The Food and Drug Administration approved two new indications for the interleukin-17A inhibitor secukinumab (Cosentyx) – psoriatic arthritis in adults and ankylosing spondylitis in adults – on Jan. 15. These join the approval for moderate to severe plaque psoriasis in adults it received in January 2015, according to an announcement from the drug’s manufacturer, Novartis.

The approvals are based on the efficacy and safety outcomes from four placebo-controlled, phase III studies, which included more than 1,500 adult patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) who were biologic treatment naive or had an inadequate response or were intolerant to anti-TNF agents.

Pivotal phase III studies in the secukinumab clinical trial program, which provided key data for the submission, were MEASURE 1 and MEASURE 2 involving 590 patients with AS, and FUTURE 1 and FUTURE 2 involving 1,003 patients with PsA. Novartis continues to investigate the fully human monoclonal antibody against IL-17A for its potential in preventing radiographic progression of spinal and joint structural damage in AS and PsA patients, respectively.

The European Medicines Agency approved secukinumab for PsA and AS in November 2015.

[email protected]

The Food and Drug Administration approved two new indications for the interleukin-17A inhibitor secukinumab (Cosentyx) – psoriatic arthritis in adults and ankylosing spondylitis in adults – on Jan. 15. These join the approval for moderate to severe plaque psoriasis in adults it received in January 2015, according to an announcement from the drug’s manufacturer, Novartis.

The approvals are based on the efficacy and safety outcomes from four placebo-controlled, phase III studies, which included more than 1,500 adult patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) who were biologic treatment naive or had an inadequate response or were intolerant to anti-TNF agents.

Pivotal phase III studies in the secukinumab clinical trial program, which provided key data for the submission, were MEASURE 1 and MEASURE 2 involving 590 patients with AS, and FUTURE 1 and FUTURE 2 involving 1,003 patients with PsA. Novartis continues to investigate the fully human monoclonal antibody against IL-17A for its potential in preventing radiographic progression of spinal and joint structural damage in AS and PsA patients, respectively.

The European Medicines Agency approved secukinumab for PsA and AS in November 2015.

[email protected]

The Food and Drug Administration approved two new indications for the interleukin-17A inhibitor secukinumab (Cosentyx) – psoriatic arthritis in adults and ankylosing spondylitis in adults – on Jan. 15. These join the approval for moderate to severe plaque psoriasis in adults it received in January 2015, according to an announcement from the drug’s manufacturer, Novartis.

The approvals are based on the efficacy and safety outcomes from four placebo-controlled, phase III studies, which included more than 1,500 adult patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) who were biologic treatment naive or had an inadequate response or were intolerant to anti-TNF agents.

Pivotal phase III studies in the secukinumab clinical trial program, which provided key data for the submission, were MEASURE 1 and MEASURE 2 involving 590 patients with AS, and FUTURE 1 and FUTURE 2 involving 1,003 patients with PsA. Novartis continues to investigate the fully human monoclonal antibody against IL-17A for its potential in preventing radiographic progression of spinal and joint structural damage in AS and PsA patients, respectively.

The European Medicines Agency approved secukinumab for PsA and AS in November 2015.

[email protected]

In a letter dated Nov. 20, 2015, a particular insurance company reminded me that I need to think about healthcare costs. I got a breakdown of how often in the quarter I used proprietary vs. generic drugs, how I compared to other rheumatologists, and how I compared to other physicians. I also got a list of the drugs that I used and alternatives that I should be thinking about instead. In principle, this is not a terrible idea. But let me describe some glaring mistakes that show that these letters are in fact a contradiction in themselves. They are a huge waste of resources.

The letter suggested that my number one “prescribed brand drug with potential member savings opportunities” was Uloric, costing an average of $302 per prescription. The suggested “generic” alternative was Colcrys, leading to a “potential annual cost savings” of $600.

Third drug on my list? Colcrys, coming in at $165 per prescription with a potential annual savings of $300. Listed alternative: allopurinol.

We rheumatologists know that Colcrys is not an alternative to Uloric, and allopurinol is not an alternative to Colcrys. Also, suggesting an alternative only to suggest an alternative to that alternative is idiotic. Obviously, the letter is generated by a data-crunching algorithm. But an algorithm can only be as good as the programmer creating it.

As for my other proprietary prescriptions: Lyrica was the second on my list, and Celebrex the fourth. Let me explain why this is both annoying and inefficient. Before I could prescribe those drugs, this insurer made me jump through hoops to get them. In other words, there already exists in their database proof that I had already tried their recommended alternatives.

I can only conclude that within the bowels of health insurance corporate offices, and probably in more places than I care to imagine, there are people who are either incompetent or lazy, or both, making healthcare decisions.

So, to the health insurer: Forgive me if I ignore your reminder. I already know that healthcare costs are bloated. I am already quite conscientious about my prescribing practices. I think I can speak for all rheumatologists who receive these notices: You’re barking up the wrong tree.

Dr. Chan practices rheumatology in Pawtucket, R.I.

In a letter dated Nov. 20, 2015, a particular insurance company reminded me that I need to think about healthcare costs. I got a breakdown of how often in the quarter I used proprietary vs. generic drugs, how I compared to other rheumatologists, and how I compared to other physicians. I also got a list of the drugs that I used and alternatives that I should be thinking about instead. In principle, this is not a terrible idea. But let me describe some glaring mistakes that show that these letters are in fact a contradiction in themselves. They are a huge waste of resources.

The letter suggested that my number one “prescribed brand drug with potential member savings opportunities” was Uloric, costing an average of $302 per prescription. The suggested “generic” alternative was Colcrys, leading to a “potential annual cost savings” of $600.

Third drug on my list? Colcrys, coming in at $165 per prescription with a potential annual savings of $300. Listed alternative: allopurinol.

We rheumatologists know that Colcrys is not an alternative to Uloric, and allopurinol is not an alternative to Colcrys. Also, suggesting an alternative only to suggest an alternative to that alternative is idiotic. Obviously, the letter is generated by a data-crunching algorithm. But an algorithm can only be as good as the programmer creating it.

As for my other proprietary prescriptions: Lyrica was the second on my list, and Celebrex the fourth. Let me explain why this is both annoying and inefficient. Before I could prescribe those drugs, this insurer made me jump through hoops to get them. In other words, there already exists in their database proof that I had already tried their recommended alternatives.

I can only conclude that within the bowels of health insurance corporate offices, and probably in more places than I care to imagine, there are people who are either incompetent or lazy, or both, making healthcare decisions.

So, to the health insurer: Forgive me if I ignore your reminder. I already know that healthcare costs are bloated. I am already quite conscientious about my prescribing practices. I think I can speak for all rheumatologists who receive these notices: You’re barking up the wrong tree.

Dr. Chan practices rheumatology in Pawtucket, R.I.

In a letter dated Nov. 20, 2015, a particular insurance company reminded me that I need to think about healthcare costs. I got a breakdown of how often in the quarter I used proprietary vs. generic drugs, how I compared to other rheumatologists, and how I compared to other physicians. I also got a list of the drugs that I used and alternatives that I should be thinking about instead. In principle, this is not a terrible idea. But let me describe some glaring mistakes that show that these letters are in fact a contradiction in themselves. They are a huge waste of resources.

The letter suggested that my number one “prescribed brand drug with potential member savings opportunities” was Uloric, costing an average of $302 per prescription. The suggested “generic” alternative was Colcrys, leading to a “potential annual cost savings” of $600.

Third drug on my list? Colcrys, coming in at $165 per prescription with a potential annual savings of $300. Listed alternative: allopurinol.

We rheumatologists know that Colcrys is not an alternative to Uloric, and allopurinol is not an alternative to Colcrys. Also, suggesting an alternative only to suggest an alternative to that alternative is idiotic. Obviously, the letter is generated by a data-crunching algorithm. But an algorithm can only be as good as the programmer creating it.

As for my other proprietary prescriptions: Lyrica was the second on my list, and Celebrex the fourth. Let me explain why this is both annoying and inefficient. Before I could prescribe those drugs, this insurer made me jump through hoops to get them. In other words, there already exists in their database proof that I had already tried their recommended alternatives.

I can only conclude that within the bowels of health insurance corporate offices, and probably in more places than I care to imagine, there are people who are either incompetent or lazy, or both, making healthcare decisions.

So, to the health insurer: Forgive me if I ignore your reminder. I already know that healthcare costs are bloated. I am already quite conscientious about my prescribing practices. I think I can speak for all rheumatologists who receive these notices: You’re barking up the wrong tree.

Dr. Chan practices rheumatology in Pawtucket, R.I.

To the Editor:

There are a wide variety of zoonotic diseases that can be transmitted from birds to humans. Pigeons, chickens, starlings, canaries, and parakeets are known reservoirs of one particular zoonotic infection caused by the parasitic arthropod Dermanyssus gallinae.¹ Dermanyssus gallinae (chicken mite) and Ornithonyssus sylviarum (northern fowl mite) are collectively referred to as bird mites. When these mites are unable to take blood meals from birds, they search out alternative hosts²; in humans, this often leads to the development of pruritic dermatitis.³

A 30-year-old woman presented to our clinic for evaluation of severe generalized pruritus accompanied by a sensation of “bugs on the skin” of 2 weeks’ duration. She noted the pruritus worsened when she was sitting outside on her porch. A few days prior to presentation, she noticed a small, “pinpoint-sized bug” on her arm (<1 mm in size), which she brought in for identification (Figure).

The bug was identified as a bird mite (Dermanyssus gallinae) on light microscopy, which was later confirmed by a medical entomologist. After the diagnosis of bird mite dermatitis was made, the patient noted there was a nest of starlings above the light on her porch. When she later investigated the nest following the current presentation, she noted many small mites crawling around the nest. The nest was removed and her symptoms resolved completely within 2 weeks without treatment.

Bird mites belong to the Arachnida class, under the order Acari. In 1958, Williams⁴ noted D gallinae’s ability to feed on human blood. Bird mites have 5 stages of development: egg, larva, protonymph, deutonymph, and adult. Protonymphs, deutonymphs, and adults can bite humans for a blood meal.⁵ Bird mites range from 0.3 to 1 mm in length and have nonsegmented, egg-shaped bodies with 4 pairs of legs. Before taking a blood meal, bird mites generally are a translucent brown color, and appear red when engorged with blood.² Their small size makes them barely visible to the unaided eye. Of note, D gallinae and O sylviarum can be distinguished from each other based on subtle differences in morphology; for instance, the posterior genitoventral shield of O sylviarum is narrowly rounded, whereas it is broadly rounded in D gallinae. The dorsal shield of O sylviarum abruptly narrows posteriorly but is more smoothly narrowed in D gallinae.⁶ Additionally, O sylviarum tends to cause more irritating dermatitis in humans than D gallinae.³

Although they can be found worldwide, D gallinae and O sylviarum undergo optimal development at 20°C to 25°C and 70% humidity.^3,5,7 Bird mites generally develop over the course of 5 to 12 days; thus, the population of bird mites in a single nest may grow to the tens of thousands before young birds permanently leave. Dermanyssus gallinae can survive for months in abandoned nests without a blood meal, while O sylviarum can survive for several weeks.⁸ It is important to note that humans are not ideal hosts for bird mites, as they are unable to survive for extended periods of time or reproduce on human hosts.⁹

When bird mites are no longer able to obtain blood meals from nesting birds, they begin their nocturnal migration to find suitable hosts. Bird nests generally are abandoned in late spring; thus, most patients with bird mite dermatitis present to clinics with bird mite dermatitis in late spring and early summer.¹⁰ Mites often travel through cracks in doors, floors, walls, and ceilings but also can gain access to living areas through ventilation ducts and air conditioning units.¹ The mite’s bite and crawling on the skin is sometimes noticed by the patient. In general, however, intense itching is not observed until about 1 to 3 days after the mite makes contact with the skin. Patients often report that pruritus is worst at night.⁹ Papules and vesicles (bite reactions) may accompany the pruritus, and physicians commonly find bloody crust and excoriations in particularly pruritic areas.⁵ Urticarial plaques and diffuse erythema occasionally also may be present.⁹ Bird mites sometimes can be scraped from the skin and observed under light microscopy.¹¹ Blood eosinophilia is not found in bird mite dermatitis. On histologic examination, perivascular eosinophilic infiltration can be seen in the upper part of the dermis.¹²

The differential diagnosis in patients with pruritic dermatitis of unknown origin generally includes scabies, pediculosis, and dermatitis caused by other types of infestation. However, unlike scabies, bird mites do not cause burrows to form on the skin.⁹ The presence of a bird’s nest near the area where the patient lives places bird mite dermatitis higher in the differential.

Dermanyssus gallinae is a known vector of bacteria (eg, Salmonella, Shigella, Staphylococcus, Spirochaete, Rickettsia, Pasteurella, Chlamydia psittaci, Erysipelothrix rhusiopathiae) as well as the viruses that cause Eastern and Western equine encephalitis and St. Louis encephalitis. Transmission of these bacteria and viruses is known in birds, but transmission to humans has not been reported.^2,5,9,13

The management of bird mite dermatitis is straightforward. Usually mites can be successfully removed from the skin simply by bathing. Symptomatic treatment for bites with antihistamines and topical corticosteroids is sometimes but not always necessary.² Unlike scabies or lice, there is no need for treatment with lindane.¹ In terms of the prevention of additional bites, any bird nests located near living areas should be removed. Because bird mites often retreat back to nests between blood meals, insecticide sprays generally are unnecessary in interior spaces. Synthetic pyrethroids (eg, bifenthrin, cyfluthrin, cypermethrin, deltamethrin, cyhalothrin) can be used outside and in attics where nests may be located.^2,14,15 However, the ability of bird mites to develop resistance to repeated chemical control could become a future concern.¹⁶

Research regarding the true incidence of bird mite dermatitis is lacking. Some researchers believe that the condition is underreported, possibly due to its uncommon environmental origin.³ Reports of bird mite dermatitis in the literature also are scarce. Our case demonstrates the importance of taking a thorough patient history to rule out exposure to bird mites. All patients with pruritic dermatitis of unknown origin should be questioned about possible contact or proximity to bird nests. These simple questions can lead to the correct diagnosis and a treatment plan that will quickly and effectively resolve the pruritic skin eruption.

To the Editor:

There are a wide variety of zoonotic diseases that can be transmitted from birds to humans. Pigeons, chickens, starlings, canaries, and parakeets are known reservoirs of one particular zoonotic infection caused by the parasitic arthropod Dermanyssus gallinae.¹ Dermanyssus gallinae (chicken mite) and Ornithonyssus sylviarum (northern fowl mite) are collectively referred to as bird mites. When these mites are unable to take blood meals from birds, they search out alternative hosts²; in humans, this often leads to the development of pruritic dermatitis.³

A 30-year-old woman presented to our clinic for evaluation of severe generalized pruritus accompanied by a sensation of “bugs on the skin” of 2 weeks’ duration. She noted the pruritus worsened when she was sitting outside on her porch. A few days prior to presentation, she noticed a small, “pinpoint-sized bug” on her arm (<1 mm in size), which she brought in for identification (Figure).

The bug was identified as a bird mite (Dermanyssus gallinae) on light microscopy, which was later confirmed by a medical entomologist. After the diagnosis of bird mite dermatitis was made, the patient noted there was a nest of starlings above the light on her porch. When she later investigated the nest following the current presentation, she noted many small mites crawling around the nest. The nest was removed and her symptoms resolved completely within 2 weeks without treatment.

Bird mites belong to the Arachnida class, under the order Acari. In 1958, Williams⁴ noted D gallinae’s ability to feed on human blood. Bird mites have 5 stages of development: egg, larva, protonymph, deutonymph, and adult. Protonymphs, deutonymphs, and adults can bite humans for a blood meal.⁵ Bird mites range from 0.3 to 1 mm in length and have nonsegmented, egg-shaped bodies with 4 pairs of legs. Before taking a blood meal, bird mites generally are a translucent brown color, and appear red when engorged with blood.² Their small size makes them barely visible to the unaided eye. Of note, D gallinae and O sylviarum can be distinguished from each other based on subtle differences in morphology; for instance, the posterior genitoventral shield of O sylviarum is narrowly rounded, whereas it is broadly rounded in D gallinae. The dorsal shield of O sylviarum abruptly narrows posteriorly but is more smoothly narrowed in D gallinae.⁶ Additionally, O sylviarum tends to cause more irritating dermatitis in humans than D gallinae.³

Although they can be found worldwide, D gallinae and O sylviarum undergo optimal development at 20°C to 25°C and 70% humidity.^3,5,7 Bird mites generally develop over the course of 5 to 12 days; thus, the population of bird mites in a single nest may grow to the tens of thousands before young birds permanently leave. Dermanyssus gallinae can survive for months in abandoned nests without a blood meal, while O sylviarum can survive for several weeks.⁸ It is important to note that humans are not ideal hosts for bird mites, as they are unable to survive for extended periods of time or reproduce on human hosts.⁹

When bird mites are no longer able to obtain blood meals from nesting birds, they begin their nocturnal migration to find suitable hosts. Bird nests generally are abandoned in late spring; thus, most patients with bird mite dermatitis present to clinics with bird mite dermatitis in late spring and early summer.¹⁰ Mites often travel through cracks in doors, floors, walls, and ceilings but also can gain access to living areas through ventilation ducts and air conditioning units.¹ The mite’s bite and crawling on the skin is sometimes noticed by the patient. In general, however, intense itching is not observed until about 1 to 3 days after the mite makes contact with the skin. Patients often report that pruritus is worst at night.⁹ Papules and vesicles (bite reactions) may accompany the pruritus, and physicians commonly find bloody crust and excoriations in particularly pruritic areas.⁵ Urticarial plaques and diffuse erythema occasionally also may be present.⁹ Bird mites sometimes can be scraped from the skin and observed under light microscopy.¹¹ Blood eosinophilia is not found in bird mite dermatitis. On histologic examination, perivascular eosinophilic infiltration can be seen in the upper part of the dermis.¹²

The differential diagnosis in patients with pruritic dermatitis of unknown origin generally includes scabies, pediculosis, and dermatitis caused by other types of infestation. However, unlike scabies, bird mites do not cause burrows to form on the skin.⁹ The presence of a bird’s nest near the area where the patient lives places bird mite dermatitis higher in the differential.

Dermanyssus gallinae is a known vector of bacteria (eg, Salmonella, Shigella, Staphylococcus, Spirochaete, Rickettsia, Pasteurella, Chlamydia psittaci, Erysipelothrix rhusiopathiae) as well as the viruses that cause Eastern and Western equine encephalitis and St. Louis encephalitis. Transmission of these bacteria and viruses is known in birds, but transmission to humans has not been reported.^2,5,9,13

The management of bird mite dermatitis is straightforward. Usually mites can be successfully removed from the skin simply by bathing. Symptomatic treatment for bites with antihistamines and topical corticosteroids is sometimes but not always necessary.² Unlike scabies or lice, there is no need for treatment with lindane.¹ In terms of the prevention of additional bites, any bird nests located near living areas should be removed. Because bird mites often retreat back to nests between blood meals, insecticide sprays generally are unnecessary in interior spaces. Synthetic pyrethroids (eg, bifenthrin, cyfluthrin, cypermethrin, deltamethrin, cyhalothrin) can be used outside and in attics where nests may be located.^2,14,15 However, the ability of bird mites to develop resistance to repeated chemical control could become a future concern.¹⁶

Research regarding the true incidence of bird mite dermatitis is lacking. Some researchers believe that the condition is underreported, possibly due to its uncommon environmental origin.³ Reports of bird mite dermatitis in the literature also are scarce. Our case demonstrates the importance of taking a thorough patient history to rule out exposure to bird mites. All patients with pruritic dermatitis of unknown origin should be questioned about possible contact or proximity to bird nests. These simple questions can lead to the correct diagnosis and a treatment plan that will quickly and effectively resolve the pruritic skin eruption.

To the Editor:

There are a wide variety of zoonotic diseases that can be transmitted from birds to humans. Pigeons, chickens, starlings, canaries, and parakeets are known reservoirs of one particular zoonotic infection caused by the parasitic arthropod Dermanyssus gallinae.¹ Dermanyssus gallinae (chicken mite) and Ornithonyssus sylviarum (northern fowl mite) are collectively referred to as bird mites. When these mites are unable to take blood meals from birds, they search out alternative hosts²; in humans, this often leads to the development of pruritic dermatitis.³

A 30-year-old woman presented to our clinic for evaluation of severe generalized pruritus accompanied by a sensation of “bugs on the skin” of 2 weeks’ duration. She noted the pruritus worsened when she was sitting outside on her porch. A few days prior to presentation, she noticed a small, “pinpoint-sized bug” on her arm (<1 mm in size), which she brought in for identification (Figure).

The bug was identified as a bird mite (Dermanyssus gallinae) on light microscopy, which was later confirmed by a medical entomologist. After the diagnosis of bird mite dermatitis was made, the patient noted there was a nest of starlings above the light on her porch. When she later investigated the nest following the current presentation, she noted many small mites crawling around the nest. The nest was removed and her symptoms resolved completely within 2 weeks without treatment.

Bird mites belong to the Arachnida class, under the order Acari. In 1958, Williams⁴ noted D gallinae’s ability to feed on human blood. Bird mites have 5 stages of development: egg, larva, protonymph, deutonymph, and adult. Protonymphs, deutonymphs, and adults can bite humans for a blood meal.⁵ Bird mites range from 0.3 to 1 mm in length and have nonsegmented, egg-shaped bodies with 4 pairs of legs. Before taking a blood meal, bird mites generally are a translucent brown color, and appear red when engorged with blood.² Their small size makes them barely visible to the unaided eye. Of note, D gallinae and O sylviarum can be distinguished from each other based on subtle differences in morphology; for instance, the posterior genitoventral shield of O sylviarum is narrowly rounded, whereas it is broadly rounded in D gallinae. The dorsal shield of O sylviarum abruptly narrows posteriorly but is more smoothly narrowed in D gallinae.⁶ Additionally, O sylviarum tends to cause more irritating dermatitis in humans than D gallinae.³

Although they can be found worldwide, D gallinae and O sylviarum undergo optimal development at 20°C to 25°C and 70% humidity.^3,5,7 Bird mites generally develop over the course of 5 to 12 days; thus, the population of bird mites in a single nest may grow to the tens of thousands before young birds permanently leave. Dermanyssus gallinae can survive for months in abandoned nests without a blood meal, while O sylviarum can survive for several weeks.⁸ It is important to note that humans are not ideal hosts for bird mites, as they are unable to survive for extended periods of time or reproduce on human hosts.⁹

When bird mites are no longer able to obtain blood meals from nesting birds, they begin their nocturnal migration to find suitable hosts. Bird nests generally are abandoned in late spring; thus, most patients with bird mite dermatitis present to clinics with bird mite dermatitis in late spring and early summer.¹⁰ Mites often travel through cracks in doors, floors, walls, and ceilings but also can gain access to living areas through ventilation ducts and air conditioning units.¹ The mite’s bite and crawling on the skin is sometimes noticed by the patient. In general, however, intense itching is not observed until about 1 to 3 days after the mite makes contact with the skin. Patients often report that pruritus is worst at night.⁹ Papules and vesicles (bite reactions) may accompany the pruritus, and physicians commonly find bloody crust and excoriations in particularly pruritic areas.⁵ Urticarial plaques and diffuse erythema occasionally also may be present.⁹ Bird mites sometimes can be scraped from the skin and observed under light microscopy.¹¹ Blood eosinophilia is not found in bird mite dermatitis. On histologic examination, perivascular eosinophilic infiltration can be seen in the upper part of the dermis.¹²

The differential diagnosis in patients with pruritic dermatitis of unknown origin generally includes scabies, pediculosis, and dermatitis caused by other types of infestation. However, unlike scabies, bird mites do not cause burrows to form on the skin.⁹ The presence of a bird’s nest near the area where the patient lives places bird mite dermatitis higher in the differential.

Dermanyssus gallinae is a known vector of bacteria (eg, Salmonella, Shigella, Staphylococcus, Spirochaete, Rickettsia, Pasteurella, Chlamydia psittaci, Erysipelothrix rhusiopathiae) as well as the viruses that cause Eastern and Western equine encephalitis and St. Louis encephalitis. Transmission of these bacteria and viruses is known in birds, but transmission to humans has not been reported.^2,5,9,13

The management of bird mite dermatitis is straightforward. Usually mites can be successfully removed from the skin simply by bathing. Symptomatic treatment for bites with antihistamines and topical corticosteroids is sometimes but not always necessary.² Unlike scabies or lice, there is no need for treatment with lindane.¹ In terms of the prevention of additional bites, any bird nests located near living areas should be removed. Because bird mites often retreat back to nests between blood meals, insecticide sprays generally are unnecessary in interior spaces. Synthetic pyrethroids (eg, bifenthrin, cyfluthrin, cypermethrin, deltamethrin, cyhalothrin) can be used outside and in attics where nests may be located.^2,14,15 However, the ability of bird mites to develop resistance to repeated chemical control could become a future concern.¹⁶

Research regarding the true incidence of bird mite dermatitis is lacking. Some researchers believe that the condition is underreported, possibly due to its uncommon environmental origin.³ Reports of bird mite dermatitis in the literature also are scarce. Our case demonstrates the importance of taking a thorough patient history to rule out exposure to bird mites. All patients with pruritic dermatitis of unknown origin should be questioned about possible contact or proximity to bird nests. These simple questions can lead to the correct diagnosis and a treatment plan that will quickly and effectively resolve the pruritic skin eruption.

Years ago, I had a colleague who’d once worked for the prison system, treating people who were some of the more dangerous elements of society.

Once I asked if he’d ever gotten curious about what they were in for. He answered that, while he was always curious, he never asked. He felt as if knowing might prejudice his care. Since a key part of being a doctor is being impartial and objective, he was afraid that knowing about their previous heinous behavior would make him less concerned about treating them properly. And I agree.

When I was a younger doctor, I’d sometimes Google patients. I’d be curious about their backgrounds, or I wanted to see if there was anything on their social media I should be aware of they hadn’t told me. Maybe something like “I scored 20 percs off a neurologist today!”

I stopped after a while, and haven’t done it since. I never saw anything that would affect my treatment plan. I did, however, often learn about their political and religious views, some of which were distasteful to me. I respect anyone’s right to have an opinion, but that doesn’t mean I have to agree with them.

Like I’ve written before, I specifically avoid any discussion of religion or politics with my patients because doing so can lead to antagonism and dislike, with the potential to impact my objectivity.

The same can be said about what else you might learn online: their habits and hobbies, unflattering pictures, stories about their backgrounds, etc. All of those things can, in the right circumstances, lead to a bias against them. Perhaps it may just exist subconsciously, but it’s still there. A recent Medscape report noted the number of physicians who admitted having biases against patients, as well as the things that can trigger our visceral reactions: emotional state, weight, and intelligence, to name a few. We try hard to overcome negative feelings to provide proper care, but are still human and 100% objectivity is often difficult.

To me, Googling a patient became the same thing as asking inmates what they’d been locked up for: You learn things about them that might change how you view and care for them.

The only way to effectively treat patients is to see them as just people, like yourself. Knowing too much about their background that isn’t medically relevant is just asking for trouble.

I’d rather know less and be more objective.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Years ago, I had a colleague who’d once worked for the prison system, treating people who were some of the more dangerous elements of society.

Once I asked if he’d ever gotten curious about what they were in for. He answered that, while he was always curious, he never asked. He felt as if knowing might prejudice his care. Since a key part of being a doctor is being impartial and objective, he was afraid that knowing about their previous heinous behavior would make him less concerned about treating them properly. And I agree.

When I was a younger doctor, I’d sometimes Google patients. I’d be curious about their backgrounds, or I wanted to see if there was anything on their social media I should be aware of they hadn’t told me. Maybe something like “I scored 20 percs off a neurologist today!”

I stopped after a while, and haven’t done it since. I never saw anything that would affect my treatment plan. I did, however, often learn about their political and religious views, some of which were distasteful to me. I respect anyone’s right to have an opinion, but that doesn’t mean I have to agree with them.

Like I’ve written before, I specifically avoid any discussion of religion or politics with my patients because doing so can lead to antagonism and dislike, with the potential to impact my objectivity.

The same can be said about what else you might learn online: their habits and hobbies, unflattering pictures, stories about their backgrounds, etc. All of those things can, in the right circumstances, lead to a bias against them. Perhaps it may just exist subconsciously, but it’s still there. A recent Medscape report noted the number of physicians who admitted having biases against patients, as well as the things that can trigger our visceral reactions: emotional state, weight, and intelligence, to name a few. We try hard to overcome negative feelings to provide proper care, but are still human and 100% objectivity is often difficult.

To me, Googling a patient became the same thing as asking inmates what they’d been locked up for: You learn things about them that might change how you view and care for them.

The only way to effectively treat patients is to see them as just people, like yourself. Knowing too much about their background that isn’t medically relevant is just asking for trouble.

I’d rather know less and be more objective.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Years ago, I had a colleague who’d once worked for the prison system, treating people who were some of the more dangerous elements of society.

Once I asked if he’d ever gotten curious about what they were in for. He answered that, while he was always curious, he never asked. He felt as if knowing might prejudice his care. Since a key part of being a doctor is being impartial and objective, he was afraid that knowing about their previous heinous behavior would make him less concerned about treating them properly. And I agree.

When I was a younger doctor, I’d sometimes Google patients. I’d be curious about their backgrounds, or I wanted to see if there was anything on their social media I should be aware of they hadn’t told me. Maybe something like “I scored 20 percs off a neurologist today!”

I stopped after a while, and haven’t done it since. I never saw anything that would affect my treatment plan. I did, however, often learn about their political and religious views, some of which were distasteful to me. I respect anyone’s right to have an opinion, but that doesn’t mean I have to agree with them.

Like I’ve written before, I specifically avoid any discussion of religion or politics with my patients because doing so can lead to antagonism and dislike, with the potential to impact my objectivity.

The same can be said about what else you might learn online: their habits and hobbies, unflattering pictures, stories about their backgrounds, etc. All of those things can, in the right circumstances, lead to a bias against them. Perhaps it may just exist subconsciously, but it’s still there. A recent Medscape report noted the number of physicians who admitted having biases against patients, as well as the things that can trigger our visceral reactions: emotional state, weight, and intelligence, to name a few. We try hard to overcome negative feelings to provide proper care, but are still human and 100% objectivity is often difficult.

To me, Googling a patient became the same thing as asking inmates what they’d been locked up for: You learn things about them that might change how you view and care for them.

The only way to effectively treat patients is to see them as just people, like yourself. Knowing too much about their background that isn’t medically relevant is just asking for trouble.

I’d rather know less and be more objective.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Clinical question: Is there an improved 30-day mortality rate if patients receive blood transfusion at higher hematocrit values after postoperative myocardial infarction (MI)?

Background: Prior studies evaluating patients with a history of coronary artery disease (CAD) who undergo non-cardiac surgery have shown similar mortality outcomes with liberal and restrictive transfusion strategies. Data are lacking for transfusion strategies in patients with CAD who experience postoperative MI after non-cardiac surgeries.

Study design: Retrospective cohort.

Setting: Veterans Affairs health system.

Synopsis: The study included 7,361 patients with a history of CAD who underwent non-cardiac surgery whose postoperative hematocrit was between 20% and 30%. Patients were stratified by postoperative hematocrit nadir and presence of postoperative MI. In patients with postoperative MI, transfusion was associated with lower mortality with hematocrit nadir of 20%–24% but not with hematocrit of 24%–27% or 27%–30%. In patients without postoperative MI, transfusion was associated with higher mortality in patients with hematocrit of 27%–30%.

This retrospective study was limited to the VA population of mostly male patients. The sample size was limited. The study was unable to determine if postoperative blood transfusion is a risk for developing MI.

Bottom line: Patients with a history of CAD and MI who have a postoperative MI following non-cardiac surgery may benefit from higher blood transfusion thresholds; however, further controlled studies are needed.

Citation: Hollis RH, Singeltary BA, McMurtrie JT, et al. Blood transfusion and 30-day mortality in patients with coronary artery disease and anemia following noncardiac surgery [published online ahead of print October 7, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.3420.

Clinical question: Is there an improved 30-day mortality rate if patients receive blood transfusion at higher hematocrit values after postoperative myocardial infarction (MI)?

Background: Prior studies evaluating patients with a history of coronary artery disease (CAD) who undergo non-cardiac surgery have shown similar mortality outcomes with liberal and restrictive transfusion strategies. Data are lacking for transfusion strategies in patients with CAD who experience postoperative MI after non-cardiac surgeries.

Study design: Retrospective cohort.

Setting: Veterans Affairs health system.

Synopsis: The study included 7,361 patients with a history of CAD who underwent non-cardiac surgery whose postoperative hematocrit was between 20% and 30%. Patients were stratified by postoperative hematocrit nadir and presence of postoperative MI. In patients with postoperative MI, transfusion was associated with lower mortality with hematocrit nadir of 20%–24% but not with hematocrit of 24%–27% or 27%–30%. In patients without postoperative MI, transfusion was associated with higher mortality in patients with hematocrit of 27%–30%.

This retrospective study was limited to the VA population of mostly male patients. The sample size was limited. The study was unable to determine if postoperative blood transfusion is a risk for developing MI.

Bottom line: Patients with a history of CAD and MI who have a postoperative MI following non-cardiac surgery may benefit from higher blood transfusion thresholds; however, further controlled studies are needed.

Citation: Hollis RH, Singeltary BA, McMurtrie JT, et al. Blood transfusion and 30-day mortality in patients with coronary artery disease and anemia following noncardiac surgery [published online ahead of print October 7, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.3420.

Clinical question: Is there an improved 30-day mortality rate if patients receive blood transfusion at higher hematocrit values after postoperative myocardial infarction (MI)?

Background: Prior studies evaluating patients with a history of coronary artery disease (CAD) who undergo non-cardiac surgery have shown similar mortality outcomes with liberal and restrictive transfusion strategies. Data are lacking for transfusion strategies in patients with CAD who experience postoperative MI after non-cardiac surgeries.

Study design: Retrospective cohort.

Setting: Veterans Affairs health system.

Synopsis: The study included 7,361 patients with a history of CAD who underwent non-cardiac surgery whose postoperative hematocrit was between 20% and 30%. Patients were stratified by postoperative hematocrit nadir and presence of postoperative MI. In patients with postoperative MI, transfusion was associated with lower mortality with hematocrit nadir of 20%–24% but not with hematocrit of 24%–27% or 27%–30%. In patients without postoperative MI, transfusion was associated with higher mortality in patients with hematocrit of 27%–30%.

This retrospective study was limited to the VA population of mostly male patients. The sample size was limited. The study was unable to determine if postoperative blood transfusion is a risk for developing MI.

Bottom line: Patients with a history of CAD and MI who have a postoperative MI following non-cardiac surgery may benefit from higher blood transfusion thresholds; however, further controlled studies are needed.

Citation: Hollis RH, Singeltary BA, McMurtrie JT, et al. Blood transfusion and 30-day mortality in patients with coronary artery disease and anemia following noncardiac surgery [published online ahead of print October 7, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.3420.

Clinical question: Does the use of nebulized 3% hypertonic saline shorten length of stay (LOS) in infants hospitalized with acute bronchiolitis?

Background: Acute bronchiolitis is a disease primarily of infants and young children, triggered by a viral infection that leads to variable inflammation, edema, and inspissated mucus in the lower airways. Although bronchiolitis is the most common cause of hospitalization in children under the age of two, few interventions have been shown to improve patient-level outcomes.

Hypertonic saline (generally 3%) has been one of the few interventions that has improved outcomes in some studies, leading the most recent American Academy of Pediatrics (AAP) clinical practice guideline (CPG) to state that nebulized hypertonic saline may be considered for infants and children hospitalized for bronchiolitis. The studies cited in this CPG statement were heterogeneous, with many of them performed in Europe, where the LOS for bronchiolitis is generally longer than in the U.S. In addition, most of the studies administered hypertonic saline (HS) with a bronchodilator, confounding the outcomes with an intervention not recommended in the most recent bronchiolitis CPG.

Study design: Prospective, randomized controlled, double-blinded, parallel-group study.

Setting: Urban, tertiary-care, 136-bed children’s hospital.

Synopsis: Infants 4 points received a bronchodilator and were withdrawn from the study.

Of the 227 patients enrolled after application of inclusion and exclusion criteria, 113 were randomized to receive HS and 114 to NS. Twenty patients in the HS group and 17 in the NS group discontinued intervention due to ICU transfer, provider choice to use albuterol, parental request, or protocol deviation, but patients were analyzed by intention-to-treat (ITT) assignments. No significant difference in LOS between the HS and NS groups was found, either by the traditional definition or the treatment-to-discharge order definition. No significant differences were found in secondary outcomes between the two groups, including readmission rates or clinical worsening. In addition, pre- to post-treatment RDAI score changes were not significantly different for HS versus NS.

Bottom line: Treating infants

Citation: Silver AH, Esteban-Cruciani N, Azzarone G, et al. 3% hypertonic saline versus normal saline in inpatient bronchiolitis: a randomized controlled trial. Pediatrics. 2015;136(6):1036-1043. TH

Clinical question: Does the use of nebulized 3% hypertonic saline shorten length of stay (LOS) in infants hospitalized with acute bronchiolitis?

Background: Acute bronchiolitis is a disease primarily of infants and young children, triggered by a viral infection that leads to variable inflammation, edema, and inspissated mucus in the lower airways. Although bronchiolitis is the most common cause of hospitalization in children under the age of two, few interventions have been shown to improve patient-level outcomes.

Hypertonic saline (generally 3%) has been one of the few interventions that has improved outcomes in some studies, leading the most recent American Academy of Pediatrics (AAP) clinical practice guideline (CPG) to state that nebulized hypertonic saline may be considered for infants and children hospitalized for bronchiolitis. The studies cited in this CPG statement were heterogeneous, with many of them performed in Europe, where the LOS for bronchiolitis is generally longer than in the U.S. In addition, most of the studies administered hypertonic saline (HS) with a bronchodilator, confounding the outcomes with an intervention not recommended in the most recent bronchiolitis CPG.

Study design: Prospective, randomized controlled, double-blinded, parallel-group study.

Setting: Urban, tertiary-care, 136-bed children’s hospital.

Synopsis: Infants 4 points received a bronchodilator and were withdrawn from the study.

Of the 227 patients enrolled after application of inclusion and exclusion criteria, 113 were randomized to receive HS and 114 to NS. Twenty patients in the HS group and 17 in the NS group discontinued intervention due to ICU transfer, provider choice to use albuterol, parental request, or protocol deviation, but patients were analyzed by intention-to-treat (ITT) assignments. No significant difference in LOS between the HS and NS groups was found, either by the traditional definition or the treatment-to-discharge order definition. No significant differences were found in secondary outcomes between the two groups, including readmission rates or clinical worsening. In addition, pre- to post-treatment RDAI score changes were not significantly different for HS versus NS.

Bottom line: Treating infants

Citation: Silver AH, Esteban-Cruciani N, Azzarone G, et al. 3% hypertonic saline versus normal saline in inpatient bronchiolitis: a randomized controlled trial. Pediatrics. 2015;136(6):1036-1043. TH

Clinical question: Does the use of nebulized 3% hypertonic saline shorten length of stay (LOS) in infants hospitalized with acute bronchiolitis?

Background: Acute bronchiolitis is a disease primarily of infants and young children, triggered by a viral infection that leads to variable inflammation, edema, and inspissated mucus in the lower airways. Although bronchiolitis is the most common cause of hospitalization in children under the age of two, few interventions have been shown to improve patient-level outcomes.

Hypertonic saline (generally 3%) has been one of the few interventions that has improved outcomes in some studies, leading the most recent American Academy of Pediatrics (AAP) clinical practice guideline (CPG) to state that nebulized hypertonic saline may be considered for infants and children hospitalized for bronchiolitis. The studies cited in this CPG statement were heterogeneous, with many of them performed in Europe, where the LOS for bronchiolitis is generally longer than in the U.S. In addition, most of the studies administered hypertonic saline (HS) with a bronchodilator, confounding the outcomes with an intervention not recommended in the most recent bronchiolitis CPG.

Study design: Prospective, randomized controlled, double-blinded, parallel-group study.

Setting: Urban, tertiary-care, 136-bed children’s hospital.

Synopsis: Infants 4 points received a bronchodilator and were withdrawn from the study.

Of the 227 patients enrolled after application of inclusion and exclusion criteria, 113 were randomized to receive HS and 114 to NS. Twenty patients in the HS group and 17 in the NS group discontinued intervention due to ICU transfer, provider choice to use albuterol, parental request, or protocol deviation, but patients were analyzed by intention-to-treat (ITT) assignments. No significant difference in LOS between the HS and NS groups was found, either by the traditional definition or the treatment-to-discharge order definition. No significant differences were found in secondary outcomes between the two groups, including readmission rates or clinical worsening. In addition, pre- to post-treatment RDAI score changes were not significantly different for HS versus NS.

Bottom line: Treating infants

Citation: Silver AH, Esteban-Cruciani N, Azzarone G, et al. 3% hypertonic saline versus normal saline in inpatient bronchiolitis: a randomized controlled trial. Pediatrics. 2015;136(6):1036-1043. TH

Lab mouse

In studying a mouse model of anaplastic large cell lymphoma (ALCL), investigators may have discovered how the disease develops.

“The origins of ALCL could be traced to a gene disorder in the development of blood-producing stem cells which are located in the thymus,” explained study author Lukas Kenner, MD, of the Medical University of Vienna in Austria.

He and his colleagues found that ALCL began in early thymocytes before T-cell receptor (TCR) β-rearrangement.

And the spread of ALCL required a major change in the TCR. A TCR was required for thymic emigration and peripheral tumor development, but the TCR had to be downregulated for T-cell lymphomagenesis.

In mice in which ALCL had spread, the TCR was initially required but was then lost from the surface of lymphoma cells.

“This means that the TCR molecule has a strong suppressive effect on tumor development,” Dr Kenner said.

He and his colleagues recounted these findings in Nature Communications.

“We now have a better understanding of the origin of this type of lymphoma and the crucial role played by the major changes to the immune system in the spread of this tumor through the body,” said study author Suzanne Turner, PhD, of the University of Cambridge in the UK.

“With this knowledge, we can better combat the cancer genes which are key to the formation and development of lymphomas and, in the future, develop new treatments which offer a better possibility of finding a long-term cure.”

“Current chemotherapy is particularly exhausting for children and adolescents, especially if a relapse occurs and additional treatment is needed,” Dr Kenner added.

“Our new findings about this lymphoma enable the development of more efficient and less toxic medicines, with which every child will soon be able to return to a normal life after treatment.”

Lab mouse

In studying a mouse model of anaplastic large cell lymphoma (ALCL), investigators may have discovered how the disease develops.

“The origins of ALCL could be traced to a gene disorder in the development of blood-producing stem cells which are located in the thymus,” explained study author Lukas Kenner, MD, of the Medical University of Vienna in Austria.

He and his colleagues found that ALCL began in early thymocytes before T-cell receptor (TCR) β-rearrangement.

And the spread of ALCL required a major change in the TCR. A TCR was required for thymic emigration and peripheral tumor development, but the TCR had to be downregulated for T-cell lymphomagenesis.

In mice in which ALCL had spread, the TCR was initially required but was then lost from the surface of lymphoma cells.

“This means that the TCR molecule has a strong suppressive effect on tumor development,” Dr Kenner said.

He and his colleagues recounted these findings in Nature Communications.

“We now have a better understanding of the origin of this type of lymphoma and the crucial role played by the major changes to the immune system in the spread of this tumor through the body,” said study author Suzanne Turner, PhD, of the University of Cambridge in the UK.

“With this knowledge, we can better combat the cancer genes which are key to the formation and development of lymphomas and, in the future, develop new treatments which offer a better possibility of finding a long-term cure.”

“Current chemotherapy is particularly exhausting for children and adolescents, especially if a relapse occurs and additional treatment is needed,” Dr Kenner added.

“Our new findings about this lymphoma enable the development of more efficient and less toxic medicines, with which every child will soon be able to return to a normal life after treatment.”

Lab mouse

In studying a mouse model of anaplastic large cell lymphoma (ALCL), investigators may have discovered how the disease develops.

“The origins of ALCL could be traced to a gene disorder in the development of blood-producing stem cells which are located in the thymus,” explained study author Lukas Kenner, MD, of the Medical University of Vienna in Austria.

He and his colleagues found that ALCL began in early thymocytes before T-cell receptor (TCR) β-rearrangement.

And the spread of ALCL required a major change in the TCR. A TCR was required for thymic emigration and peripheral tumor development, but the TCR had to be downregulated for T-cell lymphomagenesis.

In mice in which ALCL had spread, the TCR was initially required but was then lost from the surface of lymphoma cells.

“This means that the TCR molecule has a strong suppressive effect on tumor development,” Dr Kenner said.

He and his colleagues recounted these findings in Nature Communications.

“We now have a better understanding of the origin of this type of lymphoma and the crucial role played by the major changes to the immune system in the spread of this tumor through the body,” said study author Suzanne Turner, PhD, of the University of Cambridge in the UK.

“With this knowledge, we can better combat the cancer genes which are key to the formation and development of lymphomas and, in the future, develop new treatments which offer a better possibility of finding a long-term cure.”

“Current chemotherapy is particularly exhausting for children and adolescents, especially if a relapse occurs and additional treatment is needed,” Dr Kenner added.

“Our new findings about this lymphoma enable the development of more efficient and less toxic medicines, with which every child will soon be able to return to a normal life after treatment.”

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Researchers have reconstructed how malaria parasite proteins bind to the antibodies that act as the first line of defense against the parasite.

The team described the binding of immunoglobulin M (IgM) to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1).

They said their findings, published in Cell Reports, may provide valuable knowledge for the design of antimalarial drugs.

One strategy the malaria parasite Plasmodium falciparum uses to amplify its probability of spreading is the formation of rosette-shaped clusters of uninfected red blood cells (RBCs) surrounding a malaria-infected RBC.

Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Rosetting is associated with severe malaria and high fever.

One of the key players in the formation of the rosette is PfEMP1. PfEMP1 sticks out of the infected RBC and deceives one of the first defenses against malaria—IgM antibodies.

IgMs bind to the parasite or parasite-infected cells and call other immune molecules, like the complement system, for backup.

With the current study, researchers have shown that IgMs bind 1 or 2 PfEMP1 proteins, forming a bouquet-type shape on the surface of the infected cells.

Plasmodium falciparum exploits these IgMs to its own advantage because the bouquet attracts more RBCs, facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and destroy the infected cell.

“The bond between PfEMP1s and IgMs is like the perfect Velcro—not too loose, not too strong,” said Ulf Skoglund, PhD, of Okinawa Institute for Science and Technology Graduate University in Japan.

“It is devilishly engineered to fool our immune system.”

The technique Dr Skoglund and his colleagues used to assess this bond allowed them to have a unique view of the proteins’ conformation.

“We have seen that PfEMP1 is a stiff, C-shaped protein,” he said. “Being stiff is an advantage. If it was floppy, it would not work so well. IgM, instead, assume 3 conformations: extended, bell, and turtle shape.”

Dr Skoglund and his colleagues believe that having this 3D structural model of the PfEMP1 and IgM complex can help scientists design antimalarial treatments that can break down or wash out malaria rosettes without hurting the patient.

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Researchers have reconstructed how malaria parasite proteins bind to the antibodies that act as the first line of defense against the parasite.

The team described the binding of immunoglobulin M (IgM) to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1).

They said their findings, published in Cell Reports, may provide valuable knowledge for the design of antimalarial drugs.

One strategy the malaria parasite Plasmodium falciparum uses to amplify its probability of spreading is the formation of rosette-shaped clusters of uninfected red blood cells (RBCs) surrounding a malaria-infected RBC.

Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Rosetting is associated with severe malaria and high fever.

One of the key players in the formation of the rosette is PfEMP1. PfEMP1 sticks out of the infected RBC and deceives one of the first defenses against malaria—IgM antibodies.

IgMs bind to the parasite or parasite-infected cells and call other immune molecules, like the complement system, for backup.

With the current study, researchers have shown that IgMs bind 1 or 2 PfEMP1 proteins, forming a bouquet-type shape on the surface of the infected cells.

Plasmodium falciparum exploits these IgMs to its own advantage because the bouquet attracts more RBCs, facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and destroy the infected cell.

“The bond between PfEMP1s and IgMs is like the perfect Velcro—not too loose, not too strong,” said Ulf Skoglund, PhD, of Okinawa Institute for Science and Technology Graduate University in Japan.

“It is devilishly engineered to fool our immune system.”

The technique Dr Skoglund and his colleagues used to assess this bond allowed them to have a unique view of the proteins’ conformation.

“We have seen that PfEMP1 is a stiff, C-shaped protein,” he said. “Being stiff is an advantage. If it was floppy, it would not work so well. IgM, instead, assume 3 conformations: extended, bell, and turtle shape.”

Dr Skoglund and his colleagues believe that having this 3D structural model of the PfEMP1 and IgM complex can help scientists design antimalarial treatments that can break down or wash out malaria rosettes without hurting the patient.

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Researchers have reconstructed how malaria parasite proteins bind to the antibodies that act as the first line of defense against the parasite.

The team described the binding of immunoglobulin M (IgM) to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1).

They said their findings, published in Cell Reports, may provide valuable knowledge for the design of antimalarial drugs.

One strategy the malaria parasite Plasmodium falciparum uses to amplify its probability of spreading is the formation of rosette-shaped clusters of uninfected red blood cells (RBCs) surrounding a malaria-infected RBC.

Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Rosetting is associated with severe malaria and high fever.

One of the key players in the formation of the rosette is PfEMP1. PfEMP1 sticks out of the infected RBC and deceives one of the first defenses against malaria—IgM antibodies.

IgMs bind to the parasite or parasite-infected cells and call other immune molecules, like the complement system, for backup.

With the current study, researchers have shown that IgMs bind 1 or 2 PfEMP1 proteins, forming a bouquet-type shape on the surface of the infected cells.

Plasmodium falciparum exploits these IgMs to its own advantage because the bouquet attracts more RBCs, facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and destroy the infected cell.

“The bond between PfEMP1s and IgMs is like the perfect Velcro—not too loose, not too strong,” said Ulf Skoglund, PhD, of Okinawa Institute for Science and Technology Graduate University in Japan.

“It is devilishly engineered to fool our immune system.”

The technique Dr Skoglund and his colleagues used to assess this bond allowed them to have a unique view of the proteins’ conformation.

“We have seen that PfEMP1 is a stiff, C-shaped protein,” he said. “Being stiff is an advantage. If it was floppy, it would not work so well. IgM, instead, assume 3 conformations: extended, bell, and turtle shape.”

Dr Skoglund and his colleagues believe that having this 3D structural model of the PfEMP1 and IgM complex can help scientists design antimalarial treatments that can break down or wash out malaria rosettes without hurting the patient.

New guidelines on the diagnosis and management of primary adrenal insufficiency stress the importance of early recognition and the need to prevent life-threatening adrenal crises in these patients.

©SomkiatFakmee/thinkstockphotos.com

These are the first clinical practice guidelines on primary adrenal insufficiency (PAI), also known as Addison’s disease, issued by Endocrine Society (J Clin Endocrinol Metab. 2016 Jan 13:jc20151710 [Epub ahead of print]).

“Because it’s a rare disease and symptoms can mimic common conditions, adrenal insufficiency is often, at least initially, overlooked,” guideline co-author Dr. Deborah Merke, a senior investigator with the National Institutes of Health Clinical Center in Bethesda, Md., said. “So the main goal of these clinical practice guidelines is to improve patient care.”

The guidelines suggest clinicians should have a low diagnostic threshold in acutely ill patients with unexplained symptoms or signs suggestive of PAI such as volume depletion, hypotension, hyponatremia, hyperkalemia, fever, abdominal pain, hyperpigmentation, or, especially in children, hypoglycemia.

This low diagnostic threshold for PAI should also be extended to pregnant women with unexplained persistent nausea, fatigue, and hypotension.

For adult patients with a suspected adrenal crisis, an immediate parenteral injection of hydrocortisone 100 mg should be given, followed by appropriate fluid resuscitation and 200 mg of hydrocortisone for 24 hours, according to the guidelines, which were co-sponsored by the European Society of Endocrinology and American Association for Clinical Chemistry.

Despite a known association between adrenal crisis and mortality, there is a knowledge gap regarding how to prevent, recognize, and reduce the risk of these life-threatening events, Dr. Merke said.

To that end, the task force has taken a page from the diabetes community in recommending all PAI patients carry steroid emergency identification cards and be equipped with a glucocorticoid injection kit for emergency use and be educated on how to use it.

The guidelines also advocate education about stress dosing to counter the increased demand for corticosteroids during periods of stress, which can encompass something as common as the flu.

“Just like diabetics carry around emergency medicines, it’s important for patients with adrenal insufficiency to carry around an emergency kit and to realize that should they start to get sick, they need to increase their doses,” she said. “There often seems to be a lack of awareness among physicians as well that these patients have a potentially life-threatening condition, should they get a common illness.”

One of the key unanswered clinical questions the task force sought to address was whether the widely used high-dose (250 mcg) corticotropin stimulation test, also known as the adrenocorticotropin (ACTH) or short Synacthen test, should be replaced by the low-dose test (1 mcg) to diagnosis PAI.

Despite a review of published data and a systematic review commissioned by the task force, “We didn’t come up with much scientific evidence to say we should be changing the historic standard,” Dr. Merke said.

The systematic review identified only five studies of high-dose corticotropin testing specifically in PAI and none of low-dose testing. The low-dose test has shown higher sensitivity in the detection of adrenal insufficiency in critically ill patients and secondary adrenal insufficiency, but the limited available data suggest it does not provide better diagnostic accuracy for PAI than the high-dose test.

As a result, the guidelines recommend the standard, short corticotropin test (250 mcg for adults and children aged at least 2 years) as the “gold standard” diagnostic test to establish a PAI diagnosis.

The low-dose (1 mcg) test is recommended only when corticotropin is in short supply, which is not typically a problem in the United States, she said.

If corticotropin testing isn’t feasible, a combination of a morning plasma ACTH and cortisol levels (less than 5 mcg/dL) can be used as an initial screening, though confirmatory testing with corticotropin stimulation is strongly recommended.

Glucocorticoid therapy is recommended in all patients with confirmed PAI based on the highest quality of evidence, with a clear preference given for the short-acting steroids, Dr. Merke observed.

Hydrocortisone 15 mg-25 mg or cortisone acetate 20 mg-35 mg given in two to three divided doses per day is suggested for adults, with the highest dose to be given in the morning. Once- or twice-daily prednisolone 3 mg-5 mg is suggested as an alternative.

Hydrocortisone is also suggested over cortisone acetate, prednisolone, or prednisone for pregnant women and recommended for children (about 8 mg/m² per day), but the evidence supporting these items was of low quality.

The guidelines suggest against using dexamethasone, the longest-acting glucocorticoid, because of the potential long-term side effects of overt-treatment and the frequent appearance of cushingoid side effects. They also recommend against dexamethasone in pregnant women because it is not inactivated in the placenta.

The guidelines are also quite clear in their suggestion against hormonal monitoring of glucocorticoid replacement and instead favor adjusting treatment based only on clinical response.

“This is a very important suggestion that we made because often clinicians use ACTH to adjust doses and this commonly results in overreplacement and there are side effects to overreplacement,” including weight gain, insomnia, and peripheral edema, Dr. Merke said.

A second systematic review commissioned by the task force involving 15 observational studies of glucocorticoid replacement regimens uncovered very sparse data on mortality, bone density, and incidence of adrenal crisis.

It has been suggested that newer extended-release and dual-release glucocorticoid formulations may result in higher health-reality quality of life than once-, twice-, or thrice-daily regimens, but once again, the evidence was insufficient to support a specific recommendation.

Dr. Merke acknowledged that many of the guidelines recommendations were ungraded or best practices, reflecting the lack of randomized clinical trials in PAI.

“I think that’s why it was so important for us to do this,” she said. “We had a group of experts that were very familiar with this disease providing guidance, but I think it’s also one reason why physicians out there in practice get confused about exactly what to do because of the lack of hard evidence. ... It does certainly cry for the need for more studies in these rare diseases.”

The guidelines were funded by the Endocrine Society, and the authors reported receiving no external funding or remuneration.

[email protected]

New guidelines on the diagnosis and management of primary adrenal insufficiency stress the importance of early recognition and the need to prevent life-threatening adrenal crises in these patients.

©SomkiatFakmee/thinkstockphotos.com

These are the first clinical practice guidelines on primary adrenal insufficiency (PAI), also known as Addison’s disease, issued by Endocrine Society (J Clin Endocrinol Metab. 2016 Jan 13:jc20151710 [Epub ahead of print]).

“Because it’s a rare disease and symptoms can mimic common conditions, adrenal insufficiency is often, at least initially, overlooked,” guideline co-author Dr. Deborah Merke, a senior investigator with the National Institutes of Health Clinical Center in Bethesda, Md., said. “So the main goal of these clinical practice guidelines is to improve patient care.”

The guidelines suggest clinicians should have a low diagnostic threshold in acutely ill patients with unexplained symptoms or signs suggestive of PAI such as volume depletion, hypotension, hyponatremia, hyperkalemia, fever, abdominal pain, hyperpigmentation, or, especially in children, hypoglycemia.

This low diagnostic threshold for PAI should also be extended to pregnant women with unexplained persistent nausea, fatigue, and hypotension.

For adult patients with a suspected adrenal crisis, an immediate parenteral injection of hydrocortisone 100 mg should be given, followed by appropriate fluid resuscitation and 200 mg of hydrocortisone for 24 hours, according to the guidelines, which were co-sponsored by the European Society of Endocrinology and American Association for Clinical Chemistry.

Despite a known association between adrenal crisis and mortality, there is a knowledge gap regarding how to prevent, recognize, and reduce the risk of these life-threatening events, Dr. Merke said.

To that end, the task force has taken a page from the diabetes community in recommending all PAI patients carry steroid emergency identification cards and be equipped with a glucocorticoid injection kit for emergency use and be educated on how to use it.

The guidelines also advocate education about stress dosing to counter the increased demand for corticosteroids during periods of stress, which can encompass something as common as the flu.

“Just like diabetics carry around emergency medicines, it’s important for patients with adrenal insufficiency to carry around an emergency kit and to realize that should they start to get sick, they need to increase their doses,” she said. “There often seems to be a lack of awareness among physicians as well that these patients have a potentially life-threatening condition, should they get a common illness.”

One of the key unanswered clinical questions the task force sought to address was whether the widely used high-dose (250 mcg) corticotropin stimulation test, also known as the adrenocorticotropin (ACTH) or short Synacthen test, should be replaced by the low-dose test (1 mcg) to diagnosis PAI.

Despite a review of published data and a systematic review commissioned by the task force, “We didn’t come up with much scientific evidence to say we should be changing the historic standard,” Dr. Merke said.

The systematic review identified only five studies of high-dose corticotropin testing specifically in PAI and none of low-dose testing. The low-dose test has shown higher sensitivity in the detection of adrenal insufficiency in critically ill patients and secondary adrenal insufficiency, but the limited available data suggest it does not provide better diagnostic accuracy for PAI than the high-dose test.

As a result, the guidelines recommend the standard, short corticotropin test (250 mcg for adults and children aged at least 2 years) as the “gold standard” diagnostic test to establish a PAI diagnosis.

The low-dose (1 mcg) test is recommended only when corticotropin is in short supply, which is not typically a problem in the United States, she said.

If corticotropin testing isn’t feasible, a combination of a morning plasma ACTH and cortisol levels (less than 5 mcg/dL) can be used as an initial screening, though confirmatory testing with corticotropin stimulation is strongly recommended.

Glucocorticoid therapy is recommended in all patients with confirmed PAI based on the highest quality of evidence, with a clear preference given for the short-acting steroids, Dr. Merke observed.

Hydrocortisone 15 mg-25 mg or cortisone acetate 20 mg-35 mg given in two to three divided doses per day is suggested for adults, with the highest dose to be given in the morning. Once- or twice-daily prednisolone 3 mg-5 mg is suggested as an alternative.

Hydrocortisone is also suggested over cortisone acetate, prednisolone, or prednisone for pregnant women and recommended for children (about 8 mg/m² per day), but the evidence supporting these items was of low quality.

The guidelines suggest against using dexamethasone, the longest-acting glucocorticoid, because of the potential long-term side effects of overt-treatment and the frequent appearance of cushingoid side effects. They also recommend against dexamethasone in pregnant women because it is not inactivated in the placenta.

The guidelines are also quite clear in their suggestion against hormonal monitoring of glucocorticoid replacement and instead favor adjusting treatment based only on clinical response.

“This is a very important suggestion that we made because often clinicians use ACTH to adjust doses and this commonly results in overreplacement and there are side effects to overreplacement,” including weight gain, insomnia, and peripheral edema, Dr. Merke said.

A second systematic review commissioned by the task force involving 15 observational studies of glucocorticoid replacement regimens uncovered very sparse data on mortality, bone density, and incidence of adrenal crisis.

It has been suggested that newer extended-release and dual-release glucocorticoid formulations may result in higher health-reality quality of life than once-, twice-, or thrice-daily regimens, but once again, the evidence was insufficient to support a specific recommendation.

Dr. Merke acknowledged that many of the guidelines recommendations were ungraded or best practices, reflecting the lack of randomized clinical trials in PAI.

“I think that’s why it was so important for us to do this,” she said. “We had a group of experts that were very familiar with this disease providing guidance, but I think it’s also one reason why physicians out there in practice get confused about exactly what to do because of the lack of hard evidence. ... It does certainly cry for the need for more studies in these rare diseases.”

The guidelines were funded by the Endocrine Society, and the authors reported receiving no external funding or remuneration.

[email protected]

New guidelines on the diagnosis and management of primary adrenal insufficiency stress the importance of early recognition and the need to prevent life-threatening adrenal crises in these patients.

©SomkiatFakmee/thinkstockphotos.com

These are the first clinical practice guidelines on primary adrenal insufficiency (PAI), also known as Addison’s disease, issued by Endocrine Society (J Clin Endocrinol Metab. 2016 Jan 13:jc20151710 [Epub ahead of print]).

“Because it’s a rare disease and symptoms can mimic common conditions, adrenal insufficiency is often, at least initially, overlooked,” guideline co-author Dr. Deborah Merke, a senior investigator with the National Institutes of Health Clinical Center in Bethesda, Md., said. “So the main goal of these clinical practice guidelines is to improve patient care.”

The guidelines suggest clinicians should have a low diagnostic threshold in acutely ill patients with unexplained symptoms or signs suggestive of PAI such as volume depletion, hypotension, hyponatremia, hyperkalemia, fever, abdominal pain, hyperpigmentation, or, especially in children, hypoglycemia.

This low diagnostic threshold for PAI should also be extended to pregnant women with unexplained persistent nausea, fatigue, and hypotension.

For adult patients with a suspected adrenal crisis, an immediate parenteral injection of hydrocortisone 100 mg should be given, followed by appropriate fluid resuscitation and 200 mg of hydrocortisone for 24 hours, according to the guidelines, which were co-sponsored by the European Society of Endocrinology and American Association for Clinical Chemistry.

Despite a known association between adrenal crisis and mortality, there is a knowledge gap regarding how to prevent, recognize, and reduce the risk of these life-threatening events, Dr. Merke said.

To that end, the task force has taken a page from the diabetes community in recommending all PAI patients carry steroid emergency identification cards and be equipped with a glucocorticoid injection kit for emergency use and be educated on how to use it.

The guidelines also advocate education about stress dosing to counter the increased demand for corticosteroids during periods of stress, which can encompass something as common as the flu.

“Just like diabetics carry around emergency medicines, it’s important for patients with adrenal insufficiency to carry around an emergency kit and to realize that should they start to get sick, they need to increase their doses,” she said. “There often seems to be a lack of awareness among physicians as well that these patients have a potentially life-threatening condition, should they get a common illness.”

One of the key unanswered clinical questions the task force sought to address was whether the widely used high-dose (250 mcg) corticotropin stimulation test, also known as the adrenocorticotropin (ACTH) or short Synacthen test, should be replaced by the low-dose test (1 mcg) to diagnosis PAI.

Despite a review of published data and a systematic review commissioned by the task force, “We didn’t come up with much scientific evidence to say we should be changing the historic standard,” Dr. Merke said.

The systematic review identified only five studies of high-dose corticotropin testing specifically in PAI and none of low-dose testing. The low-dose test has shown higher sensitivity in the detection of adrenal insufficiency in critically ill patients and secondary adrenal insufficiency, but the limited available data suggest it does not provide better diagnostic accuracy for PAI than the high-dose test.

As a result, the guidelines recommend the standard, short corticotropin test (250 mcg for adults and children aged at least 2 years) as the “gold standard” diagnostic test to establish a PAI diagnosis.

The low-dose (1 mcg) test is recommended only when corticotropin is in short supply, which is not typically a problem in the United States, she said.

If corticotropin testing isn’t feasible, a combination of a morning plasma ACTH and cortisol levels (less than 5 mcg/dL) can be used as an initial screening, though confirmatory testing with corticotropin stimulation is strongly recommended.

Glucocorticoid therapy is recommended in all patients with confirmed PAI based on the highest quality of evidence, with a clear preference given for the short-acting steroids, Dr. Merke observed.

Hydrocortisone 15 mg-25 mg or cortisone acetate 20 mg-35 mg given in two to three divided doses per day is suggested for adults, with the highest dose to be given in the morning. Once- or twice-daily prednisolone 3 mg-5 mg is suggested as an alternative.

Hydrocortisone is also suggested over cortisone acetate, prednisolone, or prednisone for pregnant women and recommended for children (about 8 mg/m² per day), but the evidence supporting these items was of low quality.

The guidelines suggest against using dexamethasone, the longest-acting glucocorticoid, because of the potential long-term side effects of overt-treatment and the frequent appearance of cushingoid side effects. They also recommend against dexamethasone in pregnant women because it is not inactivated in the placenta.

The guidelines are also quite clear in their suggestion against hormonal monitoring of glucocorticoid replacement and instead favor adjusting treatment based only on clinical response.

“This is a very important suggestion that we made because often clinicians use ACTH to adjust doses and this commonly results in overreplacement and there are side effects to overreplacement,” including weight gain, insomnia, and peripheral edema, Dr. Merke said.

A second systematic review commissioned by the task force involving 15 observational studies of glucocorticoid replacement regimens uncovered very sparse data on mortality, bone density, and incidence of adrenal crisis.

It has been suggested that newer extended-release and dual-release glucocorticoid formulations may result in higher health-reality quality of life than once-, twice-, or thrice-daily regimens, but once again, the evidence was insufficient to support a specific recommendation.

Dr. Merke acknowledged that many of the guidelines recommendations were ungraded or best practices, reflecting the lack of randomized clinical trials in PAI.

“I think that’s why it was so important for us to do this,” she said. “We had a group of experts that were very familiar with this disease providing guidance, but I think it’s also one reason why physicians out there in practice get confused about exactly what to do because of the lack of hard evidence. ... It does certainly cry for the need for more studies in these rare diseases.”

The guidelines were funded by the Endocrine Society, and the authors reported receiving no external funding or remuneration.

[email protected]