MDedge Dermatology

Fastest peptide north, south, east, aaaaand west of the Pecos

Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.

Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.

Ilana Camargo

Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.

The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.

The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
 

Speed healing: The wavy wound gets the swirl

Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?

You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.

NTU Singapore

They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.

The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.

Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.

The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.

As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
 

A little Jekyll, a little Hyde, and a little shop of horrors

More “Little Shop of Horrors” references are coming, so be prepared.

We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.

No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.

T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.

Traud Winkelmann/University of Hannover

A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”

Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.

Fastest peptide north, south, east, aaaaand west of the Pecos

Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.

Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.

Ilana Camargo

Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.

The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.

The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
 

Speed healing: The wavy wound gets the swirl

Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?

You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.

NTU Singapore

They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.

The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.

Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.

The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.

As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
 

A little Jekyll, a little Hyde, and a little shop of horrors

More “Little Shop of Horrors” references are coming, so be prepared.

We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.

No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.

T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.

Traud Winkelmann/University of Hannover

A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”

Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.

Fastest peptide north, south, east, aaaaand west of the Pecos

Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.

Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.

Ilana Camargo

Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.

The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.

The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
 

Speed healing: The wavy wound gets the swirl

Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?

You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.

NTU Singapore

They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.

The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.

Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.

The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.

As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
 

A little Jekyll, a little Hyde, and a little shop of horrors

More “Little Shop of Horrors” references are coming, so be prepared.

We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.

No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.

T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.

Traud Winkelmann/University of Hannover

A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”

Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.

Last month, I described a 28-year-old patient with a history of injection drug use who presented with pain in his left forearm. His history showed that, within the past 2 years, he’d been seen for cutaneous infections multiple times as an outpatient and in the emergency department. His records indicated that he was diagnosed with a penicillin allergy as a child when he developed a rash after receiving amoxicillin. I believed the next course of action should be to test for a penicillin allergy with an oral amoxicillin challenge.
 

Thank you for your excellent questions regarding this case. Great to hear the enthusiasm for testing for penicillin allergy!

One question focused on the course of action in the case of a mild or moderate IgE-mediated reaction after a single dose test with amoxicillin. Treatment for these reactions should include an antihistamine. I would reserve intravenous antihistamines for more severe cases, which also require treatment with a course of corticosteroids. However, the risk for a moderate to severe reaction to amoxicillin on retesting is quite low.

Clinicians need to exercise caution in the use of systemic corticosteroids. These drugs can be lifesaving, but even short courses of corticosteroids are associated with potentially serious adverse events. In a review of adverse events associated with short-course systemic corticosteroids among children, the rate of vomiting was 5.4%; behavioral change, 4.7%; and sleep disturbance, 4.3%. One child died after contracting herpes zoster, more than one-third of children developed elevated blood pressure, and 81.1% had evidence of suppression of the hypothalamic-pituitary-adrenal axis.

Among adults, short courses of systemic corticosteroids are associated with acute increases in the risks for gastrointestinal bleeding and hypertension. Cumulative exposure to short courses of corticosteroids over time results in higher risks for obesity, type 2 diabetes, and osteoporosis.

Another question prompted by this young man’s case focused on the durability of IgE reactions against penicillin. The IgE response to penicillin does indeed wane over time; 80% of patients with a previous true penicillin allergy can tolerate the antibiotic after 10 years. Thus, about 95% of patients with a remote history of penicillin allergy are tolerant of penicillin, and testing can be performed using the algorithm described.

Clinicians should avoid applying current guidelines for the evaluation of patients with penicillin allergy to other common drug allergies. The overall prevalence of sulfonamide allergy is 3%-8%, and the vast majority of these reactions follow treatment with trimethoprim-sulfamethoxazole. Sulfa allergy is even more common among persons living with HIV infection. The natural history of sulfa allergy is not as well established as penicillin allergy. Allergy testing is encouraged in these cases. Graded oral challenge testing is best reserved for patients who are unlikely to have a true sulfa allergy based on their history.

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

Last month, I described a 28-year-old patient with a history of injection drug use who presented with pain in his left forearm. His history showed that, within the past 2 years, he’d been seen for cutaneous infections multiple times as an outpatient and in the emergency department. His records indicated that he was diagnosed with a penicillin allergy as a child when he developed a rash after receiving amoxicillin. I believed the next course of action should be to test for a penicillin allergy with an oral amoxicillin challenge.
 

Thank you for your excellent questions regarding this case. Great to hear the enthusiasm for testing for penicillin allergy!

One question focused on the course of action in the case of a mild or moderate IgE-mediated reaction after a single dose test with amoxicillin. Treatment for these reactions should include an antihistamine. I would reserve intravenous antihistamines for more severe cases, which also require treatment with a course of corticosteroids. However, the risk for a moderate to severe reaction to amoxicillin on retesting is quite low.

Clinicians need to exercise caution in the use of systemic corticosteroids. These drugs can be lifesaving, but even short courses of corticosteroids are associated with potentially serious adverse events. In a review of adverse events associated with short-course systemic corticosteroids among children, the rate of vomiting was 5.4%; behavioral change, 4.7%; and sleep disturbance, 4.3%. One child died after contracting herpes zoster, more than one-third of children developed elevated blood pressure, and 81.1% had evidence of suppression of the hypothalamic-pituitary-adrenal axis.

Among adults, short courses of systemic corticosteroids are associated with acute increases in the risks for gastrointestinal bleeding and hypertension. Cumulative exposure to short courses of corticosteroids over time results in higher risks for obesity, type 2 diabetes, and osteoporosis.

Another question prompted by this young man’s case focused on the durability of IgE reactions against penicillin. The IgE response to penicillin does indeed wane over time; 80% of patients with a previous true penicillin allergy can tolerate the antibiotic after 10 years. Thus, about 95% of patients with a remote history of penicillin allergy are tolerant of penicillin, and testing can be performed using the algorithm described.

Clinicians should avoid applying current guidelines for the evaluation of patients with penicillin allergy to other common drug allergies. The overall prevalence of sulfonamide allergy is 3%-8%, and the vast majority of these reactions follow treatment with trimethoprim-sulfamethoxazole. Sulfa allergy is even more common among persons living with HIV infection. The natural history of sulfa allergy is not as well established as penicillin allergy. Allergy testing is encouraged in these cases. Graded oral challenge testing is best reserved for patients who are unlikely to have a true sulfa allergy based on their history.

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

Last month, I described a 28-year-old patient with a history of injection drug use who presented with pain in his left forearm. His history showed that, within the past 2 years, he’d been seen for cutaneous infections multiple times as an outpatient and in the emergency department. His records indicated that he was diagnosed with a penicillin allergy as a child when he developed a rash after receiving amoxicillin. I believed the next course of action should be to test for a penicillin allergy with an oral amoxicillin challenge.
 

Thank you for your excellent questions regarding this case. Great to hear the enthusiasm for testing for penicillin allergy!

One question focused on the course of action in the case of a mild or moderate IgE-mediated reaction after a single dose test with amoxicillin. Treatment for these reactions should include an antihistamine. I would reserve intravenous antihistamines for more severe cases, which also require treatment with a course of corticosteroids. However, the risk for a moderate to severe reaction to amoxicillin on retesting is quite low.

Clinicians need to exercise caution in the use of systemic corticosteroids. These drugs can be lifesaving, but even short courses of corticosteroids are associated with potentially serious adverse events. In a review of adverse events associated with short-course systemic corticosteroids among children, the rate of vomiting was 5.4%; behavioral change, 4.7%; and sleep disturbance, 4.3%. One child died after contracting herpes zoster, more than one-third of children developed elevated blood pressure, and 81.1% had evidence of suppression of the hypothalamic-pituitary-adrenal axis.

Among adults, short courses of systemic corticosteroids are associated with acute increases in the risks for gastrointestinal bleeding and hypertension. Cumulative exposure to short courses of corticosteroids over time results in higher risks for obesity, type 2 diabetes, and osteoporosis.

Another question prompted by this young man’s case focused on the durability of IgE reactions against penicillin. The IgE response to penicillin does indeed wane over time; 80% of patients with a previous true penicillin allergy can tolerate the antibiotic after 10 years. Thus, about 95% of patients with a remote history of penicillin allergy are tolerant of penicillin, and testing can be performed using the algorithm described.

Clinicians should avoid applying current guidelines for the evaluation of patients with penicillin allergy to other common drug allergies. The overall prevalence of sulfonamide allergy is 3%-8%, and the vast majority of these reactions follow treatment with trimethoprim-sulfamethoxazole. Sulfa allergy is even more common among persons living with HIV infection. The natural history of sulfa allergy is not as well established as penicillin allergy. Allergy testing is encouraged in these cases. Graded oral challenge testing is best reserved for patients who are unlikely to have a true sulfa allergy based on their history.

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

To the Editor:

A 67-year-old woman presented to the hospital with painful hands and feet. Two weeks prior, the patient experienced a few days of intermittent purple discoloration of the fingers, followed by black discoloration of the fingers, toes, and nose with notable pain. She reported no illness preceding the presenting symptoms, and there was no progression of symptoms in the days preceding presentation.

The patient had a history of smoking. She had a medical history of chronic obstructive pulmonary disease as well as recurrent non–small cell lung cancer that was treated most recently with a 1-year course of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor durvalumab (last treatment was 4 months prior to the current presentation).

Physical examination revealed necrosis of the tips of the second, third, and fourth fingers of the left hand, as well as the tips of the third and fourth fingers of the right hand, progressing to purpura proximally on all involved fingers (Figure, A); scattered purpura and necrotic papules on the toe pads (Figure, B); and a 2- to 3-cm black plaque on the nasal tip. The patient was afebrile.

An embolic and vascular workup was performed. Transthoracic echocardiography was negative for thrombi, ankle brachial indices were within reference range, and computed tomography angiography revealed a few nonocclusive coronary plaques. Conventional angiography was not performed.

Laboratory testing revealed a mildly elevated level of cryofibrinogens (cryocrit, 2.5%); cold agglutinins (1:32); mild monoclonal κ IgG gammopathy (0.1 g/dL); and elevated inflammatory markers (C-reactive protein, 76 mg/L [reference range, 0–10 mg/L]; erythrocyte sedimentation rate, 38 mm/h [reference range, 0–20 mm/h]; fibrinogen, 571 mg/dL [reference range, 150–450 mg/dL]; and ferritin, 394 ng/mL [reference range, 10–180 ng/mL]). Additional laboratory studies were negative or within reference range, including tests of anti-RNA polymerase antibody, rheumatoid factor, antinuclear antibody, anticardiolipin antibody, anti-β₂ glycoprotein antibody, antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase-3), cryoglobulins, and complement; human immunodeficiency virus and hepatitis B and C virus serologic studies; prothrombin time, partial thromboplastin time, and lupus anticoagulant; and a heparin-induced thrombocytopenia panel.

A skin biopsy adjacent to an area of necrosis on the finger showed thickened walls of dermal vessels, sparse leukocytoclastic debris, and evidence of recanalizing medium-sized vessels. Direct immunofluorescence studies were negative.

Based on the clinical history and histologic findings showing an absence of vasculitis, a diagnosis of acral necrosis associated with the PD-L1 immune checkpoint inhibitor durvalumab—a delayed immune-related event (DIRE)—was favored. The calcium channel blocker amlodipine was started at a dosage of 2.5 mg/d orally. Necrosis of the toes resolved over the course of 1 week; however, necrosis of the fingers remained unchanged. After 1 week of hospitalization, the patient was discharged at her request.

Acral necrosis following immune checkpoint inhibitor therapy has been reported as a rare and recalcitrant immune-related adverse event (AE).^1-4 However, our patient’s symptoms occurred months after treatment was discontinued, which is consistent with a DIRE.⁵ The course of acral necrosis begins with acrocyanosis (a Raynaud disease–like phenomenon) of the fingers that progresses to necrosis. A history of Raynaud disease or other autoimmune disorder generally is absent.¹ Our patient’s history indicated actively smoking at the time of presentation, similar to a case described by Khaddour et al.¹ Similarly, in a case presented by Comont et al,³ the patient also had a history of smoking. In a recent study of acute vascular events associated with immune checkpoint inhibitors, 16 of 31 patients had a history of smoking.⁶

No definitive diagnostic laboratory or pathologic findings are associated with acral necrosis following immune checkpoint inhibitor therapy. Histopathologic analysis does not demonstrate vasculitis or other overt vascular pathology.^2,3

The optimal treatment of immune checkpoint inhibitor–associated digital necrosis is unclear. Corticosteroids and discontinuation of the immune checkpoint inhibitor generally are employed,^1-4 though treatment response has been variable. Other therapies such as calcium channel blockers (as in our case), sympathectomy,¹ epoprostenol, botulinum injection, rituximab,² and alprostadil⁴ have been attempted without clear effect.

We considered a diagnosis of paraneoplastic acral vascular syndrome in our patient, which was ruled out because the syndrome typically occurs in the setting of a worsening underlying malignancy⁷; our patient’s cancer was stable to improved. Thromboangiitis obliterans was ruled out by the absence of a characteristic thrombus on biopsy, the patient’s older age, and involvement of the nose.

We report an unusual case of acral necrosis occurring as a DIRE in response to administration of an immune checkpoint inhibitor. Further description is needed to clarify the diagnostic criteria for and treatment of this rare autoimmune phenomenon.

To the Editor:

A 67-year-old woman presented to the hospital with painful hands and feet. Two weeks prior, the patient experienced a few days of intermittent purple discoloration of the fingers, followed by black discoloration of the fingers, toes, and nose with notable pain. She reported no illness preceding the presenting symptoms, and there was no progression of symptoms in the days preceding presentation.

The patient had a history of smoking. She had a medical history of chronic obstructive pulmonary disease as well as recurrent non–small cell lung cancer that was treated most recently with a 1-year course of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor durvalumab (last treatment was 4 months prior to the current presentation).

Physical examination revealed necrosis of the tips of the second, third, and fourth fingers of the left hand, as well as the tips of the third and fourth fingers of the right hand, progressing to purpura proximally on all involved fingers (Figure, A); scattered purpura and necrotic papules on the toe pads (Figure, B); and a 2- to 3-cm black plaque on the nasal tip. The patient was afebrile.

An embolic and vascular workup was performed. Transthoracic echocardiography was negative for thrombi, ankle brachial indices were within reference range, and computed tomography angiography revealed a few nonocclusive coronary plaques. Conventional angiography was not performed.

Laboratory testing revealed a mildly elevated level of cryofibrinogens (cryocrit, 2.5%); cold agglutinins (1:32); mild monoclonal κ IgG gammopathy (0.1 g/dL); and elevated inflammatory markers (C-reactive protein, 76 mg/L [reference range, 0–10 mg/L]; erythrocyte sedimentation rate, 38 mm/h [reference range, 0–20 mm/h]; fibrinogen, 571 mg/dL [reference range, 150–450 mg/dL]; and ferritin, 394 ng/mL [reference range, 10–180 ng/mL]). Additional laboratory studies were negative or within reference range, including tests of anti-RNA polymerase antibody, rheumatoid factor, antinuclear antibody, anticardiolipin antibody, anti-β₂ glycoprotein antibody, antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase-3), cryoglobulins, and complement; human immunodeficiency virus and hepatitis B and C virus serologic studies; prothrombin time, partial thromboplastin time, and lupus anticoagulant; and a heparin-induced thrombocytopenia panel.

A skin biopsy adjacent to an area of necrosis on the finger showed thickened walls of dermal vessels, sparse leukocytoclastic debris, and evidence of recanalizing medium-sized vessels. Direct immunofluorescence studies were negative.

Based on the clinical history and histologic findings showing an absence of vasculitis, a diagnosis of acral necrosis associated with the PD-L1 immune checkpoint inhibitor durvalumab—a delayed immune-related event (DIRE)—was favored. The calcium channel blocker amlodipine was started at a dosage of 2.5 mg/d orally. Necrosis of the toes resolved over the course of 1 week; however, necrosis of the fingers remained unchanged. After 1 week of hospitalization, the patient was discharged at her request.

Acral necrosis following immune checkpoint inhibitor therapy has been reported as a rare and recalcitrant immune-related adverse event (AE).^1-4 However, our patient’s symptoms occurred months after treatment was discontinued, which is consistent with a DIRE.⁵ The course of acral necrosis begins with acrocyanosis (a Raynaud disease–like phenomenon) of the fingers that progresses to necrosis. A history of Raynaud disease or other autoimmune disorder generally is absent.¹ Our patient’s history indicated actively smoking at the time of presentation, similar to a case described by Khaddour et al.¹ Similarly, in a case presented by Comont et al,³ the patient also had a history of smoking. In a recent study of acute vascular events associated with immune checkpoint inhibitors, 16 of 31 patients had a history of smoking.⁶

No definitive diagnostic laboratory or pathologic findings are associated with acral necrosis following immune checkpoint inhibitor therapy. Histopathologic analysis does not demonstrate vasculitis or other overt vascular pathology.^2,3

The optimal treatment of immune checkpoint inhibitor–associated digital necrosis is unclear. Corticosteroids and discontinuation of the immune checkpoint inhibitor generally are employed,^1-4 though treatment response has been variable. Other therapies such as calcium channel blockers (as in our case), sympathectomy,¹ epoprostenol, botulinum injection, rituximab,² and alprostadil⁴ have been attempted without clear effect.

We considered a diagnosis of paraneoplastic acral vascular syndrome in our patient, which was ruled out because the syndrome typically occurs in the setting of a worsening underlying malignancy⁷; our patient’s cancer was stable to improved. Thromboangiitis obliterans was ruled out by the absence of a characteristic thrombus on biopsy, the patient’s older age, and involvement of the nose.

We report an unusual case of acral necrosis occurring as a DIRE in response to administration of an immune checkpoint inhibitor. Further description is needed to clarify the diagnostic criteria for and treatment of this rare autoimmune phenomenon.

To the Editor:

A 67-year-old woman presented to the hospital with painful hands and feet. Two weeks prior, the patient experienced a few days of intermittent purple discoloration of the fingers, followed by black discoloration of the fingers, toes, and nose with notable pain. She reported no illness preceding the presenting symptoms, and there was no progression of symptoms in the days preceding presentation.

The patient had a history of smoking. She had a medical history of chronic obstructive pulmonary disease as well as recurrent non–small cell lung cancer that was treated most recently with a 1-year course of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor durvalumab (last treatment was 4 months prior to the current presentation).

Physical examination revealed necrosis of the tips of the second, third, and fourth fingers of the left hand, as well as the tips of the third and fourth fingers of the right hand, progressing to purpura proximally on all involved fingers (Figure, A); scattered purpura and necrotic papules on the toe pads (Figure, B); and a 2- to 3-cm black plaque on the nasal tip. The patient was afebrile.

An embolic and vascular workup was performed. Transthoracic echocardiography was negative for thrombi, ankle brachial indices were within reference range, and computed tomography angiography revealed a few nonocclusive coronary plaques. Conventional angiography was not performed.

Laboratory testing revealed a mildly elevated level of cryofibrinogens (cryocrit, 2.5%); cold agglutinins (1:32); mild monoclonal κ IgG gammopathy (0.1 g/dL); and elevated inflammatory markers (C-reactive protein, 76 mg/L [reference range, 0–10 mg/L]; erythrocyte sedimentation rate, 38 mm/h [reference range, 0–20 mm/h]; fibrinogen, 571 mg/dL [reference range, 150–450 mg/dL]; and ferritin, 394 ng/mL [reference range, 10–180 ng/mL]). Additional laboratory studies were negative or within reference range, including tests of anti-RNA polymerase antibody, rheumatoid factor, antinuclear antibody, anticardiolipin antibody, anti-β₂ glycoprotein antibody, antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase-3), cryoglobulins, and complement; human immunodeficiency virus and hepatitis B and C virus serologic studies; prothrombin time, partial thromboplastin time, and lupus anticoagulant; and a heparin-induced thrombocytopenia panel.

A skin biopsy adjacent to an area of necrosis on the finger showed thickened walls of dermal vessels, sparse leukocytoclastic debris, and evidence of recanalizing medium-sized vessels. Direct immunofluorescence studies were negative.

Based on the clinical history and histologic findings showing an absence of vasculitis, a diagnosis of acral necrosis associated with the PD-L1 immune checkpoint inhibitor durvalumab—a delayed immune-related event (DIRE)—was favored. The calcium channel blocker amlodipine was started at a dosage of 2.5 mg/d orally. Necrosis of the toes resolved over the course of 1 week; however, necrosis of the fingers remained unchanged. After 1 week of hospitalization, the patient was discharged at her request.

Acral necrosis following immune checkpoint inhibitor therapy has been reported as a rare and recalcitrant immune-related adverse event (AE).^1-4 However, our patient’s symptoms occurred months after treatment was discontinued, which is consistent with a DIRE.⁵ The course of acral necrosis begins with acrocyanosis (a Raynaud disease–like phenomenon) of the fingers that progresses to necrosis. A history of Raynaud disease or other autoimmune disorder generally is absent.¹ Our patient’s history indicated actively smoking at the time of presentation, similar to a case described by Khaddour et al.¹ Similarly, in a case presented by Comont et al,³ the patient also had a history of smoking. In a recent study of acute vascular events associated with immune checkpoint inhibitors, 16 of 31 patients had a history of smoking.⁶

No definitive diagnostic laboratory or pathologic findings are associated with acral necrosis following immune checkpoint inhibitor therapy. Histopathologic analysis does not demonstrate vasculitis or other overt vascular pathology.^2,3

The optimal treatment of immune checkpoint inhibitor–associated digital necrosis is unclear. Corticosteroids and discontinuation of the immune checkpoint inhibitor generally are employed,^1-4 though treatment response has been variable. Other therapies such as calcium channel blockers (as in our case), sympathectomy,¹ epoprostenol, botulinum injection, rituximab,² and alprostadil⁴ have been attempted without clear effect.

We considered a diagnosis of paraneoplastic acral vascular syndrome in our patient, which was ruled out because the syndrome typically occurs in the setting of a worsening underlying malignancy⁷; our patient’s cancer was stable to improved. Thromboangiitis obliterans was ruled out by the absence of a characteristic thrombus on biopsy, the patient’s older age, and involvement of the nose.

We report an unusual case of acral necrosis occurring as a DIRE in response to administration of an immune checkpoint inhibitor. Further description is needed to clarify the diagnostic criteria for and treatment of this rare autoimmune phenomenon.

To the Editor:

Programmed cell death protein 1 (PD-1) inhibitors have been widely used in the treatment of various cancers. Programmed cell death-ligand 1 (PD-L1) and programmed cell death-ligand 2 located on cancer cells will bind to PD-1 receptors on T cells and suppress them, which will prevent cancer cell destruction. Programmed cell death protein 1 inhibitors block the binding of PD-L1 to cancer cells, which then prevents T-cell immunosuppression.¹ However, cutaneous adverse effects have been associated with PD-1 inhibitors. Dermatitis associated with PD-1 inhibitor therapy occurs more frequently in patients with cutaneous tumors such as melanoma compared to those with head and neck cancers.² Curry et al¹ reported that treatment with an immune checkpoint blockade can lead to immune-related adverse effects, most commonly affecting the gastrointestinal tract, liver, and skin. The same report cited dermatologic toxicity as an adverse effect in approximately 39% of patients treated with anti–PD-1 and approximately 17% of anti–PD-L1.¹ The 4 main categories of dermatologic toxicities to immunotherapies in general include inflammatory disorders, immunobullous disorders, alterations of keratinocytes, and alteration of melanocytes. The most common adverse effects from the use of the PD-1 inhibitor nivolumab were skin rashes, not otherwise specified (14%–20%), pruritus (13%–18%), and vitiligo (~8%).¹ Of the cutaneous dermatitic reactions to PD-1 and PD-L1 inhibitors that were biopsied, the 2 most common were lichenoid dermatitis and spongiotic dermatitis.² Seldomly, there have been reports of keratoacanthomas (KAs) in association with anti–PD-1 therapy.³

A KA is a common skin tumor that appears most frequently as a solitary lesion and is thought to arise from the hair follicle.⁴ It resembles squamous cell carcinoma and commonly regresses within months without intervention. Exposure to UV light is a known risk factor for the development of KAs.

Eruptive KAs have been found in association with 10 cases of various cancers treated with the PD-1 inhibitors pembrolizumab and nivolumab.³ Multiple lesions on photodistributed areas of the body were reported in all 10 cases. Various treatments were used in these 10 cases—doxycycline and niacinamide, electrodesiccation and curettage, clobetasol ointment and/or intralesional triamcinolone, cryotherapy, imiquimod, or no treatment—as well as the cessation of PD-1 inhibitor therapy, with 4 cases continuing therapy and 6 cases discontinuing therapy. Nine cases regressed by 6 months; electrodesiccation and curettage of the lesions was used in the tenth case.³ We report a case of eruptive KA after 1 cycle of nivolumab therapy for metastatic melanoma.

A 79-year-old woman with stage III melanoma presented to her dermatologist after developing generalized pruritic lichenoid eruptions involving the torso, arms, and legs, as well as erosions on the lips, buccal mucosa, and palate 1 month after starting nivolumab therapy. The patient initially presented to dermatology with an irregularly shaped lesion on the left upper back 3 months prior. Biopsy results at that time revealed a diagnosis of malignant melanoma, lentigo maligna type. The lesion was 1.5-mm thick and classified as Clark level IV with a mitotic count of 6 per mm². Molecular genetic studies showed expression of PD-L1 and no expression of c-KIT. The patient underwent wide local excision, and a sentinel lymph node biopsy was positive. Positron emission tomography did not show any hypermetabolic lesions, and magnetic resonance imaging did not indicate brain metastasis. The patient underwent an axillary dissection, which did not show any residual melanoma. She was started on adjuvant immunotherapy with intravenous nivolumab 480 mg monthly and developed pruritic crusted lesions on the arms, legs, and torso 1 month later, which prompted follow-up to dermatology.

At the current presentation 4 months after the onset of lesions, physical examination revealed lichenoid patches with serous crusting that were concentrated on the torso but also affected the arms and legs. She developed erosions on the upper and lower lips, buccal mucosa, and hard and soft palates, as well as painful, erythematous, dome-shaped papules and nodules on the legs (Figure 1). Her oncologist previously had initiated treatment at the onset of the lesions with clobetasol cream and valacyclovir for the lesions, but the patient showed no improvement.

Four months after the onset of the lesions, the patient was re-referred to her dermatologist, and a biopsy was performed on the left lower leg that showed squamous cell carcinoma, KA type. Additionally, flat erythematous patches were seen on the legs that were consistent with a lichenoid drug eruption. Two weeks later, she was started on halobetasol propionate ointment 0.05% for treatment of the KAs. At 2-week follow-up, 5 months after the onset of the lesions, the patient showed no signs of improvement. An oral prednisone taper of 60 mg for 3 days, 40 mg for 3 days, and then 20 mg daily for a total of 4 weeks was started to treat the lichenoid dermatitis and eruptive KAs. At the next follow-up 6.5 months following the first eruptive KAs, she was no longer using topical or oral steroids, she did not have any new eruptive KAs, and old lesions showed regression (Figure 2). The patient still experienced postinflammatory erythema and hyperpigmentation at the location of the KAs but showed improvement of the lichenoid drug eruption.

We describe a case of eruptive KAs after use of a PD-1 inhibitor for treatment of melanoma. Our patient developed eruptive KAs after only 1 nivolumab treatment. Another report described onset of eruptive KAs after 1 month of nivolumab infusions.³ The KAs experienced by our patient took 6.5 months to regress, which is unusual compared to other case reports in which the KAs self-resolved within a few months, though one other case described lesions that persisted for 6 months.³

Our patient was treated with topical steroids and an oral steroid taper for the concomitant lichenoid drug eruption. It is unknown if the steroids affected the course of the KAs or if they spontaneously regressed on their own. Freites-Martinez et al⁵ described that regression of KAs may be related to an immune response, but corticosteroids are inherently immunosuppressive. They hypothesized that corticosteroids help to temper the heightened immune response of eruptive KAs.⁵

Our patient had oral ulcers, which may have been indicative of an oral lichenoid drug eruption, as well as skin lesions representative of a cutaneous lichenoid drug eruption. This is a favorable reaction, as lichenoid dermatitis is thought to represent successful PD-1 inhibition and therefore a better response to oncologic therapies.² Comorbid lichenoid drug eruption lesions and eruptive KAs may be suggestive of increased T-cell activity,^2,6,7 though some prior case studies have reported eruptive KAs in isolation.³

Discontinuation of immunotherapy due to development of eruptive KAs presents a challenge in the treatment of underlying malignancies such as melanoma. Immunotherapy was discontinued in 7 of 11 cases due to these cutaneous reactions.³ Similarly, our patient underwent only 1 cycle of immunotherapy before developing eruptive KAs and discontinuing PD-1 inhibitor therapy. If we are better able to treat eruptive KAs, then patients can remain on immunotherapy to treat underlying malignancies. Crow et al⁸ showed improvement in lesions when 3 patients with eruptive KAs were treated with hydroxychloroquine; the Goeckerman regimen consisting of steroids, UVB phototherapy, and crude coal tar; and Unna boots with zinc oxide and compression stockings. The above may be added to a list of possible treatments to consider for hastening the regression of eruptive KAs.

Our patient’s clinical course was similar to reports on the regressive nature of eruptive KAs within 6 months after initial eruption. Although it is likely that KAs will regress on their own, treatment modalities that speed up recovery are a future source for research.

To the Editor:

Programmed cell death protein 1 (PD-1) inhibitors have been widely used in the treatment of various cancers. Programmed cell death-ligand 1 (PD-L1) and programmed cell death-ligand 2 located on cancer cells will bind to PD-1 receptors on T cells and suppress them, which will prevent cancer cell destruction. Programmed cell death protein 1 inhibitors block the binding of PD-L1 to cancer cells, which then prevents T-cell immunosuppression.¹ However, cutaneous adverse effects have been associated with PD-1 inhibitors. Dermatitis associated with PD-1 inhibitor therapy occurs more frequently in patients with cutaneous tumors such as melanoma compared to those with head and neck cancers.² Curry et al¹ reported that treatment with an immune checkpoint blockade can lead to immune-related adverse effects, most commonly affecting the gastrointestinal tract, liver, and skin. The same report cited dermatologic toxicity as an adverse effect in approximately 39% of patients treated with anti–PD-1 and approximately 17% of anti–PD-L1.¹ The 4 main categories of dermatologic toxicities to immunotherapies in general include inflammatory disorders, immunobullous disorders, alterations of keratinocytes, and alteration of melanocytes. The most common adverse effects from the use of the PD-1 inhibitor nivolumab were skin rashes, not otherwise specified (14%–20%), pruritus (13%–18%), and vitiligo (~8%).¹ Of the cutaneous dermatitic reactions to PD-1 and PD-L1 inhibitors that were biopsied, the 2 most common were lichenoid dermatitis and spongiotic dermatitis.² Seldomly, there have been reports of keratoacanthomas (KAs) in association with anti–PD-1 therapy.³

A KA is a common skin tumor that appears most frequently as a solitary lesion and is thought to arise from the hair follicle.⁴ It resembles squamous cell carcinoma and commonly regresses within months without intervention. Exposure to UV light is a known risk factor for the development of KAs.

Eruptive KAs have been found in association with 10 cases of various cancers treated with the PD-1 inhibitors pembrolizumab and nivolumab.³ Multiple lesions on photodistributed areas of the body were reported in all 10 cases. Various treatments were used in these 10 cases—doxycycline and niacinamide, electrodesiccation and curettage, clobetasol ointment and/or intralesional triamcinolone, cryotherapy, imiquimod, or no treatment—as well as the cessation of PD-1 inhibitor therapy, with 4 cases continuing therapy and 6 cases discontinuing therapy. Nine cases regressed by 6 months; electrodesiccation and curettage of the lesions was used in the tenth case.³ We report a case of eruptive KA after 1 cycle of nivolumab therapy for metastatic melanoma.

A 79-year-old woman with stage III melanoma presented to her dermatologist after developing generalized pruritic lichenoid eruptions involving the torso, arms, and legs, as well as erosions on the lips, buccal mucosa, and palate 1 month after starting nivolumab therapy. The patient initially presented to dermatology with an irregularly shaped lesion on the left upper back 3 months prior. Biopsy results at that time revealed a diagnosis of malignant melanoma, lentigo maligna type. The lesion was 1.5-mm thick and classified as Clark level IV with a mitotic count of 6 per mm². Molecular genetic studies showed expression of PD-L1 and no expression of c-KIT. The patient underwent wide local excision, and a sentinel lymph node biopsy was positive. Positron emission tomography did not show any hypermetabolic lesions, and magnetic resonance imaging did not indicate brain metastasis. The patient underwent an axillary dissection, which did not show any residual melanoma. She was started on adjuvant immunotherapy with intravenous nivolumab 480 mg monthly and developed pruritic crusted lesions on the arms, legs, and torso 1 month later, which prompted follow-up to dermatology.

At the current presentation 4 months after the onset of lesions, physical examination revealed lichenoid patches with serous crusting that were concentrated on the torso but also affected the arms and legs. She developed erosions on the upper and lower lips, buccal mucosa, and hard and soft palates, as well as painful, erythematous, dome-shaped papules and nodules on the legs (Figure 1). Her oncologist previously had initiated treatment at the onset of the lesions with clobetasol cream and valacyclovir for the lesions, but the patient showed no improvement.

Four months after the onset of the lesions, the patient was re-referred to her dermatologist, and a biopsy was performed on the left lower leg that showed squamous cell carcinoma, KA type. Additionally, flat erythematous patches were seen on the legs that were consistent with a lichenoid drug eruption. Two weeks later, she was started on halobetasol propionate ointment 0.05% for treatment of the KAs. At 2-week follow-up, 5 months after the onset of the lesions, the patient showed no signs of improvement. An oral prednisone taper of 60 mg for 3 days, 40 mg for 3 days, and then 20 mg daily for a total of 4 weeks was started to treat the lichenoid dermatitis and eruptive KAs. At the next follow-up 6.5 months following the first eruptive KAs, she was no longer using topical or oral steroids, she did not have any new eruptive KAs, and old lesions showed regression (Figure 2). The patient still experienced postinflammatory erythema and hyperpigmentation at the location of the KAs but showed improvement of the lichenoid drug eruption.

We describe a case of eruptive KAs after use of a PD-1 inhibitor for treatment of melanoma. Our patient developed eruptive KAs after only 1 nivolumab treatment. Another report described onset of eruptive KAs after 1 month of nivolumab infusions.³ The KAs experienced by our patient took 6.5 months to regress, which is unusual compared to other case reports in which the KAs self-resolved within a few months, though one other case described lesions that persisted for 6 months.³

Our patient was treated with topical steroids and an oral steroid taper for the concomitant lichenoid drug eruption. It is unknown if the steroids affected the course of the KAs or if they spontaneously regressed on their own. Freites-Martinez et al⁵ described that regression of KAs may be related to an immune response, but corticosteroids are inherently immunosuppressive. They hypothesized that corticosteroids help to temper the heightened immune response of eruptive KAs.⁵

Our patient had oral ulcers, which may have been indicative of an oral lichenoid drug eruption, as well as skin lesions representative of a cutaneous lichenoid drug eruption. This is a favorable reaction, as lichenoid dermatitis is thought to represent successful PD-1 inhibition and therefore a better response to oncologic therapies.² Comorbid lichenoid drug eruption lesions and eruptive KAs may be suggestive of increased T-cell activity,^2,6,7 though some prior case studies have reported eruptive KAs in isolation.³

Discontinuation of immunotherapy due to development of eruptive KAs presents a challenge in the treatment of underlying malignancies such as melanoma. Immunotherapy was discontinued in 7 of 11 cases due to these cutaneous reactions.³ Similarly, our patient underwent only 1 cycle of immunotherapy before developing eruptive KAs and discontinuing PD-1 inhibitor therapy. If we are better able to treat eruptive KAs, then patients can remain on immunotherapy to treat underlying malignancies. Crow et al⁸ showed improvement in lesions when 3 patients with eruptive KAs were treated with hydroxychloroquine; the Goeckerman regimen consisting of steroids, UVB phototherapy, and crude coal tar; and Unna boots with zinc oxide and compression stockings. The above may be added to a list of possible treatments to consider for hastening the regression of eruptive KAs.

Our patient’s clinical course was similar to reports on the regressive nature of eruptive KAs within 6 months after initial eruption. Although it is likely that KAs will regress on their own, treatment modalities that speed up recovery are a future source for research.

To the Editor:

Programmed cell death protein 1 (PD-1) inhibitors have been widely used in the treatment of various cancers. Programmed cell death-ligand 1 (PD-L1) and programmed cell death-ligand 2 located on cancer cells will bind to PD-1 receptors on T cells and suppress them, which will prevent cancer cell destruction. Programmed cell death protein 1 inhibitors block the binding of PD-L1 to cancer cells, which then prevents T-cell immunosuppression.¹ However, cutaneous adverse effects have been associated with PD-1 inhibitors. Dermatitis associated with PD-1 inhibitor therapy occurs more frequently in patients with cutaneous tumors such as melanoma compared to those with head and neck cancers.² Curry et al¹ reported that treatment with an immune checkpoint blockade can lead to immune-related adverse effects, most commonly affecting the gastrointestinal tract, liver, and skin. The same report cited dermatologic toxicity as an adverse effect in approximately 39% of patients treated with anti–PD-1 and approximately 17% of anti–PD-L1.¹ The 4 main categories of dermatologic toxicities to immunotherapies in general include inflammatory disorders, immunobullous disorders, alterations of keratinocytes, and alteration of melanocytes. The most common adverse effects from the use of the PD-1 inhibitor nivolumab were skin rashes, not otherwise specified (14%–20%), pruritus (13%–18%), and vitiligo (~8%).¹ Of the cutaneous dermatitic reactions to PD-1 and PD-L1 inhibitors that were biopsied, the 2 most common were lichenoid dermatitis and spongiotic dermatitis.² Seldomly, there have been reports of keratoacanthomas (KAs) in association with anti–PD-1 therapy.³

A KA is a common skin tumor that appears most frequently as a solitary lesion and is thought to arise from the hair follicle.⁴ It resembles squamous cell carcinoma and commonly regresses within months without intervention. Exposure to UV light is a known risk factor for the development of KAs.

Eruptive KAs have been found in association with 10 cases of various cancers treated with the PD-1 inhibitors pembrolizumab and nivolumab.³ Multiple lesions on photodistributed areas of the body were reported in all 10 cases. Various treatments were used in these 10 cases—doxycycline and niacinamide, electrodesiccation and curettage, clobetasol ointment and/or intralesional triamcinolone, cryotherapy, imiquimod, or no treatment—as well as the cessation of PD-1 inhibitor therapy, with 4 cases continuing therapy and 6 cases discontinuing therapy. Nine cases regressed by 6 months; electrodesiccation and curettage of the lesions was used in the tenth case.³ We report a case of eruptive KA after 1 cycle of nivolumab therapy for metastatic melanoma.

A 79-year-old woman with stage III melanoma presented to her dermatologist after developing generalized pruritic lichenoid eruptions involving the torso, arms, and legs, as well as erosions on the lips, buccal mucosa, and palate 1 month after starting nivolumab therapy. The patient initially presented to dermatology with an irregularly shaped lesion on the left upper back 3 months prior. Biopsy results at that time revealed a diagnosis of malignant melanoma, lentigo maligna type. The lesion was 1.5-mm thick and classified as Clark level IV with a mitotic count of 6 per mm². Molecular genetic studies showed expression of PD-L1 and no expression of c-KIT. The patient underwent wide local excision, and a sentinel lymph node biopsy was positive. Positron emission tomography did not show any hypermetabolic lesions, and magnetic resonance imaging did not indicate brain metastasis. The patient underwent an axillary dissection, which did not show any residual melanoma. She was started on adjuvant immunotherapy with intravenous nivolumab 480 mg monthly and developed pruritic crusted lesions on the arms, legs, and torso 1 month later, which prompted follow-up to dermatology.

At the current presentation 4 months after the onset of lesions, physical examination revealed lichenoid patches with serous crusting that were concentrated on the torso but also affected the arms and legs. She developed erosions on the upper and lower lips, buccal mucosa, and hard and soft palates, as well as painful, erythematous, dome-shaped papules and nodules on the legs (Figure 1). Her oncologist previously had initiated treatment at the onset of the lesions with clobetasol cream and valacyclovir for the lesions, but the patient showed no improvement.

Four months after the onset of the lesions, the patient was re-referred to her dermatologist, and a biopsy was performed on the left lower leg that showed squamous cell carcinoma, KA type. Additionally, flat erythematous patches were seen on the legs that were consistent with a lichenoid drug eruption. Two weeks later, she was started on halobetasol propionate ointment 0.05% for treatment of the KAs. At 2-week follow-up, 5 months after the onset of the lesions, the patient showed no signs of improvement. An oral prednisone taper of 60 mg for 3 days, 40 mg for 3 days, and then 20 mg daily for a total of 4 weeks was started to treat the lichenoid dermatitis and eruptive KAs. At the next follow-up 6.5 months following the first eruptive KAs, she was no longer using topical or oral steroids, she did not have any new eruptive KAs, and old lesions showed regression (Figure 2). The patient still experienced postinflammatory erythema and hyperpigmentation at the location of the KAs but showed improvement of the lichenoid drug eruption.

We describe a case of eruptive KAs after use of a PD-1 inhibitor for treatment of melanoma. Our patient developed eruptive KAs after only 1 nivolumab treatment. Another report described onset of eruptive KAs after 1 month of nivolumab infusions.³ The KAs experienced by our patient took 6.5 months to regress, which is unusual compared to other case reports in which the KAs self-resolved within a few months, though one other case described lesions that persisted for 6 months.³

Our patient was treated with topical steroids and an oral steroid taper for the concomitant lichenoid drug eruption. It is unknown if the steroids affected the course of the KAs or if they spontaneously regressed on their own. Freites-Martinez et al⁵ described that regression of KAs may be related to an immune response, but corticosteroids are inherently immunosuppressive. They hypothesized that corticosteroids help to temper the heightened immune response of eruptive KAs.⁵

Our patient had oral ulcers, which may have been indicative of an oral lichenoid drug eruption, as well as skin lesions representative of a cutaneous lichenoid drug eruption. This is a favorable reaction, as lichenoid dermatitis is thought to represent successful PD-1 inhibition and therefore a better response to oncologic therapies.² Comorbid lichenoid drug eruption lesions and eruptive KAs may be suggestive of increased T-cell activity,^2,6,7 though some prior case studies have reported eruptive KAs in isolation.³

Discontinuation of immunotherapy due to development of eruptive KAs presents a challenge in the treatment of underlying malignancies such as melanoma. Immunotherapy was discontinued in 7 of 11 cases due to these cutaneous reactions.³ Similarly, our patient underwent only 1 cycle of immunotherapy before developing eruptive KAs and discontinuing PD-1 inhibitor therapy. If we are better able to treat eruptive KAs, then patients can remain on immunotherapy to treat underlying malignancies. Crow et al⁸ showed improvement in lesions when 3 patients with eruptive KAs were treated with hydroxychloroquine; the Goeckerman regimen consisting of steroids, UVB phototherapy, and crude coal tar; and Unna boots with zinc oxide and compression stockings. The above may be added to a list of possible treatments to consider for hastening the regression of eruptive KAs.

Our patient’s clinical course was similar to reports on the regressive nature of eruptive KAs within 6 months after initial eruption. Although it is likely that KAs will regress on their own, treatment modalities that speed up recovery are a future source for research.

Inpatient dermatology consultation services are becoming increasingly prevalent in hospital institutions.^1-3 Although often underutilized as a consulting service, dermatology-related admissions cost hundreds of millions of dollars for the health care system.^1,2 Misdiagnosis, prolonged hospital stays, and incorrect treatment are common results of lack of involvement by a skin expert.^1-3 The importance of consultative inpatient dermatology cannot be understated. Accreditation Council for Graduate Medical Education requirements for proficiency in dermatology residency include exposure to inpatient dermatology, and it is our duty as residents to aid our colleagues in the management and treatment of cutaneous disease.

Although exposure to inpatient dermatology varies across residency programs, nearly every dermatology resident is bound to perform a consultation and be involved in the care of a hospitalized patient. At our program at the University of Utah (Salt Lake City), we have robust inpatient exposure, and after numerous hours spent on the forefront of inpatient dermatology, I have accrued a list of specific tips and techniques that have aided me as a resident clinician.

Pre-Rounding More Thoroughly

When I started as a postgraduate year 2 (PGY-2) on the inpatient dermatology rotation, I found myself perplexed. I had learned how to round in internal medicine but was unaccustomed to the nuances of specialty rounds. My list included calciphylaxis, small vessel vasculitis, cellulitis, stasis dermatitis, toxic epidermal necrolysis, and atypical mycobacterial infection. The first few days of service were undeniably difficult due to the daily consultations, complexity of admitted patients, and need for efficiency. I sometimes overlooked important laboratory test results, medication changes, and interdisciplinary discussions that prolonged rounding. As dermatologists, we are responsible for the largest organ of the body, and it is important to approach patients in a comprehensive manner. Pre-rounding should include reviewing interdisciplinary notes, laboratory values/results, and medications, and performing a focused skin examination with a review of systems during the encounter. Importantly, most electronic medical record systems offer an automated rounding sheet. In Epic (Epic Systems Corporation), I would use the bone marrow transplant rounding sheet, which includes laboratory test results, vitals, and medications. After printing out the rounding sheet, I would note important updates for each patient. Although pre-rounding and chart review requires time and effort, it aided me in providing elevated patient care and becoming more efficient during rounds. Over time I have come to strongly appreciate the term dermatology hospitalist. Cutaneous manifestations of systemic disease require thoughtful consideration and workup.

New Patient Consultations: Must-Ask Questions

Holding the university inpatient pager can be stressful. At the University of Utah, we often carry 5 to 10 patients on our list and receive 3 to 4 new consultations a day, sometimes right before 5 pm. When receiving new consultations, it is important to obtain the whole story from the requesting provider. Some of the questions may seem obvious, but I am frequently reminded of the inefficiencies I encountered as a first-year dermatology resident. Remember to always be kind to your consulting colleagues. Dermatology is a difficult discipline, and describing rashes is no easy task. Here is my systematic approach to questions that should be asked of the requesting provider during each new patient consultation:

• What is the patient’s name, room number, and medical record number?
• Is this patient getting admitted or admitted currently?
• Is the rash the reason for admission? (This can greatly help with triaging the urgency of evaluation.)
• Is the rash painful?
• Is this patient ill?
• How would you describe the rash?

When evaluating new patients, it is crucial to remember the morphology camps. Formulating a differential diagnosis on a complex patient can be difficult; however, remembering the morphology camps of acneiform, dermal, eczematous, erythematous, subcutaneous, vasculitic, vasculopathic, and vesiculobullous lesions can be extremely helpful. Additionally, it is crucial to perform a thorough and complete skin examination on every patient. When emphasizing the importance of this, I often am reminded of a humbling moment early in my training. Our team was consulted on a patient with cellulitis and stasis dermatitis. It was a busy day, and my examination was quick and focused on the lower and upper extremities, chest, and back. The patient improved from a cutaneous standpoint and was discharged. At follow-up the next week, one of my attending providers biopsied an atypical macule on the retroauricular region, which was found to be consistent with a stage 1A melanoma. Even on the longest and most tiring hospital days, it is important to perform a full-body skin examination on each patient. You may end up saving a life.

An Organized Toolbox: What to Carry

Similar to our ophthalmology colleagues who are seen carrying around a suitcase in the hospital, I highly recommend some form of a toolbox or bag for performing inpatient biopsies (Table). Carrying around an organized bag, albeit bulky and unfashionable, has saved me numerous trips back to clinic for unexpected complications including fixing leaky vessels, closing stubborn ulcers, and coordinating sedated biopsies in the operating room.

Final Thoughts

As I near the completion of my residency journey, I hope these tips will aid budding and current dermatology residents at excelling as dermatology hospitalists during inpatient rotations. Dermatologists can make a profound impact on a variety of patients, especially when treating hospitalized patients on the clinical forefront. Our role extends beyond the skin, as cutaneous manifestations of internal disease are not uncommon.

Inpatient dermatology consultation services are becoming increasingly prevalent in hospital institutions.^1-3 Although often underutilized as a consulting service, dermatology-related admissions cost hundreds of millions of dollars for the health care system.^1,2 Misdiagnosis, prolonged hospital stays, and incorrect treatment are common results of lack of involvement by a skin expert.^1-3 The importance of consultative inpatient dermatology cannot be understated. Accreditation Council for Graduate Medical Education requirements for proficiency in dermatology residency include exposure to inpatient dermatology, and it is our duty as residents to aid our colleagues in the management and treatment of cutaneous disease.

Although exposure to inpatient dermatology varies across residency programs, nearly every dermatology resident is bound to perform a consultation and be involved in the care of a hospitalized patient. At our program at the University of Utah (Salt Lake City), we have robust inpatient exposure, and after numerous hours spent on the forefront of inpatient dermatology, I have accrued a list of specific tips and techniques that have aided me as a resident clinician.

Pre-Rounding More Thoroughly

When I started as a postgraduate year 2 (PGY-2) on the inpatient dermatology rotation, I found myself perplexed. I had learned how to round in internal medicine but was unaccustomed to the nuances of specialty rounds. My list included calciphylaxis, small vessel vasculitis, cellulitis, stasis dermatitis, toxic epidermal necrolysis, and atypical mycobacterial infection. The first few days of service were undeniably difficult due to the daily consultations, complexity of admitted patients, and need for efficiency. I sometimes overlooked important laboratory test results, medication changes, and interdisciplinary discussions that prolonged rounding. As dermatologists, we are responsible for the largest organ of the body, and it is important to approach patients in a comprehensive manner. Pre-rounding should include reviewing interdisciplinary notes, laboratory values/results, and medications, and performing a focused skin examination with a review of systems during the encounter. Importantly, most electronic medical record systems offer an automated rounding sheet. In Epic (Epic Systems Corporation), I would use the bone marrow transplant rounding sheet, which includes laboratory test results, vitals, and medications. After printing out the rounding sheet, I would note important updates for each patient. Although pre-rounding and chart review requires time and effort, it aided me in providing elevated patient care and becoming more efficient during rounds. Over time I have come to strongly appreciate the term dermatology hospitalist. Cutaneous manifestations of systemic disease require thoughtful consideration and workup.

New Patient Consultations: Must-Ask Questions

Holding the university inpatient pager can be stressful. At the University of Utah, we often carry 5 to 10 patients on our list and receive 3 to 4 new consultations a day, sometimes right before 5 pm. When receiving new consultations, it is important to obtain the whole story from the requesting provider. Some of the questions may seem obvious, but I am frequently reminded of the inefficiencies I encountered as a first-year dermatology resident. Remember to always be kind to your consulting colleagues. Dermatology is a difficult discipline, and describing rashes is no easy task. Here is my systematic approach to questions that should be asked of the requesting provider during each new patient consultation:

• What is the patient’s name, room number, and medical record number?
• Is this patient getting admitted or admitted currently?
• Is the rash the reason for admission? (This can greatly help with triaging the urgency of evaluation.)
• Is the rash painful?
• Is this patient ill?
• How would you describe the rash?

When evaluating new patients, it is crucial to remember the morphology camps. Formulating a differential diagnosis on a complex patient can be difficult; however, remembering the morphology camps of acneiform, dermal, eczematous, erythematous, subcutaneous, vasculitic, vasculopathic, and vesiculobullous lesions can be extremely helpful. Additionally, it is crucial to perform a thorough and complete skin examination on every patient. When emphasizing the importance of this, I often am reminded of a humbling moment early in my training. Our team was consulted on a patient with cellulitis and stasis dermatitis. It was a busy day, and my examination was quick and focused on the lower and upper extremities, chest, and back. The patient improved from a cutaneous standpoint and was discharged. At follow-up the next week, one of my attending providers biopsied an atypical macule on the retroauricular region, which was found to be consistent with a stage 1A melanoma. Even on the longest and most tiring hospital days, it is important to perform a full-body skin examination on each patient. You may end up saving a life.

An Organized Toolbox: What to Carry

Similar to our ophthalmology colleagues who are seen carrying around a suitcase in the hospital, I highly recommend some form of a toolbox or bag for performing inpatient biopsies (Table). Carrying around an organized bag, albeit bulky and unfashionable, has saved me numerous trips back to clinic for unexpected complications including fixing leaky vessels, closing stubborn ulcers, and coordinating sedated biopsies in the operating room.

Final Thoughts

As I near the completion of my residency journey, I hope these tips will aid budding and current dermatology residents at excelling as dermatology hospitalists during inpatient rotations. Dermatologists can make a profound impact on a variety of patients, especially when treating hospitalized patients on the clinical forefront. Our role extends beyond the skin, as cutaneous manifestations of internal disease are not uncommon.

Inpatient dermatology consultation services are becoming increasingly prevalent in hospital institutions.^1-3 Although often underutilized as a consulting service, dermatology-related admissions cost hundreds of millions of dollars for the health care system.^1,2 Misdiagnosis, prolonged hospital stays, and incorrect treatment are common results of lack of involvement by a skin expert.^1-3 The importance of consultative inpatient dermatology cannot be understated. Accreditation Council for Graduate Medical Education requirements for proficiency in dermatology residency include exposure to inpatient dermatology, and it is our duty as residents to aid our colleagues in the management and treatment of cutaneous disease.

Although exposure to inpatient dermatology varies across residency programs, nearly every dermatology resident is bound to perform a consultation and be involved in the care of a hospitalized patient. At our program at the University of Utah (Salt Lake City), we have robust inpatient exposure, and after numerous hours spent on the forefront of inpatient dermatology, I have accrued a list of specific tips and techniques that have aided me as a resident clinician.

Pre-Rounding More Thoroughly

When I started as a postgraduate year 2 (PGY-2) on the inpatient dermatology rotation, I found myself perplexed. I had learned how to round in internal medicine but was unaccustomed to the nuances of specialty rounds. My list included calciphylaxis, small vessel vasculitis, cellulitis, stasis dermatitis, toxic epidermal necrolysis, and atypical mycobacterial infection. The first few days of service were undeniably difficult due to the daily consultations, complexity of admitted patients, and need for efficiency. I sometimes overlooked important laboratory test results, medication changes, and interdisciplinary discussions that prolonged rounding. As dermatologists, we are responsible for the largest organ of the body, and it is important to approach patients in a comprehensive manner. Pre-rounding should include reviewing interdisciplinary notes, laboratory values/results, and medications, and performing a focused skin examination with a review of systems during the encounter. Importantly, most electronic medical record systems offer an automated rounding sheet. In Epic (Epic Systems Corporation), I would use the bone marrow transplant rounding sheet, which includes laboratory test results, vitals, and medications. After printing out the rounding sheet, I would note important updates for each patient. Although pre-rounding and chart review requires time and effort, it aided me in providing elevated patient care and becoming more efficient during rounds. Over time I have come to strongly appreciate the term dermatology hospitalist. Cutaneous manifestations of systemic disease require thoughtful consideration and workup.

New Patient Consultations: Must-Ask Questions

Holding the university inpatient pager can be stressful. At the University of Utah, we often carry 5 to 10 patients on our list and receive 3 to 4 new consultations a day, sometimes right before 5 pm. When receiving new consultations, it is important to obtain the whole story from the requesting provider. Some of the questions may seem obvious, but I am frequently reminded of the inefficiencies I encountered as a first-year dermatology resident. Remember to always be kind to your consulting colleagues. Dermatology is a difficult discipline, and describing rashes is no easy task. Here is my systematic approach to questions that should be asked of the requesting provider during each new patient consultation:

• What is the patient’s name, room number, and medical record number?
• Is this patient getting admitted or admitted currently?
• Is the rash the reason for admission? (This can greatly help with triaging the urgency of evaluation.)
• Is the rash painful?
• Is this patient ill?
• How would you describe the rash?

When evaluating new patients, it is crucial to remember the morphology camps. Formulating a differential diagnosis on a complex patient can be difficult; however, remembering the morphology camps of acneiform, dermal, eczematous, erythematous, subcutaneous, vasculitic, vasculopathic, and vesiculobullous lesions can be extremely helpful. Additionally, it is crucial to perform a thorough and complete skin examination on every patient. When emphasizing the importance of this, I often am reminded of a humbling moment early in my training. Our team was consulted on a patient with cellulitis and stasis dermatitis. It was a busy day, and my examination was quick and focused on the lower and upper extremities, chest, and back. The patient improved from a cutaneous standpoint and was discharged. At follow-up the next week, one of my attending providers biopsied an atypical macule on the retroauricular region, which was found to be consistent with a stage 1A melanoma. Even on the longest and most tiring hospital days, it is important to perform a full-body skin examination on each patient. You may end up saving a life.

An Organized Toolbox: What to Carry

Similar to our ophthalmology colleagues who are seen carrying around a suitcase in the hospital, I highly recommend some form of a toolbox or bag for performing inpatient biopsies (Table). Carrying around an organized bag, albeit bulky and unfashionable, has saved me numerous trips back to clinic for unexpected complications including fixing leaky vessels, closing stubborn ulcers, and coordinating sedated biopsies in the operating room.

Final Thoughts

As I near the completion of my residency journey, I hope these tips will aid budding and current dermatology residents at excelling as dermatology hospitalists during inpatient rotations. Dermatologists can make a profound impact on a variety of patients, especially when treating hospitalized patients on the clinical forefront. Our role extends beyond the skin, as cutaneous manifestations of internal disease are not uncommon.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

The Federal Trade Commission’s proposed regulation that would ban noncompete agreements across the country seems like potential good news for doctors. Of course, many hospitals and employers are against it. As a result, the FTC’s sweeping proposal has tongues wagging on both sides of the issue.

Many physicians are thrilled that they may soon have more control over their career and not be stuck in jobs where they feel frustrated, underpaid, or blocked in their progress.

If passed, the proposed ban would allow physicians to get a new job with a competing organization, bucking a long-standing trend that hospitals and health care systems have heavily relied on to keep staff in place. As of 2018, as many as 45% of primary care physicians had inked such agreements with their employers.

Typically, the agreements prevent physicians from practicing medicine with a new employer for a defined period within a specific geographic area. No matter how attractive an alternate offer of employment might be, doctors are bound by the agreements to say no if the offer exists in that defined area and time period.

The period for public comment on the proposed regulation ended on April 19, and there is currently no set date for a decision.

In a Medscape poll of 558 physicians, more than 9 out of 10 respondents said that they were either currently bound by a noncompete clause or that they had been bound by one in the past that had forced them to temporarily stop working, commute long distances, move to a different area, or switch fields.

The new proposal would make it illegal for an employer, such as a hospital or large group, to enter a noncompete with a worker; maintain a noncompete with a worker; or represent to a worker, under certain circumstances, that the worker is subject to a noncompete.

It also would not only ban future noncompete agreements but also retroactively invalidate existing ones. The FTC reasons that noncompete clauses could potentially increase worker earnings as well as lower health care costs by billions of dollars. If the ruling were to move forward, it would represent part of President Biden’s “worker-forward” priorities, focusing on how competition can be a good thing for employees. The President billed the FTC’s announcement as a “huge win for workers.”

In its statements on the proposed ban, the FTC claimed that it could lower consumer prices across the board by as much as $150 billion per year and return nearly $300 million to workers each year.

However, even if passed, the draft rule would keep in place nonsolicitation rules that many health care organizations have put into place. That means that, if a physician leaves an employer, he or she cannot reach out to former patients and colleagues to bring them along or invite them to switch to him or her in the new job.

Within that clause, however, the FTC has specified that if such nonsolicitation agreement has the “equivalent effect” of a noncompete, the agency would deem it such. That means, even if that rule stays, it could be contested and may be interpreted as violating the noncompete law. So there’s value in reading all the fine print should the ban move forward.
 

Could the ban bring potential downsides?

Most physicians view the potential to break free of a noncompete agreement as a victory. Peter Glennon, an employment litigation attorney with The Glennon Law Firm in Rochester, N.Y., says not so fast. “If you ask anyone if they’d prefer a noncompete agreement, of course they’re going to say no,” he said in an interview. “It sounds like a restriction, one that can hold you back.”

Mr. Glennon believes that there are actually upsides to physician noncompetes. For instance, many noncompetes come with sign-on bonuses that could potentially disappear without the agreements. There’s also the fact that when some physicians sign a noncompete agreement, they then receive pro bono training and continuing education along with marketing and promotion of their skills. Without signing a noncompete, employers may be less incentivized to provide all those benefits to their physician employers.

Those benefits – and the noncompetes – also vary by specialty, Mr. Glennon said. “In 2021, Washington, DC, banned noncompetes for doctors making less than $250,000. So, most generalists there can walk across the street and get a new job. For specialists like cardiologists or neurosurgeons, however, advanced training and marketing benefits matter, so many of them don’t want to lose noncompetes.”

Still, most physicians hope that the FTC’s ban takes hold. Manan Shah, MD, founder, and chief medical officer at Wyndly, an allergy relief startup practice, is one of them.

“Initially, it might disincentivize hospital systems from helping new physicians build up their name and practice because they might be concerned about a physician leaving and starting anew,” he said. “But in the long term, hospitals require physicians to bring their patients to them for care, so the best hospitals will always compete for the best physicians and support them as they build up their practice.”

Dr. Shah views noncompetes as overly prohibitive to physicians. “Right now, if a physician starts a job at a large hospital system and realizes they want to switch jobs, the noncompete distances are so wide they often have to move cities to continue practicing,” he said. “Picking up and starting over in a new city isn’t an option for everyone and can be especially difficult for someone with a family.”

Where Mr. Glennon argued that a physician leaving a team-based practice might harm patients, Shah takes a different perspective. “Imagine you have a doctor whom you trust and have been working with,” he said. “If something changes at their hospital and they decide to move, you literally have to find a new doctor instead of just being able to see them at another location down the street.”

Another potential burden of the noncompete agreements is that they could possibly squelch doctor’s desires to hang up their own shingle. According to Dr. Shah, the agreements make it so that if a physician wants to work independently, it’s nearly impossible to fly solo. “This is frustrating because independent practices have been shown to be more cost effective and allow patients to build better relationships with their doctors,” he claimed.

A 2016 study from Annals of Family Medicine supports that claim, at least for small general practices. Another study appearing in JAMA concurred. It does point out, however, that the cost equation is nuanced and that benefits of larger systems include more resilience to economic downturns and can provide more specialized care.
 

Will nonprofit hospitals be subject to this noncompete ban?

Further complicating the noncompete ban issue is how it might impact nonprofit institutions versus their for-profit peers. Most hospitals structured as nonprofits would be exempt from the rule because the FTC Act provides that it can enforce against “persons, partnerships, or corporations,” which are further defined as entities “organized to carry on business for their own profit or that of their members.”

The fallout from this, said Dr. Shah, is that it “would disproportionately affect health care providers, since many hospital systems are nonprofits. This is disconcerting because we know that many nonprofit systems make large profits anyway and can offer executive teams’ lucrative packages, while the nurses, assistants, and physicians providing the care are generally not well compensated.”

So far, about nine states plus Washington, D.C., have already put noncompete bans in place, and they may serve as a harbinger of things to come should the federal ban go into effect. Each varies in its specifics. Some, like Indiana, outright ban them, whereas others limit them based on variables like income and industry. “We’re seeing these states responding to local market conditions,” said Darryl Drevna, senior director of regulatory affairs at the American Medical Group Association. “Health care is a hyperlocal market. Depending on the situation, the bans adapt and respond specific to those states.”

Should the federal ban take hold, however, it will supersede whatever rules the individual states have in place.

Some opponents of the federal ban proposal question its authority to begin with, however, Mr. Glennon included. “Many people believe the FTC is overstepping,” he said. “Some people believe that Section 5 of the FTC Act does not give it the authority to police labor markets.”

Mr. Drevna noted that the FTC has taken an aggressive stance, one that will ultimately wind up in the courts. “How it works out is anyone’s guess,” he said. “Ideally, the FTC will consider the comments and concerns of groups like AMGA and realize that states are best suited to regulate in this area.”

In general, the ban’s supporters are employees/physicians; those who oppose it are their employers. Joining the AMGA in speaking out against the noncompete ban is the American Hospital Association, whereas the American College of Emergency Physicians has come out largely in support of the ban.

Still, doctors like Dr. Shah remain hopeful. “I am optimistic that perhaps my colleagues will not continue to be stuck in overrestrictive noncompetes, but I am also realistic,” he said. “Hospital systems are already coming out strongly against this and they have deep pockets, so I won’t be surprised if it does not come to pass.”

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

The Federal Trade Commission’s proposed regulation that would ban noncompete agreements across the country seems like potential good news for doctors. Of course, many hospitals and employers are against it. As a result, the FTC’s sweeping proposal has tongues wagging on both sides of the issue.

Many physicians are thrilled that they may soon have more control over their career and not be stuck in jobs where they feel frustrated, underpaid, or blocked in their progress.

If passed, the proposed ban would allow physicians to get a new job with a competing organization, bucking a long-standing trend that hospitals and health care systems have heavily relied on to keep staff in place. As of 2018, as many as 45% of primary care physicians had inked such agreements with their employers.

Typically, the agreements prevent physicians from practicing medicine with a new employer for a defined period within a specific geographic area. No matter how attractive an alternate offer of employment might be, doctors are bound by the agreements to say no if the offer exists in that defined area and time period.

The period for public comment on the proposed regulation ended on April 19, and there is currently no set date for a decision.

In a Medscape poll of 558 physicians, more than 9 out of 10 respondents said that they were either currently bound by a noncompete clause or that they had been bound by one in the past that had forced them to temporarily stop working, commute long distances, move to a different area, or switch fields.

The new proposal would make it illegal for an employer, such as a hospital or large group, to enter a noncompete with a worker; maintain a noncompete with a worker; or represent to a worker, under certain circumstances, that the worker is subject to a noncompete.

It also would not only ban future noncompete agreements but also retroactively invalidate existing ones. The FTC reasons that noncompete clauses could potentially increase worker earnings as well as lower health care costs by billions of dollars. If the ruling were to move forward, it would represent part of President Biden’s “worker-forward” priorities, focusing on how competition can be a good thing for employees. The President billed the FTC’s announcement as a “huge win for workers.”

In its statements on the proposed ban, the FTC claimed that it could lower consumer prices across the board by as much as $150 billion per year and return nearly $300 million to workers each year.

However, even if passed, the draft rule would keep in place nonsolicitation rules that many health care organizations have put into place. That means that, if a physician leaves an employer, he or she cannot reach out to former patients and colleagues to bring them along or invite them to switch to him or her in the new job.

Within that clause, however, the FTC has specified that if such nonsolicitation agreement has the “equivalent effect” of a noncompete, the agency would deem it such. That means, even if that rule stays, it could be contested and may be interpreted as violating the noncompete law. So there’s value in reading all the fine print should the ban move forward.
 

Could the ban bring potential downsides?

Most physicians view the potential to break free of a noncompete agreement as a victory. Peter Glennon, an employment litigation attorney with The Glennon Law Firm in Rochester, N.Y., says not so fast. “If you ask anyone if they’d prefer a noncompete agreement, of course they’re going to say no,” he said in an interview. “It sounds like a restriction, one that can hold you back.”

Mr. Glennon believes that there are actually upsides to physician noncompetes. For instance, many noncompetes come with sign-on bonuses that could potentially disappear without the agreements. There’s also the fact that when some physicians sign a noncompete agreement, they then receive pro bono training and continuing education along with marketing and promotion of their skills. Without signing a noncompete, employers may be less incentivized to provide all those benefits to their physician employers.

Those benefits – and the noncompetes – also vary by specialty, Mr. Glennon said. “In 2021, Washington, DC, banned noncompetes for doctors making less than $250,000. So, most generalists there can walk across the street and get a new job. For specialists like cardiologists or neurosurgeons, however, advanced training and marketing benefits matter, so many of them don’t want to lose noncompetes.”

Still, most physicians hope that the FTC’s ban takes hold. Manan Shah, MD, founder, and chief medical officer at Wyndly, an allergy relief startup practice, is one of them.

“Initially, it might disincentivize hospital systems from helping new physicians build up their name and practice because they might be concerned about a physician leaving and starting anew,” he said. “But in the long term, hospitals require physicians to bring their patients to them for care, so the best hospitals will always compete for the best physicians and support them as they build up their practice.”

Dr. Shah views noncompetes as overly prohibitive to physicians. “Right now, if a physician starts a job at a large hospital system and realizes they want to switch jobs, the noncompete distances are so wide they often have to move cities to continue practicing,” he said. “Picking up and starting over in a new city isn’t an option for everyone and can be especially difficult for someone with a family.”

Where Mr. Glennon argued that a physician leaving a team-based practice might harm patients, Shah takes a different perspective. “Imagine you have a doctor whom you trust and have been working with,” he said. “If something changes at their hospital and they decide to move, you literally have to find a new doctor instead of just being able to see them at another location down the street.”

Another potential burden of the noncompete agreements is that they could possibly squelch doctor’s desires to hang up their own shingle. According to Dr. Shah, the agreements make it so that if a physician wants to work independently, it’s nearly impossible to fly solo. “This is frustrating because independent practices have been shown to be more cost effective and allow patients to build better relationships with their doctors,” he claimed.

A 2016 study from Annals of Family Medicine supports that claim, at least for small general practices. Another study appearing in JAMA concurred. It does point out, however, that the cost equation is nuanced and that benefits of larger systems include more resilience to economic downturns and can provide more specialized care.
 

Will nonprofit hospitals be subject to this noncompete ban?

Further complicating the noncompete ban issue is how it might impact nonprofit institutions versus their for-profit peers. Most hospitals structured as nonprofits would be exempt from the rule because the FTC Act provides that it can enforce against “persons, partnerships, or corporations,” which are further defined as entities “organized to carry on business for their own profit or that of their members.”

The fallout from this, said Dr. Shah, is that it “would disproportionately affect health care providers, since many hospital systems are nonprofits. This is disconcerting because we know that many nonprofit systems make large profits anyway and can offer executive teams’ lucrative packages, while the nurses, assistants, and physicians providing the care are generally not well compensated.”

So far, about nine states plus Washington, D.C., have already put noncompete bans in place, and they may serve as a harbinger of things to come should the federal ban go into effect. Each varies in its specifics. Some, like Indiana, outright ban them, whereas others limit them based on variables like income and industry. “We’re seeing these states responding to local market conditions,” said Darryl Drevna, senior director of regulatory affairs at the American Medical Group Association. “Health care is a hyperlocal market. Depending on the situation, the bans adapt and respond specific to those states.”

Should the federal ban take hold, however, it will supersede whatever rules the individual states have in place.

Some opponents of the federal ban proposal question its authority to begin with, however, Mr. Glennon included. “Many people believe the FTC is overstepping,” he said. “Some people believe that Section 5 of the FTC Act does not give it the authority to police labor markets.”

Mr. Drevna noted that the FTC has taken an aggressive stance, one that will ultimately wind up in the courts. “How it works out is anyone’s guess,” he said. “Ideally, the FTC will consider the comments and concerns of groups like AMGA and realize that states are best suited to regulate in this area.”

In general, the ban’s supporters are employees/physicians; those who oppose it are their employers. Joining the AMGA in speaking out against the noncompete ban is the American Hospital Association, whereas the American College of Emergency Physicians has come out largely in support of the ban.

Still, doctors like Dr. Shah remain hopeful. “I am optimistic that perhaps my colleagues will not continue to be stuck in overrestrictive noncompetes, but I am also realistic,” he said. “Hospital systems are already coming out strongly against this and they have deep pockets, so I won’t be surprised if it does not come to pass.”

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

The Federal Trade Commission’s proposed regulation that would ban noncompete agreements across the country seems like potential good news for doctors. Of course, many hospitals and employers are against it. As a result, the FTC’s sweeping proposal has tongues wagging on both sides of the issue.

Many physicians are thrilled that they may soon have more control over their career and not be stuck in jobs where they feel frustrated, underpaid, or blocked in their progress.

If passed, the proposed ban would allow physicians to get a new job with a competing organization, bucking a long-standing trend that hospitals and health care systems have heavily relied on to keep staff in place. As of 2018, as many as 45% of primary care physicians had inked such agreements with their employers.

Typically, the agreements prevent physicians from practicing medicine with a new employer for a defined period within a specific geographic area. No matter how attractive an alternate offer of employment might be, doctors are bound by the agreements to say no if the offer exists in that defined area and time period.

The period for public comment on the proposed regulation ended on April 19, and there is currently no set date for a decision.

In a Medscape poll of 558 physicians, more than 9 out of 10 respondents said that they were either currently bound by a noncompete clause or that they had been bound by one in the past that had forced them to temporarily stop working, commute long distances, move to a different area, or switch fields.

The new proposal would make it illegal for an employer, such as a hospital or large group, to enter a noncompete with a worker; maintain a noncompete with a worker; or represent to a worker, under certain circumstances, that the worker is subject to a noncompete.

It also would not only ban future noncompete agreements but also retroactively invalidate existing ones. The FTC reasons that noncompete clauses could potentially increase worker earnings as well as lower health care costs by billions of dollars. If the ruling were to move forward, it would represent part of President Biden’s “worker-forward” priorities, focusing on how competition can be a good thing for employees. The President billed the FTC’s announcement as a “huge win for workers.”

In its statements on the proposed ban, the FTC claimed that it could lower consumer prices across the board by as much as $150 billion per year and return nearly $300 million to workers each year.

However, even if passed, the draft rule would keep in place nonsolicitation rules that many health care organizations have put into place. That means that, if a physician leaves an employer, he or she cannot reach out to former patients and colleagues to bring them along or invite them to switch to him or her in the new job.

Within that clause, however, the FTC has specified that if such nonsolicitation agreement has the “equivalent effect” of a noncompete, the agency would deem it such. That means, even if that rule stays, it could be contested and may be interpreted as violating the noncompete law. So there’s value in reading all the fine print should the ban move forward.
 

Could the ban bring potential downsides?

Most physicians view the potential to break free of a noncompete agreement as a victory. Peter Glennon, an employment litigation attorney with The Glennon Law Firm in Rochester, N.Y., says not so fast. “If you ask anyone if they’d prefer a noncompete agreement, of course they’re going to say no,” he said in an interview. “It sounds like a restriction, one that can hold you back.”

Mr. Glennon believes that there are actually upsides to physician noncompetes. For instance, many noncompetes come with sign-on bonuses that could potentially disappear without the agreements. There’s also the fact that when some physicians sign a noncompete agreement, they then receive pro bono training and continuing education along with marketing and promotion of their skills. Without signing a noncompete, employers may be less incentivized to provide all those benefits to their physician employers.

Those benefits – and the noncompetes – also vary by specialty, Mr. Glennon said. “In 2021, Washington, DC, banned noncompetes for doctors making less than $250,000. So, most generalists there can walk across the street and get a new job. For specialists like cardiologists or neurosurgeons, however, advanced training and marketing benefits matter, so many of them don’t want to lose noncompetes.”

Still, most physicians hope that the FTC’s ban takes hold. Manan Shah, MD, founder, and chief medical officer at Wyndly, an allergy relief startup practice, is one of them.

“Initially, it might disincentivize hospital systems from helping new physicians build up their name and practice because they might be concerned about a physician leaving and starting anew,” he said. “But in the long term, hospitals require physicians to bring their patients to them for care, so the best hospitals will always compete for the best physicians and support them as they build up their practice.”

Dr. Shah views noncompetes as overly prohibitive to physicians. “Right now, if a physician starts a job at a large hospital system and realizes they want to switch jobs, the noncompete distances are so wide they often have to move cities to continue practicing,” he said. “Picking up and starting over in a new city isn’t an option for everyone and can be especially difficult for someone with a family.”

Where Mr. Glennon argued that a physician leaving a team-based practice might harm patients, Shah takes a different perspective. “Imagine you have a doctor whom you trust and have been working with,” he said. “If something changes at their hospital and they decide to move, you literally have to find a new doctor instead of just being able to see them at another location down the street.”

Another potential burden of the noncompete agreements is that they could possibly squelch doctor’s desires to hang up their own shingle. According to Dr. Shah, the agreements make it so that if a physician wants to work independently, it’s nearly impossible to fly solo. “This is frustrating because independent practices have been shown to be more cost effective and allow patients to build better relationships with their doctors,” he claimed.

A 2016 study from Annals of Family Medicine supports that claim, at least for small general practices. Another study appearing in JAMA concurred. It does point out, however, that the cost equation is nuanced and that benefits of larger systems include more resilience to economic downturns and can provide more specialized care.
 

Will nonprofit hospitals be subject to this noncompete ban?

Further complicating the noncompete ban issue is how it might impact nonprofit institutions versus their for-profit peers. Most hospitals structured as nonprofits would be exempt from the rule because the FTC Act provides that it can enforce against “persons, partnerships, or corporations,” which are further defined as entities “organized to carry on business for their own profit or that of their members.”

The fallout from this, said Dr. Shah, is that it “would disproportionately affect health care providers, since many hospital systems are nonprofits. This is disconcerting because we know that many nonprofit systems make large profits anyway and can offer executive teams’ lucrative packages, while the nurses, assistants, and physicians providing the care are generally not well compensated.”

So far, about nine states plus Washington, D.C., have already put noncompete bans in place, and they may serve as a harbinger of things to come should the federal ban go into effect. Each varies in its specifics. Some, like Indiana, outright ban them, whereas others limit them based on variables like income and industry. “We’re seeing these states responding to local market conditions,” said Darryl Drevna, senior director of regulatory affairs at the American Medical Group Association. “Health care is a hyperlocal market. Depending on the situation, the bans adapt and respond specific to those states.”

Should the federal ban take hold, however, it will supersede whatever rules the individual states have in place.

Some opponents of the federal ban proposal question its authority to begin with, however, Mr. Glennon included. “Many people believe the FTC is overstepping,” he said. “Some people believe that Section 5 of the FTC Act does not give it the authority to police labor markets.”

Mr. Drevna noted that the FTC has taken an aggressive stance, one that will ultimately wind up in the courts. “How it works out is anyone’s guess,” he said. “Ideally, the FTC will consider the comments and concerns of groups like AMGA and realize that states are best suited to regulate in this area.”

In general, the ban’s supporters are employees/physicians; those who oppose it are their employers. Joining the AMGA in speaking out against the noncompete ban is the American Hospital Association, whereas the American College of Emergency Physicians has come out largely in support of the ban.

Still, doctors like Dr. Shah remain hopeful. “I am optimistic that perhaps my colleagues will not continue to be stuck in overrestrictive noncompetes, but I am also realistic,” he said. “Hospital systems are already coming out strongly against this and they have deep pockets, so I won’t be surprised if it does not come to pass.”

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

SEATTLE – The majority of patients who underwent a teledermatology follow-up after Mohs micrographic surgery reported that they preferred it to in-person follow up, according to new findings.

In addition, nearly all patients surveyed (91.4%) were willing to go through electronic follow-up again.

“A big takeaway from our study is that streamlining this process is really essential for successful implementation,” said study author Laura Rezac, MD, a PGY IV dermatology resident at the University of Mississippi, Jackson. “This study demonstrated the flexibility and convenience for both patients and surgeons and can serve as a prototype for future innovation.”

The study results were presented at the annual meeting of the American College of Mohs Surgery.

The role of telehealth has rapidly expanded over the past decade, with its use accelerating during the COVID-19 pandemic and transforming into an indispensable resource. It can be synchronous, Dr. Rezac explained, which is when telehealth happens in live, real-time settings where the patient interacts with a clinician. This usually occurs via phone or video, and providers and patients communicate directly.

Conversely, asynchronous telehealth, also known as “store-and-forward,” is often used for patient intake or follow-up care. For example, in dermatology, a patient can send a photo of a skin condition that is then reviewed by a dermatologist later.

“A pilot survey regarding the adoption of telemedicine in Mohs surgery found that, although most dermatologic surgeons felt that it can play a role, most said that they didn’t plan on using it after the pandemic,” said Dr. Rezac.

The survey, which was reported by this news organization, found that 80% of surveyed surgeons said that they turned to telemedicine during the pandemic, compared with just 23% who relied on the technology prior to the pandemic.

There were numerous perceived barriers to the use of telemedicine, and the one most commonly cited was the uncertainty of how telemedicine fits in the workflow of clinical practice. Other limitations reported were for physical exams (88%), patient response and training (57%), reimbursement concerns (50%), implementation of the technology (37%), regulations such as HIPAA (24%), training of staff (17%), and licensing (8%).

“The survey did identify one key use of telemedicine in Mohs and that was for [postoperative] visits,” she said. “But thus far, a postoperative evaluation after Mohs via an integrated asynchronous ‘store and forward’ teledermatology platform has not yet been evaluated.”

In the study, Dr. Rezac and colleagues sought to evaluate feasibility and efficacy, as well as patient attitudes, using a telemedicine platform for postoperative follow-up. A total of 163 patients who were treated with Mohs at a single academic institution during the 9-month study period (December 2021 through August 2022) responded to a survey and elected to participate in postoperative follow-up using telemedicine.

Dr. Rezac explained how their procedure was implemented for the patient. “On the day of the follow-up, the patient receives a text with a link that takes them to the MyChart website or app on their phone,” she said. “Once they log in, they see that they have a message telling them that they have a teledermatology message waiting for them. When they view it, they are taken to the curated message with instructions and a phone call if they need assistance, and then at the bottom, it shows they have a task to complete, which is the questionnaire.”

The patient will then be prompted to upload photos, which can be taken with their phone camera. The next step is to answer questions regarding the surgical site or pain concerns, and finally, patients are asked to respond to a few short questions about this type of follow-up. Once submitted, then they wait to be contacted by the surgeon.

On the surgeon’s side, these answers come into their EPIC inbox, and they can respond via a MyChart message.

Patient response was overwhelmingly positive, Dr. Rezac noted. Of the patients, 80.4% found the electronic surgery follow-up process to be “easy” or “very easy,” while only 4% found it “difficult” or “very difficult,” she said. “Also, 75.5% preferred electronic follow-up while 17.2% preferred in-person follow-up.”

There were limitations to this study, primarily that the asynchronous method does reduce live interaction, which could be an issue, depending on person’s needs, she pointed out. “But it is easy to schedule a phone call or video call or office visit.”

“The universal barrier is how to adopt it into the workflow, which includes training of staff,” she continued, “But this was a very streamlined process and gave very detailed instructions to the staff. Additionally, widespread use is limited to dermatological proficiency and access, and patients have to be amenable to it, so there is a selection bias since these patients chose to participate.”

Asked to comment on the study, Vishal Patel, MD, director of cutaneous oncology at George Washington University in Washington, said: “The COVID pandemic changed how practices and providers considered follow-up visits for small routine matters. Postoperative visits are often simple and do not require an in-depth, in-person evaluation.” Dr. Patel was not involved with this research.

“This study highlights the comfort of the vast majority of patients to have follow-up postoperative visits conducted via teledermatology – an approach that can help cut overall costs and also increase access for patients who are more in need of in-office care,” he added.

No external funding of the study was reported. Dr. Rezac reported no relevant financial relationships. Dr. Patel is a consultant for Sanofi, Regeneron, and Almirall.
 

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

SEATTLE – The majority of patients who underwent a teledermatology follow-up after Mohs micrographic surgery reported that they preferred it to in-person follow up, according to new findings.

In addition, nearly all patients surveyed (91.4%) were willing to go through electronic follow-up again.

“A big takeaway from our study is that streamlining this process is really essential for successful implementation,” said study author Laura Rezac, MD, a PGY IV dermatology resident at the University of Mississippi, Jackson. “This study demonstrated the flexibility and convenience for both patients and surgeons and can serve as a prototype for future innovation.”

The study results were presented at the annual meeting of the American College of Mohs Surgery.

The role of telehealth has rapidly expanded over the past decade, with its use accelerating during the COVID-19 pandemic and transforming into an indispensable resource. It can be synchronous, Dr. Rezac explained, which is when telehealth happens in live, real-time settings where the patient interacts with a clinician. This usually occurs via phone or video, and providers and patients communicate directly.

Conversely, asynchronous telehealth, also known as “store-and-forward,” is often used for patient intake or follow-up care. For example, in dermatology, a patient can send a photo of a skin condition that is then reviewed by a dermatologist later.

“A pilot survey regarding the adoption of telemedicine in Mohs surgery found that, although most dermatologic surgeons felt that it can play a role, most said that they didn’t plan on using it after the pandemic,” said Dr. Rezac.

The survey, which was reported by this news organization, found that 80% of surveyed surgeons said that they turned to telemedicine during the pandemic, compared with just 23% who relied on the technology prior to the pandemic.

There were numerous perceived barriers to the use of telemedicine, and the one most commonly cited was the uncertainty of how telemedicine fits in the workflow of clinical practice. Other limitations reported were for physical exams (88%), patient response and training (57%), reimbursement concerns (50%), implementation of the technology (37%), regulations such as HIPAA (24%), training of staff (17%), and licensing (8%).

“The survey did identify one key use of telemedicine in Mohs and that was for [postoperative] visits,” she said. “But thus far, a postoperative evaluation after Mohs via an integrated asynchronous ‘store and forward’ teledermatology platform has not yet been evaluated.”

In the study, Dr. Rezac and colleagues sought to evaluate feasibility and efficacy, as well as patient attitudes, using a telemedicine platform for postoperative follow-up. A total of 163 patients who were treated with Mohs at a single academic institution during the 9-month study period (December 2021 through August 2022) responded to a survey and elected to participate in postoperative follow-up using telemedicine.

Dr. Rezac explained how their procedure was implemented for the patient. “On the day of the follow-up, the patient receives a text with a link that takes them to the MyChart website or app on their phone,” she said. “Once they log in, they see that they have a message telling them that they have a teledermatology message waiting for them. When they view it, they are taken to the curated message with instructions and a phone call if they need assistance, and then at the bottom, it shows they have a task to complete, which is the questionnaire.”

The patient will then be prompted to upload photos, which can be taken with their phone camera. The next step is to answer questions regarding the surgical site or pain concerns, and finally, patients are asked to respond to a few short questions about this type of follow-up. Once submitted, then they wait to be contacted by the surgeon.

On the surgeon’s side, these answers come into their EPIC inbox, and they can respond via a MyChart message.

Patient response was overwhelmingly positive, Dr. Rezac noted. Of the patients, 80.4% found the electronic surgery follow-up process to be “easy” or “very easy,” while only 4% found it “difficult” or “very difficult,” she said. “Also, 75.5% preferred electronic follow-up while 17.2% preferred in-person follow-up.”

There were limitations to this study, primarily that the asynchronous method does reduce live interaction, which could be an issue, depending on person’s needs, she pointed out. “But it is easy to schedule a phone call or video call or office visit.”

“The universal barrier is how to adopt it into the workflow, which includes training of staff,” she continued, “But this was a very streamlined process and gave very detailed instructions to the staff. Additionally, widespread use is limited to dermatological proficiency and access, and patients have to be amenable to it, so there is a selection bias since these patients chose to participate.”

Asked to comment on the study, Vishal Patel, MD, director of cutaneous oncology at George Washington University in Washington, said: “The COVID pandemic changed how practices and providers considered follow-up visits for small routine matters. Postoperative visits are often simple and do not require an in-depth, in-person evaluation.” Dr. Patel was not involved with this research.

“This study highlights the comfort of the vast majority of patients to have follow-up postoperative visits conducted via teledermatology – an approach that can help cut overall costs and also increase access for patients who are more in need of in-office care,” he added.

No external funding of the study was reported. Dr. Rezac reported no relevant financial relationships. Dr. Patel is a consultant for Sanofi, Regeneron, and Almirall.
 

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

SEATTLE – The majority of patients who underwent a teledermatology follow-up after Mohs micrographic surgery reported that they preferred it to in-person follow up, according to new findings.

In addition, nearly all patients surveyed (91.4%) were willing to go through electronic follow-up again.

“A big takeaway from our study is that streamlining this process is really essential for successful implementation,” said study author Laura Rezac, MD, a PGY IV dermatology resident at the University of Mississippi, Jackson. “This study demonstrated the flexibility and convenience for both patients and surgeons and can serve as a prototype for future innovation.”

The study results were presented at the annual meeting of the American College of Mohs Surgery.

The role of telehealth has rapidly expanded over the past decade, with its use accelerating during the COVID-19 pandemic and transforming into an indispensable resource. It can be synchronous, Dr. Rezac explained, which is when telehealth happens in live, real-time settings where the patient interacts with a clinician. This usually occurs via phone or video, and providers and patients communicate directly.

Conversely, asynchronous telehealth, also known as “store-and-forward,” is often used for patient intake or follow-up care. For example, in dermatology, a patient can send a photo of a skin condition that is then reviewed by a dermatologist later.

“A pilot survey regarding the adoption of telemedicine in Mohs surgery found that, although most dermatologic surgeons felt that it can play a role, most said that they didn’t plan on using it after the pandemic,” said Dr. Rezac.

The survey, which was reported by this news organization, found that 80% of surveyed surgeons said that they turned to telemedicine during the pandemic, compared with just 23% who relied on the technology prior to the pandemic.

There were numerous perceived barriers to the use of telemedicine, and the one most commonly cited was the uncertainty of how telemedicine fits in the workflow of clinical practice. Other limitations reported were for physical exams (88%), patient response and training (57%), reimbursement concerns (50%), implementation of the technology (37%), regulations such as HIPAA (24%), training of staff (17%), and licensing (8%).

“The survey did identify one key use of telemedicine in Mohs and that was for [postoperative] visits,” she said. “But thus far, a postoperative evaluation after Mohs via an integrated asynchronous ‘store and forward’ teledermatology platform has not yet been evaluated.”

In the study, Dr. Rezac and colleagues sought to evaluate feasibility and efficacy, as well as patient attitudes, using a telemedicine platform for postoperative follow-up. A total of 163 patients who were treated with Mohs at a single academic institution during the 9-month study period (December 2021 through August 2022) responded to a survey and elected to participate in postoperative follow-up using telemedicine.

Dr. Rezac explained how their procedure was implemented for the patient. “On the day of the follow-up, the patient receives a text with a link that takes them to the MyChart website or app on their phone,” she said. “Once they log in, they see that they have a message telling them that they have a teledermatology message waiting for them. When they view it, they are taken to the curated message with instructions and a phone call if they need assistance, and then at the bottom, it shows they have a task to complete, which is the questionnaire.”

The patient will then be prompted to upload photos, which can be taken with their phone camera. The next step is to answer questions regarding the surgical site or pain concerns, and finally, patients are asked to respond to a few short questions about this type of follow-up. Once submitted, then they wait to be contacted by the surgeon.

On the surgeon’s side, these answers come into their EPIC inbox, and they can respond via a MyChart message.

Patient response was overwhelmingly positive, Dr. Rezac noted. Of the patients, 80.4% found the electronic surgery follow-up process to be “easy” or “very easy,” while only 4% found it “difficult” or “very difficult,” she said. “Also, 75.5% preferred electronic follow-up while 17.2% preferred in-person follow-up.”

There were limitations to this study, primarily that the asynchronous method does reduce live interaction, which could be an issue, depending on person’s needs, she pointed out. “But it is easy to schedule a phone call or video call or office visit.”

“The universal barrier is how to adopt it into the workflow, which includes training of staff,” she continued, “But this was a very streamlined process and gave very detailed instructions to the staff. Additionally, widespread use is limited to dermatological proficiency and access, and patients have to be amenable to it, so there is a selection bias since these patients chose to participate.”

Asked to comment on the study, Vishal Patel, MD, director of cutaneous oncology at George Washington University in Washington, said: “The COVID pandemic changed how practices and providers considered follow-up visits for small routine matters. Postoperative visits are often simple and do not require an in-depth, in-person evaluation.” Dr. Patel was not involved with this research.

“This study highlights the comfort of the vast majority of patients to have follow-up postoperative visits conducted via teledermatology – an approach that can help cut overall costs and also increase access for patients who are more in need of in-office care,” he added.

No external funding of the study was reported. Dr. Rezac reported no relevant financial relationships. Dr. Patel is a consultant for Sanofi, Regeneron, and Almirall.
 

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

The Diagnosis: PASH (Pyoderma Gangrenosum, Acne, Hidradenitis Suppurativa) Syndrome

Obtaining our patient’s history of hidradenitis suppurativa (HS), a hallmark sterile neutrophilic dermatosis, was key to making the correct diagnosis of PASH (pyoderma gangrenosum, acne, HS) syndrome. In our patient, the history of HS increased the consideration of pyoderma gangrenosum (PG) due to the persistent breast and leg wounds. Additionally, it was important to consider a diagnosis of PG in lesions that were not responding to broad-spectrum antimicrobial treatment. In our patient, the concurrent presentation of draining abscesses in the axillae (Figure, A) and inflammatory nodulocystic facial acne (Figure, B) were additional diagnostic clues that suggested the triad of PASH syndrome.

Although SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome also can present with cutaneous features of acne and HS, the lack of bone and joint involvement in our patient made this diagnosis less likely. Calciphylaxis can present as ulcerations on the lower extremities, but it usually presents with a livedolike pattern with overlying black eschar and is unlikely in the absence of underlying metabolic or renal disease. PAPA (pyogenic arthritis, PG, acne) syndrome is characterized by recurrent joint involvement and lacks features of HS. Lastly, our patient was immunocompetent with no risk factors for mycobacterial infection.

PASH syndrome is a rare inherited syndrome, but its constituent inflammatory conditions are ubiquitous. They share a common underlying mechanism consisting of overactivation of the innate immune systems driven by increased production of the inflammatory cytokines IL-1, IL-17, and tumor necrosis factor α, resulting in sterile neutrophilic dermatoses.¹ The diagnosis is based on the clinical presentation, as laboratory investigations are nondiagnostic. Biopsies and cultures can be performed to rule out infectious etiologies. Additionally, PASH syndrome is considered part of a larger spectrum of syndromes including PAPA and PAPASH (pyogenic arthritis, acne, PG, HS) syndromes. The absence of pyogenic arthritis distinguishes PASH syndrome from PAPA and PAPASH syndromes.² Clinically, PASH syndrome and the related sterile neutrophilic dermatoses share the characteristic of pronounced cutaneous involvement that substantially alters the patient’s quality of life. Cigarette smoking is an exacerbating factor and has a well-established association with HS.³ Therefore, smoking cessation should be encouraged in these patients to avoid exacerbation of the disease process.

Maintaining adequate immunosuppression is key to managing the underlying disease processes. Classic immunosuppressive agents such as systemic glucocorticoids and methotrexate may fail to satisfactorily control the disease.⁴ Treatment options currently are somewhat limited and are aimed at targeting the inflammatory cytokines that propagate the disease. The most consistent responses have been observed with anti–tumor necrosis factor α antagonists such as adalimumab, infliximab, and etanercept.⁵ Additionally, there is varied response to anakinra, suggesting the importance of selectively targeting IL-1β.⁶ Unfortunately, misdiagnosis for an infectious etiology is common, and antibiotics and debridement are of limited use for the underlying pathophysiology of PASH syndrome. Importantly, biopsy and debridement often are discouraged due to the risk of pathergy.⁷

Our case demonstrates the importance of maintaining a high clinical suspicion for immune-mediated lesions that are refractory to antimicrobial agents. Additionally, prior history of multiple neutrophilic dermatoses should prompt consideration for the PASH/PAPA/PAPASH disease spectrum. Early and accurate identification of neutrophilic dermatoses such as PG and HS are crucial to initiating proper cytokine-targeting treatment and achieving disease remission.

The Diagnosis: PASH (Pyoderma Gangrenosum, Acne, Hidradenitis Suppurativa) Syndrome

Obtaining our patient’s history of hidradenitis suppurativa (HS), a hallmark sterile neutrophilic dermatosis, was key to making the correct diagnosis of PASH (pyoderma gangrenosum, acne, HS) syndrome. In our patient, the history of HS increased the consideration of pyoderma gangrenosum (PG) due to the persistent breast and leg wounds. Additionally, it was important to consider a diagnosis of PG in lesions that were not responding to broad-spectrum antimicrobial treatment. In our patient, the concurrent presentation of draining abscesses in the axillae (Figure, A) and inflammatory nodulocystic facial acne (Figure, B) were additional diagnostic clues that suggested the triad of PASH syndrome.

Although SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome also can present with cutaneous features of acne and HS, the lack of bone and joint involvement in our patient made this diagnosis less likely. Calciphylaxis can present as ulcerations on the lower extremities, but it usually presents with a livedolike pattern with overlying black eschar and is unlikely in the absence of underlying metabolic or renal disease. PAPA (pyogenic arthritis, PG, acne) syndrome is characterized by recurrent joint involvement and lacks features of HS. Lastly, our patient was immunocompetent with no risk factors for mycobacterial infection.

PASH syndrome is a rare inherited syndrome, but its constituent inflammatory conditions are ubiquitous. They share a common underlying mechanism consisting of overactivation of the innate immune systems driven by increased production of the inflammatory cytokines IL-1, IL-17, and tumor necrosis factor α, resulting in sterile neutrophilic dermatoses.¹ The diagnosis is based on the clinical presentation, as laboratory investigations are nondiagnostic. Biopsies and cultures can be performed to rule out infectious etiologies. Additionally, PASH syndrome is considered part of a larger spectrum of syndromes including PAPA and PAPASH (pyogenic arthritis, acne, PG, HS) syndromes. The absence of pyogenic arthritis distinguishes PASH syndrome from PAPA and PAPASH syndromes.² Clinically, PASH syndrome and the related sterile neutrophilic dermatoses share the characteristic of pronounced cutaneous involvement that substantially alters the patient’s quality of life. Cigarette smoking is an exacerbating factor and has a well-established association with HS.³ Therefore, smoking cessation should be encouraged in these patients to avoid exacerbation of the disease process.

Maintaining adequate immunosuppression is key to managing the underlying disease processes. Classic immunosuppressive agents such as systemic glucocorticoids and methotrexate may fail to satisfactorily control the disease.⁴ Treatment options currently are somewhat limited and are aimed at targeting the inflammatory cytokines that propagate the disease. The most consistent responses have been observed with anti–tumor necrosis factor α antagonists such as adalimumab, infliximab, and etanercept.⁵ Additionally, there is varied response to anakinra, suggesting the importance of selectively targeting IL-1β.⁶ Unfortunately, misdiagnosis for an infectious etiology is common, and antibiotics and debridement are of limited use for the underlying pathophysiology of PASH syndrome. Importantly, biopsy and debridement often are discouraged due to the risk of pathergy.⁷

Our case demonstrates the importance of maintaining a high clinical suspicion for immune-mediated lesions that are refractory to antimicrobial agents. Additionally, prior history of multiple neutrophilic dermatoses should prompt consideration for the PASH/PAPA/PAPASH disease spectrum. Early and accurate identification of neutrophilic dermatoses such as PG and HS are crucial to initiating proper cytokine-targeting treatment and achieving disease remission.

The Diagnosis: PASH (Pyoderma Gangrenosum, Acne, Hidradenitis Suppurativa) Syndrome

Obtaining our patient’s history of hidradenitis suppurativa (HS), a hallmark sterile neutrophilic dermatosis, was key to making the correct diagnosis of PASH (pyoderma gangrenosum, acne, HS) syndrome. In our patient, the history of HS increased the consideration of pyoderma gangrenosum (PG) due to the persistent breast and leg wounds. Additionally, it was important to consider a diagnosis of PG in lesions that were not responding to broad-spectrum antimicrobial treatment. In our patient, the concurrent presentation of draining abscesses in the axillae (Figure, A) and inflammatory nodulocystic facial acne (Figure, B) were additional diagnostic clues that suggested the triad of PASH syndrome.

Although SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome also can present with cutaneous features of acne and HS, the lack of bone and joint involvement in our patient made this diagnosis less likely. Calciphylaxis can present as ulcerations on the lower extremities, but it usually presents with a livedolike pattern with overlying black eschar and is unlikely in the absence of underlying metabolic or renal disease. PAPA (pyogenic arthritis, PG, acne) syndrome is characterized by recurrent joint involvement and lacks features of HS. Lastly, our patient was immunocompetent with no risk factors for mycobacterial infection.

PASH syndrome is a rare inherited syndrome, but its constituent inflammatory conditions are ubiquitous. They share a common underlying mechanism consisting of overactivation of the innate immune systems driven by increased production of the inflammatory cytokines IL-1, IL-17, and tumor necrosis factor α, resulting in sterile neutrophilic dermatoses.¹ The diagnosis is based on the clinical presentation, as laboratory investigations are nondiagnostic. Biopsies and cultures can be performed to rule out infectious etiologies. Additionally, PASH syndrome is considered part of a larger spectrum of syndromes including PAPA and PAPASH (pyogenic arthritis, acne, PG, HS) syndromes. The absence of pyogenic arthritis distinguishes PASH syndrome from PAPA and PAPASH syndromes.² Clinically, PASH syndrome and the related sterile neutrophilic dermatoses share the characteristic of pronounced cutaneous involvement that substantially alters the patient’s quality of life. Cigarette smoking is an exacerbating factor and has a well-established association with HS.³ Therefore, smoking cessation should be encouraged in these patients to avoid exacerbation of the disease process.

Maintaining adequate immunosuppression is key to managing the underlying disease processes. Classic immunosuppressive agents such as systemic glucocorticoids and methotrexate may fail to satisfactorily control the disease.⁴ Treatment options currently are somewhat limited and are aimed at targeting the inflammatory cytokines that propagate the disease. The most consistent responses have been observed with anti–tumor necrosis factor α antagonists such as adalimumab, infliximab, and etanercept.⁵ Additionally, there is varied response to anakinra, suggesting the importance of selectively targeting IL-1β.⁶ Unfortunately, misdiagnosis for an infectious etiology is common, and antibiotics and debridement are of limited use for the underlying pathophysiology of PASH syndrome. Importantly, biopsy and debridement often are discouraged due to the risk of pathergy.⁷

Our case demonstrates the importance of maintaining a high clinical suspicion for immune-mediated lesions that are refractory to antimicrobial agents. Additionally, prior history of multiple neutrophilic dermatoses should prompt consideration for the PASH/PAPA/PAPASH disease spectrum. Early and accurate identification of neutrophilic dermatoses such as PG and HS are crucial to initiating proper cytokine-targeting treatment and achieving disease remission.

Sores on the feet can signal problems with the eyes in patients with diabetes.

Prior research and anecdotal experience show that diabetic foot ulcers and diabetic retinopathy frequently co-occur. New research further clarifies this link and shows that patients with foot ulcers may receive fewer treatments to protect their sight.

David J. Ramsey, MD, PhD, MPH, director of ophthalmic research at Lahey Hospital & Medical Center, Burlington, Mass., said when clinicians detect either condition, they should involve a team that can intervene to help protect a patient’s vision and mobility.

For example, they should ensure patients receive comprehensive eye and foot evaluations and help them optimize diabetes management.

The new study, presented at the annual meeting of the Association for Research in Vision and Ophthalmology, “adds an important dimension” to understanding the association between the conditions, said Dr. Ramsey, who recently reviewed correlations between diabetic foot ulcers and diabetic retinopathy and their underlying causes.

“Patients with diabetic foot ulcers appear to receive less attention to their diabetic retinopathy and may receive fewer treatments with eye injections targeting vascular endothelial growth factor (VEGF), an important driver of progression of diabetic retinopathy,” said Dr. Ramsey, who is also an associate professor of ophthalmology at Tufts University School of Medicine, Boston. He was not involved in the study presented at ARVO 2023.

In the new study, Christopher T. Zhu, a medical student at UT Health San Antonio, and colleagues analyzed data from 426 eyes of 213 patients with type 2 diabetes who had had at least two eye exams between 2012 and 2022; 72 of the patients had diabetic foot ulcers. Patients were followed for about 4 years on average.

Patients with diabetic foot ulcers had a higher percentage of eyes with macular edema on their initial exam (32.6% vs. 28%). By the final exam, the percentage of eyes with macular edema was significantly greater in the group with diabetic foot ulcers (64.6% vs. 37.6%; P < .0001), Mr. Zhu’s group reported.

Eyes with nonproliferative diabetic retinopathy progressed to proliferative diabetic retinopathy, the worst grade, at a higher rate in the group with foot ulcers (50.6% vs. 35.6%; P = .03). In addition, patients with foot ulcers were more likely to experience vitreous hemorrhage (55.6% vs. 38.7%), the researchers found.

Despite patients with foot ulcers tending to have worse disease, they received fewer treatments for retinopathy. Those without ulcers received an average of 6.9 anti-VEGF injections per eye, while those with ulcers averaged 4.3.

Foot ulcers may hinder the ability of patients to get to appointments to receive the injections, Mr. Zhu and colleagues wrote. “For many patients in our part of the country [South Texas], a lack of transportation is a particular barrier to health care access,” Mr. Zhu told this news organization.

Mr. Zhu’s team conducted their study after noticing that patients with diabetes and foot ulcers who presented to their eye clinics “appeared to progress faster to worse grades of retinopathy” than patients with diabetes who did not have ulcers.

“Similar to how foot ulcers develop due to a severe disruption in blood flow [vascular] and a loss of sensation [neurologic], diabetic retinopathy may have a relation to microvascular disease, neurologic degeneration, and inflammation,” he said.

The findings confirm “that poor perfusion of the eye and foot are linked and can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy and vitreous hemorrhages, both serious, vision-threatening conditions,” Dr. Ramsey said.

To some extent, fewer treatments with anti-VEGF agents may account for why patients with foot ulcers have more eye complications, Dr. Ramsey added. “Additional research needs to be done to further dissect the cause and the effect, but it’s a very important finding that we need to increase awareness about,” he said.

Dr. Ramsey and Mr. Zhu reported no relevant financial relationships.

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

Sores on the feet can signal problems with the eyes in patients with diabetes.

Prior research and anecdotal experience show that diabetic foot ulcers and diabetic retinopathy frequently co-occur. New research further clarifies this link and shows that patients with foot ulcers may receive fewer treatments to protect their sight.

David J. Ramsey, MD, PhD, MPH, director of ophthalmic research at Lahey Hospital & Medical Center, Burlington, Mass., said when clinicians detect either condition, they should involve a team that can intervene to help protect a patient’s vision and mobility.

For example, they should ensure patients receive comprehensive eye and foot evaluations and help them optimize diabetes management.

The new study, presented at the annual meeting of the Association for Research in Vision and Ophthalmology, “adds an important dimension” to understanding the association between the conditions, said Dr. Ramsey, who recently reviewed correlations between diabetic foot ulcers and diabetic retinopathy and their underlying causes.

“Patients with diabetic foot ulcers appear to receive less attention to their diabetic retinopathy and may receive fewer treatments with eye injections targeting vascular endothelial growth factor (VEGF), an important driver of progression of diabetic retinopathy,” said Dr. Ramsey, who is also an associate professor of ophthalmology at Tufts University School of Medicine, Boston. He was not involved in the study presented at ARVO 2023.

In the new study, Christopher T. Zhu, a medical student at UT Health San Antonio, and colleagues analyzed data from 426 eyes of 213 patients with type 2 diabetes who had had at least two eye exams between 2012 and 2022; 72 of the patients had diabetic foot ulcers. Patients were followed for about 4 years on average.

Patients with diabetic foot ulcers had a higher percentage of eyes with macular edema on their initial exam (32.6% vs. 28%). By the final exam, the percentage of eyes with macular edema was significantly greater in the group with diabetic foot ulcers (64.6% vs. 37.6%; P < .0001), Mr. Zhu’s group reported.

Eyes with nonproliferative diabetic retinopathy progressed to proliferative diabetic retinopathy, the worst grade, at a higher rate in the group with foot ulcers (50.6% vs. 35.6%; P = .03). In addition, patients with foot ulcers were more likely to experience vitreous hemorrhage (55.6% vs. 38.7%), the researchers found.

Despite patients with foot ulcers tending to have worse disease, they received fewer treatments for retinopathy. Those without ulcers received an average of 6.9 anti-VEGF injections per eye, while those with ulcers averaged 4.3.

Foot ulcers may hinder the ability of patients to get to appointments to receive the injections, Mr. Zhu and colleagues wrote. “For many patients in our part of the country [South Texas], a lack of transportation is a particular barrier to health care access,” Mr. Zhu told this news organization.

Mr. Zhu’s team conducted their study after noticing that patients with diabetes and foot ulcers who presented to their eye clinics “appeared to progress faster to worse grades of retinopathy” than patients with diabetes who did not have ulcers.

“Similar to how foot ulcers develop due to a severe disruption in blood flow [vascular] and a loss of sensation [neurologic], diabetic retinopathy may have a relation to microvascular disease, neurologic degeneration, and inflammation,” he said.

The findings confirm “that poor perfusion of the eye and foot are linked and can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy and vitreous hemorrhages, both serious, vision-threatening conditions,” Dr. Ramsey said.

To some extent, fewer treatments with anti-VEGF agents may account for why patients with foot ulcers have more eye complications, Dr. Ramsey added. “Additional research needs to be done to further dissect the cause and the effect, but it’s a very important finding that we need to increase awareness about,” he said.

Dr. Ramsey and Mr. Zhu reported no relevant financial relationships.

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

Sores on the feet can signal problems with the eyes in patients with diabetes.

Prior research and anecdotal experience show that diabetic foot ulcers and diabetic retinopathy frequently co-occur. New research further clarifies this link and shows that patients with foot ulcers may receive fewer treatments to protect their sight.

David J. Ramsey, MD, PhD, MPH, director of ophthalmic research at Lahey Hospital & Medical Center, Burlington, Mass., said when clinicians detect either condition, they should involve a team that can intervene to help protect a patient’s vision and mobility.

For example, they should ensure patients receive comprehensive eye and foot evaluations and help them optimize diabetes management.

The new study, presented at the annual meeting of the Association for Research in Vision and Ophthalmology, “adds an important dimension” to understanding the association between the conditions, said Dr. Ramsey, who recently reviewed correlations between diabetic foot ulcers and diabetic retinopathy and their underlying causes.

“Patients with diabetic foot ulcers appear to receive less attention to their diabetic retinopathy and may receive fewer treatments with eye injections targeting vascular endothelial growth factor (VEGF), an important driver of progression of diabetic retinopathy,” said Dr. Ramsey, who is also an associate professor of ophthalmology at Tufts University School of Medicine, Boston. He was not involved in the study presented at ARVO 2023.

In the new study, Christopher T. Zhu, a medical student at UT Health San Antonio, and colleagues analyzed data from 426 eyes of 213 patients with type 2 diabetes who had had at least two eye exams between 2012 and 2022; 72 of the patients had diabetic foot ulcers. Patients were followed for about 4 years on average.

Patients with diabetic foot ulcers had a higher percentage of eyes with macular edema on their initial exam (32.6% vs. 28%). By the final exam, the percentage of eyes with macular edema was significantly greater in the group with diabetic foot ulcers (64.6% vs. 37.6%; P < .0001), Mr. Zhu’s group reported.

Eyes with nonproliferative diabetic retinopathy progressed to proliferative diabetic retinopathy, the worst grade, at a higher rate in the group with foot ulcers (50.6% vs. 35.6%; P = .03). In addition, patients with foot ulcers were more likely to experience vitreous hemorrhage (55.6% vs. 38.7%), the researchers found.

Despite patients with foot ulcers tending to have worse disease, they received fewer treatments for retinopathy. Those without ulcers received an average of 6.9 anti-VEGF injections per eye, while those with ulcers averaged 4.3.

Foot ulcers may hinder the ability of patients to get to appointments to receive the injections, Mr. Zhu and colleagues wrote. “For many patients in our part of the country [South Texas], a lack of transportation is a particular barrier to health care access,” Mr. Zhu told this news organization.

Mr. Zhu’s team conducted their study after noticing that patients with diabetes and foot ulcers who presented to their eye clinics “appeared to progress faster to worse grades of retinopathy” than patients with diabetes who did not have ulcers.

“Similar to how foot ulcers develop due to a severe disruption in blood flow [vascular] and a loss of sensation [neurologic], diabetic retinopathy may have a relation to microvascular disease, neurologic degeneration, and inflammation,” he said.

The findings confirm “that poor perfusion of the eye and foot are linked and can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy and vitreous hemorrhages, both serious, vision-threatening conditions,” Dr. Ramsey said.

To some extent, fewer treatments with anti-VEGF agents may account for why patients with foot ulcers have more eye complications, Dr. Ramsey added. “Additional research needs to be done to further dissect the cause and the effect, but it’s a very important finding that we need to increase awareness about,” he said.

Dr. Ramsey and Mr. Zhu reported no relevant financial relationships.

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