should be continued and consultation should be obtained with a cardiologist to determine optimal timing to resume the second antiplatelet agent.¹ In patients on anticoagulants, anticoagulation should be resumed once hemostasis is achieved when the risk of withholding anticoagulation is thought to be greater than the risk of rebleeding. For example, anticoagulation should be resumed early in a patient with a mechanical heart valve to prevent thrombosis.^1,27 Following upper GIB from peptic ulcer disease, patients who will require long-term aspirin, DAPT, or anticoagulation with either warfarin or DOACs should be maintained on long-term PPI therapy to reduce the risk of recurrent bleeding.^9,27

Failure of Endoscopic Therapy to Control Peptic Ulcer Bleeding

Bleeding recurs in as many as 10% to 20% of patients after initial endoscopic control of peptic ulcer bleeding.^4,31 In this context, repeat upper endoscopy for hemostasis is preferred to surgery, as it leads to less morbidity while providing long-term control of bleeding in more than 70% of cases.^31,32 Two potential endoscopic rescue therapies that may be employed are over-the-scope clips (OTSCs) and hemostatic powder.^32,33

While through-the-scope (TTS) hemostatic clips are often used during endoscopy to control active peptic ulcer bleeding, their use may be limited in large or fibrotic ulcers due to the smaller size of the clips and method of application. OTSCs have several advantages over TTS clips; notably, their larger size allows the endoscopist to achieve deeper mucosal or submucosal clip attachment via suction of the targeted tissue into the endoscopic cap (Figure 2). In a systematic review of OTSCs, successful hemostasis was achieved in 84% of 761 lesions, including 75% of lesions due to peptic ulcer disease.³⁴ Some have argued that OTSCs may be preferred as first-line therapy over epinephrine with TTS clips for hemostasis in bleeding from high-risk peptic ulcers (ie, those with visualized arterial bleeding or a visible vessel) given observed decreases in rebleeding events.³⁵

Despite the advantages of OTSCs, endoscopists should be mindful of the potential complications of OTSC use, including luminal obstruction, particularly in the duodenum, and perforation, which occurs in 0.3% to 2% of cases. Additionally, retrieval of misplaced OTSCs presents a significant challenge. Careful decision-making with consideration of the location, size, and depth of lesions is required when deciding on OTSC placement.^34,36

A newer endoscopic tool developed for refractory bleeding from peptic ulcers and other causes is hemostatic powder. Hemostatic powders accelerate the coagulation cascade, leading to shortened coagulation times and enhanced clot formation.³⁷ A recent meta-analysis showed that immediate hemostasis could be achieved in 95% of cases of bleeding, including in 96% of cases of bleeding from peptic ulcer disease.³⁸ The primary limitation of hemostatic powders is the temporary nature of hemostasis, which requires the underlying etiology of bleeding to be addressed in order to provide long-term hemostasis. In the above meta-analysis, rebleeding occurred in 17% of cases after 30 days.³⁸

Hypotension and ulcer diameter ≥ 2 cm are independent predictors of failure of endoscopic salvage therapy.³¹ When severe bleeding is not controlled with initial endoscopic therapy or bleeding recurs despite salvage endoscopic therapy, transcatheter angiographic embolization (TAE) is the treatment of choice.⁴ Systematic reviews and meta-analyses of studies that compared TAE to surgery have shown that the rate of rebleeding may be higher with TAE, but with less morbidity and either decreased or equivalent rates of mortality, with no increased need for additional interventions.^4,32 In a case series examining 5 years of experience at a single medical center in China, massive GIB from duodenal ulcers was successfully treated with TAE in 27 of 29 cases (93% clinical success rate), with no mucosal ischemic necrosis observed.³⁹

If repeated endoscopic therapy has not led to hemostasis of a bleeding peptic ulcer and TAE is not available, then surgery is the next best option. Bleeding gastric ulcers may be excised, wedge resected, or oversewn after an anterior gastrostomy. Bleeding duodenal ulcers may require use of a Kocher maneuver and linear incision of the anterior duodenum followed by ligation of the gastroduodenal artery. Fortunately, such surgical management is rarely necessary given the availability of TAE at most centers.⁴

Conclusion

Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with adequate frequency and duration of PPI therapy, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Acknowledgment: We thank Dr. Nipun Reddy from our institution for providing the endoscopic images used in this article.

Corresponding author: Adam L. Edwards, MD, MS; aledwards@uabmc.edu.

Financial disclosures: None.