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Synthetic chemical in consumer products linked to early death, study says
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Children and COVID-19: U.S. adds latest million cases in record time
The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.
The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.
New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.
Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.
The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.
That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”
The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.
The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.
New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.
Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.
The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.
That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”
The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.
The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.
New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.
Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.
The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.
That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”
Acyclovir-Resistant Cutaneous Herpes Simplex Virus in DOCK8 Deficiency
Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. 1 Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). 1 In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. 2 Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. 1 Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV.
Case Report
A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.
During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.
After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion. The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.
Comment
Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.3 Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.4
Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.5 Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.6 However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.
Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.6 Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.
Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.6 For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.
Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.6 Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.12 Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).7 There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.7-9
The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.
Conclusion
DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.
- Chu EY, Freeman AF, Jing H, et al. Cutaneous manifestations of DOCK8 deficiency syndrome. Arch Dermatol. 2012;148:79-84. doi:10.1001/archdermatol.2011.262
- Aydin SE, Kilic SS, Aytekin C, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options—a review of 136 patients. J Clin Immunol. 2015;35:189-198. doi:10.1007/s10875-014-0126-0
- Kearney CJ, Randall KL, Oliaro J. DOCK8 regulates signal transduction events to control immunity. Cell Mol Immunol. 2017;14:406-411. doi:10.1038/cmi.2017.9
- Zhang Q, Dove CG, Hor JL, et al. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med. 2014;211:2549-2566. doi:10.1084/jem.20141307
- Engelhardt KR, Gertz EM, Keles S, et al. The extended clinical phenotype of 64 patients with DOCK8 deficiency. J Allergy Clin Immunol. 2015;136:402-412. doi:10.1016/j.jaci.2014.12.1945
- Chilukuri S, Rosen T. Management of acyclovir-resistant herpes simplex virus. Dermatol Clin. 2003;21:311-320. doi:10.1016/S0733-8635(02)00093-1
- Keles S, Jabara HH, Reisli I, et al. Plasmacytoid dendritic cell depletion in DOCK8 deficiency: rescue of severe herpetic infections with interferon alpha-2b therapy. J Allergy Clin Immunol. 2014;133:1753-1755.e3. doi:10.1016/j.jaci.2014.03.032
- Papan C, Hagl B, Heinz V, et al Beneficial IFN-α treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2014;133:1456-1458. doi:10.1016/j.jaci.2014.02.008
- Metin A, Kanik-Yuksek S, Ozkaya-Parlakay A, et al. Giant herpes labialis in a child with DOCK8-deficient hyper-IgE syndrome. Pediatr Neonatol. 2016;57:79-80. doi:10.1016/j.pedneo.2015.04.011
- Zhang Q, Davis JC, Lamborn IT, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009;361:2046-2055. doi:10.1056/NEJMoa0905506
- Lei JY, Wang Y, Jaffe ES, et al. Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma. Am J Dermatopathol. 2000;22:524-529. doi:10.1097/00000372-200012000-00008
- Castelo-Soccio L, Bernardin R, Stern J, et al. Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146:124-126. doi:10.1001/archdermatol.2009.363
- Shah NN, Freeman AF, Hickstein DD. Addendum to: haploidentical related donor hematopoietic stem cell transplantation for DOCK8 deficiency using post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2019;25:E65-E67. doi:10.1016/j.bbmt.2018.11.014
- Freeman AF, Yazigi N, Shah NN, et al. Tandem orthotopic living donor liver transplantation followed by same donor haploidentical hematopoietic stem cell transplantation for DOCK8 deficiency. Transplantation. 2019;103:2144-2149. doi:10.1097/TP.0000000000002649
- Casto AM, Stout SC, Selvarangan R, et al. Evaluation of genotypic antiviral resistance testing as an alternative to phenotypic testing in a patient with DOCK8 deficiency and severe HSV-1 disease. J Infect Dis. 2020;221:2035-2042. doi:10.1093/infdis/jiaa020
Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. 1 Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). 1 In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. 2 Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. 1 Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV.
Case Report
A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.
During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.
After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion. The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.
Comment
Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.3 Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.4
Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.5 Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.6 However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.
Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.6 Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.
Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.6 For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.
Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.6 Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.12 Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).7 There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.7-9
The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.
Conclusion
DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.
Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. 1 Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). 1 In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. 2 Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. 1 Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV.
Case Report
A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.
During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.
After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion. The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.
Comment
Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.3 Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.4
Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.5 Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.6 However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.
Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.6 Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.
Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.6 For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.
Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.6 Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.12 Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).7 There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.7-9
The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.
Conclusion
DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.
- Chu EY, Freeman AF, Jing H, et al. Cutaneous manifestations of DOCK8 deficiency syndrome. Arch Dermatol. 2012;148:79-84. doi:10.1001/archdermatol.2011.262
- Aydin SE, Kilic SS, Aytekin C, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options—a review of 136 patients. J Clin Immunol. 2015;35:189-198. doi:10.1007/s10875-014-0126-0
- Kearney CJ, Randall KL, Oliaro J. DOCK8 regulates signal transduction events to control immunity. Cell Mol Immunol. 2017;14:406-411. doi:10.1038/cmi.2017.9
- Zhang Q, Dove CG, Hor JL, et al. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med. 2014;211:2549-2566. doi:10.1084/jem.20141307
- Engelhardt KR, Gertz EM, Keles S, et al. The extended clinical phenotype of 64 patients with DOCK8 deficiency. J Allergy Clin Immunol. 2015;136:402-412. doi:10.1016/j.jaci.2014.12.1945
- Chilukuri S, Rosen T. Management of acyclovir-resistant herpes simplex virus. Dermatol Clin. 2003;21:311-320. doi:10.1016/S0733-8635(02)00093-1
- Keles S, Jabara HH, Reisli I, et al. Plasmacytoid dendritic cell depletion in DOCK8 deficiency: rescue of severe herpetic infections with interferon alpha-2b therapy. J Allergy Clin Immunol. 2014;133:1753-1755.e3. doi:10.1016/j.jaci.2014.03.032
- Papan C, Hagl B, Heinz V, et al Beneficial IFN-α treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2014;133:1456-1458. doi:10.1016/j.jaci.2014.02.008
- Metin A, Kanik-Yuksek S, Ozkaya-Parlakay A, et al. Giant herpes labialis in a child with DOCK8-deficient hyper-IgE syndrome. Pediatr Neonatol. 2016;57:79-80. doi:10.1016/j.pedneo.2015.04.011
- Zhang Q, Davis JC, Lamborn IT, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009;361:2046-2055. doi:10.1056/NEJMoa0905506
- Lei JY, Wang Y, Jaffe ES, et al. Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma. Am J Dermatopathol. 2000;22:524-529. doi:10.1097/00000372-200012000-00008
- Castelo-Soccio L, Bernardin R, Stern J, et al. Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146:124-126. doi:10.1001/archdermatol.2009.363
- Shah NN, Freeman AF, Hickstein DD. Addendum to: haploidentical related donor hematopoietic stem cell transplantation for DOCK8 deficiency using post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2019;25:E65-E67. doi:10.1016/j.bbmt.2018.11.014
- Freeman AF, Yazigi N, Shah NN, et al. Tandem orthotopic living donor liver transplantation followed by same donor haploidentical hematopoietic stem cell transplantation for DOCK8 deficiency. Transplantation. 2019;103:2144-2149. doi:10.1097/TP.0000000000002649
- Casto AM, Stout SC, Selvarangan R, et al. Evaluation of genotypic antiviral resistance testing as an alternative to phenotypic testing in a patient with DOCK8 deficiency and severe HSV-1 disease. J Infect Dis. 2020;221:2035-2042. doi:10.1093/infdis/jiaa020
- Chu EY, Freeman AF, Jing H, et al. Cutaneous manifestations of DOCK8 deficiency syndrome. Arch Dermatol. 2012;148:79-84. doi:10.1001/archdermatol.2011.262
- Aydin SE, Kilic SS, Aytekin C, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options—a review of 136 patients. J Clin Immunol. 2015;35:189-198. doi:10.1007/s10875-014-0126-0
- Kearney CJ, Randall KL, Oliaro J. DOCK8 regulates signal transduction events to control immunity. Cell Mol Immunol. 2017;14:406-411. doi:10.1038/cmi.2017.9
- Zhang Q, Dove CG, Hor JL, et al. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med. 2014;211:2549-2566. doi:10.1084/jem.20141307
- Engelhardt KR, Gertz EM, Keles S, et al. The extended clinical phenotype of 64 patients with DOCK8 deficiency. J Allergy Clin Immunol. 2015;136:402-412. doi:10.1016/j.jaci.2014.12.1945
- Chilukuri S, Rosen T. Management of acyclovir-resistant herpes simplex virus. Dermatol Clin. 2003;21:311-320. doi:10.1016/S0733-8635(02)00093-1
- Keles S, Jabara HH, Reisli I, et al. Plasmacytoid dendritic cell depletion in DOCK8 deficiency: rescue of severe herpetic infections with interferon alpha-2b therapy. J Allergy Clin Immunol. 2014;133:1753-1755.e3. doi:10.1016/j.jaci.2014.03.032
- Papan C, Hagl B, Heinz V, et al Beneficial IFN-α treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2014;133:1456-1458. doi:10.1016/j.jaci.2014.02.008
- Metin A, Kanik-Yuksek S, Ozkaya-Parlakay A, et al. Giant herpes labialis in a child with DOCK8-deficient hyper-IgE syndrome. Pediatr Neonatol. 2016;57:79-80. doi:10.1016/j.pedneo.2015.04.011
- Zhang Q, Davis JC, Lamborn IT, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009;361:2046-2055. doi:10.1056/NEJMoa0905506
- Lei JY, Wang Y, Jaffe ES, et al. Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma. Am J Dermatopathol. 2000;22:524-529. doi:10.1097/00000372-200012000-00008
- Castelo-Soccio L, Bernardin R, Stern J, et al. Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146:124-126. doi:10.1001/archdermatol.2009.363
- Shah NN, Freeman AF, Hickstein DD. Addendum to: haploidentical related donor hematopoietic stem cell transplantation for DOCK8 deficiency using post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2019;25:E65-E67. doi:10.1016/j.bbmt.2018.11.014
- Freeman AF, Yazigi N, Shah NN, et al. Tandem orthotopic living donor liver transplantation followed by same donor haploidentical hematopoietic stem cell transplantation for DOCK8 deficiency. Transplantation. 2019;103:2144-2149. doi:10.1097/TP.0000000000002649
- Casto AM, Stout SC, Selvarangan R, et al. Evaluation of genotypic antiviral resistance testing as an alternative to phenotypic testing in a patient with DOCK8 deficiency and severe HSV-1 disease. J Infect Dis. 2020;221:2035-2042. doi:10.1093/infdis/jiaa020
Practice Points
- Patients with dedicator of cytokinesis 8 ( DOCK 8 ) deficiency are susceptible to development of severe recalcitrant viral cutaneous infections, including herpes simplex virus (HSV).
- Dermatologists should be aware that prophylactic acyclovir may not be sufficient for HSV suppression in the setting of severe immunodeficiency.
- Acyclovir-resistant cutaneous HSV lesions require escalation of therapy, which may include addition of foscarnet, cidofovir, or subcutaneous pegylated interferon alfa-2b to the therapeutic regimen.
- Viral culture should be performed on suspicious lesions in DOCK 8 -deficient patients despite acyclovir prophylaxis, and the threshold for HSV resistance testing should be low.
Bystander actions can reduce children’s risk of drowning
The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.
“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.
“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.
The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.
“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”
Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.
In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.
They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.
Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).
The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).
However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.
The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.
“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.
Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.
“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”
The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.
The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.
“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.
Dr. Shenoi echoed this sentiment.
“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”
The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.
Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.
A version of this article first appeared on Medscape.com.
The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.
“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.
“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.
The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.
“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”
Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.
In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.
They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.
Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).
The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).
However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.
The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.
“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.
Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.
“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”
The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.
The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.
“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.
Dr. Shenoi echoed this sentiment.
“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”
The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.
Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.
A version of this article first appeared on Medscape.com.
The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.
“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.
“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.
The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.
“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”
Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.
In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.
They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.
Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).
The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).
However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.
The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.
“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.
Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.
“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”
The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.
The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.
“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.
Dr. Shenoi echoed this sentiment.
“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”
The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.
Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.
A version of this article first appeared on Medscape.com.
Effect of COVID-19 pandemic on respiratory infectious diseases in primary care practice
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
Family violence patterns change during pandemic
Among adolescents treated for injuries caused by family-member violence, the proportion of incidents that involved illegal drugs or weapons more than doubled during the pandemic, and incidents that involved alcohol nearly doubled, according to data presented October 10 at the American Academy of Pediatrics 2021 National Conference.
“The COVID-19 pandemic amplified risk factors known to increase family interpersonal violence, such as increased need for parental supervision, parental stress, financial hardship, poor mental health, and isolation,” said investigator Mattea Miller, an MD candidate at the Johns Hopkins University School of Medicine, Baltimore.
To examine the issue, she and her colleagues “sought to characterize the prevalence and circumstances of adolescent injuries resulting from family interpersonal violence,” Ms. Miller told this news organization.
Their retrospective analysis involved children 10 to 15 years of age seen before or during the pandemic in the emergency department at Johns Hopkins Children’s Center for injuries that resulted from a violent incident with a family member.
Of the 819 incidents of violence-related injuries seen during the study period – the prepandemic ran from Jan. 1, 2019 to March 29, 2020, and the pandemic period ran from March 30, 2020, the date a stay-at-home order was first issued in Maryland, to Dec. 31, 2020 – 448 (54.7%) involved a family member. The proportion of such injuries was similar before and during the pandemic (54.6% vs. 54.9%; P = .99).
Most (83.9%) of these incidents occurred at home, 76.6% involved a parent or guardian, and 66.7% involved the youth being transported to the hospital by police.
It is surprising that families accounted for such a high level of violence involving adolescents, said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine, Houston, who was not involved in the research.
“The most common source of child physical abuse in younger children – infants and toddlers – [is the] parents,” who account for about 75% of cases, “but to see that amount of violence in adolescents was unexpected,” he told this news organization.
Patients in the study cohort were more likely to be Black than the hospital’s overall emergency-department population (84.4% vs. 60.0%), and more likely to be covered by public insurance (71.2% vs. 60.0%).
In the study cohort, 54.0% of the patients were female.
“We were surprised to see that 8% of visits did not have a referral to a social worker” – 92% of patients in the study cohort received a social work consult during their visit to the emergency department – and that number “did not vary during the COVID-19 pandemic,” Ms. Miller said. The pandemic exacerbated the types of stresses that social workers can help address, so “this potentially represents a gap in care that is important to address,” she added.
Increase in use of alcohol, drugs, weapons
The most significant increases from the prepandemic period to the pandemic period were in incidents that involved alcohol (10.0% vs. 18.8%; P ≤ .001), illegal drugs (6.5% vs. 14.9%; P ≤ .001), and weapons, most often a knife (10.7% vs. 23.8%; P ≤ .001).
“An obvious potential explanation for the increase in alcohol, drug, and weapons [involvement] would be the mental health impact of the pandemic in conjunction with the economic stressors that some families may be feeling,” Dr. Greeley said. Teachers are the most common reporters of child abuse, so it’s possible that reports of violence decreased when schools switched to remote learning. But with most schools back to in-person learning, data have not yet shown a surge in reporting, he noted.
The “epidemiology of family violence may be impacted by increased time at home, disruptions in school and family routines, exacerbations in mental health conditions, and financial stresses common during the pandemic,” said senior study investigator Leticia Ryan, MD, MPH, director of research in pediatrics at Johns Hopkins Medicine.
And research has shown increases in the use of alcohol and illegal drugs during the pandemic, she noted.
“As we transition to postpandemic life, it will be important to identify at-risk adolescents and families and provide supports,” Dr. Ryan told this news organization. “The emergency department is an appropriate setting to intervene with youth who have experienced family violence and initiate preventive strategies to avoid future violence.”
Among the strategies to identify and intervene for at-risk patients is the CRAFFT substance use screening tool. Furthermore, “case management, involvement of child protection services, and linkage with relevant support services may all be appropriate, depending on circumstances,” Ms. Miller added.
“Exposure to family violence at a young age increases the likelihood that a child will be exposed to additional violence or become a perpetrator of violence in the future, continuing a cycle of violence,” Ms. Miller explained. “Given that studies of adolescent violence often focus on peer violence, a better understanding of the epidemiology of violence-related injuries resulting from family violence is needed to better inform the development of more comprehensive prevention strategies.”
This study did not note any external funding. Ms. Miller, Dr. Greeley, and Dr. Ryan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among adolescents treated for injuries caused by family-member violence, the proportion of incidents that involved illegal drugs or weapons more than doubled during the pandemic, and incidents that involved alcohol nearly doubled, according to data presented October 10 at the American Academy of Pediatrics 2021 National Conference.
“The COVID-19 pandemic amplified risk factors known to increase family interpersonal violence, such as increased need for parental supervision, parental stress, financial hardship, poor mental health, and isolation,” said investigator Mattea Miller, an MD candidate at the Johns Hopkins University School of Medicine, Baltimore.
To examine the issue, she and her colleagues “sought to characterize the prevalence and circumstances of adolescent injuries resulting from family interpersonal violence,” Ms. Miller told this news organization.
Their retrospective analysis involved children 10 to 15 years of age seen before or during the pandemic in the emergency department at Johns Hopkins Children’s Center for injuries that resulted from a violent incident with a family member.
Of the 819 incidents of violence-related injuries seen during the study period – the prepandemic ran from Jan. 1, 2019 to March 29, 2020, and the pandemic period ran from March 30, 2020, the date a stay-at-home order was first issued in Maryland, to Dec. 31, 2020 – 448 (54.7%) involved a family member. The proportion of such injuries was similar before and during the pandemic (54.6% vs. 54.9%; P = .99).
Most (83.9%) of these incidents occurred at home, 76.6% involved a parent or guardian, and 66.7% involved the youth being transported to the hospital by police.
It is surprising that families accounted for such a high level of violence involving adolescents, said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine, Houston, who was not involved in the research.
“The most common source of child physical abuse in younger children – infants and toddlers – [is the] parents,” who account for about 75% of cases, “but to see that amount of violence in adolescents was unexpected,” he told this news organization.
Patients in the study cohort were more likely to be Black than the hospital’s overall emergency-department population (84.4% vs. 60.0%), and more likely to be covered by public insurance (71.2% vs. 60.0%).
In the study cohort, 54.0% of the patients were female.
“We were surprised to see that 8% of visits did not have a referral to a social worker” – 92% of patients in the study cohort received a social work consult during their visit to the emergency department – and that number “did not vary during the COVID-19 pandemic,” Ms. Miller said. The pandemic exacerbated the types of stresses that social workers can help address, so “this potentially represents a gap in care that is important to address,” she added.
Increase in use of alcohol, drugs, weapons
The most significant increases from the prepandemic period to the pandemic period were in incidents that involved alcohol (10.0% vs. 18.8%; P ≤ .001), illegal drugs (6.5% vs. 14.9%; P ≤ .001), and weapons, most often a knife (10.7% vs. 23.8%; P ≤ .001).
“An obvious potential explanation for the increase in alcohol, drug, and weapons [involvement] would be the mental health impact of the pandemic in conjunction with the economic stressors that some families may be feeling,” Dr. Greeley said. Teachers are the most common reporters of child abuse, so it’s possible that reports of violence decreased when schools switched to remote learning. But with most schools back to in-person learning, data have not yet shown a surge in reporting, he noted.
The “epidemiology of family violence may be impacted by increased time at home, disruptions in school and family routines, exacerbations in mental health conditions, and financial stresses common during the pandemic,” said senior study investigator Leticia Ryan, MD, MPH, director of research in pediatrics at Johns Hopkins Medicine.
And research has shown increases in the use of alcohol and illegal drugs during the pandemic, she noted.
“As we transition to postpandemic life, it will be important to identify at-risk adolescents and families and provide supports,” Dr. Ryan told this news organization. “The emergency department is an appropriate setting to intervene with youth who have experienced family violence and initiate preventive strategies to avoid future violence.”
Among the strategies to identify and intervene for at-risk patients is the CRAFFT substance use screening tool. Furthermore, “case management, involvement of child protection services, and linkage with relevant support services may all be appropriate, depending on circumstances,” Ms. Miller added.
“Exposure to family violence at a young age increases the likelihood that a child will be exposed to additional violence or become a perpetrator of violence in the future, continuing a cycle of violence,” Ms. Miller explained. “Given that studies of adolescent violence often focus on peer violence, a better understanding of the epidemiology of violence-related injuries resulting from family violence is needed to better inform the development of more comprehensive prevention strategies.”
This study did not note any external funding. Ms. Miller, Dr. Greeley, and Dr. Ryan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among adolescents treated for injuries caused by family-member violence, the proportion of incidents that involved illegal drugs or weapons more than doubled during the pandemic, and incidents that involved alcohol nearly doubled, according to data presented October 10 at the American Academy of Pediatrics 2021 National Conference.
“The COVID-19 pandemic amplified risk factors known to increase family interpersonal violence, such as increased need for parental supervision, parental stress, financial hardship, poor mental health, and isolation,” said investigator Mattea Miller, an MD candidate at the Johns Hopkins University School of Medicine, Baltimore.
To examine the issue, she and her colleagues “sought to characterize the prevalence and circumstances of adolescent injuries resulting from family interpersonal violence,” Ms. Miller told this news organization.
Their retrospective analysis involved children 10 to 15 years of age seen before or during the pandemic in the emergency department at Johns Hopkins Children’s Center for injuries that resulted from a violent incident with a family member.
Of the 819 incidents of violence-related injuries seen during the study period – the prepandemic ran from Jan. 1, 2019 to March 29, 2020, and the pandemic period ran from March 30, 2020, the date a stay-at-home order was first issued in Maryland, to Dec. 31, 2020 – 448 (54.7%) involved a family member. The proportion of such injuries was similar before and during the pandemic (54.6% vs. 54.9%; P = .99).
Most (83.9%) of these incidents occurred at home, 76.6% involved a parent or guardian, and 66.7% involved the youth being transported to the hospital by police.
It is surprising that families accounted for such a high level of violence involving adolescents, said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine, Houston, who was not involved in the research.
“The most common source of child physical abuse in younger children – infants and toddlers – [is the] parents,” who account for about 75% of cases, “but to see that amount of violence in adolescents was unexpected,” he told this news organization.
Patients in the study cohort were more likely to be Black than the hospital’s overall emergency-department population (84.4% vs. 60.0%), and more likely to be covered by public insurance (71.2% vs. 60.0%).
In the study cohort, 54.0% of the patients were female.
“We were surprised to see that 8% of visits did not have a referral to a social worker” – 92% of patients in the study cohort received a social work consult during their visit to the emergency department – and that number “did not vary during the COVID-19 pandemic,” Ms. Miller said. The pandemic exacerbated the types of stresses that social workers can help address, so “this potentially represents a gap in care that is important to address,” she added.
Increase in use of alcohol, drugs, weapons
The most significant increases from the prepandemic period to the pandemic period were in incidents that involved alcohol (10.0% vs. 18.8%; P ≤ .001), illegal drugs (6.5% vs. 14.9%; P ≤ .001), and weapons, most often a knife (10.7% vs. 23.8%; P ≤ .001).
“An obvious potential explanation for the increase in alcohol, drug, and weapons [involvement] would be the mental health impact of the pandemic in conjunction with the economic stressors that some families may be feeling,” Dr. Greeley said. Teachers are the most common reporters of child abuse, so it’s possible that reports of violence decreased when schools switched to remote learning. But with most schools back to in-person learning, data have not yet shown a surge in reporting, he noted.
The “epidemiology of family violence may be impacted by increased time at home, disruptions in school and family routines, exacerbations in mental health conditions, and financial stresses common during the pandemic,” said senior study investigator Leticia Ryan, MD, MPH, director of research in pediatrics at Johns Hopkins Medicine.
And research has shown increases in the use of alcohol and illegal drugs during the pandemic, she noted.
“As we transition to postpandemic life, it will be important to identify at-risk adolescents and families and provide supports,” Dr. Ryan told this news organization. “The emergency department is an appropriate setting to intervene with youth who have experienced family violence and initiate preventive strategies to avoid future violence.”
Among the strategies to identify and intervene for at-risk patients is the CRAFFT substance use screening tool. Furthermore, “case management, involvement of child protection services, and linkage with relevant support services may all be appropriate, depending on circumstances,” Ms. Miller added.
“Exposure to family violence at a young age increases the likelihood that a child will be exposed to additional violence or become a perpetrator of violence in the future, continuing a cycle of violence,” Ms. Miller explained. “Given that studies of adolescent violence often focus on peer violence, a better understanding of the epidemiology of violence-related injuries resulting from family violence is needed to better inform the development of more comprehensive prevention strategies.”
This study did not note any external funding. Ms. Miller, Dr. Greeley, and Dr. Ryan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Psychiatrists shift stance on gender dysphoria, recommend therapy
A new position statement from the Royal Australian and New Zealand College of Psychiatrists (RANZCP) stresses the importance of a mental health evaluation for people with gender dysphoria – in particular for children and adolescents – before any firm decisions are made on whether to prescribe hormonal treatments to transition, or perform surgeries, often referred to as “gender-affirming care.”
“There is a paucity of quality evidence on the outcomes of those presenting with gender dysphoria. In particular, there is a need for better evidence in relation to outcomes for children and young people,” the guidance states.
Because gender dysphoria “is associated with significant distress ... each case should be assessed by a mental health professional, which will frequently be a psychiatrist, with the person at the center of care. It is important the psychological state and context in which gender dysphoria has arisen is explored to assess the most appropriate treatment,” it adds.
The move by the psychiatry body represents a big shift in the landscape regarding recommendations for the treatment of gender dysphoria in Australia and New Zealand.
Asked to explain the new RANZCP position, Philip Morris, MBBS, FRANZCP, said: “The College acknowledged the complexity of the issues and the legitimacy of different approaches.”
Exploration of a patient’s reasons for identifying as transgender is essential, he said in an interview, especially when it comes to young people.
“There may be other reasons for doing it, and we need to look for those, identify them and treat them. This needs to be done before initiating hormones and changing the whole physical nature of the child,” he said.
“A cautious psychotherapy-first approach makes sense. If we can do that with adolescents, then we will take a big step in the right direction,” stressed Dr. Morris, who is president of the National Association of Practising Psychiatrists in Australia.
Keira Bell case and Scandinavian stance lead to more open discussion
The rapid rise in gender dysphoria among adolescents in the Western world, referred to as “rapid-onset” or “late-onset” gender dysphoria, has seen a huge increase in the number of natal girls presenting and created frenzied debate that has intensified worldwide in the last 12 months about how to best treat youth with gender dysphoria.
Concerns have arisen that some transgender identification is due to social contagion, and there is a growing number of “detransitioners” – people who identified as transgender, transitioned to the opposite gender, but then regretted their decision, changed their minds, and “detransitioned” back to their birth sex. If they have had hormone therapy, and in some cases surgery, they are left with irreversible changes to their bodies.
As a result, Scandinavian countries, most notably Finland, once eager advocates of the gender-affirmative approach, have pulled back and issued new treatment guidelines in 2020 stating that psychotherapy, rather than gender reassignment, should be the first line of treatment for gender-dysphoric youth.
This, along with a landmark High Court decision in the U.K. regarding the use of puberty-blocking drugs for children with gender dysphoria, brought by detransitioner Keira Bell, which was recently overturned by the Appeal Court, but which Ms. Bell now says she will take to the Supreme Court, has led to a considerable shift in the conversation around treating transgender adolescents with hormonal therapy, says Dr. Morris.
“This [has moved from] ... a topic that could previously not be talked about freely to one that we can discuss more openly now. This is a big improvement. Previously, everyone thought it was all settled, but it’s not, certainly not from a medical angle,” he states.
At odds with prior Australian recommendations
The RANZCP had previously endorsed the standard guidelines of the Royal Children’s Hospital (RCH) Melbourne, followed by most gender-identity services in Australia and similar guidance from New Zealand, which both recommend gender-affirming care.
“Increasing evidence demonstrates that with supportive, gender-affirming care during childhood and adolescence, harms can be ameliorated and mental health and well-being outcomes can be significantly improved,” state the RCH guidelines.
But in 2019, RANZCP removed its endorsement of the RCH guidelines and started a consultation, which resulted in the new position statement.
However, Ken Pang, MD, of the Murdoch Children’s Research Institute in Melbourne and an author of the RCH guidelines, says the key recommendations of the new RANZCP position statement are consistent with their own guidelines.
The former note “the need for a skilled mental health clinician in providing comprehensive exploration of a child or adolescent’s biopsychosocial context,” Dr. Pang says.
However, it’s difficult not to see the contrast in stance when the new RANZCP statement maintains: “Research on gender dysphoria is still emerging. There are polarized views and mixed evidence regarding treatment options for people presenting with gender identity concerns, especially children and young people.”
Dr. Pang says the RCH guidelines do, however, recognize the need for further research in the field.
“I look forward to being able to incorporate such research, including from our own Trans20 study, into future revisions of our guidelines,” he told this news organization.
Watch your backs with affirmative therapy: Will there be a compromise?
Dr. Morris says there will obviously be cases where “the child might transition with a medical intervention, but that wouldn’t be the first step.”
And yet, he adds, “There are those who push the pro-trans view that everyone should be allowed to transition, and the doctors are only technicians that provide hormones with no questions asked.”
But from a doctor’s perspective, clinicians will still be held responsible in medical and legal terms for the treatments given, he stressed.
“I don’t think they will ever not be accountable for that. They will always need to determine in their own mind whether their actions have positive value that outweigh any disadvantages,” Dr. Morris continues.
The RANZCP statement does, in fact, stress just this.
All health care professionals need to “be aware of ethical and medicolegal dilemmas” pertaining to affirmative therapy, it indicates. “Psychiatrists should practice within the relevant laws and accepted professional standards in relation to assessing capacity and obtaining consent...”
Dr. Morris hopes there will ultimately be many more checks and balances in place and that courts and clinicians will need to step back and not assume every child who seeks to transition is doing it as a result of pure gender dysphoria.
He predicts that things will end in a compromise.
“In my view, this compromise will treat children with respect and approach them like any other patient that presents with a condition that requires proper assessment and treatment.”
“In the end, some cases will be transitioned, but there will be fewer than [are] transitioned at the moment,” he predicts.
Dr. Morris has reported no relevant financial relationships. Dr. Pang is a member of the Australian Professional Association for Trans Health and its research committee.
A version of this article first appeared on Medscape.com.
A new position statement from the Royal Australian and New Zealand College of Psychiatrists (RANZCP) stresses the importance of a mental health evaluation for people with gender dysphoria – in particular for children and adolescents – before any firm decisions are made on whether to prescribe hormonal treatments to transition, or perform surgeries, often referred to as “gender-affirming care.”
“There is a paucity of quality evidence on the outcomes of those presenting with gender dysphoria. In particular, there is a need for better evidence in relation to outcomes for children and young people,” the guidance states.
Because gender dysphoria “is associated with significant distress ... each case should be assessed by a mental health professional, which will frequently be a psychiatrist, with the person at the center of care. It is important the psychological state and context in which gender dysphoria has arisen is explored to assess the most appropriate treatment,” it adds.
The move by the psychiatry body represents a big shift in the landscape regarding recommendations for the treatment of gender dysphoria in Australia and New Zealand.
Asked to explain the new RANZCP position, Philip Morris, MBBS, FRANZCP, said: “The College acknowledged the complexity of the issues and the legitimacy of different approaches.”
Exploration of a patient’s reasons for identifying as transgender is essential, he said in an interview, especially when it comes to young people.
“There may be other reasons for doing it, and we need to look for those, identify them and treat them. This needs to be done before initiating hormones and changing the whole physical nature of the child,” he said.
“A cautious psychotherapy-first approach makes sense. If we can do that with adolescents, then we will take a big step in the right direction,” stressed Dr. Morris, who is president of the National Association of Practising Psychiatrists in Australia.
Keira Bell case and Scandinavian stance lead to more open discussion
The rapid rise in gender dysphoria among adolescents in the Western world, referred to as “rapid-onset” or “late-onset” gender dysphoria, has seen a huge increase in the number of natal girls presenting and created frenzied debate that has intensified worldwide in the last 12 months about how to best treat youth with gender dysphoria.
Concerns have arisen that some transgender identification is due to social contagion, and there is a growing number of “detransitioners” – people who identified as transgender, transitioned to the opposite gender, but then regretted their decision, changed their minds, and “detransitioned” back to their birth sex. If they have had hormone therapy, and in some cases surgery, they are left with irreversible changes to their bodies.
As a result, Scandinavian countries, most notably Finland, once eager advocates of the gender-affirmative approach, have pulled back and issued new treatment guidelines in 2020 stating that psychotherapy, rather than gender reassignment, should be the first line of treatment for gender-dysphoric youth.
This, along with a landmark High Court decision in the U.K. regarding the use of puberty-blocking drugs for children with gender dysphoria, brought by detransitioner Keira Bell, which was recently overturned by the Appeal Court, but which Ms. Bell now says she will take to the Supreme Court, has led to a considerable shift in the conversation around treating transgender adolescents with hormonal therapy, says Dr. Morris.
“This [has moved from] ... a topic that could previously not be talked about freely to one that we can discuss more openly now. This is a big improvement. Previously, everyone thought it was all settled, but it’s not, certainly not from a medical angle,” he states.
At odds with prior Australian recommendations
The RANZCP had previously endorsed the standard guidelines of the Royal Children’s Hospital (RCH) Melbourne, followed by most gender-identity services in Australia and similar guidance from New Zealand, which both recommend gender-affirming care.
“Increasing evidence demonstrates that with supportive, gender-affirming care during childhood and adolescence, harms can be ameliorated and mental health and well-being outcomes can be significantly improved,” state the RCH guidelines.
But in 2019, RANZCP removed its endorsement of the RCH guidelines and started a consultation, which resulted in the new position statement.
However, Ken Pang, MD, of the Murdoch Children’s Research Institute in Melbourne and an author of the RCH guidelines, says the key recommendations of the new RANZCP position statement are consistent with their own guidelines.
The former note “the need for a skilled mental health clinician in providing comprehensive exploration of a child or adolescent’s biopsychosocial context,” Dr. Pang says.
However, it’s difficult not to see the contrast in stance when the new RANZCP statement maintains: “Research on gender dysphoria is still emerging. There are polarized views and mixed evidence regarding treatment options for people presenting with gender identity concerns, especially children and young people.”
Dr. Pang says the RCH guidelines do, however, recognize the need for further research in the field.
“I look forward to being able to incorporate such research, including from our own Trans20 study, into future revisions of our guidelines,” he told this news organization.
Watch your backs with affirmative therapy: Will there be a compromise?
Dr. Morris says there will obviously be cases where “the child might transition with a medical intervention, but that wouldn’t be the first step.”
And yet, he adds, “There are those who push the pro-trans view that everyone should be allowed to transition, and the doctors are only technicians that provide hormones with no questions asked.”
But from a doctor’s perspective, clinicians will still be held responsible in medical and legal terms for the treatments given, he stressed.
“I don’t think they will ever not be accountable for that. They will always need to determine in their own mind whether their actions have positive value that outweigh any disadvantages,” Dr. Morris continues.
The RANZCP statement does, in fact, stress just this.
All health care professionals need to “be aware of ethical and medicolegal dilemmas” pertaining to affirmative therapy, it indicates. “Psychiatrists should practice within the relevant laws and accepted professional standards in relation to assessing capacity and obtaining consent...”
Dr. Morris hopes there will ultimately be many more checks and balances in place and that courts and clinicians will need to step back and not assume every child who seeks to transition is doing it as a result of pure gender dysphoria.
He predicts that things will end in a compromise.
“In my view, this compromise will treat children with respect and approach them like any other patient that presents with a condition that requires proper assessment and treatment.”
“In the end, some cases will be transitioned, but there will be fewer than [are] transitioned at the moment,” he predicts.
Dr. Morris has reported no relevant financial relationships. Dr. Pang is a member of the Australian Professional Association for Trans Health and its research committee.
A version of this article first appeared on Medscape.com.
A new position statement from the Royal Australian and New Zealand College of Psychiatrists (RANZCP) stresses the importance of a mental health evaluation for people with gender dysphoria – in particular for children and adolescents – before any firm decisions are made on whether to prescribe hormonal treatments to transition, or perform surgeries, often referred to as “gender-affirming care.”
“There is a paucity of quality evidence on the outcomes of those presenting with gender dysphoria. In particular, there is a need for better evidence in relation to outcomes for children and young people,” the guidance states.
Because gender dysphoria “is associated with significant distress ... each case should be assessed by a mental health professional, which will frequently be a psychiatrist, with the person at the center of care. It is important the psychological state and context in which gender dysphoria has arisen is explored to assess the most appropriate treatment,” it adds.
The move by the psychiatry body represents a big shift in the landscape regarding recommendations for the treatment of gender dysphoria in Australia and New Zealand.
Asked to explain the new RANZCP position, Philip Morris, MBBS, FRANZCP, said: “The College acknowledged the complexity of the issues and the legitimacy of different approaches.”
Exploration of a patient’s reasons for identifying as transgender is essential, he said in an interview, especially when it comes to young people.
“There may be other reasons for doing it, and we need to look for those, identify them and treat them. This needs to be done before initiating hormones and changing the whole physical nature of the child,” he said.
“A cautious psychotherapy-first approach makes sense. If we can do that with adolescents, then we will take a big step in the right direction,” stressed Dr. Morris, who is president of the National Association of Practising Psychiatrists in Australia.
Keira Bell case and Scandinavian stance lead to more open discussion
The rapid rise in gender dysphoria among adolescents in the Western world, referred to as “rapid-onset” or “late-onset” gender dysphoria, has seen a huge increase in the number of natal girls presenting and created frenzied debate that has intensified worldwide in the last 12 months about how to best treat youth with gender dysphoria.
Concerns have arisen that some transgender identification is due to social contagion, and there is a growing number of “detransitioners” – people who identified as transgender, transitioned to the opposite gender, but then regretted their decision, changed their minds, and “detransitioned” back to their birth sex. If they have had hormone therapy, and in some cases surgery, they are left with irreversible changes to their bodies.
As a result, Scandinavian countries, most notably Finland, once eager advocates of the gender-affirmative approach, have pulled back and issued new treatment guidelines in 2020 stating that psychotherapy, rather than gender reassignment, should be the first line of treatment for gender-dysphoric youth.
This, along with a landmark High Court decision in the U.K. regarding the use of puberty-blocking drugs for children with gender dysphoria, brought by detransitioner Keira Bell, which was recently overturned by the Appeal Court, but which Ms. Bell now says she will take to the Supreme Court, has led to a considerable shift in the conversation around treating transgender adolescents with hormonal therapy, says Dr. Morris.
“This [has moved from] ... a topic that could previously not be talked about freely to one that we can discuss more openly now. This is a big improvement. Previously, everyone thought it was all settled, but it’s not, certainly not from a medical angle,” he states.
At odds with prior Australian recommendations
The RANZCP had previously endorsed the standard guidelines of the Royal Children’s Hospital (RCH) Melbourne, followed by most gender-identity services in Australia and similar guidance from New Zealand, which both recommend gender-affirming care.
“Increasing evidence demonstrates that with supportive, gender-affirming care during childhood and adolescence, harms can be ameliorated and mental health and well-being outcomes can be significantly improved,” state the RCH guidelines.
But in 2019, RANZCP removed its endorsement of the RCH guidelines and started a consultation, which resulted in the new position statement.
However, Ken Pang, MD, of the Murdoch Children’s Research Institute in Melbourne and an author of the RCH guidelines, says the key recommendations of the new RANZCP position statement are consistent with their own guidelines.
The former note “the need for a skilled mental health clinician in providing comprehensive exploration of a child or adolescent’s biopsychosocial context,” Dr. Pang says.
However, it’s difficult not to see the contrast in stance when the new RANZCP statement maintains: “Research on gender dysphoria is still emerging. There are polarized views and mixed evidence regarding treatment options for people presenting with gender identity concerns, especially children and young people.”
Dr. Pang says the RCH guidelines do, however, recognize the need for further research in the field.
“I look forward to being able to incorporate such research, including from our own Trans20 study, into future revisions of our guidelines,” he told this news organization.
Watch your backs with affirmative therapy: Will there be a compromise?
Dr. Morris says there will obviously be cases where “the child might transition with a medical intervention, but that wouldn’t be the first step.”
And yet, he adds, “There are those who push the pro-trans view that everyone should be allowed to transition, and the doctors are only technicians that provide hormones with no questions asked.”
But from a doctor’s perspective, clinicians will still be held responsible in medical and legal terms for the treatments given, he stressed.
“I don’t think they will ever not be accountable for that. They will always need to determine in their own mind whether their actions have positive value that outweigh any disadvantages,” Dr. Morris continues.
The RANZCP statement does, in fact, stress just this.
All health care professionals need to “be aware of ethical and medicolegal dilemmas” pertaining to affirmative therapy, it indicates. “Psychiatrists should practice within the relevant laws and accepted professional standards in relation to assessing capacity and obtaining consent...”
Dr. Morris hopes there will ultimately be many more checks and balances in place and that courts and clinicians will need to step back and not assume every child who seeks to transition is doing it as a result of pure gender dysphoria.
He predicts that things will end in a compromise.
“In my view, this compromise will treat children with respect and approach them like any other patient that presents with a condition that requires proper assessment and treatment.”
“In the end, some cases will be transitioned, but there will be fewer than [are] transitioned at the moment,” he predicts.
Dr. Morris has reported no relevant financial relationships. Dr. Pang is a member of the Australian Professional Association for Trans Health and its research committee.
A version of this article first appeared on Medscape.com.
Adolescents who exercised after a concussion recovered faster in RCT
After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.
The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.
Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”
“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.
The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.
For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.
“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.
The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.
A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).
Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.
More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.
The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.
The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.
After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.
The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.
Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”
“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.
The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.
For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.
“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.
The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.
A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).
Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.
More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.
The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.
The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.
After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.
The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.
Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”
“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.
The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.
For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.
“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.
The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.
A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).
Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.
More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.
The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.
The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.
FROM THE LANCET CHILD & ADOLESCENT HEALTH
Benzene prompts recalls of spray antifungals and sunscreens
Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.
Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.
The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.
Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.
In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.
“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.
In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.
In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.
Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.
Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.
Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.
The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.
Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.
In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.
“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.
In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.
In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.
Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.
Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.
Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.
The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.
Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.
In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.
“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.
In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.
In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.
Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.
Quality of Life, Diagnosis, and/or Therapeutics in Pediatric MS
Vikram Bhise, MD, Is an Associate Professor at Rutgers – Robert Wood Johnson Medical School. He specializes in Epilepsy and Pediatric Neuroimmunology, and runs the pediatric demyelinating diseases program, evaluating children with multiple sclerosis, autoimmune encephalopathy, and related diseases. He trained in Pediatrics and Pediatric Neurology, at Maimonides Medical Center and Montefiore Medical Center, respectively. He subsequently received additional training in Clinical Neurophysiology with a focus on Epilepsy at SUNY Downstate Medical Center, and in Pediatric Multiple Sclerosis at SUNY Stony Brook Medical Center. Dr. Bhise conducts clinical research focused on biomarkers and quality of life in pediatric multiple sclerosis, as well as studies in epilepsy and neurogenetics.
Q1. As a specialist who focuses on neuroimmunology, what forms of measurement do you use to make an evaluation or diagnosis for children with multiple sclerosis?
A1. There's a lot that goes into evaluating or diagnosing children with MS. Usually we start off with the story that the family brings to us. We look at what the child is experiencing and what the parents are seeing. Then we do a dedicated examination trying to substantiate the findings that they're describing and look for others they may not even be aware of. If they are having some blurred vision in their eye, can we tell if there's some abnormalities there that are correlating with what they see?
We try to get a good sense of the time-course of things, observing whether this is the first time something's happened or if this has this been going on for a while. Have there been multiple things going on, multiple episodes? We're primarily looking for events called relapses, which are neurologic attacks that are not quick. They don’t last for seconds or hours; they can last for days to weeks, sometimes even months. Individuals will have episodes that tend to get worse and then tend to get better. This is the type of description we’re looking to come from the families.
Once that assessment is complete, we've found that the MRI is one of the best tools in helping us confirm the diagnosis. It's not just diagnostic but the MRI also has some prognostic potential and we're looking specifically for patterns in the MRIs. For children, that pattern can be a little bit more challenging. Their patterns can often overlap with patterns of other inflammatory diseases of the brain like ADEM for example and make it much more difficult for us to characterize someone as truly having MS.
There are also some other diseases which have been discovered in the past decade or elaborated upon like neuromyelitis optica and MOG antibody disorder, which can look exactly like MS in the early stages. Sometimes, that's just not all the information we need. Sometimes it's more difficult to make those distinctions and in these cases, we will look at a spinal tap, a lumbar puncture, and for specific studies from those procedures to help us get a better understanding. There may be other ancillary tests that we use, such as evoked potentials, for example.
Evoked potential testing has kind of fallen to the wayside over the past decade because of the MRI studies becoming a much more useful tool, but we may still use the visual evoked potential to see if there are subtle lesions that can't be seen on the MRI. Other methods might include optical coherence tomography, which is another test looking at the eye that gives you a specific look at the retinal nerve fiber layer, which gets thinned after attacks on the eye on the optic nerve.
We may do neuropsychological testing, which is a battery of tests looking at different cognitive domains and trying to get a sense of a person's cognitive profile to see if that matches what we would expect in somebody with MS. This test could be more challenging for a teen and a child, particularly a younger child. When it comes to pediatric neuropsychology, it's a little bit harder sometimes to get good data, particularly from younger kids.
In addition, we have a battery of tests that we do on the serum. Some disorders, like NMO and MOG, have antibodies that help us identify them. We don't have a specific test that says, yes, you have MS and no, you don't have MS. It's really the combination of all the tools.
We do these tests often to look for things that mimic MS. We look for other neuroinflammatory or neurobiological diseases that can look a lot like MS and fool us. Most of the time they don't look exactly like MS, but every now and then you get a case that's virtually indistinguishable. There are other tools which may be in less use, but we put the combination of all these things together to help us make the most informed judgment.
The goal is to be able to have honest discussions with families that these tools are just tools that we're trying to play catch up with a disease and try to make a decision as fast as possible to prevent someone from going untreated.
Q2. How does a diagnosis of multiple sclerosis affect the overall quality of life for a child/teen, and how does it affect their overall psychosocial health? Education? Transition needs? Etc.
A2. It can be quite profound, just hearing the diagnosis can be truly life changing for most folks. It would really depend on the family the first time that we meet them. If they have no suspicion that this is what's going on, that can be a shock. Other families may be more aware of what’s going on. Perhaps another physician has already suggested it, or they came from the ER which had already done some of the baseline tests like the MRI, and they had some kind of suspicion. Maybe they googled it and they saw something to be worried about, so they may be prepared. But even then, once you confirm the diagnosis, it's really like the sky falling at that point.
Past the diagnosis stage, there's really an adjustment phase that we see, and we've been doing some work in this. We started doing some work looking at quality of life. We've interviewed a large number of families and asked them some key questions such as, “What's important to you?” It is key for them to tell us rather than us telling them. By doing this, we’re finding out things that may not have been on the forefront of our minds, although it was certainly in the forefront of their minds, so it's a good learning opportunity.
These may be things that we've seen in other quality of life studies in other diseases, but you also have to consider each disease unique and make sure you're looking at this from the perspective of the people that are really being affected. One of the great examples was that the teens really cared more about visible symptoms. For example, an adult with MS may have fatigue, severe fatigue. They may be unable to perform well in their job and that could be a game changer for them. Yet if they had a mild limp, they'd say, yeah, it's kind of embarrassing but I can keep going forward. I can hang in there and my colleagues at work might even support me; but for a teenager, they may care less about the fatigue and way more about having this limp that all their peers can now notice. The symptoms that are important to them can be totally different depending on the age group.
What we found is that teenagers look at things quite differently in trying to optimize their outcomes, and we don't just want them to be medically well. We want them to succeed in school, we want them to succeed in getting into college, or going into the workforce. So, we asked a lot about what it takes to get you there. We asked a lot of the young adults who had pediatric onset MS if they were successful? And if you were, what got you there; and the ones who hadn't reached that yet we asked-- what do you need?
When it came to transition needs, by far, we’ve found almost complete silence on the teenager’s part, which was a little surprising for us. We thought that there would be a little bit of discussion. They didn’t understand what a 504 is. We don't expect the average individual to know, but we thought that they might understand what the tools were, yet they really had no language for discussing that with us. We realized that the start of our transition talks had to be focused on the things that we use for that language.
For example, if I wanted to get a ding in my car fixed. I had to spend 20 minutes explaining to the dealership what I wanted. It was a regular car dealership, so it was integrated. But I had to find the right words to say. I want “auto body.” If I said vehicle repair, they said, oh, you want your car tires replaced? No, no, no. so, it’s very important to speak the right language just to get the process started. Those are some of the things that we found.
Q3. In what ways do environmental and genetic risk factors influence therapeutic decisions in pediatric patients with MS?
A3. They really play a big role in terms of the risk. We find that the more risk factors you have, likely we're dealing with a more severe disease. It doesn't necessarily always work that way, but you may be prepared to use a more potent therapy for individuals that are hitting more of the categories of concern.
But in addition to just the main disease modifying medications and MS, we look at vitamin D. And the data is yet to come out on that. There are some big studies that are trying to confirm or refute if vitamin D really has a therapeutic role, but we find that our teens and our kids have lower than average low vitamin D levels. We know that kids have low vitamin D levels nationwide in this country, but our patients are even lower than that. And that's one thing that we try to supplement and hope that by supplementing it, that it's going to be helpful. Maybe it's not as potent to therapy as the main medications, but we're hoping that's something to add on.
Q4. Overall, what are some advances, trends or recent studies regarding therapies that might support positive outcomes in children with MS?
A4 Interestingly, we just don't have a lot of that research in kids. There's been tons and tons of great research in adults. Like many other fields, you take what you learn from that and you apply it to the teens and kids. But we've learned time and time again they're not just little adults. They're truly a separate group, and we must consider them as such, and we really need those studies in kids.
The first study that came out confirmed that fingolimod was a good and effective therapy in children. But does that mean that you're only limited to using the only FDA approved option, or do you really want to try to offer families the litany of choices that you do for an adult with MS? When I meet families for the first time, we’re spending a good hour just talking about the different treatment choices with them and looking at the risks, the benefits, why one option might be chosen over another, how it's going to affect their lifestyle, and how it might fit into their life.
We want to still be able to make those decisions. I think we can make a more informed decision with fingolimod, but we don't want to just jump to conclusions with all those other therapies. We're a little bit behind the mark when it comes to therapies with kids, and we really need all those studies. They are active, and they are being done now; we're really waiting for those results to come out. That's going to be a huge change. Basically, that's the real trend. We're now going to see those studies in adults being replicated in kids one by one. Every time a new therapy comes out for adults, it must be validated in children as well.
Part of the regulations now do stipulate that these studies must be done. If you do a study in the adult population, you must see if you can do it in the pediatric population. You can't just say, hey, you know we're done. That's really what we're looking for in terms of getting the big therapeutic outcomes.
Chitnis, T., et al. 2021. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis | NEJM. [online] New England Journal of Medicine. Available at: <https://www.nejm.org/doi/
Vikram Bhise, MD, Is an Associate Professor at Rutgers – Robert Wood Johnson Medical School. He specializes in Epilepsy and Pediatric Neuroimmunology, and runs the pediatric demyelinating diseases program, evaluating children with multiple sclerosis, autoimmune encephalopathy, and related diseases. He trained in Pediatrics and Pediatric Neurology, at Maimonides Medical Center and Montefiore Medical Center, respectively. He subsequently received additional training in Clinical Neurophysiology with a focus on Epilepsy at SUNY Downstate Medical Center, and in Pediatric Multiple Sclerosis at SUNY Stony Brook Medical Center. Dr. Bhise conducts clinical research focused on biomarkers and quality of life in pediatric multiple sclerosis, as well as studies in epilepsy and neurogenetics.
Q1. As a specialist who focuses on neuroimmunology, what forms of measurement do you use to make an evaluation or diagnosis for children with multiple sclerosis?
A1. There's a lot that goes into evaluating or diagnosing children with MS. Usually we start off with the story that the family brings to us. We look at what the child is experiencing and what the parents are seeing. Then we do a dedicated examination trying to substantiate the findings that they're describing and look for others they may not even be aware of. If they are having some blurred vision in their eye, can we tell if there's some abnormalities there that are correlating with what they see?
We try to get a good sense of the time-course of things, observing whether this is the first time something's happened or if this has this been going on for a while. Have there been multiple things going on, multiple episodes? We're primarily looking for events called relapses, which are neurologic attacks that are not quick. They don’t last for seconds or hours; they can last for days to weeks, sometimes even months. Individuals will have episodes that tend to get worse and then tend to get better. This is the type of description we’re looking to come from the families.
Once that assessment is complete, we've found that the MRI is one of the best tools in helping us confirm the diagnosis. It's not just diagnostic but the MRI also has some prognostic potential and we're looking specifically for patterns in the MRIs. For children, that pattern can be a little bit more challenging. Their patterns can often overlap with patterns of other inflammatory diseases of the brain like ADEM for example and make it much more difficult for us to characterize someone as truly having MS.
There are also some other diseases which have been discovered in the past decade or elaborated upon like neuromyelitis optica and MOG antibody disorder, which can look exactly like MS in the early stages. Sometimes, that's just not all the information we need. Sometimes it's more difficult to make those distinctions and in these cases, we will look at a spinal tap, a lumbar puncture, and for specific studies from those procedures to help us get a better understanding. There may be other ancillary tests that we use, such as evoked potentials, for example.
Evoked potential testing has kind of fallen to the wayside over the past decade because of the MRI studies becoming a much more useful tool, but we may still use the visual evoked potential to see if there are subtle lesions that can't be seen on the MRI. Other methods might include optical coherence tomography, which is another test looking at the eye that gives you a specific look at the retinal nerve fiber layer, which gets thinned after attacks on the eye on the optic nerve.
We may do neuropsychological testing, which is a battery of tests looking at different cognitive domains and trying to get a sense of a person's cognitive profile to see if that matches what we would expect in somebody with MS. This test could be more challenging for a teen and a child, particularly a younger child. When it comes to pediatric neuropsychology, it's a little bit harder sometimes to get good data, particularly from younger kids.
In addition, we have a battery of tests that we do on the serum. Some disorders, like NMO and MOG, have antibodies that help us identify them. We don't have a specific test that says, yes, you have MS and no, you don't have MS. It's really the combination of all the tools.
We do these tests often to look for things that mimic MS. We look for other neuroinflammatory or neurobiological diseases that can look a lot like MS and fool us. Most of the time they don't look exactly like MS, but every now and then you get a case that's virtually indistinguishable. There are other tools which may be in less use, but we put the combination of all these things together to help us make the most informed judgment.
The goal is to be able to have honest discussions with families that these tools are just tools that we're trying to play catch up with a disease and try to make a decision as fast as possible to prevent someone from going untreated.
Q2. How does a diagnosis of multiple sclerosis affect the overall quality of life for a child/teen, and how does it affect their overall psychosocial health? Education? Transition needs? Etc.
A2. It can be quite profound, just hearing the diagnosis can be truly life changing for most folks. It would really depend on the family the first time that we meet them. If they have no suspicion that this is what's going on, that can be a shock. Other families may be more aware of what’s going on. Perhaps another physician has already suggested it, or they came from the ER which had already done some of the baseline tests like the MRI, and they had some kind of suspicion. Maybe they googled it and they saw something to be worried about, so they may be prepared. But even then, once you confirm the diagnosis, it's really like the sky falling at that point.
Past the diagnosis stage, there's really an adjustment phase that we see, and we've been doing some work in this. We started doing some work looking at quality of life. We've interviewed a large number of families and asked them some key questions such as, “What's important to you?” It is key for them to tell us rather than us telling them. By doing this, we’re finding out things that may not have been on the forefront of our minds, although it was certainly in the forefront of their minds, so it's a good learning opportunity.
These may be things that we've seen in other quality of life studies in other diseases, but you also have to consider each disease unique and make sure you're looking at this from the perspective of the people that are really being affected. One of the great examples was that the teens really cared more about visible symptoms. For example, an adult with MS may have fatigue, severe fatigue. They may be unable to perform well in their job and that could be a game changer for them. Yet if they had a mild limp, they'd say, yeah, it's kind of embarrassing but I can keep going forward. I can hang in there and my colleagues at work might even support me; but for a teenager, they may care less about the fatigue and way more about having this limp that all their peers can now notice. The symptoms that are important to them can be totally different depending on the age group.
What we found is that teenagers look at things quite differently in trying to optimize their outcomes, and we don't just want them to be medically well. We want them to succeed in school, we want them to succeed in getting into college, or going into the workforce. So, we asked a lot about what it takes to get you there. We asked a lot of the young adults who had pediatric onset MS if they were successful? And if you were, what got you there; and the ones who hadn't reached that yet we asked-- what do you need?
When it came to transition needs, by far, we’ve found almost complete silence on the teenager’s part, which was a little surprising for us. We thought that there would be a little bit of discussion. They didn’t understand what a 504 is. We don't expect the average individual to know, but we thought that they might understand what the tools were, yet they really had no language for discussing that with us. We realized that the start of our transition talks had to be focused on the things that we use for that language.
For example, if I wanted to get a ding in my car fixed. I had to spend 20 minutes explaining to the dealership what I wanted. It was a regular car dealership, so it was integrated. But I had to find the right words to say. I want “auto body.” If I said vehicle repair, they said, oh, you want your car tires replaced? No, no, no. so, it’s very important to speak the right language just to get the process started. Those are some of the things that we found.
Q3. In what ways do environmental and genetic risk factors influence therapeutic decisions in pediatric patients with MS?
A3. They really play a big role in terms of the risk. We find that the more risk factors you have, likely we're dealing with a more severe disease. It doesn't necessarily always work that way, but you may be prepared to use a more potent therapy for individuals that are hitting more of the categories of concern.
But in addition to just the main disease modifying medications and MS, we look at vitamin D. And the data is yet to come out on that. There are some big studies that are trying to confirm or refute if vitamin D really has a therapeutic role, but we find that our teens and our kids have lower than average low vitamin D levels. We know that kids have low vitamin D levels nationwide in this country, but our patients are even lower than that. And that's one thing that we try to supplement and hope that by supplementing it, that it's going to be helpful. Maybe it's not as potent to therapy as the main medications, but we're hoping that's something to add on.
Q4. Overall, what are some advances, trends or recent studies regarding therapies that might support positive outcomes in children with MS?
A4 Interestingly, we just don't have a lot of that research in kids. There's been tons and tons of great research in adults. Like many other fields, you take what you learn from that and you apply it to the teens and kids. But we've learned time and time again they're not just little adults. They're truly a separate group, and we must consider them as such, and we really need those studies in kids.
The first study that came out confirmed that fingolimod was a good and effective therapy in children. But does that mean that you're only limited to using the only FDA approved option, or do you really want to try to offer families the litany of choices that you do for an adult with MS? When I meet families for the first time, we’re spending a good hour just talking about the different treatment choices with them and looking at the risks, the benefits, why one option might be chosen over another, how it's going to affect their lifestyle, and how it might fit into their life.
We want to still be able to make those decisions. I think we can make a more informed decision with fingolimod, but we don't want to just jump to conclusions with all those other therapies. We're a little bit behind the mark when it comes to therapies with kids, and we really need all those studies. They are active, and they are being done now; we're really waiting for those results to come out. That's going to be a huge change. Basically, that's the real trend. We're now going to see those studies in adults being replicated in kids one by one. Every time a new therapy comes out for adults, it must be validated in children as well.
Part of the regulations now do stipulate that these studies must be done. If you do a study in the adult population, you must see if you can do it in the pediatric population. You can't just say, hey, you know we're done. That's really what we're looking for in terms of getting the big therapeutic outcomes.
Vikram Bhise, MD, Is an Associate Professor at Rutgers – Robert Wood Johnson Medical School. He specializes in Epilepsy and Pediatric Neuroimmunology, and runs the pediatric demyelinating diseases program, evaluating children with multiple sclerosis, autoimmune encephalopathy, and related diseases. He trained in Pediatrics and Pediatric Neurology, at Maimonides Medical Center and Montefiore Medical Center, respectively. He subsequently received additional training in Clinical Neurophysiology with a focus on Epilepsy at SUNY Downstate Medical Center, and in Pediatric Multiple Sclerosis at SUNY Stony Brook Medical Center. Dr. Bhise conducts clinical research focused on biomarkers and quality of life in pediatric multiple sclerosis, as well as studies in epilepsy and neurogenetics.
Q1. As a specialist who focuses on neuroimmunology, what forms of measurement do you use to make an evaluation or diagnosis for children with multiple sclerosis?
A1. There's a lot that goes into evaluating or diagnosing children with MS. Usually we start off with the story that the family brings to us. We look at what the child is experiencing and what the parents are seeing. Then we do a dedicated examination trying to substantiate the findings that they're describing and look for others they may not even be aware of. If they are having some blurred vision in their eye, can we tell if there's some abnormalities there that are correlating with what they see?
We try to get a good sense of the time-course of things, observing whether this is the first time something's happened or if this has this been going on for a while. Have there been multiple things going on, multiple episodes? We're primarily looking for events called relapses, which are neurologic attacks that are not quick. They don’t last for seconds or hours; they can last for days to weeks, sometimes even months. Individuals will have episodes that tend to get worse and then tend to get better. This is the type of description we’re looking to come from the families.
Once that assessment is complete, we've found that the MRI is one of the best tools in helping us confirm the diagnosis. It's not just diagnostic but the MRI also has some prognostic potential and we're looking specifically for patterns in the MRIs. For children, that pattern can be a little bit more challenging. Their patterns can often overlap with patterns of other inflammatory diseases of the brain like ADEM for example and make it much more difficult for us to characterize someone as truly having MS.
There are also some other diseases which have been discovered in the past decade or elaborated upon like neuromyelitis optica and MOG antibody disorder, which can look exactly like MS in the early stages. Sometimes, that's just not all the information we need. Sometimes it's more difficult to make those distinctions and in these cases, we will look at a spinal tap, a lumbar puncture, and for specific studies from those procedures to help us get a better understanding. There may be other ancillary tests that we use, such as evoked potentials, for example.
Evoked potential testing has kind of fallen to the wayside over the past decade because of the MRI studies becoming a much more useful tool, but we may still use the visual evoked potential to see if there are subtle lesions that can't be seen on the MRI. Other methods might include optical coherence tomography, which is another test looking at the eye that gives you a specific look at the retinal nerve fiber layer, which gets thinned after attacks on the eye on the optic nerve.
We may do neuropsychological testing, which is a battery of tests looking at different cognitive domains and trying to get a sense of a person's cognitive profile to see if that matches what we would expect in somebody with MS. This test could be more challenging for a teen and a child, particularly a younger child. When it comes to pediatric neuropsychology, it's a little bit harder sometimes to get good data, particularly from younger kids.
In addition, we have a battery of tests that we do on the serum. Some disorders, like NMO and MOG, have antibodies that help us identify them. We don't have a specific test that says, yes, you have MS and no, you don't have MS. It's really the combination of all the tools.
We do these tests often to look for things that mimic MS. We look for other neuroinflammatory or neurobiological diseases that can look a lot like MS and fool us. Most of the time they don't look exactly like MS, but every now and then you get a case that's virtually indistinguishable. There are other tools which may be in less use, but we put the combination of all these things together to help us make the most informed judgment.
The goal is to be able to have honest discussions with families that these tools are just tools that we're trying to play catch up with a disease and try to make a decision as fast as possible to prevent someone from going untreated.
Q2. How does a diagnosis of multiple sclerosis affect the overall quality of life for a child/teen, and how does it affect their overall psychosocial health? Education? Transition needs? Etc.
A2. It can be quite profound, just hearing the diagnosis can be truly life changing for most folks. It would really depend on the family the first time that we meet them. If they have no suspicion that this is what's going on, that can be a shock. Other families may be more aware of what’s going on. Perhaps another physician has already suggested it, or they came from the ER which had already done some of the baseline tests like the MRI, and they had some kind of suspicion. Maybe they googled it and they saw something to be worried about, so they may be prepared. But even then, once you confirm the diagnosis, it's really like the sky falling at that point.
Past the diagnosis stage, there's really an adjustment phase that we see, and we've been doing some work in this. We started doing some work looking at quality of life. We've interviewed a large number of families and asked them some key questions such as, “What's important to you?” It is key for them to tell us rather than us telling them. By doing this, we’re finding out things that may not have been on the forefront of our minds, although it was certainly in the forefront of their minds, so it's a good learning opportunity.
These may be things that we've seen in other quality of life studies in other diseases, but you also have to consider each disease unique and make sure you're looking at this from the perspective of the people that are really being affected. One of the great examples was that the teens really cared more about visible symptoms. For example, an adult with MS may have fatigue, severe fatigue. They may be unable to perform well in their job and that could be a game changer for them. Yet if they had a mild limp, they'd say, yeah, it's kind of embarrassing but I can keep going forward. I can hang in there and my colleagues at work might even support me; but for a teenager, they may care less about the fatigue and way more about having this limp that all their peers can now notice. The symptoms that are important to them can be totally different depending on the age group.
What we found is that teenagers look at things quite differently in trying to optimize their outcomes, and we don't just want them to be medically well. We want them to succeed in school, we want them to succeed in getting into college, or going into the workforce. So, we asked a lot about what it takes to get you there. We asked a lot of the young adults who had pediatric onset MS if they were successful? And if you were, what got you there; and the ones who hadn't reached that yet we asked-- what do you need?
When it came to transition needs, by far, we’ve found almost complete silence on the teenager’s part, which was a little surprising for us. We thought that there would be a little bit of discussion. They didn’t understand what a 504 is. We don't expect the average individual to know, but we thought that they might understand what the tools were, yet they really had no language for discussing that with us. We realized that the start of our transition talks had to be focused on the things that we use for that language.
For example, if I wanted to get a ding in my car fixed. I had to spend 20 minutes explaining to the dealership what I wanted. It was a regular car dealership, so it was integrated. But I had to find the right words to say. I want “auto body.” If I said vehicle repair, they said, oh, you want your car tires replaced? No, no, no. so, it’s very important to speak the right language just to get the process started. Those are some of the things that we found.
Q3. In what ways do environmental and genetic risk factors influence therapeutic decisions in pediatric patients with MS?
A3. They really play a big role in terms of the risk. We find that the more risk factors you have, likely we're dealing with a more severe disease. It doesn't necessarily always work that way, but you may be prepared to use a more potent therapy for individuals that are hitting more of the categories of concern.
But in addition to just the main disease modifying medications and MS, we look at vitamin D. And the data is yet to come out on that. There are some big studies that are trying to confirm or refute if vitamin D really has a therapeutic role, but we find that our teens and our kids have lower than average low vitamin D levels. We know that kids have low vitamin D levels nationwide in this country, but our patients are even lower than that. And that's one thing that we try to supplement and hope that by supplementing it, that it's going to be helpful. Maybe it's not as potent to therapy as the main medications, but we're hoping that's something to add on.
Q4. Overall, what are some advances, trends or recent studies regarding therapies that might support positive outcomes in children with MS?
A4 Interestingly, we just don't have a lot of that research in kids. There's been tons and tons of great research in adults. Like many other fields, you take what you learn from that and you apply it to the teens and kids. But we've learned time and time again they're not just little adults. They're truly a separate group, and we must consider them as such, and we really need those studies in kids.
The first study that came out confirmed that fingolimod was a good and effective therapy in children. But does that mean that you're only limited to using the only FDA approved option, or do you really want to try to offer families the litany of choices that you do for an adult with MS? When I meet families for the first time, we’re spending a good hour just talking about the different treatment choices with them and looking at the risks, the benefits, why one option might be chosen over another, how it's going to affect their lifestyle, and how it might fit into their life.
We want to still be able to make those decisions. I think we can make a more informed decision with fingolimod, but we don't want to just jump to conclusions with all those other therapies. We're a little bit behind the mark when it comes to therapies with kids, and we really need all those studies. They are active, and they are being done now; we're really waiting for those results to come out. That's going to be a huge change. Basically, that's the real trend. We're now going to see those studies in adults being replicated in kids one by one. Every time a new therapy comes out for adults, it must be validated in children as well.
Part of the regulations now do stipulate that these studies must be done. If you do a study in the adult population, you must see if you can do it in the pediatric population. You can't just say, hey, you know we're done. That's really what we're looking for in terms of getting the big therapeutic outcomes.
Chitnis, T., et al. 2021. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis | NEJM. [online] New England Journal of Medicine. Available at: <https://www.nejm.org/doi/
Chitnis, T., et al. 2021. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis | NEJM. [online] New England Journal of Medicine. Available at: <https://www.nejm.org/doi/