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Children with Down syndrome may need more screening for sleep-disordered breathing
because the condition frequently persists and recurs.
“Current screening recommendations to assess for SDB at a particular age may not be adequate in this population,” the authors of the study stated, adding that “persistence/recurrence of SDB is not easily predicted.”
The study, led by Joy Nehme, BSc, of Children’s Hospital of Eastern Ontario and the University of Ottawa, was published in Pediatric Pulmonology.
According to the study, research suggests that 43%-66% of children with Down syndrome have SDB, a category that encompasses sleep apnea (both obstructive and central) and hypoventilation. Those numbers are several times higher than the prevalence of SDB in children in the general population (1%-5%).
“Because SDB is associated with cardiometabolic and neurocognitive morbidity, its prompt and accurate diagnosis is important,” the researchers wrote. However, diagnosis requires a sleep study, which is not always performed although the American Academy of Pediatrics recommends children with Down syndrome undergo one by age 4.
Treatments include adenotonsillectomy (considered first-line), positive airway pressure, and lingual tonsillectomy.
The study aims to fill in gaps in knowledge about the condition over the long term since “there is little available literature on the trajectory of SDB in children and youth with Down syndrome over time.”
The researchers launched a retrospective study of 560 children with Down syndrome who were treated from 2004 to 2015 at Children’s Hospital of Eastern Ontario. Of those, 120 showed signs of SDB and underwent sleep studies (48% male, median age 6.6 years [range 4.5-10.5], median total apnea‐hypopnea index events per hour = 3.4 [1.6-10.8]).
Of the 120 children, 67 (56%) had obstructive-mixed SDB, 9 (8%) had central sleep apnea, and 5 (4%) had hypoventilation. The others (39, 32%) had no SDB.
Fifty-four children underwent at least two sleep studies during the period of the study, with at least one undergoing seven.
Researchers found weak, nonsignificant evidence that SDB persistence/occurrence varied by age (odds ratio per year = 1.15; 95% confidence interval, 0.96-1.41; P = .13).
As for treatment, adenotonsillectomy was most common, although “previous studies have ... shown that moderate to severe OSA in children with Down syndrome is likely to persist after a tonsillectomy.”
In regard to obstructive sleep apnea (OSA) specifically, the authors wrote, “our study ... showed that OSA‐SDB persisted or recurred in the vast majority of children. Further, persistence/recurrence could not be predicted by clinical features or SDB severity in our study. This, therefore, highlights the need for serial longitudinal screening for SDB in this population and for follow‐up PSG to ensure the success of treatment interventions.”
No study funding was reported. The study authors reported no disclosures.
SOURCE: Nehme J et al. Pediatr Pulmonol. 2019 Jun 6. doi: 10.1002/ppul.24380.
because the condition frequently persists and recurs.
“Current screening recommendations to assess for SDB at a particular age may not be adequate in this population,” the authors of the study stated, adding that “persistence/recurrence of SDB is not easily predicted.”
The study, led by Joy Nehme, BSc, of Children’s Hospital of Eastern Ontario and the University of Ottawa, was published in Pediatric Pulmonology.
According to the study, research suggests that 43%-66% of children with Down syndrome have SDB, a category that encompasses sleep apnea (both obstructive and central) and hypoventilation. Those numbers are several times higher than the prevalence of SDB in children in the general population (1%-5%).
“Because SDB is associated with cardiometabolic and neurocognitive morbidity, its prompt and accurate diagnosis is important,” the researchers wrote. However, diagnosis requires a sleep study, which is not always performed although the American Academy of Pediatrics recommends children with Down syndrome undergo one by age 4.
Treatments include adenotonsillectomy (considered first-line), positive airway pressure, and lingual tonsillectomy.
The study aims to fill in gaps in knowledge about the condition over the long term since “there is little available literature on the trajectory of SDB in children and youth with Down syndrome over time.”
The researchers launched a retrospective study of 560 children with Down syndrome who were treated from 2004 to 2015 at Children’s Hospital of Eastern Ontario. Of those, 120 showed signs of SDB and underwent sleep studies (48% male, median age 6.6 years [range 4.5-10.5], median total apnea‐hypopnea index events per hour = 3.4 [1.6-10.8]).
Of the 120 children, 67 (56%) had obstructive-mixed SDB, 9 (8%) had central sleep apnea, and 5 (4%) had hypoventilation. The others (39, 32%) had no SDB.
Fifty-four children underwent at least two sleep studies during the period of the study, with at least one undergoing seven.
Researchers found weak, nonsignificant evidence that SDB persistence/occurrence varied by age (odds ratio per year = 1.15; 95% confidence interval, 0.96-1.41; P = .13).
As for treatment, adenotonsillectomy was most common, although “previous studies have ... shown that moderate to severe OSA in children with Down syndrome is likely to persist after a tonsillectomy.”
In regard to obstructive sleep apnea (OSA) specifically, the authors wrote, “our study ... showed that OSA‐SDB persisted or recurred in the vast majority of children. Further, persistence/recurrence could not be predicted by clinical features or SDB severity in our study. This, therefore, highlights the need for serial longitudinal screening for SDB in this population and for follow‐up PSG to ensure the success of treatment interventions.”
No study funding was reported. The study authors reported no disclosures.
SOURCE: Nehme J et al. Pediatr Pulmonol. 2019 Jun 6. doi: 10.1002/ppul.24380.
because the condition frequently persists and recurs.
“Current screening recommendations to assess for SDB at a particular age may not be adequate in this population,” the authors of the study stated, adding that “persistence/recurrence of SDB is not easily predicted.”
The study, led by Joy Nehme, BSc, of Children’s Hospital of Eastern Ontario and the University of Ottawa, was published in Pediatric Pulmonology.
According to the study, research suggests that 43%-66% of children with Down syndrome have SDB, a category that encompasses sleep apnea (both obstructive and central) and hypoventilation. Those numbers are several times higher than the prevalence of SDB in children in the general population (1%-5%).
“Because SDB is associated with cardiometabolic and neurocognitive morbidity, its prompt and accurate diagnosis is important,” the researchers wrote. However, diagnosis requires a sleep study, which is not always performed although the American Academy of Pediatrics recommends children with Down syndrome undergo one by age 4.
Treatments include adenotonsillectomy (considered first-line), positive airway pressure, and lingual tonsillectomy.
The study aims to fill in gaps in knowledge about the condition over the long term since “there is little available literature on the trajectory of SDB in children and youth with Down syndrome over time.”
The researchers launched a retrospective study of 560 children with Down syndrome who were treated from 2004 to 2015 at Children’s Hospital of Eastern Ontario. Of those, 120 showed signs of SDB and underwent sleep studies (48% male, median age 6.6 years [range 4.5-10.5], median total apnea‐hypopnea index events per hour = 3.4 [1.6-10.8]).
Of the 120 children, 67 (56%) had obstructive-mixed SDB, 9 (8%) had central sleep apnea, and 5 (4%) had hypoventilation. The others (39, 32%) had no SDB.
Fifty-four children underwent at least two sleep studies during the period of the study, with at least one undergoing seven.
Researchers found weak, nonsignificant evidence that SDB persistence/occurrence varied by age (odds ratio per year = 1.15; 95% confidence interval, 0.96-1.41; P = .13).
As for treatment, adenotonsillectomy was most common, although “previous studies have ... shown that moderate to severe OSA in children with Down syndrome is likely to persist after a tonsillectomy.”
In regard to obstructive sleep apnea (OSA) specifically, the authors wrote, “our study ... showed that OSA‐SDB persisted or recurred in the vast majority of children. Further, persistence/recurrence could not be predicted by clinical features or SDB severity in our study. This, therefore, highlights the need for serial longitudinal screening for SDB in this population and for follow‐up PSG to ensure the success of treatment interventions.”
No study funding was reported. The study authors reported no disclosures.
SOURCE: Nehme J et al. Pediatr Pulmonol. 2019 Jun 6. doi: 10.1002/ppul.24380.
FROM PEDIATRIC PULMONOLOGY
Key clinical point: Sleep-disordered breathing (SDB) can be persistent and recurrent in children with Down syndrome, and long-term monitoring is warranted.
Major finding: SDB persistence/recurrence did not vary by age (odds ratio per year = 1.15; 95% confidence interval, 0.96-1.41; P = .13).
Study details: Retrospective cohort analysis of 120 children with Down syndrome tested via sleep study at least once for SDB (48% male, median age 6.6 years).
Disclosures: No study funding or author disclosures were reported.
Source: Nehme J et al. Pediatr Pulmonol. 2019 Jun 6. doi: 10.1002/ppul.24380.
Efforts toward producing CNO/CRMO classification criteria show first results
MADRID – according to recent findings from international surveys of pediatric rheumatologists that were presented at the European Congress of Rheumatology.
Melissa Oliver, MD, a pediatric rheumatologist at Riley Hospital for Children, Indianapolis, and colleagues recently undertook the multiphase study as part of an international collaborative effort led by the Childhood Arthritis and Rheumatology Research Alliance to establish consensus-based diagnostic and classification criteria for CNO, an autoinflammatory bone disease of unknown cause that primarily affects children and adolescents. CNO is also known as chronic recurrent multifocal osteomyelitis (CRMO). If this disease is not diagnosed and treated appropriately in a timely fashion, damage and long-term disability is possible. In the absence of widely accepted, consensus-driven criteria, treatment is based largely on expert opinion, Dr. Oliver explained in an interview.
“There is an urgent need for a new and more robust set of classification criteria for CRMO, based on large expert consensus and the analysis of a large sample of patients and controls,” she said.
There are two proposed diagnostic criteria, the 2007 classification of nonbacterial osteitis and the 2016 Bristol diagnostic criteria for CRMO, but both are derived from single-center cohort studies and have not been validated, Dr. Oliver explained.
The list of candidate items that have come out of the study is moving clinicians a step closer toward the design of a practical patient data collection form that appropriately weighs each item included in the classification criteria.
The study employed anonymous survey and nominal group techniques with the goal of developing a set of classification criteria sensitive and specific enough to identify CRMO/CNO patients. In phase 1, a Delphi survey was administered among international rheumatologists to generate candidate criteria items. Phase 2 sought to reduce candidate criteria items through consensus processes via input from physicians managing CNO and patients or caregivers of children with CNO.
Altogether, 259 of 865 pediatric rheumatologists (30%) completed an online questionnaire addressing features key to the classification of CNO, including 77 who practice in Europe (30%), 132 in North America (51%), and 50 on other continents (19%). Of these, 138 (53%) had greater than 10 years of clinical practice experience, and 108 (42%) had managed more than 10 CNO patients.
Initially, Dr. Oliver and colleagues identified 33 candidate criteria items that fell into six domains: clinical presentation, physical exam, laboratory findings, imaging findings, bone biopsy, and treatment response. The top eight weighted items that increased the likelihood of CNO/CRMO were exclusion of malignancy by bone biopsy; multifocal bone lesions; presence of bone pain, swelling, and/or warmth; signs of fibrosis and/or inflammation on bone biopsy; typical location of CNO/CRMO lesion, such as the clavicle, metaphysis of long bones, the mandible, and vertebrae; presence of CNO/CRMO–related comorbidities; normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR); and typical MRI findings of CNO/CRMO.
By phase 2, candidate items, which were presented to 39 rheumatologists and 7 parents, were refined or eliminated using item-reduction techniques. A second survey was issued to 77 of 82 members of a work group so that the remaining items could be ranked by their power of distinguishing CNO from conditions that merely mimicked the disease. The greatest mean discriminatory scores were identified with multifocal lesions (ruling out malignancy and infection) and typical location on imaging. Normal C-reactive protein and/or an erythrocyte sedimentation rate more than three times the upper limit of normal had the greatest negative mean discriminatory scores.
The next steps will be to form an expert panel who will use 1000minds software to determine the final criteria and identify a threshold for disease. The investigators hope to build a large multinational case repository of at least 500 patients with CNO/CRMO and 500 patients with mimicking conditions from which to derive a development cohort and an external validation cohort. So far, 10 sites, including 4 in Europe, have obtained approval from an institutional review board. The group has also submitted a proposal for classification criteria to the American College of Rheumatology and the European League Against Rheumatism, Dr. Oliver said.
Dr. Oliver had no disclosures to report, but several coauthors reported financial ties to industry.
SOURCE: Oliver M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):254-5, Abstract OP0342. doi: 10.1136/annrheumdis-2019-eular.1539.
MADRID – according to recent findings from international surveys of pediatric rheumatologists that were presented at the European Congress of Rheumatology.
Melissa Oliver, MD, a pediatric rheumatologist at Riley Hospital for Children, Indianapolis, and colleagues recently undertook the multiphase study as part of an international collaborative effort led by the Childhood Arthritis and Rheumatology Research Alliance to establish consensus-based diagnostic and classification criteria for CNO, an autoinflammatory bone disease of unknown cause that primarily affects children and adolescents. CNO is also known as chronic recurrent multifocal osteomyelitis (CRMO). If this disease is not diagnosed and treated appropriately in a timely fashion, damage and long-term disability is possible. In the absence of widely accepted, consensus-driven criteria, treatment is based largely on expert opinion, Dr. Oliver explained in an interview.
“There is an urgent need for a new and more robust set of classification criteria for CRMO, based on large expert consensus and the analysis of a large sample of patients and controls,” she said.
There are two proposed diagnostic criteria, the 2007 classification of nonbacterial osteitis and the 2016 Bristol diagnostic criteria for CRMO, but both are derived from single-center cohort studies and have not been validated, Dr. Oliver explained.
The list of candidate items that have come out of the study is moving clinicians a step closer toward the design of a practical patient data collection form that appropriately weighs each item included in the classification criteria.
The study employed anonymous survey and nominal group techniques with the goal of developing a set of classification criteria sensitive and specific enough to identify CRMO/CNO patients. In phase 1, a Delphi survey was administered among international rheumatologists to generate candidate criteria items. Phase 2 sought to reduce candidate criteria items through consensus processes via input from physicians managing CNO and patients or caregivers of children with CNO.
Altogether, 259 of 865 pediatric rheumatologists (30%) completed an online questionnaire addressing features key to the classification of CNO, including 77 who practice in Europe (30%), 132 in North America (51%), and 50 on other continents (19%). Of these, 138 (53%) had greater than 10 years of clinical practice experience, and 108 (42%) had managed more than 10 CNO patients.
Initially, Dr. Oliver and colleagues identified 33 candidate criteria items that fell into six domains: clinical presentation, physical exam, laboratory findings, imaging findings, bone biopsy, and treatment response. The top eight weighted items that increased the likelihood of CNO/CRMO were exclusion of malignancy by bone biopsy; multifocal bone lesions; presence of bone pain, swelling, and/or warmth; signs of fibrosis and/or inflammation on bone biopsy; typical location of CNO/CRMO lesion, such as the clavicle, metaphysis of long bones, the mandible, and vertebrae; presence of CNO/CRMO–related comorbidities; normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR); and typical MRI findings of CNO/CRMO.
By phase 2, candidate items, which were presented to 39 rheumatologists and 7 parents, were refined or eliminated using item-reduction techniques. A second survey was issued to 77 of 82 members of a work group so that the remaining items could be ranked by their power of distinguishing CNO from conditions that merely mimicked the disease. The greatest mean discriminatory scores were identified with multifocal lesions (ruling out malignancy and infection) and typical location on imaging. Normal C-reactive protein and/or an erythrocyte sedimentation rate more than three times the upper limit of normal had the greatest negative mean discriminatory scores.
The next steps will be to form an expert panel who will use 1000minds software to determine the final criteria and identify a threshold for disease. The investigators hope to build a large multinational case repository of at least 500 patients with CNO/CRMO and 500 patients with mimicking conditions from which to derive a development cohort and an external validation cohort. So far, 10 sites, including 4 in Europe, have obtained approval from an institutional review board. The group has also submitted a proposal for classification criteria to the American College of Rheumatology and the European League Against Rheumatism, Dr. Oliver said.
Dr. Oliver had no disclosures to report, but several coauthors reported financial ties to industry.
SOURCE: Oliver M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):254-5, Abstract OP0342. doi: 10.1136/annrheumdis-2019-eular.1539.
MADRID – according to recent findings from international surveys of pediatric rheumatologists that were presented at the European Congress of Rheumatology.
Melissa Oliver, MD, a pediatric rheumatologist at Riley Hospital for Children, Indianapolis, and colleagues recently undertook the multiphase study as part of an international collaborative effort led by the Childhood Arthritis and Rheumatology Research Alliance to establish consensus-based diagnostic and classification criteria for CNO, an autoinflammatory bone disease of unknown cause that primarily affects children and adolescents. CNO is also known as chronic recurrent multifocal osteomyelitis (CRMO). If this disease is not diagnosed and treated appropriately in a timely fashion, damage and long-term disability is possible. In the absence of widely accepted, consensus-driven criteria, treatment is based largely on expert opinion, Dr. Oliver explained in an interview.
“There is an urgent need for a new and more robust set of classification criteria for CRMO, based on large expert consensus and the analysis of a large sample of patients and controls,” she said.
There are two proposed diagnostic criteria, the 2007 classification of nonbacterial osteitis and the 2016 Bristol diagnostic criteria for CRMO, but both are derived from single-center cohort studies and have not been validated, Dr. Oliver explained.
The list of candidate items that have come out of the study is moving clinicians a step closer toward the design of a practical patient data collection form that appropriately weighs each item included in the classification criteria.
The study employed anonymous survey and nominal group techniques with the goal of developing a set of classification criteria sensitive and specific enough to identify CRMO/CNO patients. In phase 1, a Delphi survey was administered among international rheumatologists to generate candidate criteria items. Phase 2 sought to reduce candidate criteria items through consensus processes via input from physicians managing CNO and patients or caregivers of children with CNO.
Altogether, 259 of 865 pediatric rheumatologists (30%) completed an online questionnaire addressing features key to the classification of CNO, including 77 who practice in Europe (30%), 132 in North America (51%), and 50 on other continents (19%). Of these, 138 (53%) had greater than 10 years of clinical practice experience, and 108 (42%) had managed more than 10 CNO patients.
Initially, Dr. Oliver and colleagues identified 33 candidate criteria items that fell into six domains: clinical presentation, physical exam, laboratory findings, imaging findings, bone biopsy, and treatment response. The top eight weighted items that increased the likelihood of CNO/CRMO were exclusion of malignancy by bone biopsy; multifocal bone lesions; presence of bone pain, swelling, and/or warmth; signs of fibrosis and/or inflammation on bone biopsy; typical location of CNO/CRMO lesion, such as the clavicle, metaphysis of long bones, the mandible, and vertebrae; presence of CNO/CRMO–related comorbidities; normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR); and typical MRI findings of CNO/CRMO.
By phase 2, candidate items, which were presented to 39 rheumatologists and 7 parents, were refined or eliminated using item-reduction techniques. A second survey was issued to 77 of 82 members of a work group so that the remaining items could be ranked by their power of distinguishing CNO from conditions that merely mimicked the disease. The greatest mean discriminatory scores were identified with multifocal lesions (ruling out malignancy and infection) and typical location on imaging. Normal C-reactive protein and/or an erythrocyte sedimentation rate more than three times the upper limit of normal had the greatest negative mean discriminatory scores.
The next steps will be to form an expert panel who will use 1000minds software to determine the final criteria and identify a threshold for disease. The investigators hope to build a large multinational case repository of at least 500 patients with CNO/CRMO and 500 patients with mimicking conditions from which to derive a development cohort and an external validation cohort. So far, 10 sites, including 4 in Europe, have obtained approval from an institutional review board. The group has also submitted a proposal for classification criteria to the American College of Rheumatology and the European League Against Rheumatism, Dr. Oliver said.
Dr. Oliver had no disclosures to report, but several coauthors reported financial ties to industry.
SOURCE: Oliver M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):254-5, Abstract OP0342. doi: 10.1136/annrheumdis-2019-eular.1539.
REPORTING FROM EULAR 2019 CONGRESS
Scoring below the cut but still depressed: What to do?
Depression is one of the most common mental health conditions in childhood, especially during socially turbulent adolescence when the brain is rapidly changing and parent-child relationships are strained by the teen’s striving for independence and identity. Often parents of teens call me worrying about possible depression, but in the next breath say “but maybe it is just puberty.” Because suicide is one of the most common causes of death among teens and is often associated with depression, we pediatricians have the scary job of sorting out symptoms and making a plan.
The Guidelines for Adolescent Depression in Primary Care (GLAD-PC)1,2 were revised in 2018 to help. This expert consensus document contains specific and practical guidance for all levels of depression. But for mild depression, GLAD-PC now advises pediatricians in Recommendation II to go beyond “watchful waiting.” It states, “After initial diagnosis,
Although a little vague, mild depression is diagnosed when there are “closer to 5” significant symptoms of depression, with “distressing but manageable” severity and only “mildly impaired” functioning. The most commonly used self-report adolescent depression screen, the Patient Health Questionnaire–Modified–9 (PHQ-9), has a recommended cut score of greater than 10, but 5-9 is considered mild depression symptoms. A clinical interview also is always required.
So what is this “active support” being recommended? After making an assessment of symptoms, severity, and impact – and ruling out significant suicide risk – the task is rather familiar to us from other medical conditions. We need to talk clearly and empathetically with the teen (and parents with consent) about depression and its neurological etiology, ask about contributing stress and genetic factors, and describe the typical course with optimism. This discussion is critical to pushing guilt or blame aside to rally family support. Substance use – (including alcohol) both a cause and attempted coping strategy for depression – must be addressed because it adds to risk for suicide or crashes and because it interacts with medicines.
Perhaps the biggest difference between active support for depression versus that for other conditions is that teens are likely reluctant, hopeless, and/or lacking energy to participate in the plan. The plan, therefore, needs to be approached in smaller steps and build on prior teen strengths, goals, or talents to motivate them and create reward to counteract general lethargy. You may know this teen used to play basketball, or sing at church, or love playing with a baby sister – all activities to try to reawaken. Parents can help recall these and are key to setting up opportunities.
GLAD-PC provides a “Self-Care Success!” worksheet of categories for goal setting for active support. These goals include:
- Stay physically active. Specified days/month, minutes/session, and dates and times.
- Engage spirituality and fun activities. Specify times/week, when, and with whom).
- Eat balanced meals. Specify number/day and names of foods.
- Spend time with people who can support you. Specify number/month, minutes/time, with whom, and doing what.
- Spend time relaxing. Specify days/week, minutes/time, and doing what.
- Determine small goals and simple steps. Establish these for a specified problem.
There is now evidence for these you can share with your teen patients and families.
Exercise
Exercise has a moderate effect size of 0.56 on depression, comparable to medications for mild to moderate depression and a useful adjunct to medications. The national Office of Disease Prevention and Health Promotion recommends that 6- to 17-year-olds get 60 minutes/day of moderate exercise or undertake vigorous “out of breath” exercise three times a week to maintain health. A meta-analysis of studies of yoga for people with depressive symptoms (not necessarily diagnosed depression) found reduced symptoms in 14 of 23 studies.
Pleasure
Advising fun has to include acknowledgment that a depressed teen is not motivated to do formerly fun things and may not get as much/any pleasure from it. You need to explain that “doing precedes feeling.” While what is fun is personal, new findings indicate that 2 hours/week “in nature” lowers stress, boosts mental health, and increases sense of well-being.
Nutrition
The MIND diet (Mediterranean-type diet high in leafy vegetables and berries but low in red meat) has evidence for lower odds of depression and psychological distress. Fatty acid supplements, specifically eicosapentaenoic acid at greater than 800 mg/day (930 mg), is better than placebo (P less than .001) for reducing mild depression within as little as 4 weeks. Natural S-Adenosyl-L-methionine (SAMe) has many studies showing benefit, according to National Center for Complementary and Alternative Medicine, a government-run website. NCCAM notes that St. John’s Wort has evidence for effectiveness equal to prescribed antidepressants for mild depression but with dangerous potential side effects, such as worsening of psychotic symptoms in bipolar disorder or schizophrenia, plus potentially life threatening drug interactions. While safe, valerian and probiotics have no evidence for reducing depression.
Social support
Family is usually the most important support for depressed teens even though they may be pushing family away, may refuse to come on outings, or may even refuse to come out of the bedroom. We should encourage parents and siblings to “hang out,” sitting quietly, available to listen rather than probing, cajoling, or nagging as they may have been doing. Parents also provide support by assuring adherence to visits, goals, and medications. Peer support helps a teen feel less alone and may increase social skills, but it can be difficult to sustain because friends may find depression threatening or give up when the teen avoids them and refuses activities. The National Association for Mental Illness has an online support group (www.strengthofus.org), as well as many excellent family resources. Sometimes medical efforts to be nonsectarian result in failure to recognize and remind teens and families of the value of religion, which is free and universally available, as a source of social support.
Relaxation
An evaluation of 15 studies concluded that relaxation techniques reduced depressive symptoms better than no treatment but not as much cognitive-behavior therapy (CBT). Yoga is another source of relaxation training. Mindfulness includes relaxation and specifies working to stay nonjudgmental about thoughts passing through one’s mind, recognizing and “arguing” with negative thinking, which is also part of CBT. Guided relaxation with a person, audiotape, or app (Calm or Headspace, among others) may be better for depressed teens because it inserts a voice to guide thoughts, which could potentially fend off ruminating on sad things.
Setting goals to address problems
In mild depression, compared with more endogenous moderate to severe major depressive disorder, a specific life stressor or relationship issue may be the precipitant. Identifying such factors (never forgetting possible trauma or abuse, which are harder to reveal), empathizing with the pain, and addressing them such as using Problem Solving Treatment for Primary Care (PST-PC) are within primary care skills. PST-PC involves four to six 30-minute sessions over 6-10 weeks during which you can provide perspective, help your patient set realistic goals and solutions to try out for situations that can be changed or coping strategies for emotion-focused unchangeable issues, iteratively check on progress via calls or televisits (the monitoring component), and renew problem-solving efforts as needed.
If mild depression fails to improve over several months or worsens, GLAD-PC describes evidence-based treatments. Even if it remits, your active support and monitoring should continue because depression tends to recur. You may not realize how valuable these seemingly simple active supports are to keeping mild depression in your teen patients at bay.
Dr. Howard is an assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
References
1. Pediatrics. 2018 Mar 1. doi: 10.1542/peds.2017-4081.
2. Pediatrics. 2018 Mar 1. doi: 10.1542/peds.2017-4082.
Depression is one of the most common mental health conditions in childhood, especially during socially turbulent adolescence when the brain is rapidly changing and parent-child relationships are strained by the teen’s striving for independence and identity. Often parents of teens call me worrying about possible depression, but in the next breath say “but maybe it is just puberty.” Because suicide is one of the most common causes of death among teens and is often associated with depression, we pediatricians have the scary job of sorting out symptoms and making a plan.
The Guidelines for Adolescent Depression in Primary Care (GLAD-PC)1,2 were revised in 2018 to help. This expert consensus document contains specific and practical guidance for all levels of depression. But for mild depression, GLAD-PC now advises pediatricians in Recommendation II to go beyond “watchful waiting.” It states, “After initial diagnosis,
Although a little vague, mild depression is diagnosed when there are “closer to 5” significant symptoms of depression, with “distressing but manageable” severity and only “mildly impaired” functioning. The most commonly used self-report adolescent depression screen, the Patient Health Questionnaire–Modified–9 (PHQ-9), has a recommended cut score of greater than 10, but 5-9 is considered mild depression symptoms. A clinical interview also is always required.
So what is this “active support” being recommended? After making an assessment of symptoms, severity, and impact – and ruling out significant suicide risk – the task is rather familiar to us from other medical conditions. We need to talk clearly and empathetically with the teen (and parents with consent) about depression and its neurological etiology, ask about contributing stress and genetic factors, and describe the typical course with optimism. This discussion is critical to pushing guilt or blame aside to rally family support. Substance use – (including alcohol) both a cause and attempted coping strategy for depression – must be addressed because it adds to risk for suicide or crashes and because it interacts with medicines.
Perhaps the biggest difference between active support for depression versus that for other conditions is that teens are likely reluctant, hopeless, and/or lacking energy to participate in the plan. The plan, therefore, needs to be approached in smaller steps and build on prior teen strengths, goals, or talents to motivate them and create reward to counteract general lethargy. You may know this teen used to play basketball, or sing at church, or love playing with a baby sister – all activities to try to reawaken. Parents can help recall these and are key to setting up opportunities.
GLAD-PC provides a “Self-Care Success!” worksheet of categories for goal setting for active support. These goals include:
- Stay physically active. Specified days/month, minutes/session, and dates and times.
- Engage spirituality and fun activities. Specify times/week, when, and with whom).
- Eat balanced meals. Specify number/day and names of foods.
- Spend time with people who can support you. Specify number/month, minutes/time, with whom, and doing what.
- Spend time relaxing. Specify days/week, minutes/time, and doing what.
- Determine small goals and simple steps. Establish these for a specified problem.
There is now evidence for these you can share with your teen patients and families.
Exercise
Exercise has a moderate effect size of 0.56 on depression, comparable to medications for mild to moderate depression and a useful adjunct to medications. The national Office of Disease Prevention and Health Promotion recommends that 6- to 17-year-olds get 60 minutes/day of moderate exercise or undertake vigorous “out of breath” exercise three times a week to maintain health. A meta-analysis of studies of yoga for people with depressive symptoms (not necessarily diagnosed depression) found reduced symptoms in 14 of 23 studies.
Pleasure
Advising fun has to include acknowledgment that a depressed teen is not motivated to do formerly fun things and may not get as much/any pleasure from it. You need to explain that “doing precedes feeling.” While what is fun is personal, new findings indicate that 2 hours/week “in nature” lowers stress, boosts mental health, and increases sense of well-being.
Nutrition
The MIND diet (Mediterranean-type diet high in leafy vegetables and berries but low in red meat) has evidence for lower odds of depression and psychological distress. Fatty acid supplements, specifically eicosapentaenoic acid at greater than 800 mg/day (930 mg), is better than placebo (P less than .001) for reducing mild depression within as little as 4 weeks. Natural S-Adenosyl-L-methionine (SAMe) has many studies showing benefit, according to National Center for Complementary and Alternative Medicine, a government-run website. NCCAM notes that St. John’s Wort has evidence for effectiveness equal to prescribed antidepressants for mild depression but with dangerous potential side effects, such as worsening of psychotic symptoms in bipolar disorder or schizophrenia, plus potentially life threatening drug interactions. While safe, valerian and probiotics have no evidence for reducing depression.
Social support
Family is usually the most important support for depressed teens even though they may be pushing family away, may refuse to come on outings, or may even refuse to come out of the bedroom. We should encourage parents and siblings to “hang out,” sitting quietly, available to listen rather than probing, cajoling, or nagging as they may have been doing. Parents also provide support by assuring adherence to visits, goals, and medications. Peer support helps a teen feel less alone and may increase social skills, but it can be difficult to sustain because friends may find depression threatening or give up when the teen avoids them and refuses activities. The National Association for Mental Illness has an online support group (www.strengthofus.org), as well as many excellent family resources. Sometimes medical efforts to be nonsectarian result in failure to recognize and remind teens and families of the value of religion, which is free and universally available, as a source of social support.
Relaxation
An evaluation of 15 studies concluded that relaxation techniques reduced depressive symptoms better than no treatment but not as much cognitive-behavior therapy (CBT). Yoga is another source of relaxation training. Mindfulness includes relaxation and specifies working to stay nonjudgmental about thoughts passing through one’s mind, recognizing and “arguing” with negative thinking, which is also part of CBT. Guided relaxation with a person, audiotape, or app (Calm or Headspace, among others) may be better for depressed teens because it inserts a voice to guide thoughts, which could potentially fend off ruminating on sad things.
Setting goals to address problems
In mild depression, compared with more endogenous moderate to severe major depressive disorder, a specific life stressor or relationship issue may be the precipitant. Identifying such factors (never forgetting possible trauma or abuse, which are harder to reveal), empathizing with the pain, and addressing them such as using Problem Solving Treatment for Primary Care (PST-PC) are within primary care skills. PST-PC involves four to six 30-minute sessions over 6-10 weeks during which you can provide perspective, help your patient set realistic goals and solutions to try out for situations that can be changed or coping strategies for emotion-focused unchangeable issues, iteratively check on progress via calls or televisits (the monitoring component), and renew problem-solving efforts as needed.
If mild depression fails to improve over several months or worsens, GLAD-PC describes evidence-based treatments. Even if it remits, your active support and monitoring should continue because depression tends to recur. You may not realize how valuable these seemingly simple active supports are to keeping mild depression in your teen patients at bay.
Dr. Howard is an assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
References
1. Pediatrics. 2018 Mar 1. doi: 10.1542/peds.2017-4081.
2. Pediatrics. 2018 Mar 1. doi: 10.1542/peds.2017-4082.
Depression is one of the most common mental health conditions in childhood, especially during socially turbulent adolescence when the brain is rapidly changing and parent-child relationships are strained by the teen’s striving for independence and identity. Often parents of teens call me worrying about possible depression, but in the next breath say “but maybe it is just puberty.” Because suicide is one of the most common causes of death among teens and is often associated with depression, we pediatricians have the scary job of sorting out symptoms and making a plan.
The Guidelines for Adolescent Depression in Primary Care (GLAD-PC)1,2 were revised in 2018 to help. This expert consensus document contains specific and practical guidance for all levels of depression. But for mild depression, GLAD-PC now advises pediatricians in Recommendation II to go beyond “watchful waiting.” It states, “After initial diagnosis,
Although a little vague, mild depression is diagnosed when there are “closer to 5” significant symptoms of depression, with “distressing but manageable” severity and only “mildly impaired” functioning. The most commonly used self-report adolescent depression screen, the Patient Health Questionnaire–Modified–9 (PHQ-9), has a recommended cut score of greater than 10, but 5-9 is considered mild depression symptoms. A clinical interview also is always required.
So what is this “active support” being recommended? After making an assessment of symptoms, severity, and impact – and ruling out significant suicide risk – the task is rather familiar to us from other medical conditions. We need to talk clearly and empathetically with the teen (and parents with consent) about depression and its neurological etiology, ask about contributing stress and genetic factors, and describe the typical course with optimism. This discussion is critical to pushing guilt or blame aside to rally family support. Substance use – (including alcohol) both a cause and attempted coping strategy for depression – must be addressed because it adds to risk for suicide or crashes and because it interacts with medicines.
Perhaps the biggest difference between active support for depression versus that for other conditions is that teens are likely reluctant, hopeless, and/or lacking energy to participate in the plan. The plan, therefore, needs to be approached in smaller steps and build on prior teen strengths, goals, or talents to motivate them and create reward to counteract general lethargy. You may know this teen used to play basketball, or sing at church, or love playing with a baby sister – all activities to try to reawaken. Parents can help recall these and are key to setting up opportunities.
GLAD-PC provides a “Self-Care Success!” worksheet of categories for goal setting for active support. These goals include:
- Stay physically active. Specified days/month, minutes/session, and dates and times.
- Engage spirituality and fun activities. Specify times/week, when, and with whom).
- Eat balanced meals. Specify number/day and names of foods.
- Spend time with people who can support you. Specify number/month, minutes/time, with whom, and doing what.
- Spend time relaxing. Specify days/week, minutes/time, and doing what.
- Determine small goals and simple steps. Establish these for a specified problem.
There is now evidence for these you can share with your teen patients and families.
Exercise
Exercise has a moderate effect size of 0.56 on depression, comparable to medications for mild to moderate depression and a useful adjunct to medications. The national Office of Disease Prevention and Health Promotion recommends that 6- to 17-year-olds get 60 minutes/day of moderate exercise or undertake vigorous “out of breath” exercise three times a week to maintain health. A meta-analysis of studies of yoga for people with depressive symptoms (not necessarily diagnosed depression) found reduced symptoms in 14 of 23 studies.
Pleasure
Advising fun has to include acknowledgment that a depressed teen is not motivated to do formerly fun things and may not get as much/any pleasure from it. You need to explain that “doing precedes feeling.” While what is fun is personal, new findings indicate that 2 hours/week “in nature” lowers stress, boosts mental health, and increases sense of well-being.
Nutrition
The MIND diet (Mediterranean-type diet high in leafy vegetables and berries but low in red meat) has evidence for lower odds of depression and psychological distress. Fatty acid supplements, specifically eicosapentaenoic acid at greater than 800 mg/day (930 mg), is better than placebo (P less than .001) for reducing mild depression within as little as 4 weeks. Natural S-Adenosyl-L-methionine (SAMe) has many studies showing benefit, according to National Center for Complementary and Alternative Medicine, a government-run website. NCCAM notes that St. John’s Wort has evidence for effectiveness equal to prescribed antidepressants for mild depression but with dangerous potential side effects, such as worsening of psychotic symptoms in bipolar disorder or schizophrenia, plus potentially life threatening drug interactions. While safe, valerian and probiotics have no evidence for reducing depression.
Social support
Family is usually the most important support for depressed teens even though they may be pushing family away, may refuse to come on outings, or may even refuse to come out of the bedroom. We should encourage parents and siblings to “hang out,” sitting quietly, available to listen rather than probing, cajoling, or nagging as they may have been doing. Parents also provide support by assuring adherence to visits, goals, and medications. Peer support helps a teen feel less alone and may increase social skills, but it can be difficult to sustain because friends may find depression threatening or give up when the teen avoids them and refuses activities. The National Association for Mental Illness has an online support group (www.strengthofus.org), as well as many excellent family resources. Sometimes medical efforts to be nonsectarian result in failure to recognize and remind teens and families of the value of religion, which is free and universally available, as a source of social support.
Relaxation
An evaluation of 15 studies concluded that relaxation techniques reduced depressive symptoms better than no treatment but not as much cognitive-behavior therapy (CBT). Yoga is another source of relaxation training. Mindfulness includes relaxation and specifies working to stay nonjudgmental about thoughts passing through one’s mind, recognizing and “arguing” with negative thinking, which is also part of CBT. Guided relaxation with a person, audiotape, or app (Calm or Headspace, among others) may be better for depressed teens because it inserts a voice to guide thoughts, which could potentially fend off ruminating on sad things.
Setting goals to address problems
In mild depression, compared with more endogenous moderate to severe major depressive disorder, a specific life stressor or relationship issue may be the precipitant. Identifying such factors (never forgetting possible trauma or abuse, which are harder to reveal), empathizing with the pain, and addressing them such as using Problem Solving Treatment for Primary Care (PST-PC) are within primary care skills. PST-PC involves four to six 30-minute sessions over 6-10 weeks during which you can provide perspective, help your patient set realistic goals and solutions to try out for situations that can be changed or coping strategies for emotion-focused unchangeable issues, iteratively check on progress via calls or televisits (the monitoring component), and renew problem-solving efforts as needed.
If mild depression fails to improve over several months or worsens, GLAD-PC describes evidence-based treatments. Even if it remits, your active support and monitoring should continue because depression tends to recur. You may not realize how valuable these seemingly simple active supports are to keeping mild depression in your teen patients at bay.
Dr. Howard is an assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
References
1. Pediatrics. 2018 Mar 1. doi: 10.1542/peds.2017-4081.
2. Pediatrics. 2018 Mar 1. doi: 10.1542/peds.2017-4082.
Vaping among teens increased significantly from 2017 to 2018
according to data from national cross-sectional surveys.
The prevalence of vaping in the past 30 days rose from 11% to 16% in the United States and from 8% to 14.6% in Canada, while use in England showed an nonsignificant increase of 8.7% to 8.9%, David Hammond, PhD, of the University of Waterloo (Canada) and associates said in the BMJ.
Embedded in those U.S. and Canadian increases is the recent evolution of the vaping market brought about by “the growth of JUUL e-cigarettes and similar products [that use] benzoic acid and nicotine salt technology to deliver higher concentrations of nicotine than conventional e-cigarettes,” they explained.
In England, the JUUL system is limited to less than half the nicotine concentration, at 20 mg/mL, compared with more than 50 mg/mL in the United States and Canada, and it was not available at all types of retail outlets at the time of the surveys. That situation changed in March 2019, when the company expanded to convenience stores, the investigators noted.
In the United States, JUUL was the second-most popular product among past–30-day vapers who had a usual brand in 2017, with 9% reporting use. In 2018, JUUL was the most popular brand and use was up to 28%. In Canada, the brand was not among the top five in 2017, but was third in 2018 at 10% in those who reported vaping in the past 30 days. The leading Canadian brand in 2018 was Smok, which released a nicotine-salt version in March of 2018, Dr. Hammond and associates reported.
“Before 2018, there was relatively little evidence of regular vaping among adolescents that might be indicative of nicotine addiction; however, the emergence of JUUL and nicotine salt–based products might signal a change,” they wrote.
The International Tobacco Control Policy Evaluation Project’s Youth Tobacco and Vaping Survey was conducted online in each country in two waves – July to August 2017 and August to September 2018 – with a sample size of approximately 12,000 for each.
The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
SOURCE: Hammond D et al. BMJ 2019 Jun 19. doi: 10.1136/bmj.l2219.
according to data from national cross-sectional surveys.
The prevalence of vaping in the past 30 days rose from 11% to 16% in the United States and from 8% to 14.6% in Canada, while use in England showed an nonsignificant increase of 8.7% to 8.9%, David Hammond, PhD, of the University of Waterloo (Canada) and associates said in the BMJ.
Embedded in those U.S. and Canadian increases is the recent evolution of the vaping market brought about by “the growth of JUUL e-cigarettes and similar products [that use] benzoic acid and nicotine salt technology to deliver higher concentrations of nicotine than conventional e-cigarettes,” they explained.
In England, the JUUL system is limited to less than half the nicotine concentration, at 20 mg/mL, compared with more than 50 mg/mL in the United States and Canada, and it was not available at all types of retail outlets at the time of the surveys. That situation changed in March 2019, when the company expanded to convenience stores, the investigators noted.
In the United States, JUUL was the second-most popular product among past–30-day vapers who had a usual brand in 2017, with 9% reporting use. In 2018, JUUL was the most popular brand and use was up to 28%. In Canada, the brand was not among the top five in 2017, but was third in 2018 at 10% in those who reported vaping in the past 30 days. The leading Canadian brand in 2018 was Smok, which released a nicotine-salt version in March of 2018, Dr. Hammond and associates reported.
“Before 2018, there was relatively little evidence of regular vaping among adolescents that might be indicative of nicotine addiction; however, the emergence of JUUL and nicotine salt–based products might signal a change,” they wrote.
The International Tobacco Control Policy Evaluation Project’s Youth Tobacco and Vaping Survey was conducted online in each country in two waves – July to August 2017 and August to September 2018 – with a sample size of approximately 12,000 for each.
The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
SOURCE: Hammond D et al. BMJ 2019 Jun 19. doi: 10.1136/bmj.l2219.
according to data from national cross-sectional surveys.
The prevalence of vaping in the past 30 days rose from 11% to 16% in the United States and from 8% to 14.6% in Canada, while use in England showed an nonsignificant increase of 8.7% to 8.9%, David Hammond, PhD, of the University of Waterloo (Canada) and associates said in the BMJ.
Embedded in those U.S. and Canadian increases is the recent evolution of the vaping market brought about by “the growth of JUUL e-cigarettes and similar products [that use] benzoic acid and nicotine salt technology to deliver higher concentrations of nicotine than conventional e-cigarettes,” they explained.
In England, the JUUL system is limited to less than half the nicotine concentration, at 20 mg/mL, compared with more than 50 mg/mL in the United States and Canada, and it was not available at all types of retail outlets at the time of the surveys. That situation changed in March 2019, when the company expanded to convenience stores, the investigators noted.
In the United States, JUUL was the second-most popular product among past–30-day vapers who had a usual brand in 2017, with 9% reporting use. In 2018, JUUL was the most popular brand and use was up to 28%. In Canada, the brand was not among the top five in 2017, but was third in 2018 at 10% in those who reported vaping in the past 30 days. The leading Canadian brand in 2018 was Smok, which released a nicotine-salt version in March of 2018, Dr. Hammond and associates reported.
“Before 2018, there was relatively little evidence of regular vaping among adolescents that might be indicative of nicotine addiction; however, the emergence of JUUL and nicotine salt–based products might signal a change,” they wrote.
The International Tobacco Control Policy Evaluation Project’s Youth Tobacco and Vaping Survey was conducted online in each country in two waves – July to August 2017 and August to September 2018 – with a sample size of approximately 12,000 for each.
The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
SOURCE: Hammond D et al. BMJ 2019 Jun 19. doi: 10.1136/bmj.l2219.
FROM THE BMJ
Key clinical point: Recent increases in vaping prevalence among teens “might be indicative of nicotine addiction.”
Major finding: Vaping prevalence increased from 11% to 16% in the United States and from 8% to 14.6% in Canada.
Study details: Two waves of a national, cross-sectional survey that included approximately 12,000 respondents each.
Disclosures: The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
Source: Hammond D et al. BMJ. 2019 Jun 19. doi: 10.1136/bmj.l2219.
A healthy 8-year-old boy presents with several skin-colored, round 1-3 mm papules on the nose, forehead, and cheeks
A shave biopsy of one of the lesions was performed that showed a proliferation of nests of basaloid cells on the dermis with palisading and rare vacuolated clear cell change. A rare ductal structure with luminal proteinaceous contents was noted. The findings were consistent with a trichoepithelioma.
Trichoepitheliomas are rare, benign, adnexal skin tumors that can start in early childhood or during puberty. The lesions are most commonly seen in girls as skin color papules on the face, and sometimes on the trunk and the neck. Trichoepitheliomas can appear as a benign single lesion nonfamilial form or as a familial form with multiple lesions.1 Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant condition where affected individuals have multiple trichoepitheliomas, cylindromas, and spiradenomas. Depending on the predominant type of lesion, phenotypic variants include multiple familial trichoepithelioma type 1 and familial cylindromatosis.2 BSS is caused by mutations within CYLD, a tumor-suppressor gene located on chromosome 16q12-q13.3 Our patient presented only with trichoepitheliomas with no other lesions on the scalp, neck, or torso.
Multiple trichoepitheliomas also can be seen in other syndromes including Rombo syndrome, which is characterized by basal cell carcinomas, milia, hypotrichosis, distal vasodilation, and atrophoderma vermiculata; none seen in our patient. Bazex-Dupré-Christol syndrome is an X-linked dominant condition in which affected individuals can present with multiple trichoepitheliomas, as well as milia, hypotrichosis, follicular atrophoderma, and basal cell carcinomas.
The differential diagnosis of skin color papules on the central face on a child should include acne, flat warts, and angiofibromas seen in tuberous sclerosis. Our patient’s lesions were monomorphous, and there were no comedones, pustules, or inflammatory papules characteristic of acne.
He had warts on his hands which could make it suspicious for the face lesions to be verrucous in nature. Flat warts also present as skin color papules, but characteristically are flat, not round and shiny as our patient’s lesions were. Angiofibromas, as seen in individuals with tuberous sclerosis, also can start at an early age in the same location as trichoepitheliomas in BSS, but clinically the lesions are pinker and redder rather than the skin-color, round shape papules characteristic of trichoepitheliomas. Patients may have other findings suggestive of tuberous sclerosis including confetti hypopigmentation, ash leaf spots, shagreen patch, and a history of seizures or developmental delay – none of which were present in our patient. Children with basal cell nevus syndrome can present with skin color to shiny telangiectatic papules (basal cell carcinomas) that can be single or multiple on the face, chest, and back. The lesions usually are not seen in clusters around the nose and central face as seen in patients with BSS. Patients with basal cell nevus syndrome can develop jaw bone cysts, brain tumors (medulloblastoma), and fibromas on the heart or ovaries, palmar pits and be macrocephalic.4
Trichoepitheliomas usually are treated surgically but other nonsurgical removing techniques include laser resurfacing, curettage, and electrocautery.5 Malignant transformation can occur in 5%-10% of the individuals and should be managed by a multidisciplinary team. Topical treatment with sirolimus previously has been reported to be effective in young patients.6
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email Dr. Matiz at [email protected].
References
1. Acta Dermatovenerol Croat. 2018 Jun;26(2):162-5.
2. Eur J Med Genet. 2015;58(5):271-8.
3. Am J Dermatopathol. 2014;36(11):868-74.
4. Int J Dermatol. 2016 Apr;55(4):367-75.
5. Int J Dermatol. 2007;46(6):583-6.
6. Dermatol Ther. 2017 Mar. doi: 10.1111/dth.12458.
A shave biopsy of one of the lesions was performed that showed a proliferation of nests of basaloid cells on the dermis with palisading and rare vacuolated clear cell change. A rare ductal structure with luminal proteinaceous contents was noted. The findings were consistent with a trichoepithelioma.
Trichoepitheliomas are rare, benign, adnexal skin tumors that can start in early childhood or during puberty. The lesions are most commonly seen in girls as skin color papules on the face, and sometimes on the trunk and the neck. Trichoepitheliomas can appear as a benign single lesion nonfamilial form or as a familial form with multiple lesions.1 Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant condition where affected individuals have multiple trichoepitheliomas, cylindromas, and spiradenomas. Depending on the predominant type of lesion, phenotypic variants include multiple familial trichoepithelioma type 1 and familial cylindromatosis.2 BSS is caused by mutations within CYLD, a tumor-suppressor gene located on chromosome 16q12-q13.3 Our patient presented only with trichoepitheliomas with no other lesions on the scalp, neck, or torso.
Multiple trichoepitheliomas also can be seen in other syndromes including Rombo syndrome, which is characterized by basal cell carcinomas, milia, hypotrichosis, distal vasodilation, and atrophoderma vermiculata; none seen in our patient. Bazex-Dupré-Christol syndrome is an X-linked dominant condition in which affected individuals can present with multiple trichoepitheliomas, as well as milia, hypotrichosis, follicular atrophoderma, and basal cell carcinomas.
The differential diagnosis of skin color papules on the central face on a child should include acne, flat warts, and angiofibromas seen in tuberous sclerosis. Our patient’s lesions were monomorphous, and there were no comedones, pustules, or inflammatory papules characteristic of acne.
He had warts on his hands which could make it suspicious for the face lesions to be verrucous in nature. Flat warts also present as skin color papules, but characteristically are flat, not round and shiny as our patient’s lesions were. Angiofibromas, as seen in individuals with tuberous sclerosis, also can start at an early age in the same location as trichoepitheliomas in BSS, but clinically the lesions are pinker and redder rather than the skin-color, round shape papules characteristic of trichoepitheliomas. Patients may have other findings suggestive of tuberous sclerosis including confetti hypopigmentation, ash leaf spots, shagreen patch, and a history of seizures or developmental delay – none of which were present in our patient. Children with basal cell nevus syndrome can present with skin color to shiny telangiectatic papules (basal cell carcinomas) that can be single or multiple on the face, chest, and back. The lesions usually are not seen in clusters around the nose and central face as seen in patients with BSS. Patients with basal cell nevus syndrome can develop jaw bone cysts, brain tumors (medulloblastoma), and fibromas on the heart or ovaries, palmar pits and be macrocephalic.4
Trichoepitheliomas usually are treated surgically but other nonsurgical removing techniques include laser resurfacing, curettage, and electrocautery.5 Malignant transformation can occur in 5%-10% of the individuals and should be managed by a multidisciplinary team. Topical treatment with sirolimus previously has been reported to be effective in young patients.6
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email Dr. Matiz at [email protected].
References
1. Acta Dermatovenerol Croat. 2018 Jun;26(2):162-5.
2. Eur J Med Genet. 2015;58(5):271-8.
3. Am J Dermatopathol. 2014;36(11):868-74.
4. Int J Dermatol. 2016 Apr;55(4):367-75.
5. Int J Dermatol. 2007;46(6):583-6.
6. Dermatol Ther. 2017 Mar. doi: 10.1111/dth.12458.
A shave biopsy of one of the lesions was performed that showed a proliferation of nests of basaloid cells on the dermis with palisading and rare vacuolated clear cell change. A rare ductal structure with luminal proteinaceous contents was noted. The findings were consistent with a trichoepithelioma.
Trichoepitheliomas are rare, benign, adnexal skin tumors that can start in early childhood or during puberty. The lesions are most commonly seen in girls as skin color papules on the face, and sometimes on the trunk and the neck. Trichoepitheliomas can appear as a benign single lesion nonfamilial form or as a familial form with multiple lesions.1 Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant condition where affected individuals have multiple trichoepitheliomas, cylindromas, and spiradenomas. Depending on the predominant type of lesion, phenotypic variants include multiple familial trichoepithelioma type 1 and familial cylindromatosis.2 BSS is caused by mutations within CYLD, a tumor-suppressor gene located on chromosome 16q12-q13.3 Our patient presented only with trichoepitheliomas with no other lesions on the scalp, neck, or torso.
Multiple trichoepitheliomas also can be seen in other syndromes including Rombo syndrome, which is characterized by basal cell carcinomas, milia, hypotrichosis, distal vasodilation, and atrophoderma vermiculata; none seen in our patient. Bazex-Dupré-Christol syndrome is an X-linked dominant condition in which affected individuals can present with multiple trichoepitheliomas, as well as milia, hypotrichosis, follicular atrophoderma, and basal cell carcinomas.
The differential diagnosis of skin color papules on the central face on a child should include acne, flat warts, and angiofibromas seen in tuberous sclerosis. Our patient’s lesions were monomorphous, and there were no comedones, pustules, or inflammatory papules characteristic of acne.
He had warts on his hands which could make it suspicious for the face lesions to be verrucous in nature. Flat warts also present as skin color papules, but characteristically are flat, not round and shiny as our patient’s lesions were. Angiofibromas, as seen in individuals with tuberous sclerosis, also can start at an early age in the same location as trichoepitheliomas in BSS, but clinically the lesions are pinker and redder rather than the skin-color, round shape papules characteristic of trichoepitheliomas. Patients may have other findings suggestive of tuberous sclerosis including confetti hypopigmentation, ash leaf spots, shagreen patch, and a history of seizures or developmental delay – none of which were present in our patient. Children with basal cell nevus syndrome can present with skin color to shiny telangiectatic papules (basal cell carcinomas) that can be single or multiple on the face, chest, and back. The lesions usually are not seen in clusters around the nose and central face as seen in patients with BSS. Patients with basal cell nevus syndrome can develop jaw bone cysts, brain tumors (medulloblastoma), and fibromas on the heart or ovaries, palmar pits and be macrocephalic.4
Trichoepitheliomas usually are treated surgically but other nonsurgical removing techniques include laser resurfacing, curettage, and electrocautery.5 Malignant transformation can occur in 5%-10% of the individuals and should be managed by a multidisciplinary team. Topical treatment with sirolimus previously has been reported to be effective in young patients.6
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email Dr. Matiz at [email protected].
References
1. Acta Dermatovenerol Croat. 2018 Jun;26(2):162-5.
2. Eur J Med Genet. 2015;58(5):271-8.
3. Am J Dermatopathol. 2014;36(11):868-74.
4. Int J Dermatol. 2016 Apr;55(4):367-75.
5. Int J Dermatol. 2007;46(6):583-6.
6. Dermatol Ther. 2017 Mar. doi: 10.1111/dth.12458.
A white 8-year-old boy comes to our pediatric dermatology clinic with his mother for evaluation of acne. The lesions started about a year ago on his nose and now have spread to his cheeks. The bumps are not symptomatic. He has been applying over the counter salicylic acid and benzoyl peroxide gels with no help. The mother reports he has been growing well, denies any growth spurt, no axillary or genital hair or body odor noted.
None of the family members have a history of acne. The mother cannot recall any family members with similar lesions on the face. He has had some warts on his fingers for years and has been treated with over the counter salicylic acid. There is no family history of skin cancer.
On physical exam, he is a healthy young boy with several skin color, round papules 1-3 mm on the nose, forehead, and cheeks. There are no lesions on the scalp. He has abundant brown hair. He has few verrucous papules on the fingers. Axillary and genital hair is not noted. There is no body odor and he is Tanner stage I.
Rapidly Growing Cutaneous Nodules on the Scalp
The Diagnosis: B-Cell Acute Lymphoblastic Leukemia
A 4-mm punch biopsy of one of the scalp lesions showed a diffuse infiltrate of intermediately sized cells with variably mature chromatin and irregular nuclear contours, consistent with a neoplastic process. Numerous mitotic figures were present, indicating a high proliferation rate (Figure 1). At that time there was no evidence of systemic involvement. A repeat biopsy with concurrent bone marrow biopsy was scheduled 10 days after the patient's initial presentation for further classification. Laboratory studies at that time revealed leukocytosis with elevated neutrophils and lymphocytes as well as a high absolute blast count.
On immunohistochemical staining, the neoplastic cells were positive for CD45, which indicated the neoplasm was hematopoietic, as well as CD10 and the B-cell antigens PAX-5 and CD79a. The cells were negative for CD20, which also is a B-cell marker, but this marker is only expressed in approximately half of pediatric acute lymphoblastic leukemia (ALL) cases with B-cell precursor origin.1 Markers that typically are expressed in B-cell acute lymphoblastic leukemia (B-ALL)--CD34 and terminal deoxynucleotidyl transferase--were both negative. These results were somewhat contradictory, and the differential remained open to both B-ALL and mature B-cell lymphoma. A bone marrow biopsy showed approximately 65% blasts or leukemic cells (Figure 2). Flow cytometry showed the cells were positive for CD10, CD19, weak CD79a, and variable lambda surface antigen expression. The cells were negative for expression of CD20, CD34, terminal deoxynucleotidyl transferase, myeloid antigens, and CD3. Ultimately, the morphology and immunophenotype were most consistent with a diagnosis of B-ALL. Fluorescence in situ hybridization revealed mixed lineage leukemia, MLL, gene rearrangements.
In general, when considering the differential diagnosis of superficial nodules, 5 elements are helpful to consider: the number of nodules (single vs multiple); the location; and the presence or absence of tenderness, pigmentation or erythema, and firmness.2 Our patient had multiple nodules on the scalp, which were erythematous to slightly purple and firm. The differential diagnosis can be categorized into malignant; infectious; and benign inflammatory, vascular, and fibrous tumors.
Potential oncologic processes include leukemia cutis, lymphoblastic leukemia/lymphoma, Langerhans cell histiocytosis, and rhabdomyosarcoma. Initial laboratory test results were reassuring. Infectious processes in the differential include deep fungal infections such as coccidioidomycosis and nontuberculous mycobacterial infections. Coccidioidomycosis was the most likely to cause skin lesions or masses in our patient; however, it was considered less likely because the patient's family had not traveled or been exposed to an endemic area.3
Benign tumors in the differential include deep hemangioma, which was deemed less likely in our patient because most hemangiomas reach 80% of their maximum size by 5 months of age.4 Another possible benign tumor is infantile myofibromatosis, which is rare but is the most common fibrous tumor of infancy.5
Early-onset childhood sarcoidosis also has been shown to produce multiple nontender firm nodules.2 This process was considered unlikely in our patient because not only is the disease relatively rare in the pediatric population, but most reported childhood cases have occurred in patients aged 13 to 15 years.6 Additionally, no uveitis or arthritis was observed in this case.
Ultimately, histopathology and bone marrow biopsy were necessary to determine the diagnosis of B-ALL. Although uncommon, cutaneous involvement can be an early sign of ALL in children.7 Thus, neoplastic etiologies should be considered in the workup of cutaneous nodules in children, especially when these nodules are hard, rapidly growing, ulcerated, fixed, and/or vascular.8 Once the diagnosis is established, initial workup of ALL in children should include complete blood cell count with manual differential, prothrombin time, partial thromboplastin time, electrolytes, uric acid, and renal and liver function tests. Often, baseline viral titers such as cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, and varicella-zoster virus also are included. Patients are risk stratified to the appropriate level of treatment based on tumor immunophenotype, cytogenetic findings, patient age, white blood cell count at the time of diagnosis, and response to initial therapy. Treatment typically is comprised of a multidrug regimen divided into several phases--induction, consolidation, and maintenance--as well as therapy directed to the central nervous system. Treatment protocols usually take 2 to 3 years to complete.
Our patient was treated with 1 dose of intrathecal methotrexate before starting the Interfant-06 protocol with a 7-day methylprednisolone prophase. The patient's nodules shrank over time and were no longer present after 14 days of treatment.
- Dworzak MN, Schumich A, Printz D, et al. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood. 2008;112:3982-3988.
- Whelan JP, Zembowicz A. Case records of the Massachusetts General Hospital. case 19-2006. a 22-month-old boy with the rapid growth of subcutaneous nodules. N Engl J Med. 2006;354:2697-2704.
- Malo J, Luraschi-Monjagatta C, Wolk DM, et al. Update on the diagnosis of pulmonary coccidioidomycosis. Ann Am Thorac Soc. 2014;11:243-253.
- Chang LC, Haggstrom AN, Drolet BA, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122:360-367.
- Schurr P, Moulsdale W. Infantile myofibroma. Adv Neonatal Care. 2008;8:13-20.
- Shetty AK, Gedalia A. Childhood sarcoidosis: a rare but fascinating disorder. Pediatr Rheumatol Online J. 2008;6:16.
- Millot F, Robert A, Bertrand Y, et al. Cutaneous involvement in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC). Pediatrics. 1997;100:60-64.
- Fogelson S, Dohil M. Papular and nodular skin lesions in children. Semin Plast Surg. 2006;20:180-191.
The Diagnosis: B-Cell Acute Lymphoblastic Leukemia
A 4-mm punch biopsy of one of the scalp lesions showed a diffuse infiltrate of intermediately sized cells with variably mature chromatin and irregular nuclear contours, consistent with a neoplastic process. Numerous mitotic figures were present, indicating a high proliferation rate (Figure 1). At that time there was no evidence of systemic involvement. A repeat biopsy with concurrent bone marrow biopsy was scheduled 10 days after the patient's initial presentation for further classification. Laboratory studies at that time revealed leukocytosis with elevated neutrophils and lymphocytes as well as a high absolute blast count.
On immunohistochemical staining, the neoplastic cells were positive for CD45, which indicated the neoplasm was hematopoietic, as well as CD10 and the B-cell antigens PAX-5 and CD79a. The cells were negative for CD20, which also is a B-cell marker, but this marker is only expressed in approximately half of pediatric acute lymphoblastic leukemia (ALL) cases with B-cell precursor origin.1 Markers that typically are expressed in B-cell acute lymphoblastic leukemia (B-ALL)--CD34 and terminal deoxynucleotidyl transferase--were both negative. These results were somewhat contradictory, and the differential remained open to both B-ALL and mature B-cell lymphoma. A bone marrow biopsy showed approximately 65% blasts or leukemic cells (Figure 2). Flow cytometry showed the cells were positive for CD10, CD19, weak CD79a, and variable lambda surface antigen expression. The cells were negative for expression of CD20, CD34, terminal deoxynucleotidyl transferase, myeloid antigens, and CD3. Ultimately, the morphology and immunophenotype were most consistent with a diagnosis of B-ALL. Fluorescence in situ hybridization revealed mixed lineage leukemia, MLL, gene rearrangements.
In general, when considering the differential diagnosis of superficial nodules, 5 elements are helpful to consider: the number of nodules (single vs multiple); the location; and the presence or absence of tenderness, pigmentation or erythema, and firmness.2 Our patient had multiple nodules on the scalp, which were erythematous to slightly purple and firm. The differential diagnosis can be categorized into malignant; infectious; and benign inflammatory, vascular, and fibrous tumors.
Potential oncologic processes include leukemia cutis, lymphoblastic leukemia/lymphoma, Langerhans cell histiocytosis, and rhabdomyosarcoma. Initial laboratory test results were reassuring. Infectious processes in the differential include deep fungal infections such as coccidioidomycosis and nontuberculous mycobacterial infections. Coccidioidomycosis was the most likely to cause skin lesions or masses in our patient; however, it was considered less likely because the patient's family had not traveled or been exposed to an endemic area.3
Benign tumors in the differential include deep hemangioma, which was deemed less likely in our patient because most hemangiomas reach 80% of their maximum size by 5 months of age.4 Another possible benign tumor is infantile myofibromatosis, which is rare but is the most common fibrous tumor of infancy.5
Early-onset childhood sarcoidosis also has been shown to produce multiple nontender firm nodules.2 This process was considered unlikely in our patient because not only is the disease relatively rare in the pediatric population, but most reported childhood cases have occurred in patients aged 13 to 15 years.6 Additionally, no uveitis or arthritis was observed in this case.
Ultimately, histopathology and bone marrow biopsy were necessary to determine the diagnosis of B-ALL. Although uncommon, cutaneous involvement can be an early sign of ALL in children.7 Thus, neoplastic etiologies should be considered in the workup of cutaneous nodules in children, especially when these nodules are hard, rapidly growing, ulcerated, fixed, and/or vascular.8 Once the diagnosis is established, initial workup of ALL in children should include complete blood cell count with manual differential, prothrombin time, partial thromboplastin time, electrolytes, uric acid, and renal and liver function tests. Often, baseline viral titers such as cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, and varicella-zoster virus also are included. Patients are risk stratified to the appropriate level of treatment based on tumor immunophenotype, cytogenetic findings, patient age, white blood cell count at the time of diagnosis, and response to initial therapy. Treatment typically is comprised of a multidrug regimen divided into several phases--induction, consolidation, and maintenance--as well as therapy directed to the central nervous system. Treatment protocols usually take 2 to 3 years to complete.
Our patient was treated with 1 dose of intrathecal methotrexate before starting the Interfant-06 protocol with a 7-day methylprednisolone prophase. The patient's nodules shrank over time and were no longer present after 14 days of treatment.
The Diagnosis: B-Cell Acute Lymphoblastic Leukemia
A 4-mm punch biopsy of one of the scalp lesions showed a diffuse infiltrate of intermediately sized cells with variably mature chromatin and irregular nuclear contours, consistent with a neoplastic process. Numerous mitotic figures were present, indicating a high proliferation rate (Figure 1). At that time there was no evidence of systemic involvement. A repeat biopsy with concurrent bone marrow biopsy was scheduled 10 days after the patient's initial presentation for further classification. Laboratory studies at that time revealed leukocytosis with elevated neutrophils and lymphocytes as well as a high absolute blast count.
On immunohistochemical staining, the neoplastic cells were positive for CD45, which indicated the neoplasm was hematopoietic, as well as CD10 and the B-cell antigens PAX-5 and CD79a. The cells were negative for CD20, which also is a B-cell marker, but this marker is only expressed in approximately half of pediatric acute lymphoblastic leukemia (ALL) cases with B-cell precursor origin.1 Markers that typically are expressed in B-cell acute lymphoblastic leukemia (B-ALL)--CD34 and terminal deoxynucleotidyl transferase--were both negative. These results were somewhat contradictory, and the differential remained open to both B-ALL and mature B-cell lymphoma. A bone marrow biopsy showed approximately 65% blasts or leukemic cells (Figure 2). Flow cytometry showed the cells were positive for CD10, CD19, weak CD79a, and variable lambda surface antigen expression. The cells were negative for expression of CD20, CD34, terminal deoxynucleotidyl transferase, myeloid antigens, and CD3. Ultimately, the morphology and immunophenotype were most consistent with a diagnosis of B-ALL. Fluorescence in situ hybridization revealed mixed lineage leukemia, MLL, gene rearrangements.
In general, when considering the differential diagnosis of superficial nodules, 5 elements are helpful to consider: the number of nodules (single vs multiple); the location; and the presence or absence of tenderness, pigmentation or erythema, and firmness.2 Our patient had multiple nodules on the scalp, which were erythematous to slightly purple and firm. The differential diagnosis can be categorized into malignant; infectious; and benign inflammatory, vascular, and fibrous tumors.
Potential oncologic processes include leukemia cutis, lymphoblastic leukemia/lymphoma, Langerhans cell histiocytosis, and rhabdomyosarcoma. Initial laboratory test results were reassuring. Infectious processes in the differential include deep fungal infections such as coccidioidomycosis and nontuberculous mycobacterial infections. Coccidioidomycosis was the most likely to cause skin lesions or masses in our patient; however, it was considered less likely because the patient's family had not traveled or been exposed to an endemic area.3
Benign tumors in the differential include deep hemangioma, which was deemed less likely in our patient because most hemangiomas reach 80% of their maximum size by 5 months of age.4 Another possible benign tumor is infantile myofibromatosis, which is rare but is the most common fibrous tumor of infancy.5
Early-onset childhood sarcoidosis also has been shown to produce multiple nontender firm nodules.2 This process was considered unlikely in our patient because not only is the disease relatively rare in the pediatric population, but most reported childhood cases have occurred in patients aged 13 to 15 years.6 Additionally, no uveitis or arthritis was observed in this case.
Ultimately, histopathology and bone marrow biopsy were necessary to determine the diagnosis of B-ALL. Although uncommon, cutaneous involvement can be an early sign of ALL in children.7 Thus, neoplastic etiologies should be considered in the workup of cutaneous nodules in children, especially when these nodules are hard, rapidly growing, ulcerated, fixed, and/or vascular.8 Once the diagnosis is established, initial workup of ALL in children should include complete blood cell count with manual differential, prothrombin time, partial thromboplastin time, electrolytes, uric acid, and renal and liver function tests. Often, baseline viral titers such as cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, and varicella-zoster virus also are included. Patients are risk stratified to the appropriate level of treatment based on tumor immunophenotype, cytogenetic findings, patient age, white blood cell count at the time of diagnosis, and response to initial therapy. Treatment typically is comprised of a multidrug regimen divided into several phases--induction, consolidation, and maintenance--as well as therapy directed to the central nervous system. Treatment protocols usually take 2 to 3 years to complete.
Our patient was treated with 1 dose of intrathecal methotrexate before starting the Interfant-06 protocol with a 7-day methylprednisolone prophase. The patient's nodules shrank over time and were no longer present after 14 days of treatment.
- Dworzak MN, Schumich A, Printz D, et al. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood. 2008;112:3982-3988.
- Whelan JP, Zembowicz A. Case records of the Massachusetts General Hospital. case 19-2006. a 22-month-old boy with the rapid growth of subcutaneous nodules. N Engl J Med. 2006;354:2697-2704.
- Malo J, Luraschi-Monjagatta C, Wolk DM, et al. Update on the diagnosis of pulmonary coccidioidomycosis. Ann Am Thorac Soc. 2014;11:243-253.
- Chang LC, Haggstrom AN, Drolet BA, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122:360-367.
- Schurr P, Moulsdale W. Infantile myofibroma. Adv Neonatal Care. 2008;8:13-20.
- Shetty AK, Gedalia A. Childhood sarcoidosis: a rare but fascinating disorder. Pediatr Rheumatol Online J. 2008;6:16.
- Millot F, Robert A, Bertrand Y, et al. Cutaneous involvement in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC). Pediatrics. 1997;100:60-64.
- Fogelson S, Dohil M. Papular and nodular skin lesions in children. Semin Plast Surg. 2006;20:180-191.
- Dworzak MN, Schumich A, Printz D, et al. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood. 2008;112:3982-3988.
- Whelan JP, Zembowicz A. Case records of the Massachusetts General Hospital. case 19-2006. a 22-month-old boy with the rapid growth of subcutaneous nodules. N Engl J Med. 2006;354:2697-2704.
- Malo J, Luraschi-Monjagatta C, Wolk DM, et al. Update on the diagnosis of pulmonary coccidioidomycosis. Ann Am Thorac Soc. 2014;11:243-253.
- Chang LC, Haggstrom AN, Drolet BA, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122:360-367.
- Schurr P, Moulsdale W. Infantile myofibroma. Adv Neonatal Care. 2008;8:13-20.
- Shetty AK, Gedalia A. Childhood sarcoidosis: a rare but fascinating disorder. Pediatr Rheumatol Online J. 2008;6:16.
- Millot F, Robert A, Bertrand Y, et al. Cutaneous involvement in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC). Pediatrics. 1997;100:60-64.
- Fogelson S, Dohil M. Papular and nodular skin lesions in children. Semin Plast Surg. 2006;20:180-191.
An 8-month-old infant girl presented with rapidly growing cutaneous nodules on the scalp of 1 month's duration. Her parents reported that she disliked lying flat but was otherwise growing and developing normally. Nondiagnostic ultrasonography of the head and brain had been performed as well as a skull radiograph, which found no evidence of lytic lesions. On physical examination, 3 erythematous to violaceous, subcutaneous, firm, fixed nodules were observed on the scalp. Notable cervical lymphadenopathy with several distinct, fixed, firm, subcutaneous nodules in the postauricular lymph chains also were noted. The patient had no pertinent medical history and was born via normal spontaneous vaginal delivery to healthy parents. The remainder of the physical examination and review of systems was negative.
Liraglutide indication expanded to include children
news release from the agency. The approval comes after granting the application Priority Review, which means the FDA aimed to take action on it within 6 months instead of the usual 10 months seen with a Standard Review.
according to aLiraglutide injection has been approved for treatment of adults with type 2 diabetes since 2010, but this is the first noninsulin treatment for pediatric patients since metformin received approval for this population in 2000.
“The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with [type 2 diabetes],” said Lisa Yanoff, MD, acting director of the division of metabolism and endocrinology products in the agency’s Center for Drug Evaluation and Research.
The approval is based on efficacy and safety results from several placebo-controlled trials in adults, and one trial in 134 pediatric patients aged 10 years or older. In the latter trial, which ran for more than 26 weeks, hemoglobin A1c levels fell below 7% in approximately 64% of patients treated with liraglutide injection, compared with 37% of those who received placebo. Those results were seen regardless of whether patients concomitantly used insulin.
Although an increase in hypoglycemia risk has sometimes been seen in adult patients taking liraglutide injection with insulin or other drugs that raise insulin production, this heightened risk was seen in the pediatric patients regardless of whether they took other therapies for diabetes.
Liraglutide injection carries a Boxed Warning, the FDA’s strongest warning, for heightened risk of thyroid C-cell tumors. Therefore, the agency recommends against patients with history or family members with history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 using this treatment. Among its other warnings are those pertaining to patients with renal impairment or kidney failure, pancreatitis, and/or acute gallbladder disease.
The most common side effects are nausea, diarrhea, vomiting, decreased appetite, indigestion, and constipation. The full prescribing information can be found on the FDA website.
news release from the agency. The approval comes after granting the application Priority Review, which means the FDA aimed to take action on it within 6 months instead of the usual 10 months seen with a Standard Review.
according to aLiraglutide injection has been approved for treatment of adults with type 2 diabetes since 2010, but this is the first noninsulin treatment for pediatric patients since metformin received approval for this population in 2000.
“The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with [type 2 diabetes],” said Lisa Yanoff, MD, acting director of the division of metabolism and endocrinology products in the agency’s Center for Drug Evaluation and Research.
The approval is based on efficacy and safety results from several placebo-controlled trials in adults, and one trial in 134 pediatric patients aged 10 years or older. In the latter trial, which ran for more than 26 weeks, hemoglobin A1c levels fell below 7% in approximately 64% of patients treated with liraglutide injection, compared with 37% of those who received placebo. Those results were seen regardless of whether patients concomitantly used insulin.
Although an increase in hypoglycemia risk has sometimes been seen in adult patients taking liraglutide injection with insulin or other drugs that raise insulin production, this heightened risk was seen in the pediatric patients regardless of whether they took other therapies for diabetes.
Liraglutide injection carries a Boxed Warning, the FDA’s strongest warning, for heightened risk of thyroid C-cell tumors. Therefore, the agency recommends against patients with history or family members with history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 using this treatment. Among its other warnings are those pertaining to patients with renal impairment or kidney failure, pancreatitis, and/or acute gallbladder disease.
The most common side effects are nausea, diarrhea, vomiting, decreased appetite, indigestion, and constipation. The full prescribing information can be found on the FDA website.
news release from the agency. The approval comes after granting the application Priority Review, which means the FDA aimed to take action on it within 6 months instead of the usual 10 months seen with a Standard Review.
according to aLiraglutide injection has been approved for treatment of adults with type 2 diabetes since 2010, but this is the first noninsulin treatment for pediatric patients since metformin received approval for this population in 2000.
“The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with [type 2 diabetes],” said Lisa Yanoff, MD, acting director of the division of metabolism and endocrinology products in the agency’s Center for Drug Evaluation and Research.
The approval is based on efficacy and safety results from several placebo-controlled trials in adults, and one trial in 134 pediatric patients aged 10 years or older. In the latter trial, which ran for more than 26 weeks, hemoglobin A1c levels fell below 7% in approximately 64% of patients treated with liraglutide injection, compared with 37% of those who received placebo. Those results were seen regardless of whether patients concomitantly used insulin.
Although an increase in hypoglycemia risk has sometimes been seen in adult patients taking liraglutide injection with insulin or other drugs that raise insulin production, this heightened risk was seen in the pediatric patients regardless of whether they took other therapies for diabetes.
Liraglutide injection carries a Boxed Warning, the FDA’s strongest warning, for heightened risk of thyroid C-cell tumors. Therefore, the agency recommends against patients with history or family members with history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 using this treatment. Among its other warnings are those pertaining to patients with renal impairment or kidney failure, pancreatitis, and/or acute gallbladder disease.
The most common side effects are nausea, diarrhea, vomiting, decreased appetite, indigestion, and constipation. The full prescribing information can be found on the FDA website.
Obesity and overweight declined among lower-income kids
The combined rate of
, according to a study in JAMA.Liping Pan, MD, MPH, of the Centers for Disease Control and Prevention and colleagues used data from the WIC Participant and Program Characteristics survey from 2010, 2012, 2014, and 2016 for 12,403,629 children aged 2-4 years from 50 states, Washington, D.C., and 5 territories. In addition to a –3.2% change (95% confidence interval, –3.3% to –3.2%) in adjusted prevalence difference for the combined rate of obesity and overweight seen between 2010 and 2016, the researchers found the crude prevalence decreased from 32.5% to 29.1%. A decrease was also seen for obesity alone (crude prevalence, 15.9% to 13.9%; adjusted prevalence difference, –1.9%; 95% CI, –1.9% to –1.8%).
One of the limitations of the study is that the characteristics of enrolled children might differ from those of children not enrolled in this WIC program; however, the researchers noted that they accounted for many demographic characteristics in the trend analyses.
“Reasons for the declines in obesity among young children in WIC remain undetermined but may include WIC food package revisions and local, state, and national initiatives,” they wrote.
SOURCE: Pan L et al. JAMA. 2019 Jun 18;321(23):2364-6.
The combined rate of
, according to a study in JAMA.Liping Pan, MD, MPH, of the Centers for Disease Control and Prevention and colleagues used data from the WIC Participant and Program Characteristics survey from 2010, 2012, 2014, and 2016 for 12,403,629 children aged 2-4 years from 50 states, Washington, D.C., and 5 territories. In addition to a –3.2% change (95% confidence interval, –3.3% to –3.2%) in adjusted prevalence difference for the combined rate of obesity and overweight seen between 2010 and 2016, the researchers found the crude prevalence decreased from 32.5% to 29.1%. A decrease was also seen for obesity alone (crude prevalence, 15.9% to 13.9%; adjusted prevalence difference, –1.9%; 95% CI, –1.9% to –1.8%).
One of the limitations of the study is that the characteristics of enrolled children might differ from those of children not enrolled in this WIC program; however, the researchers noted that they accounted for many demographic characteristics in the trend analyses.
“Reasons for the declines in obesity among young children in WIC remain undetermined but may include WIC food package revisions and local, state, and national initiatives,” they wrote.
SOURCE: Pan L et al. JAMA. 2019 Jun 18;321(23):2364-6.
The combined rate of
, according to a study in JAMA.Liping Pan, MD, MPH, of the Centers for Disease Control and Prevention and colleagues used data from the WIC Participant and Program Characteristics survey from 2010, 2012, 2014, and 2016 for 12,403,629 children aged 2-4 years from 50 states, Washington, D.C., and 5 territories. In addition to a –3.2% change (95% confidence interval, –3.3% to –3.2%) in adjusted prevalence difference for the combined rate of obesity and overweight seen between 2010 and 2016, the researchers found the crude prevalence decreased from 32.5% to 29.1%. A decrease was also seen for obesity alone (crude prevalence, 15.9% to 13.9%; adjusted prevalence difference, –1.9%; 95% CI, –1.9% to –1.8%).
One of the limitations of the study is that the characteristics of enrolled children might differ from those of children not enrolled in this WIC program; however, the researchers noted that they accounted for many demographic characteristics in the trend analyses.
“Reasons for the declines in obesity among young children in WIC remain undetermined but may include WIC food package revisions and local, state, and national initiatives,” they wrote.
SOURCE: Pan L et al. JAMA. 2019 Jun 18;321(23):2364-6.
FROM JAMA
Suicide rates rise in U.S. adolescents and young adults
Suicides in teens and young adults reached 6,241 in 2017, the highest since 2000, according to data from a review of the Centers for Disease Control and Prevention Underlying Cause of Death database.
The suicide rate overall was 12 per 100,000 in 2017 for 15-19 year olds.
Although suicide rates have increased across all age groups in the United States since 2000, “adolescents are of particular concern, with increases in social media use, anxiety, depression, and self-inflicted injuries,” wrote Oren Miron of Harvard Medical School, Boston, and colleagues.
In a research letter published in JAMA, the researchers analyzed trends in teen and young adult suicides from 2000 to 2017. The combined suicide rate for males and females aged 15-19 years in 2000 was 8 per 100,000 with no significant changes until 2007, followed by an annual percentage change (APC) of 3% from 2007 to 2014 and 10% from 2014 to 2017.
When the data were broken out by gender, Of note, these young men showed a decreasing trend in APC of –2% from 2000 to 2007 before increasing.
Among females aged 15-19 years, no increase was noted until 2010, then researchers identified an APC of 8% from 2010 to 2017.
For ages 20-24 years, the combined suicide rate for males and females was 13 per 100,000 in 2000, which rose to 17 per 100,000 in 2017. The APC in the older group was 1% from 2000 to 2013 and 6% from 2013 to 2017. Increasing trends were observed for both males and females over the study period.
The study was limited by the potential inaccuracy in cause of death listed on death certificates, such as mistaking a suicide for an accidental overdose, and the increased suicide rate could reflect more accurate reporting, the researchers noted.
Nonetheless, the results support the need for more studies of contributing factors to teen and young adult suicides to help develop prevention strategies and analysis of factors that may have contributed to declines in suicide rates in the past, they said.
Coauthor Dr. Yu was supported by the Harvard Data Science Fellowship. The researchers had no relevant financial disclosures.
SOURCE: Miron O et al. JAMA. 2019 Jun 28;321:2362-4.
Suicides in teens and young adults reached 6,241 in 2017, the highest since 2000, according to data from a review of the Centers for Disease Control and Prevention Underlying Cause of Death database.
The suicide rate overall was 12 per 100,000 in 2017 for 15-19 year olds.
Although suicide rates have increased across all age groups in the United States since 2000, “adolescents are of particular concern, with increases in social media use, anxiety, depression, and self-inflicted injuries,” wrote Oren Miron of Harvard Medical School, Boston, and colleagues.
In a research letter published in JAMA, the researchers analyzed trends in teen and young adult suicides from 2000 to 2017. The combined suicide rate for males and females aged 15-19 years in 2000 was 8 per 100,000 with no significant changes until 2007, followed by an annual percentage change (APC) of 3% from 2007 to 2014 and 10% from 2014 to 2017.
When the data were broken out by gender, Of note, these young men showed a decreasing trend in APC of –2% from 2000 to 2007 before increasing.
Among females aged 15-19 years, no increase was noted until 2010, then researchers identified an APC of 8% from 2010 to 2017.
For ages 20-24 years, the combined suicide rate for males and females was 13 per 100,000 in 2000, which rose to 17 per 100,000 in 2017. The APC in the older group was 1% from 2000 to 2013 and 6% from 2013 to 2017. Increasing trends were observed for both males and females over the study period.
The study was limited by the potential inaccuracy in cause of death listed on death certificates, such as mistaking a suicide for an accidental overdose, and the increased suicide rate could reflect more accurate reporting, the researchers noted.
Nonetheless, the results support the need for more studies of contributing factors to teen and young adult suicides to help develop prevention strategies and analysis of factors that may have contributed to declines in suicide rates in the past, they said.
Coauthor Dr. Yu was supported by the Harvard Data Science Fellowship. The researchers had no relevant financial disclosures.
SOURCE: Miron O et al. JAMA. 2019 Jun 28;321:2362-4.
Suicides in teens and young adults reached 6,241 in 2017, the highest since 2000, according to data from a review of the Centers for Disease Control and Prevention Underlying Cause of Death database.
The suicide rate overall was 12 per 100,000 in 2017 for 15-19 year olds.
Although suicide rates have increased across all age groups in the United States since 2000, “adolescents are of particular concern, with increases in social media use, anxiety, depression, and self-inflicted injuries,” wrote Oren Miron of Harvard Medical School, Boston, and colleagues.
In a research letter published in JAMA, the researchers analyzed trends in teen and young adult suicides from 2000 to 2017. The combined suicide rate for males and females aged 15-19 years in 2000 was 8 per 100,000 with no significant changes until 2007, followed by an annual percentage change (APC) of 3% from 2007 to 2014 and 10% from 2014 to 2017.
When the data were broken out by gender, Of note, these young men showed a decreasing trend in APC of –2% from 2000 to 2007 before increasing.
Among females aged 15-19 years, no increase was noted until 2010, then researchers identified an APC of 8% from 2010 to 2017.
For ages 20-24 years, the combined suicide rate for males and females was 13 per 100,000 in 2000, which rose to 17 per 100,000 in 2017. The APC in the older group was 1% from 2000 to 2013 and 6% from 2013 to 2017. Increasing trends were observed for both males and females over the study period.
The study was limited by the potential inaccuracy in cause of death listed on death certificates, such as mistaking a suicide for an accidental overdose, and the increased suicide rate could reflect more accurate reporting, the researchers noted.
Nonetheless, the results support the need for more studies of contributing factors to teen and young adult suicides to help develop prevention strategies and analysis of factors that may have contributed to declines in suicide rates in the past, they said.
Coauthor Dr. Yu was supported by the Harvard Data Science Fellowship. The researchers had no relevant financial disclosures.
SOURCE: Miron O et al. JAMA. 2019 Jun 28;321:2362-4.
FROM JAMA
Key clinical point: Suicide rates in U.S. adolescents and young adults have increased since 2000.
Major finding: The combined suicide rate for males and females aged 15-19 years underwent an annual percentage change of 3% from 2007 to 2014 and 10% from 2014 to 2017.
Study details: The data come from the CDC Underlying Cause of Death database.
Disclosures: Coauthor Dr. Yu was supported by the Harvard Data Science Fellowship. The researchers had no relevant financial disclosures.
Source: Miron O et al. JAMA. 2019 Jun 28;321:2362-4.
Pediatric-onset MS may slow information processing in adulthood
independent of age or disease duration, according to a study published in
Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).
“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.
Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.
Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.
To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.
SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.
The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.
The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.
Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).
“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.
The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.
SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
The study by McKay et al. indicates that onset of multiple sclerosis (MS) during childhood or adolescence has long-term effects, Lauren B. Krupp, MD, and Leigh E. Charvet, PhD, wrote in an accompanying editorial.
In early adulthood, patients with pediatric-onset MS initially may perform better on the Symbol Digit Modalities Test, compared with patients with adult-onset MS. “However, the two groups diverged by the time the [pediatric-onset MS] patients reached 30 years of age, with slower performance in the [pediatric-onset MS] group relative to the [adult-onset MS] group, a difference that persisted over time,” Dr. Krupp and Dr. Charvet wrote. The findings remained even when the researchers adjusted for disease duration.
“Despite initial resiliency and age-based advantages, the study’s findings suggest greater deleterious long-term consequences from developing MS during a period of ongoing brain development,” they wrote.
The effect of slowed cognitive processing on quality of life is unclear, however. “The key question for future research is whether those with [pediatric-onset MS] attain their anticipated educational and occupational achievements in a manner comparable to those with [adult-onset MS],” Dr. Krupp and Dr. Charvet concluded.
Dr. Krupp and Dr. Charvet are affiliated with the Multiple Sclerosis Comprehensive Care Center at New York University. These comments are adapted from an editorial accompanying the article by McKay et al. ( JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546 ). Dr. Krupp reported receiving grants from the National Multiple Sclerosis Society; grants and personal fees from Biogen; and personal fees from Novartis, Sanofi Aventis, Sanofi Genzyme, Shire Pharmaceuticals, Roche, and RedHill Biopharma outside the submitted work. Dr. Charvet reported receiving grants and personal fees from Biogen, grants from the National Multiple Sclerosis Society, and research funding from Novartis and Biogen outside the submitted work.
The study by McKay et al. indicates that onset of multiple sclerosis (MS) during childhood or adolescence has long-term effects, Lauren B. Krupp, MD, and Leigh E. Charvet, PhD, wrote in an accompanying editorial.
In early adulthood, patients with pediatric-onset MS initially may perform better on the Symbol Digit Modalities Test, compared with patients with adult-onset MS. “However, the two groups diverged by the time the [pediatric-onset MS] patients reached 30 years of age, with slower performance in the [pediatric-onset MS] group relative to the [adult-onset MS] group, a difference that persisted over time,” Dr. Krupp and Dr. Charvet wrote. The findings remained even when the researchers adjusted for disease duration.
“Despite initial resiliency and age-based advantages, the study’s findings suggest greater deleterious long-term consequences from developing MS during a period of ongoing brain development,” they wrote.
The effect of slowed cognitive processing on quality of life is unclear, however. “The key question for future research is whether those with [pediatric-onset MS] attain their anticipated educational and occupational achievements in a manner comparable to those with [adult-onset MS],” Dr. Krupp and Dr. Charvet concluded.
Dr. Krupp and Dr. Charvet are affiliated with the Multiple Sclerosis Comprehensive Care Center at New York University. These comments are adapted from an editorial accompanying the article by McKay et al. ( JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546 ). Dr. Krupp reported receiving grants from the National Multiple Sclerosis Society; grants and personal fees from Biogen; and personal fees from Novartis, Sanofi Aventis, Sanofi Genzyme, Shire Pharmaceuticals, Roche, and RedHill Biopharma outside the submitted work. Dr. Charvet reported receiving grants and personal fees from Biogen, grants from the National Multiple Sclerosis Society, and research funding from Novartis and Biogen outside the submitted work.
The study by McKay et al. indicates that onset of multiple sclerosis (MS) during childhood or adolescence has long-term effects, Lauren B. Krupp, MD, and Leigh E. Charvet, PhD, wrote in an accompanying editorial.
In early adulthood, patients with pediatric-onset MS initially may perform better on the Symbol Digit Modalities Test, compared with patients with adult-onset MS. “However, the two groups diverged by the time the [pediatric-onset MS] patients reached 30 years of age, with slower performance in the [pediatric-onset MS] group relative to the [adult-onset MS] group, a difference that persisted over time,” Dr. Krupp and Dr. Charvet wrote. The findings remained even when the researchers adjusted for disease duration.
“Despite initial resiliency and age-based advantages, the study’s findings suggest greater deleterious long-term consequences from developing MS during a period of ongoing brain development,” they wrote.
The effect of slowed cognitive processing on quality of life is unclear, however. “The key question for future research is whether those with [pediatric-onset MS] attain their anticipated educational and occupational achievements in a manner comparable to those with [adult-onset MS],” Dr. Krupp and Dr. Charvet concluded.
Dr. Krupp and Dr. Charvet are affiliated with the Multiple Sclerosis Comprehensive Care Center at New York University. These comments are adapted from an editorial accompanying the article by McKay et al. ( JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546 ). Dr. Krupp reported receiving grants from the National Multiple Sclerosis Society; grants and personal fees from Biogen; and personal fees from Novartis, Sanofi Aventis, Sanofi Genzyme, Shire Pharmaceuticals, Roche, and RedHill Biopharma outside the submitted work. Dr. Charvet reported receiving grants and personal fees from Biogen, grants from the National Multiple Sclerosis Society, and research funding from Novartis and Biogen outside the submitted work.
independent of age or disease duration, according to a study published in
Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).
“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.
Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.
Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.
To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.
SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.
The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.
The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.
Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).
“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.
The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.
SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
independent of age or disease duration, according to a study published in
Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).
“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.
Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.
Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.
To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.
SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.
The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.
The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.
Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).
“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.
The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.
SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
FROM JAMA NEUROLOGY