Key clinical point: Lenvatinib plus nivolumab shows a promising efficacy and safety profile against advanced hepatocellular carcinoma (HCC) in the real-world setting.

Major finding: The lenvatinib plus nivolumab vs lenvatinib group showed a higher objective response rate (45.0% vs 23.4%; P = .03) and longer progression-free survival (7.5 vs 4.8 months; P = .05) and overall survival (22.9 vs 10.3 months; P = .01). Only a few patients developed grade 3/4 toxicities, such as dermatitis (15.0%), gastrointestinal bleeding (7.5%), and hypertension (5.0%).

Study details: This was a retrospective study including 87 patients aged ≥20 years with advanced HCC who received lenvatinib plus nivolumab (n = 40) or lenvatinib alone (n = 47).

Disclosures: The study was funded by the Ministry of Health and Welfare and the Center of Excellence for Cancer Research and Taipei Veterans General Hospital. The authors declared no conflicts if interest.

Source: Wu W-C et al. Lenvatinib combined with nivolumab in advanced hepatocellular carcinoma-real-world experience. Invest New Drugs. 2022 (Apr 28). Doi: 10.1007/s10637-022-01248-0

Key clinical point: Lenvatinib plus nivolumab shows a promising efficacy and safety profile against advanced hepatocellular carcinoma (HCC) in the real-world setting.

Major finding: The lenvatinib plus nivolumab vs lenvatinib group showed a higher objective response rate (45.0% vs 23.4%; P = .03) and longer progression-free survival (7.5 vs 4.8 months; P = .05) and overall survival (22.9 vs 10.3 months; P = .01). Only a few patients developed grade 3/4 toxicities, such as dermatitis (15.0%), gastrointestinal bleeding (7.5%), and hypertension (5.0%).

Study details: This was a retrospective study including 87 patients aged ≥20 years with advanced HCC who received lenvatinib plus nivolumab (n = 40) or lenvatinib alone (n = 47).

Disclosures: The study was funded by the Ministry of Health and Welfare and the Center of Excellence for Cancer Research and Taipei Veterans General Hospital. The authors declared no conflicts if interest.

Source: Wu W-C et al. Lenvatinib combined with nivolumab in advanced hepatocellular carcinoma-real-world experience. Invest New Drugs. 2022 (Apr 28). Doi: 10.1007/s10637-022-01248-0

Key clinical point: Lenvatinib plus nivolumab shows a promising efficacy and safety profile against advanced hepatocellular carcinoma (HCC) in the real-world setting.

Major finding: The lenvatinib plus nivolumab vs lenvatinib group showed a higher objective response rate (45.0% vs 23.4%; P = .03) and longer progression-free survival (7.5 vs 4.8 months; P = .05) and overall survival (22.9 vs 10.3 months; P = .01). Only a few patients developed grade 3/4 toxicities, such as dermatitis (15.0%), gastrointestinal bleeding (7.5%), and hypertension (5.0%).

Study details: This was a retrospective study including 87 patients aged ≥20 years with advanced HCC who received lenvatinib plus nivolumab (n = 40) or lenvatinib alone (n = 47).

Disclosures: The study was funded by the Ministry of Health and Welfare and the Center of Excellence for Cancer Research and Taipei Veterans General Hospital. The authors declared no conflicts if interest.

Source: Wu W-C et al. Lenvatinib combined with nivolumab in advanced hepatocellular carcinoma-real-world experience. Invest New Drugs. 2022 (Apr 28). Doi: 10.1007/s10637-022-01248-0

Key clinical point: Immunotherapy was associated with prolonged survival compared with chemotherapy in patients with advanced hepatocellular carcinoma (HCC).

Major finding: After adjusting for confounding variables, immunotherapy was independently associated with improved overall survival (adjusted hazard ratio 0.76; 95% CI 0.65-0.88) compared with chemotherapy.

Study details: Findings are from a retrospective cohort study that included 3990 patients with advanced HCC (tumor-node-metastasis stage III or IV) from the National Cancer Database who received chemotherapy (n = 3248) or immunotherapy (n = 742) as the first-line systemic treatment.

Disclosures: No funding source was reported. Some authors declared serving as consultants or advisors or receiving institutional research support from various organizations.

Source: Ahn JC et al. Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States. Hepatology. 2022 (Apr 16). Doi: 10.1002/hep.32527

Key clinical point: Immunotherapy was associated with prolonged survival compared with chemotherapy in patients with advanced hepatocellular carcinoma (HCC).

Major finding: After adjusting for confounding variables, immunotherapy was independently associated with improved overall survival (adjusted hazard ratio 0.76; 95% CI 0.65-0.88) compared with chemotherapy.

Study details: Findings are from a retrospective cohort study that included 3990 patients with advanced HCC (tumor-node-metastasis stage III or IV) from the National Cancer Database who received chemotherapy (n = 3248) or immunotherapy (n = 742) as the first-line systemic treatment.

Disclosures: No funding source was reported. Some authors declared serving as consultants or advisors or receiving institutional research support from various organizations.

Source: Ahn JC et al. Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States. Hepatology. 2022 (Apr 16). Doi: 10.1002/hep.32527

Key clinical point: Immunotherapy was associated with prolonged survival compared with chemotherapy in patients with advanced hepatocellular carcinoma (HCC).

Major finding: After adjusting for confounding variables, immunotherapy was independently associated with improved overall survival (adjusted hazard ratio 0.76; 95% CI 0.65-0.88) compared with chemotherapy.

Study details: Findings are from a retrospective cohort study that included 3990 patients with advanced HCC (tumor-node-metastasis stage III or IV) from the National Cancer Database who received chemotherapy (n = 3248) or immunotherapy (n = 742) as the first-line systemic treatment.

Disclosures: No funding source was reported. Some authors declared serving as consultants or advisors or receiving institutional research support from various organizations.

Source: Ahn JC et al. Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States. Hepatology. 2022 (Apr 16). Doi: 10.1002/hep.32527

Key clinical point: As laparoscopic anatomical hepatectomy (LAH) is associated with increased disease-free survival (DFS) and comparable long-term overall survival (OS) and postoperative complications compared with non-anatomical hepatectomy (LNAH), it is recommended over LNAH for selected patients with HCC.

Major finding: Patients who underwent LAH vs LNAH showed significantly higher 5-year DFS rate (33.9% vs 30.1%; P = .009) and comparable long-term OS (43.2% vs 35.2%; P = .054) and postoperative complication (8.9% vs 12.4%; P = .255) rates.

Study details: Findings are from a single-center, prospective randomized controlled trial including 385 adult patients with HCC (single tumor ≤10 cm in size) who were randomly assigned to undergo LAH (n = 192) or LNAH (n = 193).

Disclosures: The study was sponsored by the National Natural Science Foundation of China and Project of Chongqing Municipality. The authors reported no conflicts of interest.

Source: Liao K et al. Laparoscopic anatomical versus non-anatomical hepatectomy in the treatment of hepatocellular carcinoma: A randomised controlled trial. Int J Surg. 2022;102:106652 (May 4). Doi: 10.1016/j.ijsu.2022.106652

Key clinical point: As laparoscopic anatomical hepatectomy (LAH) is associated with increased disease-free survival (DFS) and comparable long-term overall survival (OS) and postoperative complications compared with non-anatomical hepatectomy (LNAH), it is recommended over LNAH for selected patients with HCC.

Major finding: Patients who underwent LAH vs LNAH showed significantly higher 5-year DFS rate (33.9% vs 30.1%; P = .009) and comparable long-term OS (43.2% vs 35.2%; P = .054) and postoperative complication (8.9% vs 12.4%; P = .255) rates.

Study details: Findings are from a single-center, prospective randomized controlled trial including 385 adult patients with HCC (single tumor ≤10 cm in size) who were randomly assigned to undergo LAH (n = 192) or LNAH (n = 193).

Disclosures: The study was sponsored by the National Natural Science Foundation of China and Project of Chongqing Municipality. The authors reported no conflicts of interest.

Source: Liao K et al. Laparoscopic anatomical versus non-anatomical hepatectomy in the treatment of hepatocellular carcinoma: A randomised controlled trial. Int J Surg. 2022;102:106652 (May 4). Doi: 10.1016/j.ijsu.2022.106652

Key clinical point: As laparoscopic anatomical hepatectomy (LAH) is associated with increased disease-free survival (DFS) and comparable long-term overall survival (OS) and postoperative complications compared with non-anatomical hepatectomy (LNAH), it is recommended over LNAH for selected patients with HCC.

Major finding: Patients who underwent LAH vs LNAH showed significantly higher 5-year DFS rate (33.9% vs 30.1%; P = .009) and comparable long-term OS (43.2% vs 35.2%; P = .054) and postoperative complication (8.9% vs 12.4%; P = .255) rates.

Study details: Findings are from a single-center, prospective randomized controlled trial including 385 adult patients with HCC (single tumor ≤10 cm in size) who were randomly assigned to undergo LAH (n = 192) or LNAH (n = 193).

Disclosures: The study was sponsored by the National Natural Science Foundation of China and Project of Chongqing Municipality. The authors reported no conflicts of interest.

Source: Liao K et al. Laparoscopic anatomical versus non-anatomical hepatectomy in the treatment of hepatocellular carcinoma: A randomised controlled trial. Int J Surg. 2022;102:106652 (May 4). Doi: 10.1016/j.ijsu.2022.106652

Key clinical point: Compared with the standard ultrasonography (US)-based imaging surveillance for hepatocellular carcinoma (HCC), intensive surveillance using alternative computed tomography (CT)/magnetic resonance imaging (MRI) in addition to US may facilitate the diagnosis of very early-stage HCC without providing any survival advantage.

Major finding: Diagnosis of very early-stage HCC was better in the low- (adjusted odds ratio [aOR] 0.44; P = .034) and high- (aOR 0.40; P = .014) intensive surveillance groups than in the standard surveillance group. However, overall survival remained unaffected by the surveillance intensity (P > .05).

Study details: This was a retrospective cohort study including 529 patients with newly diagnosed HCC who were on regular surveillance and were monitored using only US (standard group; n = 62) or CT/MRI plus US (categorized into low-intensive group [n = 232] and high-intensive group [n = 235] based on the median percentage of CT/MRI investigations [cut-off, 27%]).

Disclosures: The study did not receive any funding. The authors disclosed no conflicts of interest.

Source: Hwang JA et al. Association between intensity of imaging surveillance and clinical outcomes in patients with hepatocellular carcinoma. Eur J Radiol. 2022;151:110328 (Apr 21). Doi: 10.1016/j.ejrad.2022.110328

Key clinical point: Compared with the standard ultrasonography (US)-based imaging surveillance for hepatocellular carcinoma (HCC), intensive surveillance using alternative computed tomography (CT)/magnetic resonance imaging (MRI) in addition to US may facilitate the diagnosis of very early-stage HCC without providing any survival advantage.

Major finding: Diagnosis of very early-stage HCC was better in the low- (adjusted odds ratio [aOR] 0.44; P = .034) and high- (aOR 0.40; P = .014) intensive surveillance groups than in the standard surveillance group. However, overall survival remained unaffected by the surveillance intensity (P > .05).

Study details: This was a retrospective cohort study including 529 patients with newly diagnosed HCC who were on regular surveillance and were monitored using only US (standard group; n = 62) or CT/MRI plus US (categorized into low-intensive group [n = 232] and high-intensive group [n = 235] based on the median percentage of CT/MRI investigations [cut-off, 27%]).

Disclosures: The study did not receive any funding. The authors disclosed no conflicts of interest.

Source: Hwang JA et al. Association between intensity of imaging surveillance and clinical outcomes in patients with hepatocellular carcinoma. Eur J Radiol. 2022;151:110328 (Apr 21). Doi: 10.1016/j.ejrad.2022.110328

Key clinical point: Compared with the standard ultrasonography (US)-based imaging surveillance for hepatocellular carcinoma (HCC), intensive surveillance using alternative computed tomography (CT)/magnetic resonance imaging (MRI) in addition to US may facilitate the diagnosis of very early-stage HCC without providing any survival advantage.

Major finding: Diagnosis of very early-stage HCC was better in the low- (adjusted odds ratio [aOR] 0.44; P = .034) and high- (aOR 0.40; P = .014) intensive surveillance groups than in the standard surveillance group. However, overall survival remained unaffected by the surveillance intensity (P > .05).

Study details: This was a retrospective cohort study including 529 patients with newly diagnosed HCC who were on regular surveillance and were monitored using only US (standard group; n = 62) or CT/MRI plus US (categorized into low-intensive group [n = 232] and high-intensive group [n = 235] based on the median percentage of CT/MRI investigations [cut-off, 27%]).

Disclosures: The study did not receive any funding. The authors disclosed no conflicts of interest.

Source: Hwang JA et al. Association between intensity of imaging surveillance and clinical outcomes in patients with hepatocellular carcinoma. Eur J Radiol. 2022;151:110328 (Apr 21). Doi: 10.1016/j.ejrad.2022.110328

Key clinical point: Compared with best supportive care (BSC), treatment with any type of anticancer therapy after immune checkpoint inhibitor (ICI) therapy discontinuation in hepatocellular carcinoma (HCC) is associated with a significant improvement in overall survival.

Major finding: After ICI therapy discontinuation, patients who received anticancer therapy vs. BSC showed a significantly improved median overall survival (12.2 vs 3.2 months; hazard ratio 0.4; P < .001).

Study details: This was a retrospective, multicenter study that included 420 patients with HCC who were treated with ICI followed by subsequent anticancer treatment (n = 163) or BSC (n = 152).

Disclosures: The study was supported by the Wellcome Trust Strategic Fund, UK. Some authors declared serving as advisors, consultants, or speakers for and receiving grants from various sources.

Source: Sharma R et al. Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC. Hepatol Commun. 2022 (Apr 28). Doi: 10.1002/hep4.1927

Key clinical point: Compared with best supportive care (BSC), treatment with any type of anticancer therapy after immune checkpoint inhibitor (ICI) therapy discontinuation in hepatocellular carcinoma (HCC) is associated with a significant improvement in overall survival.

Major finding: After ICI therapy discontinuation, patients who received anticancer therapy vs. BSC showed a significantly improved median overall survival (12.2 vs 3.2 months; hazard ratio 0.4; P < .001).

Study details: This was a retrospective, multicenter study that included 420 patients with HCC who were treated with ICI followed by subsequent anticancer treatment (n = 163) or BSC (n = 152).

Disclosures: The study was supported by the Wellcome Trust Strategic Fund, UK. Some authors declared serving as advisors, consultants, or speakers for and receiving grants from various sources.

Source: Sharma R et al. Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC. Hepatol Commun. 2022 (Apr 28). Doi: 10.1002/hep4.1927

Key clinical point: Compared with best supportive care (BSC), treatment with any type of anticancer therapy after immune checkpoint inhibitor (ICI) therapy discontinuation in hepatocellular carcinoma (HCC) is associated with a significant improvement in overall survival.

Major finding: After ICI therapy discontinuation, patients who received anticancer therapy vs. BSC showed a significantly improved median overall survival (12.2 vs 3.2 months; hazard ratio 0.4; P < .001).

Study details: This was a retrospective, multicenter study that included 420 patients with HCC who were treated with ICI followed by subsequent anticancer treatment (n = 163) or BSC (n = 152).

Disclosures: The study was supported by the Wellcome Trust Strategic Fund, UK. Some authors declared serving as advisors, consultants, or speakers for and receiving grants from various sources.

Source: Sharma R et al. Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC. Hepatol Commun. 2022 (Apr 28). Doi: 10.1002/hep4.1927

Key clinical point: Pembrolizumab monotherapy showed favorable efficacy in systemic therapy-naive patients with advanced hepatocellular carcinoma (aHCC), with no new safety signals in addition to those observed for pembrolizumab in aHCC in a second-line setting.

Major finding: The objective response rate was 16% (95% CI 7%-29%), and the median duration of response was 16 months. The median progression-free and overall survival were 4 (95% CI 2-8) and 17 (95% CI 8-23) months, respectively. Only 16% of patients experienced grade ≥3 treatment-related adverse events.

Study details: Findings are from the phase 2  KEYNOTE-224 trial including 51 adult, systemic therapy-naive patients with aHCC who received 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles.

Disclosures: The study was sponsored by Merck Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co., Inc., USA. Some authors reported being advisory board members, consultants, or advisors or receiving research grants, speaker honoraria, or travel and accommodation expenses from various sources, including MSD. The other authors are employees and stock owners of MSD.

Source: Verset G et al. Pembrolizumab monotherapy for previously untreated advanced hepatocellular carcinoma: Data from the open-label, phase II KEYNOTE-224 trial. Clin Cancer Res. 2022 (Apr 14). Doi: 10.1158/1078-0432.CCR-21-3807

Key clinical point: Pembrolizumab monotherapy showed favorable efficacy in systemic therapy-naive patients with advanced hepatocellular carcinoma (aHCC), with no new safety signals in addition to those observed for pembrolizumab in aHCC in a second-line setting.

Major finding: The objective response rate was 16% (95% CI 7%-29%), and the median duration of response was 16 months. The median progression-free and overall survival were 4 (95% CI 2-8) and 17 (95% CI 8-23) months, respectively. Only 16% of patients experienced grade ≥3 treatment-related adverse events.

Study details: Findings are from the phase 2  KEYNOTE-224 trial including 51 adult, systemic therapy-naive patients with aHCC who received 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles.

Disclosures: The study was sponsored by Merck Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co., Inc., USA. Some authors reported being advisory board members, consultants, or advisors or receiving research grants, speaker honoraria, or travel and accommodation expenses from various sources, including MSD. The other authors are employees and stock owners of MSD.

Source: Verset G et al. Pembrolizumab monotherapy for previously untreated advanced hepatocellular carcinoma: Data from the open-label, phase II KEYNOTE-224 trial. Clin Cancer Res. 2022 (Apr 14). Doi: 10.1158/1078-0432.CCR-21-3807

Key clinical point: Pembrolizumab monotherapy showed favorable efficacy in systemic therapy-naive patients with advanced hepatocellular carcinoma (aHCC), with no new safety signals in addition to those observed for pembrolizumab in aHCC in a second-line setting.

Major finding: The objective response rate was 16% (95% CI 7%-29%), and the median duration of response was 16 months. The median progression-free and overall survival were 4 (95% CI 2-8) and 17 (95% CI 8-23) months, respectively. Only 16% of patients experienced grade ≥3 treatment-related adverse events.

Study details: Findings are from the phase 2  KEYNOTE-224 trial including 51 adult, systemic therapy-naive patients with aHCC who received 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles.

Disclosures: The study was sponsored by Merck Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co., Inc., USA. Some authors reported being advisory board members, consultants, or advisors or receiving research grants, speaker honoraria, or travel and accommodation expenses from various sources, including MSD. The other authors are employees and stock owners of MSD.

Source: Verset G et al. Pembrolizumab monotherapy for previously untreated advanced hepatocellular carcinoma: Data from the open-label, phase II KEYNOTE-224 trial. Clin Cancer Res. 2022 (Apr 14). Doi: 10.1158/1078-0432.CCR-21-3807

Key clinical point: Compared with liver-directed ablative therapies, orthotopic liver transplantation (OLT) offers a survival advantage for elderly patients with early-stage hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) levels <500 ng/mL.

Major finding: Multivariable analysis revealed a significant survival benefit of OLT compared with ablative therapy alone (adjusted hazard ratio [aHR] 0.31; P < .001), with OLT being associated with better survival even after adjusting for imbalanced factors after propensity matching (aHR 0.35; P < .001).

Study details: The data come from a retrospective review study that propensity score matched patients aged ≥70 years with stage I-II HCC and AFP levels of <500 ng/mL receiving OLT (n = 170) with those undergoing liver-directed ablative therapy (n = 170).

Disclosures: No source of funding or conflicts of interest was declared by the authors.

Source: Shah MB et al. Outcomes in elderly patients undergoing liver transplantation compared with liver-directed ablative therapy in early-stage hepatocellular carcinoma. J Am Coll Surg. 2022;234(5):892-899 (Apr 15). Doi: 10.1097/XCS.0000000000000135

Key clinical point: Compared with liver-directed ablative therapies, orthotopic liver transplantation (OLT) offers a survival advantage for elderly patients with early-stage hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) levels <500 ng/mL.

Major finding: Multivariable analysis revealed a significant survival benefit of OLT compared with ablative therapy alone (adjusted hazard ratio [aHR] 0.31; P < .001), with OLT being associated with better survival even after adjusting for imbalanced factors after propensity matching (aHR 0.35; P < .001).

Study details: The data come from a retrospective review study that propensity score matched patients aged ≥70 years with stage I-II HCC and AFP levels of <500 ng/mL receiving OLT (n = 170) with those undergoing liver-directed ablative therapy (n = 170).

Disclosures: No source of funding or conflicts of interest was declared by the authors.

Source: Shah MB et al. Outcomes in elderly patients undergoing liver transplantation compared with liver-directed ablative therapy in early-stage hepatocellular carcinoma. J Am Coll Surg. 2022;234(5):892-899 (Apr 15). Doi: 10.1097/XCS.0000000000000135

Key clinical point: Compared with liver-directed ablative therapies, orthotopic liver transplantation (OLT) offers a survival advantage for elderly patients with early-stage hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) levels <500 ng/mL.

Major finding: Multivariable analysis revealed a significant survival benefit of OLT compared with ablative therapy alone (adjusted hazard ratio [aHR] 0.31; P < .001), with OLT being associated with better survival even after adjusting for imbalanced factors after propensity matching (aHR 0.35; P < .001).

Study details: The data come from a retrospective review study that propensity score matched patients aged ≥70 years with stage I-II HCC and AFP levels of <500 ng/mL receiving OLT (n = 170) with those undergoing liver-directed ablative therapy (n = 170).

Disclosures: No source of funding or conflicts of interest was declared by the authors.

Source: Shah MB et al. Outcomes in elderly patients undergoing liver transplantation compared with liver-directed ablative therapy in early-stage hepatocellular carcinoma. J Am Coll Surg. 2022;234(5):892-899 (Apr 15). Doi: 10.1097/XCS.0000000000000135

A study that tracked psychopathology in 13,000 children and adolescents found that mental health difficulties fluctuate over time, especially in younger children, and those trajectories differ among boys and girls.

Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.

Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.

The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.

He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.

“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.

The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.

Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
 

Four developmental profiles

Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).

Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.

Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.

The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
 

Externalizing problems link to high psychopathology

Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.

It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”

In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).

This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.

A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.

Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
 

Differences between boys, girls

In both cohorts, investigators noticed significant differences between the sexes.

Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.

Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.

Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
 

Study draws mixed reviews

Clinical psychiatrists not involved in the study had varying reactions to the results.

“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.

The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.

Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.

He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.

“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.

Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.

“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.

No disclosures were reported.

A study that tracked psychopathology in 13,000 children and adolescents found that mental health difficulties fluctuate over time, especially in younger children, and those trajectories differ among boys and girls.

Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.

Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.

The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.

He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.

“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.

The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.

Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
 

Four developmental profiles

Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).

Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.

Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.

The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
 

Externalizing problems link to high psychopathology

Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.

It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”

In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).

This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.

A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.

Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
 

Differences between boys, girls

In both cohorts, investigators noticed significant differences between the sexes.

Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.

Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.

Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
 

Study draws mixed reviews

Clinical psychiatrists not involved in the study had varying reactions to the results.

“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.

The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.

Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.

He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.

“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.

Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.

“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.

No disclosures were reported.

A study that tracked psychopathology in 13,000 children and adolescents found that mental health difficulties fluctuate over time, especially in younger children, and those trajectories differ among boys and girls.

Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.

Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.

The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.

He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.

“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.

The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.

Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
 

Four developmental profiles

Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).

Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.

Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.

The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
 

Externalizing problems link to high psychopathology

Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.

It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”

In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).

This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.

A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.

Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
 

Differences between boys, girls

In both cohorts, investigators noticed significant differences between the sexes.

Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.

Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.

Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
 

Study draws mixed reviews

Clinical psychiatrists not involved in the study had varying reactions to the results.

“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.

The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.

Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.

He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.

“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.

Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.

“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.

No disclosures were reported.

The Diagnosis: Lupus Erythematosus Tumidus

Histopathologic evaluation of a punch biopsy revealed focal dermal mucin deposition and CD123+ discrete clusters of plasmacytoid dendritic cells without interface changes (Figure 1), favoring a diagnosis of lupus erythematosus tumidus (LET) in our patient. There was no clinical improvement in symptoms when she previously was treated with topical antifungals or class III corticosteroid creams. Tacrolimus ointment 0.1% twice daily for 1 month did not result in substantial improvement in the appearance of the plaque, and it spontaneously resolved after 2 to 3 months. She declined treatment with hydroxychloroquine.

Lupus erythematosus tumidus is an uncommon subtype of chronic cutaneous lupus erythematosus with no distinct etiology. It is clinically characterized by edematous, urticarial, single or multiple plaques with a smooth surface affecting sun-exposed areas that can last for months to years.¹ In contrast to other variations of chronic cutaneous lupus such as discoid lupus erythematosus, LET lesions lack surface papulosquamous features such as scaling, atrophy, and follicular plugging.^1-4 Based solely on histologic findings, LET may be indistinguishable from reticular erythematous mucinosis and Jessner lymphocytic infiltration of the skin (JLIS) due to a similar lack of epidermal involvement and presence of a perivascular lymphocytic infiltrate (Figure 2).

The average age at disease onset is 36 years, nearly the same as that described in discoid lupus erythematosus.⁴ Lupus erythematosus tumidus has a favorable prognosis and commonly presents without other autoimmune signs, serologic abnormalities, or gender preference, with concomitant systemic lupus erythematosus sometimes reported.⁵

The absence of clinical and histological epidermal involvement are the most important clues to aid in the diagnosis. It has been postulated that JLIS could be an early cutaneous manifestation of LET.⁶ The differential diagnosis also may include erythema annulare centrifugum, granuloma annulare, and urticarial vasculitis. Lesions typically respond well to photoprotection, topical corticosteroids, and/or antimalarials. The addition of tacrolimus ointment 0.1% may result in complete regression without recurrence.⁷

Erythema annulare centrifugum is a reactive erythema that classically begins as a pink papule that gradually enlarges to form an annular erythematous plaque with a fine trailing scale that may recur.⁸ The histopathology of erythema annulare centrifugum shares features seen in LET, making the diagnosis difficult; however, secondary changes to the epidermis (eg, spongiosis, hyperkeratosis) may be seen. This condition has been associated with lymphoproliferative malignancies.⁸

Reticular erythematous mucinosis is clinically distinguished from LET, as it presents as reticular, rather than arciform, erythematous macules, papules, or plaques that may be asymptomatic or pruritic.⁹ Histopathology typically shows more superficial mucin deposition than in LET as well as superficial to mid-dermal perivascular and periadnexal lymphocytic infiltrates. Reticular erythematous mucinosis more frequently is reported in women in their 30s and 40s and has been associated with UV exposure and hormonal triggers, such as oral contraceptive medications and pregnancy.⁹

Granuloma annulare typically presents as asymptomatic, erythematous, annular plaques or papules in young women.¹⁰ There are several histologic subtypes that show focal collagen degeneration, inflammation with palisaded or interstitial histiocytes, and mucin deposition, regardless of clinical presentation. Granuloma annulare has been associated with systemic diseases including type 2 diabetes mellitus and thyroid disease. Localized granuloma annulare most commonly presents on the dorsal aspects of the hands or feet.¹⁰

We present a case of LET on the face. Although histologically similar to other dermatoses, LET often lacks epidermal involvement and presents on sun-exposed areas of the body. Jessner lymphocytic infiltration of the skin also should be considered in the differential, as there is an overlap of clinical and histopathological features; JLIS lacks mucin deposits.⁶ This case reinforces the importance of correlating clinical with histopathologic findings. Our patient was treated with tacrolimus ointment 0.1%, and the plaque eventually resolved in 2 to 3 months without recurrence. This condition should be included in the differential diagnosis of recurring annular plaques on sunexposed areas, particularly in middle-aged adults, even in the absence of systemic involvement.

The Diagnosis: Lupus Erythematosus Tumidus

Histopathologic evaluation of a punch biopsy revealed focal dermal mucin deposition and CD123+ discrete clusters of plasmacytoid dendritic cells without interface changes (Figure 1), favoring a diagnosis of lupus erythematosus tumidus (LET) in our patient. There was no clinical improvement in symptoms when she previously was treated with topical antifungals or class III corticosteroid creams. Tacrolimus ointment 0.1% twice daily for 1 month did not result in substantial improvement in the appearance of the plaque, and it spontaneously resolved after 2 to 3 months. She declined treatment with hydroxychloroquine.

Lupus erythematosus tumidus is an uncommon subtype of chronic cutaneous lupus erythematosus with no distinct etiology. It is clinically characterized by edematous, urticarial, single or multiple plaques with a smooth surface affecting sun-exposed areas that can last for months to years.¹ In contrast to other variations of chronic cutaneous lupus such as discoid lupus erythematosus, LET lesions lack surface papulosquamous features such as scaling, atrophy, and follicular plugging.^1-4 Based solely on histologic findings, LET may be indistinguishable from reticular erythematous mucinosis and Jessner lymphocytic infiltration of the skin (JLIS) due to a similar lack of epidermal involvement and presence of a perivascular lymphocytic infiltrate (Figure 2).

The average age at disease onset is 36 years, nearly the same as that described in discoid lupus erythematosus.⁴ Lupus erythematosus tumidus has a favorable prognosis and commonly presents without other autoimmune signs, serologic abnormalities, or gender preference, with concomitant systemic lupus erythematosus sometimes reported.⁵

The absence of clinical and histological epidermal involvement are the most important clues to aid in the diagnosis. It has been postulated that JLIS could be an early cutaneous manifestation of LET.⁶ The differential diagnosis also may include erythema annulare centrifugum, granuloma annulare, and urticarial vasculitis. Lesions typically respond well to photoprotection, topical corticosteroids, and/or antimalarials. The addition of tacrolimus ointment 0.1% may result in complete regression without recurrence.⁷

Erythema annulare centrifugum is a reactive erythema that classically begins as a pink papule that gradually enlarges to form an annular erythematous plaque with a fine trailing scale that may recur.⁸ The histopathology of erythema annulare centrifugum shares features seen in LET, making the diagnosis difficult; however, secondary changes to the epidermis (eg, spongiosis, hyperkeratosis) may be seen. This condition has been associated with lymphoproliferative malignancies.⁸

Reticular erythematous mucinosis is clinically distinguished from LET, as it presents as reticular, rather than arciform, erythematous macules, papules, or plaques that may be asymptomatic or pruritic.⁹ Histopathology typically shows more superficial mucin deposition than in LET as well as superficial to mid-dermal perivascular and periadnexal lymphocytic infiltrates. Reticular erythematous mucinosis more frequently is reported in women in their 30s and 40s and has been associated with UV exposure and hormonal triggers, such as oral contraceptive medications and pregnancy.⁹

Granuloma annulare typically presents as asymptomatic, erythematous, annular plaques or papules in young women.¹⁰ There are several histologic subtypes that show focal collagen degeneration, inflammation with palisaded or interstitial histiocytes, and mucin deposition, regardless of clinical presentation. Granuloma annulare has been associated with systemic diseases including type 2 diabetes mellitus and thyroid disease. Localized granuloma annulare most commonly presents on the dorsal aspects of the hands or feet.¹⁰

We present a case of LET on the face. Although histologically similar to other dermatoses, LET often lacks epidermal involvement and presents on sun-exposed areas of the body. Jessner lymphocytic infiltration of the skin also should be considered in the differential, as there is an overlap of clinical and histopathological features; JLIS lacks mucin deposits.⁶ This case reinforces the importance of correlating clinical with histopathologic findings. Our patient was treated with tacrolimus ointment 0.1%, and the plaque eventually resolved in 2 to 3 months without recurrence. This condition should be included in the differential diagnosis of recurring annular plaques on sunexposed areas, particularly in middle-aged adults, even in the absence of systemic involvement.

The Diagnosis: Lupus Erythematosus Tumidus

Histopathologic evaluation of a punch biopsy revealed focal dermal mucin deposition and CD123+ discrete clusters of plasmacytoid dendritic cells without interface changes (Figure 1), favoring a diagnosis of lupus erythematosus tumidus (LET) in our patient. There was no clinical improvement in symptoms when she previously was treated with topical antifungals or class III corticosteroid creams. Tacrolimus ointment 0.1% twice daily for 1 month did not result in substantial improvement in the appearance of the plaque, and it spontaneously resolved after 2 to 3 months. She declined treatment with hydroxychloroquine.

Lupus erythematosus tumidus is an uncommon subtype of chronic cutaneous lupus erythematosus with no distinct etiology. It is clinically characterized by edematous, urticarial, single or multiple plaques with a smooth surface affecting sun-exposed areas that can last for months to years.¹ In contrast to other variations of chronic cutaneous lupus such as discoid lupus erythematosus, LET lesions lack surface papulosquamous features such as scaling, atrophy, and follicular plugging.^1-4 Based solely on histologic findings, LET may be indistinguishable from reticular erythematous mucinosis and Jessner lymphocytic infiltration of the skin (JLIS) due to a similar lack of epidermal involvement and presence of a perivascular lymphocytic infiltrate (Figure 2).

The average age at disease onset is 36 years, nearly the same as that described in discoid lupus erythematosus.⁴ Lupus erythematosus tumidus has a favorable prognosis and commonly presents without other autoimmune signs, serologic abnormalities, or gender preference, with concomitant systemic lupus erythematosus sometimes reported.⁵

The absence of clinical and histological epidermal involvement are the most important clues to aid in the diagnosis. It has been postulated that JLIS could be an early cutaneous manifestation of LET.⁶ The differential diagnosis also may include erythema annulare centrifugum, granuloma annulare, and urticarial vasculitis. Lesions typically respond well to photoprotection, topical corticosteroids, and/or antimalarials. The addition of tacrolimus ointment 0.1% may result in complete regression without recurrence.⁷

Erythema annulare centrifugum is a reactive erythema that classically begins as a pink papule that gradually enlarges to form an annular erythematous plaque with a fine trailing scale that may recur.⁸ The histopathology of erythema annulare centrifugum shares features seen in LET, making the diagnosis difficult; however, secondary changes to the epidermis (eg, spongiosis, hyperkeratosis) may be seen. This condition has been associated with lymphoproliferative malignancies.⁸

Reticular erythematous mucinosis is clinically distinguished from LET, as it presents as reticular, rather than arciform, erythematous macules, papules, or plaques that may be asymptomatic or pruritic.⁹ Histopathology typically shows more superficial mucin deposition than in LET as well as superficial to mid-dermal perivascular and periadnexal lymphocytic infiltrates. Reticular erythematous mucinosis more frequently is reported in women in their 30s and 40s and has been associated with UV exposure and hormonal triggers, such as oral contraceptive medications and pregnancy.⁹

Granuloma annulare typically presents as asymptomatic, erythematous, annular plaques or papules in young women.¹⁰ There are several histologic subtypes that show focal collagen degeneration, inflammation with palisaded or interstitial histiocytes, and mucin deposition, regardless of clinical presentation. Granuloma annulare has been associated with systemic diseases including type 2 diabetes mellitus and thyroid disease. Localized granuloma annulare most commonly presents on the dorsal aspects of the hands or feet.¹⁰

We present a case of LET on the face. Although histologically similar to other dermatoses, LET often lacks epidermal involvement and presents on sun-exposed areas of the body. Jessner lymphocytic infiltration of the skin also should be considered in the differential, as there is an overlap of clinical and histopathological features; JLIS lacks mucin deposits.⁶ This case reinforces the importance of correlating clinical with histopathologic findings. Our patient was treated with tacrolimus ointment 0.1%, and the plaque eventually resolved in 2 to 3 months without recurrence. This condition should be included in the differential diagnosis of recurring annular plaques on sunexposed areas, particularly in middle-aged adults, even in the absence of systemic involvement.

Something different appears to be going on when an older adult develops inflammatory bowel disease (IBD), and now researchers offer more evidence that antibiotics could be playing a role.

Most studies to date have assessed a link between antibiotics and IBD in younger patients, lead researcher Adam S. Faye, MD, said during a media briefing that previewed select research for the annual Digestive Disease Week® (DDW).

The impact of antibiotic use on the incidence of IBD in older adults is really unknown, he added.

In contrast to younger people with IBD, who tend to have a strong family history or genetic predisposition to developing Crohn’s disease or ulcerative colitis, the cause is likely different in older populations.

“There’s clearly something in the environment that’s driving this new older-onset IBD,” said Dr. Faye, who is an assistant professor of medicine and population health at New York University.
 

Antibiotics as a contributing link

Dr. Faye and colleagues took a closer look at antibiotics as contributing to this link. They studied 2.3 million patient records in Denmark’s national medical registry from 2000 to 2018. They identified people aged 60 years and older who were newly diagnosed with IBD, and they then assessed the number, frequency, and timing of any antibiotic prescriptions.

They found that IBD was 27% more likely in this age group if the patients had received any antibiotic prescription.

They also found that the chance of developing IBD was higher as the number of antibiotic prescriptions increased. For example, IBD was 55% more likely if a person had received two prescriptions, and it was 96% more likely with four prescriptions. The risk really jumped with five or more antibiotic prescriptions – a person with this many prescriptions was more than 2.3 times (236%) more likely to be diagnosed with IBD than those who had not been prescribed antibiotics in the prior 5 years.

Not all antibiotics were equal, however. For example, the investigators found no link with nitrofurantoin, an antibiotic commonly prescribed for urinary tract infections. In contrast, all other antibiotic agents that were evaluated, and especially fluoroquinolones, nitroimidazoles, and macrolides, were associated with IBD.

Timing made some difference.

“The risk was highest if antibiotics were prescribed within the 1- to 2-year period before diagnosis, and it declined as you go farther out. But the risks persist,” Dr. Faye said. He noted that they even found that risk was elevated 10 years out.

The investigators also considered whether the antibiotic agent or infection was behind the association.

Dr. Faye cited previous research, again in younger people with IBD, that revealed that “infections plus antibiotics substantially increase the odds or risk of developing IBD more than the infection alone.

“So there really does seem to be something that the antibiotics are doing here,” Dr. Faye said.

A leading theory is that antibiotics disrupt the gut microbiota and increase the risk for developing IBD. “But, obviously, it’s quite complicated,” he said.
 

Clinical implications

The findings suggest that older people who may have IBD should be screened for prior antibiotic use, Dr. Faye said.

“This is a result that really has important implications for diagnosing older adults with new gastrointestinal symptoms,” he said. “Inflammatory bowel disease often can be overlooked in older adults because there’s a lot of different diagnoses you’re thinking of.”

IBD “should be considered, especially if you have a patient who’s reporting multiple courses of antibiotics in the last few years,” he added.

The results suggest another reason that antimicrobial stewardship programs should promote judicial use of these agents beyond concerns about resistance.

“We think of antibiotic stewardship to prevent the development of multidrug-resistant organisms, but we should be thinking about it to also prevent the development of inflammatory bowel disease,” Dr. Faye said.

Although this study adds to the evidence implicating antibiotics and expands the concept to an older population, “we really don’t have a great handle on what all of the environmental and other factors are,” he said.

Some researchers point to smoking and diet, among other factors, but the interplay remains unknown, Dr. Faye added.

The study is important because the incidence of IBD is increasing within the older population, “and this is one of the first studies to look at it,” he said.

Dr. Faye and colleagues plan to start a new study to evaluate other environmental factors.

“Hopefully, we’ll have more within the next few years to report,” he said.
 

Shedding more light on older-onset IBD worldwide

“It’s a well-done study,” Aline Charabaty, MD, said in a comment. “We are seeing that there’s an increase of incidence of IBD in the entire population, but even more so in the elderly.”

IBD is likely caused by a combination of factors, including genetics, environmental influences, and dysfunction of the gut immune system, agreed Dr. Charabaty, who is an assistant clinical professor in the division of gastroenterology at Johns Hopkins University, Baltimore.

The research “goes along with other studies that we’ve done in the pediatric and adult populations that show antibiotics exposure increases the risk of developing inflammatory bowel disease,” she said.

For a broader perspective of the study’s findings, Dr. Faye was asked during the media briefing if the results of this Danish registry study would be generalizable to the U.S. population.

“The simplest answer is we’ll need to redo this study within the U.S. to make absolutely sure,” Dr. Faye said. She noted that prior studies in the United States and elsewhere have found a risk associated with antibiotics, although again these studies focused on younger patients.

Dr. Charabaty was more certain that the findings were meaningful outside of Denmark.

“I definitely think this will apply to our U.S. population,” added Dr. Charabaty, who is also the clinical director of the IBD Center at Johns Hopkins–Sibley Memorial Hospital, Washington. “We have very similar practices in terms of how we approach antibiotic use.

“This could be one of the risk factors that’s promoting an increase in IBD everywhere,” she added.

The study was conducted in partnership with the Danish National Center of Excellence PREDICT Program. Dr. Faye and Dr. Charabaty did not report any conflicts of interest related to this study.

A version of this article first appeared on Medscape.com.

Something different appears to be going on when an older adult develops inflammatory bowel disease (IBD), and now researchers offer more evidence that antibiotics could be playing a role.

Most studies to date have assessed a link between antibiotics and IBD in younger patients, lead researcher Adam S. Faye, MD, said during a media briefing that previewed select research for the annual Digestive Disease Week® (DDW).

The impact of antibiotic use on the incidence of IBD in older adults is really unknown, he added.

In contrast to younger people with IBD, who tend to have a strong family history or genetic predisposition to developing Crohn’s disease or ulcerative colitis, the cause is likely different in older populations.

“There’s clearly something in the environment that’s driving this new older-onset IBD,” said Dr. Faye, who is an assistant professor of medicine and population health at New York University.
 

Antibiotics as a contributing link

Dr. Faye and colleagues took a closer look at antibiotics as contributing to this link. They studied 2.3 million patient records in Denmark’s national medical registry from 2000 to 2018. They identified people aged 60 years and older who were newly diagnosed with IBD, and they then assessed the number, frequency, and timing of any antibiotic prescriptions.

They found that IBD was 27% more likely in this age group if the patients had received any antibiotic prescription.

They also found that the chance of developing IBD was higher as the number of antibiotic prescriptions increased. For example, IBD was 55% more likely if a person had received two prescriptions, and it was 96% more likely with four prescriptions. The risk really jumped with five or more antibiotic prescriptions – a person with this many prescriptions was more than 2.3 times (236%) more likely to be diagnosed with IBD than those who had not been prescribed antibiotics in the prior 5 years.

Not all antibiotics were equal, however. For example, the investigators found no link with nitrofurantoin, an antibiotic commonly prescribed for urinary tract infections. In contrast, all other antibiotic agents that were evaluated, and especially fluoroquinolones, nitroimidazoles, and macrolides, were associated with IBD.

Timing made some difference.

“The risk was highest if antibiotics were prescribed within the 1- to 2-year period before diagnosis, and it declined as you go farther out. But the risks persist,” Dr. Faye said. He noted that they even found that risk was elevated 10 years out.

The investigators also considered whether the antibiotic agent or infection was behind the association.

Dr. Faye cited previous research, again in younger people with IBD, that revealed that “infections plus antibiotics substantially increase the odds or risk of developing IBD more than the infection alone.

“So there really does seem to be something that the antibiotics are doing here,” Dr. Faye said.

A leading theory is that antibiotics disrupt the gut microbiota and increase the risk for developing IBD. “But, obviously, it’s quite complicated,” he said.
 

Clinical implications

The findings suggest that older people who may have IBD should be screened for prior antibiotic use, Dr. Faye said.

“This is a result that really has important implications for diagnosing older adults with new gastrointestinal symptoms,” he said. “Inflammatory bowel disease often can be overlooked in older adults because there’s a lot of different diagnoses you’re thinking of.”

IBD “should be considered, especially if you have a patient who’s reporting multiple courses of antibiotics in the last few years,” he added.

The results suggest another reason that antimicrobial stewardship programs should promote judicial use of these agents beyond concerns about resistance.

“We think of antibiotic stewardship to prevent the development of multidrug-resistant organisms, but we should be thinking about it to also prevent the development of inflammatory bowel disease,” Dr. Faye said.

Although this study adds to the evidence implicating antibiotics and expands the concept to an older population, “we really don’t have a great handle on what all of the environmental and other factors are,” he said.

Some researchers point to smoking and diet, among other factors, but the interplay remains unknown, Dr. Faye added.

The study is important because the incidence of IBD is increasing within the older population, “and this is one of the first studies to look at it,” he said.

Dr. Faye and colleagues plan to start a new study to evaluate other environmental factors.

“Hopefully, we’ll have more within the next few years to report,” he said.
 

Shedding more light on older-onset IBD worldwide

“It’s a well-done study,” Aline Charabaty, MD, said in a comment. “We are seeing that there’s an increase of incidence of IBD in the entire population, but even more so in the elderly.”

IBD is likely caused by a combination of factors, including genetics, environmental influences, and dysfunction of the gut immune system, agreed Dr. Charabaty, who is an assistant clinical professor in the division of gastroenterology at Johns Hopkins University, Baltimore.

The research “goes along with other studies that we’ve done in the pediatric and adult populations that show antibiotics exposure increases the risk of developing inflammatory bowel disease,” she said.

For a broader perspective of the study’s findings, Dr. Faye was asked during the media briefing if the results of this Danish registry study would be generalizable to the U.S. population.

“The simplest answer is we’ll need to redo this study within the U.S. to make absolutely sure,” Dr. Faye said. She noted that prior studies in the United States and elsewhere have found a risk associated with antibiotics, although again these studies focused on younger patients.

Dr. Charabaty was more certain that the findings were meaningful outside of Denmark.

“I definitely think this will apply to our U.S. population,” added Dr. Charabaty, who is also the clinical director of the IBD Center at Johns Hopkins–Sibley Memorial Hospital, Washington. “We have very similar practices in terms of how we approach antibiotic use.

“This could be one of the risk factors that’s promoting an increase in IBD everywhere,” she added.

The study was conducted in partnership with the Danish National Center of Excellence PREDICT Program. Dr. Faye and Dr. Charabaty did not report any conflicts of interest related to this study.

A version of this article first appeared on Medscape.com.

Something different appears to be going on when an older adult develops inflammatory bowel disease (IBD), and now researchers offer more evidence that antibiotics could be playing a role.

Most studies to date have assessed a link between antibiotics and IBD in younger patients, lead researcher Adam S. Faye, MD, said during a media briefing that previewed select research for the annual Digestive Disease Week® (DDW).

The impact of antibiotic use on the incidence of IBD in older adults is really unknown, he added.

In contrast to younger people with IBD, who tend to have a strong family history or genetic predisposition to developing Crohn’s disease or ulcerative colitis, the cause is likely different in older populations.

“There’s clearly something in the environment that’s driving this new older-onset IBD,” said Dr. Faye, who is an assistant professor of medicine and population health at New York University.
 

Antibiotics as a contributing link

Dr. Faye and colleagues took a closer look at antibiotics as contributing to this link. They studied 2.3 million patient records in Denmark’s national medical registry from 2000 to 2018. They identified people aged 60 years and older who were newly diagnosed with IBD, and they then assessed the number, frequency, and timing of any antibiotic prescriptions.

They found that IBD was 27% more likely in this age group if the patients had received any antibiotic prescription.

They also found that the chance of developing IBD was higher as the number of antibiotic prescriptions increased. For example, IBD was 55% more likely if a person had received two prescriptions, and it was 96% more likely with four prescriptions. The risk really jumped with five or more antibiotic prescriptions – a person with this many prescriptions was more than 2.3 times (236%) more likely to be diagnosed with IBD than those who had not been prescribed antibiotics in the prior 5 years.

Not all antibiotics were equal, however. For example, the investigators found no link with nitrofurantoin, an antibiotic commonly prescribed for urinary tract infections. In contrast, all other antibiotic agents that were evaluated, and especially fluoroquinolones, nitroimidazoles, and macrolides, were associated with IBD.

Timing made some difference.

“The risk was highest if antibiotics were prescribed within the 1- to 2-year period before diagnosis, and it declined as you go farther out. But the risks persist,” Dr. Faye said. He noted that they even found that risk was elevated 10 years out.

The investigators also considered whether the antibiotic agent or infection was behind the association.

Dr. Faye cited previous research, again in younger people with IBD, that revealed that “infections plus antibiotics substantially increase the odds or risk of developing IBD more than the infection alone.

“So there really does seem to be something that the antibiotics are doing here,” Dr. Faye said.

A leading theory is that antibiotics disrupt the gut microbiota and increase the risk for developing IBD. “But, obviously, it’s quite complicated,” he said.
 

Clinical implications

The findings suggest that older people who may have IBD should be screened for prior antibiotic use, Dr. Faye said.

“This is a result that really has important implications for diagnosing older adults with new gastrointestinal symptoms,” he said. “Inflammatory bowel disease often can be overlooked in older adults because there’s a lot of different diagnoses you’re thinking of.”

IBD “should be considered, especially if you have a patient who’s reporting multiple courses of antibiotics in the last few years,” he added.

The results suggest another reason that antimicrobial stewardship programs should promote judicial use of these agents beyond concerns about resistance.

“We think of antibiotic stewardship to prevent the development of multidrug-resistant organisms, but we should be thinking about it to also prevent the development of inflammatory bowel disease,” Dr. Faye said.

Although this study adds to the evidence implicating antibiotics and expands the concept to an older population, “we really don’t have a great handle on what all of the environmental and other factors are,” he said.

Some researchers point to smoking and diet, among other factors, but the interplay remains unknown, Dr. Faye added.

The study is important because the incidence of IBD is increasing within the older population, “and this is one of the first studies to look at it,” he said.

Dr. Faye and colleagues plan to start a new study to evaluate other environmental factors.

“Hopefully, we’ll have more within the next few years to report,” he said.
 

Shedding more light on older-onset IBD worldwide

“It’s a well-done study,” Aline Charabaty, MD, said in a comment. “We are seeing that there’s an increase of incidence of IBD in the entire population, but even more so in the elderly.”

IBD is likely caused by a combination of factors, including genetics, environmental influences, and dysfunction of the gut immune system, agreed Dr. Charabaty, who is an assistant clinical professor in the division of gastroenterology at Johns Hopkins University, Baltimore.

The research “goes along with other studies that we’ve done in the pediatric and adult populations that show antibiotics exposure increases the risk of developing inflammatory bowel disease,” she said.

For a broader perspective of the study’s findings, Dr. Faye was asked during the media briefing if the results of this Danish registry study would be generalizable to the U.S. population.

“The simplest answer is we’ll need to redo this study within the U.S. to make absolutely sure,” Dr. Faye said. She noted that prior studies in the United States and elsewhere have found a risk associated with antibiotics, although again these studies focused on younger patients.

Dr. Charabaty was more certain that the findings were meaningful outside of Denmark.

“I definitely think this will apply to our U.S. population,” added Dr. Charabaty, who is also the clinical director of the IBD Center at Johns Hopkins–Sibley Memorial Hospital, Washington. “We have very similar practices in terms of how we approach antibiotic use.

“This could be one of the risk factors that’s promoting an increase in IBD everywhere,” she added.

The study was conducted in partnership with the Danish National Center of Excellence PREDICT Program. Dr. Faye and Dr. Charabaty did not report any conflicts of interest related to this study.

A version of this article first appeared on Medscape.com.