The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.

Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.

Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.

Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.

The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

Specific indications for the biosimilar are as follows:

Metastatic colorectal cancer

Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.

Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.

Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.

First-line nonsquamous non–small cell lung cancer

Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.

Recurrent glioblastoma

Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.

Metastatic renal cell carcinoma

Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.

Persistent, recurrent, or metastatic cervical cancer

Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Complete prescribing information can be found on the FDA website.

The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.

Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.

Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.

Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.

The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

Specific indications for the biosimilar are as follows:

Metastatic colorectal cancer

Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.

Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.

Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.

First-line nonsquamous non–small cell lung cancer

Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.

Recurrent glioblastoma

Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.

Metastatic renal cell carcinoma

Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.

Persistent, recurrent, or metastatic cervical cancer

Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Complete prescribing information can be found on the FDA website.

The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.

Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.

Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.

Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.

The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

Specific indications for the biosimilar are as follows:

Metastatic colorectal cancer

Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.

Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.

Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.

First-line nonsquamous non–small cell lung cancer

Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.

Recurrent glioblastoma

Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.

Metastatic renal cell carcinoma

Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.

Persistent, recurrent, or metastatic cervical cancer

Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Complete prescribing information can be found on the FDA website.

Have you noticed that you and your staff are spending more time on prior authorization than in the past? Insurance companies are increasing the number of Current Procedural Terminology (CPT®) codes for services and procedures included in their prior authorization programs. More importantly, they are doing so without providing evidence that this approach improves patient safety or decreases unindicated medical procedures. There is also no transparency about how these prior authorization processes are developed, evaluated, or adjusted over time. Physicians and their staff are pushing back on social media, calling prior authorization programs a hassle and citing lengthy waits to speak to a physician reviewer who is often not even in their specialty.

Historically, insurers have used prior authorization to control costs, particularly those related to procedures and tests that may be inappropriately overutilized or no longer the standard of care; however, current activity suggests a much broader, indiscriminate approach. For example, insurers are requiring prior authorization for whole families of services and procedures. Anthem, the second largest insurance company in the United States, recently added the entire family of esophagogastroduodenoscopy (EGD) codes to its list of procedures requiring prior authorization in 10 states including Calif., Conn., Ind, Ohio, Ky., Mo., Nev., N.H., Va., and Wisc. A conversation earlier this year with the Anthem national prior authorization team revealed that they intend to keep adding codes for all specialties to their prior authorization program, portraying the process conducted by AIM Specialty Health® (a wholly-owned subsidiary of Anthem, Inc.), as fast, simple, and easy. However, many physicians and their office staff find the prior authorization process complex, time consuming, and frustrating.

Social media is rife with accounts from physicians who were forced to cancel planned procedures because the prior authorization process took weeks instead of days, received denials, and later found out that procedures were actually approved, or found themselves in peer-to-peer review with nonphysicians. Gastroenterologists have also reported cases of patients having flares of inflammatory bowel disease because of medication delays related to a cumbersome preauthorization process.

Because prior authorization impacts gastroenterologists’ ability to provide timely care to patients, AGA and the entire physician community have been calling for regulatory change related to prior authorization in Medicare Advantage (MA) plans to reduce physician burden and enhance patient safety and care.

Last year, AGA worked with our congressional champions Reps. Phil Roe, MD, (R-Tenn.) and Ami Bera, MD, (D-Calif.) to secure 150 signatures on a letter to the CMS Administrator requesting the agency provide guidance to MA plans to ensure that prior authorization requirements do not create barriers to care.

One in every three people with Medicare is enrolled in a Medicare Advantage (MA) plan. Under current law, MA plans may not create inappropriate barriers to care that do not already exist within the original Medicare program. A recent survey by the American Medical Association found that over 90% of physician respondents felt that the prior authorization process led to delays in care for patients that could negatively impact clinical outcomes. AGA and other physician organizations are advocating for regulatory changes related to how MA plans use prior authorization.

In addition to our regulatory efforts, the AGA is working with members of Congress on legislative solutions to require the MA plans to increase transparency, streamline the prior authorization process, and minimize the impact on Medicare beneficiaries. Reps. Susan DelBene, D-Wash., Mike Kelly, R-Penna., Ami Bera, D-Calif., and Roger Marshall, R-Kans. introduced the Improving Seniors Timely Access to Care Act of 2019, legislation that would streamline the prior authorization process in the Medicare Advantage program to relieve the administrative burdens this poses for physicians and help patients receive quicker access to the medical care they need. Although this legislation only addresses MA plans, we are hopeful that this will be the first step in requiring health plans to streamline this process and ease administrative burden. Please help us increase support for this bill by contacting your legislators and asking that they cosponsor. It will take less than 5 minutes of your time and will have a significant effect, given the opposition we face from insurers. The AGA is working on your behalf to address prior authorization hassles with private payors, but to be effective we need to hear your experiences. We know private payors continue to develop more and more restrictive prior authorization policies covering an increasing number of services and procedures without evidence that these actions provide benefit to patients. Frequently, these policies are put into action without advance warning and your reports are the first signs we have that a change has been made. Reach out to the AGA via the AGA Community or Twitter to let us know what’s happening. We will take your stories directly to the insurance companies and demand that they work with us to reduce physician burden and improve transparency.

You may also consider filing a complaint with the State Insurance Commissioner. State Insurance Commissioners are responsible for regulating the insurance industry in their state and can investigate to make sure the laws in their state are being followed and providers and patients are being treated fairly. While insurance law and regulation are established at the state level, the insurance commissioners are members of the National Association of Insurance Commissioners (NAIC), which allows them to coordinate insurance regulation among the states and territories.

If you decide to file a complaint with your State Insurance Commissioner, first familiarize yourself with your state’s complaint process. Many state insurance commissioners have a standard complaint form you can download or fill out online. Be sure to keep records of all conversations and interactions with the insurance company to document the steps you’ve taken to attempt to resolve the issue. Consider creating a log of the dates, times, and nature of your contact with the insurance company.

Once you have filed a complaint, the commissioner may send a copy to the insurance company and give them a date by which they must respond. If the commissioner believes the response is sufficient, she or he will send a copy of the insurance company’s response to you. If the commissioner feels the insurance company’s response is inadequate, staff from the commissioner’s office will work with you and the insurer to resolve the issue.

While a report of one negative experience with an insurer may not be enough to elicit action, a pattern of delays and difficulties with an insurer’s prior authorization process noted by many physicians is likely to catch an Insurance Commissioner’s attention. The NAIC cannot tell a problem is widespread if providers and patients don’t report it to the State Insurance Commissioners.

Please reach out to AGA with your stories about prior authorization problems, consider reporting insurance companies that employ systems that cause undue burden and delay to your State Insurance Commissioner and help us increase support for the Improving Seniors Timely Access to Care Act of 2019 by contacting your legislators and asking that they cosponsor using this link https://app.govpredict.com/portal/grassroots/campaigns/io77ozaa/take_action. Together, we can pressure insurers, Congress, and Medicare to relieve physician burden and help our patients receive the timely care they need.
 

Dr. Garcia is a member of the AGA Practice Management and Economics Committee’s Coverage And Reimbursement Subcommittee and clinical assistant professor of medicine, gastroenterology & hepatology, Stanford Medicine, Stanford, California. Dr. Mathews is a member of the AGA Government Affairs Committee and leads efforts in clinical innovation at the Johns Hopkins Armstrong Institute for Patient Safety and Quality, Baltimore.

Tihs story was updated on July 29, 2019.
 

[email protected]

Have you noticed that you and your staff are spending more time on prior authorization than in the past? Insurance companies are increasing the number of Current Procedural Terminology (CPT®) codes for services and procedures included in their prior authorization programs. More importantly, they are doing so without providing evidence that this approach improves patient safety or decreases unindicated medical procedures. There is also no transparency about how these prior authorization processes are developed, evaluated, or adjusted over time. Physicians and their staff are pushing back on social media, calling prior authorization programs a hassle and citing lengthy waits to speak to a physician reviewer who is often not even in their specialty.

Historically, insurers have used prior authorization to control costs, particularly those related to procedures and tests that may be inappropriately overutilized or no longer the standard of care; however, current activity suggests a much broader, indiscriminate approach. For example, insurers are requiring prior authorization for whole families of services and procedures. Anthem, the second largest insurance company in the United States, recently added the entire family of esophagogastroduodenoscopy (EGD) codes to its list of procedures requiring prior authorization in 10 states including Calif., Conn., Ind, Ohio, Ky., Mo., Nev., N.H., Va., and Wisc. A conversation earlier this year with the Anthem national prior authorization team revealed that they intend to keep adding codes for all specialties to their prior authorization program, portraying the process conducted by AIM Specialty Health® (a wholly-owned subsidiary of Anthem, Inc.), as fast, simple, and easy. However, many physicians and their office staff find the prior authorization process complex, time consuming, and frustrating.

Social media is rife with accounts from physicians who were forced to cancel planned procedures because the prior authorization process took weeks instead of days, received denials, and later found out that procedures were actually approved, or found themselves in peer-to-peer review with nonphysicians. Gastroenterologists have also reported cases of patients having flares of inflammatory bowel disease because of medication delays related to a cumbersome preauthorization process.

Because prior authorization impacts gastroenterologists’ ability to provide timely care to patients, AGA and the entire physician community have been calling for regulatory change related to prior authorization in Medicare Advantage (MA) plans to reduce physician burden and enhance patient safety and care.

Last year, AGA worked with our congressional champions Reps. Phil Roe, MD, (R-Tenn.) and Ami Bera, MD, (D-Calif.) to secure 150 signatures on a letter to the CMS Administrator requesting the agency provide guidance to MA plans to ensure that prior authorization requirements do not create barriers to care.

One in every three people with Medicare is enrolled in a Medicare Advantage (MA) plan. Under current law, MA plans may not create inappropriate barriers to care that do not already exist within the original Medicare program. A recent survey by the American Medical Association found that over 90% of physician respondents felt that the prior authorization process led to delays in care for patients that could negatively impact clinical outcomes. AGA and other physician organizations are advocating for regulatory changes related to how MA plans use prior authorization.

In addition to our regulatory efforts, the AGA is working with members of Congress on legislative solutions to require the MA plans to increase transparency, streamline the prior authorization process, and minimize the impact on Medicare beneficiaries. Reps. Susan DelBene, D-Wash., Mike Kelly, R-Penna., Ami Bera, D-Calif., and Roger Marshall, R-Kans. introduced the Improving Seniors Timely Access to Care Act of 2019, legislation that would streamline the prior authorization process in the Medicare Advantage program to relieve the administrative burdens this poses for physicians and help patients receive quicker access to the medical care they need. Although this legislation only addresses MA plans, we are hopeful that this will be the first step in requiring health plans to streamline this process and ease administrative burden. Please help us increase support for this bill by contacting your legislators and asking that they cosponsor. It will take less than 5 minutes of your time and will have a significant effect, given the opposition we face from insurers. The AGA is working on your behalf to address prior authorization hassles with private payors, but to be effective we need to hear your experiences. We know private payors continue to develop more and more restrictive prior authorization policies covering an increasing number of services and procedures without evidence that these actions provide benefit to patients. Frequently, these policies are put into action without advance warning and your reports are the first signs we have that a change has been made. Reach out to the AGA via the AGA Community or Twitter to let us know what’s happening. We will take your stories directly to the insurance companies and demand that they work with us to reduce physician burden and improve transparency.

You may also consider filing a complaint with the State Insurance Commissioner. State Insurance Commissioners are responsible for regulating the insurance industry in their state and can investigate to make sure the laws in their state are being followed and providers and patients are being treated fairly. While insurance law and regulation are established at the state level, the insurance commissioners are members of the National Association of Insurance Commissioners (NAIC), which allows them to coordinate insurance regulation among the states and territories.

If you decide to file a complaint with your State Insurance Commissioner, first familiarize yourself with your state’s complaint process. Many state insurance commissioners have a standard complaint form you can download or fill out online. Be sure to keep records of all conversations and interactions with the insurance company to document the steps you’ve taken to attempt to resolve the issue. Consider creating a log of the dates, times, and nature of your contact with the insurance company.

Once you have filed a complaint, the commissioner may send a copy to the insurance company and give them a date by which they must respond. If the commissioner believes the response is sufficient, she or he will send a copy of the insurance company’s response to you. If the commissioner feels the insurance company’s response is inadequate, staff from the commissioner’s office will work with you and the insurer to resolve the issue.

While a report of one negative experience with an insurer may not be enough to elicit action, a pattern of delays and difficulties with an insurer’s prior authorization process noted by many physicians is likely to catch an Insurance Commissioner’s attention. The NAIC cannot tell a problem is widespread if providers and patients don’t report it to the State Insurance Commissioners.

Please reach out to AGA with your stories about prior authorization problems, consider reporting insurance companies that employ systems that cause undue burden and delay to your State Insurance Commissioner and help us increase support for the Improving Seniors Timely Access to Care Act of 2019 by contacting your legislators and asking that they cosponsor using this link https://app.govpredict.com/portal/grassroots/campaigns/io77ozaa/take_action. Together, we can pressure insurers, Congress, and Medicare to relieve physician burden and help our patients receive the timely care they need.
 

Dr. Garcia is a member of the AGA Practice Management and Economics Committee’s Coverage And Reimbursement Subcommittee and clinical assistant professor of medicine, gastroenterology & hepatology, Stanford Medicine, Stanford, California. Dr. Mathews is a member of the AGA Government Affairs Committee and leads efforts in clinical innovation at the Johns Hopkins Armstrong Institute for Patient Safety and Quality, Baltimore.

Tihs story was updated on July 29, 2019.
 

[email protected]

Have you noticed that you and your staff are spending more time on prior authorization than in the past? Insurance companies are increasing the number of Current Procedural Terminology (CPT®) codes for services and procedures included in their prior authorization programs. More importantly, they are doing so without providing evidence that this approach improves patient safety or decreases unindicated medical procedures. There is also no transparency about how these prior authorization processes are developed, evaluated, or adjusted over time. Physicians and their staff are pushing back on social media, calling prior authorization programs a hassle and citing lengthy waits to speak to a physician reviewer who is often not even in their specialty.

Historically, insurers have used prior authorization to control costs, particularly those related to procedures and tests that may be inappropriately overutilized or no longer the standard of care; however, current activity suggests a much broader, indiscriminate approach. For example, insurers are requiring prior authorization for whole families of services and procedures. Anthem, the second largest insurance company in the United States, recently added the entire family of esophagogastroduodenoscopy (EGD) codes to its list of procedures requiring prior authorization in 10 states including Calif., Conn., Ind, Ohio, Ky., Mo., Nev., N.H., Va., and Wisc. A conversation earlier this year with the Anthem national prior authorization team revealed that they intend to keep adding codes for all specialties to their prior authorization program, portraying the process conducted by AIM Specialty Health® (a wholly-owned subsidiary of Anthem, Inc.), as fast, simple, and easy. However, many physicians and their office staff find the prior authorization process complex, time consuming, and frustrating.

Social media is rife with accounts from physicians who were forced to cancel planned procedures because the prior authorization process took weeks instead of days, received denials, and later found out that procedures were actually approved, or found themselves in peer-to-peer review with nonphysicians. Gastroenterologists have also reported cases of patients having flares of inflammatory bowel disease because of medication delays related to a cumbersome preauthorization process.

Because prior authorization impacts gastroenterologists’ ability to provide timely care to patients, AGA and the entire physician community have been calling for regulatory change related to prior authorization in Medicare Advantage (MA) plans to reduce physician burden and enhance patient safety and care.

Last year, AGA worked with our congressional champions Reps. Phil Roe, MD, (R-Tenn.) and Ami Bera, MD, (D-Calif.) to secure 150 signatures on a letter to the CMS Administrator requesting the agency provide guidance to MA plans to ensure that prior authorization requirements do not create barriers to care.

One in every three people with Medicare is enrolled in a Medicare Advantage (MA) plan. Under current law, MA plans may not create inappropriate barriers to care that do not already exist within the original Medicare program. A recent survey by the American Medical Association found that over 90% of physician respondents felt that the prior authorization process led to delays in care for patients that could negatively impact clinical outcomes. AGA and other physician organizations are advocating for regulatory changes related to how MA plans use prior authorization.

In addition to our regulatory efforts, the AGA is working with members of Congress on legislative solutions to require the MA plans to increase transparency, streamline the prior authorization process, and minimize the impact on Medicare beneficiaries. Reps. Susan DelBene, D-Wash., Mike Kelly, R-Penna., Ami Bera, D-Calif., and Roger Marshall, R-Kans. introduced the Improving Seniors Timely Access to Care Act of 2019, legislation that would streamline the prior authorization process in the Medicare Advantage program to relieve the administrative burdens this poses for physicians and help patients receive quicker access to the medical care they need. Although this legislation only addresses MA plans, we are hopeful that this will be the first step in requiring health plans to streamline this process and ease administrative burden. Please help us increase support for this bill by contacting your legislators and asking that they cosponsor. It will take less than 5 minutes of your time and will have a significant effect, given the opposition we face from insurers. The AGA is working on your behalf to address prior authorization hassles with private payors, but to be effective we need to hear your experiences. We know private payors continue to develop more and more restrictive prior authorization policies covering an increasing number of services and procedures without evidence that these actions provide benefit to patients. Frequently, these policies are put into action without advance warning and your reports are the first signs we have that a change has been made. Reach out to the AGA via the AGA Community or Twitter to let us know what’s happening. We will take your stories directly to the insurance companies and demand that they work with us to reduce physician burden and improve transparency.

You may also consider filing a complaint with the State Insurance Commissioner. State Insurance Commissioners are responsible for regulating the insurance industry in their state and can investigate to make sure the laws in their state are being followed and providers and patients are being treated fairly. While insurance law and regulation are established at the state level, the insurance commissioners are members of the National Association of Insurance Commissioners (NAIC), which allows them to coordinate insurance regulation among the states and territories.

If you decide to file a complaint with your State Insurance Commissioner, first familiarize yourself with your state’s complaint process. Many state insurance commissioners have a standard complaint form you can download or fill out online. Be sure to keep records of all conversations and interactions with the insurance company to document the steps you’ve taken to attempt to resolve the issue. Consider creating a log of the dates, times, and nature of your contact with the insurance company.

Once you have filed a complaint, the commissioner may send a copy to the insurance company and give them a date by which they must respond. If the commissioner believes the response is sufficient, she or he will send a copy of the insurance company’s response to you. If the commissioner feels the insurance company’s response is inadequate, staff from the commissioner’s office will work with you and the insurer to resolve the issue.

While a report of one negative experience with an insurer may not be enough to elicit action, a pattern of delays and difficulties with an insurer’s prior authorization process noted by many physicians is likely to catch an Insurance Commissioner’s attention. The NAIC cannot tell a problem is widespread if providers and patients don’t report it to the State Insurance Commissioners.

Please reach out to AGA with your stories about prior authorization problems, consider reporting insurance companies that employ systems that cause undue burden and delay to your State Insurance Commissioner and help us increase support for the Improving Seniors Timely Access to Care Act of 2019 by contacting your legislators and asking that they cosponsor using this link https://app.govpredict.com/portal/grassroots/campaigns/io77ozaa/take_action. Together, we can pressure insurers, Congress, and Medicare to relieve physician burden and help our patients receive the timely care they need.
 

Dr. Garcia is a member of the AGA Practice Management and Economics Committee’s Coverage And Reimbursement Subcommittee and clinical assistant professor of medicine, gastroenterology & hepatology, Stanford Medicine, Stanford, California. Dr. Mathews is a member of the AGA Government Affairs Committee and leads efforts in clinical innovation at the Johns Hopkins Armstrong Institute for Patient Safety and Quality, Baltimore.

Tihs story was updated on July 29, 2019.
 

[email protected]

Management of psoriasis as a systemic disease: What is the evidence?

Korman NJ. Br J Dermatol. 2019 Jun 21.

This narrative review explores the pathophysiological relationship between psoriasis and its common comorbidities and discusses the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis.

Managing Psoriasis in Patients with HBV or HCV Infection: Practical Considerations.

Piaserico S, Messina F, Russo FP. Am J Clin Dermatol. 2019 Jun 20.

It has been estimated that two billion individuals are infected with HBV worldwide and approximately 240 million have chronic HBV infection. Moreover, there are approximately 71 million individuals with chronic HCV infection worldwide, with a high percentage of them unaware of being infected. As patients with HBV and HCV infections are excluded from controlled clinical trials investigating new drugs, data regarding their safety in patients with psoriasis are based almost exclusively on case reports and small retrospective cohort studies and need to be constantly updated.

Effects of Online Care on Functional and Psychological Outcomes in Patients with Psoriasis: A Randomized Controlled Trial.

Young PM, Chen AY, Ford AR, Cheng MY, Lane CJ, Armstrong AW. J Am Acad Dermatol. 2019 Jun 5.

The impact of online care on patients' functional and psychological outcomes is critical to determine yet still unknown. This 12-month randomized controlled equivalency trial evaluated how a novel online health model that facilitates physician-patient collaboration compares with in-person care for improving psoriasis patients' functional status and mental health.

Feasibility and Utility of the Psoriasis Symptom Inventory (PSI) in Clinical Care Settings: A Study from the International Psoriasis Council.

Strober B, van de Kerkhof PCM, Callis Duffin K, et al.  Am J Clin Dermatol. 2019 Jun 21.

The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome measure designed to assess psoriasis signs and symptoms. The aim of the study was to assess the usefulness of the PSI in enhancing patient care in the clinical setting. Eight dermatology clinics in six countries enrolled adults representing the full spectrum of psoriasis severity who regularly received care at the clinic. Key benefits of PSI discussions included the following: new information regarding symptom location and severity for physicians; prompting of quality-of-life discussions; better understanding of patient treatment priorities; change in treatment regimens to target specific symptoms or areas; and improvement of patient-physician relationship.

Socioeconomic Costs and Health Inequalities from Psoriasis: A Cohort Study.

Thomsen SF, Skov L, Dodge R, Hedegaard MS, Kjellberg J. Dermatology. 2019 Jun 25:1-8.  

Incentives for health care management based on patient-related outcomes and value (IMPROVE) in psoriasis and psoriatic arthritis is a project aimed at assisting movement from activity-based to outcome-based health care management. One of the key objectives in IMPROVE is to describe the disease-associated socioeconomic burden of psoriasis. The IMPROVE study was a retrospective analysis of patients with a hospital diagnosis of psoriasis identified from the Danish National Patient Registry.

Management of psoriasis as a systemic disease: What is the evidence?

Korman NJ. Br J Dermatol. 2019 Jun 21.

This narrative review explores the pathophysiological relationship between psoriasis and its common comorbidities and discusses the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis.

Managing Psoriasis in Patients with HBV or HCV Infection: Practical Considerations.

Piaserico S, Messina F, Russo FP. Am J Clin Dermatol. 2019 Jun 20.

It has been estimated that two billion individuals are infected with HBV worldwide and approximately 240 million have chronic HBV infection. Moreover, there are approximately 71 million individuals with chronic HCV infection worldwide, with a high percentage of them unaware of being infected. As patients with HBV and HCV infections are excluded from controlled clinical trials investigating new drugs, data regarding their safety in patients with psoriasis are based almost exclusively on case reports and small retrospective cohort studies and need to be constantly updated.

Effects of Online Care on Functional and Psychological Outcomes in Patients with Psoriasis: A Randomized Controlled Trial.

Young PM, Chen AY, Ford AR, Cheng MY, Lane CJ, Armstrong AW. J Am Acad Dermatol. 2019 Jun 5.

The impact of online care on patients' functional and psychological outcomes is critical to determine yet still unknown. This 12-month randomized controlled equivalency trial evaluated how a novel online health model that facilitates physician-patient collaboration compares with in-person care for improving psoriasis patients' functional status and mental health.

Feasibility and Utility of the Psoriasis Symptom Inventory (PSI) in Clinical Care Settings: A Study from the International Psoriasis Council.

Strober B, van de Kerkhof PCM, Callis Duffin K, et al.  Am J Clin Dermatol. 2019 Jun 21.

The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome measure designed to assess psoriasis signs and symptoms. The aim of the study was to assess the usefulness of the PSI in enhancing patient care in the clinical setting. Eight dermatology clinics in six countries enrolled adults representing the full spectrum of psoriasis severity who regularly received care at the clinic. Key benefits of PSI discussions included the following: new information regarding symptom location and severity for physicians; prompting of quality-of-life discussions; better understanding of patient treatment priorities; change in treatment regimens to target specific symptoms or areas; and improvement of patient-physician relationship.

Socioeconomic Costs and Health Inequalities from Psoriasis: A Cohort Study.

Thomsen SF, Skov L, Dodge R, Hedegaard MS, Kjellberg J. Dermatology. 2019 Jun 25:1-8.  

Incentives for health care management based on patient-related outcomes and value (IMPROVE) in psoriasis and psoriatic arthritis is a project aimed at assisting movement from activity-based to outcome-based health care management. One of the key objectives in IMPROVE is to describe the disease-associated socioeconomic burden of psoriasis. The IMPROVE study was a retrospective analysis of patients with a hospital diagnosis of psoriasis identified from the Danish National Patient Registry.

Management of psoriasis as a systemic disease: What is the evidence?

Korman NJ. Br J Dermatol. 2019 Jun 21.

This narrative review explores the pathophysiological relationship between psoriasis and its common comorbidities and discusses the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis.

Managing Psoriasis in Patients with HBV or HCV Infection: Practical Considerations.

Piaserico S, Messina F, Russo FP. Am J Clin Dermatol. 2019 Jun 20.

It has been estimated that two billion individuals are infected with HBV worldwide and approximately 240 million have chronic HBV infection. Moreover, there are approximately 71 million individuals with chronic HCV infection worldwide, with a high percentage of them unaware of being infected. As patients with HBV and HCV infections are excluded from controlled clinical trials investigating new drugs, data regarding their safety in patients with psoriasis are based almost exclusively on case reports and small retrospective cohort studies and need to be constantly updated.

Effects of Online Care on Functional and Psychological Outcomes in Patients with Psoriasis: A Randomized Controlled Trial.

Young PM, Chen AY, Ford AR, Cheng MY, Lane CJ, Armstrong AW. J Am Acad Dermatol. 2019 Jun 5.

The impact of online care on patients' functional and psychological outcomes is critical to determine yet still unknown. This 12-month randomized controlled equivalency trial evaluated how a novel online health model that facilitates physician-patient collaboration compares with in-person care for improving psoriasis patients' functional status and mental health.

Feasibility and Utility of the Psoriasis Symptom Inventory (PSI) in Clinical Care Settings: A Study from the International Psoriasis Council.

Strober B, van de Kerkhof PCM, Callis Duffin K, et al.  Am J Clin Dermatol. 2019 Jun 21.

The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome measure designed to assess psoriasis signs and symptoms. The aim of the study was to assess the usefulness of the PSI in enhancing patient care in the clinical setting. Eight dermatology clinics in six countries enrolled adults representing the full spectrum of psoriasis severity who regularly received care at the clinic. Key benefits of PSI discussions included the following: new information regarding symptom location and severity for physicians; prompting of quality-of-life discussions; better understanding of patient treatment priorities; change in treatment regimens to target specific symptoms or areas; and improvement of patient-physician relationship.

Socioeconomic Costs and Health Inequalities from Psoriasis: A Cohort Study.

Thomsen SF, Skov L, Dodge R, Hedegaard MS, Kjellberg J. Dermatology. 2019 Jun 25:1-8.  

Incentives for health care management based on patient-related outcomes and value (IMPROVE) in psoriasis and psoriatic arthritis is a project aimed at assisting movement from activity-based to outcome-based health care management. One of the key objectives in IMPROVE is to describe the disease-associated socioeconomic burden of psoriasis. The IMPROVE study was a retrospective analysis of patients with a hospital diagnosis of psoriasis identified from the Danish National Patient Registry.

Treating Psoriatic Arthritis to Target: Defining Psoriatic Arthritis Disease Activity Score (PASDAS) That Reflects State Of Minimal Disease Activity (MDA).

Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. J Rheumatol. 2019 Jun 15.

PsA Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis. The study aimed to validate a cutoff value of PASDAS that defines minimal disease activity state, as well as validate previously defined PASDAS cutoffs for low and high disease activity.

Evaluating current definitions of low disease activity in psoriatic arthritis using ultrasound.

Bosch P, Husic R, Ficjan A, et al. Rheumatology (Oxford). 2019 Jun 14.

The aim of the study was to evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire.

Tillett W, Lin CY, Zbrozek A, Sprabery AT, Birt J.  Rheumatol Ther. 2019 Jun 1.

The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). The objective of the study was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA.

Measuring Psoriatic Arthritis Symptoms, A Core Domain in Psoriasis Clinical Trials.

Perez-Chada LM, Gottlieb AB, Cohen J, et al. J Am Acad Dermatol. 2019 Jun 1.

The International Dermatology Outcome Measures (IDEOM) established a set of core domains to be measured in all psoriasis trials. This set indicates that symptoms of psoriatic arthritis (PsA) should be measured in all psoriasis studies. The objective of the study was to identify the approach to PsA screening, and the most appropriate outcome measure for capturing PsA symptoms. The overwhelming majority of expert stakeholders agreed that all psoriasis trial subjects should be screened for PsA with subsequent measurement of PsA symptoms with use of the PsAID9 (with the RAPID3 as an acceptable alternative measure).

The Genetics of Psoriasis and Psoriatic Arthritis.

O'Rielly DD, Jani M, Rahman P, Elder JT. J Rheumatol Suppl. 2019 Jun;95:46-50.

Psoriatic arthritis (PsA) is an inflammatory arthritis that manifests in 20-30% of patients diagnosed with psoriasis. Epidemiologic studies suggest a substantial genetic contribution to PsA. There is a strong need for genome-wide association studies on patients with PsA, including PsA-weighted or specific variants. Genomics and serological factors may also predict treatment response in tumor necrosis factor inhibitors (TNFi) in PsA, and genetics may play a role in treatment response to TNFi. Collaborations through the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are essential to increase study population size, which will enhance the ability to detect the genetic variants that create a predisposition to psoriatic disease and to predict response to biological therapy.

Treating Psoriatic Arthritis to Target: Defining Psoriatic Arthritis Disease Activity Score (PASDAS) That Reflects State Of Minimal Disease Activity (MDA).

Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. J Rheumatol. 2019 Jun 15.

PsA Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis. The study aimed to validate a cutoff value of PASDAS that defines minimal disease activity state, as well as validate previously defined PASDAS cutoffs for low and high disease activity.

Evaluating current definitions of low disease activity in psoriatic arthritis using ultrasound.

Bosch P, Husic R, Ficjan A, et al. Rheumatology (Oxford). 2019 Jun 14.

The aim of the study was to evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire.

Tillett W, Lin CY, Zbrozek A, Sprabery AT, Birt J.  Rheumatol Ther. 2019 Jun 1.

The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). The objective of the study was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA.

Measuring Psoriatic Arthritis Symptoms, A Core Domain in Psoriasis Clinical Trials.

Perez-Chada LM, Gottlieb AB, Cohen J, et al. J Am Acad Dermatol. 2019 Jun 1.

The International Dermatology Outcome Measures (IDEOM) established a set of core domains to be measured in all psoriasis trials. This set indicates that symptoms of psoriatic arthritis (PsA) should be measured in all psoriasis studies. The objective of the study was to identify the approach to PsA screening, and the most appropriate outcome measure for capturing PsA symptoms. The overwhelming majority of expert stakeholders agreed that all psoriasis trial subjects should be screened for PsA with subsequent measurement of PsA symptoms with use of the PsAID9 (with the RAPID3 as an acceptable alternative measure).

The Genetics of Psoriasis and Psoriatic Arthritis.

O'Rielly DD, Jani M, Rahman P, Elder JT. J Rheumatol Suppl. 2019 Jun;95:46-50.

Psoriatic arthritis (PsA) is an inflammatory arthritis that manifests in 20-30% of patients diagnosed with psoriasis. Epidemiologic studies suggest a substantial genetic contribution to PsA. There is a strong need for genome-wide association studies on patients with PsA, including PsA-weighted or specific variants. Genomics and serological factors may also predict treatment response in tumor necrosis factor inhibitors (TNFi) in PsA, and genetics may play a role in treatment response to TNFi. Collaborations through the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are essential to increase study population size, which will enhance the ability to detect the genetic variants that create a predisposition to psoriatic disease and to predict response to biological therapy.

Treating Psoriatic Arthritis to Target: Defining Psoriatic Arthritis Disease Activity Score (PASDAS) That Reflects State Of Minimal Disease Activity (MDA).

Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. J Rheumatol. 2019 Jun 15.

PsA Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis. The study aimed to validate a cutoff value of PASDAS that defines minimal disease activity state, as well as validate previously defined PASDAS cutoffs for low and high disease activity.

Evaluating current definitions of low disease activity in psoriatic arthritis using ultrasound.

Bosch P, Husic R, Ficjan A, et al. Rheumatology (Oxford). 2019 Jun 14.

The aim of the study was to evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire.

Tillett W, Lin CY, Zbrozek A, Sprabery AT, Birt J.  Rheumatol Ther. 2019 Jun 1.

The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). The objective of the study was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA.

Measuring Psoriatic Arthritis Symptoms, A Core Domain in Psoriasis Clinical Trials.

Perez-Chada LM, Gottlieb AB, Cohen J, et al. J Am Acad Dermatol. 2019 Jun 1.

The International Dermatology Outcome Measures (IDEOM) established a set of core domains to be measured in all psoriasis trials. This set indicates that symptoms of psoriatic arthritis (PsA) should be measured in all psoriasis studies. The objective of the study was to identify the approach to PsA screening, and the most appropriate outcome measure for capturing PsA symptoms. The overwhelming majority of expert stakeholders agreed that all psoriasis trial subjects should be screened for PsA with subsequent measurement of PsA symptoms with use of the PsAID9 (with the RAPID3 as an acceptable alternative measure).

The Genetics of Psoriasis and Psoriatic Arthritis.

O'Rielly DD, Jani M, Rahman P, Elder JT. J Rheumatol Suppl. 2019 Jun;95:46-50.

Psoriatic arthritis (PsA) is an inflammatory arthritis that manifests in 20-30% of patients diagnosed with psoriasis. Epidemiologic studies suggest a substantial genetic contribution to PsA. There is a strong need for genome-wide association studies on patients with PsA, including PsA-weighted or specific variants. Genomics and serological factors may also predict treatment response in tumor necrosis factor inhibitors (TNFi) in PsA, and genetics may play a role in treatment response to TNFi. Collaborations through the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are essential to increase study population size, which will enhance the ability to detect the genetic variants that create a predisposition to psoriatic disease and to predict response to biological therapy.

MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.

Mitchel L. Zoler/MDedge News

The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.

The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.

The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.

Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.

The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.


During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.

The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).

This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.

All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.

[email protected]

SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.

MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.

Mitchel L. Zoler/MDedge News

The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.

The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.

The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.

Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.

The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.


During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.

The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).

This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.

All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.

[email protected]

SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.

MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.

Mitchel L. Zoler/MDedge News

The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.

The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.

The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.

Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.

The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.


During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.

The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).

This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.

All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.

[email protected]

SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.

Key clinical point: Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS.

Major finding: The rate of brain atrophy for untreated patients with primary progressive MS was about twice as fast as that for those with secondary progressive MS.

Study details: The randomized, placebo-controlled phase 2 SPRINT-MS trial of ibudilast included 134 patients with primary progressive MS and 121 with secondary progressive MS.

Disclosures: The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

Citation: Goodman A et al. AAN 2019, Abstract S12.007.

Key clinical point: Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS.

Major finding: The rate of brain atrophy for untreated patients with primary progressive MS was about twice as fast as that for those with secondary progressive MS.

Study details: The randomized, placebo-controlled phase 2 SPRINT-MS trial of ibudilast included 134 patients with primary progressive MS and 121 with secondary progressive MS.

Disclosures: The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

Citation: Goodman A et al. AAN 2019, Abstract S12.007.

Key clinical point: Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS.

Major finding: The rate of brain atrophy for untreated patients with primary progressive MS was about twice as fast as that for those with secondary progressive MS.

Study details: The randomized, placebo-controlled phase 2 SPRINT-MS trial of ibudilast included 134 patients with primary progressive MS and 121 with secondary progressive MS.

Disclosures: The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

Citation: Goodman A et al. AAN 2019, Abstract S12.007.

Simply adding a default order to the electronic health record that automatically opts patients out of commonly used but unnecessary radiation oncology procedures can dramatically curtail their use, suggests a stepped-wedge, cluster-randomized, controlled trial.

Daily x-ray or CT imaging is often used to better reproducibly position patients during curative radiotherapy, but guidelines consider it unnecessary during palliative radiotherapy because of limited clinical benefit, according to the investigators, led by Sonam Sharma, MD, of the Icahn School of Medicine at Mount Sinai, New York, and the Abramson Cancer Center at the University of Pennsylvania, Philadelphia. “Unnecessary imaging can increase treatment time and expense for patients in distress,” they noted.

The investigators conducted a 2-year trial among 21 radiation oncologists from five practices (one university, four community) in which they added to the EHR a default order that specified no daily imaging during palliative radiation therapy. (Radiation oncologists could select another imaging frequency if they preferred.) The default order was first rolled out in the university practice and subsequently in the community practices.

Study analyses were based on 1,019 adult patients with bone, soft tissue, or brain metastases who received 1,188 courses of palliative three-dimensional conformal radiotherapy during the trial.

Results reported in a JAMA Oncology research letter showed that the proportion of patients receiving daily imaging during their palliative radiotherapy (imaging during 80% or more of treatments) fell from 68.2% during the combined preintervention periods to 32.4% during the combined intervention periods.

After potential confounders were taken into account, implementation of the default order in the EHR was associated with a more than halving of the odds of daily imaging during palliative radiotherapy (adjusted odds ratio, 0.37; P = .003), with an adjusted percentage point reduction of –18.8.

Findings were similar in the university practice alone (aOR, 0.33; P = .01; –22.3 percentage points) and in the community practices alone (aOR, 0.45; P = .02; –27.5 percentage points).

“In a network of five radiation oncology practices, introducing a default order in the EHR reduced unnecessary daily imaging during palliative radiotherapy,” Dr. Sharma and colleagues concluded. “Our findings suggest that simple nudges, such as setting default orders, can meaningfully reduce unnecessary care.”

Dr. Sharma reported that she had no relevant conflicts of interest. The study was funded in part by the National Cancer Institute and the University of Pennsylvania Health System through the Penn Medicine Nudge Unit and the department of radiation oncology.

SOURCE: Sharma S et al. JAMA Oncol. 2019 Jun 27. doi: 10.1001/jamaoncol.2019.1432.

Simply adding a default order to the electronic health record that automatically opts patients out of commonly used but unnecessary radiation oncology procedures can dramatically curtail their use, suggests a stepped-wedge, cluster-randomized, controlled trial.

Daily x-ray or CT imaging is often used to better reproducibly position patients during curative radiotherapy, but guidelines consider it unnecessary during palliative radiotherapy because of limited clinical benefit, according to the investigators, led by Sonam Sharma, MD, of the Icahn School of Medicine at Mount Sinai, New York, and the Abramson Cancer Center at the University of Pennsylvania, Philadelphia. “Unnecessary imaging can increase treatment time and expense for patients in distress,” they noted.

The investigators conducted a 2-year trial among 21 radiation oncologists from five practices (one university, four community) in which they added to the EHR a default order that specified no daily imaging during palliative radiation therapy. (Radiation oncologists could select another imaging frequency if they preferred.) The default order was first rolled out in the university practice and subsequently in the community practices.

Study analyses were based on 1,019 adult patients with bone, soft tissue, or brain metastases who received 1,188 courses of palliative three-dimensional conformal radiotherapy during the trial.

Results reported in a JAMA Oncology research letter showed that the proportion of patients receiving daily imaging during their palliative radiotherapy (imaging during 80% or more of treatments) fell from 68.2% during the combined preintervention periods to 32.4% during the combined intervention periods.

After potential confounders were taken into account, implementation of the default order in the EHR was associated with a more than halving of the odds of daily imaging during palliative radiotherapy (adjusted odds ratio, 0.37; P = .003), with an adjusted percentage point reduction of –18.8.

Findings were similar in the university practice alone (aOR, 0.33; P = .01; –22.3 percentage points) and in the community practices alone (aOR, 0.45; P = .02; –27.5 percentage points).

“In a network of five radiation oncology practices, introducing a default order in the EHR reduced unnecessary daily imaging during palliative radiotherapy,” Dr. Sharma and colleagues concluded. “Our findings suggest that simple nudges, such as setting default orders, can meaningfully reduce unnecessary care.”

Dr. Sharma reported that she had no relevant conflicts of interest. The study was funded in part by the National Cancer Institute and the University of Pennsylvania Health System through the Penn Medicine Nudge Unit and the department of radiation oncology.

SOURCE: Sharma S et al. JAMA Oncol. 2019 Jun 27. doi: 10.1001/jamaoncol.2019.1432.

Simply adding a default order to the electronic health record that automatically opts patients out of commonly used but unnecessary radiation oncology procedures can dramatically curtail their use, suggests a stepped-wedge, cluster-randomized, controlled trial.

Daily x-ray or CT imaging is often used to better reproducibly position patients during curative radiotherapy, but guidelines consider it unnecessary during palliative radiotherapy because of limited clinical benefit, according to the investigators, led by Sonam Sharma, MD, of the Icahn School of Medicine at Mount Sinai, New York, and the Abramson Cancer Center at the University of Pennsylvania, Philadelphia. “Unnecessary imaging can increase treatment time and expense for patients in distress,” they noted.

The investigators conducted a 2-year trial among 21 radiation oncologists from five practices (one university, four community) in which they added to the EHR a default order that specified no daily imaging during palliative radiation therapy. (Radiation oncologists could select another imaging frequency if they preferred.) The default order was first rolled out in the university practice and subsequently in the community practices.

Study analyses were based on 1,019 adult patients with bone, soft tissue, or brain metastases who received 1,188 courses of palliative three-dimensional conformal radiotherapy during the trial.

Results reported in a JAMA Oncology research letter showed that the proportion of patients receiving daily imaging during their palliative radiotherapy (imaging during 80% or more of treatments) fell from 68.2% during the combined preintervention periods to 32.4% during the combined intervention periods.

After potential confounders were taken into account, implementation of the default order in the EHR was associated with a more than halving of the odds of daily imaging during palliative radiotherapy (adjusted odds ratio, 0.37; P = .003), with an adjusted percentage point reduction of –18.8.

Findings were similar in the university practice alone (aOR, 0.33; P = .01; –22.3 percentage points) and in the community practices alone (aOR, 0.45; P = .02; –27.5 percentage points).

“In a network of five radiation oncology practices, introducing a default order in the EHR reduced unnecessary daily imaging during palliative radiotherapy,” Dr. Sharma and colleagues concluded. “Our findings suggest that simple nudges, such as setting default orders, can meaningfully reduce unnecessary care.”

Dr. Sharma reported that she had no relevant conflicts of interest. The study was funded in part by the National Cancer Institute and the University of Pennsylvania Health System through the Penn Medicine Nudge Unit and the department of radiation oncology.

SOURCE: Sharma S et al. JAMA Oncol. 2019 Jun 27. doi: 10.1001/jamaoncol.2019.1432.

Key clinical point: Treatment with eculizumab substantially reduced risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica spectrum disorder.

Major finding: Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant (P less than .0001) effect in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse.

Study details: A phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT) including 143 adult patients.

Disclosures: The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

Citation: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

Key clinical point: Treatment with eculizumab substantially reduced risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica spectrum disorder.

Major finding: Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant (P less than .0001) effect in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse.

Study details: A phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT) including 143 adult patients.

Disclosures: The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

Citation: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

Key clinical point: Treatment with eculizumab substantially reduced risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica spectrum disorder.

Major finding: Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant (P less than .0001) effect in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse.

Study details: A phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT) including 143 adult patients.

Disclosures: The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

Citation: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

Key clinical point: Physicians face considerable uncertainty regarding how to treat pediatric patients with MS.

Major finding: About 65% of pediatric patients with multiple sclerosis do not receive disease-modifying therapy within 1 year of diagnosis.

Study details: Retrospective, observational study of claims data from 288 patients with pediatric MS.

Disclosures: Novartis funded the study, and Dr. Deshpande, who presented the findings, and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

Citation: Greenberg B et al. CMSC 2019, Abstract DXM02.

Key clinical point: Physicians face considerable uncertainty regarding how to treat pediatric patients with MS.

Major finding: About 65% of pediatric patients with multiple sclerosis do not receive disease-modifying therapy within 1 year of diagnosis.

Study details: Retrospective, observational study of claims data from 288 patients with pediatric MS.

Disclosures: Novartis funded the study, and Dr. Deshpande, who presented the findings, and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

Citation: Greenberg B et al. CMSC 2019, Abstract DXM02.

Key clinical point: Physicians face considerable uncertainty regarding how to treat pediatric patients with MS.

Major finding: About 65% of pediatric patients with multiple sclerosis do not receive disease-modifying therapy within 1 year of diagnosis.

Study details: Retrospective, observational study of claims data from 288 patients with pediatric MS.

Disclosures: Novartis funded the study, and Dr. Deshpande, who presented the findings, and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

Citation: Greenberg B et al. CMSC 2019, Abstract DXM02.

The diagnosis

von Hippel-Lindau disease

The diagnosis is von Hippel-Lindau disease (VHL). Subsequent brain and renal magnetic resonance imaging showed features suggestive of a 5-mm right cerebellar hemangioblastoma and right renal cell carcinoma (RCC), respectively. Fundoscopy showed bilateral small retinal angiomas. Plasma and 24-hour urinary metenephrine levels were normal. Genetic testing confirmed a germline VHL mutation.

VHL is a rare autosomal-dominant hereditary multicancer condition characterized by germline mutations of the VHL tumor suppressor gene, with an incidence of 1 in 36,000 live births. The commonest associated tumors are retinal and central nervous system hemangioblastomas, RCC, pheochromocytoma, pancreatic islet cell tumors, and endolymphatic sac tumors.¹ Cystic lesions may also be seen in other viscera such as the liver and ovaries. Clinical diagnostic criteria require the presence of any of these tumors in a patient with a positive family history, or alternatively, at least 2 retinal or cerebellar hemangioblastomas, or 1 hemangioblastoma plus 1 visceral tumor.²

Pancreatic involvement occurs in 65%–77% of patients with VHL, and may be the sole manifestation in 7.6%. Findings include multiple true cysts (91%), microcystic serous cystadenomas (12%), solid pancreatic neuroendocrine tumors (5%–10%), or a combination (11.5%). Most lesions are asymptomatic, but may present with vague symptoms of epigastric pain, diarrhea, dyspepsia, obstructive jaundice, or endocrine and/or exocrine pancreatic insufficiency. Surgery is required for symptomatic cysts or large pancreatic neuroendocrine tumors. The main causes of death are RCC and central nervous system hemangioblastomas.³ Our patient underwent laser therapy for her retinal angiomas, and is currently undergoing close regular surveillance. Clinicians should have a high index of suspicion for diagnosing VHL in patients with multiple pancreatic cysts. Because EUS is now widely used for the evaluation of pancreatic cysts, gastroenterologists may be first in making the diagnosis, as in this patient.
 

References

1. Lonser R.R., Glenn G.M., Walther M. et al. von Hippel-Lindau disease. Lancet. 2003;361:2059-67.

2. Melmon K., Rosen S. Lindau’s disease. Am J Med. 1964;36:595-617

3. Hammel P.R., Vilgrain V., Terris B. et al. Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d’Etude de la Maladie de von Hippel-Lindau. Gastroenterology. 2000;119:1087-95.
 

[email protected]

The diagnosis

von Hippel-Lindau disease

The diagnosis is von Hippel-Lindau disease (VHL). Subsequent brain and renal magnetic resonance imaging showed features suggestive of a 5-mm right cerebellar hemangioblastoma and right renal cell carcinoma (RCC), respectively. Fundoscopy showed bilateral small retinal angiomas. Plasma and 24-hour urinary metenephrine levels were normal. Genetic testing confirmed a germline VHL mutation.

VHL is a rare autosomal-dominant hereditary multicancer condition characterized by germline mutations of the VHL tumor suppressor gene, with an incidence of 1 in 36,000 live births. The commonest associated tumors are retinal and central nervous system hemangioblastomas, RCC, pheochromocytoma, pancreatic islet cell tumors, and endolymphatic sac tumors.¹ Cystic lesions may also be seen in other viscera such as the liver and ovaries. Clinical diagnostic criteria require the presence of any of these tumors in a patient with a positive family history, or alternatively, at least 2 retinal or cerebellar hemangioblastomas, or 1 hemangioblastoma plus 1 visceral tumor.²

Pancreatic involvement occurs in 65%–77% of patients with VHL, and may be the sole manifestation in 7.6%. Findings include multiple true cysts (91%), microcystic serous cystadenomas (12%), solid pancreatic neuroendocrine tumors (5%–10%), or a combination (11.5%). Most lesions are asymptomatic, but may present with vague symptoms of epigastric pain, diarrhea, dyspepsia, obstructive jaundice, or endocrine and/or exocrine pancreatic insufficiency. Surgery is required for symptomatic cysts or large pancreatic neuroendocrine tumors. The main causes of death are RCC and central nervous system hemangioblastomas.³ Our patient underwent laser therapy for her retinal angiomas, and is currently undergoing close regular surveillance. Clinicians should have a high index of suspicion for diagnosing VHL in patients with multiple pancreatic cysts. Because EUS is now widely used for the evaluation of pancreatic cysts, gastroenterologists may be first in making the diagnosis, as in this patient.
 

References

1. Lonser R.R., Glenn G.M., Walther M. et al. von Hippel-Lindau disease. Lancet. 2003;361:2059-67.

2. Melmon K., Rosen S. Lindau’s disease. Am J Med. 1964;36:595-617

3. Hammel P.R., Vilgrain V., Terris B. et al. Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d’Etude de la Maladie de von Hippel-Lindau. Gastroenterology. 2000;119:1087-95.
 

[email protected]

The diagnosis

von Hippel-Lindau disease

The diagnosis is von Hippel-Lindau disease (VHL). Subsequent brain and renal magnetic resonance imaging showed features suggestive of a 5-mm right cerebellar hemangioblastoma and right renal cell carcinoma (RCC), respectively. Fundoscopy showed bilateral small retinal angiomas. Plasma and 24-hour urinary metenephrine levels were normal. Genetic testing confirmed a germline VHL mutation.

VHL is a rare autosomal-dominant hereditary multicancer condition characterized by germline mutations of the VHL tumor suppressor gene, with an incidence of 1 in 36,000 live births. The commonest associated tumors are retinal and central nervous system hemangioblastomas, RCC, pheochromocytoma, pancreatic islet cell tumors, and endolymphatic sac tumors.¹ Cystic lesions may also be seen in other viscera such as the liver and ovaries. Clinical diagnostic criteria require the presence of any of these tumors in a patient with a positive family history, or alternatively, at least 2 retinal or cerebellar hemangioblastomas, or 1 hemangioblastoma plus 1 visceral tumor.²

Pancreatic involvement occurs in 65%–77% of patients with VHL, and may be the sole manifestation in 7.6%. Findings include multiple true cysts (91%), microcystic serous cystadenomas (12%), solid pancreatic neuroendocrine tumors (5%–10%), or a combination (11.5%). Most lesions are asymptomatic, but may present with vague symptoms of epigastric pain, diarrhea, dyspepsia, obstructive jaundice, or endocrine and/or exocrine pancreatic insufficiency. Surgery is required for symptomatic cysts or large pancreatic neuroendocrine tumors. The main causes of death are RCC and central nervous system hemangioblastomas.³ Our patient underwent laser therapy for her retinal angiomas, and is currently undergoing close regular surveillance. Clinicians should have a high index of suspicion for diagnosing VHL in patients with multiple pancreatic cysts. Because EUS is now widely used for the evaluation of pancreatic cysts, gastroenterologists may be first in making the diagnosis, as in this patient.
 

References

1. Lonser R.R., Glenn G.M., Walther M. et al. von Hippel-Lindau disease. Lancet. 2003;361:2059-67.

2. Melmon K., Rosen S. Lindau’s disease. Am J Med. 1964;36:595-617

3. Hammel P.R., Vilgrain V., Terris B. et al. Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d’Etude de la Maladie de von Hippel-Lindau. Gastroenterology. 2000;119:1087-95.
 

[email protected]