User login
MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.
“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.
Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.
Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.
“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.
At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.
In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.
“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
Red flags for underlying PID
Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.
“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.
A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
Testing for PID
It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.
“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.
Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.
Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.
“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
Get to know your local allergist/immunologist
Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.
“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”
Dr. Postolova reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.
“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.
Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.
Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.
“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.
At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.
In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.
“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
Red flags for underlying PID
Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.
“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.
A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
Testing for PID
It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.
“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.
Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.
Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.
“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
Get to know your local allergist/immunologist
Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.
“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”
Dr. Postolova reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.
“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.
Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.
Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.
“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.
At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.
In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.
“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
Red flags for underlying PID
Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.
“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.
A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
Testing for PID
It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.
“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.
Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.
Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.
“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
Get to know your local allergist/immunologist
Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.
“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”
Dr. Postolova reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2020