Pediatrics

WASHINGTON – A novel, standardized preparation of topical cantharidin effectively cleared lesions in patients with molluscum contagiosum, compared with placebo, according to the results of two trials presented at the annual meeting of the American Academy of Dermatology.

VP-102, a drug-device combination, was well tolerated and was not associated with serious adverse events.

No Food and Drug Administration–approved treatment is available for treating molluscum contagiosum, which is routinely treated with cantharidin, a naturally occurring vesicant.

VP-102 is a novel formulation of 0.7% cantharidin solution, provided in a single-use applicator, to provide consistent delivery and long-term drug stability.

To test the efficacy and safety of VP-102, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and his associates conducted the CAMP-1 (Cantharidin Application in Molluscum Patients) and CAMP-2 phase 3 studies, which had similar designs. The studies enrolled patients with molluscum contagiosum aged 2 years and older who had not received any treatment in the 2 weeks before enrollment. Patients were randomized to VP-102 or vehicle for 12 weeks. Treatment was administered topically to each lesion every 3 weeks for a maximum of four applications, and washed off with soap and warm water 24 hours after application.

The trials’ primary endpoint was the percentage of patients with complete clearance of their lesions. Secondary endpoints were the percentage of patients with complete clearance at 3, 6, and 9 weeks, and decrease in lesions over time. The researchers also assessed safety and tolerability.


In the two studies, 528 patients aged 2-60 years (mean age, approximately 7 years) were randomized to treatment or vehicle. About 30% of participants had prior treatment. The baseline lesion count ranged from 1 to 184.

At day 84, the proportion of patients in the VP-102 arm who achieved complete clearance of lesions was 46% in CAMP-1 and 54% in CAMP-2, compared with 18% and 13%, respectively, among controls (P less than .0001). By day 84, among treated patients, the lesion count had decreased by a mean of 69% in CAMP-1 and 83% in CAMP-2, compared with 20% and 19%, respectively, among controls. Results among controls were “probably consistent with natural history,” Dr. Eichenfield observed.

The researchers observed a high incidence of treatment-emergent adverse events among patients receiving VP-102. “Any crust or vesiculation was considered to be a treatment-emergent adverse event,” Dr. Eichenfield said. Most adverse events were mild, although five patients discontinued the studies because of treatment-emergent adverse events. Vesiculation was a common adverse event in the VP-102 group; pruritus and application-site pain were reported as well.

Verrica Pharmaceuticals developed VP-102 and funded the study. Dr. Eichenfield reported receiving no funding from the company; several other investigators are employees of Verrica, which plans to submit for FDA approval in the second half of 2019.

egreb@mdedge.com

SOURCE: Eichenfield L et al. AAD 19, Abstract 11251.

WASHINGTON – A novel, standardized preparation of topical cantharidin effectively cleared lesions in patients with molluscum contagiosum, compared with placebo, according to the results of two trials presented at the annual meeting of the American Academy of Dermatology.

VP-102, a drug-device combination, was well tolerated and was not associated with serious adverse events.

No Food and Drug Administration–approved treatment is available for treating molluscum contagiosum, which is routinely treated with cantharidin, a naturally occurring vesicant.

VP-102 is a novel formulation of 0.7% cantharidin solution, provided in a single-use applicator, to provide consistent delivery and long-term drug stability.

To test the efficacy and safety of VP-102, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and his associates conducted the CAMP-1 (Cantharidin Application in Molluscum Patients) and CAMP-2 phase 3 studies, which had similar designs. The studies enrolled patients with molluscum contagiosum aged 2 years and older who had not received any treatment in the 2 weeks before enrollment. Patients were randomized to VP-102 or vehicle for 12 weeks. Treatment was administered topically to each lesion every 3 weeks for a maximum of four applications, and washed off with soap and warm water 24 hours after application.

The trials’ primary endpoint was the percentage of patients with complete clearance of their lesions. Secondary endpoints were the percentage of patients with complete clearance at 3, 6, and 9 weeks, and decrease in lesions over time. The researchers also assessed safety and tolerability.


In the two studies, 528 patients aged 2-60 years (mean age, approximately 7 years) were randomized to treatment or vehicle. About 30% of participants had prior treatment. The baseline lesion count ranged from 1 to 184.

At day 84, the proportion of patients in the VP-102 arm who achieved complete clearance of lesions was 46% in CAMP-1 and 54% in CAMP-2, compared with 18% and 13%, respectively, among controls (P less than .0001). By day 84, among treated patients, the lesion count had decreased by a mean of 69% in CAMP-1 and 83% in CAMP-2, compared with 20% and 19%, respectively, among controls. Results among controls were “probably consistent with natural history,” Dr. Eichenfield observed.

The researchers observed a high incidence of treatment-emergent adverse events among patients receiving VP-102. “Any crust or vesiculation was considered to be a treatment-emergent adverse event,” Dr. Eichenfield said. Most adverse events were mild, although five patients discontinued the studies because of treatment-emergent adverse events. Vesiculation was a common adverse event in the VP-102 group; pruritus and application-site pain were reported as well.

Verrica Pharmaceuticals developed VP-102 and funded the study. Dr. Eichenfield reported receiving no funding from the company; several other investigators are employees of Verrica, which plans to submit for FDA approval in the second half of 2019.

egreb@mdedge.com

SOURCE: Eichenfield L et al. AAD 19, Abstract 11251.

WASHINGTON – A novel, standardized preparation of topical cantharidin effectively cleared lesions in patients with molluscum contagiosum, compared with placebo, according to the results of two trials presented at the annual meeting of the American Academy of Dermatology.

VP-102, a drug-device combination, was well tolerated and was not associated with serious adverse events.

No Food and Drug Administration–approved treatment is available for treating molluscum contagiosum, which is routinely treated with cantharidin, a naturally occurring vesicant.

VP-102 is a novel formulation of 0.7% cantharidin solution, provided in a single-use applicator, to provide consistent delivery and long-term drug stability.

To test the efficacy and safety of VP-102, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and his associates conducted the CAMP-1 (Cantharidin Application in Molluscum Patients) and CAMP-2 phase 3 studies, which had similar designs. The studies enrolled patients with molluscum contagiosum aged 2 years and older who had not received any treatment in the 2 weeks before enrollment. Patients were randomized to VP-102 or vehicle for 12 weeks. Treatment was administered topically to each lesion every 3 weeks for a maximum of four applications, and washed off with soap and warm water 24 hours after application.

The trials’ primary endpoint was the percentage of patients with complete clearance of their lesions. Secondary endpoints were the percentage of patients with complete clearance at 3, 6, and 9 weeks, and decrease in lesions over time. The researchers also assessed safety and tolerability.


In the two studies, 528 patients aged 2-60 years (mean age, approximately 7 years) were randomized to treatment or vehicle. About 30% of participants had prior treatment. The baseline lesion count ranged from 1 to 184.

At day 84, the proportion of patients in the VP-102 arm who achieved complete clearance of lesions was 46% in CAMP-1 and 54% in CAMP-2, compared with 18% and 13%, respectively, among controls (P less than .0001). By day 84, among treated patients, the lesion count had decreased by a mean of 69% in CAMP-1 and 83% in CAMP-2, compared with 20% and 19%, respectively, among controls. Results among controls were “probably consistent with natural history,” Dr. Eichenfield observed.

The researchers observed a high incidence of treatment-emergent adverse events among patients receiving VP-102. “Any crust or vesiculation was considered to be a treatment-emergent adverse event,” Dr. Eichenfield said. Most adverse events were mild, although five patients discontinued the studies because of treatment-emergent adverse events. Vesiculation was a common adverse event in the VP-102 group; pruritus and application-site pain were reported as well.

Verrica Pharmaceuticals developed VP-102 and funded the study. Dr. Eichenfield reported receiving no funding from the company; several other investigators are employees of Verrica, which plans to submit for FDA approval in the second half of 2019.

egreb@mdedge.com

SOURCE: Eichenfield L et al. AAD 19, Abstract 11251.

Paul is 13-year-old male in seventh grade with a history of inattentive ADHD and a positive family history of depression and anxiety in his mother. He always has had a few friends, but recently they have not wanted to hang out with him; he feels like people are ignoring him. For the past 2 months, Paul’s mood has gotten very low. He feels sad and also bored because he is not enjoying anything anymore. He feels as though he is “a loser,” and as though nothing will ever get better. His grades have dropped. He has thoughts of wishing he were dead, although he has no specific plan and says he wouldn’t do it because he doesn’t want to hurt his parents. He is looking at his phone at night and gets to bed late, then doesn’t want to get up in the morning. He sleeps until noon on weekends. Appetite is increased. He doesn’t have energy to do things on the weekends.

Discussion

Paul clearly meets diagnostic criteria for depression. He feels sad and has lost pleasure in activities he used to enjoy. He has negative, hopeless thoughts, and vague thoughts of death although no specific plans. He has vegetative signs of depression with increased appetite and sleep; he likely has worse concentration than usual, given that his grades have dropped. Energy is low.

Both medications and specific types of psychotherapy are effective for treating depression in adolescents.

Meta-analyses have demonstrated the efficacy of SSRIs (fluoxetine, sertraline, citalopram, escitalopram) as well as venlafaxine, mirtazapine, and nefazodone with small to very small effect sizes.¹ A large placebo effect is seen in many of these studies, correlating with the number of study sites – a feature of many industry-sponsored studies.

John Walkup, MD, a leading researcher on both medication and psychotherapeutic interventions in children’s mood disorders, has pointed out that the quality of industry-sponsored studies (vs. National Institute of Mental Health–sponsored studies) is likely lower, with more pressure to get in large numbers of patients in a short period of time, less trained investigators leading to less clear-cut diagnoses, and other sources of bias.² This raises the question of whether we should weight NIMH-sponsored studies more heavily in meta-analyses.

A second factor to consider is the risk of harm, and a significant issue here is the question of whether suicidal ideation is increased among those patients taking SSRIs. Meta-analyses from the late 2000s, which balanced the number needed to treat vs. the number needed to harm, judged that for children under age 13 years, fluoxetine was the only antidepressant that was worth the cost-benefit ratio. However, in the past several years there has been a major improvement in the assessment of suicidal ideation in the form of the Columbia Suicide Severity Rating Scale, a standardized method of assessing the presence and significance of suicidal thoughts and behaviors. Studies that have used this assessment have found no significant increase in suicidal ideation with SSRIs vs. placebo.

The takeaway here is that the SSRIs can work, with fluoxetine, sertraline, and escitalopram leading the evidence, and that with refinements of the assessment they do not appear to increase the risk of suicidal ideation.³ Of course, it remains important to discuss this issue with families.

Flamingo_Photography/Getty Images

Psychotherapy is the other major treatment for depression. Cognitive behavioral therapy (CBT) and Interpersonal therapy (IPT) for adolescents show effectiveness in teens.⁴ Recent meta-analyses have gotten stronger through the use of stringent quality criteria and the inclusion of negative studies; these therapies continue to be considered well established. It is worthwhile to talk to therapists in your community to understand what type of treatment they offer. If you are hiring therapists to be embedded in your practice, look for people who have been trained in CBT or IPT. It is particularly helpful to know whether therapists have seen patients using CBT or IPT while getting supervision in these modalities.

CBT and IPT are different. CBT puts an emphasis on the thought-feeling-behavior triangle while IPT focuses more on relationships. Someone who has tried one and has not benefited nevertheless may benefit from the other.

Working with your patients to choose what type of psychotherapy modality for depression they would like is particularly effective.

Finally, be aware of how the environment may be affecting your patient. School issues related to peers, learning style or disabilities, and organization have a major effect on teens. In this case, Paul is looking at his phone nightly, which may be affecting both his sleep and self-esteem. Family issues continue to play a key role.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

References

1. JAMA. 2007 Apr 18;297(15):1683-96.

2. Am J Psychiatry. 2017 May 1;174(5):430-7.

3. J Child Adolesc Psychopharmacol. 2018. doi: 10.1089/cap.2017.0174.

4. J Clin Child Adolesc Psychol. 2017 Jan-Feb;46(1):11-43.

Paul is 13-year-old male in seventh grade with a history of inattentive ADHD and a positive family history of depression and anxiety in his mother. He always has had a few friends, but recently they have not wanted to hang out with him; he feels like people are ignoring him. For the past 2 months, Paul’s mood has gotten very low. He feels sad and also bored because he is not enjoying anything anymore. He feels as though he is “a loser,” and as though nothing will ever get better. His grades have dropped. He has thoughts of wishing he were dead, although he has no specific plan and says he wouldn’t do it because he doesn’t want to hurt his parents. He is looking at his phone at night and gets to bed late, then doesn’t want to get up in the morning. He sleeps until noon on weekends. Appetite is increased. He doesn’t have energy to do things on the weekends.

Discussion

Paul clearly meets diagnostic criteria for depression. He feels sad and has lost pleasure in activities he used to enjoy. He has negative, hopeless thoughts, and vague thoughts of death although no specific plans. He has vegetative signs of depression with increased appetite and sleep; he likely has worse concentration than usual, given that his grades have dropped. Energy is low.

Both medications and specific types of psychotherapy are effective for treating depression in adolescents.

Meta-analyses have demonstrated the efficacy of SSRIs (fluoxetine, sertraline, citalopram, escitalopram) as well as venlafaxine, mirtazapine, and nefazodone with small to very small effect sizes.¹ A large placebo effect is seen in many of these studies, correlating with the number of study sites – a feature of many industry-sponsored studies.

John Walkup, MD, a leading researcher on both medication and psychotherapeutic interventions in children’s mood disorders, has pointed out that the quality of industry-sponsored studies (vs. National Institute of Mental Health–sponsored studies) is likely lower, with more pressure to get in large numbers of patients in a short period of time, less trained investigators leading to less clear-cut diagnoses, and other sources of bias.² This raises the question of whether we should weight NIMH-sponsored studies more heavily in meta-analyses.

A second factor to consider is the risk of harm, and a significant issue here is the question of whether suicidal ideation is increased among those patients taking SSRIs. Meta-analyses from the late 2000s, which balanced the number needed to treat vs. the number needed to harm, judged that for children under age 13 years, fluoxetine was the only antidepressant that was worth the cost-benefit ratio. However, in the past several years there has been a major improvement in the assessment of suicidal ideation in the form of the Columbia Suicide Severity Rating Scale, a standardized method of assessing the presence and significance of suicidal thoughts and behaviors. Studies that have used this assessment have found no significant increase in suicidal ideation with SSRIs vs. placebo.

The takeaway here is that the SSRIs can work, with fluoxetine, sertraline, and escitalopram leading the evidence, and that with refinements of the assessment they do not appear to increase the risk of suicidal ideation.³ Of course, it remains important to discuss this issue with families.

Flamingo_Photography/Getty Images

Psychotherapy is the other major treatment for depression. Cognitive behavioral therapy (CBT) and Interpersonal therapy (IPT) for adolescents show effectiveness in teens.⁴ Recent meta-analyses have gotten stronger through the use of stringent quality criteria and the inclusion of negative studies; these therapies continue to be considered well established. It is worthwhile to talk to therapists in your community to understand what type of treatment they offer. If you are hiring therapists to be embedded in your practice, look for people who have been trained in CBT or IPT. It is particularly helpful to know whether therapists have seen patients using CBT or IPT while getting supervision in these modalities.

CBT and IPT are different. CBT puts an emphasis on the thought-feeling-behavior triangle while IPT focuses more on relationships. Someone who has tried one and has not benefited nevertheless may benefit from the other.

Working with your patients to choose what type of psychotherapy modality for depression they would like is particularly effective.

Finally, be aware of how the environment may be affecting your patient. School issues related to peers, learning style or disabilities, and organization have a major effect on teens. In this case, Paul is looking at his phone nightly, which may be affecting both his sleep and self-esteem. Family issues continue to play a key role.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

References

1. JAMA. 2007 Apr 18;297(15):1683-96.

2. Am J Psychiatry. 2017 May 1;174(5):430-7.

3. J Child Adolesc Psychopharmacol. 2018. doi: 10.1089/cap.2017.0174.

4. J Clin Child Adolesc Psychol. 2017 Jan-Feb;46(1):11-43.

Paul is 13-year-old male in seventh grade with a history of inattentive ADHD and a positive family history of depression and anxiety in his mother. He always has had a few friends, but recently they have not wanted to hang out with him; he feels like people are ignoring him. For the past 2 months, Paul’s mood has gotten very low. He feels sad and also bored because he is not enjoying anything anymore. He feels as though he is “a loser,” and as though nothing will ever get better. His grades have dropped. He has thoughts of wishing he were dead, although he has no specific plan and says he wouldn’t do it because he doesn’t want to hurt his parents. He is looking at his phone at night and gets to bed late, then doesn’t want to get up in the morning. He sleeps until noon on weekends. Appetite is increased. He doesn’t have energy to do things on the weekends.

Discussion

Paul clearly meets diagnostic criteria for depression. He feels sad and has lost pleasure in activities he used to enjoy. He has negative, hopeless thoughts, and vague thoughts of death although no specific plans. He has vegetative signs of depression with increased appetite and sleep; he likely has worse concentration than usual, given that his grades have dropped. Energy is low.

Both medications and specific types of psychotherapy are effective for treating depression in adolescents.

Meta-analyses have demonstrated the efficacy of SSRIs (fluoxetine, sertraline, citalopram, escitalopram) as well as venlafaxine, mirtazapine, and nefazodone with small to very small effect sizes.¹ A large placebo effect is seen in many of these studies, correlating with the number of study sites – a feature of many industry-sponsored studies.

John Walkup, MD, a leading researcher on both medication and psychotherapeutic interventions in children’s mood disorders, has pointed out that the quality of industry-sponsored studies (vs. National Institute of Mental Health–sponsored studies) is likely lower, with more pressure to get in large numbers of patients in a short period of time, less trained investigators leading to less clear-cut diagnoses, and other sources of bias.² This raises the question of whether we should weight NIMH-sponsored studies more heavily in meta-analyses.

A second factor to consider is the risk of harm, and a significant issue here is the question of whether suicidal ideation is increased among those patients taking SSRIs. Meta-analyses from the late 2000s, which balanced the number needed to treat vs. the number needed to harm, judged that for children under age 13 years, fluoxetine was the only antidepressant that was worth the cost-benefit ratio. However, in the past several years there has been a major improvement in the assessment of suicidal ideation in the form of the Columbia Suicide Severity Rating Scale, a standardized method of assessing the presence and significance of suicidal thoughts and behaviors. Studies that have used this assessment have found no significant increase in suicidal ideation with SSRIs vs. placebo.

The takeaway here is that the SSRIs can work, with fluoxetine, sertraline, and escitalopram leading the evidence, and that with refinements of the assessment they do not appear to increase the risk of suicidal ideation.³ Of course, it remains important to discuss this issue with families.

Flamingo_Photography/Getty Images

Psychotherapy is the other major treatment for depression. Cognitive behavioral therapy (CBT) and Interpersonal therapy (IPT) for adolescents show effectiveness in teens.⁴ Recent meta-analyses have gotten stronger through the use of stringent quality criteria and the inclusion of negative studies; these therapies continue to be considered well established. It is worthwhile to talk to therapists in your community to understand what type of treatment they offer. If you are hiring therapists to be embedded in your practice, look for people who have been trained in CBT or IPT. It is particularly helpful to know whether therapists have seen patients using CBT or IPT while getting supervision in these modalities.

CBT and IPT are different. CBT puts an emphasis on the thought-feeling-behavior triangle while IPT focuses more on relationships. Someone who has tried one and has not benefited nevertheless may benefit from the other.

Working with your patients to choose what type of psychotherapy modality for depression they would like is particularly effective.

Finally, be aware of how the environment may be affecting your patient. School issues related to peers, learning style or disabilities, and organization have a major effect on teens. In this case, Paul is looking at his phone nightly, which may be affecting both his sleep and self-esteem. Family issues continue to play a key role.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

References

1. JAMA. 2007 Apr 18;297(15):1683-96.

2. Am J Psychiatry. 2017 May 1;174(5):430-7.

3. J Child Adolesc Psychopharmacol. 2018. doi: 10.1089/cap.2017.0174.

4. J Clin Child Adolesc Psychol. 2017 Jan-Feb;46(1):11-43.

Reducing fear and anxiety in children undergoing dermatologic procedures is possible with techniques based on cognitive behavioral therapy, according to a report published in Pediatric Dermatology.

fotostorm/Getty Images

For many children, the anticipation of pain and the anxiety about a procedure results in a more painful experience, wrote Andrew M. Armenta of the University of Texas, Galveston, and his colleagues. Preparing children in advance and using cognitive behavioral therapy (CBT) strategies in the moment can help reduce their anxiety.

“CBT is a skill‐based approach that focuses on the present and aims to teach efficient ways of identifying distorted thinking, modifying beliefs, and changing behaviors for a more favorable outcome of real‐life situations,” they wrote.

First, Dr. Armenta and his associates advised, be honest with children about what to expect from a procedure. Evidence does not support phrases such as, “It won’t hurt,” or “It will be over soon,” to reduce anxiety.

Timing the disclosure of a procedure and creating the appropriate setting also can help reduce anxiety. For very young children, short notice of a procedure is often best, with the promise of a small reward or outing afterward. Older children may want some advance notice so they can feel prepared, but their specific concerns should be addressed.

CBT-based techniques include deep breathing and positive coping statements such as “I can do this” for older children, or encouraging them to talk about a family pet or listen to music. Younger children may be distracted with pinwheels, rattles, or songs. “Additionally, in recent years, virtual reality headsets have even proved to be effective distractors, resulting in an overall reduction in both pain and fear,” Dr. Armenta and his associates noted.

Other useful strategies include allowing children to choose their position and location for an injection or procedure when possible. Small children may be able to sit on the lap of an adult, and older children may prefer sitting up to lying down. Avoid physical restraint unless it is absolutely necessary for safety, the researchers emphasized.

Incorporating CBT-based strategies of breathing and distraction with honesty and respectful disclosure of what is being done and why “not only makes practicing pediatric dermatology easier, but also can improve patient adherence to painful procedures,” they said.

No disclosure information was given.

SOURCE: Armenta AM et al. Pediatr Dermatol. 2019. doi: 10.1111/pde.13739.

Reducing fear and anxiety in children undergoing dermatologic procedures is possible with techniques based on cognitive behavioral therapy, according to a report published in Pediatric Dermatology.

fotostorm/Getty Images

For many children, the anticipation of pain and the anxiety about a procedure results in a more painful experience, wrote Andrew M. Armenta of the University of Texas, Galveston, and his colleagues. Preparing children in advance and using cognitive behavioral therapy (CBT) strategies in the moment can help reduce their anxiety.

“CBT is a skill‐based approach that focuses on the present and aims to teach efficient ways of identifying distorted thinking, modifying beliefs, and changing behaviors for a more favorable outcome of real‐life situations,” they wrote.

First, Dr. Armenta and his associates advised, be honest with children about what to expect from a procedure. Evidence does not support phrases such as, “It won’t hurt,” or “It will be over soon,” to reduce anxiety.

Timing the disclosure of a procedure and creating the appropriate setting also can help reduce anxiety. For very young children, short notice of a procedure is often best, with the promise of a small reward or outing afterward. Older children may want some advance notice so they can feel prepared, but their specific concerns should be addressed.

CBT-based techniques include deep breathing and positive coping statements such as “I can do this” for older children, or encouraging them to talk about a family pet or listen to music. Younger children may be distracted with pinwheels, rattles, or songs. “Additionally, in recent years, virtual reality headsets have even proved to be effective distractors, resulting in an overall reduction in both pain and fear,” Dr. Armenta and his associates noted.

Other useful strategies include allowing children to choose their position and location for an injection or procedure when possible. Small children may be able to sit on the lap of an adult, and older children may prefer sitting up to lying down. Avoid physical restraint unless it is absolutely necessary for safety, the researchers emphasized.

Incorporating CBT-based strategies of breathing and distraction with honesty and respectful disclosure of what is being done and why “not only makes practicing pediatric dermatology easier, but also can improve patient adherence to painful procedures,” they said.

No disclosure information was given.

SOURCE: Armenta AM et al. Pediatr Dermatol. 2019. doi: 10.1111/pde.13739.

Reducing fear and anxiety in children undergoing dermatologic procedures is possible with techniques based on cognitive behavioral therapy, according to a report published in Pediatric Dermatology.

fotostorm/Getty Images

For many children, the anticipation of pain and the anxiety about a procedure results in a more painful experience, wrote Andrew M. Armenta of the University of Texas, Galveston, and his colleagues. Preparing children in advance and using cognitive behavioral therapy (CBT) strategies in the moment can help reduce their anxiety.

“CBT is a skill‐based approach that focuses on the present and aims to teach efficient ways of identifying distorted thinking, modifying beliefs, and changing behaviors for a more favorable outcome of real‐life situations,” they wrote.

First, Dr. Armenta and his associates advised, be honest with children about what to expect from a procedure. Evidence does not support phrases such as, “It won’t hurt,” or “It will be over soon,” to reduce anxiety.

Timing the disclosure of a procedure and creating the appropriate setting also can help reduce anxiety. For very young children, short notice of a procedure is often best, with the promise of a small reward or outing afterward. Older children may want some advance notice so they can feel prepared, but their specific concerns should be addressed.

CBT-based techniques include deep breathing and positive coping statements such as “I can do this” for older children, or encouraging them to talk about a family pet or listen to music. Younger children may be distracted with pinwheels, rattles, or songs. “Additionally, in recent years, virtual reality headsets have even proved to be effective distractors, resulting in an overall reduction in both pain and fear,” Dr. Armenta and his associates noted.

Other useful strategies include allowing children to choose their position and location for an injection or procedure when possible. Small children may be able to sit on the lap of an adult, and older children may prefer sitting up to lying down. Avoid physical restraint unless it is absolutely necessary for safety, the researchers emphasized.

Incorporating CBT-based strategies of breathing and distraction with honesty and respectful disclosure of what is being done and why “not only makes practicing pediatric dermatology easier, but also can improve patient adherence to painful procedures,” they said.

No disclosure information was given.

SOURCE: Armenta AM et al. Pediatr Dermatol. 2019. doi: 10.1111/pde.13739.

The Food and Drug Administration has approved dupilumab for adolescents with moderate to severe atopic dermatitis (AD) that has been inadequately controlled with topical prescription treatments “or when those therapies are not advisable.” 

Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, was initially approved in March 2017, for the same indication, becoming the first targeted biologic treatment for AD. The adolescent approval was announced by the manufacturer.

While there are several systemic medications used as second-line therapy for treatment of pediatric AD, dupilumab is the first FDA-approved biologic for treatment of the disease in adolescents aged 12-17 years, Dawn Marie R. Davis, MD, a pediatric dermatologist at the Mayo Clinic, Rochester (MN), and current president of the Society for Pediatric Dermatology, said in an interview.

FDA approval should decrease insurance barriers and the need for prior authorization, thus increasing access to the drug, she noted, adding, “I hope it will offer a successful alternative to other advanced therapies, as the medicine works through a different mechanism of action, compared to the current systemic medications available.”

With the expanded indication to include adolescents, “patients with more moderate to severe disease who aren’t well controlled with a topical therapy are going to get treatment that will change their lives for many years to come,” dupilumab investigator Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview. “On the whole, patients are likely being undertreated and suffering from the disease more than they need to be,” said Dr. Simpson, “With the advent of this new therapy and the new data, it’s going to change the risk benefit calculation for providers and for patients.”

Results from a phase 3 clinical trial of dupilumab in adolescents with moderate to severe AD were presented last fall at the European Academy of Dermatology and Venereology Congress in Paris. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo. Dr. Simpson, the first author of this study, presented the results at that meeting.

Dr. Simpson said that he hopes dupilumab approval for adolescents and the clinical trial results will help providers recognize when patients are not in good control of their AD, and which patients qualify for a step-up in therapy when treatments such as topical therapy or prednisone are not effective. “There are so many patients out there who qualify for a step-up in therapy,” he commented. “I hope that provides comfort to both patients and providers, that it’s OK to take the next step, because the results show us that, not only it can improve your skin rash, but it can have dramatic effects on all the downstream effects of the condition.”

These downstream effects include not only quality of life and comorbidities of mental health but also the patient’s emotional state. Hopefully, dupilumab can reduce stigmatization of AD and feelings of embarrassment for adolescents at a time in life when “socialization, education, and activity is so important in creating your kind of identity in yourself and your sense of self-worth,” Dr. Simpson said.

“It is important to remember atopic dermatitis is a disease that impacts not only the skin, but the patient as a whole,” said Dr. Davis. “It is an exciting time to be caring for atopic dermatitis patients with the various new medications coming to market.”

The FDA had granted a priority review for the adolescent indication; previously the FDA had granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications

The dosing for adolescents is weight based; two doses are available, 200 mg and 300 mg, administered subcutaneously, every other week after a loading dose. The updated prescribing information is available at https://www.regeneron.com/sites/default/files/Dupixent_FPI.pdf.Dr. Simpson reports relationships with Sanofi and Regeneron Pharmaceuticals. Dr. Davis reports no relevant financial disclosures.

The Food and Drug Administration has approved dupilumab for adolescents with moderate to severe atopic dermatitis (AD) that has been inadequately controlled with topical prescription treatments “or when those therapies are not advisable.” 

Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, was initially approved in March 2017, for the same indication, becoming the first targeted biologic treatment for AD. The adolescent approval was announced by the manufacturer.

While there are several systemic medications used as second-line therapy for treatment of pediatric AD, dupilumab is the first FDA-approved biologic for treatment of the disease in adolescents aged 12-17 years, Dawn Marie R. Davis, MD, a pediatric dermatologist at the Mayo Clinic, Rochester (MN), and current president of the Society for Pediatric Dermatology, said in an interview.

FDA approval should decrease insurance barriers and the need for prior authorization, thus increasing access to the drug, she noted, adding, “I hope it will offer a successful alternative to other advanced therapies, as the medicine works through a different mechanism of action, compared to the current systemic medications available.”

With the expanded indication to include adolescents, “patients with more moderate to severe disease who aren’t well controlled with a topical therapy are going to get treatment that will change their lives for many years to come,” dupilumab investigator Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview. “On the whole, patients are likely being undertreated and suffering from the disease more than they need to be,” said Dr. Simpson, “With the advent of this new therapy and the new data, it’s going to change the risk benefit calculation for providers and for patients.”

Results from a phase 3 clinical trial of dupilumab in adolescents with moderate to severe AD were presented last fall at the European Academy of Dermatology and Venereology Congress in Paris. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo. Dr. Simpson, the first author of this study, presented the results at that meeting.

Dr. Simpson said that he hopes dupilumab approval for adolescents and the clinical trial results will help providers recognize when patients are not in good control of their AD, and which patients qualify for a step-up in therapy when treatments such as topical therapy or prednisone are not effective. “There are so many patients out there who qualify for a step-up in therapy,” he commented. “I hope that provides comfort to both patients and providers, that it’s OK to take the next step, because the results show us that, not only it can improve your skin rash, but it can have dramatic effects on all the downstream effects of the condition.”

These downstream effects include not only quality of life and comorbidities of mental health but also the patient’s emotional state. Hopefully, dupilumab can reduce stigmatization of AD and feelings of embarrassment for adolescents at a time in life when “socialization, education, and activity is so important in creating your kind of identity in yourself and your sense of self-worth,” Dr. Simpson said.

“It is important to remember atopic dermatitis is a disease that impacts not only the skin, but the patient as a whole,” said Dr. Davis. “It is an exciting time to be caring for atopic dermatitis patients with the various new medications coming to market.”

The FDA had granted a priority review for the adolescent indication; previously the FDA had granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications

The dosing for adolescents is weight based; two doses are available, 200 mg and 300 mg, administered subcutaneously, every other week after a loading dose. The updated prescribing information is available at https://www.regeneron.com/sites/default/files/Dupixent_FPI.pdf.Dr. Simpson reports relationships with Sanofi and Regeneron Pharmaceuticals. Dr. Davis reports no relevant financial disclosures.

The Food and Drug Administration has approved dupilumab for adolescents with moderate to severe atopic dermatitis (AD) that has been inadequately controlled with topical prescription treatments “or when those therapies are not advisable.” 

Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, was initially approved in March 2017, for the same indication, becoming the first targeted biologic treatment for AD. The adolescent approval was announced by the manufacturer.

While there are several systemic medications used as second-line therapy for treatment of pediatric AD, dupilumab is the first FDA-approved biologic for treatment of the disease in adolescents aged 12-17 years, Dawn Marie R. Davis, MD, a pediatric dermatologist at the Mayo Clinic, Rochester (MN), and current president of the Society for Pediatric Dermatology, said in an interview.

FDA approval should decrease insurance barriers and the need for prior authorization, thus increasing access to the drug, she noted, adding, “I hope it will offer a successful alternative to other advanced therapies, as the medicine works through a different mechanism of action, compared to the current systemic medications available.”

With the expanded indication to include adolescents, “patients with more moderate to severe disease who aren’t well controlled with a topical therapy are going to get treatment that will change their lives for many years to come,” dupilumab investigator Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview. “On the whole, patients are likely being undertreated and suffering from the disease more than they need to be,” said Dr. Simpson, “With the advent of this new therapy and the new data, it’s going to change the risk benefit calculation for providers and for patients.”

Results from a phase 3 clinical trial of dupilumab in adolescents with moderate to severe AD were presented last fall at the European Academy of Dermatology and Venereology Congress in Paris. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo. Dr. Simpson, the first author of this study, presented the results at that meeting.

Dr. Simpson said that he hopes dupilumab approval for adolescents and the clinical trial results will help providers recognize when patients are not in good control of their AD, and which patients qualify for a step-up in therapy when treatments such as topical therapy or prednisone are not effective. “There are so many patients out there who qualify for a step-up in therapy,” he commented. “I hope that provides comfort to both patients and providers, that it’s OK to take the next step, because the results show us that, not only it can improve your skin rash, but it can have dramatic effects on all the downstream effects of the condition.”

These downstream effects include not only quality of life and comorbidities of mental health but also the patient’s emotional state. Hopefully, dupilumab can reduce stigmatization of AD and feelings of embarrassment for adolescents at a time in life when “socialization, education, and activity is so important in creating your kind of identity in yourself and your sense of self-worth,” Dr. Simpson said.

“It is important to remember atopic dermatitis is a disease that impacts not only the skin, but the patient as a whole,” said Dr. Davis. “It is an exciting time to be caring for atopic dermatitis patients with the various new medications coming to market.”

The FDA had granted a priority review for the adolescent indication; previously the FDA had granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications

The dosing for adolescents is weight based; two doses are available, 200 mg and 300 mg, administered subcutaneously, every other week after a loading dose. The updated prescribing information is available at https://www.regeneron.com/sites/default/files/Dupixent_FPI.pdf.Dr. Simpson reports relationships with Sanofi and Regeneron Pharmaceuticals. Dr. Davis reports no relevant financial disclosures.

The number of new measles cases was down by more than half last week, but another state has been added to the list of those with reported cases in 2019, according to the Centers for Disease Control and Prevention.

There were 21 new measles cases reported to the CDC during the week ending March 7 – down from 47 the week before. The total for the year is 228 cases, which moves 2019 ahead of 2011 for third place over the last decade, the CDC reported March 11. Going back even further in time, the 206 measles cases reported through January and February is the highest 2-month total in a quarter of a century, the Washington Post said.

New Hampshire became the 12th and latest state to report a case of measles this year, joining California, Colorado, Connecticut, Georgia, Illinois, Kentucky, New Jersey, New York, Oregon, Texas, and Washington. California’s situation is now considered an outbreak (defined as three or more cases), but one of the three outbreaks in New York has been taken off the list, so total outbreaks for 2019 remain at six, the CDC said.

For the third consecutive week, New York City produced the most measles cases, with Brooklyn’s Williamsburg neighborhood recording 11 of the U.S. total of 21. The outbreak in King County, Wash., – totaling 70 cases this year – may be winding down as only one new case was reported last week, and no new cases are being investigated, the county’s public health service reported.

rfranki@mdedge.com

The number of new measles cases was down by more than half last week, but another state has been added to the list of those with reported cases in 2019, according to the Centers for Disease Control and Prevention.

There were 21 new measles cases reported to the CDC during the week ending March 7 – down from 47 the week before. The total for the year is 228 cases, which moves 2019 ahead of 2011 for third place over the last decade, the CDC reported March 11. Going back even further in time, the 206 measles cases reported through January and February is the highest 2-month total in a quarter of a century, the Washington Post said.

New Hampshire became the 12th and latest state to report a case of measles this year, joining California, Colorado, Connecticut, Georgia, Illinois, Kentucky, New Jersey, New York, Oregon, Texas, and Washington. California’s situation is now considered an outbreak (defined as three or more cases), but one of the three outbreaks in New York has been taken off the list, so total outbreaks for 2019 remain at six, the CDC said.

For the third consecutive week, New York City produced the most measles cases, with Brooklyn’s Williamsburg neighborhood recording 11 of the U.S. total of 21. The outbreak in King County, Wash., – totaling 70 cases this year – may be winding down as only one new case was reported last week, and no new cases are being investigated, the county’s public health service reported.

rfranki@mdedge.com

The number of new measles cases was down by more than half last week, but another state has been added to the list of those with reported cases in 2019, according to the Centers for Disease Control and Prevention.

There were 21 new measles cases reported to the CDC during the week ending March 7 – down from 47 the week before. The total for the year is 228 cases, which moves 2019 ahead of 2011 for third place over the last decade, the CDC reported March 11. Going back even further in time, the 206 measles cases reported through January and February is the highest 2-month total in a quarter of a century, the Washington Post said.

New Hampshire became the 12th and latest state to report a case of measles this year, joining California, Colorado, Connecticut, Georgia, Illinois, Kentucky, New Jersey, New York, Oregon, Texas, and Washington. California’s situation is now considered an outbreak (defined as three or more cases), but one of the three outbreaks in New York has been taken off the list, so total outbreaks for 2019 remain at six, the CDC said.

For the third consecutive week, New York City produced the most measles cases, with Brooklyn’s Williamsburg neighborhood recording 11 of the U.S. total of 21. The outbreak in King County, Wash., – totaling 70 cases this year – may be winding down as only one new case was reported last week, and no new cases are being investigated, the county’s public health service reported.

rfranki@mdedge.com

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of arthritides that are characterized by onset before 16 years of age and defined in part as lasting ≥6 weeks.¹ Significantly, the etiology of JIA is unknown, making it a diagnosis of exclusion.²

The most common autoimmune condition of childhood, JIA has a prevalence of 3.8 to 400 affected children for every 100,000 people.^3,4 As the leading cause of musculoskeletal disability in children,⁵ and comprising 7 categories of disease, JIA must be managed with appropriate initial and ongoing intervention.

The amalgam of care that a JIA patient requires—medical, social, physical, psychological—calls for a primary care physician’s expert ability to collaborate and coordinate with medical specialists and subspecialists, including rheumatology, ophthalmology, social work, physical and occupational therapy, and psychology. The goal? As this article describes, the goal is to provide prompt diagnosis, suitable and effective intervention, and continuity of care. (JIA is a lifelong disease, in many cases.)

How JIA is classifiedfor diagnosis and treatment

JIA comprises 7 categories, or classes.⁶ The scheme devised by the International League of Associations for Rheumatology (ILAR), now widely accepted, classifies JIA on the basis of clinical and biochemical markers that aid detection and treatment of the disorder, as well as research. (See “How efforts to classify JIA have caused confusion.”^7-10) The ILAR classes (TABLE¹¹) are:

• enthesitis-related arthritis (ERA)
• extended oligo-articular JIA (eoJIA), which involves ≤4 joints
• juvenile psoriatic arthritis (jPsA)
• rheumatoid factor (RF)-positive polyarticular JIA (RF+ pJIA)
• RF-negative polyarticular JIA (RF– pJIA)
• systemic-onset JIA (sJIA)
• undifferentiated JIA, which, generally, involves ≥4 joints.

Updated guidelines regarding the 7 ILAR classes of JIA emphasize heterogeneity among disease subtypes, with overlapping and exclusive features noted from class to class.¹¹

Extended oligo-articular JIA (27%-56%), pJIA (13%-35%), sJIA (4%-17%), and ERA,(3%-11%) are the most common JIA subtypes,¹² with age of onset and sex predilection differing according to JIA class.¹¹ The disease occurs more often in girls than in boys,¹¹ and the predisposition is higher among Whites and Asians. The incidence of JIA (all classes taken together, for every 100,000 people) is: in Japan, 10 to 15 cases¹³; in Turkey, 64 cases¹⁴; in Norway, 65 cases¹⁵; and in the United States and Canada, taken together, 10 to 15 cases.¹⁶

What causes JIA?

The etiology of JIA remains unclear. It is known that the disease involves inflammation of the synovium and destruction of hard and soft tissues in joints.¹⁷ It has been postulated, therefore, that a combination of genetic, environmental, and immunogenic mechanisms might be responsible for JIA.

Continue to: For example, there is an increased...

For example, there is an increased frequency of autoimmune diseases among JIA patients.¹⁸ There are also reports documenting an increased rate of infection, including with enteric pathogens, parvovirus B,¹⁹ rubella, mumps, hepatitis B, Epstein-Barr virus, mycoplasma, and chlamydia.¹⁹ Stress and trauma have also been implicated.¹²

The T-lymphocyte percentage is increased in the synovial fluid of JIA patients, although that percentage varies from subtype to subtype.²⁰ This elevation results in an increase in the number of macrophages, which are induced by secreted cytokines to produce interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-a). This activity of cellular immunity leads to joint destruction.²¹

Clinical features

The most common signs and symptoms of JIA are arthralgias (39%), arthritis (25%), fever (18%), limping (9%), rash (8%), abdominal pain (1.3%), and uveitis (1.3%).¹⁵ Forty percent of JIA patients are reported to have temporomandibular joint involvement at some point in their life; mandibular asymmetry secondary to condylar resorption and remodeling¹⁷ is the most common presenting complaint—not arthralgia or pain, as would be expected.

Most JIA patients (52%) first present to the emergency department; another 42% present to the office of a general medical practitioner.¹⁵ On average, 3 visits to a physician, over the course of approximately 3 months, are made before a definitive diagnosis (usually by a pediatric rheumatologist) is made.¹⁵

Pertinent questions to ask a patient who has a confirmed diagnosis of JIA include the nature, severity, and duration of morning stiffness and pain, as well as any encumbering factors to regular functioning at home or school.²² Different scoring charts can be used to determine the extent of pain and disability, including the Juvenile Arthritis Disease Activity Score (JADAS)²³ and the clinical JADAS (cJADAS),²⁴ which measure minimal disease activity²⁵ and clinically inactive disease²⁶ cutoffs.

Continue to: Macrophage-activating syndrome increases risk of morbidity, mortality

 

 

Macrophage-activating syndrome increases risk of morbidity, mortality

An overactivation and expansion of T lymphocytes and macrophagic histiocytes with hemophagocytic activity, macrophage-activating syndrome (MAS) occurs in approximately 10% of JIA patients,²⁷ increasing their risk of morbidity and mortality. The syndrome, which typically presents as fever, seizures, hypotension, purpura, hepatitis, splenomegaly, and occasionally, multisystem organ failure, is seen in 30% to 40% of sJIA patients; approximately 11% of them experience sudden death as a consequence.²⁸

The clinical setting of MAS includes presenting symptoms of fever and a salmon-pink macular rash (FIGURE). For many sJIA patients with MAS, the diagnosis is made when laboratory results show hyperferritinemia, thrombocytopenia, anemia, leukopenia, coagulopathy, and elevated levels of C-reactive protein and D-dimer.²⁷

Different classes, different features

The following clinical profiles have been documented in different classes of JIA:

Systemic JIA presents with intermittent fever of at least 2 weeks’ duration, arthritis, and occasionally, a rash.

Extended oligo-articular JIA involves pain, in a mono-articular lower-extremity joint, that can develop suddenly or insidiously, and is characterized by early-morning stiffness and uveitis (especially in early-onset, antinuclear antibody-positive JIA patients).

Continue to: Poly-articular JIA

Poly-articular JIA patients present with mild fever, weight loss, and anemia.

Enthesis-related arthritis patients have findings of enthesopathy; asymmetric arthritis of the lower extremities, particularly the Achilles tendon²⁹; and recurrent acute, symptomatic iridocyclitis.³⁰

Juvenile psoriatic arthritis can involve any joint but is readily differentiated from pJIA by involvement of distal interphalangeal joints and psoriatic skin and nail changes.²⁹

Investigations

Imaging

Radiography is still the most widely used imaging tool for making the diagnosis of JIA. Plain films demonstrate structural joint damage and disturbances of growth and maturation in bones. Radiography has poor sensitivity for detecting acute synovitis and limited utility in visualizing erosion changes early in the course of disease, however, which has led to increased use of ultrasonography (US) and contrast-enhanced magnetic resonance imaging (MRI) to diagnose JIA.³⁰

Contrast-enhanced MRI is superior to US for detecting early inflammation and monitoring subsequent joint disease. Of course, MRI is more expensive than US, and less widely available. Other imaging options are computed tomography and positron emission tomography, but these scans are not as sensitive as contrast-enhanced MRI and have the disadvantage of radiation exposure (in the former) and cost (in the latter).

Continue to: Laboratory testing

 

 

Laboratory testing

Mandibular asymmetry secondary to condylar resorption and remodeling is the most common presenting complaint of juvenile idiopathic arthritis—not arthralgia or pain, as you might expect.

No diagnostic tests for JIA exist. Assays of acute-phase reactants, including C-reactive protein, the erythrocyte sedimentation rate, and serum amyloid-A proteins, can be utilized to demonstrate inflammation but not to confirm the diagnosis. For some classes of JIA, various tests, including rheumatoid factor, antinuclear antibody, human leukocyte antigen B-27, and cyclic citrullated peptide antibodies, can be used to confirm a specific class but, again, are not recommended for confirming JIA.⁶

The complete blood count, blood cultures, and tests of uric acid and lactate dehydrogenase can be ordered during treatment to monitor for complications, such as malignancy, infection, MAS, and sepsis.

Treatment is based on disease class

Nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular steroids are used in all JIA classes, as an adjunct to class-specific treatment, or as induction agents.³¹ These therapies, although they alleviate acute signs and symptoms, such as pain, inflammation, swelling and joint contractures, are not useful for long-term treatment of JIA because they do not halt disease progression.

Systemic steroids can be utilized in exceptional cases, including chronic uveitis with arthritis or in patients with destructive arthritis and poor prognostic features, including cyclic citrullated peptide antibodies, positive RF, erosions, and joint-space narrowing.³²

Other drugs. Options include traditional disease-modifying anti-rheumatic drugs (csDMARDs), such as methotrexate and leflunomide; biologic agents, such as TNF-a inhibitors (eg, etanercept, adalimumab, and infliximab); and anti-IL monoclonal antibody drugs (eg, the IL-6 inhibitor tocilizumab and IL-1 inhibitors anakinra, and canakinumab).³¹ Indications by class include:

• csDMARDs as first-line therapy in persistent eoJIA and pJIA;
• TNF-Symbolα inhibitors for refractory eoJIA and for pJIA episodes³¹;
• tocilizumab, recommended for sJIA patients who have persistent systemic signs; and
• anakinra and canakinumab for refractory SJIA patients.³²

Continue to: Failure

 

 

Failure

When treatment of JIA fails with a given drug, options include increasing the dosage; switching to another agent in the same drug class; switching to a different class; and combining an NSAID with a csDMARD or a biologic agent.³² In class-specific JIA cases, a change in a drug regimen is warranted on the basis of the evidence-based historical clinical response rate.³²

What is the prognosis?

Treatment of JIA with novel agents, such as biologics, has opened up the possibility that JIA patients can live not just with suppressed symptoms but immunologically inactive disease. This is the result of better understanding of the pathogenesis of JIA and the mechanism of action of targeted drugs, and identification of biomarkers that are helpful in predicting prognosis, adverse effects, and response to treatment.

On average, it takes 3 visits to a physician, over the course of about 3 months, before definitive diagnosis of JIA is made.

JIA is often a lifelong disease; one-third of patients continue to exhibit symptoms into adulthood.⁴ If their disease is properly managed, however, these patients do not develop typical features of rheumatoid arthritis, including hand, limb, and spine deformities. Last, patients with JIA who have only intermittent disease tend to do better over the long term than those whose disease is continual.³²

The mortality rate of JIA has dropped: from 1% to 4% in the mid-1970s to 0.3% to 1% today⁴—an improvement in life expectancy that is echoed in enhanced quality of life for patients. According to the 4-level Steinbrocker functional classification scale³³ (used to rate the extent of physical disability), 15% of JIA patients were Class III (limited to few or no activities of the patient’s usual occupation) or Class IV (bedridden with little or no self-care) in the period from 1976 to 1994—a percentage that had declined to 5% by 2002.³⁴

The family physician plays pivotal role in JIA care

For the family physician, appropriate initial intervention in the management of JIA is imperative. This includes ordering imaging (whether plain films or MRI), laboratory tests as described earlier (although not to make the diagnosis), and the use of NSAIDs, intra-articular steroids, and other induction agents. Once the diagnosis is made, and a drug regimen is put in place, you will need to monitor for adverse effects. This monitoring will need to occur when a patient is escalated to csDMARDs, biological agents, or systemic steroids; is maintained on an NSAID; or is placed on a combination regimen.

Continue to: Before beginning therapy with a biologic agent...

Before beginning therapy with a biologic agent, it’s important to screen for hepatitis B, hepatitis C, human immunodeficiency virus infection, tuberculosis, and fungal infection (eg, Histoplasma capsulatum, Coccidioides immitis³²). Be sure to make a timely referral to the ophthalmology service for a bi-annual eye exam and, in the event that surgery is necessary, conduct a preoperative evaluation, with the knowledge of how long before surgery a biologic agent must be withheld (duration varies by drug).³²

CORRESPONDENCE
Tobe Momah, MD, Department of Family Medicine, Clinical Science Building, 4th Floor, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; tmomah@umc.edu.

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of arthritides that are characterized by onset before 16 years of age and defined in part as lasting ≥6 weeks.¹ Significantly, the etiology of JIA is unknown, making it a diagnosis of exclusion.²

The most common autoimmune condition of childhood, JIA has a prevalence of 3.8 to 400 affected children for every 100,000 people.^3,4 As the leading cause of musculoskeletal disability in children,⁵ and comprising 7 categories of disease, JIA must be managed with appropriate initial and ongoing intervention.

The amalgam of care that a JIA patient requires—medical, social, physical, psychological—calls for a primary care physician’s expert ability to collaborate and coordinate with medical specialists and subspecialists, including rheumatology, ophthalmology, social work, physical and occupational therapy, and psychology. The goal? As this article describes, the goal is to provide prompt diagnosis, suitable and effective intervention, and continuity of care. (JIA is a lifelong disease, in many cases.)

How JIA is classifiedfor diagnosis and treatment

JIA comprises 7 categories, or classes.⁶ The scheme devised by the International League of Associations for Rheumatology (ILAR), now widely accepted, classifies JIA on the basis of clinical and biochemical markers that aid detection and treatment of the disorder, as well as research. (See “How efforts to classify JIA have caused confusion.”^7-10) The ILAR classes (TABLE¹¹) are:

• enthesitis-related arthritis (ERA)
• extended oligo-articular JIA (eoJIA), which involves ≤4 joints
• juvenile psoriatic arthritis (jPsA)
• rheumatoid factor (RF)-positive polyarticular JIA (RF+ pJIA)
• RF-negative polyarticular JIA (RF– pJIA)
• systemic-onset JIA (sJIA)
• undifferentiated JIA, which, generally, involves ≥4 joints.

Updated guidelines regarding the 7 ILAR classes of JIA emphasize heterogeneity among disease subtypes, with overlapping and exclusive features noted from class to class.¹¹

Extended oligo-articular JIA (27%-56%), pJIA (13%-35%), sJIA (4%-17%), and ERA,(3%-11%) are the most common JIA subtypes,¹² with age of onset and sex predilection differing according to JIA class.¹¹ The disease occurs more often in girls than in boys,¹¹ and the predisposition is higher among Whites and Asians. The incidence of JIA (all classes taken together, for every 100,000 people) is: in Japan, 10 to 15 cases¹³; in Turkey, 64 cases¹⁴; in Norway, 65 cases¹⁵; and in the United States and Canada, taken together, 10 to 15 cases.¹⁶

What causes JIA?

The etiology of JIA remains unclear. It is known that the disease involves inflammation of the synovium and destruction of hard and soft tissues in joints.¹⁷ It has been postulated, therefore, that a combination of genetic, environmental, and immunogenic mechanisms might be responsible for JIA.

Continue to: For example, there is an increased...

For example, there is an increased frequency of autoimmune diseases among JIA patients.¹⁸ There are also reports documenting an increased rate of infection, including with enteric pathogens, parvovirus B,¹⁹ rubella, mumps, hepatitis B, Epstein-Barr virus, mycoplasma, and chlamydia.¹⁹ Stress and trauma have also been implicated.¹²

The T-lymphocyte percentage is increased in the synovial fluid of JIA patients, although that percentage varies from subtype to subtype.²⁰ This elevation results in an increase in the number of macrophages, which are induced by secreted cytokines to produce interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-a). This activity of cellular immunity leads to joint destruction.²¹

Clinical features

The most common signs and symptoms of JIA are arthralgias (39%), arthritis (25%), fever (18%), limping (9%), rash (8%), abdominal pain (1.3%), and uveitis (1.3%).¹⁵ Forty percent of JIA patients are reported to have temporomandibular joint involvement at some point in their life; mandibular asymmetry secondary to condylar resorption and remodeling¹⁷ is the most common presenting complaint—not arthralgia or pain, as would be expected.

Most JIA patients (52%) first present to the emergency department; another 42% present to the office of a general medical practitioner.¹⁵ On average, 3 visits to a physician, over the course of approximately 3 months, are made before a definitive diagnosis (usually by a pediatric rheumatologist) is made.¹⁵

Pertinent questions to ask a patient who has a confirmed diagnosis of JIA include the nature, severity, and duration of morning stiffness and pain, as well as any encumbering factors to regular functioning at home or school.²² Different scoring charts can be used to determine the extent of pain and disability, including the Juvenile Arthritis Disease Activity Score (JADAS)²³ and the clinical JADAS (cJADAS),²⁴ which measure minimal disease activity²⁵ and clinically inactive disease²⁶ cutoffs.

Continue to: Macrophage-activating syndrome increases risk of morbidity, mortality

 

 

Macrophage-activating syndrome increases risk of morbidity, mortality

An overactivation and expansion of T lymphocytes and macrophagic histiocytes with hemophagocytic activity, macrophage-activating syndrome (MAS) occurs in approximately 10% of JIA patients,²⁷ increasing their risk of morbidity and mortality. The syndrome, which typically presents as fever, seizures, hypotension, purpura, hepatitis, splenomegaly, and occasionally, multisystem organ failure, is seen in 30% to 40% of sJIA patients; approximately 11% of them experience sudden death as a consequence.²⁸

The clinical setting of MAS includes presenting symptoms of fever and a salmon-pink macular rash (FIGURE). For many sJIA patients with MAS, the diagnosis is made when laboratory results show hyperferritinemia, thrombocytopenia, anemia, leukopenia, coagulopathy, and elevated levels of C-reactive protein and D-dimer.²⁷

Different classes, different features

The following clinical profiles have been documented in different classes of JIA:

Systemic JIA presents with intermittent fever of at least 2 weeks’ duration, arthritis, and occasionally, a rash.

Extended oligo-articular JIA involves pain, in a mono-articular lower-extremity joint, that can develop suddenly or insidiously, and is characterized by early-morning stiffness and uveitis (especially in early-onset, antinuclear antibody-positive JIA patients).

Continue to: Poly-articular JIA

Poly-articular JIA patients present with mild fever, weight loss, and anemia.

Enthesis-related arthritis patients have findings of enthesopathy; asymmetric arthritis of the lower extremities, particularly the Achilles tendon²⁹; and recurrent acute, symptomatic iridocyclitis.³⁰

Juvenile psoriatic arthritis can involve any joint but is readily differentiated from pJIA by involvement of distal interphalangeal joints and psoriatic skin and nail changes.²⁹

Investigations

Imaging

Radiography is still the most widely used imaging tool for making the diagnosis of JIA. Plain films demonstrate structural joint damage and disturbances of growth and maturation in bones. Radiography has poor sensitivity for detecting acute synovitis and limited utility in visualizing erosion changes early in the course of disease, however, which has led to increased use of ultrasonography (US) and contrast-enhanced magnetic resonance imaging (MRI) to diagnose JIA.³⁰

Contrast-enhanced MRI is superior to US for detecting early inflammation and monitoring subsequent joint disease. Of course, MRI is more expensive than US, and less widely available. Other imaging options are computed tomography and positron emission tomography, but these scans are not as sensitive as contrast-enhanced MRI and have the disadvantage of radiation exposure (in the former) and cost (in the latter).

Continue to: Laboratory testing

 

 

Laboratory testing

Mandibular asymmetry secondary to condylar resorption and remodeling is the most common presenting complaint of juvenile idiopathic arthritis—not arthralgia or pain, as you might expect.

No diagnostic tests for JIA exist. Assays of acute-phase reactants, including C-reactive protein, the erythrocyte sedimentation rate, and serum amyloid-A proteins, can be utilized to demonstrate inflammation but not to confirm the diagnosis. For some classes of JIA, various tests, including rheumatoid factor, antinuclear antibody, human leukocyte antigen B-27, and cyclic citrullated peptide antibodies, can be used to confirm a specific class but, again, are not recommended for confirming JIA.⁶

The complete blood count, blood cultures, and tests of uric acid and lactate dehydrogenase can be ordered during treatment to monitor for complications, such as malignancy, infection, MAS, and sepsis.

Treatment is based on disease class

Nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular steroids are used in all JIA classes, as an adjunct to class-specific treatment, or as induction agents.³¹ These therapies, although they alleviate acute signs and symptoms, such as pain, inflammation, swelling and joint contractures, are not useful for long-term treatment of JIA because they do not halt disease progression.

Systemic steroids can be utilized in exceptional cases, including chronic uveitis with arthritis or in patients with destructive arthritis and poor prognostic features, including cyclic citrullated peptide antibodies, positive RF, erosions, and joint-space narrowing.³²

Other drugs. Options include traditional disease-modifying anti-rheumatic drugs (csDMARDs), such as methotrexate and leflunomide; biologic agents, such as TNF-a inhibitors (eg, etanercept, adalimumab, and infliximab); and anti-IL monoclonal antibody drugs (eg, the IL-6 inhibitor tocilizumab and IL-1 inhibitors anakinra, and canakinumab).³¹ Indications by class include:

• csDMARDs as first-line therapy in persistent eoJIA and pJIA;
• TNF-Symbolα inhibitors for refractory eoJIA and for pJIA episodes³¹;
• tocilizumab, recommended for sJIA patients who have persistent systemic signs; and
• anakinra and canakinumab for refractory SJIA patients.³²

Continue to: Failure

 

 

Failure

When treatment of JIA fails with a given drug, options include increasing the dosage; switching to another agent in the same drug class; switching to a different class; and combining an NSAID with a csDMARD or a biologic agent.³² In class-specific JIA cases, a change in a drug regimen is warranted on the basis of the evidence-based historical clinical response rate.³²

What is the prognosis?

Treatment of JIA with novel agents, such as biologics, has opened up the possibility that JIA patients can live not just with suppressed symptoms but immunologically inactive disease. This is the result of better understanding of the pathogenesis of JIA and the mechanism of action of targeted drugs, and identification of biomarkers that are helpful in predicting prognosis, adverse effects, and response to treatment.

On average, it takes 3 visits to a physician, over the course of about 3 months, before definitive diagnosis of JIA is made.

JIA is often a lifelong disease; one-third of patients continue to exhibit symptoms into adulthood.⁴ If their disease is properly managed, however, these patients do not develop typical features of rheumatoid arthritis, including hand, limb, and spine deformities. Last, patients with JIA who have only intermittent disease tend to do better over the long term than those whose disease is continual.³²

The mortality rate of JIA has dropped: from 1% to 4% in the mid-1970s to 0.3% to 1% today⁴—an improvement in life expectancy that is echoed in enhanced quality of life for patients. According to the 4-level Steinbrocker functional classification scale³³ (used to rate the extent of physical disability), 15% of JIA patients were Class III (limited to few or no activities of the patient’s usual occupation) or Class IV (bedridden with little or no self-care) in the period from 1976 to 1994—a percentage that had declined to 5% by 2002.³⁴

The family physician plays pivotal role in JIA care

For the family physician, appropriate initial intervention in the management of JIA is imperative. This includes ordering imaging (whether plain films or MRI), laboratory tests as described earlier (although not to make the diagnosis), and the use of NSAIDs, intra-articular steroids, and other induction agents. Once the diagnosis is made, and a drug regimen is put in place, you will need to monitor for adverse effects. This monitoring will need to occur when a patient is escalated to csDMARDs, biological agents, or systemic steroids; is maintained on an NSAID; or is placed on a combination regimen.

Continue to: Before beginning therapy with a biologic agent...

Before beginning therapy with a biologic agent, it’s important to screen for hepatitis B, hepatitis C, human immunodeficiency virus infection, tuberculosis, and fungal infection (eg, Histoplasma capsulatum, Coccidioides immitis³²). Be sure to make a timely referral to the ophthalmology service for a bi-annual eye exam and, in the event that surgery is necessary, conduct a preoperative evaluation, with the knowledge of how long before surgery a biologic agent must be withheld (duration varies by drug).³²

CORRESPONDENCE
Tobe Momah, MD, Department of Family Medicine, Clinical Science Building, 4th Floor, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; tmomah@umc.edu.

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of arthritides that are characterized by onset before 16 years of age and defined in part as lasting ≥6 weeks.¹ Significantly, the etiology of JIA is unknown, making it a diagnosis of exclusion.²

The most common autoimmune condition of childhood, JIA has a prevalence of 3.8 to 400 affected children for every 100,000 people.^3,4 As the leading cause of musculoskeletal disability in children,⁵ and comprising 7 categories of disease, JIA must be managed with appropriate initial and ongoing intervention.

The amalgam of care that a JIA patient requires—medical, social, physical, psychological—calls for a primary care physician’s expert ability to collaborate and coordinate with medical specialists and subspecialists, including rheumatology, ophthalmology, social work, physical and occupational therapy, and psychology. The goal? As this article describes, the goal is to provide prompt diagnosis, suitable and effective intervention, and continuity of care. (JIA is a lifelong disease, in many cases.)

How JIA is classifiedfor diagnosis and treatment

JIA comprises 7 categories, or classes.⁶ The scheme devised by the International League of Associations for Rheumatology (ILAR), now widely accepted, classifies JIA on the basis of clinical and biochemical markers that aid detection and treatment of the disorder, as well as research. (See “How efforts to classify JIA have caused confusion.”^7-10) The ILAR classes (TABLE¹¹) are:

• enthesitis-related arthritis (ERA)
• extended oligo-articular JIA (eoJIA), which involves ≤4 joints
• juvenile psoriatic arthritis (jPsA)
• rheumatoid factor (RF)-positive polyarticular JIA (RF+ pJIA)
• RF-negative polyarticular JIA (RF– pJIA)
• systemic-onset JIA (sJIA)
• undifferentiated JIA, which, generally, involves ≥4 joints.

Updated guidelines regarding the 7 ILAR classes of JIA emphasize heterogeneity among disease subtypes, with overlapping and exclusive features noted from class to class.¹¹

Extended oligo-articular JIA (27%-56%), pJIA (13%-35%), sJIA (4%-17%), and ERA,(3%-11%) are the most common JIA subtypes,¹² with age of onset and sex predilection differing according to JIA class.¹¹ The disease occurs more often in girls than in boys,¹¹ and the predisposition is higher among Whites and Asians. The incidence of JIA (all classes taken together, for every 100,000 people) is: in Japan, 10 to 15 cases¹³; in Turkey, 64 cases¹⁴; in Norway, 65 cases¹⁵; and in the United States and Canada, taken together, 10 to 15 cases.¹⁶

What causes JIA?

The etiology of JIA remains unclear. It is known that the disease involves inflammation of the synovium and destruction of hard and soft tissues in joints.¹⁷ It has been postulated, therefore, that a combination of genetic, environmental, and immunogenic mechanisms might be responsible for JIA.

Continue to: For example, there is an increased...

For example, there is an increased frequency of autoimmune diseases among JIA patients.¹⁸ There are also reports documenting an increased rate of infection, including with enteric pathogens, parvovirus B,¹⁹ rubella, mumps, hepatitis B, Epstein-Barr virus, mycoplasma, and chlamydia.¹⁹ Stress and trauma have also been implicated.¹²

The T-lymphocyte percentage is increased in the synovial fluid of JIA patients, although that percentage varies from subtype to subtype.²⁰ This elevation results in an increase in the number of macrophages, which are induced by secreted cytokines to produce interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-a). This activity of cellular immunity leads to joint destruction.²¹

Clinical features

The most common signs and symptoms of JIA are arthralgias (39%), arthritis (25%), fever (18%), limping (9%), rash (8%), abdominal pain (1.3%), and uveitis (1.3%).¹⁵ Forty percent of JIA patients are reported to have temporomandibular joint involvement at some point in their life; mandibular asymmetry secondary to condylar resorption and remodeling¹⁷ is the most common presenting complaint—not arthralgia or pain, as would be expected.

Most JIA patients (52%) first present to the emergency department; another 42% present to the office of a general medical practitioner.¹⁵ On average, 3 visits to a physician, over the course of approximately 3 months, are made before a definitive diagnosis (usually by a pediatric rheumatologist) is made.¹⁵

Pertinent questions to ask a patient who has a confirmed diagnosis of JIA include the nature, severity, and duration of morning stiffness and pain, as well as any encumbering factors to regular functioning at home or school.²² Different scoring charts can be used to determine the extent of pain and disability, including the Juvenile Arthritis Disease Activity Score (JADAS)²³ and the clinical JADAS (cJADAS),²⁴ which measure minimal disease activity²⁵ and clinically inactive disease²⁶ cutoffs.

Continue to: Macrophage-activating syndrome increases risk of morbidity, mortality

 

 

Macrophage-activating syndrome increases risk of morbidity, mortality

An overactivation and expansion of T lymphocytes and macrophagic histiocytes with hemophagocytic activity, macrophage-activating syndrome (MAS) occurs in approximately 10% of JIA patients,²⁷ increasing their risk of morbidity and mortality. The syndrome, which typically presents as fever, seizures, hypotension, purpura, hepatitis, splenomegaly, and occasionally, multisystem organ failure, is seen in 30% to 40% of sJIA patients; approximately 11% of them experience sudden death as a consequence.²⁸

The clinical setting of MAS includes presenting symptoms of fever and a salmon-pink macular rash (FIGURE). For many sJIA patients with MAS, the diagnosis is made when laboratory results show hyperferritinemia, thrombocytopenia, anemia, leukopenia, coagulopathy, and elevated levels of C-reactive protein and D-dimer.²⁷

Different classes, different features

The following clinical profiles have been documented in different classes of JIA:

Systemic JIA presents with intermittent fever of at least 2 weeks’ duration, arthritis, and occasionally, a rash.

Extended oligo-articular JIA involves pain, in a mono-articular lower-extremity joint, that can develop suddenly or insidiously, and is characterized by early-morning stiffness and uveitis (especially in early-onset, antinuclear antibody-positive JIA patients).

Continue to: Poly-articular JIA

Poly-articular JIA patients present with mild fever, weight loss, and anemia.

Enthesis-related arthritis patients have findings of enthesopathy; asymmetric arthritis of the lower extremities, particularly the Achilles tendon²⁹; and recurrent acute, symptomatic iridocyclitis.³⁰

Juvenile psoriatic arthritis can involve any joint but is readily differentiated from pJIA by involvement of distal interphalangeal joints and psoriatic skin and nail changes.²⁹

Investigations

Imaging

Radiography is still the most widely used imaging tool for making the diagnosis of JIA. Plain films demonstrate structural joint damage and disturbances of growth and maturation in bones. Radiography has poor sensitivity for detecting acute synovitis and limited utility in visualizing erosion changes early in the course of disease, however, which has led to increased use of ultrasonography (US) and contrast-enhanced magnetic resonance imaging (MRI) to diagnose JIA.³⁰

Contrast-enhanced MRI is superior to US for detecting early inflammation and monitoring subsequent joint disease. Of course, MRI is more expensive than US, and less widely available. Other imaging options are computed tomography and positron emission tomography, but these scans are not as sensitive as contrast-enhanced MRI and have the disadvantage of radiation exposure (in the former) and cost (in the latter).

Continue to: Laboratory testing

 

 

Laboratory testing

Mandibular asymmetry secondary to condylar resorption and remodeling is the most common presenting complaint of juvenile idiopathic arthritis—not arthralgia or pain, as you might expect.

No diagnostic tests for JIA exist. Assays of acute-phase reactants, including C-reactive protein, the erythrocyte sedimentation rate, and serum amyloid-A proteins, can be utilized to demonstrate inflammation but not to confirm the diagnosis. For some classes of JIA, various tests, including rheumatoid factor, antinuclear antibody, human leukocyte antigen B-27, and cyclic citrullated peptide antibodies, can be used to confirm a specific class but, again, are not recommended for confirming JIA.⁶

The complete blood count, blood cultures, and tests of uric acid and lactate dehydrogenase can be ordered during treatment to monitor for complications, such as malignancy, infection, MAS, and sepsis.

Treatment is based on disease class

Nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular steroids are used in all JIA classes, as an adjunct to class-specific treatment, or as induction agents.³¹ These therapies, although they alleviate acute signs and symptoms, such as pain, inflammation, swelling and joint contractures, are not useful for long-term treatment of JIA because they do not halt disease progression.

Systemic steroids can be utilized in exceptional cases, including chronic uveitis with arthritis or in patients with destructive arthritis and poor prognostic features, including cyclic citrullated peptide antibodies, positive RF, erosions, and joint-space narrowing.³²

Other drugs. Options include traditional disease-modifying anti-rheumatic drugs (csDMARDs), such as methotrexate and leflunomide; biologic agents, such as TNF-a inhibitors (eg, etanercept, adalimumab, and infliximab); and anti-IL monoclonal antibody drugs (eg, the IL-6 inhibitor tocilizumab and IL-1 inhibitors anakinra, and canakinumab).³¹ Indications by class include:

• csDMARDs as first-line therapy in persistent eoJIA and pJIA;
• TNF-Symbolα inhibitors for refractory eoJIA and for pJIA episodes³¹;
• tocilizumab, recommended for sJIA patients who have persistent systemic signs; and
• anakinra and canakinumab for refractory SJIA patients.³²

Continue to: Failure

 

 

Failure

When treatment of JIA fails with a given drug, options include increasing the dosage; switching to another agent in the same drug class; switching to a different class; and combining an NSAID with a csDMARD or a biologic agent.³² In class-specific JIA cases, a change in a drug regimen is warranted on the basis of the evidence-based historical clinical response rate.³²

What is the prognosis?

Treatment of JIA with novel agents, such as biologics, has opened up the possibility that JIA patients can live not just with suppressed symptoms but immunologically inactive disease. This is the result of better understanding of the pathogenesis of JIA and the mechanism of action of targeted drugs, and identification of biomarkers that are helpful in predicting prognosis, adverse effects, and response to treatment.

On average, it takes 3 visits to a physician, over the course of about 3 months, before definitive diagnosis of JIA is made.

JIA is often a lifelong disease; one-third of patients continue to exhibit symptoms into adulthood.⁴ If their disease is properly managed, however, these patients do not develop typical features of rheumatoid arthritis, including hand, limb, and spine deformities. Last, patients with JIA who have only intermittent disease tend to do better over the long term than those whose disease is continual.³²

The mortality rate of JIA has dropped: from 1% to 4% in the mid-1970s to 0.3% to 1% today⁴—an improvement in life expectancy that is echoed in enhanced quality of life for patients. According to the 4-level Steinbrocker functional classification scale³³ (used to rate the extent of physical disability), 15% of JIA patients were Class III (limited to few or no activities of the patient’s usual occupation) or Class IV (bedridden with little or no self-care) in the period from 1976 to 1994—a percentage that had declined to 5% by 2002.³⁴

The family physician plays pivotal role in JIA care

For the family physician, appropriate initial intervention in the management of JIA is imperative. This includes ordering imaging (whether plain films or MRI), laboratory tests as described earlier (although not to make the diagnosis), and the use of NSAIDs, intra-articular steroids, and other induction agents. Once the diagnosis is made, and a drug regimen is put in place, you will need to monitor for adverse effects. This monitoring will need to occur when a patient is escalated to csDMARDs, biological agents, or systemic steroids; is maintained on an NSAID; or is placed on a combination regimen.

Continue to: Before beginning therapy with a biologic agent...

Before beginning therapy with a biologic agent, it’s important to screen for hepatitis B, hepatitis C, human immunodeficiency virus infection, tuberculosis, and fungal infection (eg, Histoplasma capsulatum, Coccidioides immitis³²). Be sure to make a timely referral to the ophthalmology service for a bi-annual eye exam and, in the event that surgery is necessary, conduct a preoperative evaluation, with the knowledge of how long before surgery a biologic agent must be withheld (duration varies by drug).³²

CORRESPONDENCE
Tobe Momah, MD, Department of Family Medicine, Clinical Science Building, 4th Floor, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; tmomah@umc.edu.

Odds of sudden unexpected infant death (SUID) more than doubled with maternal prenatal smoking and increased linearly with each additional cigarette mothers smoked during pregnancy, but quitting smoking during pregnancy cut SUID risk, according to a new study in Pediatrics.

Jasmin Merdan/fotolia

“As prevalence of prone sleeping has declined, the relative contribution of prenatal maternal smoking to the risk of sudden infant death has increased,” Tatiana M. Anderson, PhD, of the Seattle Children’s Research Institute and her associates reported. When the researchers considered causality, they estimated that approximately 800 infants (22% of all SUID cases) per year in the United States could be attributed to maternal smoking during pregnancy.

The researchers analyzed 19,127 SUID cases among 20,685,463 births included in the Centers for Disease Control and Prevention Birth Cohort Linked Birth/Infant Death Data Set for 2007-2011. A SUID diagnosis included sudden infant death syndrome, infant death from ill-defined or unknown cause, and accidental suffocation or strangulation in bed for any infants under 1 year old.

When the authors calculated odds related to prenatal maternal smoking and SUID, they adjusted for infant sex and birth weight, gestational length of pregnancy, delivery method (vaginal or cesarean), total prenatal visits, live birth order, maternal marital status and education, and maternal and paternal age and race/ethnicity.

Any maternal smoking at all during pregnancy was associated with more than twice the odds of SUID (adjusted odds ratio, 2.44). Odds of SUID also doubled for smoking one cigarette daily during pregnancy versus smoking none. For each additional cigarette smoked daily during pregnancy, odds of SUID increased by 0.07 up until 20 cigarettes, when the risk evened out, which suggests “that smoking cessation efforts may have greater impact on decreasing SUID rates when directed toward those who smoke fewer than 1 pack per day versus the more traditionally targeted heavy ([more than] 20 cigarettes per day) smokers,” the authors wrote.

Odds of SUID dropped 12% when mothers cut down on smoking during pregnancy and dropped 23% when they quit altogether (aORs, 0.88 and 0.77, respectively). “However, there may be some selection bias because the group who reduced smoking started at a higher average number of cigarettes in the first trimester, whereas those who successfully quit smoked fewer cigarettes in the first trimester,” the authors noted.

Among the 11.6% of mothers who said in 2011 that they smoked in the 3 months leading up to pregnancy, only a quarter quit while pregnant, the authors wrote. Quitting after having smoked before pregnancy was linked to a 47% increased risk of SUID, although the researchers noted that second- and third-hand smoke may have played a role since mothers who smoke may begin smoking again post partum and/or often have a partner who smokes.

“This group may have also included women who stopped smoking as soon as they knew they were pregnant and thus reported that they were nonsmokers in the first trimester, but the fetus had been exposed to maternal smoking during the period before pregnancy was diagnosed,” the authors wrote. They also acknowledged the possibility of residual confounding, particularly from socioeconomic factors or alcohol consumption during pregnancy.

The research was funded by the National Institutes of Health, Microsoft, and the Aaron Matthew Sudden Infant Death Syndrome Research Guild. One author has testified as a paid expert in a SUID case. No other authors reported conflicts of interest.

SOURCE: Anderson TM et al. Pediatrics. 2019 March 11. doi: 10.1542/peds.2018-3325.

Odds of sudden unexpected infant death (SUID) more than doubled with maternal prenatal smoking and increased linearly with each additional cigarette mothers smoked during pregnancy, but quitting smoking during pregnancy cut SUID risk, according to a new study in Pediatrics.

Jasmin Merdan/fotolia

“As prevalence of prone sleeping has declined, the relative contribution of prenatal maternal smoking to the risk of sudden infant death has increased,” Tatiana M. Anderson, PhD, of the Seattle Children’s Research Institute and her associates reported. When the researchers considered causality, they estimated that approximately 800 infants (22% of all SUID cases) per year in the United States could be attributed to maternal smoking during pregnancy.

The researchers analyzed 19,127 SUID cases among 20,685,463 births included in the Centers for Disease Control and Prevention Birth Cohort Linked Birth/Infant Death Data Set for 2007-2011. A SUID diagnosis included sudden infant death syndrome, infant death from ill-defined or unknown cause, and accidental suffocation or strangulation in bed for any infants under 1 year old.

When the authors calculated odds related to prenatal maternal smoking and SUID, they adjusted for infant sex and birth weight, gestational length of pregnancy, delivery method (vaginal or cesarean), total prenatal visits, live birth order, maternal marital status and education, and maternal and paternal age and race/ethnicity.

Any maternal smoking at all during pregnancy was associated with more than twice the odds of SUID (adjusted odds ratio, 2.44). Odds of SUID also doubled for smoking one cigarette daily during pregnancy versus smoking none. For each additional cigarette smoked daily during pregnancy, odds of SUID increased by 0.07 up until 20 cigarettes, when the risk evened out, which suggests “that smoking cessation efforts may have greater impact on decreasing SUID rates when directed toward those who smoke fewer than 1 pack per day versus the more traditionally targeted heavy ([more than] 20 cigarettes per day) smokers,” the authors wrote.

Odds of SUID dropped 12% when mothers cut down on smoking during pregnancy and dropped 23% when they quit altogether (aORs, 0.88 and 0.77, respectively). “However, there may be some selection bias because the group who reduced smoking started at a higher average number of cigarettes in the first trimester, whereas those who successfully quit smoked fewer cigarettes in the first trimester,” the authors noted.

Among the 11.6% of mothers who said in 2011 that they smoked in the 3 months leading up to pregnancy, only a quarter quit while pregnant, the authors wrote. Quitting after having smoked before pregnancy was linked to a 47% increased risk of SUID, although the researchers noted that second- and third-hand smoke may have played a role since mothers who smoke may begin smoking again post partum and/or often have a partner who smokes.

“This group may have also included women who stopped smoking as soon as they knew they were pregnant and thus reported that they were nonsmokers in the first trimester, but the fetus had been exposed to maternal smoking during the period before pregnancy was diagnosed,” the authors wrote. They also acknowledged the possibility of residual confounding, particularly from socioeconomic factors or alcohol consumption during pregnancy.

The research was funded by the National Institutes of Health, Microsoft, and the Aaron Matthew Sudden Infant Death Syndrome Research Guild. One author has testified as a paid expert in a SUID case. No other authors reported conflicts of interest.

SOURCE: Anderson TM et al. Pediatrics. 2019 March 11. doi: 10.1542/peds.2018-3325.

Odds of sudden unexpected infant death (SUID) more than doubled with maternal prenatal smoking and increased linearly with each additional cigarette mothers smoked during pregnancy, but quitting smoking during pregnancy cut SUID risk, according to a new study in Pediatrics.

Jasmin Merdan/fotolia

“As prevalence of prone sleeping has declined, the relative contribution of prenatal maternal smoking to the risk of sudden infant death has increased,” Tatiana M. Anderson, PhD, of the Seattle Children’s Research Institute and her associates reported. When the researchers considered causality, they estimated that approximately 800 infants (22% of all SUID cases) per year in the United States could be attributed to maternal smoking during pregnancy.

The researchers analyzed 19,127 SUID cases among 20,685,463 births included in the Centers for Disease Control and Prevention Birth Cohort Linked Birth/Infant Death Data Set for 2007-2011. A SUID diagnosis included sudden infant death syndrome, infant death from ill-defined or unknown cause, and accidental suffocation or strangulation in bed for any infants under 1 year old.

When the authors calculated odds related to prenatal maternal smoking and SUID, they adjusted for infant sex and birth weight, gestational length of pregnancy, delivery method (vaginal or cesarean), total prenatal visits, live birth order, maternal marital status and education, and maternal and paternal age and race/ethnicity.

Any maternal smoking at all during pregnancy was associated with more than twice the odds of SUID (adjusted odds ratio, 2.44). Odds of SUID also doubled for smoking one cigarette daily during pregnancy versus smoking none. For each additional cigarette smoked daily during pregnancy, odds of SUID increased by 0.07 up until 20 cigarettes, when the risk evened out, which suggests “that smoking cessation efforts may have greater impact on decreasing SUID rates when directed toward those who smoke fewer than 1 pack per day versus the more traditionally targeted heavy ([more than] 20 cigarettes per day) smokers,” the authors wrote.

Odds of SUID dropped 12% when mothers cut down on smoking during pregnancy and dropped 23% when they quit altogether (aORs, 0.88 and 0.77, respectively). “However, there may be some selection bias because the group who reduced smoking started at a higher average number of cigarettes in the first trimester, whereas those who successfully quit smoked fewer cigarettes in the first trimester,” the authors noted.

Among the 11.6% of mothers who said in 2011 that they smoked in the 3 months leading up to pregnancy, only a quarter quit while pregnant, the authors wrote. Quitting after having smoked before pregnancy was linked to a 47% increased risk of SUID, although the researchers noted that second- and third-hand smoke may have played a role since mothers who smoke may begin smoking again post partum and/or often have a partner who smokes.

“This group may have also included women who stopped smoking as soon as they knew they were pregnant and thus reported that they were nonsmokers in the first trimester, but the fetus had been exposed to maternal smoking during the period before pregnancy was diagnosed,” the authors wrote. They also acknowledged the possibility of residual confounding, particularly from socioeconomic factors or alcohol consumption during pregnancy.

The research was funded by the National Institutes of Health, Microsoft, and the Aaron Matthew Sudden Infant Death Syndrome Research Guild. One author has testified as a paid expert in a SUID case. No other authors reported conflicts of interest.

SOURCE: Anderson TM et al. Pediatrics. 2019 March 11. doi: 10.1542/peds.2018-3325.

Children whose mothers experienced any type of infection during pregnancy were nearly 80 times more likely to be diagnosed with autism than those whose mothers did not have infections, based on data from more than one million children in Sweden.

Katarzyna Bialasiewicz/Thinkstock

Although previous studies have shown associations between specific infections in utero and specific conditions, such as schizophrenia, “Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” wrote Benjamin J. S. al-Haddad, MD, formerly of Seattle Children’s Hospital, Washington, currently with Doctors without Borders,Katiola, Côte d’Ivoire, and his colleagues.

In a study published In JAMA Psychiatry, the researchers followed 1,791,520 children (48.6% girls) born between Jan. 1, 1973, and Dec. 31, 2014, for up to 41 years using population-based registry data.

Overall, researchers found a 79% increased risk of an autism diagnosis (hazard ratio 1.79) and a 24% increased risk of a depression diagnosis (HR 1.24) for individuals exposed to any maternal infection in utero compared with those not exposed.

Similar increases in risk appeared when the data were broken down by type of infection. Hazard ratios for an autism diagnosis were 1.81 for exposure to a severe maternal infection and 1.89 for a maternal urinary tract infection; hazard ratios for depression were 1.24 and 1.30, respectively, for severe maternal infection and maternal urinary tract infection.

No increased risk in bipolar disorder, or other psychoses including schizophrenia were observed.

The findings were limited by several factors including the inclusion only of infections diagnosed in a hospital setting, and thus may not be generalizable to infections diagnosed in an outpatient setting, the researchers noted. However, the results “amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (such as by influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they said.

The researchers had no conflicts to disclose. The study was funded by grants from several organizations including the National Institutes of Health.

SOURCE: al-Haddad BJS et al. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0029.

Children whose mothers experienced any type of infection during pregnancy were nearly 80 times more likely to be diagnosed with autism than those whose mothers did not have infections, based on data from more than one million children in Sweden.

Katarzyna Bialasiewicz/Thinkstock

Although previous studies have shown associations between specific infections in utero and specific conditions, such as schizophrenia, “Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” wrote Benjamin J. S. al-Haddad, MD, formerly of Seattle Children’s Hospital, Washington, currently with Doctors without Borders,Katiola, Côte d’Ivoire, and his colleagues.

In a study published In JAMA Psychiatry, the researchers followed 1,791,520 children (48.6% girls) born between Jan. 1, 1973, and Dec. 31, 2014, for up to 41 years using population-based registry data.

Overall, researchers found a 79% increased risk of an autism diagnosis (hazard ratio 1.79) and a 24% increased risk of a depression diagnosis (HR 1.24) for individuals exposed to any maternal infection in utero compared with those not exposed.

Similar increases in risk appeared when the data were broken down by type of infection. Hazard ratios for an autism diagnosis were 1.81 for exposure to a severe maternal infection and 1.89 for a maternal urinary tract infection; hazard ratios for depression were 1.24 and 1.30, respectively, for severe maternal infection and maternal urinary tract infection.

No increased risk in bipolar disorder, or other psychoses including schizophrenia were observed.

The findings were limited by several factors including the inclusion only of infections diagnosed in a hospital setting, and thus may not be generalizable to infections diagnosed in an outpatient setting, the researchers noted. However, the results “amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (such as by influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they said.

The researchers had no conflicts to disclose. The study was funded by grants from several organizations including the National Institutes of Health.

SOURCE: al-Haddad BJS et al. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0029.

Children whose mothers experienced any type of infection during pregnancy were nearly 80 times more likely to be diagnosed with autism than those whose mothers did not have infections, based on data from more than one million children in Sweden.

Katarzyna Bialasiewicz/Thinkstock

Although previous studies have shown associations between specific infections in utero and specific conditions, such as schizophrenia, “Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” wrote Benjamin J. S. al-Haddad, MD, formerly of Seattle Children’s Hospital, Washington, currently with Doctors without Borders,Katiola, Côte d’Ivoire, and his colleagues.

In a study published In JAMA Psychiatry, the researchers followed 1,791,520 children (48.6% girls) born between Jan. 1, 1973, and Dec. 31, 2014, for up to 41 years using population-based registry data.

Overall, researchers found a 79% increased risk of an autism diagnosis (hazard ratio 1.79) and a 24% increased risk of a depression diagnosis (HR 1.24) for individuals exposed to any maternal infection in utero compared with those not exposed.

Similar increases in risk appeared when the data were broken down by type of infection. Hazard ratios for an autism diagnosis were 1.81 for exposure to a severe maternal infection and 1.89 for a maternal urinary tract infection; hazard ratios for depression were 1.24 and 1.30, respectively, for severe maternal infection and maternal urinary tract infection.

No increased risk in bipolar disorder, or other psychoses including schizophrenia were observed.

The findings were limited by several factors including the inclusion only of infections diagnosed in a hospital setting, and thus may not be generalizable to infections diagnosed in an outpatient setting, the researchers noted. However, the results “amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (such as by influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they said.

The researchers had no conflicts to disclose. The study was funded by grants from several organizations including the National Institutes of Health.

SOURCE: al-Haddad BJS et al. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0029.

More sleep can lead to better glycemic control in youth with type 1 diabetes mellitus, according to a study of sleep duration and quality in young diabetes patients.

Jovanmandic/Getty Images

“This study adds to the growing body of literature that supports the cascading effects of sleep on multiple aspects of diabetes-related outcomes,” wrote lead author Sara S. Frye, PhD, of the University of Arizona, Tucson, and her coauthors, adding that the results “highlight the importance of assessing sleep in this population that appears to be at high risk for insufficient sleep duration.” The study was published in Sleep Medicine.

Dr. Frye and her colleagues recruited 111 children between the ages of 10 and 16 with type 1 diabetes mellitus to participate in their Glucose Regulation and Neurobehavioral Effects of Sleep (GRANES) study. The participants wore wrist actigraphs for an average of 5.5 nights to objectively measure sleep, including duration, quality, timing, and consistency. They completed self-reported sleep diaries each morning of the study. Glycemic control and diabetes management were assessed via hemoglobin A_1c (HbA_1c) levels and self-monitoring of blood glucose (SMBG) frequency, which were obtained via medical records. The participants and their parents also completed the Diabetes Management Scale.

Based on actigraphy data, the average total sleep time was 7.45 hours (standard deviation, 0.74), below the recommended duration of 9 hours for youths in this age group. All but one participant was recorded as sleeping less than the recommended amount. Average HbA_1c of 9.11% (SD, 1.95) indicated poor diabetic control, and the average SMBG frequency was 4.90 (SD, 2.71) with a range of 1-14 checks per day. Per mediation analysis, for every additional hour of sleep, HbA_1c was reduced by 0.33% and SMBG frequency went up by 0.88. In addition, SMBG frequency was related to HbA_1c, supporting previous findings that “self-management behaviors play a critical role in maintaining diabetes control.”

The coauthors acknowledged the limitations of their study, including actigraphy data being logged over a 1-week period instead of the recommended 2 weeks. They also relied on medical records to determine HbA_1c and SMBG rather than collecting that information along with the actigraphy data. However, they did note that HbA1c measures glucose levels over a 3-month period, which would have covered their participation in the study.

The study was supported by American Diabetes Association and cosponsored by the Order of the Amaranth Diabetes Foundation. The authors reported no conflicts of interest.

SOURCE: Frye SS et al. Sleep Med. 2019 Feb 16. doi: 10.1016/j.sleep.2019.01.043.

More sleep can lead to better glycemic control in youth with type 1 diabetes mellitus, according to a study of sleep duration and quality in young diabetes patients.

Jovanmandic/Getty Images

“This study adds to the growing body of literature that supports the cascading effects of sleep on multiple aspects of diabetes-related outcomes,” wrote lead author Sara S. Frye, PhD, of the University of Arizona, Tucson, and her coauthors, adding that the results “highlight the importance of assessing sleep in this population that appears to be at high risk for insufficient sleep duration.” The study was published in Sleep Medicine.

Dr. Frye and her colleagues recruited 111 children between the ages of 10 and 16 with type 1 diabetes mellitus to participate in their Glucose Regulation and Neurobehavioral Effects of Sleep (GRANES) study. The participants wore wrist actigraphs for an average of 5.5 nights to objectively measure sleep, including duration, quality, timing, and consistency. They completed self-reported sleep diaries each morning of the study. Glycemic control and diabetes management were assessed via hemoglobin A_1c (HbA_1c) levels and self-monitoring of blood glucose (SMBG) frequency, which were obtained via medical records. The participants and their parents also completed the Diabetes Management Scale.

Based on actigraphy data, the average total sleep time was 7.45 hours (standard deviation, 0.74), below the recommended duration of 9 hours for youths in this age group. All but one participant was recorded as sleeping less than the recommended amount. Average HbA_1c of 9.11% (SD, 1.95) indicated poor diabetic control, and the average SMBG frequency was 4.90 (SD, 2.71) with a range of 1-14 checks per day. Per mediation analysis, for every additional hour of sleep, HbA_1c was reduced by 0.33% and SMBG frequency went up by 0.88. In addition, SMBG frequency was related to HbA_1c, supporting previous findings that “self-management behaviors play a critical role in maintaining diabetes control.”

The coauthors acknowledged the limitations of their study, including actigraphy data being logged over a 1-week period instead of the recommended 2 weeks. They also relied on medical records to determine HbA_1c and SMBG rather than collecting that information along with the actigraphy data. However, they did note that HbA1c measures glucose levels over a 3-month period, which would have covered their participation in the study.

The study was supported by American Diabetes Association and cosponsored by the Order of the Amaranth Diabetes Foundation. The authors reported no conflicts of interest.

SOURCE: Frye SS et al. Sleep Med. 2019 Feb 16. doi: 10.1016/j.sleep.2019.01.043.

More sleep can lead to better glycemic control in youth with type 1 diabetes mellitus, according to a study of sleep duration and quality in young diabetes patients.

Jovanmandic/Getty Images

“This study adds to the growing body of literature that supports the cascading effects of sleep on multiple aspects of diabetes-related outcomes,” wrote lead author Sara S. Frye, PhD, of the University of Arizona, Tucson, and her coauthors, adding that the results “highlight the importance of assessing sleep in this population that appears to be at high risk for insufficient sleep duration.” The study was published in Sleep Medicine.

Dr. Frye and her colleagues recruited 111 children between the ages of 10 and 16 with type 1 diabetes mellitus to participate in their Glucose Regulation and Neurobehavioral Effects of Sleep (GRANES) study. The participants wore wrist actigraphs for an average of 5.5 nights to objectively measure sleep, including duration, quality, timing, and consistency. They completed self-reported sleep diaries each morning of the study. Glycemic control and diabetes management were assessed via hemoglobin A_1c (HbA_1c) levels and self-monitoring of blood glucose (SMBG) frequency, which were obtained via medical records. The participants and their parents also completed the Diabetes Management Scale.

Based on actigraphy data, the average total sleep time was 7.45 hours (standard deviation, 0.74), below the recommended duration of 9 hours for youths in this age group. All but one participant was recorded as sleeping less than the recommended amount. Average HbA_1c of 9.11% (SD, 1.95) indicated poor diabetic control, and the average SMBG frequency was 4.90 (SD, 2.71) with a range of 1-14 checks per day. Per mediation analysis, for every additional hour of sleep, HbA_1c was reduced by 0.33% and SMBG frequency went up by 0.88. In addition, SMBG frequency was related to HbA_1c, supporting previous findings that “self-management behaviors play a critical role in maintaining diabetes control.”

The coauthors acknowledged the limitations of their study, including actigraphy data being logged over a 1-week period instead of the recommended 2 weeks. They also relied on medical records to determine HbA_1c and SMBG rather than collecting that information along with the actigraphy data. However, they did note that HbA1c measures glucose levels over a 3-month period, which would have covered their participation in the study.

The study was supported by American Diabetes Association and cosponsored by the Order of the Amaranth Diabetes Foundation. The authors reported no conflicts of interest.

SOURCE: Frye SS et al. Sleep Med. 2019 Feb 16. doi: 10.1016/j.sleep.2019.01.043.

Smoking a water pipe, or hookah, can result in significant inhalation of toxins and an increased risk for short- and long-term cardiovascular health problems, according to a scientific statement issued by the American Heart Association on March 8.

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In the statement, published in the journal Circulation, Aruni Bhatnagar, PhD, of the University of Louisville (Ky.) and his colleagues reviewed the potential dangers of water pipe use and offered strategies for prevention.

Data from the 2016 National Youth Tobacco Survey showed that current use (defined as use within the past 30 days) of water pipes by high school students increased in a nonlinear trend from 4.1% in 2011 to 4.8% in 2016, with a peak of 9.4% in 2014. Water pipe tobacco is sold in flavors such as cherry, chocolate, and coffee that appeal to younger consumers, and epidemiology data suggest that youth view water pipes as safer than conventional cigarettes because the water “filters out toxins” according to the statement.

Findings from the National Adult Tobacco Survey showed an increase as well, from 1.5% during 2009-2010 to 3.2% during 2013-2014. Adults cite cultural and social influences, as well as psychological benefits of reduced stress and anger and improved concentration, which may be attributable to nicotine, the researchers noted.

Water pipe smoking involves placing charcoal briquettes on top of a tobacco-filled bowl with a stem immersed in water such that the smoke is pulled through and bubbles up through the water into a mouthpiece. The harmful or potentially harmful constituents (HPHCs) involved in water pipe are similar to those in standard cigarettes and include tar, phenanthrene, carbon monoxide, heavy metals, and arsenic, as well as nicotine.

The patterns of exposure to toxins during water pipe smoking are unclear, the authors noted.

However, the risks for both short-term and long-term health effects are similar to those associated with cigarettes. “Overall, the short-term cardiovascular effects are consistent with the sympathomimetic effects of nicotine,” according to the statement.

Data on the long-term effects of water pipe smoking on cardiovascular health are limited, but “lifetime exposures exceeding 40 water pipe–years (2 water pipes per day for a total of 20 years or 1 water pipe for 40 years) are associated with a threefold increase in the odds of angiographically diagnosed coronary artery stenosis,” according to the statement. Additional research on long-term health effects may help guide regulation of water pipe products, the authors suggested.

The AHA statement encourages health care providers to take a proactive approach in addressing hookah use by asking patients about it, by advising those who use water pipes to quit, by assisting those who want to quit by providing counseling and social support, and by referring water pipe smokers to legitimate resources for information on the potential for addiction and health risks.

Dr. Bhatnagar received funding from the National Institutes of Health, but he had no other financial conflicts to disclose.

SOURCE: Bhatnagar A et al. Circulation. 2019 Mar 8. doi: 10.1161/CIR.0000000000000671.

Smoking a water pipe, or hookah, can result in significant inhalation of toxins and an increased risk for short- and long-term cardiovascular health problems, according to a scientific statement issued by the American Heart Association on March 8.

Gina Smith/Thinkstock

In the statement, published in the journal Circulation, Aruni Bhatnagar, PhD, of the University of Louisville (Ky.) and his colleagues reviewed the potential dangers of water pipe use and offered strategies for prevention.

Data from the 2016 National Youth Tobacco Survey showed that current use (defined as use within the past 30 days) of water pipes by high school students increased in a nonlinear trend from 4.1% in 2011 to 4.8% in 2016, with a peak of 9.4% in 2014. Water pipe tobacco is sold in flavors such as cherry, chocolate, and coffee that appeal to younger consumers, and epidemiology data suggest that youth view water pipes as safer than conventional cigarettes because the water “filters out toxins” according to the statement.

Findings from the National Adult Tobacco Survey showed an increase as well, from 1.5% during 2009-2010 to 3.2% during 2013-2014. Adults cite cultural and social influences, as well as psychological benefits of reduced stress and anger and improved concentration, which may be attributable to nicotine, the researchers noted.

Water pipe smoking involves placing charcoal briquettes on top of a tobacco-filled bowl with a stem immersed in water such that the smoke is pulled through and bubbles up through the water into a mouthpiece. The harmful or potentially harmful constituents (HPHCs) involved in water pipe are similar to those in standard cigarettes and include tar, phenanthrene, carbon monoxide, heavy metals, and arsenic, as well as nicotine.

The patterns of exposure to toxins during water pipe smoking are unclear, the authors noted.

However, the risks for both short-term and long-term health effects are similar to those associated with cigarettes. “Overall, the short-term cardiovascular effects are consistent with the sympathomimetic effects of nicotine,” according to the statement.

Data on the long-term effects of water pipe smoking on cardiovascular health are limited, but “lifetime exposures exceeding 40 water pipe–years (2 water pipes per day for a total of 20 years or 1 water pipe for 40 years) are associated with a threefold increase in the odds of angiographically diagnosed coronary artery stenosis,” according to the statement. Additional research on long-term health effects may help guide regulation of water pipe products, the authors suggested.

The AHA statement encourages health care providers to take a proactive approach in addressing hookah use by asking patients about it, by advising those who use water pipes to quit, by assisting those who want to quit by providing counseling and social support, and by referring water pipe smokers to legitimate resources for information on the potential for addiction and health risks.

Dr. Bhatnagar received funding from the National Institutes of Health, but he had no other financial conflicts to disclose.

SOURCE: Bhatnagar A et al. Circulation. 2019 Mar 8. doi: 10.1161/CIR.0000000000000671.

Smoking a water pipe, or hookah, can result in significant inhalation of toxins and an increased risk for short- and long-term cardiovascular health problems, according to a scientific statement issued by the American Heart Association on March 8.

Gina Smith/Thinkstock

In the statement, published in the journal Circulation, Aruni Bhatnagar, PhD, of the University of Louisville (Ky.) and his colleagues reviewed the potential dangers of water pipe use and offered strategies for prevention.

Data from the 2016 National Youth Tobacco Survey showed that current use (defined as use within the past 30 days) of water pipes by high school students increased in a nonlinear trend from 4.1% in 2011 to 4.8% in 2016, with a peak of 9.4% in 2014. Water pipe tobacco is sold in flavors such as cherry, chocolate, and coffee that appeal to younger consumers, and epidemiology data suggest that youth view water pipes as safer than conventional cigarettes because the water “filters out toxins” according to the statement.

Findings from the National Adult Tobacco Survey showed an increase as well, from 1.5% during 2009-2010 to 3.2% during 2013-2014. Adults cite cultural and social influences, as well as psychological benefits of reduced stress and anger and improved concentration, which may be attributable to nicotine, the researchers noted.

Water pipe smoking involves placing charcoal briquettes on top of a tobacco-filled bowl with a stem immersed in water such that the smoke is pulled through and bubbles up through the water into a mouthpiece. The harmful or potentially harmful constituents (HPHCs) involved in water pipe are similar to those in standard cigarettes and include tar, phenanthrene, carbon monoxide, heavy metals, and arsenic, as well as nicotine.

The patterns of exposure to toxins during water pipe smoking are unclear, the authors noted.

However, the risks for both short-term and long-term health effects are similar to those associated with cigarettes. “Overall, the short-term cardiovascular effects are consistent with the sympathomimetic effects of nicotine,” according to the statement.

Data on the long-term effects of water pipe smoking on cardiovascular health are limited, but “lifetime exposures exceeding 40 water pipe–years (2 water pipes per day for a total of 20 years or 1 water pipe for 40 years) are associated with a threefold increase in the odds of angiographically diagnosed coronary artery stenosis,” according to the statement. Additional research on long-term health effects may help guide regulation of water pipe products, the authors suggested.

The AHA statement encourages health care providers to take a proactive approach in addressing hookah use by asking patients about it, by advising those who use water pipes to quit, by assisting those who want to quit by providing counseling and social support, and by referring water pipe smokers to legitimate resources for information on the potential for addiction and health risks.

Dr. Bhatnagar received funding from the National Institutes of Health, but he had no other financial conflicts to disclose.

SOURCE: Bhatnagar A et al. Circulation. 2019 Mar 8. doi: 10.1161/CIR.0000000000000671.