Latex allergy is an all-encompassing term used to describe hypersensitivity reactions to products containing natural rubber latex from the Hevea brasiliensis tree and affects approximately 1% to 2% of the general population.¹ Although latex gloves are the most widely known culprits, several other commonly used products can contain natural rubber latex, including adhesive tape, balloons, condoms, rubber bands, paint, tourniquets, electrode pads, and Foley catheters.² The term latex allergy often is used as a general diagnosis, but there are in fact 3 distinct mechanisms by which individuals may develop an adverse reaction to latex-containing products: irritant contact dermatitis, allergic contact dermatitis (type IV hypersensitivity) and true latex allergy (type I hypersensitivity).

Irritant Contact Dermatitis

Irritant contact dermatitis, a nonimmunologic reaction, occurs due to mechanical factors (eg, friction) or contact with chemicals, which can have irritating and dehydrating effects. Individuals with irritant contact dermatitis do not have true latex allergy and will not necessarily develop a reaction to products containing natural rubber latex. Incorrectly attributing these irritant contact dermatitis reactions to latex allergy and simply advising patients to avoid all latex products (eg, use nitrile gloves rather than latex gloves) will not address the underlying problem. Rather, these patients must be informed that the dermatitis is a result of a disruption to the natural, protective skin barrier and not an allergic reaction.

Allergic Contact Dermatitis

Allergic contact dermatitis to rubber is caused by a type IV (delayed) hypersensitivity reaction and is the result of exposure to the accelerators present in rubber products in sensitive individuals. Individuals experiencing this type of reaction typically develop localized erythema, pruritus, and urticarial lesions 48 hours after exposure.³ Incorrectly labeling this problem as latex allergy and recommending nonlatex rubber substitutes (eg, hypoallergenic gloves) likely will not be effective, as these nonlatex replacement products contain the same accelerators as do latex gloves.

True Latex Allergy

The most severe form of latex allergy, often referred to as true latex allergy, is caused by a type I (immediate) hypersensitivity reaction mediated by immunoglobulin E (IgE) antibodies. Individuals experiencing this type of reaction have a systemic response to latex proteins that may result in fulminant anaphylaxis. Individuals with true latex allergy must absolutely avoid latex products, and substituting nonlatex products is the most effective approach.

Latex Reactions in Medical Practice

The varying propensity of certain populations to develop latex allergy has been well documented; for example, the prevalence of hypersensitivity in patients with spina bifida ranges from 20% to 65%, figures that are much higher than those reported in the general population.³ This hypersensitivity in patients with spina bifida most likely results from repeated exposure to latex products during corrective surgeries and diagnostic procedures early in life. Atopic individuals, such as those with allergic rhinitis, eczema, and asthma, have a 4-fold increased risk for developing latex allergy compared to nonatopic individuals.⁴ The risk of latex allergy among health care workers is increased due to increased exposure to rubber products. One study found that the risk of latex sensitization among health care workers exposed to products containing latex was 4.3%, while the risk in the general population was only 1.37%.¹ Those at highest risk for sensitization include dental assistants, operating room personnel, hospital housekeeping staff, and paramedics or emergency medical technicians.³ However, sensitization documented on laboratory assessment does not reliably correlate with symptomatic allergy, as many patients with a positive IgE test do not show clinical symptoms. Schmid et al⁴ demonstrated that a 1.3% prevalence of clinically symptomatic latex allergy among health care workers may approximate the prevalence of latex allergy in the general population. In a study by Brown et al,⁵ although 12.5% of anesthesiologists were found to be sensitized to latex, only 2.4% had clinically symptomatic allergic reactions.

Testing for Latex Allergy

Several diagnostic tests are available to establish a diagnosis of type I sensitization or true latex allergy. Skin prick testing is an in vivo assay and is the gold standard for diagnosing IgE-mediated type I hypersensitivity to latex. The test involves pricking the skin of the forearm and applying a commercial extract of nonammoniated latex to monitor for development of a wheal within several minutes. The skin prick test should be performed in a health care setting equipped with oxygen, epinephrine, and latex-free resuscitation equipment in case of anaphylaxis following exposure. Although latex skin prick testing is the gold standard, it is rarely performed in the United States because there is no US Food and Drug Administration–approved natural rubber latex reagent.³ Consequently, physicians who wish to perform skin prick testing for latex allergy are forced to develop improvised reagents from the H brasiliensis tree itself or from highly allergenic latex gloves. Standardized latex allergens are commercially available in Europe.

The most noninvasive method of latex allergy testing is an in vitro assay for latex-specific IgE antibodies, which can be detected by either a radioallergosorbent test (RAST) or enzyme-linked immunosorbent assay (ELISA). The presence of antilatex IgE antibodies confirms sensitization but does not necessarily mean the patient will develop a symptomatic reaction following exposure. Due to the unavailability of a standardized reagent for the skin prick test in the United States, evaluation of latex-specific serum IgE levels may be the best alternative. While the skin prick test has the highest sensitivity, the sensitivity and specificity of latex-specific serum IgE testing are 50% to 90% and 80% to 87%, respectively.⁶

The wear test (also known as the use or glove provocation test), can be used to diagnose clinically symptomatic latex allergy when there is a discrepancy between the patient’s clinical history and results from skin prick or serum IgE antibody testing. To perform the wear test, place a natural rubber latex glove on one of the patient’s fingers for 15 minutes and monitor the area for development of urticaria. If there is no evidence of allergic reaction within 15 minutes, place the glove on the whole hand for an additional 15 minutes. The patient is said to be nonreactive if a latex glove can be placed on the entire hand for 15 minutes without evidence of reaction.³

Lastly, patch testing can differentiate between irritant contact and allergic contact (type IV hypersensitivity) dermatitis. Apply a small amount of each substance of interest onto a separate disc and place the discs in direct contact with the skin using hypoallergenic tape. With type IV latex hypersensitivity, the skin underneath the disc will become erythematous with developing papulovesicles, starting between 2 and 5 days after exposure. The Figure outlines the differentiation of true latex allergy from irritant and allergic contact dermatitis and identifies methods for making these diagnoses.

General Medical Protocol With Latex Reactions

To reduce the incidence of latex allergic reactions among health care workers and patients, Kumar² recommends putting a protocol in place to document steps in preventing, diagnosing, and treating latex allergy. This protocol includes employee and patient education about the risks for developing latex allergy and the signs and symptoms of a reaction; available diagnostic testing; and alternative products (eg, hypoallergenic gloves) that are available to individuals with a known or suspected allergy. At-risk health care workers who have not been sensitized should be advised to avoid latex-containing products.³ Routine questioning and diagnostic testing may be necessary as part of every preoperative assessment, as there have been reported cases of anaphylaxis in patients with undocumented allergies.⁷ Anaphylaxis caused by latex allergy is the second leading cause of perioperative anaphylaxis, accounting for as many as 20% of cases.⁸ With the use of preventative measures and early identification of at-risk patients, the incidence of latex-related anaphylaxis is decreasing.⁸ Ascertaining valuable information about the patient’s medical history, such as known allergies to foods that have cross-reactivity to latex (eg, bananas, mango, kiwi, avocado), is one simple way of identifying a patient who should be tested for possible underlying latex allergy.⁸ Total avoidance of latex-containing products (eg, in the workplace) can further reduce the incidence of allergic reactions by decreasing primary sensitization and risk of exposure.

Conclusion

Patients claiming to be allergic to latex without documentation should be tested. The diagnostic testing available in the United States includes patch testing, wear (or glove provocation) testing, or assessment of IgE antibody titer. Accurate differentiation among irritant contact dermatitis, allergic contact dermatitis, and true latex allergy is paramount for properly educating patients and effectively treating these conditions. Additionally, distinguishing patients with true latex allergy from those who have been misdiagnosed can save resources and reduce health care costs.

Latex allergy is an all-encompassing term used to describe hypersensitivity reactions to products containing natural rubber latex from the Hevea brasiliensis tree and affects approximately 1% to 2% of the general population.¹ Although latex gloves are the most widely known culprits, several other commonly used products can contain natural rubber latex, including adhesive tape, balloons, condoms, rubber bands, paint, tourniquets, electrode pads, and Foley catheters.² The term latex allergy often is used as a general diagnosis, but there are in fact 3 distinct mechanisms by which individuals may develop an adverse reaction to latex-containing products: irritant contact dermatitis, allergic contact dermatitis (type IV hypersensitivity) and true latex allergy (type I hypersensitivity).

Irritant Contact Dermatitis

Irritant contact dermatitis, a nonimmunologic reaction, occurs due to mechanical factors (eg, friction) or contact with chemicals, which can have irritating and dehydrating effects. Individuals with irritant contact dermatitis do not have true latex allergy and will not necessarily develop a reaction to products containing natural rubber latex. Incorrectly attributing these irritant contact dermatitis reactions to latex allergy and simply advising patients to avoid all latex products (eg, use nitrile gloves rather than latex gloves) will not address the underlying problem. Rather, these patients must be informed that the dermatitis is a result of a disruption to the natural, protective skin barrier and not an allergic reaction.

Allergic Contact Dermatitis

Allergic contact dermatitis to rubber is caused by a type IV (delayed) hypersensitivity reaction and is the result of exposure to the accelerators present in rubber products in sensitive individuals. Individuals experiencing this type of reaction typically develop localized erythema, pruritus, and urticarial lesions 48 hours after exposure.³ Incorrectly labeling this problem as latex allergy and recommending nonlatex rubber substitutes (eg, hypoallergenic gloves) likely will not be effective, as these nonlatex replacement products contain the same accelerators as do latex gloves.

True Latex Allergy

The most severe form of latex allergy, often referred to as true latex allergy, is caused by a type I (immediate) hypersensitivity reaction mediated by immunoglobulin E (IgE) antibodies. Individuals experiencing this type of reaction have a systemic response to latex proteins that may result in fulminant anaphylaxis. Individuals with true latex allergy must absolutely avoid latex products, and substituting nonlatex products is the most effective approach.

Latex Reactions in Medical Practice

The varying propensity of certain populations to develop latex allergy has been well documented; for example, the prevalence of hypersensitivity in patients with spina bifida ranges from 20% to 65%, figures that are much higher than those reported in the general population.³ This hypersensitivity in patients with spina bifida most likely results from repeated exposure to latex products during corrective surgeries and diagnostic procedures early in life. Atopic individuals, such as those with allergic rhinitis, eczema, and asthma, have a 4-fold increased risk for developing latex allergy compared to nonatopic individuals.⁴ The risk of latex allergy among health care workers is increased due to increased exposure to rubber products. One study found that the risk of latex sensitization among health care workers exposed to products containing latex was 4.3%, while the risk in the general population was only 1.37%.¹ Those at highest risk for sensitization include dental assistants, operating room personnel, hospital housekeeping staff, and paramedics or emergency medical technicians.³ However, sensitization documented on laboratory assessment does not reliably correlate with symptomatic allergy, as many patients with a positive IgE test do not show clinical symptoms. Schmid et al⁴ demonstrated that a 1.3% prevalence of clinically symptomatic latex allergy among health care workers may approximate the prevalence of latex allergy in the general population. In a study by Brown et al,⁵ although 12.5% of anesthesiologists were found to be sensitized to latex, only 2.4% had clinically symptomatic allergic reactions.

Testing for Latex Allergy

Several diagnostic tests are available to establish a diagnosis of type I sensitization or true latex allergy. Skin prick testing is an in vivo assay and is the gold standard for diagnosing IgE-mediated type I hypersensitivity to latex. The test involves pricking the skin of the forearm and applying a commercial extract of nonammoniated latex to monitor for development of a wheal within several minutes. The skin prick test should be performed in a health care setting equipped with oxygen, epinephrine, and latex-free resuscitation equipment in case of anaphylaxis following exposure. Although latex skin prick testing is the gold standard, it is rarely performed in the United States because there is no US Food and Drug Administration–approved natural rubber latex reagent.³ Consequently, physicians who wish to perform skin prick testing for latex allergy are forced to develop improvised reagents from the H brasiliensis tree itself or from highly allergenic latex gloves. Standardized latex allergens are commercially available in Europe.

The most noninvasive method of latex allergy testing is an in vitro assay for latex-specific IgE antibodies, which can be detected by either a radioallergosorbent test (RAST) or enzyme-linked immunosorbent assay (ELISA). The presence of antilatex IgE antibodies confirms sensitization but does not necessarily mean the patient will develop a symptomatic reaction following exposure. Due to the unavailability of a standardized reagent for the skin prick test in the United States, evaluation of latex-specific serum IgE levels may be the best alternative. While the skin prick test has the highest sensitivity, the sensitivity and specificity of latex-specific serum IgE testing are 50% to 90% and 80% to 87%, respectively.⁶

The wear test (also known as the use or glove provocation test), can be used to diagnose clinically symptomatic latex allergy when there is a discrepancy between the patient’s clinical history and results from skin prick or serum IgE antibody testing. To perform the wear test, place a natural rubber latex glove on one of the patient’s fingers for 15 minutes and monitor the area for development of urticaria. If there is no evidence of allergic reaction within 15 minutes, place the glove on the whole hand for an additional 15 minutes. The patient is said to be nonreactive if a latex glove can be placed on the entire hand for 15 minutes without evidence of reaction.³

Lastly, patch testing can differentiate between irritant contact and allergic contact (type IV hypersensitivity) dermatitis. Apply a small amount of each substance of interest onto a separate disc and place the discs in direct contact with the skin using hypoallergenic tape. With type IV latex hypersensitivity, the skin underneath the disc will become erythematous with developing papulovesicles, starting between 2 and 5 days after exposure. The Figure outlines the differentiation of true latex allergy from irritant and allergic contact dermatitis and identifies methods for making these diagnoses.

General Medical Protocol With Latex Reactions

To reduce the incidence of latex allergic reactions among health care workers and patients, Kumar² recommends putting a protocol in place to document steps in preventing, diagnosing, and treating latex allergy. This protocol includes employee and patient education about the risks for developing latex allergy and the signs and symptoms of a reaction; available diagnostic testing; and alternative products (eg, hypoallergenic gloves) that are available to individuals with a known or suspected allergy. At-risk health care workers who have not been sensitized should be advised to avoid latex-containing products.³ Routine questioning and diagnostic testing may be necessary as part of every preoperative assessment, as there have been reported cases of anaphylaxis in patients with undocumented allergies.⁷ Anaphylaxis caused by latex allergy is the second leading cause of perioperative anaphylaxis, accounting for as many as 20% of cases.⁸ With the use of preventative measures and early identification of at-risk patients, the incidence of latex-related anaphylaxis is decreasing.⁸ Ascertaining valuable information about the patient’s medical history, such as known allergies to foods that have cross-reactivity to latex (eg, bananas, mango, kiwi, avocado), is one simple way of identifying a patient who should be tested for possible underlying latex allergy.⁸ Total avoidance of latex-containing products (eg, in the workplace) can further reduce the incidence of allergic reactions by decreasing primary sensitization and risk of exposure.

Conclusion

Patients claiming to be allergic to latex without documentation should be tested. The diagnostic testing available in the United States includes patch testing, wear (or glove provocation) testing, or assessment of IgE antibody titer. Accurate differentiation among irritant contact dermatitis, allergic contact dermatitis, and true latex allergy is paramount for properly educating patients and effectively treating these conditions. Additionally, distinguishing patients with true latex allergy from those who have been misdiagnosed can save resources and reduce health care costs.

Latex allergy is an all-encompassing term used to describe hypersensitivity reactions to products containing natural rubber latex from the Hevea brasiliensis tree and affects approximately 1% to 2% of the general population.¹ Although latex gloves are the most widely known culprits, several other commonly used products can contain natural rubber latex, including adhesive tape, balloons, condoms, rubber bands, paint, tourniquets, electrode pads, and Foley catheters.² The term latex allergy often is used as a general diagnosis, but there are in fact 3 distinct mechanisms by which individuals may develop an adverse reaction to latex-containing products: irritant contact dermatitis, allergic contact dermatitis (type IV hypersensitivity) and true latex allergy (type I hypersensitivity).

Irritant Contact Dermatitis

Irritant contact dermatitis, a nonimmunologic reaction, occurs due to mechanical factors (eg, friction) or contact with chemicals, which can have irritating and dehydrating effects. Individuals with irritant contact dermatitis do not have true latex allergy and will not necessarily develop a reaction to products containing natural rubber latex. Incorrectly attributing these irritant contact dermatitis reactions to latex allergy and simply advising patients to avoid all latex products (eg, use nitrile gloves rather than latex gloves) will not address the underlying problem. Rather, these patients must be informed that the dermatitis is a result of a disruption to the natural, protective skin barrier and not an allergic reaction.

Allergic Contact Dermatitis

Allergic contact dermatitis to rubber is caused by a type IV (delayed) hypersensitivity reaction and is the result of exposure to the accelerators present in rubber products in sensitive individuals. Individuals experiencing this type of reaction typically develop localized erythema, pruritus, and urticarial lesions 48 hours after exposure.³ Incorrectly labeling this problem as latex allergy and recommending nonlatex rubber substitutes (eg, hypoallergenic gloves) likely will not be effective, as these nonlatex replacement products contain the same accelerators as do latex gloves.

True Latex Allergy

The most severe form of latex allergy, often referred to as true latex allergy, is caused by a type I (immediate) hypersensitivity reaction mediated by immunoglobulin E (IgE) antibodies. Individuals experiencing this type of reaction have a systemic response to latex proteins that may result in fulminant anaphylaxis. Individuals with true latex allergy must absolutely avoid latex products, and substituting nonlatex products is the most effective approach.

Latex Reactions in Medical Practice

The varying propensity of certain populations to develop latex allergy has been well documented; for example, the prevalence of hypersensitivity in patients with spina bifida ranges from 20% to 65%, figures that are much higher than those reported in the general population.³ This hypersensitivity in patients with spina bifida most likely results from repeated exposure to latex products during corrective surgeries and diagnostic procedures early in life. Atopic individuals, such as those with allergic rhinitis, eczema, and asthma, have a 4-fold increased risk for developing latex allergy compared to nonatopic individuals.⁴ The risk of latex allergy among health care workers is increased due to increased exposure to rubber products. One study found that the risk of latex sensitization among health care workers exposed to products containing latex was 4.3%, while the risk in the general population was only 1.37%.¹ Those at highest risk for sensitization include dental assistants, operating room personnel, hospital housekeeping staff, and paramedics or emergency medical technicians.³ However, sensitization documented on laboratory assessment does not reliably correlate with symptomatic allergy, as many patients with a positive IgE test do not show clinical symptoms. Schmid et al⁴ demonstrated that a 1.3% prevalence of clinically symptomatic latex allergy among health care workers may approximate the prevalence of latex allergy in the general population. In a study by Brown et al,⁵ although 12.5% of anesthesiologists were found to be sensitized to latex, only 2.4% had clinically symptomatic allergic reactions.

Testing for Latex Allergy

Several diagnostic tests are available to establish a diagnosis of type I sensitization or true latex allergy. Skin prick testing is an in vivo assay and is the gold standard for diagnosing IgE-mediated type I hypersensitivity to latex. The test involves pricking the skin of the forearm and applying a commercial extract of nonammoniated latex to monitor for development of a wheal within several minutes. The skin prick test should be performed in a health care setting equipped with oxygen, epinephrine, and latex-free resuscitation equipment in case of anaphylaxis following exposure. Although latex skin prick testing is the gold standard, it is rarely performed in the United States because there is no US Food and Drug Administration–approved natural rubber latex reagent.³ Consequently, physicians who wish to perform skin prick testing for latex allergy are forced to develop improvised reagents from the H brasiliensis tree itself or from highly allergenic latex gloves. Standardized latex allergens are commercially available in Europe.

The most noninvasive method of latex allergy testing is an in vitro assay for latex-specific IgE antibodies, which can be detected by either a radioallergosorbent test (RAST) or enzyme-linked immunosorbent assay (ELISA). The presence of antilatex IgE antibodies confirms sensitization but does not necessarily mean the patient will develop a symptomatic reaction following exposure. Due to the unavailability of a standardized reagent for the skin prick test in the United States, evaluation of latex-specific serum IgE levels may be the best alternative. While the skin prick test has the highest sensitivity, the sensitivity and specificity of latex-specific serum IgE testing are 50% to 90% and 80% to 87%, respectively.⁶

The wear test (also known as the use or glove provocation test), can be used to diagnose clinically symptomatic latex allergy when there is a discrepancy between the patient’s clinical history and results from skin prick or serum IgE antibody testing. To perform the wear test, place a natural rubber latex glove on one of the patient’s fingers for 15 minutes and monitor the area for development of urticaria. If there is no evidence of allergic reaction within 15 minutes, place the glove on the whole hand for an additional 15 minutes. The patient is said to be nonreactive if a latex glove can be placed on the entire hand for 15 minutes without evidence of reaction.³

Lastly, patch testing can differentiate between irritant contact and allergic contact (type IV hypersensitivity) dermatitis. Apply a small amount of each substance of interest onto a separate disc and place the discs in direct contact with the skin using hypoallergenic tape. With type IV latex hypersensitivity, the skin underneath the disc will become erythematous with developing papulovesicles, starting between 2 and 5 days after exposure. The Figure outlines the differentiation of true latex allergy from irritant and allergic contact dermatitis and identifies methods for making these diagnoses.

General Medical Protocol With Latex Reactions

To reduce the incidence of latex allergic reactions among health care workers and patients, Kumar² recommends putting a protocol in place to document steps in preventing, diagnosing, and treating latex allergy. This protocol includes employee and patient education about the risks for developing latex allergy and the signs and symptoms of a reaction; available diagnostic testing; and alternative products (eg, hypoallergenic gloves) that are available to individuals with a known or suspected allergy. At-risk health care workers who have not been sensitized should be advised to avoid latex-containing products.³ Routine questioning and diagnostic testing may be necessary as part of every preoperative assessment, as there have been reported cases of anaphylaxis in patients with undocumented allergies.⁷ Anaphylaxis caused by latex allergy is the second leading cause of perioperative anaphylaxis, accounting for as many as 20% of cases.⁸ With the use of preventative measures and early identification of at-risk patients, the incidence of latex-related anaphylaxis is decreasing.⁸ Ascertaining valuable information about the patient’s medical history, such as known allergies to foods that have cross-reactivity to latex (eg, bananas, mango, kiwi, avocado), is one simple way of identifying a patient who should be tested for possible underlying latex allergy.⁸ Total avoidance of latex-containing products (eg, in the workplace) can further reduce the incidence of allergic reactions by decreasing primary sensitization and risk of exposure.

Conclusion

Patients claiming to be allergic to latex without documentation should be tested. The diagnostic testing available in the United States includes patch testing, wear (or glove provocation) testing, or assessment of IgE antibody titer. Accurate differentiation among irritant contact dermatitis, allergic contact dermatitis, and true latex allergy is paramount for properly educating patients and effectively treating these conditions. Additionally, distinguishing patients with true latex allergy from those who have been misdiagnosed can save resources and reduce health care costs.

I was taught—and still believe—that obtaining a thorough history can direct you to a good working diagnosis. About 20 years ago, while in the Navy, I had a patient who showed me that I should not be fooled by a history that does not fit the current presentation.

The patient was a 34-year-old sailor with right-side knee pain, occurring intermittently for a long time but worsening in recent months. The pain did not prevent him from running, performing in the Navy’s semi-annual fitness test, or participating in departmental physical fitness activities.

However, his pain worsened after he was assigned to a ship, which required him to ascend and descend the steep shipboard stairs or ladders. He also complained of some intermittent buckling or “giving out.” But he was quite clear when he stated that he had sustained no recent injury to explain his condition.

The pain did not prevent him from running, performing in the Navy's semi-annual fitness test, or participating in departmental activities.

His history was notable for an injury he sustained six years earlier, while running. Although he could not remember the exact mechanism of injury, he recalled that his knee hurt and was swollen the next day. He was seen in medical, where he was given crutches, modified duty, and ibuprofen for a few days. After a relatively short time, his activity returned to normal.

I had seen a lot of knee pain on board ship, mostly of the patellar tendonitis or patellofemoral syndrome types, that could often be treated conservatively with temporary duty modification to avoid aggravating activity. More serious injuries—such as meniscal, collateral, or cruciate ligament tears—were associated with recent or acute injuries and a history including a suspicious mechanism of injury.

This patient’s complete knee exam was largely unremarkable, except his anterior drawer test seemed to have no distinct endpoint. When I compared the results with his asymptomatic left knee, I could not appreciate any difference.

So I relayed to him my thought process: If he had done something serious to his knee six years ago, it probably would have manifested sooner. As other clinicians did previously, I treated him conservatively with duty limitations and advised him that if he failed to improve soon, I would refer him to an orthopedist for a second opinion.

Well, he did not improve soon. Since he was still concerned, I provided the referral, without obtaining an MRI.

To perhaps everyone’s surprise—but most definitely mine—the patient was diagnosed with a complete ACL tear by the orthopedist (again, without MRI). He was scheduled for surgery at a later date.

What surprised me most was that someone could perform the way he was required to perform in the Navy for six years with a torn ACL. As a result of this case, I have not let a remote history of injury cloud my judgment since!

I was taught—and still believe—that obtaining a thorough history can direct you to a good working diagnosis. About 20 years ago, while in the Navy, I had a patient who showed me that I should not be fooled by a history that does not fit the current presentation.

The patient was a 34-year-old sailor with right-side knee pain, occurring intermittently for a long time but worsening in recent months. The pain did not prevent him from running, performing in the Navy’s semi-annual fitness test, or participating in departmental physical fitness activities.

However, his pain worsened after he was assigned to a ship, which required him to ascend and descend the steep shipboard stairs or ladders. He also complained of some intermittent buckling or “giving out.” But he was quite clear when he stated that he had sustained no recent injury to explain his condition.

The pain did not prevent him from running, performing in the Navy's semi-annual fitness test, or participating in departmental activities.

His history was notable for an injury he sustained six years earlier, while running. Although he could not remember the exact mechanism of injury, he recalled that his knee hurt and was swollen the next day. He was seen in medical, where he was given crutches, modified duty, and ibuprofen for a few days. After a relatively short time, his activity returned to normal.

I had seen a lot of knee pain on board ship, mostly of the patellar tendonitis or patellofemoral syndrome types, that could often be treated conservatively with temporary duty modification to avoid aggravating activity. More serious injuries—such as meniscal, collateral, or cruciate ligament tears—were associated with recent or acute injuries and a history including a suspicious mechanism of injury.

This patient’s complete knee exam was largely unremarkable, except his anterior drawer test seemed to have no distinct endpoint. When I compared the results with his asymptomatic left knee, I could not appreciate any difference.

So I relayed to him my thought process: If he had done something serious to his knee six years ago, it probably would have manifested sooner. As other clinicians did previously, I treated him conservatively with duty limitations and advised him that if he failed to improve soon, I would refer him to an orthopedist for a second opinion.

Well, he did not improve soon. Since he was still concerned, I provided the referral, without obtaining an MRI.

To perhaps everyone’s surprise—but most definitely mine—the patient was diagnosed with a complete ACL tear by the orthopedist (again, without MRI). He was scheduled for surgery at a later date.

What surprised me most was that someone could perform the way he was required to perform in the Navy for six years with a torn ACL. As a result of this case, I have not let a remote history of injury cloud my judgment since!

I was taught—and still believe—that obtaining a thorough history can direct you to a good working diagnosis. About 20 years ago, while in the Navy, I had a patient who showed me that I should not be fooled by a history that does not fit the current presentation.

The patient was a 34-year-old sailor with right-side knee pain, occurring intermittently for a long time but worsening in recent months. The pain did not prevent him from running, performing in the Navy’s semi-annual fitness test, or participating in departmental physical fitness activities.

However, his pain worsened after he was assigned to a ship, which required him to ascend and descend the steep shipboard stairs or ladders. He also complained of some intermittent buckling or “giving out.” But he was quite clear when he stated that he had sustained no recent injury to explain his condition.

The pain did not prevent him from running, performing in the Navy's semi-annual fitness test, or participating in departmental activities.

His history was notable for an injury he sustained six years earlier, while running. Although he could not remember the exact mechanism of injury, he recalled that his knee hurt and was swollen the next day. He was seen in medical, where he was given crutches, modified duty, and ibuprofen for a few days. After a relatively short time, his activity returned to normal.

I had seen a lot of knee pain on board ship, mostly of the patellar tendonitis or patellofemoral syndrome types, that could often be treated conservatively with temporary duty modification to avoid aggravating activity. More serious injuries—such as meniscal, collateral, or cruciate ligament tears—were associated with recent or acute injuries and a history including a suspicious mechanism of injury.

This patient’s complete knee exam was largely unremarkable, except his anterior drawer test seemed to have no distinct endpoint. When I compared the results with his asymptomatic left knee, I could not appreciate any difference.

So I relayed to him my thought process: If he had done something serious to his knee six years ago, it probably would have manifested sooner. As other clinicians did previously, I treated him conservatively with duty limitations and advised him that if he failed to improve soon, I would refer him to an orthopedist for a second opinion.

Well, he did not improve soon. Since he was still concerned, I provided the referral, without obtaining an MRI.

To perhaps everyone’s surprise—but most definitely mine—the patient was diagnosed with a complete ACL tear by the orthopedist (again, without MRI). He was scheduled for surgery at a later date.

What surprised me most was that someone could perform the way he was required to perform in the Navy for six years with a torn ACL. As a result of this case, I have not let a remote history of injury cloud my judgment since!

Russel Ware, MD, PhD

Photo courtesy of ASH

ORLANDO, FL—Hydroxyurea (HU) is noninferior to chronic blood transfusions for reducing the risk of stroke in children with sickle cell disease (SCD), results of the TWiTCH trial suggest.

The trial showed that daily doses of HU lower the transcranial Doppler (TCD) blood velocity in children with SCD to a similar degree as blood transfusions, thereby decreasing the risk of stroke.

Because of these findings, the trial was terminated early, in November of last year.

Last week, results from TWiTCH were presented at the 2015 ASH Annual Meeting (abstract 3*) and published in The Lancet. The study was funded by the National Heart Lung and Blood Institute.

“Stroke . . . is one of the most severe and catastrophic clinical events that occurs in children with sickle cell, with serious motor and cognitive sequelae,” said study investigator and ASH presenter Russell E. Ware, MD, of Cincinnati Children’s Hospital Medical Center in Ohio.

“With the advent of TCD, we now have the ability to identify high-risk children and use chronic transfusion therapy to prevent primary stroke.”

Dr Ware noted that results of the STOP trial showed that chronic transfusion reduced the risk of stroke in high-risk children with SCD, but the transfusions could not be stopped. The STOP 2 trial confirmed this, showing that stopping transfusions led to an increase in TCD blood velocity and stroke risk.

Because transfusions must be continued indefinitely and are associated with morbidity, an alternative stroke prevention strategy is needed, Dr Ware said. He and his colleagues conducted the TWiTCH trial to determine if HU would fit the bill.

Study design

For this phase 3 study, the researchers compared 24 months of transfusions to HU in children with SCD and abnormal TCD velocities. Study enrollment began in September 2011 and ended in April 2013.

All eligible children had received at least 12 months of transfusions prior to enrollment. They were randomized 1:1 to continue receiving transfusions or to receive the maximum-tolerated dose (MTD) of HU.

In the transfusion arm, the goal was to keep hemoglobin S levels below 30%, and iron overload was managed with daily oral chelation.

In the HU arm, the drug was escalated to the MTD, and children continued receiving transfusions until the MTD was achieved. Iron overload was managed with monthly phlebotomy.

The study had a noninferiority design, and the primary endpoint was the 24-month TCD velocity (with a noninferiority margin of 15 cm/sec). TCD velocities were obtained every 12 weeks and reviewed centrally. Local researchers were masked to the results.

Results

In all, 121 children were randomized—61 to transfusions and 60 to HU. Patient characteristics—baseline TCD velocities, age, duration of transfusion, etc.—were well balanced between the treatment arms.

“The average age of the patients was 9 or 10 years old, with about 3 or 4 years of transfusions coming in to the study,” Dr Ware noted.

In the transfusion arm, the children maintained a hemoglobin level of about 9 g/dL and hemoglobin S levels of less than 30%. Most patients received chelation with deferasirox at 26 ±6 mg/kg/day.

In the HU arm, 57 of 60 patients reached the MTD, which was 27 ± 4 mg/kg/day, on average. The median transfusion overlap was 6 months, the average absolute neutrophil count was 3.5 ± 1.6 x 10⁹/L, the average hemoglobin was about 9 g/dL, and fetal hemoglobin rose to about 25%. There were 756 phlebotomy procedures performed in 54 children.

“[In the HU arm,] very quickly after enrollment, the sickle hemoglobin rises, as the transfusions are weaned,” Dr Ware noted.

“Commensurately, the hemoglobin F rises as a protection. The neutrophil count and reticulocyte count drops, and those curves [counts in the HU and transfusion arms] diverge fairly quickly. The serum ferritin [curves] diverged as well.”

Early termination and noninferiority

Interim data analyses were scheduled to take place after one-third of the patients had exited the study and after two-thirds had exited. The first interim analysis demonstrated noninferiority, and the trial was closed early. An analysis was repeated after half of the patients had exited the study, and the trial was terminated.

At that point, 42 children had completed 24 months of treatment in the transfusion arm, 11 patients had truncated treatment, and 8 had early exits. Forty-one patients had completed 24 months of therapy in the HU arm, 13 had truncated treatment, and 6 had early exits.

The final TCD velocity (mean ± standard error) was 143 ± 1.6 cm/sec in the transfusion arm and 138 ± 1.6 cm/sec in the HU arm. The P value for noninferiority (in the intent-to-treat population) was 8.82 x 10^-16. By post-hoc analysis, the P value for superiority was 0.023.

Secondary endpoints

There were 29 new neurological events during the trial—12 in the transfusion arm and 17 in the HU arm. There were no new strokes, but there were 6 new transient ischemic attacks—3 in each arm.

There were no new cerebral infarcts in either arm. But there was 1 new progressive vasculopathy in the transfusion arm. And 1 child in the transfusion arm was withdrawn from the study for increasing TCD (>240 cm/sec).

Iron overload improved more in the HU arm than the transfusion arm, with a greater average change in both serum ferritin (P<0.001) and liver iron concentration (P=0.001).

Serious adverse events were more common in the HU arm than the transfusion arm—23 events in 9 patients and 10 events in 6 patients, respectively. But none of these events were thought to be related to study treatment or procedures.

The most common serious adverse event in both groups was vaso-occlusive pain—11 events in 5 HU-treated patients and 3 events in 1 transfusion-treated patient.

Dr Ware noted that there were no secondary leukemias associated with HU in this trial, and there is “a cumulative body of evidence” spanning 20 years that suggests the drug is not carcinogenic in this patient population.

*Data in the abstract differ from data presented at the meeting.

Russel Ware, MD, PhD

Photo courtesy of ASH

ORLANDO, FL—Hydroxyurea (HU) is noninferior to chronic blood transfusions for reducing the risk of stroke in children with sickle cell disease (SCD), results of the TWiTCH trial suggest.

The trial showed that daily doses of HU lower the transcranial Doppler (TCD) blood velocity in children with SCD to a similar degree as blood transfusions, thereby decreasing the risk of stroke.

Because of these findings, the trial was terminated early, in November of last year.

Last week, results from TWiTCH were presented at the 2015 ASH Annual Meeting (abstract 3*) and published in The Lancet. The study was funded by the National Heart Lung and Blood Institute.

“Stroke . . . is one of the most severe and catastrophic clinical events that occurs in children with sickle cell, with serious motor and cognitive sequelae,” said study investigator and ASH presenter Russell E. Ware, MD, of Cincinnati Children’s Hospital Medical Center in Ohio.

“With the advent of TCD, we now have the ability to identify high-risk children and use chronic transfusion therapy to prevent primary stroke.”

Dr Ware noted that results of the STOP trial showed that chronic transfusion reduced the risk of stroke in high-risk children with SCD, but the transfusions could not be stopped. The STOP 2 trial confirmed this, showing that stopping transfusions led to an increase in TCD blood velocity and stroke risk.

Because transfusions must be continued indefinitely and are associated with morbidity, an alternative stroke prevention strategy is needed, Dr Ware said. He and his colleagues conducted the TWiTCH trial to determine if HU would fit the bill.

Study design

For this phase 3 study, the researchers compared 24 months of transfusions to HU in children with SCD and abnormal TCD velocities. Study enrollment began in September 2011 and ended in April 2013.

All eligible children had received at least 12 months of transfusions prior to enrollment. They were randomized 1:1 to continue receiving transfusions or to receive the maximum-tolerated dose (MTD) of HU.

In the transfusion arm, the goal was to keep hemoglobin S levels below 30%, and iron overload was managed with daily oral chelation.

In the HU arm, the drug was escalated to the MTD, and children continued receiving transfusions until the MTD was achieved. Iron overload was managed with monthly phlebotomy.

The study had a noninferiority design, and the primary endpoint was the 24-month TCD velocity (with a noninferiority margin of 15 cm/sec). TCD velocities were obtained every 12 weeks and reviewed centrally. Local researchers were masked to the results.

Results

In all, 121 children were randomized—61 to transfusions and 60 to HU. Patient characteristics—baseline TCD velocities, age, duration of transfusion, etc.—were well balanced between the treatment arms.

“The average age of the patients was 9 or 10 years old, with about 3 or 4 years of transfusions coming in to the study,” Dr Ware noted.

In the transfusion arm, the children maintained a hemoglobin level of about 9 g/dL and hemoglobin S levels of less than 30%. Most patients received chelation with deferasirox at 26 ±6 mg/kg/day.

In the HU arm, 57 of 60 patients reached the MTD, which was 27 ± 4 mg/kg/day, on average. The median transfusion overlap was 6 months, the average absolute neutrophil count was 3.5 ± 1.6 x 10⁹/L, the average hemoglobin was about 9 g/dL, and fetal hemoglobin rose to about 25%. There were 756 phlebotomy procedures performed in 54 children.

“[In the HU arm,] very quickly after enrollment, the sickle hemoglobin rises, as the transfusions are weaned,” Dr Ware noted.

“Commensurately, the hemoglobin F rises as a protection. The neutrophil count and reticulocyte count drops, and those curves [counts in the HU and transfusion arms] diverge fairly quickly. The serum ferritin [curves] diverged as well.”

Early termination and noninferiority

Interim data analyses were scheduled to take place after one-third of the patients had exited the study and after two-thirds had exited. The first interim analysis demonstrated noninferiority, and the trial was closed early. An analysis was repeated after half of the patients had exited the study, and the trial was terminated.

At that point, 42 children had completed 24 months of treatment in the transfusion arm, 11 patients had truncated treatment, and 8 had early exits. Forty-one patients had completed 24 months of therapy in the HU arm, 13 had truncated treatment, and 6 had early exits.

The final TCD velocity (mean ± standard error) was 143 ± 1.6 cm/sec in the transfusion arm and 138 ± 1.6 cm/sec in the HU arm. The P value for noninferiority (in the intent-to-treat population) was 8.82 x 10^-16. By post-hoc analysis, the P value for superiority was 0.023.

Secondary endpoints

There were 29 new neurological events during the trial—12 in the transfusion arm and 17 in the HU arm. There were no new strokes, but there were 6 new transient ischemic attacks—3 in each arm.

There were no new cerebral infarcts in either arm. But there was 1 new progressive vasculopathy in the transfusion arm. And 1 child in the transfusion arm was withdrawn from the study for increasing TCD (>240 cm/sec).

Iron overload improved more in the HU arm than the transfusion arm, with a greater average change in both serum ferritin (P<0.001) and liver iron concentration (P=0.001).

Serious adverse events were more common in the HU arm than the transfusion arm—23 events in 9 patients and 10 events in 6 patients, respectively. But none of these events were thought to be related to study treatment or procedures.

The most common serious adverse event in both groups was vaso-occlusive pain—11 events in 5 HU-treated patients and 3 events in 1 transfusion-treated patient.

Dr Ware noted that there were no secondary leukemias associated with HU in this trial, and there is “a cumulative body of evidence” spanning 20 years that suggests the drug is not carcinogenic in this patient population.

*Data in the abstract differ from data presented at the meeting.

Russel Ware, MD, PhD

Photo courtesy of ASH

ORLANDO, FL—Hydroxyurea (HU) is noninferior to chronic blood transfusions for reducing the risk of stroke in children with sickle cell disease (SCD), results of the TWiTCH trial suggest.

The trial showed that daily doses of HU lower the transcranial Doppler (TCD) blood velocity in children with SCD to a similar degree as blood transfusions, thereby decreasing the risk of stroke.

Because of these findings, the trial was terminated early, in November of last year.

Last week, results from TWiTCH were presented at the 2015 ASH Annual Meeting (abstract 3*) and published in The Lancet. The study was funded by the National Heart Lung and Blood Institute.

“Stroke . . . is one of the most severe and catastrophic clinical events that occurs in children with sickle cell, with serious motor and cognitive sequelae,” said study investigator and ASH presenter Russell E. Ware, MD, of Cincinnati Children’s Hospital Medical Center in Ohio.

“With the advent of TCD, we now have the ability to identify high-risk children and use chronic transfusion therapy to prevent primary stroke.”

Dr Ware noted that results of the STOP trial showed that chronic transfusion reduced the risk of stroke in high-risk children with SCD, but the transfusions could not be stopped. The STOP 2 trial confirmed this, showing that stopping transfusions led to an increase in TCD blood velocity and stroke risk.

Because transfusions must be continued indefinitely and are associated with morbidity, an alternative stroke prevention strategy is needed, Dr Ware said. He and his colleagues conducted the TWiTCH trial to determine if HU would fit the bill.

Study design

For this phase 3 study, the researchers compared 24 months of transfusions to HU in children with SCD and abnormal TCD velocities. Study enrollment began in September 2011 and ended in April 2013.

All eligible children had received at least 12 months of transfusions prior to enrollment. They were randomized 1:1 to continue receiving transfusions or to receive the maximum-tolerated dose (MTD) of HU.

In the transfusion arm, the goal was to keep hemoglobin S levels below 30%, and iron overload was managed with daily oral chelation.

In the HU arm, the drug was escalated to the MTD, and children continued receiving transfusions until the MTD was achieved. Iron overload was managed with monthly phlebotomy.

The study had a noninferiority design, and the primary endpoint was the 24-month TCD velocity (with a noninferiority margin of 15 cm/sec). TCD velocities were obtained every 12 weeks and reviewed centrally. Local researchers were masked to the results.

Results

In all, 121 children were randomized—61 to transfusions and 60 to HU. Patient characteristics—baseline TCD velocities, age, duration of transfusion, etc.—were well balanced between the treatment arms.

“The average age of the patients was 9 or 10 years old, with about 3 or 4 years of transfusions coming in to the study,” Dr Ware noted.

In the transfusion arm, the children maintained a hemoglobin level of about 9 g/dL and hemoglobin S levels of less than 30%. Most patients received chelation with deferasirox at 26 ±6 mg/kg/day.

In the HU arm, 57 of 60 patients reached the MTD, which was 27 ± 4 mg/kg/day, on average. The median transfusion overlap was 6 months, the average absolute neutrophil count was 3.5 ± 1.6 x 10⁹/L, the average hemoglobin was about 9 g/dL, and fetal hemoglobin rose to about 25%. There were 756 phlebotomy procedures performed in 54 children.

“[In the HU arm,] very quickly after enrollment, the sickle hemoglobin rises, as the transfusions are weaned,” Dr Ware noted.

“Commensurately, the hemoglobin F rises as a protection. The neutrophil count and reticulocyte count drops, and those curves [counts in the HU and transfusion arms] diverge fairly quickly. The serum ferritin [curves] diverged as well.”

Early termination and noninferiority

Interim data analyses were scheduled to take place after one-third of the patients had exited the study and after two-thirds had exited. The first interim analysis demonstrated noninferiority, and the trial was closed early. An analysis was repeated after half of the patients had exited the study, and the trial was terminated.

At that point, 42 children had completed 24 months of treatment in the transfusion arm, 11 patients had truncated treatment, and 8 had early exits. Forty-one patients had completed 24 months of therapy in the HU arm, 13 had truncated treatment, and 6 had early exits.

The final TCD velocity (mean ± standard error) was 143 ± 1.6 cm/sec in the transfusion arm and 138 ± 1.6 cm/sec in the HU arm. The P value for noninferiority (in the intent-to-treat population) was 8.82 x 10^-16. By post-hoc analysis, the P value for superiority was 0.023.

Secondary endpoints

There were 29 new neurological events during the trial—12 in the transfusion arm and 17 in the HU arm. There were no new strokes, but there were 6 new transient ischemic attacks—3 in each arm.

There were no new cerebral infarcts in either arm. But there was 1 new progressive vasculopathy in the transfusion arm. And 1 child in the transfusion arm was withdrawn from the study for increasing TCD (>240 cm/sec).

Iron overload improved more in the HU arm than the transfusion arm, with a greater average change in both serum ferritin (P<0.001) and liver iron concentration (P=0.001).

Serious adverse events were more common in the HU arm than the transfusion arm—23 events in 9 patients and 10 events in 6 patients, respectively. But none of these events were thought to be related to study treatment or procedures.

The most common serious adverse event in both groups was vaso-occlusive pain—11 events in 5 HU-treated patients and 3 events in 1 transfusion-treated patient.

Dr Ware noted that there were no secondary leukemias associated with HU in this trial, and there is “a cumulative body of evidence” spanning 20 years that suggests the drug is not carcinogenic in this patient population.

*Data in the abstract differ from data presented at the meeting.

Team performing surgery

Photo by Piotr Bodzek

New research suggests that individualized feedback is more effective than group instructions for helping general surgery residents prevent venous thromboembolism (VTE) in their patients.

The single-center study showed that regular, one-on-one feedback and written report cards helped ensure the use of correct VTE prophylaxis more effectively than the usual group lectures that newly minted surgeons receive as part of their training.

These results were published in Annals of Surgery.

The study, conducted between July 2013 and March 2014, involved 49 general surgery residents in their first through fifth year of training at Johns Hopkins Hospital in Baltimore, Maryland.

For the first 3 months, residents received no personalized feedback. For the following 3 months, they received an electronic score card via email detailing their individual performance, including how many times they prescribed the appropriate VTE prophylaxis, how many times they failed to do so, and how they fared compared with others.

For the next 3 months, all residents continued to receive monthly scores, but subpar performers—those who failed to prescribe appropriate treatment to every single patient they cared for—also received one-on-one coaching from a senior resident.

In the span of 6 months, this approach decreased—from 3 to 0—the number of preventable complications among surgery patients (complications occurring in patients who didn’t receive appropriate VTE prophylaxis).

In the 3-month period prior to deploying the personalized feedback strategy, 7 out of 865 surgical patients developed complications. Three of the 7 cases were subsequently identified as preventable. In comparison, there were no such preventable complications after residents received individualized feedback.

As a result of the feedback, the number of patients getting appropriate treatment increased from 89% to 96%.

The number of residents who performed at 100% (prescribing the correct treatment to every patient all the time) went up from 22 (45%) to 38 (78%). Most of the prescription failures—19 out of 28 such cases—were clustered in a group of 4 residents.

“Our results show that personalized, concrete feedback can be a form of forced introspection that improves self-awareness and decision-making on clotting prophylaxis,” said Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine.

Beyond that, Dr Haut and his colleagues believe these results illustrate the notion that simple interventions can be harnessed to foster learning and improve performance among any frontline clinician.

“Speaking more broadly, why stop with residents? Why stop with anticlotting prophylaxis?” Dr Haut asked. “If our findings are borne out by larger studies, this approach could be harnessed to improve training and outcomes for anyone who touches a patient, from nurses to physicians to physical therapists.”

Team performing surgery

Photo by Piotr Bodzek

New research suggests that individualized feedback is more effective than group instructions for helping general surgery residents prevent venous thromboembolism (VTE) in their patients.

The single-center study showed that regular, one-on-one feedback and written report cards helped ensure the use of correct VTE prophylaxis more effectively than the usual group lectures that newly minted surgeons receive as part of their training.

These results were published in Annals of Surgery.

The study, conducted between July 2013 and March 2014, involved 49 general surgery residents in their first through fifth year of training at Johns Hopkins Hospital in Baltimore, Maryland.

For the first 3 months, residents received no personalized feedback. For the following 3 months, they received an electronic score card via email detailing their individual performance, including how many times they prescribed the appropriate VTE prophylaxis, how many times they failed to do so, and how they fared compared with others.

For the next 3 months, all residents continued to receive monthly scores, but subpar performers—those who failed to prescribe appropriate treatment to every single patient they cared for—also received one-on-one coaching from a senior resident.

In the span of 6 months, this approach decreased—from 3 to 0—the number of preventable complications among surgery patients (complications occurring in patients who didn’t receive appropriate VTE prophylaxis).

In the 3-month period prior to deploying the personalized feedback strategy, 7 out of 865 surgical patients developed complications. Three of the 7 cases were subsequently identified as preventable. In comparison, there were no such preventable complications after residents received individualized feedback.

As a result of the feedback, the number of patients getting appropriate treatment increased from 89% to 96%.

The number of residents who performed at 100% (prescribing the correct treatment to every patient all the time) went up from 22 (45%) to 38 (78%). Most of the prescription failures—19 out of 28 such cases—were clustered in a group of 4 residents.

“Our results show that personalized, concrete feedback can be a form of forced introspection that improves self-awareness and decision-making on clotting prophylaxis,” said Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine.

Beyond that, Dr Haut and his colleagues believe these results illustrate the notion that simple interventions can be harnessed to foster learning and improve performance among any frontline clinician.

“Speaking more broadly, why stop with residents? Why stop with anticlotting prophylaxis?” Dr Haut asked. “If our findings are borne out by larger studies, this approach could be harnessed to improve training and outcomes for anyone who touches a patient, from nurses to physicians to physical therapists.”

Team performing surgery

Photo by Piotr Bodzek

New research suggests that individualized feedback is more effective than group instructions for helping general surgery residents prevent venous thromboembolism (VTE) in their patients.

The single-center study showed that regular, one-on-one feedback and written report cards helped ensure the use of correct VTE prophylaxis more effectively than the usual group lectures that newly minted surgeons receive as part of their training.

These results were published in Annals of Surgery.

The study, conducted between July 2013 and March 2014, involved 49 general surgery residents in their first through fifth year of training at Johns Hopkins Hospital in Baltimore, Maryland.

For the first 3 months, residents received no personalized feedback. For the following 3 months, they received an electronic score card via email detailing their individual performance, including how many times they prescribed the appropriate VTE prophylaxis, how many times they failed to do so, and how they fared compared with others.

For the next 3 months, all residents continued to receive monthly scores, but subpar performers—those who failed to prescribe appropriate treatment to every single patient they cared for—also received one-on-one coaching from a senior resident.

In the span of 6 months, this approach decreased—from 3 to 0—the number of preventable complications among surgery patients (complications occurring in patients who didn’t receive appropriate VTE prophylaxis).

In the 3-month period prior to deploying the personalized feedback strategy, 7 out of 865 surgical patients developed complications. Three of the 7 cases were subsequently identified as preventable. In comparison, there were no such preventable complications after residents received individualized feedback.

As a result of the feedback, the number of patients getting appropriate treatment increased from 89% to 96%.

The number of residents who performed at 100% (prescribing the correct treatment to every patient all the time) went up from 22 (45%) to 38 (78%). Most of the prescription failures—19 out of 28 such cases—were clustered in a group of 4 residents.

“Our results show that personalized, concrete feedback can be a form of forced introspection that improves self-awareness and decision-making on clotting prophylaxis,” said Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine.

Beyond that, Dr Haut and his colleagues believe these results illustrate the notion that simple interventions can be harnessed to foster learning and improve performance among any frontline clinician.

“Speaking more broadly, why stop with residents? Why stop with anticlotting prophylaxis?” Dr Haut asked. “If our findings are borne out by larger studies, this approach could be harnessed to improve training and outcomes for anyone who touches a patient, from nurses to physicians to physical therapists.”

Port-wine stains (PWSs) are common congenital capillary vascular malformations with an incidence of 3 per 1000 neonates.¹ Rarely, acquired PWSs are seen, sometimes appearing following trauma.^2-5 Port-wine stains are diagnosed clinically and present as painless, partially or entirely blanchable pink patches that respect the median (midline) plane.⁶ Although histopathologic examination is not necessary for diagnosis of PWS, typical findings include dilated, ectatic capillaries.^7,8 Since it was first reported by Traub⁹ in 1939, more than 60 cases of acquired PWSs have been reported.¹⁰ A PubMed search of articles indexed for MEDLINE using the search terms acquired port-wine stain and port-wine stain and eczema yielded no cases of acquired PWS with associated eczematous changes and only 30 cases of congenital PWS with superimposed eczema.^11-18 We report the case of an acquired PWS with superimposed eczema in an 18-year-old man following penetrating abdominal trauma.

Case Report

An otherwise healthy 18-year-old man presented to our dermatology office for evaluation of an eruption that had developed at the site of an abdominal stab wound he sustained 2 to 3 years prior. One year after he was stabbed, the patient developed a nonpruritic, painless red patch located 1 cm anterior to the healed wound on the left abdomen. The patch gradually grew larger to involve the entire left abdomen, extending to the left lower back. The site of the healed stab wound also became raised and pruritic, and the patient noted another pruritic plaque that formed within the larger patch. The patient reported no other skin conditions prior to the current eruption. His medical history was notable for seasonal allergies and asthma, but no childhood eczema.

Physical examination revealed a healthy, well-nourished man with Fitzpatrick skin type IV. A red, purpuric, coalescent patch with slightly arcuate borders extending from the mid abdomen to the left posterior flank was noted. The left lateral aspect of the patch blanched with pressure and respected the median plane. Within the larger patch, a 4-cm×2-cm lichenified, slightly macerated, hyperpigmented plaque was noted at the site of the stab wound (Figure 1). Based on these clinical findings, a presumptive diagnosis of an acquired PWS with superimposed eczema was made.

Punch biopsy specimens were taken from the large vascular patch and the smaller lichenified plaque. Histopathologic examination of the vascular patch showed an increased number of small vessels in the superficial dermis with thickened vessel walls, ectatic lumens, and no vasculopathy, consistent with a vascular malformation or a reactive vascular proliferation (Figure 2). On histopathology, the plaque showed epidermal spongiosis and hyperplasia with serum crust and a papillary dermis containing a mixed inflammatory infiltrate with occasional eosinophils, consistent with an eczematous dermatitis (Figure 3). The histologic findings confirmed the clinical diagnosis.

The pruritic, lichenified plaque improved with application of triamcinolone ointment 0.1% twice daily for 2 weeks. Magnetic resonance imaging to rule out an underlying arteriovenous malformation was recommended, but the patient declined.

Comment

The exact cause of PWS is unknown. There have been a multitude of genomic suspects for congenital lesions, including a somatic activating mutation (ie, a mutation acquired during fetal development) of the GNAQ (guanine nucleotide binding protein [G protein], q polypeptide) gene, which may contribute to abnormal cell proliferation including the regulation of blood vessels, and inactivating mutations in the RASA1 (RAS p21 protein activator [GTPase activating protein] 1) gene, which controls endothelial cell organization.^19-22 Later mutations (ie, those occurring after the first trimester) may be more likely to result in isolated PWSs as opposed to syndromic PWSs.¹⁹ Whatever the source of genetic misinformation, it is thought that the diminished neuronal control of blood flow and the resulting alterations in dermal structure contribute to the pathogenesis of PWS and its associated histologic features.^7,23

The clinical and histopathologic features of acquired PWSs are indistinguishable from those of congenital lesions, indicating that different processes may lead to the same presentation.⁴ Abnormal innervation and decreased supportive stroma have both been identified as contributing factors in the development of congenital and acquired PWSs.^7,23-25 Rosen and Smoller²³ found that diminished nerve density affects vascular tone and caliber in PWSs and had hypothesized in a prior report that decreased perivascular Schwann cells may indicate abnormal sympathetic innervation.⁷ Since then, PWS has been shown to lack both somatic and sensory innervation.²⁴ Tsuji and Sawabe²⁵ indicated that alterations to the perivascular stroma, whether congenital or as a result of trauma, decrease support for vessels, leading to ectasia.

In addition to an acquired PWS, our patient also had associated eczema within the PWS. Eczematous lesions were absent elsewhere, and he did not have a history of childhood eczema. Our review of the literature yielded 8 studies since 1996 that collectively described 30 cases of eczema within PWSs.^11-18 Only 2 of these reports described adult patients with concomitant eczema and PWS and none described acquired PWS.^13,18

Few studies have addressed the relationship between PWSs and eczema. It is unclear if concomitant PWS and localized eczema are collision dermatoses or if a PWS may predispose the affected skin to eczema.^11-13 It has been hypothesized that the increased dermal vasculature in PWSs predisposes the skin to the development of eczema—more specifically, that ectasia may lead to increased inflammation.^12,17 The concept of the “immunocompromised district” proposed by Ruocco et al²⁶ is a unifying theory that may underlie the association noted between cases of trauma and later development of a PWS and superimposed eczematous dermatitis, such as in our case. Trauma is noted as one of a number of possible disruptive forces affecting both immunomodulation and neuromodulation within a local area of skin, leading to increased susceptibility of that district to various cutaneous diseases.²⁶

Although our patient’s eczema responded to conservative treatment with a topical steroid, several case series have reported success with laser therapy in the treatment of PWS while preventing recurrence of associated eczematous dermatitis.^12,17 Following the cessation of eczema treatment with topical steroid, which causes vasoconstriction, we suggest postponing laser therapy several weeks to allow resolution of vasoconstriction, thus providing enhanced therapeutic targeting with a vascular laser. Of particular relevance to our case, a recent study showed efficacy of the pulsed dye laser in treating PWSs in Fitzpatrick skin types IV and V.²⁷

Conclusion

Although acquired PWS is rare, it can present later in life as an acquired lesion at a site of previous trauma.^1-5 Congenital capillary malformations also can be associated with superimposed, localized eczema.^11-18 We present a rarely reported case of an acquired PWS with superimposed, localized eczema. As in cases of congenital PWS with concomitant eczema, the associated eczema in our case was responsive to topical corticosteroid therapy. Additionally, pulsed dye laser has been shown to treat PWSs while preventing the recurrence of eczema, and it has been deemed effective for individuals with darker skin types.^{12,17, 27} Further studies are needed to explore the relationship between PWS and eczema.

Port-wine stains (PWSs) are common congenital capillary vascular malformations with an incidence of 3 per 1000 neonates.¹ Rarely, acquired PWSs are seen, sometimes appearing following trauma.^2-5 Port-wine stains are diagnosed clinically and present as painless, partially or entirely blanchable pink patches that respect the median (midline) plane.⁶ Although histopathologic examination is not necessary for diagnosis of PWS, typical findings include dilated, ectatic capillaries.^7,8 Since it was first reported by Traub⁹ in 1939, more than 60 cases of acquired PWSs have been reported.¹⁰ A PubMed search of articles indexed for MEDLINE using the search terms acquired port-wine stain and port-wine stain and eczema yielded no cases of acquired PWS with associated eczematous changes and only 30 cases of congenital PWS with superimposed eczema.^11-18 We report the case of an acquired PWS with superimposed eczema in an 18-year-old man following penetrating abdominal trauma.

Case Report

An otherwise healthy 18-year-old man presented to our dermatology office for evaluation of an eruption that had developed at the site of an abdominal stab wound he sustained 2 to 3 years prior. One year after he was stabbed, the patient developed a nonpruritic, painless red patch located 1 cm anterior to the healed wound on the left abdomen. The patch gradually grew larger to involve the entire left abdomen, extending to the left lower back. The site of the healed stab wound also became raised and pruritic, and the patient noted another pruritic plaque that formed within the larger patch. The patient reported no other skin conditions prior to the current eruption. His medical history was notable for seasonal allergies and asthma, but no childhood eczema.

Physical examination revealed a healthy, well-nourished man with Fitzpatrick skin type IV. A red, purpuric, coalescent patch with slightly arcuate borders extending from the mid abdomen to the left posterior flank was noted. The left lateral aspect of the patch blanched with pressure and respected the median plane. Within the larger patch, a 4-cm×2-cm lichenified, slightly macerated, hyperpigmented plaque was noted at the site of the stab wound (Figure 1). Based on these clinical findings, a presumptive diagnosis of an acquired PWS with superimposed eczema was made.

Punch biopsy specimens were taken from the large vascular patch and the smaller lichenified plaque. Histopathologic examination of the vascular patch showed an increased number of small vessels in the superficial dermis with thickened vessel walls, ectatic lumens, and no vasculopathy, consistent with a vascular malformation or a reactive vascular proliferation (Figure 2). On histopathology, the plaque showed epidermal spongiosis and hyperplasia with serum crust and a papillary dermis containing a mixed inflammatory infiltrate with occasional eosinophils, consistent with an eczematous dermatitis (Figure 3). The histologic findings confirmed the clinical diagnosis.

The pruritic, lichenified plaque improved with application of triamcinolone ointment 0.1% twice daily for 2 weeks. Magnetic resonance imaging to rule out an underlying arteriovenous malformation was recommended, but the patient declined.

Comment

The exact cause of PWS is unknown. There have been a multitude of genomic suspects for congenital lesions, including a somatic activating mutation (ie, a mutation acquired during fetal development) of the GNAQ (guanine nucleotide binding protein [G protein], q polypeptide) gene, which may contribute to abnormal cell proliferation including the regulation of blood vessels, and inactivating mutations in the RASA1 (RAS p21 protein activator [GTPase activating protein] 1) gene, which controls endothelial cell organization.^19-22 Later mutations (ie, those occurring after the first trimester) may be more likely to result in isolated PWSs as opposed to syndromic PWSs.¹⁹ Whatever the source of genetic misinformation, it is thought that the diminished neuronal control of blood flow and the resulting alterations in dermal structure contribute to the pathogenesis of PWS and its associated histologic features.^7,23

The clinical and histopathologic features of acquired PWSs are indistinguishable from those of congenital lesions, indicating that different processes may lead to the same presentation.⁴ Abnormal innervation and decreased supportive stroma have both been identified as contributing factors in the development of congenital and acquired PWSs.^7,23-25 Rosen and Smoller²³ found that diminished nerve density affects vascular tone and caliber in PWSs and had hypothesized in a prior report that decreased perivascular Schwann cells may indicate abnormal sympathetic innervation.⁷ Since then, PWS has been shown to lack both somatic and sensory innervation.²⁴ Tsuji and Sawabe²⁵ indicated that alterations to the perivascular stroma, whether congenital or as a result of trauma, decrease support for vessels, leading to ectasia.

In addition to an acquired PWS, our patient also had associated eczema within the PWS. Eczematous lesions were absent elsewhere, and he did not have a history of childhood eczema. Our review of the literature yielded 8 studies since 1996 that collectively described 30 cases of eczema within PWSs.^11-18 Only 2 of these reports described adult patients with concomitant eczema and PWS and none described acquired PWS.^13,18

Few studies have addressed the relationship between PWSs and eczema. It is unclear if concomitant PWS and localized eczema are collision dermatoses or if a PWS may predispose the affected skin to eczema.^11-13 It has been hypothesized that the increased dermal vasculature in PWSs predisposes the skin to the development of eczema—more specifically, that ectasia may lead to increased inflammation.^12,17 The concept of the “immunocompromised district” proposed by Ruocco et al²⁶ is a unifying theory that may underlie the association noted between cases of trauma and later development of a PWS and superimposed eczematous dermatitis, such as in our case. Trauma is noted as one of a number of possible disruptive forces affecting both immunomodulation and neuromodulation within a local area of skin, leading to increased susceptibility of that district to various cutaneous diseases.²⁶

Although our patient’s eczema responded to conservative treatment with a topical steroid, several case series have reported success with laser therapy in the treatment of PWS while preventing recurrence of associated eczematous dermatitis.^12,17 Following the cessation of eczema treatment with topical steroid, which causes vasoconstriction, we suggest postponing laser therapy several weeks to allow resolution of vasoconstriction, thus providing enhanced therapeutic targeting with a vascular laser. Of particular relevance to our case, a recent study showed efficacy of the pulsed dye laser in treating PWSs in Fitzpatrick skin types IV and V.²⁷

Conclusion

Although acquired PWS is rare, it can present later in life as an acquired lesion at a site of previous trauma.^1-5 Congenital capillary malformations also can be associated with superimposed, localized eczema.^11-18 We present a rarely reported case of an acquired PWS with superimposed, localized eczema. As in cases of congenital PWS with concomitant eczema, the associated eczema in our case was responsive to topical corticosteroid therapy. Additionally, pulsed dye laser has been shown to treat PWSs while preventing the recurrence of eczema, and it has been deemed effective for individuals with darker skin types.^{12,17, 27} Further studies are needed to explore the relationship between PWS and eczema.

Port-wine stains (PWSs) are common congenital capillary vascular malformations with an incidence of 3 per 1000 neonates.¹ Rarely, acquired PWSs are seen, sometimes appearing following trauma.^2-5 Port-wine stains are diagnosed clinically and present as painless, partially or entirely blanchable pink patches that respect the median (midline) plane.⁶ Although histopathologic examination is not necessary for diagnosis of PWS, typical findings include dilated, ectatic capillaries.^7,8 Since it was first reported by Traub⁹ in 1939, more than 60 cases of acquired PWSs have been reported.¹⁰ A PubMed search of articles indexed for MEDLINE using the search terms acquired port-wine stain and port-wine stain and eczema yielded no cases of acquired PWS with associated eczematous changes and only 30 cases of congenital PWS with superimposed eczema.^11-18 We report the case of an acquired PWS with superimposed eczema in an 18-year-old man following penetrating abdominal trauma.

Case Report

An otherwise healthy 18-year-old man presented to our dermatology office for evaluation of an eruption that had developed at the site of an abdominal stab wound he sustained 2 to 3 years prior. One year after he was stabbed, the patient developed a nonpruritic, painless red patch located 1 cm anterior to the healed wound on the left abdomen. The patch gradually grew larger to involve the entire left abdomen, extending to the left lower back. The site of the healed stab wound also became raised and pruritic, and the patient noted another pruritic plaque that formed within the larger patch. The patient reported no other skin conditions prior to the current eruption. His medical history was notable for seasonal allergies and asthma, but no childhood eczema.

Physical examination revealed a healthy, well-nourished man with Fitzpatrick skin type IV. A red, purpuric, coalescent patch with slightly arcuate borders extending from the mid abdomen to the left posterior flank was noted. The left lateral aspect of the patch blanched with pressure and respected the median plane. Within the larger patch, a 4-cm×2-cm lichenified, slightly macerated, hyperpigmented plaque was noted at the site of the stab wound (Figure 1). Based on these clinical findings, a presumptive diagnosis of an acquired PWS with superimposed eczema was made.

Punch biopsy specimens were taken from the large vascular patch and the smaller lichenified plaque. Histopathologic examination of the vascular patch showed an increased number of small vessels in the superficial dermis with thickened vessel walls, ectatic lumens, and no vasculopathy, consistent with a vascular malformation or a reactive vascular proliferation (Figure 2). On histopathology, the plaque showed epidermal spongiosis and hyperplasia with serum crust and a papillary dermis containing a mixed inflammatory infiltrate with occasional eosinophils, consistent with an eczematous dermatitis (Figure 3). The histologic findings confirmed the clinical diagnosis.

The pruritic, lichenified plaque improved with application of triamcinolone ointment 0.1% twice daily for 2 weeks. Magnetic resonance imaging to rule out an underlying arteriovenous malformation was recommended, but the patient declined.

Comment

The exact cause of PWS is unknown. There have been a multitude of genomic suspects for congenital lesions, including a somatic activating mutation (ie, a mutation acquired during fetal development) of the GNAQ (guanine nucleotide binding protein [G protein], q polypeptide) gene, which may contribute to abnormal cell proliferation including the regulation of blood vessels, and inactivating mutations in the RASA1 (RAS p21 protein activator [GTPase activating protein] 1) gene, which controls endothelial cell organization.^19-22 Later mutations (ie, those occurring after the first trimester) may be more likely to result in isolated PWSs as opposed to syndromic PWSs.¹⁹ Whatever the source of genetic misinformation, it is thought that the diminished neuronal control of blood flow and the resulting alterations in dermal structure contribute to the pathogenesis of PWS and its associated histologic features.^7,23

The clinical and histopathologic features of acquired PWSs are indistinguishable from those of congenital lesions, indicating that different processes may lead to the same presentation.⁴ Abnormal innervation and decreased supportive stroma have both been identified as contributing factors in the development of congenital and acquired PWSs.^7,23-25 Rosen and Smoller²³ found that diminished nerve density affects vascular tone and caliber in PWSs and had hypothesized in a prior report that decreased perivascular Schwann cells may indicate abnormal sympathetic innervation.⁷ Since then, PWS has been shown to lack both somatic and sensory innervation.²⁴ Tsuji and Sawabe²⁵ indicated that alterations to the perivascular stroma, whether congenital or as a result of trauma, decrease support for vessels, leading to ectasia.

In addition to an acquired PWS, our patient also had associated eczema within the PWS. Eczematous lesions were absent elsewhere, and he did not have a history of childhood eczema. Our review of the literature yielded 8 studies since 1996 that collectively described 30 cases of eczema within PWSs.^11-18 Only 2 of these reports described adult patients with concomitant eczema and PWS and none described acquired PWS.^13,18

Few studies have addressed the relationship between PWSs and eczema. It is unclear if concomitant PWS and localized eczema are collision dermatoses or if a PWS may predispose the affected skin to eczema.^11-13 It has been hypothesized that the increased dermal vasculature in PWSs predisposes the skin to the development of eczema—more specifically, that ectasia may lead to increased inflammation.^12,17 The concept of the “immunocompromised district” proposed by Ruocco et al²⁶ is a unifying theory that may underlie the association noted between cases of trauma and later development of a PWS and superimposed eczematous dermatitis, such as in our case. Trauma is noted as one of a number of possible disruptive forces affecting both immunomodulation and neuromodulation within a local area of skin, leading to increased susceptibility of that district to various cutaneous diseases.²⁶

Although our patient’s eczema responded to conservative treatment with a topical steroid, several case series have reported success with laser therapy in the treatment of PWS while preventing recurrence of associated eczematous dermatitis.^12,17 Following the cessation of eczema treatment with topical steroid, which causes vasoconstriction, we suggest postponing laser therapy several weeks to allow resolution of vasoconstriction, thus providing enhanced therapeutic targeting with a vascular laser. Of particular relevance to our case, a recent study showed efficacy of the pulsed dye laser in treating PWSs in Fitzpatrick skin types IV and V.²⁷

Conclusion

Although acquired PWS is rare, it can present later in life as an acquired lesion at a site of previous trauma.^1-5 Congenital capillary malformations also can be associated with superimposed, localized eczema.^11-18 We present a rarely reported case of an acquired PWS with superimposed, localized eczema. As in cases of congenital PWS with concomitant eczema, the associated eczema in our case was responsive to topical corticosteroid therapy. Additionally, pulsed dye laser has been shown to treat PWSs while preventing the recurrence of eczema, and it has been deemed effective for individuals with darker skin types.^{12,17, 27} Further studies are needed to explore the relationship between PWS and eczema.