Article

Key clinical point: Salivary cortisol levels were neither associated with the severity of atopic dermatitis (AD) nor could measure the stress associated with it.

Major finding: Salivary cortisol levels increased in both symptomatic and asymptomatic patients, but the levels were significantly lower in symptomatic vs. asymptomatic patients (P = .011) and those with severe vs. moderate and mild disease (P = .042). However, the severity of perceived stress could neither be measured by cortisol levels nor by disease severity.

Study details: Findings are from a prospective study including symptomatic (n = 42) and asymptomatic (n =               42) patients with AD.

Disclosures: The study did not report any source of funding. The authors declared no conflicts of interest.

Source: Meštrović-Štefekov  J et al. Dermatitis. 2022 (Jan 25). Doi: 10.1097/DER.0000000000000834.

Key clinical point: Salivary cortisol levels were neither associated with the severity of atopic dermatitis (AD) nor could measure the stress associated with it.

Major finding: Salivary cortisol levels increased in both symptomatic and asymptomatic patients, but the levels were significantly lower in symptomatic vs. asymptomatic patients (P = .011) and those with severe vs. moderate and mild disease (P = .042). However, the severity of perceived stress could neither be measured by cortisol levels nor by disease severity.

Study details: Findings are from a prospective study including symptomatic (n = 42) and asymptomatic (n =               42) patients with AD.

Disclosures: The study did not report any source of funding. The authors declared no conflicts of interest.

Source: Meštrović-Štefekov  J et al. Dermatitis. 2022 (Jan 25). Doi: 10.1097/DER.0000000000000834.

Key clinical point: Salivary cortisol levels were neither associated with the severity of atopic dermatitis (AD) nor could measure the stress associated with it.

Major finding: Salivary cortisol levels increased in both symptomatic and asymptomatic patients, but the levels were significantly lower in symptomatic vs. asymptomatic patients (P = .011) and those with severe vs. moderate and mild disease (P = .042). However, the severity of perceived stress could neither be measured by cortisol levels nor by disease severity.

Study details: Findings are from a prospective study including symptomatic (n = 42) and asymptomatic (n =               42) patients with AD.

Disclosures: The study did not report any source of funding. The authors declared no conflicts of interest.

Source: Meštrović-Štefekov  J et al. Dermatitis. 2022 (Jan 25). Doi: 10.1097/DER.0000000000000834.

Key clinical point: Moderate-to-severe lower respiratory tract infection (LRTI) before 18 months of age is a significant risk factor for developing atopic dermatitis (AD) in later childhood.

Major finding: The group of infants with moderate-severe vs. no or mild LRTI had significantly higher rates of AD at age 3 years (P = .001) and 5 years (P = .006) with moderate-to-severe vs. no LRTI in the first 18 months of life being significantly associated with increased odds of AD in later childhood (odds ratio [OR] 2.19; P < .001) independent of both-parent history of asthma and both-parent genetic predisposition.

Study details: Findings are from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, comprising a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy and followed from birth onwards.

Disclosures: This study was funded by the Canadian Institutes of Health Research and Allergy, Genes, and Environment Network of Centers of Excellence. The authors declared no conflicts of interest.

Source: Medeleanu M et al. J Allergy Clin Immunol. 2022 (Jan 16). Doi: 10.1016/j.jacig.2021.12.005

Key clinical point: Moderate-to-severe lower respiratory tract infection (LRTI) before 18 months of age is a significant risk factor for developing atopic dermatitis (AD) in later childhood.

Major finding: The group of infants with moderate-severe vs. no or mild LRTI had significantly higher rates of AD at age 3 years (P = .001) and 5 years (P = .006) with moderate-to-severe vs. no LRTI in the first 18 months of life being significantly associated with increased odds of AD in later childhood (odds ratio [OR] 2.19; P < .001) independent of both-parent history of asthma and both-parent genetic predisposition.

Study details: Findings are from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, comprising a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy and followed from birth onwards.

Disclosures: This study was funded by the Canadian Institutes of Health Research and Allergy, Genes, and Environment Network of Centers of Excellence. The authors declared no conflicts of interest.

Source: Medeleanu M et al. J Allergy Clin Immunol. 2022 (Jan 16). Doi: 10.1016/j.jacig.2021.12.005

Key clinical point: Moderate-to-severe lower respiratory tract infection (LRTI) before 18 months of age is a significant risk factor for developing atopic dermatitis (AD) in later childhood.

Major finding: The group of infants with moderate-severe vs. no or mild LRTI had significantly higher rates of AD at age 3 years (P = .001) and 5 years (P = .006) with moderate-to-severe vs. no LRTI in the first 18 months of life being significantly associated with increased odds of AD in later childhood (odds ratio [OR] 2.19; P < .001) independent of both-parent history of asthma and both-parent genetic predisposition.

Study details: Findings are from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, comprising a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy and followed from birth onwards.

Disclosures: This study was funded by the Canadian Institutes of Health Research and Allergy, Genes, and Environment Network of Centers of Excellence. The authors declared no conflicts of interest.

Source: Medeleanu M et al. J Allergy Clin Immunol. 2022 (Jan 16). Doi: 10.1016/j.jacig.2021.12.005

Key clinical point: Infections in early life increase the risk of developing atopic dermatitis (AD) later in infancy and early childhood.

Major finding: Prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in patients who subsequently developed AD vs. healthy controls (P < .001), with a significant association observed between having any infection before AD diagnosis and subsequent development of AD (adjusted odds ratio, 1.40; P < .001), which persisted up to 2 years of age.

Study details: Findings are from a population-based, nationwide case-control study including 5,454 patients (mean age 2.6±2.9 years) with AD matched with 16,362 healthy controls without AD.

Disclosures: This study is supported by the Ministry of Science and Technology and Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin T-L et al. J Eur Acad Dermatol Venereol. 2022 (Jan 9). Doi: 10.1111/jdv.17908

Key clinical point: Infections in early life increase the risk of developing atopic dermatitis (AD) later in infancy and early childhood.

Major finding: Prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in patients who subsequently developed AD vs. healthy controls (P < .001), with a significant association observed between having any infection before AD diagnosis and subsequent development of AD (adjusted odds ratio, 1.40; P < .001), which persisted up to 2 years of age.

Study details: Findings are from a population-based, nationwide case-control study including 5,454 patients (mean age 2.6±2.9 years) with AD matched with 16,362 healthy controls without AD.

Disclosures: This study is supported by the Ministry of Science and Technology and Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin T-L et al. J Eur Acad Dermatol Venereol. 2022 (Jan 9). Doi: 10.1111/jdv.17908

Key clinical point: Infections in early life increase the risk of developing atopic dermatitis (AD) later in infancy and early childhood.

Major finding: Prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in patients who subsequently developed AD vs. healthy controls (P < .001), with a significant association observed between having any infection before AD diagnosis and subsequent development of AD (adjusted odds ratio, 1.40; P < .001), which persisted up to 2 years of age.

Study details: Findings are from a population-based, nationwide case-control study including 5,454 patients (mean age 2.6±2.9 years) with AD matched with 16,362 healthy controls without AD.

Disclosures: This study is supported by the Ministry of Science and Technology and Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin T-L et al. J Eur Acad Dermatol Venereol. 2022 (Jan 9). Doi: 10.1111/jdv.17908

Key clinical point: Atopic dermatitis (AD) is prevalent among young adults, with men being at increased odds of having AD in early life and decreased odds of having AD at adolescence and young adulthood.

Major finding: At 24 years, the 12-month prevalence of AD was 17.8%, with the prevalence being higher in women vs. men (20.5% vs. 14.8%; P < .0001). Men vs. women were more likely to have AD in the first year of life (odds ratio [OR] 1.31; 95% CI 1.10-1.56) but less likely to have AD at 24 years (OR 0.66; 95% CI 0.55-0.80).

Study details: This study included 3,055 individuals from the population-based BAMSE cohort, who were followed for 24 years after birth, and responded to a questionnaire regarding AD at the 24-year follow-up.

Disclosures: This study was funded by the European Research Council, Swedish Research Council, Åke Wiberg foundation, and other sources. Some of the authors declared serving as meeting experts or receiving consultancy fees and lecture fees from various sources.

Source: Johansson EK et al. J Eur Acad Dermatol Venereol. 2022 (Jan 15). Doi: 10.1111/jdv.17929

Key clinical point: Atopic dermatitis (AD) is prevalent among young adults, with men being at increased odds of having AD in early life and decreased odds of having AD at adolescence and young adulthood.

Major finding: At 24 years, the 12-month prevalence of AD was 17.8%, with the prevalence being higher in women vs. men (20.5% vs. 14.8%; P < .0001). Men vs. women were more likely to have AD in the first year of life (odds ratio [OR] 1.31; 95% CI 1.10-1.56) but less likely to have AD at 24 years (OR 0.66; 95% CI 0.55-0.80).

Study details: This study included 3,055 individuals from the population-based BAMSE cohort, who were followed for 24 years after birth, and responded to a questionnaire regarding AD at the 24-year follow-up.

Disclosures: This study was funded by the European Research Council, Swedish Research Council, Åke Wiberg foundation, and other sources. Some of the authors declared serving as meeting experts or receiving consultancy fees and lecture fees from various sources.

Source: Johansson EK et al. J Eur Acad Dermatol Venereol. 2022 (Jan 15). Doi: 10.1111/jdv.17929

Key clinical point: Atopic dermatitis (AD) is prevalent among young adults, with men being at increased odds of having AD in early life and decreased odds of having AD at adolescence and young adulthood.

Major finding: At 24 years, the 12-month prevalence of AD was 17.8%, with the prevalence being higher in women vs. men (20.5% vs. 14.8%; P < .0001). Men vs. women were more likely to have AD in the first year of life (odds ratio [OR] 1.31; 95% CI 1.10-1.56) but less likely to have AD at 24 years (OR 0.66; 95% CI 0.55-0.80).

Study details: This study included 3,055 individuals from the population-based BAMSE cohort, who were followed for 24 years after birth, and responded to a questionnaire regarding AD at the 24-year follow-up.

Disclosures: This study was funded by the European Research Council, Swedish Research Council, Åke Wiberg foundation, and other sources. Some of the authors declared serving as meeting experts or receiving consultancy fees and lecture fees from various sources.

Source: Johansson EK et al. J Eur Acad Dermatol Venereol. 2022 (Jan 15). Doi: 10.1111/jdv.17929

Key clinical point: Children with inadequately controlled moderate-to-severe atopic dermatitis (AD) presented with a high disease burden characterized by itch, impaired quality of life (QoL), and disturbed sleep, which may be attributed to lower use of systemic therapies.

Major finding: Most of the children were receiving nonsystemic medications (77.2%) and reported a mean Eczema Area and Severity Index of 14.4 and Patient-Oriented Eczema Measure score of 15.6. Patients aged 6 to <12 years reported an itch score of 4.9; infants (0-3 years) and children (4 to <12 years) reported QoL scores of 10.3 and 10.8, respectively, and 31% of patients reported disturbed sleep because of AD.

Study details: Findings are based on interim baseline data from an ongoing, longitudinal study including 732 children aged <12 years with moderate-to-severe AD.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. The authors declared serving as investigators, consultants, speakers, and advisory board members or receiving research grants and honoraria from various sources. Some authors declared being employees or stockholders of Sanofi Genzyme or Regeneron Pharmaceuticals.

Source: Paller AS et al. J Am Acad Dermatol. 2022 (Jan 23). Doi: 10.1016/j.jaad.2022.01.018

Key clinical point: Children with inadequately controlled moderate-to-severe atopic dermatitis (AD) presented with a high disease burden characterized by itch, impaired quality of life (QoL), and disturbed sleep, which may be attributed to lower use of systemic therapies.

Major finding: Most of the children were receiving nonsystemic medications (77.2%) and reported a mean Eczema Area and Severity Index of 14.4 and Patient-Oriented Eczema Measure score of 15.6. Patients aged 6 to <12 years reported an itch score of 4.9; infants (0-3 years) and children (4 to <12 years) reported QoL scores of 10.3 and 10.8, respectively, and 31% of patients reported disturbed sleep because of AD.

Study details: Findings are based on interim baseline data from an ongoing, longitudinal study including 732 children aged <12 years with moderate-to-severe AD.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. The authors declared serving as investigators, consultants, speakers, and advisory board members or receiving research grants and honoraria from various sources. Some authors declared being employees or stockholders of Sanofi Genzyme or Regeneron Pharmaceuticals.

Source: Paller AS et al. J Am Acad Dermatol. 2022 (Jan 23). Doi: 10.1016/j.jaad.2022.01.018

Key clinical point: Children with inadequately controlled moderate-to-severe atopic dermatitis (AD) presented with a high disease burden characterized by itch, impaired quality of life (QoL), and disturbed sleep, which may be attributed to lower use of systemic therapies.

Major finding: Most of the children were receiving nonsystemic medications (77.2%) and reported a mean Eczema Area and Severity Index of 14.4 and Patient-Oriented Eczema Measure score of 15.6. Patients aged 6 to <12 years reported an itch score of 4.9; infants (0-3 years) and children (4 to <12 years) reported QoL scores of 10.3 and 10.8, respectively, and 31% of patients reported disturbed sleep because of AD.

Study details: Findings are based on interim baseline data from an ongoing, longitudinal study including 732 children aged <12 years with moderate-to-severe AD.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. The authors declared serving as investigators, consultants, speakers, and advisory board members or receiving research grants and honoraria from various sources. Some authors declared being employees or stockholders of Sanofi Genzyme or Regeneron Pharmaceuticals.

Source: Paller AS et al. J Am Acad Dermatol. 2022 (Jan 23). Doi: 10.1016/j.jaad.2022.01.018

Key clinical point: Adults with atopic dermatitis (AD) who received COVID-19 vaccination did not show a higher risk for any assessed adverse events (AE) than those without AD; however, a minimal risk persisted among patients with a 1-year history of immunosuppressive or immunomodulatory therapy.

Major finding: The risk for 1-day immediate AEs, AEs at 30/60/90-day follow-up, and breakthrough infections was similar between vaccinated adults with vs. without AD; however, those who had a 1-year history of immunosuppressant or immunomodulatory therapy were at a higher risk for all-cause hospitalization at 30 days (adjusted hazard ratio [aHR] 2.14; 95% CI 1.27-3.59), 60 days (aHR 1.77; 95% CI 1.22-2.56), and 90 days (aHR 1.68; 95% CI 1.25-2.27) after vaccination.

Study details: Findings are from a retrospective cohort study including 1,262,306 vaccinated adults, of which 1.2% of adults had a history of AD.

Disclosures: This study did not report any source of funding. Some of the authors declared serving as consultants, honoraria speakers, and receiving research funding from several sources.

Source: Pakhchanian H et al. Br J Dermatol. 2022 (Jan 27). Doi: 10.1111/bjd.21038

Key clinical point: Adults with atopic dermatitis (AD) who received COVID-19 vaccination did not show a higher risk for any assessed adverse events (AE) than those without AD; however, a minimal risk persisted among patients with a 1-year history of immunosuppressive or immunomodulatory therapy.

Major finding: The risk for 1-day immediate AEs, AEs at 30/60/90-day follow-up, and breakthrough infections was similar between vaccinated adults with vs. without AD; however, those who had a 1-year history of immunosuppressant or immunomodulatory therapy were at a higher risk for all-cause hospitalization at 30 days (adjusted hazard ratio [aHR] 2.14; 95% CI 1.27-3.59), 60 days (aHR 1.77; 95% CI 1.22-2.56), and 90 days (aHR 1.68; 95% CI 1.25-2.27) after vaccination.

Study details: Findings are from a retrospective cohort study including 1,262,306 vaccinated adults, of which 1.2% of adults had a history of AD.

Disclosures: This study did not report any source of funding. Some of the authors declared serving as consultants, honoraria speakers, and receiving research funding from several sources.

Source: Pakhchanian H et al. Br J Dermatol. 2022 (Jan 27). Doi: 10.1111/bjd.21038

Key clinical point: Adults with atopic dermatitis (AD) who received COVID-19 vaccination did not show a higher risk for any assessed adverse events (AE) than those without AD; however, a minimal risk persisted among patients with a 1-year history of immunosuppressive or immunomodulatory therapy.

Major finding: The risk for 1-day immediate AEs, AEs at 30/60/90-day follow-up, and breakthrough infections was similar between vaccinated adults with vs. without AD; however, those who had a 1-year history of immunosuppressant or immunomodulatory therapy were at a higher risk for all-cause hospitalization at 30 days (adjusted hazard ratio [aHR] 2.14; 95% CI 1.27-3.59), 60 days (aHR 1.77; 95% CI 1.22-2.56), and 90 days (aHR 1.68; 95% CI 1.25-2.27) after vaccination.

Study details: Findings are from a retrospective cohort study including 1,262,306 vaccinated adults, of which 1.2% of adults had a history of AD.

Disclosures: This study did not report any source of funding. Some of the authors declared serving as consultants, honoraria speakers, and receiving research funding from several sources.

Source: Pakhchanian H et al. Br J Dermatol. 2022 (Jan 27). Doi: 10.1111/bjd.21038

            Kishan et al conducted a meta-analysis to evaluate the relative effects of the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) on metastasis-free survival (MFS) in patients with localized prostate cancer in the following three settings: 1) RT alone versus RT plus adjuvant ADT, 2) extension of ADT duration in the neoadjuvant setting before RT, and 3) extension of adjuvant ADT duration. MFS was increased in the adjuvant ADT setting, and prolongation of ADT duration was associated with a higher MFS than shorter duration. However, extension of neoadjuvant ADT was not associated with a higher MFS compared to a shorter duration. The meta-analysis further supports a longer versus shorter ADT duration, but it does not support a longer neoadjuvant ADT duration.

            To determine the effects of salvage RT on outcomes in the setting of biochemical relapse, Tilki et al conducted a retrospective cohort analysis of a multi-institutional database of patients with biochemical recurrence after radical prostatectomy (RP). MFS at 15 years post-RP was 84.3% in the RT group and 76.9% in the non-RT group, while overall survival (OS), also at 15 years post-RP, was 85.3% in the RT group versus 74.4% in the non-RT group (both analyses were statistically significant). While supportive of salvage RT, there was no data on prostate-specific antigen (PSA) doubling times, nor was it possible to control for imaging modality. It is possible that newer prostate-specific membrane antigen (PSMA)-based positron emission tomography imaging may affect MFS in studies such as these.

            Prostatectomy (with or without lymph node dissection), external beam RT (EBRT) with  ADT, or EBRT with brachytherapy (BT) with or without ADT are options in unfavorable intermediate-risk prostate cancer. The optimal use of BT in localized prostate cancer is somewhat uncertain, especially across the risk spectrum. Andruska et al conducted an analysis of the National Cancer Database (NCDB) to evaluate whether EBRT plus BT with or without ADT results in an improvement in overall survival (OS) compared with BT with or without ADT. OS was higher for the EBRT plus BT groups; however, when the ADT + EBRT + BT group was compared with EBRT + BT without ADT group, the improvement in OS was not statistically significant. Overall, the analysis favored EBRT + BT over BT alone, further supporting current guidelines.

            Kishan et al conducted a meta-analysis to evaluate the relative effects of the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) on metastasis-free survival (MFS) in patients with localized prostate cancer in the following three settings: 1) RT alone versus RT plus adjuvant ADT, 2) extension of ADT duration in the neoadjuvant setting before RT, and 3) extension of adjuvant ADT duration. MFS was increased in the adjuvant ADT setting, and prolongation of ADT duration was associated with a higher MFS than shorter duration. However, extension of neoadjuvant ADT was not associated with a higher MFS compared to a shorter duration. The meta-analysis further supports a longer versus shorter ADT duration, but it does not support a longer neoadjuvant ADT duration.

            To determine the effects of salvage RT on outcomes in the setting of biochemical relapse, Tilki et al conducted a retrospective cohort analysis of a multi-institutional database of patients with biochemical recurrence after radical prostatectomy (RP). MFS at 15 years post-RP was 84.3% in the RT group and 76.9% in the non-RT group, while overall survival (OS), also at 15 years post-RP, was 85.3% in the RT group versus 74.4% in the non-RT group (both analyses were statistically significant). While supportive of salvage RT, there was no data on prostate-specific antigen (PSA) doubling times, nor was it possible to control for imaging modality. It is possible that newer prostate-specific membrane antigen (PSMA)-based positron emission tomography imaging may affect MFS in studies such as these.

            Prostatectomy (with or without lymph node dissection), external beam RT (EBRT) with  ADT, or EBRT with brachytherapy (BT) with or without ADT are options in unfavorable intermediate-risk prostate cancer. The optimal use of BT in localized prostate cancer is somewhat uncertain, especially across the risk spectrum. Andruska et al conducted an analysis of the National Cancer Database (NCDB) to evaluate whether EBRT plus BT with or without ADT results in an improvement in overall survival (OS) compared with BT with or without ADT. OS was higher for the EBRT plus BT groups; however, when the ADT + EBRT + BT group was compared with EBRT + BT without ADT group, the improvement in OS was not statistically significant. Overall, the analysis favored EBRT + BT over BT alone, further supporting current guidelines.

            Kishan et al conducted a meta-analysis to evaluate the relative effects of the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) on metastasis-free survival (MFS) in patients with localized prostate cancer in the following three settings: 1) RT alone versus RT plus adjuvant ADT, 2) extension of ADT duration in the neoadjuvant setting before RT, and 3) extension of adjuvant ADT duration. MFS was increased in the adjuvant ADT setting, and prolongation of ADT duration was associated with a higher MFS than shorter duration. However, extension of neoadjuvant ADT was not associated with a higher MFS compared to a shorter duration. The meta-analysis further supports a longer versus shorter ADT duration, but it does not support a longer neoadjuvant ADT duration.

            To determine the effects of salvage RT on outcomes in the setting of biochemical relapse, Tilki et al conducted a retrospective cohort analysis of a multi-institutional database of patients with biochemical recurrence after radical prostatectomy (RP). MFS at 15 years post-RP was 84.3% in the RT group and 76.9% in the non-RT group, while overall survival (OS), also at 15 years post-RP, was 85.3% in the RT group versus 74.4% in the non-RT group (both analyses were statistically significant). While supportive of salvage RT, there was no data on prostate-specific antigen (PSA) doubling times, nor was it possible to control for imaging modality. It is possible that newer prostate-specific membrane antigen (PSMA)-based positron emission tomography imaging may affect MFS in studies such as these.

            Prostatectomy (with or without lymph node dissection), external beam RT (EBRT) with  ADT, or EBRT with brachytherapy (BT) with or without ADT are options in unfavorable intermediate-risk prostate cancer. The optimal use of BT in localized prostate cancer is somewhat uncertain, especially across the risk spectrum. Andruska et al conducted an analysis of the National Cancer Database (NCDB) to evaluate whether EBRT plus BT with or without ADT results in an improvement in overall survival (OS) compared with BT with or without ADT. OS was higher for the EBRT plus BT groups; however, when the ADT + EBRT + BT group was compared with EBRT + BT without ADT group, the improvement in OS was not statistically significant. Overall, the analysis favored EBRT + BT over BT alone, further supporting current guidelines.

Many neurocognitive disorders only present a phenotype after birth. Sukenik-Halevy et al sought to examine the ability to detect prenatal phenotypes in patients with a postnatally diagnosed neurocognitive syndrome and confirmed genetic diagnosis on ES. The team was not able to identify any specific prenatal phenotype associated with their cases of postnatally diagnosed neurocognitive syndromes. The interesting finding of this study is that, of the 122 patients studied, 35.3% (43) had no abnormal sonographic findings that could have been detected prenatally to suggest the need for ES testing. ES is typically used in a prenatal setting for fetuses with anomalies that have a normal KT and CMA. The results of this study raise the question of offering ES to all patients considering diagnostic genetic testing regardless of the indication, as it may be the only way to diagnose some cases of neurocognitive disorders prenatally.

Cell-free fetal DNA (cff DNA) testing for trisomy 21, 18, and 13 has classically be used for high-risk pregnant patients seeking aneuploidy screening. Dar et al sought to examine this type of testing in a low-risk population. They studied, prospectively, the performance of cff DNA testing for trisomy 21, 18, and 13 in both low and high-risk pregnant women with confirmation of results on diagnostic genetic testing. Negative predictive values (NPV) for both the low and high-risk groups were greater than 99.9%. Positive predictive value (PPV) was lower for the low-risk group in comparison to the high-risk group, with it important to note that PPV drops from 96.4% in the high-risk group to 81.8% in the low-risk group for trisomy 21. This means that low-risk patients with a positive result on cff DNA testing are at a higher risk for a false positive than patients at high-risk for an aneuploid fetus. This study shows the mounting evidence that cff DNA can be used in a low-risk population given the high NPV. Providers do still need to note the lower PPV with low-risk population patients and always offer diagnostic genetic testing with any abnormal cff DNA test result.

Many neurocognitive disorders only present a phenotype after birth. Sukenik-Halevy et al sought to examine the ability to detect prenatal phenotypes in patients with a postnatally diagnosed neurocognitive syndrome and confirmed genetic diagnosis on ES. The team was not able to identify any specific prenatal phenotype associated with their cases of postnatally diagnosed neurocognitive syndromes. The interesting finding of this study is that, of the 122 patients studied, 35.3% (43) had no abnormal sonographic findings that could have been detected prenatally to suggest the need for ES testing. ES is typically used in a prenatal setting for fetuses with anomalies that have a normal KT and CMA. The results of this study raise the question of offering ES to all patients considering diagnostic genetic testing regardless of the indication, as it may be the only way to diagnose some cases of neurocognitive disorders prenatally.

Cell-free fetal DNA (cff DNA) testing for trisomy 21, 18, and 13 has classically be used for high-risk pregnant patients seeking aneuploidy screening. Dar et al sought to examine this type of testing in a low-risk population. They studied, prospectively, the performance of cff DNA testing for trisomy 21, 18, and 13 in both low and high-risk pregnant women with confirmation of results on diagnostic genetic testing. Negative predictive values (NPV) for both the low and high-risk groups were greater than 99.9%. Positive predictive value (PPV) was lower for the low-risk group in comparison to the high-risk group, with it important to note that PPV drops from 96.4% in the high-risk group to 81.8% in the low-risk group for trisomy 21. This means that low-risk patients with a positive result on cff DNA testing are at a higher risk for a false positive than patients at high-risk for an aneuploid fetus. This study shows the mounting evidence that cff DNA can be used in a low-risk population given the high NPV. Providers do still need to note the lower PPV with low-risk population patients and always offer diagnostic genetic testing with any abnormal cff DNA test result.

Many neurocognitive disorders only present a phenotype after birth. Sukenik-Halevy et al sought to examine the ability to detect prenatal phenotypes in patients with a postnatally diagnosed neurocognitive syndrome and confirmed genetic diagnosis on ES. The team was not able to identify any specific prenatal phenotype associated with their cases of postnatally diagnosed neurocognitive syndromes. The interesting finding of this study is that, of the 122 patients studied, 35.3% (43) had no abnormal sonographic findings that could have been detected prenatally to suggest the need for ES testing. ES is typically used in a prenatal setting for fetuses with anomalies that have a normal KT and CMA. The results of this study raise the question of offering ES to all patients considering diagnostic genetic testing regardless of the indication, as it may be the only way to diagnose some cases of neurocognitive disorders prenatally.

Cell-free fetal DNA (cff DNA) testing for trisomy 21, 18, and 13 has classically be used for high-risk pregnant patients seeking aneuploidy screening. Dar et al sought to examine this type of testing in a low-risk population. They studied, prospectively, the performance of cff DNA testing for trisomy 21, 18, and 13 in both low and high-risk pregnant women with confirmation of results on diagnostic genetic testing. Negative predictive values (NPV) for both the low and high-risk groups were greater than 99.9%. Positive predictive value (PPV) was lower for the low-risk group in comparison to the high-risk group, with it important to note that PPV drops from 96.4% in the high-risk group to 81.8% in the low-risk group for trisomy 21. This means that low-risk patients with a positive result on cff DNA testing are at a higher risk for a false positive than patients at high-risk for an aneuploid fetus. This study shows the mounting evidence that cff DNA can be used in a low-risk population given the high NPV. Providers do still need to note the lower PPV with low-risk population patients and always offer diagnostic genetic testing with any abnormal cff DNA test result.

To the Editor:

Pretibial myxedema (PTM) is bilateral, nonpitting, scaly thickening and induration of the skin that most commonly occurs on the anterior aspects of the legs and feet. Pretibial myxedema occurs in approximately 0.5% to 4.3% of patients with hyperthyroidism.¹ Thyroid dermopathy often is thought of as the classic nonpitting PTM with skin induration and color change. However, rarer forms of PTM, including plaque, nodular, and elephantiasic, also are important to note.²

Elephantiasic PTM is extremely rare, occurring in less than 1% of patients with PTM.² Elephantiasic PTM is characterized by the persistent swelling of 1 or both legs; thickening of the skin overlying the dorsum of the feet, ankles, and toes; and verrucous irregular plaques that often are fleshy and flattened. The clinical differential diagnosis of elephantiasic PTM includes elephantiasis nostra verrucosa, a late-stage complication of chronic lymphedema that can be related to a variety of infectious or noninfectious obstructive processes. Few effective therapeutic modalities exist in the treatment of elephantiasic PTM. We present a case of elephantiasic PTM.

A 59-year-old man presented to dermatology with leonine facies with pronounced glabellar creases and indentations of the earlobes. He had diffuse woody induration, hyperpigmentation, and nonpitting edema of the lower extremities as well as several flesh-colored exophytic nodules scattered throughout the anterior shins and dorsal feet (Figure 1). On the left posterior calf, there was a large, 3-cm, exophytic, firm, flesh-colored nodule. Examination of the hands revealed mild hyperpigmentation of the distal digits, clubbing of the distal phalanges, and cheiroarthropathy.

The patient was diagnosed with Graves disease after experiencing the classic symptoms of hyperthyroidism, including heat intolerance, tremor, palpitations, and anxiety. He received thyroid ablation and subsequently was supplemented with levothyroxine 75 mg daily. Twelve years later, he was diagnosed with Graves ophthalmopathy with ocular proptosis requiring multiple courses of retro-orbital irradiation and surgical procedures for decompression. Approximately 1 year later, he noted increased swelling, firmness, and darkening of the pretibial surfaces. Initially, he was referred to vascular surgery and underwent bilateral saphenous vein ablation. He also was referred to a lymphedema specialist, and workup revealed an unremarkable lymphatic system. Minimal improvement was noted following the saphenous vein ablation, and he subsequently was referred to dermatology for further workup.

At the current presentation, laboratory analysis revealed a low thyrotropin level (0.03 mIU/L [reference range, 0.4–4.2 mIU/L]), and free thyroxine was within reference range. Radiography of the chest was unremarkable; however, radiography of the hand demonstrated arthrosis of the left fifth proximal interphalangeal joint. Nuclear medicine lymphoscintigraphy and lower extremity ultrasonography were unremarkable. Punch biopsies were performed of the left lateral leg and posterior calf. Hematoxylin and eosin staining demonstrated marked mucin deposition extending to the deep dermis along with deep fibroplasia and was read as consistent with PTM. Colloidal iron highlighted prominent mucin within the dermis (Figure 2).

The patient’s medical history, physical examination, laboratory analysis, imaging, and biopsies were considered, and a diagnosis of elephantiasic PTM was made. Minimal improvement was noted with initial therapeutic interventions including compression therapy and application of super high–potency topical corticosteroids. After further evaluation in our multidisciplinary rheumatology-dermatology clinic, the decision was made to initiate rituximab infusions.

Two months after 1 course of rituximab consisting of two 1000-mg infusions separated by 2 weeks, the patient showed substantial clinical improvement. There was striking improvement of the pretibial surfaces with resolution of the exophytic nodules and improvement of the induration (Figure 3). In addition, there was decreased induration of the glabella and earlobes and decreased fullness of the digital pulp on the hands. The patient also reported subjective improvements in mobility.

Our patient demonstrated all 3 aspects of the Diamond triad: PTM, exophthalmos, and acropachy. Patients present with all 3 features in less than 1% of reported cases of Graves disease.³ Although all 3 features are seen together infrequently, thyroid dermopathy and acropachy often are markers of severe Graves ophthalmopathy. In a study of 114 patients with Graves ophthalmopathy, patients who also had dermopathy and acropachy were more likely to have optic neuropathy or require orbital decompression.⁴

After overcoming the diagnostic dilemma that the elephantiasic presentation of PTM can present, therapeutic management remains a challenge. Heyes et al⁵ documented the successful treatment of highly recalcitrant elephantiasic PTM with rituximab and plasmapheresis therapy. In this case, a 44-year-old woman with an 11-year history of Graves disease and elephantiasic PTM received 29 rituximab infusions and 241 plasmapheresis treatments over the course of 3.5 years. Her elephantiasic PTM clinically resolved, and she was able to resume daily activities and wear normal shoes after being nonambulatory for years.⁵

Rituximab is a monoclonal antibody against CD20, a protein found primarily on the surface of B-cell lymphocytes. Although rituximab initially was approved by the US Food and Drug administration for the treatment of malignant lymphoma, it has had an increasing role in the treatment of autoimmune disorders such as rheumatoid arthritis. Rituximab is postulated to target B lymphocytes and halt their progression to plasma cells. By limiting the population of long-lasting, antibody-producing plasma cells and decreasing the autoantibodies that cause many of the symptoms in Graves disease, rituximab may be an effective therapy to consider in the treatment of elephantiasic PTM.⁶

Although the exact mechanism is poorly understood, PTM likely is a sequela of hyperthyroidism because of the expression of thyroid-stimulating hormone receptor proteins found on normal dermal fibroblasts. Thyroid-stimulating hormone receptor autoantibodies are thought to stimulate these fibroblasts to produce glycosaminoglycans. Histopathologically, accumulation of glycosaminoglycans deposited in the reticular dermis with high concentrations of hyaluronic acid is observed in PTM.⁷

Treatment of elephantiasic PTM remains a therapeutic challenge. Given the rarity of the disease process and limited information on effective therapeutic modalities, rituximab should be viewed as a viable treatment option in the management of recalcitrant elephantiasic PTM.

To the Editor:

Pretibial myxedema (PTM) is bilateral, nonpitting, scaly thickening and induration of the skin that most commonly occurs on the anterior aspects of the legs and feet. Pretibial myxedema occurs in approximately 0.5% to 4.3% of patients with hyperthyroidism.¹ Thyroid dermopathy often is thought of as the classic nonpitting PTM with skin induration and color change. However, rarer forms of PTM, including plaque, nodular, and elephantiasic, also are important to note.²

Elephantiasic PTM is extremely rare, occurring in less than 1% of patients with PTM.² Elephantiasic PTM is characterized by the persistent swelling of 1 or both legs; thickening of the skin overlying the dorsum of the feet, ankles, and toes; and verrucous irregular plaques that often are fleshy and flattened. The clinical differential diagnosis of elephantiasic PTM includes elephantiasis nostra verrucosa, a late-stage complication of chronic lymphedema that can be related to a variety of infectious or noninfectious obstructive processes. Few effective therapeutic modalities exist in the treatment of elephantiasic PTM. We present a case of elephantiasic PTM.

A 59-year-old man presented to dermatology with leonine facies with pronounced glabellar creases and indentations of the earlobes. He had diffuse woody induration, hyperpigmentation, and nonpitting edema of the lower extremities as well as several flesh-colored exophytic nodules scattered throughout the anterior shins and dorsal feet (Figure 1). On the left posterior calf, there was a large, 3-cm, exophytic, firm, flesh-colored nodule. Examination of the hands revealed mild hyperpigmentation of the distal digits, clubbing of the distal phalanges, and cheiroarthropathy.

The patient was diagnosed with Graves disease after experiencing the classic symptoms of hyperthyroidism, including heat intolerance, tremor, palpitations, and anxiety. He received thyroid ablation and subsequently was supplemented with levothyroxine 75 mg daily. Twelve years later, he was diagnosed with Graves ophthalmopathy with ocular proptosis requiring multiple courses of retro-orbital irradiation and surgical procedures for decompression. Approximately 1 year later, he noted increased swelling, firmness, and darkening of the pretibial surfaces. Initially, he was referred to vascular surgery and underwent bilateral saphenous vein ablation. He also was referred to a lymphedema specialist, and workup revealed an unremarkable lymphatic system. Minimal improvement was noted following the saphenous vein ablation, and he subsequently was referred to dermatology for further workup.

At the current presentation, laboratory analysis revealed a low thyrotropin level (0.03 mIU/L [reference range, 0.4–4.2 mIU/L]), and free thyroxine was within reference range. Radiography of the chest was unremarkable; however, radiography of the hand demonstrated arthrosis of the left fifth proximal interphalangeal joint. Nuclear medicine lymphoscintigraphy and lower extremity ultrasonography were unremarkable. Punch biopsies were performed of the left lateral leg and posterior calf. Hematoxylin and eosin staining demonstrated marked mucin deposition extending to the deep dermis along with deep fibroplasia and was read as consistent with PTM. Colloidal iron highlighted prominent mucin within the dermis (Figure 2).

The patient’s medical history, physical examination, laboratory analysis, imaging, and biopsies were considered, and a diagnosis of elephantiasic PTM was made. Minimal improvement was noted with initial therapeutic interventions including compression therapy and application of super high–potency topical corticosteroids. After further evaluation in our multidisciplinary rheumatology-dermatology clinic, the decision was made to initiate rituximab infusions.

Two months after 1 course of rituximab consisting of two 1000-mg infusions separated by 2 weeks, the patient showed substantial clinical improvement. There was striking improvement of the pretibial surfaces with resolution of the exophytic nodules and improvement of the induration (Figure 3). In addition, there was decreased induration of the glabella and earlobes and decreased fullness of the digital pulp on the hands. The patient also reported subjective improvements in mobility.

Our patient demonstrated all 3 aspects of the Diamond triad: PTM, exophthalmos, and acropachy. Patients present with all 3 features in less than 1% of reported cases of Graves disease.³ Although all 3 features are seen together infrequently, thyroid dermopathy and acropachy often are markers of severe Graves ophthalmopathy. In a study of 114 patients with Graves ophthalmopathy, patients who also had dermopathy and acropachy were more likely to have optic neuropathy or require orbital decompression.⁴

After overcoming the diagnostic dilemma that the elephantiasic presentation of PTM can present, therapeutic management remains a challenge. Heyes et al⁵ documented the successful treatment of highly recalcitrant elephantiasic PTM with rituximab and plasmapheresis therapy. In this case, a 44-year-old woman with an 11-year history of Graves disease and elephantiasic PTM received 29 rituximab infusions and 241 plasmapheresis treatments over the course of 3.5 years. Her elephantiasic PTM clinically resolved, and she was able to resume daily activities and wear normal shoes after being nonambulatory for years.⁵

Rituximab is a monoclonal antibody against CD20, a protein found primarily on the surface of B-cell lymphocytes. Although rituximab initially was approved by the US Food and Drug administration for the treatment of malignant lymphoma, it has had an increasing role in the treatment of autoimmune disorders such as rheumatoid arthritis. Rituximab is postulated to target B lymphocytes and halt their progression to plasma cells. By limiting the population of long-lasting, antibody-producing plasma cells and decreasing the autoantibodies that cause many of the symptoms in Graves disease, rituximab may be an effective therapy to consider in the treatment of elephantiasic PTM.⁶

Although the exact mechanism is poorly understood, PTM likely is a sequela of hyperthyroidism because of the expression of thyroid-stimulating hormone receptor proteins found on normal dermal fibroblasts. Thyroid-stimulating hormone receptor autoantibodies are thought to stimulate these fibroblasts to produce glycosaminoglycans. Histopathologically, accumulation of glycosaminoglycans deposited in the reticular dermis with high concentrations of hyaluronic acid is observed in PTM.⁷

Treatment of elephantiasic PTM remains a therapeutic challenge. Given the rarity of the disease process and limited information on effective therapeutic modalities, rituximab should be viewed as a viable treatment option in the management of recalcitrant elephantiasic PTM.

To the Editor:

Pretibial myxedema (PTM) is bilateral, nonpitting, scaly thickening and induration of the skin that most commonly occurs on the anterior aspects of the legs and feet. Pretibial myxedema occurs in approximately 0.5% to 4.3% of patients with hyperthyroidism.¹ Thyroid dermopathy often is thought of as the classic nonpitting PTM with skin induration and color change. However, rarer forms of PTM, including plaque, nodular, and elephantiasic, also are important to note.²

Elephantiasic PTM is extremely rare, occurring in less than 1% of patients with PTM.² Elephantiasic PTM is characterized by the persistent swelling of 1 or both legs; thickening of the skin overlying the dorsum of the feet, ankles, and toes; and verrucous irregular plaques that often are fleshy and flattened. The clinical differential diagnosis of elephantiasic PTM includes elephantiasis nostra verrucosa, a late-stage complication of chronic lymphedema that can be related to a variety of infectious or noninfectious obstructive processes. Few effective therapeutic modalities exist in the treatment of elephantiasic PTM. We present a case of elephantiasic PTM.

A 59-year-old man presented to dermatology with leonine facies with pronounced glabellar creases and indentations of the earlobes. He had diffuse woody induration, hyperpigmentation, and nonpitting edema of the lower extremities as well as several flesh-colored exophytic nodules scattered throughout the anterior shins and dorsal feet (Figure 1). On the left posterior calf, there was a large, 3-cm, exophytic, firm, flesh-colored nodule. Examination of the hands revealed mild hyperpigmentation of the distal digits, clubbing of the distal phalanges, and cheiroarthropathy.

The patient was diagnosed with Graves disease after experiencing the classic symptoms of hyperthyroidism, including heat intolerance, tremor, palpitations, and anxiety. He received thyroid ablation and subsequently was supplemented with levothyroxine 75 mg daily. Twelve years later, he was diagnosed with Graves ophthalmopathy with ocular proptosis requiring multiple courses of retro-orbital irradiation and surgical procedures for decompression. Approximately 1 year later, he noted increased swelling, firmness, and darkening of the pretibial surfaces. Initially, he was referred to vascular surgery and underwent bilateral saphenous vein ablation. He also was referred to a lymphedema specialist, and workup revealed an unremarkable lymphatic system. Minimal improvement was noted following the saphenous vein ablation, and he subsequently was referred to dermatology for further workup.

At the current presentation, laboratory analysis revealed a low thyrotropin level (0.03 mIU/L [reference range, 0.4–4.2 mIU/L]), and free thyroxine was within reference range. Radiography of the chest was unremarkable; however, radiography of the hand demonstrated arthrosis of the left fifth proximal interphalangeal joint. Nuclear medicine lymphoscintigraphy and lower extremity ultrasonography were unremarkable. Punch biopsies were performed of the left lateral leg and posterior calf. Hematoxylin and eosin staining demonstrated marked mucin deposition extending to the deep dermis along with deep fibroplasia and was read as consistent with PTM. Colloidal iron highlighted prominent mucin within the dermis (Figure 2).

The patient’s medical history, physical examination, laboratory analysis, imaging, and biopsies were considered, and a diagnosis of elephantiasic PTM was made. Minimal improvement was noted with initial therapeutic interventions including compression therapy and application of super high–potency topical corticosteroids. After further evaluation in our multidisciplinary rheumatology-dermatology clinic, the decision was made to initiate rituximab infusions.

Two months after 1 course of rituximab consisting of two 1000-mg infusions separated by 2 weeks, the patient showed substantial clinical improvement. There was striking improvement of the pretibial surfaces with resolution of the exophytic nodules and improvement of the induration (Figure 3). In addition, there was decreased induration of the glabella and earlobes and decreased fullness of the digital pulp on the hands. The patient also reported subjective improvements in mobility.

Our patient demonstrated all 3 aspects of the Diamond triad: PTM, exophthalmos, and acropachy. Patients present with all 3 features in less than 1% of reported cases of Graves disease.³ Although all 3 features are seen together infrequently, thyroid dermopathy and acropachy often are markers of severe Graves ophthalmopathy. In a study of 114 patients with Graves ophthalmopathy, patients who also had dermopathy and acropachy were more likely to have optic neuropathy or require orbital decompression.⁴

After overcoming the diagnostic dilemma that the elephantiasic presentation of PTM can present, therapeutic management remains a challenge. Heyes et al⁵ documented the successful treatment of highly recalcitrant elephantiasic PTM with rituximab and plasmapheresis therapy. In this case, a 44-year-old woman with an 11-year history of Graves disease and elephantiasic PTM received 29 rituximab infusions and 241 plasmapheresis treatments over the course of 3.5 years. Her elephantiasic PTM clinically resolved, and she was able to resume daily activities and wear normal shoes after being nonambulatory for years.⁵

Rituximab is a monoclonal antibody against CD20, a protein found primarily on the surface of B-cell lymphocytes. Although rituximab initially was approved by the US Food and Drug administration for the treatment of malignant lymphoma, it has had an increasing role in the treatment of autoimmune disorders such as rheumatoid arthritis. Rituximab is postulated to target B lymphocytes and halt their progression to plasma cells. By limiting the population of long-lasting, antibody-producing plasma cells and decreasing the autoantibodies that cause many of the symptoms in Graves disease, rituximab may be an effective therapy to consider in the treatment of elephantiasic PTM.⁶

Although the exact mechanism is poorly understood, PTM likely is a sequela of hyperthyroidism because of the expression of thyroid-stimulating hormone receptor proteins found on normal dermal fibroblasts. Thyroid-stimulating hormone receptor autoantibodies are thought to stimulate these fibroblasts to produce glycosaminoglycans. Histopathologically, accumulation of glycosaminoglycans deposited in the reticular dermis with high concentrations of hyaluronic acid is observed in PTM.⁷

Treatment of elephantiasic PTM remains a therapeutic challenge. Given the rarity of the disease process and limited information on effective therapeutic modalities, rituximab should be viewed as a viable treatment option in the management of recalcitrant elephantiasic PTM.