Lupus & Connective Tissue Diseases

Cutaneous lupus erythematosus (CLE) is present in 25% of patients with systemic lupus at the time of diagnosis, but it can also occur in up to 85% of cases at some point in their disease course, Eveline Y. Wu, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology.

“CLE can also occur without any systemic disease,” said Dr. Wu, associate professor of pediatrics at the University of North Carolina at Chapel Hill. “It’s been shown that the risk of developing systemic lupus differs according to the type of skin involvement, meaning that cutaneous lupus can be classified into acute, subacute, chronic, and intermittent forms.”

Malar rash is the prototypical acute cutaneous lesion and is associated with active systemic lupus erythematosus (SLE) and anti–double stranded DNA antibody positivity, while discoid lupus erythematosus is the most common chronic lesion. “A small percentage of patients with discoid lupus can develop systemic lupus, particularly when the lesions are more disseminated,” said Dr. Wu, who specializes in pediatric rheumatology as well as allergy and immunology.

In the American College of Rheumatology’s 1997 classification system, mucocutaneous manifestations constitute 4 out of the 11 criteria that clinicians use to make a diagnosis of SLE: malar rash, discoid-lupus rash, photosensitivity, and oral or nasal mucocutaneous ulcerations. Dr. Wu recommends performing an oral exam on suspect cases, “because the oral ulcers that we see in systemic lupus tend to be painless, so oftentimes patients don’t realize they have them.”

Five other organ-specific manifestations of SLE include nonerosive arthritis, nephritis, encephalopathy, pleuritis or pericarditis, and cytopenia. The two other criteria are positive immunoserology and a positive antinuclear antibody test. “If you have any individuals present with one of these [mucocutaneous manifestations criteria], you want to think about getting a CBC to look for cytopenia or a urinalysis to look for evidence of nephritis, and potentially some additional blood studies, depending on your level of suspicion for systemic lupus,” Dr. Wu said.

Other rarer CLE manifestations include lupus pernio or chilblains, lupus panniculitis, livedo reticularis, bullous LE, urticarial vasculitis, neutrophilic dermatoses, and alopecia.

Common treatments for cutaneous manifestations associated pediatric SLE include hydroxychloroquine, low dose corticosteroids, topical steroids, methotrexate, and leflunomide. Other options for increasing severity of systemic disease include lenalidomide/thalidomide, azathioprine, calcineurin inhibitors, belimumab (Benlysta), high-dose corticosteroids, mycophenolate mofetil (CellCept), rituximab (Rituxan), and cyclophosphamide. Cutaneous manifestations of pediatric SLE can often be refractory to treatments.

In 2017, Dr. Wu and associates published a retrospective chart review of 10 adolescents who received lenalidomide for refractory CLE. One of the subjects was a 21-year-old male with a significant malar rash despite being on hydroxychloroquine, azathioprine, and prednisone 40 mg daily. “One month after being on lenalidomide he had a pretty impressive response,” Dr. Wu said. “It’s not quite clear how lenalidomide works in cutaneous lupus. Currently it’s only approved for use in myelodysplastic syndromes, multiple myeloma, as well as certain lymphomas. It’s thought to modulate different parts of the immune system, which collectively result in the cytotoxicity against tumor cells.”

Lenalidomide is supplied in capsule sizes ranging from 2.5 mg to 25 mg and is given once daily. “For a smaller child, I would think about starting 5 mg once a day,” Dr. Wu said. “For an adult-sized adolescent, you could start at 10 mg once a day and then titrate up based on response. Side effects that you need to worry about are cytopenia and GI symptoms. The venous and arterial thromboembolism risk has been seen in patients with multiple myeloma, and it is unclear if this risk is applicable to all indications.” Use of the medication requires enrollment into a safety monitoring program.

She reported having no financial disclosures.

[email protected]

Cutaneous lupus erythematosus (CLE) is present in 25% of patients with systemic lupus at the time of diagnosis, but it can also occur in up to 85% of cases at some point in their disease course, Eveline Y. Wu, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology.

“CLE can also occur without any systemic disease,” said Dr. Wu, associate professor of pediatrics at the University of North Carolina at Chapel Hill. “It’s been shown that the risk of developing systemic lupus differs according to the type of skin involvement, meaning that cutaneous lupus can be classified into acute, subacute, chronic, and intermittent forms.”

Malar rash is the prototypical acute cutaneous lesion and is associated with active systemic lupus erythematosus (SLE) and anti–double stranded DNA antibody positivity, while discoid lupus erythematosus is the most common chronic lesion. “A small percentage of patients with discoid lupus can develop systemic lupus, particularly when the lesions are more disseminated,” said Dr. Wu, who specializes in pediatric rheumatology as well as allergy and immunology.

In the American College of Rheumatology’s 1997 classification system, mucocutaneous manifestations constitute 4 out of the 11 criteria that clinicians use to make a diagnosis of SLE: malar rash, discoid-lupus rash, photosensitivity, and oral or nasal mucocutaneous ulcerations. Dr. Wu recommends performing an oral exam on suspect cases, “because the oral ulcers that we see in systemic lupus tend to be painless, so oftentimes patients don’t realize they have them.”

Five other organ-specific manifestations of SLE include nonerosive arthritis, nephritis, encephalopathy, pleuritis or pericarditis, and cytopenia. The two other criteria are positive immunoserology and a positive antinuclear antibody test. “If you have any individuals present with one of these [mucocutaneous manifestations criteria], you want to think about getting a CBC to look for cytopenia or a urinalysis to look for evidence of nephritis, and potentially some additional blood studies, depending on your level of suspicion for systemic lupus,” Dr. Wu said.

Other rarer CLE manifestations include lupus pernio or chilblains, lupus panniculitis, livedo reticularis, bullous LE, urticarial vasculitis, neutrophilic dermatoses, and alopecia.

Common treatments for cutaneous manifestations associated pediatric SLE include hydroxychloroquine, low dose corticosteroids, topical steroids, methotrexate, and leflunomide. Other options for increasing severity of systemic disease include lenalidomide/thalidomide, azathioprine, calcineurin inhibitors, belimumab (Benlysta), high-dose corticosteroids, mycophenolate mofetil (CellCept), rituximab (Rituxan), and cyclophosphamide. Cutaneous manifestations of pediatric SLE can often be refractory to treatments.

In 2017, Dr. Wu and associates published a retrospective chart review of 10 adolescents who received lenalidomide for refractory CLE. One of the subjects was a 21-year-old male with a significant malar rash despite being on hydroxychloroquine, azathioprine, and prednisone 40 mg daily. “One month after being on lenalidomide he had a pretty impressive response,” Dr. Wu said. “It’s not quite clear how lenalidomide works in cutaneous lupus. Currently it’s only approved for use in myelodysplastic syndromes, multiple myeloma, as well as certain lymphomas. It’s thought to modulate different parts of the immune system, which collectively result in the cytotoxicity against tumor cells.”

Lenalidomide is supplied in capsule sizes ranging from 2.5 mg to 25 mg and is given once daily. “For a smaller child, I would think about starting 5 mg once a day,” Dr. Wu said. “For an adult-sized adolescent, you could start at 10 mg once a day and then titrate up based on response. Side effects that you need to worry about are cytopenia and GI symptoms. The venous and arterial thromboembolism risk has been seen in patients with multiple myeloma, and it is unclear if this risk is applicable to all indications.” Use of the medication requires enrollment into a safety monitoring program.

She reported having no financial disclosures.

[email protected]

Cutaneous lupus erythematosus (CLE) is present in 25% of patients with systemic lupus at the time of diagnosis, but it can also occur in up to 85% of cases at some point in their disease course, Eveline Y. Wu, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology.

“CLE can also occur without any systemic disease,” said Dr. Wu, associate professor of pediatrics at the University of North Carolina at Chapel Hill. “It’s been shown that the risk of developing systemic lupus differs according to the type of skin involvement, meaning that cutaneous lupus can be classified into acute, subacute, chronic, and intermittent forms.”

Malar rash is the prototypical acute cutaneous lesion and is associated with active systemic lupus erythematosus (SLE) and anti–double stranded DNA antibody positivity, while discoid lupus erythematosus is the most common chronic lesion. “A small percentage of patients with discoid lupus can develop systemic lupus, particularly when the lesions are more disseminated,” said Dr. Wu, who specializes in pediatric rheumatology as well as allergy and immunology.

In the American College of Rheumatology’s 1997 classification system, mucocutaneous manifestations constitute 4 out of the 11 criteria that clinicians use to make a diagnosis of SLE: malar rash, discoid-lupus rash, photosensitivity, and oral or nasal mucocutaneous ulcerations. Dr. Wu recommends performing an oral exam on suspect cases, “because the oral ulcers that we see in systemic lupus tend to be painless, so oftentimes patients don’t realize they have them.”

Five other organ-specific manifestations of SLE include nonerosive arthritis, nephritis, encephalopathy, pleuritis or pericarditis, and cytopenia. The two other criteria are positive immunoserology and a positive antinuclear antibody test. “If you have any individuals present with one of these [mucocutaneous manifestations criteria], you want to think about getting a CBC to look for cytopenia or a urinalysis to look for evidence of nephritis, and potentially some additional blood studies, depending on your level of suspicion for systemic lupus,” Dr. Wu said.

Other rarer CLE manifestations include lupus pernio or chilblains, lupus panniculitis, livedo reticularis, bullous LE, urticarial vasculitis, neutrophilic dermatoses, and alopecia.

Common treatments for cutaneous manifestations associated pediatric SLE include hydroxychloroquine, low dose corticosteroids, topical steroids, methotrexate, and leflunomide. Other options for increasing severity of systemic disease include lenalidomide/thalidomide, azathioprine, calcineurin inhibitors, belimumab (Benlysta), high-dose corticosteroids, mycophenolate mofetil (CellCept), rituximab (Rituxan), and cyclophosphamide. Cutaneous manifestations of pediatric SLE can often be refractory to treatments.

In 2017, Dr. Wu and associates published a retrospective chart review of 10 adolescents who received lenalidomide for refractory CLE. One of the subjects was a 21-year-old male with a significant malar rash despite being on hydroxychloroquine, azathioprine, and prednisone 40 mg daily. “One month after being on lenalidomide he had a pretty impressive response,” Dr. Wu said. “It’s not quite clear how lenalidomide works in cutaneous lupus. Currently it’s only approved for use in myelodysplastic syndromes, multiple myeloma, as well as certain lymphomas. It’s thought to modulate different parts of the immune system, which collectively result in the cytotoxicity against tumor cells.”

Lenalidomide is supplied in capsule sizes ranging from 2.5 mg to 25 mg and is given once daily. “For a smaller child, I would think about starting 5 mg once a day,” Dr. Wu said. “For an adult-sized adolescent, you could start at 10 mg once a day and then titrate up based on response. Side effects that you need to worry about are cytopenia and GI symptoms. The venous and arterial thromboembolism risk has been seen in patients with multiple myeloma, and it is unclear if this risk is applicable to all indications.” Use of the medication requires enrollment into a safety monitoring program.

She reported having no financial disclosures.

[email protected]

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

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

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

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

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

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

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Clinicians shouldn’t rely on pulmonary function tests (PFTs) alone to screen for interstitial lung disease (ILD). The tests performed poorly in a retrospective study of 212 patients with systemic sclerosis, reinforcing the findings of previous studies.

Any screening algorithm should include high-resolution CT (HRCT), which is good at prognosticating disease, the investigators wrote in Arthritis & Rheumatology. “I think all newly diagnosed systemic sclerosis patients should have a full set of PFTs (spirometry, lung volumes, and diffusion capacity) and an HRCT at baseline to evaluate for ILD,” the study’s lead author, Elana J. Bernstein, MD, said in an interview.

ILD is a leading cause of death in systemic sclerosis (SSc) patients, affecting 40%-60% of those with the disease. HRCT is currently the preferred option for detection of ILD. PFTs are commonly used to screen for ILD but haven’t performed well in previous studies. “Someone can have abnormalities on HRCT that are consistent with ILD but still have PFTs that are in the ‘normal’ range,” explained Dr. Bernstein of Columbia University, New York. One cross-sectional study of 102 SSc patients found that the test’s sensitivity for the detection of ILD on HRCT was just 37.5% when forced vital capacity (FVC) <80% predicted.

Investigators sought to assess performance characteristics of PFTs in patients with early diffuse cutaneous SSc, a cohort at high risk of developing ILD. The study enlisted patients from the Prospective Registry of Early Systemic Sclerosis (PRESS), a multicenter, prospective cohort study of adults with early diffuse cutaneous SSc. Overall, 212 patients at 11 U.S. academic medical centers participated in the study from April 2012 to January 2019.

All patients had spirometry (PFT) and HRCT chest scans. PFTs were conducted per American Thoracic Society/European Respiratory Society guidelines. The investigators calculated test characteristics for single PFT and combinations of PFT parameters for the detection of ILD on HRCT. The HRCTs were ordered at the discretion of treating physicians, and scrutinized for ILD features such as reticular changes, honeycombing, traction bronchiectasis, and ground-glass opacities. The investigators defined the lower limit of normal for FVC, total lung capacity, and diffusion capacity for carbon monoxide (DLCO) as 80% predicted.

Overall, Dr. Bernstein and her colleagues found that PFTs lacked sufficient sensitivity and negative predictive value for the detection of ILD on HRCT in these patients.

An FVC <80% predicted performed at only 63% sensitivity and an false negative rate of 37%. Total lung capacity or DLCO <80% predicted had a sensitivity of 46% and 80%, respectively. The combination of FVC or DLCO <80% predicted raised sensitivity to 85%. However, the addition of total lung capacity to this combination did not improve results.

Overall, PFTs had a positive predictive value of 64%-74% and an negative predictive value of 61%-70%. “This means that PFT alone will not accurately predict the presence of ILD in about 35%, and not be correctly negative in about 35%,” observed Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, and professor of rheumatology at the University of California, Los Angeles.

While the combination of FVC <80% predicted or DLCO <80% predicted performed better than the other parameters, the sensitivity “is inadequate for an ILD screening test as it results in an false negative rate of 15%, thereby falsely reassuring 15% of patients that they do not have ILD when in fact they do,” the investigators observed.

“This study reinforces the notion that PFTs alone are ineffective screening tools for ILD in the presence of systemic sclerosis, particularly for patients with early systemic sclerosis,” said Elizabeth Volkmann, MD, MS, assistant professor and codirector of the CTD-ILD program in the division of rheumatology at the University of California, Los Angeles.

The study’s scope was relatively small, yet the results provide further evidence to show that HRCT should be performed in all SSc patients to screen for the presence of ILD, Dr. Volkmann said in an interview.

Other research has demonstrated the value of baseline HRCT as a prognosticator of ILD outcomes. The method provides useful information about the degree of fibrosis and degree of damage in early-stage disease, said Dr. Furst, also an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). “If there’s honeycombing, that’s a bad prognosis. If it’s ground glass or reticular changes, the prognosis is better.

“Once there’s a lot of damage, it’s much harder to interpret disease with HRCT,” he added.

HRCT and PFT work well together to assess what’s happening in patients, Dr. Furst explained. HRCT provides an idea of anatomic changes, whereas PFT outlines aspects of functional change to diagnose early ILD in early diffuse SSc. The study results should not apply to patients with later disease who have more developed ILD, he noted.

The investigators acknowledged that they weren’t able to categorize and analyze patients according to disease extent because they didn’t quantify the extent of ILD. Another limitation was that the HRCTs and PFTs were ordered at the discretion of individual physicians, which means that not all participants received the tests.

“Although the tests were done in 90% of the population, there is still a probability of a significant selection bias,” Dr. Furst said.

Dr. Bernstein and several other coauthors in the study received grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to support their work. Dr. Furst disclosed receiving grant/research support from and/or consulting for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech. Dr. Volkmann disclosed consulting for and/or receiving grant support from Boehringer Ingelheim, Corbus, and Forbius.

SOURCE: Bernstein EJ et al. Arthritis Rheumatol. 2020 Jun 25. doi: 10.1002/art.41415.

Clinicians shouldn’t rely on pulmonary function tests (PFTs) alone to screen for interstitial lung disease (ILD). The tests performed poorly in a retrospective study of 212 patients with systemic sclerosis, reinforcing the findings of previous studies.

Any screening algorithm should include high-resolution CT (HRCT), which is good at prognosticating disease, the investigators wrote in Arthritis & Rheumatology. “I think all newly diagnosed systemic sclerosis patients should have a full set of PFTs (spirometry, lung volumes, and diffusion capacity) and an HRCT at baseline to evaluate for ILD,” the study’s lead author, Elana J. Bernstein, MD, said in an interview.

ILD is a leading cause of death in systemic sclerosis (SSc) patients, affecting 40%-60% of those with the disease. HRCT is currently the preferred option for detection of ILD. PFTs are commonly used to screen for ILD but haven’t performed well in previous studies. “Someone can have abnormalities on HRCT that are consistent with ILD but still have PFTs that are in the ‘normal’ range,” explained Dr. Bernstein of Columbia University, New York. One cross-sectional study of 102 SSc patients found that the test’s sensitivity for the detection of ILD on HRCT was just 37.5% when forced vital capacity (FVC) <80% predicted.

Investigators sought to assess performance characteristics of PFTs in patients with early diffuse cutaneous SSc, a cohort at high risk of developing ILD. The study enlisted patients from the Prospective Registry of Early Systemic Sclerosis (PRESS), a multicenter, prospective cohort study of adults with early diffuse cutaneous SSc. Overall, 212 patients at 11 U.S. academic medical centers participated in the study from April 2012 to January 2019.

All patients had spirometry (PFT) and HRCT chest scans. PFTs were conducted per American Thoracic Society/European Respiratory Society guidelines. The investigators calculated test characteristics for single PFT and combinations of PFT parameters for the detection of ILD on HRCT. The HRCTs were ordered at the discretion of treating physicians, and scrutinized for ILD features such as reticular changes, honeycombing, traction bronchiectasis, and ground-glass opacities. The investigators defined the lower limit of normal for FVC, total lung capacity, and diffusion capacity for carbon monoxide (DLCO) as 80% predicted.

Overall, Dr. Bernstein and her colleagues found that PFTs lacked sufficient sensitivity and negative predictive value for the detection of ILD on HRCT in these patients.

An FVC <80% predicted performed at only 63% sensitivity and an false negative rate of 37%. Total lung capacity or DLCO <80% predicted had a sensitivity of 46% and 80%, respectively. The combination of FVC or DLCO <80% predicted raised sensitivity to 85%. However, the addition of total lung capacity to this combination did not improve results.

Overall, PFTs had a positive predictive value of 64%-74% and an negative predictive value of 61%-70%. “This means that PFT alone will not accurately predict the presence of ILD in about 35%, and not be correctly negative in about 35%,” observed Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, and professor of rheumatology at the University of California, Los Angeles.

While the combination of FVC <80% predicted or DLCO <80% predicted performed better than the other parameters, the sensitivity “is inadequate for an ILD screening test as it results in an false negative rate of 15%, thereby falsely reassuring 15% of patients that they do not have ILD when in fact they do,” the investigators observed.

“This study reinforces the notion that PFTs alone are ineffective screening tools for ILD in the presence of systemic sclerosis, particularly for patients with early systemic sclerosis,” said Elizabeth Volkmann, MD, MS, assistant professor and codirector of the CTD-ILD program in the division of rheumatology at the University of California, Los Angeles.

The study’s scope was relatively small, yet the results provide further evidence to show that HRCT should be performed in all SSc patients to screen for the presence of ILD, Dr. Volkmann said in an interview.

Other research has demonstrated the value of baseline HRCT as a prognosticator of ILD outcomes. The method provides useful information about the degree of fibrosis and degree of damage in early-stage disease, said Dr. Furst, also an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). “If there’s honeycombing, that’s a bad prognosis. If it’s ground glass or reticular changes, the prognosis is better.

“Once there’s a lot of damage, it’s much harder to interpret disease with HRCT,” he added.

HRCT and PFT work well together to assess what’s happening in patients, Dr. Furst explained. HRCT provides an idea of anatomic changes, whereas PFT outlines aspects of functional change to diagnose early ILD in early diffuse SSc. The study results should not apply to patients with later disease who have more developed ILD, he noted.

The investigators acknowledged that they weren’t able to categorize and analyze patients according to disease extent because they didn’t quantify the extent of ILD. Another limitation was that the HRCTs and PFTs were ordered at the discretion of individual physicians, which means that not all participants received the tests.

“Although the tests were done in 90% of the population, there is still a probability of a significant selection bias,” Dr. Furst said.

Dr. Bernstein and several other coauthors in the study received grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to support their work. Dr. Furst disclosed receiving grant/research support from and/or consulting for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech. Dr. Volkmann disclosed consulting for and/or receiving grant support from Boehringer Ingelheim, Corbus, and Forbius.

SOURCE: Bernstein EJ et al. Arthritis Rheumatol. 2020 Jun 25. doi: 10.1002/art.41415.

Clinicians shouldn’t rely on pulmonary function tests (PFTs) alone to screen for interstitial lung disease (ILD). The tests performed poorly in a retrospective study of 212 patients with systemic sclerosis, reinforcing the findings of previous studies.

Any screening algorithm should include high-resolution CT (HRCT), which is good at prognosticating disease, the investigators wrote in Arthritis & Rheumatology. “I think all newly diagnosed systemic sclerosis patients should have a full set of PFTs (spirometry, lung volumes, and diffusion capacity) and an HRCT at baseline to evaluate for ILD,” the study’s lead author, Elana J. Bernstein, MD, said in an interview.

ILD is a leading cause of death in systemic sclerosis (SSc) patients, affecting 40%-60% of those with the disease. HRCT is currently the preferred option for detection of ILD. PFTs are commonly used to screen for ILD but haven’t performed well in previous studies. “Someone can have abnormalities on HRCT that are consistent with ILD but still have PFTs that are in the ‘normal’ range,” explained Dr. Bernstein of Columbia University, New York. One cross-sectional study of 102 SSc patients found that the test’s sensitivity for the detection of ILD on HRCT was just 37.5% when forced vital capacity (FVC) <80% predicted.

Investigators sought to assess performance characteristics of PFTs in patients with early diffuse cutaneous SSc, a cohort at high risk of developing ILD. The study enlisted patients from the Prospective Registry of Early Systemic Sclerosis (PRESS), a multicenter, prospective cohort study of adults with early diffuse cutaneous SSc. Overall, 212 patients at 11 U.S. academic medical centers participated in the study from April 2012 to January 2019.

All patients had spirometry (PFT) and HRCT chest scans. PFTs were conducted per American Thoracic Society/European Respiratory Society guidelines. The investigators calculated test characteristics for single PFT and combinations of PFT parameters for the detection of ILD on HRCT. The HRCTs were ordered at the discretion of treating physicians, and scrutinized for ILD features such as reticular changes, honeycombing, traction bronchiectasis, and ground-glass opacities. The investigators defined the lower limit of normal for FVC, total lung capacity, and diffusion capacity for carbon monoxide (DLCO) as 80% predicted.

Overall, Dr. Bernstein and her colleagues found that PFTs lacked sufficient sensitivity and negative predictive value for the detection of ILD on HRCT in these patients.

An FVC <80% predicted performed at only 63% sensitivity and an false negative rate of 37%. Total lung capacity or DLCO <80% predicted had a sensitivity of 46% and 80%, respectively. The combination of FVC or DLCO <80% predicted raised sensitivity to 85%. However, the addition of total lung capacity to this combination did not improve results.

Overall, PFTs had a positive predictive value of 64%-74% and an negative predictive value of 61%-70%. “This means that PFT alone will not accurately predict the presence of ILD in about 35%, and not be correctly negative in about 35%,” observed Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, and professor of rheumatology at the University of California, Los Angeles.

While the combination of FVC <80% predicted or DLCO <80% predicted performed better than the other parameters, the sensitivity “is inadequate for an ILD screening test as it results in an false negative rate of 15%, thereby falsely reassuring 15% of patients that they do not have ILD when in fact they do,” the investigators observed.

“This study reinforces the notion that PFTs alone are ineffective screening tools for ILD in the presence of systemic sclerosis, particularly for patients with early systemic sclerosis,” said Elizabeth Volkmann, MD, MS, assistant professor and codirector of the CTD-ILD program in the division of rheumatology at the University of California, Los Angeles.

The study’s scope was relatively small, yet the results provide further evidence to show that HRCT should be performed in all SSc patients to screen for the presence of ILD, Dr. Volkmann said in an interview.

Other research has demonstrated the value of baseline HRCT as a prognosticator of ILD outcomes. The method provides useful information about the degree of fibrosis and degree of damage in early-stage disease, said Dr. Furst, also an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). “If there’s honeycombing, that’s a bad prognosis. If it’s ground glass or reticular changes, the prognosis is better.

“Once there’s a lot of damage, it’s much harder to interpret disease with HRCT,” he added.

HRCT and PFT work well together to assess what’s happening in patients, Dr. Furst explained. HRCT provides an idea of anatomic changes, whereas PFT outlines aspects of functional change to diagnose early ILD in early diffuse SSc. The study results should not apply to patients with later disease who have more developed ILD, he noted.

The investigators acknowledged that they weren’t able to categorize and analyze patients according to disease extent because they didn’t quantify the extent of ILD. Another limitation was that the HRCTs and PFTs were ordered at the discretion of individual physicians, which means that not all participants received the tests.

“Although the tests were done in 90% of the population, there is still a probability of a significant selection bias,” Dr. Furst said.

Dr. Bernstein and several other coauthors in the study received grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to support their work. Dr. Furst disclosed receiving grant/research support from and/or consulting for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech. Dr. Volkmann disclosed consulting for and/or receiving grant support from Boehringer Ingelheim, Corbus, and Forbius.

SOURCE: Bernstein EJ et al. Arthritis Rheumatol. 2020 Jun 25. doi: 10.1002/art.41415.

The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.

M. Alexander Otto/MDedge News

“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”

Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”

In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.

At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.

A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.

The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).

When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).

“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”

For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.

According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.

Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”

Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.

Dr. Elman reported having no financial disclosures.

[email protected]

The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.

M. Alexander Otto/MDedge News

“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”

Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”

In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.

At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.

A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.

The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).

When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).

“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”

For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.

According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.

Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”

Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.

Dr. Elman reported having no financial disclosures.

[email protected]

The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.

M. Alexander Otto/MDedge News

“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”

Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”

In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.

At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.

A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.

The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).

When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).

“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”

For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.

According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.

Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”

Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.

Dr. Elman reported having no financial disclosures.

[email protected]

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

copyright nebari/Thinkstock

About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.

“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”

Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.

The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.

The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.

The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.

When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.

Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.

“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”

Dr. Frech reported having no financial conflicts regarding her presentation.

[email protected]

Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

copyright nebari/Thinkstock

About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.

“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”

Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.

The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.

The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.

The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.

When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.

Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.

“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”

Dr. Frech reported having no financial conflicts regarding her presentation.

[email protected]

Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

copyright nebari/Thinkstock

About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.

“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”

Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.

The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.

The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.

The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.

When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.

Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.

“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”

Dr. Frech reported having no financial conflicts regarding her presentation.

[email protected]

Treatment of patients with systemic lupus erythematosus and active lupus nephritis with belimumab (Benlysta) for 2 years with minimized background glucocorticoid treatment produced significantly better renal function, compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.

Sara Freeman/MDedge News

“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m² and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.

Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m² and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.

“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.

Results confirm benefit to subset of patients

“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.

The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
 

Thoughts on current and future use of belimumab

The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.

“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.

“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.

“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.

BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.

[email protected]

SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.

Treatment of patients with systemic lupus erythematosus and active lupus nephritis with belimumab (Benlysta) for 2 years with minimized background glucocorticoid treatment produced significantly better renal function, compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.

Sara Freeman/MDedge News

“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m² and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.

Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m² and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.

“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.

Results confirm benefit to subset of patients

“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.

The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
 

Thoughts on current and future use of belimumab

The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.

“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.

“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.

“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.

BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.

[email protected]

SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.

Treatment of patients with systemic lupus erythematosus and active lupus nephritis with belimumab (Benlysta) for 2 years with minimized background glucocorticoid treatment produced significantly better renal function, compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.

Sara Freeman/MDedge News

“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m² and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.

Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m² and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.

“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.

Results confirm benefit to subset of patients

“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.

The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
 

Thoughts on current and future use of belimumab

The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.

“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.

“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.

“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.

BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.

[email protected]

SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.

New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.

copyright Martynasfoto/Thinkstock

ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.

“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.

There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.

In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.

The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.

Which test methodology to use?

There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?

The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”

Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.

“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”

The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.

“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.

In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”

Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.

New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.

copyright Martynasfoto/Thinkstock

ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.

“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.

There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.

In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.

The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.

Which test methodology to use?

There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?

The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”

Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.

“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”

The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.

“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.

In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”

Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.

New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.

copyright Martynasfoto/Thinkstock

ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.

“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.

There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.

In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.

The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.

Which test methodology to use?

There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?

The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”

Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.

“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”

The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.

“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.

In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”

Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.

Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.

“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
 

Atypical presentations occur in 30%

Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.

While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.

The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.

Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.

“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.

Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.

Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.

Prognosis and predictors

Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.

Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.

“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.

He reported having no financial conflicts regarding his presentation.

[email protected]

Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.

“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
 

Atypical presentations occur in 30%

Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.

While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.

The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.

Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.

“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.

Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.

Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.

Prognosis and predictors

Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.

Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.

“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.

He reported having no financial conflicts regarding his presentation.

[email protected]

Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.

“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
 

Atypical presentations occur in 30%

Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.

While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.

The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.

Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.

“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.

Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.

Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.

Prognosis and predictors

Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.

Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.

“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.

He reported having no financial conflicts regarding his presentation.

[email protected]