Dermatology

EVIDENCE SUMMARY

No trials have directly assessed skin cancer morbidity associated with physician visual skin screening. A 2018 ecologic cohort study found no difference in melanoma mortality in a population undergoing a national screening program, although screening was associated with 41% more diagnoses of skin cancer.¹ A 2012 cohort study found a reduction in melanoma mortality over 7 years associated with a population-based visual skin cancer screening program compared with similar populations that didn’t undergo specific screening.² At 12-year follow-up, however, there was no longer a difference in mortality.

Primary care visual screening doesn’t decrease melanoma mortality

German researchers trained 1673 non-­dermatologists (64% of general practitioners, obstetrician-gynecologists, and urologists in that region of Germany) and 116 dermatologists (98% in the region) to recognize skin cancer through whole-body visual inspection.¹ They recruited and screened 360,000 adults (19% of the population older than 20 years; 74% women) and followed age- and sex-adjusted melanoma mortality over the next 10 years. Non-dermatologists performed most screening exams (77%); 37% of screened positive patients were lost to follow-up.

Melanoma mortality ultimately didn’t change in the screened region, compared with populations in other European countries without national screening programs. Screening detected approximately half of melanoma cases (585/1169) in the region and was associated with 41% greater detection of skin cancers compared with other countries.

Researchers recorded age-adjusted increases in incidence per 100,000 of melanoma from 14.2 (95% confidence interval [CI], 13.3-15.1) to 18 (95% CI, 16.6-19.4), melanoma in situ from 5.8 (95% CI, 5.2-6.4) to 8.5 (95% CI, 7.5-9.5), squamous cell carcinoma from 11.2 (95% CI, 10.6-11.8) to 12.9 (95% CI, 12.0-13.8), and basal cell carcinoma from 60.5 (95% CI, 59.0-62.1) to 78.4 (95% CI, 75.9-80.8).

Visual screening by primary care providers vs screening by ­dermatologists

A cohort study of 16,383 Australian adults found that visual screening by primary care physicians detected melanoma over 3 years with a sensitivity of 40.2% (95% CIs not supplied) and specificity of 86.1% (95% CI, 85.6-86.6%; positive predictive value = 1.4%).³

A second cohort study, enrolling 7436 adults, that evaluated visual screening by dermatologists and plastic surgeons over 2 years found a sensitivity for melanoma of 49% (95% CI, 34.4-63.7%) and a specificity of 97.6% (95% CI, 97.2-97.9%) with a positive predictive value of 11.9% (95% CI, 7.8-17.2%).⁴

Visual screening more often detects thinner melanomas

A 3-year case-control study (3762 cases, 3824 controls) that examined the association between visual skin screening by a physician (type of physician not specified) and thickness of melanomas detected found that thin melanomas (≤ 0.75 mm) were more common among screened patients compared with unscreened patients (odds ratio [OR] = 1.38; 95% CI, 1.22-1.56) and thicker melanomas (≥ 0.75 mm) were less common (OR = 0.86; 95% CI, 0.75-0.98).⁵

Continue to: A systematic review...

A systematic review of 8 observational cohort studies with a total of 200,000 patients found a consistent linear increase in melanoma mortality with increasing tumor thickness.⁶ The largest study (68,495 patients), which compared melanoma mortality for thinner (< 1 mm) and thicker lesions, reported risk ratios of 2.89 for lesion thicknesses of 1.01 to 2 mm (95% CI, 2.62-3.18); 4.69 for thicknesses of 2.01 to 4 mm (95% CI, 4.24-5.02); and 5.71 for thicknesses > 4 mm (95% CI, 5.10-6.39).

Training a group comprised largely of primary care physicians to perform skin cancer screening was associated with an increase in diagnoses but no change in melanoma mortality.

The downside of visual screening: False-positives

The 2012 cohort study, which reported outcomes from 16,000 biopsies performed following visual screening exams, found that 28 biopsies were performed for each diagnosis of melanoma and 9 to 10 biopsies for each basal cell carcinoma.² Diagnosis rates (number of skin biopsies performed for each case of cancer diagnosed) were equal in men and women for both types of cancer. However, researchers observed more biopsies for each diagnosis of squamous cell carcinoma in women than men (56 vs 28 biopsies per case).

Younger patients underwent more biopsies than older patients for each diagnosis of skin cancer. Women 20 to 34 years of age underwent more biopsies than women 65 years or older for each diagnosis of melanoma (19 additional excisions) and basal cell carcinoma (134 additional excisions). Women 35 to 49 years of age underwent 565 more biopsies for each diagnosis of squamous cell carcinoma than women 65 years or older. Similar patterns applied to men 20 to 34 years of age compared with men 65 years or older (24 additional biopsies per melanoma, 109 per basal cell carcinoma, and 898 per squamous cell carcinoma).

RECOMMENDATIONS

The US Preventive Services Task Force recommendations, based on a systematic review of mostly cohort studies, state that the current evidence is insufficient to assess the balance of benefits and harms of clinician visual skin cancer screening.^7,8

The American Academy of ­Dermatology states that skin cancer screening can save lives and supports research on the benefits and harms of screening in the primary care setting.⁹

Continue to: Editor's Takeaway

 

 

Editor’s Takeaway

Skin cancer screening by primary care physicians is associated with increased detection of skin cancers, including melanomas—even though we have no confirmation that it changes melanoma mortality. It is unclear what the appropriate rate of false-positive screening tests should be, but wider adoption of noninvasive diagnostic techniques such as dermoscopy might reduce unwarranted biopsies.

EVIDENCE SUMMARY

No trials have directly assessed skin cancer morbidity associated with physician visual skin screening. A 2018 ecologic cohort study found no difference in melanoma mortality in a population undergoing a national screening program, although screening was associated with 41% more diagnoses of skin cancer.¹ A 2012 cohort study found a reduction in melanoma mortality over 7 years associated with a population-based visual skin cancer screening program compared with similar populations that didn’t undergo specific screening.² At 12-year follow-up, however, there was no longer a difference in mortality.

Primary care visual screening doesn’t decrease melanoma mortality

German researchers trained 1673 non-­dermatologists (64% of general practitioners, obstetrician-gynecologists, and urologists in that region of Germany) and 116 dermatologists (98% in the region) to recognize skin cancer through whole-body visual inspection.¹ They recruited and screened 360,000 adults (19% of the population older than 20 years; 74% women) and followed age- and sex-adjusted melanoma mortality over the next 10 years. Non-dermatologists performed most screening exams (77%); 37% of screened positive patients were lost to follow-up.

Melanoma mortality ultimately didn’t change in the screened region, compared with populations in other European countries without national screening programs. Screening detected approximately half of melanoma cases (585/1169) in the region and was associated with 41% greater detection of skin cancers compared with other countries.

Researchers recorded age-adjusted increases in incidence per 100,000 of melanoma from 14.2 (95% confidence interval [CI], 13.3-15.1) to 18 (95% CI, 16.6-19.4), melanoma in situ from 5.8 (95% CI, 5.2-6.4) to 8.5 (95% CI, 7.5-9.5), squamous cell carcinoma from 11.2 (95% CI, 10.6-11.8) to 12.9 (95% CI, 12.0-13.8), and basal cell carcinoma from 60.5 (95% CI, 59.0-62.1) to 78.4 (95% CI, 75.9-80.8).

Visual screening by primary care providers vs screening by ­dermatologists

A cohort study of 16,383 Australian adults found that visual screening by primary care physicians detected melanoma over 3 years with a sensitivity of 40.2% (95% CIs not supplied) and specificity of 86.1% (95% CI, 85.6-86.6%; positive predictive value = 1.4%).³

A second cohort study, enrolling 7436 adults, that evaluated visual screening by dermatologists and plastic surgeons over 2 years found a sensitivity for melanoma of 49% (95% CI, 34.4-63.7%) and a specificity of 97.6% (95% CI, 97.2-97.9%) with a positive predictive value of 11.9% (95% CI, 7.8-17.2%).⁴

Visual screening more often detects thinner melanomas

A 3-year case-control study (3762 cases, 3824 controls) that examined the association between visual skin screening by a physician (type of physician not specified) and thickness of melanomas detected found that thin melanomas (≤ 0.75 mm) were more common among screened patients compared with unscreened patients (odds ratio [OR] = 1.38; 95% CI, 1.22-1.56) and thicker melanomas (≥ 0.75 mm) were less common (OR = 0.86; 95% CI, 0.75-0.98).⁵

Continue to: A systematic review...

A systematic review of 8 observational cohort studies with a total of 200,000 patients found a consistent linear increase in melanoma mortality with increasing tumor thickness.⁶ The largest study (68,495 patients), which compared melanoma mortality for thinner (< 1 mm) and thicker lesions, reported risk ratios of 2.89 for lesion thicknesses of 1.01 to 2 mm (95% CI, 2.62-3.18); 4.69 for thicknesses of 2.01 to 4 mm (95% CI, 4.24-5.02); and 5.71 for thicknesses > 4 mm (95% CI, 5.10-6.39).

Training a group comprised largely of primary care physicians to perform skin cancer screening was associated with an increase in diagnoses but no change in melanoma mortality.

The downside of visual screening: False-positives

The 2012 cohort study, which reported outcomes from 16,000 biopsies performed following visual screening exams, found that 28 biopsies were performed for each diagnosis of melanoma and 9 to 10 biopsies for each basal cell carcinoma.² Diagnosis rates (number of skin biopsies performed for each case of cancer diagnosed) were equal in men and women for both types of cancer. However, researchers observed more biopsies for each diagnosis of squamous cell carcinoma in women than men (56 vs 28 biopsies per case).

Younger patients underwent more biopsies than older patients for each diagnosis of skin cancer. Women 20 to 34 years of age underwent more biopsies than women 65 years or older for each diagnosis of melanoma (19 additional excisions) and basal cell carcinoma (134 additional excisions). Women 35 to 49 years of age underwent 565 more biopsies for each diagnosis of squamous cell carcinoma than women 65 years or older. Similar patterns applied to men 20 to 34 years of age compared with men 65 years or older (24 additional biopsies per melanoma, 109 per basal cell carcinoma, and 898 per squamous cell carcinoma).

RECOMMENDATIONS

The US Preventive Services Task Force recommendations, based on a systematic review of mostly cohort studies, state that the current evidence is insufficient to assess the balance of benefits and harms of clinician visual skin cancer screening.^7,8

The American Academy of ­Dermatology states that skin cancer screening can save lives and supports research on the benefits and harms of screening in the primary care setting.⁹

Continue to: Editor's Takeaway

 

 

Editor’s Takeaway

Skin cancer screening by primary care physicians is associated with increased detection of skin cancers, including melanomas—even though we have no confirmation that it changes melanoma mortality. It is unclear what the appropriate rate of false-positive screening tests should be, but wider adoption of noninvasive diagnostic techniques such as dermoscopy might reduce unwarranted biopsies.

EVIDENCE SUMMARY

No trials have directly assessed skin cancer morbidity associated with physician visual skin screening. A 2018 ecologic cohort study found no difference in melanoma mortality in a population undergoing a national screening program, although screening was associated with 41% more diagnoses of skin cancer.¹ A 2012 cohort study found a reduction in melanoma mortality over 7 years associated with a population-based visual skin cancer screening program compared with similar populations that didn’t undergo specific screening.² At 12-year follow-up, however, there was no longer a difference in mortality.

Primary care visual screening doesn’t decrease melanoma mortality

German researchers trained 1673 non-­dermatologists (64% of general practitioners, obstetrician-gynecologists, and urologists in that region of Germany) and 116 dermatologists (98% in the region) to recognize skin cancer through whole-body visual inspection.¹ They recruited and screened 360,000 adults (19% of the population older than 20 years; 74% women) and followed age- and sex-adjusted melanoma mortality over the next 10 years. Non-dermatologists performed most screening exams (77%); 37% of screened positive patients were lost to follow-up.

Melanoma mortality ultimately didn’t change in the screened region, compared with populations in other European countries without national screening programs. Screening detected approximately half of melanoma cases (585/1169) in the region and was associated with 41% greater detection of skin cancers compared with other countries.

Researchers recorded age-adjusted increases in incidence per 100,000 of melanoma from 14.2 (95% confidence interval [CI], 13.3-15.1) to 18 (95% CI, 16.6-19.4), melanoma in situ from 5.8 (95% CI, 5.2-6.4) to 8.5 (95% CI, 7.5-9.5), squamous cell carcinoma from 11.2 (95% CI, 10.6-11.8) to 12.9 (95% CI, 12.0-13.8), and basal cell carcinoma from 60.5 (95% CI, 59.0-62.1) to 78.4 (95% CI, 75.9-80.8).

Visual screening by primary care providers vs screening by ­dermatologists

A cohort study of 16,383 Australian adults found that visual screening by primary care physicians detected melanoma over 3 years with a sensitivity of 40.2% (95% CIs not supplied) and specificity of 86.1% (95% CI, 85.6-86.6%; positive predictive value = 1.4%).³

A second cohort study, enrolling 7436 adults, that evaluated visual screening by dermatologists and plastic surgeons over 2 years found a sensitivity for melanoma of 49% (95% CI, 34.4-63.7%) and a specificity of 97.6% (95% CI, 97.2-97.9%) with a positive predictive value of 11.9% (95% CI, 7.8-17.2%).⁴

Visual screening more often detects thinner melanomas

A 3-year case-control study (3762 cases, 3824 controls) that examined the association between visual skin screening by a physician (type of physician not specified) and thickness of melanomas detected found that thin melanomas (≤ 0.75 mm) were more common among screened patients compared with unscreened patients (odds ratio [OR] = 1.38; 95% CI, 1.22-1.56) and thicker melanomas (≥ 0.75 mm) were less common (OR = 0.86; 95% CI, 0.75-0.98).⁵

Continue to: A systematic review...

A systematic review of 8 observational cohort studies with a total of 200,000 patients found a consistent linear increase in melanoma mortality with increasing tumor thickness.⁶ The largest study (68,495 patients), which compared melanoma mortality for thinner (< 1 mm) and thicker lesions, reported risk ratios of 2.89 for lesion thicknesses of 1.01 to 2 mm (95% CI, 2.62-3.18); 4.69 for thicknesses of 2.01 to 4 mm (95% CI, 4.24-5.02); and 5.71 for thicknesses > 4 mm (95% CI, 5.10-6.39).

Training a group comprised largely of primary care physicians to perform skin cancer screening was associated with an increase in diagnoses but no change in melanoma mortality.

The downside of visual screening: False-positives

The 2012 cohort study, which reported outcomes from 16,000 biopsies performed following visual screening exams, found that 28 biopsies were performed for each diagnosis of melanoma and 9 to 10 biopsies for each basal cell carcinoma.² Diagnosis rates (number of skin biopsies performed for each case of cancer diagnosed) were equal in men and women for both types of cancer. However, researchers observed more biopsies for each diagnosis of squamous cell carcinoma in women than men (56 vs 28 biopsies per case).

Younger patients underwent more biopsies than older patients for each diagnosis of skin cancer. Women 20 to 34 years of age underwent more biopsies than women 65 years or older for each diagnosis of melanoma (19 additional excisions) and basal cell carcinoma (134 additional excisions). Women 35 to 49 years of age underwent 565 more biopsies for each diagnosis of squamous cell carcinoma than women 65 years or older. Similar patterns applied to men 20 to 34 years of age compared with men 65 years or older (24 additional biopsies per melanoma, 109 per basal cell carcinoma, and 898 per squamous cell carcinoma).

RECOMMENDATIONS

The US Preventive Services Task Force recommendations, based on a systematic review of mostly cohort studies, state that the current evidence is insufficient to assess the balance of benefits and harms of clinician visual skin cancer screening.^7,8

The American Academy of ­Dermatology states that skin cancer screening can save lives and supports research on the benefits and harms of screening in the primary care setting.⁹

Continue to: Editor's Takeaway

 

 

Editor’s Takeaway

Skin cancer screening by primary care physicians is associated with increased detection of skin cancers, including melanomas—even though we have no confirmation that it changes melanoma mortality. It is unclear what the appropriate rate of false-positive screening tests should be, but wider adoption of noninvasive diagnostic techniques such as dermoscopy might reduce unwarranted biopsies.

LONDON – A quarter of urgent contacts in 20 children with generalized severe recessive dystrophic epidermolysis bullosa (GS-RDEB) were tied to esophageal narrowing, according data from a 12-month review of electronic health records.

Urgent advice was sought 102 times outside of regular or scheduled appointments by the parents of 20 children with GS-RDEB, Christine Prodinger, MD, of the University Clinic of Dermatology at Paracelsus Medical University, Salzburg, Austria, and colleagues reported in a poster presentation at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). The researchers looked at the records from the EB clinic at Great Ormond Street Hospital for Children NHS Foundation Trust, London, during April 2018–April 2019.

The mean number of urgent contacts with the specialist unit was 5.1 per patient per year, the researchers reported, with 24 of the 102 contacts (23.5%) resulting in the child being admitted to a hospital. Most of the contacts were made via email or telephone to EB nurses (94%), by contacts during home visits (3%), or in an appointment with the palliative or symptom care team (3%).

“The most common reason [for the urgent contact] was acute dysphagia,” which was experienced as choking, throat pain, difficulty eating, reflux, and vomiting, the researchers observed. Dysphagia affected children in 27 of the contacts (26.5%), and resulted in esophageal dilatation in 90% of the cases. Other reasons for urgent contact were skin infection (15.7% of contacts), uncontrolled pain (15.7% of the contacts), and eye problems (11.8%).
 

Esophageal dilatation

Strictures are just one of the esophageal manifestations of the disease, noted Anna Bruckner, MD, associate professor of dermatology and pediatrics in the department of dermatology at the University of Colorado at Denver, Aurora, during an oral presentation. Other possible manifestations include blisters and erosions, the formation of webs – a thin extension of esophageal tissue, perforations, and rupture. “These are primarily problems with dystrophic EB” but can occur with other EB subtypes, she noted.

“We don’t have great evidence” on whether the onset of esophageal strictures can be delayed or prevented, Dr. Bruckner observed. As for management, “fluoroscopy-guided balloon dilatation is probably best” for most patients, but the best procedural approach needs to be discussed on a patient-by-patient basis.

Citing a paper that documents her own experience on the use of esophageal dilatation in 24 children who underwent 231 fluoroscopy-guided balloon dilatation procedures, Dr. Bruckner noted that strictures were most commonly located in the proximal part of the esophagus, with a median distance of 13 cm down from the lips (J Pediatr Gastroenterol Nutr. 2018;67[6]:701-5).

The retrospective chart review reported by Dr. Bruckner showed that there were a median of seven dilatation procedures per patient, and 20 patients had repeated procedures at a median interval of 164 days. About 10% of procedures resulted in adverse events – mostly vomiting, pain, and fever – but there were no perforations or other serious effects, and the rate of subsequent hospitalization was 6.9%.
 

Dysphagia

Dysphagia was the predominant symptom caused by esophageal stricture in another dataset reported in a poster by Elena Pope, MD, MSc, of the Hospital for Sick Children at the University of Toronto, and colleagues.

Of 125 EB patients who had experienced at least 1 esophageal stricture episode, 497 esophageal stricture events were reported, and 85.5% of patients had difficulty swallowing at presentation, with 29.8% unable to swallow solids and 7.2% unable to swallow liquids. Other symptoms at presentation were painful swallowing (11%), food being stuck in the esophagus (8%), regurgitation (5%), coughing (4.8%), and dyspepsia (2.8%).

The aim of the retrospective, multicenter cohort study was to determine the prevalence of, and predisposing factors for, restenosis of esophageal strictures and factors that may predispose to restenosis. The study population consisted of 66 men and 59 women who had experienced their esophageal stricture at around ages 12-13 years. The majority (98.4%) had dystrophic EB, of which almost half (46.5%) had GS-RDEB.

The researchers found that the location of the esophageal stricture was important for restenosis, and that strictures occurring in the lower esophagus were 67.5% less likely to result in restenosis than if they occurred in the upper esophagus (P = .057; hazard ratio, 0.675).

A higher number of strictures was associated with a higher rate of restenosis, they reported. Indeed, patients who had two esophageal strictures had a 29.4% increased risk of restenosis, compared with those who had just one stricture (P = .038; HR, 1.294), and those with three or more strictures had an increased risk of 78.5%, compared with those having one stricture (P = .005; HR, 1.785).

Strictures longer than 1 cm also were associated with a greater (34.7%) risk of restenosis, compared with shorter strictures (P = .032; HR, 1.347). Various methods of resolving the stricture were used, from fluoroscopy-guided balloon dilatation to retro- or antegrade endoscopy. “Irrespective of method, dilatations are successful,” Dr. Pope and colleagues reported. The overall success of dilatation was 99.3%, with full dilatation achieved in almost all of the patients (96%). Of note is that there was a low risk (2.6%) of complications, they observed.

Medications were used in 46.8% of the patients, with the most popular choice being corticosteroids (90.3%), but the researchers noted that the “potential benefit of periprocedural corticosteroids use in decreasing the risk of restenosis needs further exploration.”

Dr. Bruckner had noted in her presentation that her group did not favor the use of periprocedural corticosteroids, but that antifibrotic therapy “could be attractive” for preventing future strictures.

Dr. Prodinger, Dr. Pope, and their colleagues did not provide disclosure information. Dr. Bruckner is the principal investigator for the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. She disclosed the receipt of grants or research funding, honoraria, or consultation fees from a number of drug companies, as well as other support from the EB Research Partnership and the EB Medical Research Foundation.

SOURCES: Prodinger et al. EB 2020. Poster 3; Bruckner A et al. Pediatr Gastroenterol Nutr. 2018;67(6):701-5; Pope et al. EB 2020. Poster 8.

LONDON – A quarter of urgent contacts in 20 children with generalized severe recessive dystrophic epidermolysis bullosa (GS-RDEB) were tied to esophageal narrowing, according data from a 12-month review of electronic health records.

Urgent advice was sought 102 times outside of regular or scheduled appointments by the parents of 20 children with GS-RDEB, Christine Prodinger, MD, of the University Clinic of Dermatology at Paracelsus Medical University, Salzburg, Austria, and colleagues reported in a poster presentation at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). The researchers looked at the records from the EB clinic at Great Ormond Street Hospital for Children NHS Foundation Trust, London, during April 2018–April 2019.

The mean number of urgent contacts with the specialist unit was 5.1 per patient per year, the researchers reported, with 24 of the 102 contacts (23.5%) resulting in the child being admitted to a hospital. Most of the contacts were made via email or telephone to EB nurses (94%), by contacts during home visits (3%), or in an appointment with the palliative or symptom care team (3%).

“The most common reason [for the urgent contact] was acute dysphagia,” which was experienced as choking, throat pain, difficulty eating, reflux, and vomiting, the researchers observed. Dysphagia affected children in 27 of the contacts (26.5%), and resulted in esophageal dilatation in 90% of the cases. Other reasons for urgent contact were skin infection (15.7% of contacts), uncontrolled pain (15.7% of the contacts), and eye problems (11.8%).
 

Esophageal dilatation

Strictures are just one of the esophageal manifestations of the disease, noted Anna Bruckner, MD, associate professor of dermatology and pediatrics in the department of dermatology at the University of Colorado at Denver, Aurora, during an oral presentation. Other possible manifestations include blisters and erosions, the formation of webs – a thin extension of esophageal tissue, perforations, and rupture. “These are primarily problems with dystrophic EB” but can occur with other EB subtypes, she noted.

“We don’t have great evidence” on whether the onset of esophageal strictures can be delayed or prevented, Dr. Bruckner observed. As for management, “fluoroscopy-guided balloon dilatation is probably best” for most patients, but the best procedural approach needs to be discussed on a patient-by-patient basis.

Citing a paper that documents her own experience on the use of esophageal dilatation in 24 children who underwent 231 fluoroscopy-guided balloon dilatation procedures, Dr. Bruckner noted that strictures were most commonly located in the proximal part of the esophagus, with a median distance of 13 cm down from the lips (J Pediatr Gastroenterol Nutr. 2018;67[6]:701-5).

The retrospective chart review reported by Dr. Bruckner showed that there were a median of seven dilatation procedures per patient, and 20 patients had repeated procedures at a median interval of 164 days. About 10% of procedures resulted in adverse events – mostly vomiting, pain, and fever – but there were no perforations or other serious effects, and the rate of subsequent hospitalization was 6.9%.
 

Dysphagia

Dysphagia was the predominant symptom caused by esophageal stricture in another dataset reported in a poster by Elena Pope, MD, MSc, of the Hospital for Sick Children at the University of Toronto, and colleagues.

Of 125 EB patients who had experienced at least 1 esophageal stricture episode, 497 esophageal stricture events were reported, and 85.5% of patients had difficulty swallowing at presentation, with 29.8% unable to swallow solids and 7.2% unable to swallow liquids. Other symptoms at presentation were painful swallowing (11%), food being stuck in the esophagus (8%), regurgitation (5%), coughing (4.8%), and dyspepsia (2.8%).

The aim of the retrospective, multicenter cohort study was to determine the prevalence of, and predisposing factors for, restenosis of esophageal strictures and factors that may predispose to restenosis. The study population consisted of 66 men and 59 women who had experienced their esophageal stricture at around ages 12-13 years. The majority (98.4%) had dystrophic EB, of which almost half (46.5%) had GS-RDEB.

The researchers found that the location of the esophageal stricture was important for restenosis, and that strictures occurring in the lower esophagus were 67.5% less likely to result in restenosis than if they occurred in the upper esophagus (P = .057; hazard ratio, 0.675).

A higher number of strictures was associated with a higher rate of restenosis, they reported. Indeed, patients who had two esophageal strictures had a 29.4% increased risk of restenosis, compared with those who had just one stricture (P = .038; HR, 1.294), and those with three or more strictures had an increased risk of 78.5%, compared with those having one stricture (P = .005; HR, 1.785).

Strictures longer than 1 cm also were associated with a greater (34.7%) risk of restenosis, compared with shorter strictures (P = .032; HR, 1.347). Various methods of resolving the stricture were used, from fluoroscopy-guided balloon dilatation to retro- or antegrade endoscopy. “Irrespective of method, dilatations are successful,” Dr. Pope and colleagues reported. The overall success of dilatation was 99.3%, with full dilatation achieved in almost all of the patients (96%). Of note is that there was a low risk (2.6%) of complications, they observed.

Medications were used in 46.8% of the patients, with the most popular choice being corticosteroids (90.3%), but the researchers noted that the “potential benefit of periprocedural corticosteroids use in decreasing the risk of restenosis needs further exploration.”

Dr. Bruckner had noted in her presentation that her group did not favor the use of periprocedural corticosteroids, but that antifibrotic therapy “could be attractive” for preventing future strictures.

Dr. Prodinger, Dr. Pope, and their colleagues did not provide disclosure information. Dr. Bruckner is the principal investigator for the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. She disclosed the receipt of grants or research funding, honoraria, or consultation fees from a number of drug companies, as well as other support from the EB Research Partnership and the EB Medical Research Foundation.

SOURCES: Prodinger et al. EB 2020. Poster 3; Bruckner A et al. Pediatr Gastroenterol Nutr. 2018;67(6):701-5; Pope et al. EB 2020. Poster 8.

LONDON – A quarter of urgent contacts in 20 children with generalized severe recessive dystrophic epidermolysis bullosa (GS-RDEB) were tied to esophageal narrowing, according data from a 12-month review of electronic health records.

Urgent advice was sought 102 times outside of regular or scheduled appointments by the parents of 20 children with GS-RDEB, Christine Prodinger, MD, of the University Clinic of Dermatology at Paracelsus Medical University, Salzburg, Austria, and colleagues reported in a poster presentation at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). The researchers looked at the records from the EB clinic at Great Ormond Street Hospital for Children NHS Foundation Trust, London, during April 2018–April 2019.

The mean number of urgent contacts with the specialist unit was 5.1 per patient per year, the researchers reported, with 24 of the 102 contacts (23.5%) resulting in the child being admitted to a hospital. Most of the contacts were made via email or telephone to EB nurses (94%), by contacts during home visits (3%), or in an appointment with the palliative or symptom care team (3%).

“The most common reason [for the urgent contact] was acute dysphagia,” which was experienced as choking, throat pain, difficulty eating, reflux, and vomiting, the researchers observed. Dysphagia affected children in 27 of the contacts (26.5%), and resulted in esophageal dilatation in 90% of the cases. Other reasons for urgent contact were skin infection (15.7% of contacts), uncontrolled pain (15.7% of the contacts), and eye problems (11.8%).
 

Esophageal dilatation

Strictures are just one of the esophageal manifestations of the disease, noted Anna Bruckner, MD, associate professor of dermatology and pediatrics in the department of dermatology at the University of Colorado at Denver, Aurora, during an oral presentation. Other possible manifestations include blisters and erosions, the formation of webs – a thin extension of esophageal tissue, perforations, and rupture. “These are primarily problems with dystrophic EB” but can occur with other EB subtypes, she noted.

“We don’t have great evidence” on whether the onset of esophageal strictures can be delayed or prevented, Dr. Bruckner observed. As for management, “fluoroscopy-guided balloon dilatation is probably best” for most patients, but the best procedural approach needs to be discussed on a patient-by-patient basis.

Citing a paper that documents her own experience on the use of esophageal dilatation in 24 children who underwent 231 fluoroscopy-guided balloon dilatation procedures, Dr. Bruckner noted that strictures were most commonly located in the proximal part of the esophagus, with a median distance of 13 cm down from the lips (J Pediatr Gastroenterol Nutr. 2018;67[6]:701-5).

The retrospective chart review reported by Dr. Bruckner showed that there were a median of seven dilatation procedures per patient, and 20 patients had repeated procedures at a median interval of 164 days. About 10% of procedures resulted in adverse events – mostly vomiting, pain, and fever – but there were no perforations or other serious effects, and the rate of subsequent hospitalization was 6.9%.
 

Dysphagia

Dysphagia was the predominant symptom caused by esophageal stricture in another dataset reported in a poster by Elena Pope, MD, MSc, of the Hospital for Sick Children at the University of Toronto, and colleagues.

Of 125 EB patients who had experienced at least 1 esophageal stricture episode, 497 esophageal stricture events were reported, and 85.5% of patients had difficulty swallowing at presentation, with 29.8% unable to swallow solids and 7.2% unable to swallow liquids. Other symptoms at presentation were painful swallowing (11%), food being stuck in the esophagus (8%), regurgitation (5%), coughing (4.8%), and dyspepsia (2.8%).

The aim of the retrospective, multicenter cohort study was to determine the prevalence of, and predisposing factors for, restenosis of esophageal strictures and factors that may predispose to restenosis. The study population consisted of 66 men and 59 women who had experienced their esophageal stricture at around ages 12-13 years. The majority (98.4%) had dystrophic EB, of which almost half (46.5%) had GS-RDEB.

The researchers found that the location of the esophageal stricture was important for restenosis, and that strictures occurring in the lower esophagus were 67.5% less likely to result in restenosis than if they occurred in the upper esophagus (P = .057; hazard ratio, 0.675).

A higher number of strictures was associated with a higher rate of restenosis, they reported. Indeed, patients who had two esophageal strictures had a 29.4% increased risk of restenosis, compared with those who had just one stricture (P = .038; HR, 1.294), and those with three or more strictures had an increased risk of 78.5%, compared with those having one stricture (P = .005; HR, 1.785).

Strictures longer than 1 cm also were associated with a greater (34.7%) risk of restenosis, compared with shorter strictures (P = .032; HR, 1.347). Various methods of resolving the stricture were used, from fluoroscopy-guided balloon dilatation to retro- or antegrade endoscopy. “Irrespective of method, dilatations are successful,” Dr. Pope and colleagues reported. The overall success of dilatation was 99.3%, with full dilatation achieved in almost all of the patients (96%). Of note is that there was a low risk (2.6%) of complications, they observed.

Medications were used in 46.8% of the patients, with the most popular choice being corticosteroids (90.3%), but the researchers noted that the “potential benefit of periprocedural corticosteroids use in decreasing the risk of restenosis needs further exploration.”

Dr. Bruckner had noted in her presentation that her group did not favor the use of periprocedural corticosteroids, but that antifibrotic therapy “could be attractive” for preventing future strictures.

Dr. Prodinger, Dr. Pope, and their colleagues did not provide disclosure information. Dr. Bruckner is the principal investigator for the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. She disclosed the receipt of grants or research funding, honoraria, or consultation fees from a number of drug companies, as well as other support from the EB Research Partnership and the EB Medical Research Foundation.

SOURCES: Prodinger et al. EB 2020. Poster 3; Bruckner A et al. Pediatr Gastroenterol Nutr. 2018;67(6):701-5; Pope et al. EB 2020. Poster 8.

A variety of toys and other play products can cause contact dermatitis in children because of the nature of their ingredients, according to the results of a review of 25 published articles.

Motortion/Getty Images

“In recent years the products have become a reflection of the compounds used frequently in manufacturing, including metals and plastic compounds,” wrote Justine Fenner, MD, and coauthors, from the departments of dermatology and pediatrics at the Icahn School of Medicine at Mount Sinai, New York,

In a study published in Contact Dermatitis, the researchers identified 25 articles describing dermatitis, rash, or eczema associated with a range of toy and play product terms including Nintendo, PlayStation, putty, glue, doll, game, car, bicycle, slime, iPad, and iPhone.

Overall, nickel was the most common allergen. Cases of nickel dermatitis were associated with laptops, videogame controllers, iPads, and cell phones. Cell phones were the most common electronics associated with contact dermatitis, which was observed on the cheek, periauricular area, and hand, as well as the breast in one case of a patient who kept her phone in her bra.

Other sources of metal allergens were identified in toy cars and costume jewelry, the researchers noted.

In addition, temporary tattoos have been associated with contact dermatitis in children, as have homemade “slime” products, which often contain not only borax or other household detergents, but also glue, shaving cream, or coloring.

However, identification of true allergic contact dermatitis from toys “requires both identification of the chemical contents of toys, which are proprietary in nature, and then epicutaneous allergy testing of these ingredients,” the researchers said.

The study findings were limited by several factors including the consideration only of English-language articles and of cases in children, which thus eliminates other potential cases, the researchers noted. However, the results suggest that dermatologists consider toys as a source of contact dermatitis in children, especially if the time to diagnosis is months to years, they said. “Additionally, it may be useful, as it was in several of the above cases, to have the patient bring in his or her favorite toys for the dermatologist to examine and help further understand the etiology of patient’s rash,” they noted. Moreover, “there is an unmet need for corporations to reveal the chemical ingredients of their toys when allergic contact dermatitis is suspected in order to properly evaluate the patient,” they added.

“Contact dermatitis has been underreported in children and constitutes an ongoing concern,” senior author Nanette Silverberg, MD, chief of pediatric dermatology for the Mount Sinai Health System, said in an interview.

“In particular, toy-related allergy is concerning due to the rise in allergen inclusion in common play items,” she commented. The current analysis identified many case reports of allergens that pediatric dermatologists are frequently seeing in their offices, notably metals such as nickel, she pointed out. “The allergen that always stands out ahead of others is nickel,” Dr. Silverberg said. “Nickel allergy affects about 25% of Americans, often starting in early childhood,” she said. “In the European Union, legislation has been passed to reduce nickel release from metals, which has resulted in less sensitization to nickel. We lack such legislation in the United States,” she added. 

Other trending allergens include methylchloroisothiazolinone/methylisothiazolinone, which may be components of glue or other ingredients in some “slime” products, Dr. Silverberg said.

She advised clinicians to consider patch testing when addressing localized or persistent dermatitis in children. “Furthermore, consider toys as potential relevant allergens that should be modified in order to achieve skin improvement,” she said.

“Greater reporting of pediatric allergic contact dermatitis is needed,” Dr. Silverberg emphasized. “Additionally, surveillance and monitoring for trends in allergen exposures in toys and personal care items is required to analyze this ongoing concern of childhood,” she said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Fenner J et al. Contact Dermatitis. 2020 Feb 22. doi: 10.1111/cod.13500.

A variety of toys and other play products can cause contact dermatitis in children because of the nature of their ingredients, according to the results of a review of 25 published articles.

Motortion/Getty Images

“In recent years the products have become a reflection of the compounds used frequently in manufacturing, including metals and plastic compounds,” wrote Justine Fenner, MD, and coauthors, from the departments of dermatology and pediatrics at the Icahn School of Medicine at Mount Sinai, New York,

In a study published in Contact Dermatitis, the researchers identified 25 articles describing dermatitis, rash, or eczema associated with a range of toy and play product terms including Nintendo, PlayStation, putty, glue, doll, game, car, bicycle, slime, iPad, and iPhone.

Overall, nickel was the most common allergen. Cases of nickel dermatitis were associated with laptops, videogame controllers, iPads, and cell phones. Cell phones were the most common electronics associated with contact dermatitis, which was observed on the cheek, periauricular area, and hand, as well as the breast in one case of a patient who kept her phone in her bra.

Other sources of metal allergens were identified in toy cars and costume jewelry, the researchers noted.

In addition, temporary tattoos have been associated with contact dermatitis in children, as have homemade “slime” products, which often contain not only borax or other household detergents, but also glue, shaving cream, or coloring.

However, identification of true allergic contact dermatitis from toys “requires both identification of the chemical contents of toys, which are proprietary in nature, and then epicutaneous allergy testing of these ingredients,” the researchers said.

The study findings were limited by several factors including the consideration only of English-language articles and of cases in children, which thus eliminates other potential cases, the researchers noted. However, the results suggest that dermatologists consider toys as a source of contact dermatitis in children, especially if the time to diagnosis is months to years, they said. “Additionally, it may be useful, as it was in several of the above cases, to have the patient bring in his or her favorite toys for the dermatologist to examine and help further understand the etiology of patient’s rash,” they noted. Moreover, “there is an unmet need for corporations to reveal the chemical ingredients of their toys when allergic contact dermatitis is suspected in order to properly evaluate the patient,” they added.

“Contact dermatitis has been underreported in children and constitutes an ongoing concern,” senior author Nanette Silverberg, MD, chief of pediatric dermatology for the Mount Sinai Health System, said in an interview.

“In particular, toy-related allergy is concerning due to the rise in allergen inclusion in common play items,” she commented. The current analysis identified many case reports of allergens that pediatric dermatologists are frequently seeing in their offices, notably metals such as nickel, she pointed out. “The allergen that always stands out ahead of others is nickel,” Dr. Silverberg said. “Nickel allergy affects about 25% of Americans, often starting in early childhood,” she said. “In the European Union, legislation has been passed to reduce nickel release from metals, which has resulted in less sensitization to nickel. We lack such legislation in the United States,” she added. 

Other trending allergens include methylchloroisothiazolinone/methylisothiazolinone, which may be components of glue or other ingredients in some “slime” products, Dr. Silverberg said.

She advised clinicians to consider patch testing when addressing localized or persistent dermatitis in children. “Furthermore, consider toys as potential relevant allergens that should be modified in order to achieve skin improvement,” she said.

“Greater reporting of pediatric allergic contact dermatitis is needed,” Dr. Silverberg emphasized. “Additionally, surveillance and monitoring for trends in allergen exposures in toys and personal care items is required to analyze this ongoing concern of childhood,” she said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Fenner J et al. Contact Dermatitis. 2020 Feb 22. doi: 10.1111/cod.13500.

A variety of toys and other play products can cause contact dermatitis in children because of the nature of their ingredients, according to the results of a review of 25 published articles.

Motortion/Getty Images

“In recent years the products have become a reflection of the compounds used frequently in manufacturing, including metals and plastic compounds,” wrote Justine Fenner, MD, and coauthors, from the departments of dermatology and pediatrics at the Icahn School of Medicine at Mount Sinai, New York,

In a study published in Contact Dermatitis, the researchers identified 25 articles describing dermatitis, rash, or eczema associated with a range of toy and play product terms including Nintendo, PlayStation, putty, glue, doll, game, car, bicycle, slime, iPad, and iPhone.

Overall, nickel was the most common allergen. Cases of nickel dermatitis were associated with laptops, videogame controllers, iPads, and cell phones. Cell phones were the most common electronics associated with contact dermatitis, which was observed on the cheek, periauricular area, and hand, as well as the breast in one case of a patient who kept her phone in her bra.

Other sources of metal allergens were identified in toy cars and costume jewelry, the researchers noted.

In addition, temporary tattoos have been associated with contact dermatitis in children, as have homemade “slime” products, which often contain not only borax or other household detergents, but also glue, shaving cream, or coloring.

However, identification of true allergic contact dermatitis from toys “requires both identification of the chemical contents of toys, which are proprietary in nature, and then epicutaneous allergy testing of these ingredients,” the researchers said.

The study findings were limited by several factors including the consideration only of English-language articles and of cases in children, which thus eliminates other potential cases, the researchers noted. However, the results suggest that dermatologists consider toys as a source of contact dermatitis in children, especially if the time to diagnosis is months to years, they said. “Additionally, it may be useful, as it was in several of the above cases, to have the patient bring in his or her favorite toys for the dermatologist to examine and help further understand the etiology of patient’s rash,” they noted. Moreover, “there is an unmet need for corporations to reveal the chemical ingredients of their toys when allergic contact dermatitis is suspected in order to properly evaluate the patient,” they added.

“Contact dermatitis has been underreported in children and constitutes an ongoing concern,” senior author Nanette Silverberg, MD, chief of pediatric dermatology for the Mount Sinai Health System, said in an interview.

“In particular, toy-related allergy is concerning due to the rise in allergen inclusion in common play items,” she commented. The current analysis identified many case reports of allergens that pediatric dermatologists are frequently seeing in their offices, notably metals such as nickel, she pointed out. “The allergen that always stands out ahead of others is nickel,” Dr. Silverberg said. “Nickel allergy affects about 25% of Americans, often starting in early childhood,” she said. “In the European Union, legislation has been passed to reduce nickel release from metals, which has resulted in less sensitization to nickel. We lack such legislation in the United States,” she added. 

Other trending allergens include methylchloroisothiazolinone/methylisothiazolinone, which may be components of glue or other ingredients in some “slime” products, Dr. Silverberg said.

She advised clinicians to consider patch testing when addressing localized or persistent dermatitis in children. “Furthermore, consider toys as potential relevant allergens that should be modified in order to achieve skin improvement,” she said.

“Greater reporting of pediatric allergic contact dermatitis is needed,” Dr. Silverberg emphasized. “Additionally, surveillance and monitoring for trends in allergen exposures in toys and personal care items is required to analyze this ongoing concern of childhood,” she said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Fenner J et al. Contact Dermatitis. 2020 Feb 22. doi: 10.1111/cod.13500.

LAHAINA, HAWAII – Recent data on the lidose formulation of isotretinoin indicate that, when taken without food, beneficial results of treatment in patients with acne still can be expected, Hilary E. Baldwin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

It is recommended that isotretinoin, which is fat-soluble, be taken with food, preferably high-fat foods. So it has been unclear what the effect would be when taken with lower-fat food, such as low-fat cereal and raspberries, for example, Dr. Baldwin, medical director of the Acne Treatment and Research Center in New York, pointed out.

“We’ve been trying for years to figure out how we’re going to get around this,” and there have not been any relevant data available until recently, other than in the setting of taking isotretinoin on an empty stomach or with a high-fat meal, she commented.

She referred to a open-label, single-dose, randomized crossover study that compared the bioavailability of the lidose formulation of isotretinoin (Absorica) and brand name Accutane, at a dose of 40 mg either on top of a fatty meal (the Food and Drug Administration-stipulated high-fat, high-calorie diet) or after a 10-hour fast; 60 patients did all four arms, with a 21-day washout period between them (J Am Acad Dermatol. 2013 Nov;69[5]:762-7).

In the fed state, both isotretinoin formulations were absorbed to the same extent, “but in the fasting state, there was a considerable difference,” Dr. Baldwin said. Absorption of both dropped in the fasting state, but the drop was more extreme with Accutane, “about a 50% difference between the two, in terms of how much drug was getting into the system,” she noted.

That is important because weight-based dosing is considered with isotretinoin, so at the end of treatment, a patient who has been taking it on an empty stomach may be getting a 60% lower dose than prescribed, “which could lead to a lessening of the effectiveness of the drug and also an increase in relapse over time.”

But how would a low-fat meal, like low-fat cereal and raspberries, affect the absorption, and ultimate efficacy?

This question was addressed in an open-label, single-arm study of 163 patients with acne, who were taking the lidose isotretinoin formulation without food, at the standard dose, for no longer than 20 weeks. Whether they relapsed was evaluated in a 2-year observational phase of the study, Dr. Baldwin said.

At the end of the trial, the drug was considered effective, with improvements in IGA (the 5-point Investigator’s Global Assessment scale). But the change from baseline was maintained at the 2-year posttreatment period, so the benefits of treatment lasted, which indicates that patients can take it “on top of absolutely no food whatsoever ... so if they eat anything, we are headed in the right direction,” including a low-fat meal. During the 2-year period, most patients did not need to be retreated. Of those people who needed treatment, only 4.2% needed treatment with isotretinoin, which is better than the historical relapse rates with isotretinoin, she noted.

Dr. Baldwin’s disclosures included being on the speakers’ bureau, serving as an advisor, and/or an investigator for companies that include Almirall, BioPharmx, Foamix, Galderma, Ortho Dermatologics, Sun Pharmaceuticals, Johnson & Johnson, and La Roche–Posay.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

LAHAINA, HAWAII – Recent data on the lidose formulation of isotretinoin indicate that, when taken without food, beneficial results of treatment in patients with acne still can be expected, Hilary E. Baldwin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

It is recommended that isotretinoin, which is fat-soluble, be taken with food, preferably high-fat foods. So it has been unclear what the effect would be when taken with lower-fat food, such as low-fat cereal and raspberries, for example, Dr. Baldwin, medical director of the Acne Treatment and Research Center in New York, pointed out.

“We’ve been trying for years to figure out how we’re going to get around this,” and there have not been any relevant data available until recently, other than in the setting of taking isotretinoin on an empty stomach or with a high-fat meal, she commented.

She referred to a open-label, single-dose, randomized crossover study that compared the bioavailability of the lidose formulation of isotretinoin (Absorica) and brand name Accutane, at a dose of 40 mg either on top of a fatty meal (the Food and Drug Administration-stipulated high-fat, high-calorie diet) or after a 10-hour fast; 60 patients did all four arms, with a 21-day washout period between them (J Am Acad Dermatol. 2013 Nov;69[5]:762-7).

In the fed state, both isotretinoin formulations were absorbed to the same extent, “but in the fasting state, there was a considerable difference,” Dr. Baldwin said. Absorption of both dropped in the fasting state, but the drop was more extreme with Accutane, “about a 50% difference between the two, in terms of how much drug was getting into the system,” she noted.

That is important because weight-based dosing is considered with isotretinoin, so at the end of treatment, a patient who has been taking it on an empty stomach may be getting a 60% lower dose than prescribed, “which could lead to a lessening of the effectiveness of the drug and also an increase in relapse over time.”

But how would a low-fat meal, like low-fat cereal and raspberries, affect the absorption, and ultimate efficacy?

This question was addressed in an open-label, single-arm study of 163 patients with acne, who were taking the lidose isotretinoin formulation without food, at the standard dose, for no longer than 20 weeks. Whether they relapsed was evaluated in a 2-year observational phase of the study, Dr. Baldwin said.

At the end of the trial, the drug was considered effective, with improvements in IGA (the 5-point Investigator’s Global Assessment scale). But the change from baseline was maintained at the 2-year posttreatment period, so the benefits of treatment lasted, which indicates that patients can take it “on top of absolutely no food whatsoever ... so if they eat anything, we are headed in the right direction,” including a low-fat meal. During the 2-year period, most patients did not need to be retreated. Of those people who needed treatment, only 4.2% needed treatment with isotretinoin, which is better than the historical relapse rates with isotretinoin, she noted.

Dr. Baldwin’s disclosures included being on the speakers’ bureau, serving as an advisor, and/or an investigator for companies that include Almirall, BioPharmx, Foamix, Galderma, Ortho Dermatologics, Sun Pharmaceuticals, Johnson & Johnson, and La Roche–Posay.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

LAHAINA, HAWAII – Recent data on the lidose formulation of isotretinoin indicate that, when taken without food, beneficial results of treatment in patients with acne still can be expected, Hilary E. Baldwin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

It is recommended that isotretinoin, which is fat-soluble, be taken with food, preferably high-fat foods. So it has been unclear what the effect would be when taken with lower-fat food, such as low-fat cereal and raspberries, for example, Dr. Baldwin, medical director of the Acne Treatment and Research Center in New York, pointed out.

“We’ve been trying for years to figure out how we’re going to get around this,” and there have not been any relevant data available until recently, other than in the setting of taking isotretinoin on an empty stomach or with a high-fat meal, she commented.

She referred to a open-label, single-dose, randomized crossover study that compared the bioavailability of the lidose formulation of isotretinoin (Absorica) and brand name Accutane, at a dose of 40 mg either on top of a fatty meal (the Food and Drug Administration-stipulated high-fat, high-calorie diet) or after a 10-hour fast; 60 patients did all four arms, with a 21-day washout period between them (J Am Acad Dermatol. 2013 Nov;69[5]:762-7).

In the fed state, both isotretinoin formulations were absorbed to the same extent, “but in the fasting state, there was a considerable difference,” Dr. Baldwin said. Absorption of both dropped in the fasting state, but the drop was more extreme with Accutane, “about a 50% difference between the two, in terms of how much drug was getting into the system,” she noted.

That is important because weight-based dosing is considered with isotretinoin, so at the end of treatment, a patient who has been taking it on an empty stomach may be getting a 60% lower dose than prescribed, “which could lead to a lessening of the effectiveness of the drug and also an increase in relapse over time.”

But how would a low-fat meal, like low-fat cereal and raspberries, affect the absorption, and ultimate efficacy?

This question was addressed in an open-label, single-arm study of 163 patients with acne, who were taking the lidose isotretinoin formulation without food, at the standard dose, for no longer than 20 weeks. Whether they relapsed was evaluated in a 2-year observational phase of the study, Dr. Baldwin said.

At the end of the trial, the drug was considered effective, with improvements in IGA (the 5-point Investigator’s Global Assessment scale). But the change from baseline was maintained at the 2-year posttreatment period, so the benefits of treatment lasted, which indicates that patients can take it “on top of absolutely no food whatsoever ... so if they eat anything, we are headed in the right direction,” including a low-fat meal. During the 2-year period, most patients did not need to be retreated. Of those people who needed treatment, only 4.2% needed treatment with isotretinoin, which is better than the historical relapse rates with isotretinoin, she noted.

Dr. Baldwin’s disclosures included being on the speakers’ bureau, serving as an advisor, and/or an investigator for companies that include Almirall, BioPharmx, Foamix, Galderma, Ortho Dermatologics, Sun Pharmaceuticals, Johnson & Johnson, and La Roche–Posay.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.

“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.

Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.

A large multicenter, randomized, placebo-controlled, phase 3 clinical trial of topical tapinarof cream for treatment of psoriasis is underway. The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.

“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.

The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).

“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.

A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.

Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.

“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.

Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.

A large multicenter, randomized, placebo-controlled, phase 3 clinical trial of topical tapinarof cream for treatment of psoriasis is underway. The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.

“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.

The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).

“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.

A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.

Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.

“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.

Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.

A large multicenter, randomized, placebo-controlled, phase 3 clinical trial of topical tapinarof cream for treatment of psoriasis is underway. The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.

“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.

The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).

“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.

A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.

Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Recent data on the roles of caffeinated coffee and two types of Demodex species play in rosacea were discussed by Linda Stein Gold, MD, at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

When considering rosacea triggers, the role of coffee has been difficult to determine, according to Dr. Stein Gold, director of dermatology research at the Henry Ford Health System in Detroit.

“We know that caffeine can vasoconstrict, it also has anti-inflammatory properties so ... that might help rosacea,” while the heat from a hot cup of coffee may cause vasodilation “and make rosacea worse,” she noted.

But a recent study of data from the Nurses’ Health Study II that evaluated intake of coffee, tea, soda, and chocolate every 4 years in over 82,000 women shed some light on the role coffee may play (JAMA Dermatol. 2018 Dec 1;154[12]:1394-1400). There were almost 5,000 cases of physician-diagnosed rosacea in the cohort. When the investigators looked at caffeinated coffee consumption, “the more caffeine and the more coffee they drank each day, the more likely it was for them not to have rosacea,” she said.

Those who consumed four or more servings of caffeinated coffee a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001).

But there was no significant association with decaffeinated coffee or with edibles that contained caffeine such as tea, soda, and chocolate, “so something about caffeinated coffee seems to be protective for the development of rosacea,” Dr. Stein Gold said.

Demodex mites

A few years ago, “we really didn’t think much of Demodex, but now we know Demodex tends to be a key player” in people with rosacea, Dr. Stein Gold said.

National Rosacea Society

In adults, the colonization rate of Demodex ranges from 70% to 100%, but the skin of people with rosacea have a particularly high density of Demodex: About 35%-50% of patients with rosacea have an increased Demodex load above 5 mites per cm², as measured with a standard skin surface biopsy, she noted. The density of Demodex in the skin of patients with rosacea has been measured at sixfold higher, compared with age-matched controls.

There also are two different Demodex species: Demodex folliculorum, which are longer, and Demodex brevis, which are short, and there is evidence that each “may cause an individual reaction,” Dr. Stein Gold said.

She referred to a study that found a difference in the Demodex population in patients with highly inflammatory disease with a high level of Demodex, mild rosacea patients who did not have a lot of Demodex, and people with no rosacea (Dermatol Reports. 2019 Jan 23;11[1]:7675).

“Those people who had really severe, inflammatory rosacea had Demodex folliculorum,” and the patients with the more mild disease or those with clear skin had Demodex brevis, she said, so “different species of Demodex might cause a different inflammatory reaction within individual rosacea patients.”

Dr. Stein Gold reported that she has served as a consultant, investigator, or speaker for Galderma, Dermira, Foamix Pharmaceuticals, Valeant (now Bausch Health), Allergan, Actavis, and Roche.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

LAHAINA, HAWAII – Recent data on the roles of caffeinated coffee and two types of Demodex species play in rosacea were discussed by Linda Stein Gold, MD, at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

When considering rosacea triggers, the role of coffee has been difficult to determine, according to Dr. Stein Gold, director of dermatology research at the Henry Ford Health System in Detroit.

“We know that caffeine can vasoconstrict, it also has anti-inflammatory properties so ... that might help rosacea,” while the heat from a hot cup of coffee may cause vasodilation “and make rosacea worse,” she noted.

But a recent study of data from the Nurses’ Health Study II that evaluated intake of coffee, tea, soda, and chocolate every 4 years in over 82,000 women shed some light on the role coffee may play (JAMA Dermatol. 2018 Dec 1;154[12]:1394-1400). There were almost 5,000 cases of physician-diagnosed rosacea in the cohort. When the investigators looked at caffeinated coffee consumption, “the more caffeine and the more coffee they drank each day, the more likely it was for them not to have rosacea,” she said.

Those who consumed four or more servings of caffeinated coffee a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001).

But there was no significant association with decaffeinated coffee or with edibles that contained caffeine such as tea, soda, and chocolate, “so something about caffeinated coffee seems to be protective for the development of rosacea,” Dr. Stein Gold said.

Demodex mites

A few years ago, “we really didn’t think much of Demodex, but now we know Demodex tends to be a key player” in people with rosacea, Dr. Stein Gold said.

National Rosacea Society

In adults, the colonization rate of Demodex ranges from 70% to 100%, but the skin of people with rosacea have a particularly high density of Demodex: About 35%-50% of patients with rosacea have an increased Demodex load above 5 mites per cm², as measured with a standard skin surface biopsy, she noted. The density of Demodex in the skin of patients with rosacea has been measured at sixfold higher, compared with age-matched controls.

There also are two different Demodex species: Demodex folliculorum, which are longer, and Demodex brevis, which are short, and there is evidence that each “may cause an individual reaction,” Dr. Stein Gold said.

She referred to a study that found a difference in the Demodex population in patients with highly inflammatory disease with a high level of Demodex, mild rosacea patients who did not have a lot of Demodex, and people with no rosacea (Dermatol Reports. 2019 Jan 23;11[1]:7675).

“Those people who had really severe, inflammatory rosacea had Demodex folliculorum,” and the patients with the more mild disease or those with clear skin had Demodex brevis, she said, so “different species of Demodex might cause a different inflammatory reaction within individual rosacea patients.”

Dr. Stein Gold reported that she has served as a consultant, investigator, or speaker for Galderma, Dermira, Foamix Pharmaceuticals, Valeant (now Bausch Health), Allergan, Actavis, and Roche.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

LAHAINA, HAWAII – Recent data on the roles of caffeinated coffee and two types of Demodex species play in rosacea were discussed by Linda Stein Gold, MD, at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

When considering rosacea triggers, the role of coffee has been difficult to determine, according to Dr. Stein Gold, director of dermatology research at the Henry Ford Health System in Detroit.

“We know that caffeine can vasoconstrict, it also has anti-inflammatory properties so ... that might help rosacea,” while the heat from a hot cup of coffee may cause vasodilation “and make rosacea worse,” she noted.

But a recent study of data from the Nurses’ Health Study II that evaluated intake of coffee, tea, soda, and chocolate every 4 years in over 82,000 women shed some light on the role coffee may play (JAMA Dermatol. 2018 Dec 1;154[12]:1394-1400). There were almost 5,000 cases of physician-diagnosed rosacea in the cohort. When the investigators looked at caffeinated coffee consumption, “the more caffeine and the more coffee they drank each day, the more likely it was for them not to have rosacea,” she said.

Those who consumed four or more servings of caffeinated coffee a day had a significantly lower risk of rosacea, compared with those who consumed one or fewer servings per month (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87; P less than .001).

But there was no significant association with decaffeinated coffee or with edibles that contained caffeine such as tea, soda, and chocolate, “so something about caffeinated coffee seems to be protective for the development of rosacea,” Dr. Stein Gold said.

Demodex mites

A few years ago, “we really didn’t think much of Demodex, but now we know Demodex tends to be a key player” in people with rosacea, Dr. Stein Gold said.

National Rosacea Society

In adults, the colonization rate of Demodex ranges from 70% to 100%, but the skin of people with rosacea have a particularly high density of Demodex: About 35%-50% of patients with rosacea have an increased Demodex load above 5 mites per cm², as measured with a standard skin surface biopsy, she noted. The density of Demodex in the skin of patients with rosacea has been measured at sixfold higher, compared with age-matched controls.

There also are two different Demodex species: Demodex folliculorum, which are longer, and Demodex brevis, which are short, and there is evidence that each “may cause an individual reaction,” Dr. Stein Gold said.

She referred to a study that found a difference in the Demodex population in patients with highly inflammatory disease with a high level of Demodex, mild rosacea patients who did not have a lot of Demodex, and people with no rosacea (Dermatol Reports. 2019 Jan 23;11[1]:7675).

“Those people who had really severe, inflammatory rosacea had Demodex folliculorum,” and the patients with the more mild disease or those with clear skin had Demodex brevis, she said, so “different species of Demodex might cause a different inflammatory reaction within individual rosacea patients.”

Dr. Stein Gold reported that she has served as a consultant, investigator, or speaker for Galderma, Dermira, Foamix Pharmaceuticals, Valeant (now Bausch Health), Allergan, Actavis, and Roche.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

These small (1-3 mm) grouped and solitary erythematous papules distributed around the mouth and nares were classic presentations of perioral dermatitis. Although perioral dermatitis typically affects the skin around the mouth, a newer term—periorificial dermatitis—is used because the eruption can, as seen in this patient, involve the skin around the mouth, nares, and/or eyes. Pustules also may occur. There also is a granulomatous form of periorificial dermatitis that occurs in children.

Periorificial dermatitis more closely resembles a rosacea-like eruption than a true dermatitis. Patients often report that the affected areas burn or sting, although occasionally they may be pruritic. Like rosacea, the pathogenesis of periorificial dermatitis is not completely understood. A major risk factor for the development of this condition is the use of topical corticosteroids—especially high-potency products—on the face. Therefore, the most important step in treating periorificial dermatitis is the discontinuation of topical corticosteroids (if they were being used).

In adults, oral tetracycline antibiotics are the drug of choice. As in rosacea, oral antibiotics are used not for their antimicrobial effect, but for their anti-inflammatory effect. For this reason, subantimicrobial dosing of doxycycline has become increasingly common. This reduces the likelihood of antibiotic-related adverse effects and bacterial resistance. In children or adults with a contraindication to tetracyclines, erythromycin is often used. Topical alternatives include erythromycin, metronidazole, and pimecrolimus.

In this case, the patient was advised to discontinue the topical corticosteroid and was started on subantimicrobial dosing of delayed-release doxycycline 40 mg. If the delayed-release form is not available, or is prohibitively expensive, doxycycline 20 mg bid may be used. This patient was told that it could take several weeks for the condition to improve, and that tapering the medication might help reduce recurrence, which is common.

‌

Image courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of D. Alexander Phillips, MD, and Daniel Stulberg, MD, FAAFP Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

These small (1-3 mm) grouped and solitary erythematous papules distributed around the mouth and nares were classic presentations of perioral dermatitis. Although perioral dermatitis typically affects the skin around the mouth, a newer term—periorificial dermatitis—is used because the eruption can, as seen in this patient, involve the skin around the mouth, nares, and/or eyes. Pustules also may occur. There also is a granulomatous form of periorificial dermatitis that occurs in children.

Periorificial dermatitis more closely resembles a rosacea-like eruption than a true dermatitis. Patients often report that the affected areas burn or sting, although occasionally they may be pruritic. Like rosacea, the pathogenesis of periorificial dermatitis is not completely understood. A major risk factor for the development of this condition is the use of topical corticosteroids—especially high-potency products—on the face. Therefore, the most important step in treating periorificial dermatitis is the discontinuation of topical corticosteroids (if they were being used).

In adults, oral tetracycline antibiotics are the drug of choice. As in rosacea, oral antibiotics are used not for their antimicrobial effect, but for their anti-inflammatory effect. For this reason, subantimicrobial dosing of doxycycline has become increasingly common. This reduces the likelihood of antibiotic-related adverse effects and bacterial resistance. In children or adults with a contraindication to tetracyclines, erythromycin is often used. Topical alternatives include erythromycin, metronidazole, and pimecrolimus.

In this case, the patient was advised to discontinue the topical corticosteroid and was started on subantimicrobial dosing of delayed-release doxycycline 40 mg. If the delayed-release form is not available, or is prohibitively expensive, doxycycline 20 mg bid may be used. This patient was told that it could take several weeks for the condition to improve, and that tapering the medication might help reduce recurrence, which is common.

‌

Image courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of D. Alexander Phillips, MD, and Daniel Stulberg, MD, FAAFP Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

These small (1-3 mm) grouped and solitary erythematous papules distributed around the mouth and nares were classic presentations of perioral dermatitis. Although perioral dermatitis typically affects the skin around the mouth, a newer term—periorificial dermatitis—is used because the eruption can, as seen in this patient, involve the skin around the mouth, nares, and/or eyes. Pustules also may occur. There also is a granulomatous form of periorificial dermatitis that occurs in children.

Periorificial dermatitis more closely resembles a rosacea-like eruption than a true dermatitis. Patients often report that the affected areas burn or sting, although occasionally they may be pruritic. Like rosacea, the pathogenesis of periorificial dermatitis is not completely understood. A major risk factor for the development of this condition is the use of topical corticosteroids—especially high-potency products—on the face. Therefore, the most important step in treating periorificial dermatitis is the discontinuation of topical corticosteroids (if they were being used).

In adults, oral tetracycline antibiotics are the drug of choice. As in rosacea, oral antibiotics are used not for their antimicrobial effect, but for their anti-inflammatory effect. For this reason, subantimicrobial dosing of doxycycline has become increasingly common. This reduces the likelihood of antibiotic-related adverse effects and bacterial resistance. In children or adults with a contraindication to tetracyclines, erythromycin is often used. Topical alternatives include erythromycin, metronidazole, and pimecrolimus.

In this case, the patient was advised to discontinue the topical corticosteroid and was started on subantimicrobial dosing of delayed-release doxycycline 40 mg. If the delayed-release form is not available, or is prohibitively expensive, doxycycline 20 mg bid may be used. This patient was told that it could take several weeks for the condition to improve, and that tapering the medication might help reduce recurrence, which is common.

‌

Image courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of D. Alexander Phillips, MD, and Daniel Stulberg, MD, FAAFP Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

LONDON – Median survival among patients with generalized severe recessive dystrophic epidermolysis bullosa (RDEB-GS) after a first diagnosis of mucocutaneous squamous cell carcinoma (SCC) was 2.4 years in an observational, retrospective study.

The study, conducted at St. Thomas’ Hospital and Great Ormond Street Hospital in London, was a review of all individuals with EB who had developed the skin cancer over a 28-year period, from 1991 to 2019.

A total of 44 subjects were identified who together had 221 primary SCCs. Considering all study subjects, the median age at first diagnosis of SCC was 32.6 years, with a mean of five tumors present. Almost 40% had metastatic tumors, and of the 57% who died during the observation period, 88% of deaths were attributable to the SCC.

“EB-associated SCCs differ from those in the general population,” the study’s investigators wrote in a poster presented at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (debra). “They affect a younger age group, and there are often multiple primaries,” they added. Furthermore, “they behave aggressively and metastasize early despite being well differentiated.”

Most (31) of the study participants had RDEB-GS and tended to develop their first SCC at a younger age than the group overall, at a median of 29.5 years (compared with 32.6 years for the overall group). The mean number of tumors was 5.8 among those with RDEB-GS, with over half (53.4%) of the SCCs being well differentiated and located on the hands, upper arms, feet, and lower legs. Median survival after a first diagnosis in this group was 2.4 years. The short survival after a first diagnosis of SCC “underscores the poor prognosis in this group,” the researchers wrote.

“As the largest cohort of EB SCC patients with comprehensive data regarding clinical course and management to date, our data reinforce the need for regular clinical surveillance for SCCs in EB patients,” the team concluded. This surveillance should start in adolescence for those with the severe generalized RDEB subtype, they advise, and from the third or fourth decade for other at-risk groups.

These data also highlight “the pressing need for more effective treatments,” the investigators wrote. Most (86.4%) of the SCCs among the patients in the study had been surgically removed by wide local excision, with a few patients undergoing lymph node dissection, radiotherapy, chemotherapy, electrochemotherapy, or receiving targeted cancer therapies such as erlotinib, cetuximab, or cemiplimab.

Surgery may not be an option for many patients, Jemima Mellerio, MD explained in an oral presentation at the meeting. Dr. Mellerio, a consultant dermatologist and chief of St John’s Institute of Dermatology at Guy’s & St. Thomas’ NHS Foundation, London, noted that the location of the tumor was important, as sometimes it was not physically possible to excise it completely.

Guidelines on how to manage SCCs in patients with EB were published a few years ago (Br J Dermatol. 2016;174:56-67) and noted that the clinical detection of SCCs could be difficult because of chronic wound ulceration in these patients. The “possibility of malignancy should be borne in mind, with suspicious lesions biopsied for histological evaluation,” the document states. Evidence for many of the nonsurgical options – radiotherapy, conventional chemotherapy, biologic therapies – was poor, according to the guidelines, and effective nonsurgical options are still desperately needed.

Several avenues of research are being investigated, Dr. Mellerio noted, such as targeting the fibrotic process and perhaps using a micro-RNA inhibitor to stop the upregulation of certain microRNAs in fibroblasts. Targeting inflammatory mechanisms such as thrombospondin 1, which can lead to elevated levels of tumor necrosis factor–beta and contribute to extracellular matrix stiffness, also is under investigation. Raised interleukin-6 may be another target to consider.

Research shows that similar genes are mutated in EB-related and ultraviolet-related SCCs, Dr. Mellerio said. Indeed, mutations in HRAS, NOTCH1, TP53, and CDKN2A have been reported, but mutations in these genes occur much earlier in life in patients with EB. “Something else is going on,” she added, commenting that researchers are looking at apolipoprotein B editing complex (APOBEC) enzymes, which modulate DNA and can cause “particular types of genetic changes in EB cancers.”

One investigator who is studying the genetics of EB SCCs and how APOBEC enzymes might be involved is Andrew South, PhD, an associate professor at Thomas Jefferson University, Philadelphia. APOBEC enzymes are a very prominent source of mutations in RDEB. These mutations are found in 10%-20% of squamous cell carcinomas not associated with RDEB, and 80%-90% of head and neck cancers, he said during a separate talk at the meeting.

Dr. South observed that “RDEB squamous cell carcinoma does not show any particular somatic mutation or upregulation or downregulation of genes that differentiates it from other squamous cell carcinomas, which might be disappointing on the front of it, but actually it does mean that precision therapies that have been developed for other squamous cell carcinomas have application in RDEB.”

RDEB SCC shows the greatest similarity with head and neck SCC, Dr. South said. He also stressed that fibrosis is a major driver of cancer development, SCC tumors in RDEB are homogenous, and that frontline therapy is still unclear.

What is clear, however, is that interdisciplinary management of patients is crucial, said Leena Bruckner-Tuderman, MD, professor and chair of the department of dermatology at the University Medical Center, Albert Ludwig University of Freiburg, Germany.

“In severe RDEB, metastatic SCC is the leading cause of death at a young age. We need monitoring, careful diagnostics, and multidisciplinary treatment,” Dr. Bruckner-Tuderman said. The latter should be delivered by a coordinated team that consists of dermatologists, surgeons, radiologists, oncologists, pathologists, geneticists, and (molecular) tumor boards, she advised.

The study had no commercial funding. Dr. Mellerio disclosed financial relationships with Castle Creek Pharmaceuticals and ProQR Therapeutics, and acted as an unpaid advisor to Helpberby Therapeutics. Dr. South disclosed financial relationships with Krystal Biotech Inc. and Amryt Genetics and has been an advisory board member for Abeona Therapeutics and Sanofi Genzyme. Dr. Bruckner-Tuderman disclosed receiving grants or research support from Constant Pharmaceuticals/Tarix Orphan.

LONDON – Median survival among patients with generalized severe recessive dystrophic epidermolysis bullosa (RDEB-GS) after a first diagnosis of mucocutaneous squamous cell carcinoma (SCC) was 2.4 years in an observational, retrospective study.

The study, conducted at St. Thomas’ Hospital and Great Ormond Street Hospital in London, was a review of all individuals with EB who had developed the skin cancer over a 28-year period, from 1991 to 2019.

A total of 44 subjects were identified who together had 221 primary SCCs. Considering all study subjects, the median age at first diagnosis of SCC was 32.6 years, with a mean of five tumors present. Almost 40% had metastatic tumors, and of the 57% who died during the observation period, 88% of deaths were attributable to the SCC.

“EB-associated SCCs differ from those in the general population,” the study’s investigators wrote in a poster presented at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (debra). “They affect a younger age group, and there are often multiple primaries,” they added. Furthermore, “they behave aggressively and metastasize early despite being well differentiated.”

Most (31) of the study participants had RDEB-GS and tended to develop their first SCC at a younger age than the group overall, at a median of 29.5 years (compared with 32.6 years for the overall group). The mean number of tumors was 5.8 among those with RDEB-GS, with over half (53.4%) of the SCCs being well differentiated and located on the hands, upper arms, feet, and lower legs. Median survival after a first diagnosis in this group was 2.4 years. The short survival after a first diagnosis of SCC “underscores the poor prognosis in this group,” the researchers wrote.

“As the largest cohort of EB SCC patients with comprehensive data regarding clinical course and management to date, our data reinforce the need for regular clinical surveillance for SCCs in EB patients,” the team concluded. This surveillance should start in adolescence for those with the severe generalized RDEB subtype, they advise, and from the third or fourth decade for other at-risk groups.

These data also highlight “the pressing need for more effective treatments,” the investigators wrote. Most (86.4%) of the SCCs among the patients in the study had been surgically removed by wide local excision, with a few patients undergoing lymph node dissection, radiotherapy, chemotherapy, electrochemotherapy, or receiving targeted cancer therapies such as erlotinib, cetuximab, or cemiplimab.

Surgery may not be an option for many patients, Jemima Mellerio, MD explained in an oral presentation at the meeting. Dr. Mellerio, a consultant dermatologist and chief of St John’s Institute of Dermatology at Guy’s & St. Thomas’ NHS Foundation, London, noted that the location of the tumor was important, as sometimes it was not physically possible to excise it completely.

Guidelines on how to manage SCCs in patients with EB were published a few years ago (Br J Dermatol. 2016;174:56-67) and noted that the clinical detection of SCCs could be difficult because of chronic wound ulceration in these patients. The “possibility of malignancy should be borne in mind, with suspicious lesions biopsied for histological evaluation,” the document states. Evidence for many of the nonsurgical options – radiotherapy, conventional chemotherapy, biologic therapies – was poor, according to the guidelines, and effective nonsurgical options are still desperately needed.

Several avenues of research are being investigated, Dr. Mellerio noted, such as targeting the fibrotic process and perhaps using a micro-RNA inhibitor to stop the upregulation of certain microRNAs in fibroblasts. Targeting inflammatory mechanisms such as thrombospondin 1, which can lead to elevated levels of tumor necrosis factor–beta and contribute to extracellular matrix stiffness, also is under investigation. Raised interleukin-6 may be another target to consider.

Research shows that similar genes are mutated in EB-related and ultraviolet-related SCCs, Dr. Mellerio said. Indeed, mutations in HRAS, NOTCH1, TP53, and CDKN2A have been reported, but mutations in these genes occur much earlier in life in patients with EB. “Something else is going on,” she added, commenting that researchers are looking at apolipoprotein B editing complex (APOBEC) enzymes, which modulate DNA and can cause “particular types of genetic changes in EB cancers.”

One investigator who is studying the genetics of EB SCCs and how APOBEC enzymes might be involved is Andrew South, PhD, an associate professor at Thomas Jefferson University, Philadelphia. APOBEC enzymes are a very prominent source of mutations in RDEB. These mutations are found in 10%-20% of squamous cell carcinomas not associated with RDEB, and 80%-90% of head and neck cancers, he said during a separate talk at the meeting.

Dr. South observed that “RDEB squamous cell carcinoma does not show any particular somatic mutation or upregulation or downregulation of genes that differentiates it from other squamous cell carcinomas, which might be disappointing on the front of it, but actually it does mean that precision therapies that have been developed for other squamous cell carcinomas have application in RDEB.”

RDEB SCC shows the greatest similarity with head and neck SCC, Dr. South said. He also stressed that fibrosis is a major driver of cancer development, SCC tumors in RDEB are homogenous, and that frontline therapy is still unclear.

What is clear, however, is that interdisciplinary management of patients is crucial, said Leena Bruckner-Tuderman, MD, professor and chair of the department of dermatology at the University Medical Center, Albert Ludwig University of Freiburg, Germany.

“In severe RDEB, metastatic SCC is the leading cause of death at a young age. We need monitoring, careful diagnostics, and multidisciplinary treatment,” Dr. Bruckner-Tuderman said. The latter should be delivered by a coordinated team that consists of dermatologists, surgeons, radiologists, oncologists, pathologists, geneticists, and (molecular) tumor boards, she advised.

The study had no commercial funding. Dr. Mellerio disclosed financial relationships with Castle Creek Pharmaceuticals and ProQR Therapeutics, and acted as an unpaid advisor to Helpberby Therapeutics. Dr. South disclosed financial relationships with Krystal Biotech Inc. and Amryt Genetics and has been an advisory board member for Abeona Therapeutics and Sanofi Genzyme. Dr. Bruckner-Tuderman disclosed receiving grants or research support from Constant Pharmaceuticals/Tarix Orphan.

LONDON – Median survival among patients with generalized severe recessive dystrophic epidermolysis bullosa (RDEB-GS) after a first diagnosis of mucocutaneous squamous cell carcinoma (SCC) was 2.4 years in an observational, retrospective study.

The study, conducted at St. Thomas’ Hospital and Great Ormond Street Hospital in London, was a review of all individuals with EB who had developed the skin cancer over a 28-year period, from 1991 to 2019.

A total of 44 subjects were identified who together had 221 primary SCCs. Considering all study subjects, the median age at first diagnosis of SCC was 32.6 years, with a mean of five tumors present. Almost 40% had metastatic tumors, and of the 57% who died during the observation period, 88% of deaths were attributable to the SCC.

“EB-associated SCCs differ from those in the general population,” the study’s investigators wrote in a poster presented at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (debra). “They affect a younger age group, and there are often multiple primaries,” they added. Furthermore, “they behave aggressively and metastasize early despite being well differentiated.”

Most (31) of the study participants had RDEB-GS and tended to develop their first SCC at a younger age than the group overall, at a median of 29.5 years (compared with 32.6 years for the overall group). The mean number of tumors was 5.8 among those with RDEB-GS, with over half (53.4%) of the SCCs being well differentiated and located on the hands, upper arms, feet, and lower legs. Median survival after a first diagnosis in this group was 2.4 years. The short survival after a first diagnosis of SCC “underscores the poor prognosis in this group,” the researchers wrote.

“As the largest cohort of EB SCC patients with comprehensive data regarding clinical course and management to date, our data reinforce the need for regular clinical surveillance for SCCs in EB patients,” the team concluded. This surveillance should start in adolescence for those with the severe generalized RDEB subtype, they advise, and from the third or fourth decade for other at-risk groups.

These data also highlight “the pressing need for more effective treatments,” the investigators wrote. Most (86.4%) of the SCCs among the patients in the study had been surgically removed by wide local excision, with a few patients undergoing lymph node dissection, radiotherapy, chemotherapy, electrochemotherapy, or receiving targeted cancer therapies such as erlotinib, cetuximab, or cemiplimab.

Surgery may not be an option for many patients, Jemima Mellerio, MD explained in an oral presentation at the meeting. Dr. Mellerio, a consultant dermatologist and chief of St John’s Institute of Dermatology at Guy’s & St. Thomas’ NHS Foundation, London, noted that the location of the tumor was important, as sometimes it was not physically possible to excise it completely.

Guidelines on how to manage SCCs in patients with EB were published a few years ago (Br J Dermatol. 2016;174:56-67) and noted that the clinical detection of SCCs could be difficult because of chronic wound ulceration in these patients. The “possibility of malignancy should be borne in mind, with suspicious lesions biopsied for histological evaluation,” the document states. Evidence for many of the nonsurgical options – radiotherapy, conventional chemotherapy, biologic therapies – was poor, according to the guidelines, and effective nonsurgical options are still desperately needed.

Several avenues of research are being investigated, Dr. Mellerio noted, such as targeting the fibrotic process and perhaps using a micro-RNA inhibitor to stop the upregulation of certain microRNAs in fibroblasts. Targeting inflammatory mechanisms such as thrombospondin 1, which can lead to elevated levels of tumor necrosis factor–beta and contribute to extracellular matrix stiffness, also is under investigation. Raised interleukin-6 may be another target to consider.

Research shows that similar genes are mutated in EB-related and ultraviolet-related SCCs, Dr. Mellerio said. Indeed, mutations in HRAS, NOTCH1, TP53, and CDKN2A have been reported, but mutations in these genes occur much earlier in life in patients with EB. “Something else is going on,” she added, commenting that researchers are looking at apolipoprotein B editing complex (APOBEC) enzymes, which modulate DNA and can cause “particular types of genetic changes in EB cancers.”

One investigator who is studying the genetics of EB SCCs and how APOBEC enzymes might be involved is Andrew South, PhD, an associate professor at Thomas Jefferson University, Philadelphia. APOBEC enzymes are a very prominent source of mutations in RDEB. These mutations are found in 10%-20% of squamous cell carcinomas not associated with RDEB, and 80%-90% of head and neck cancers, he said during a separate talk at the meeting.

Dr. South observed that “RDEB squamous cell carcinoma does not show any particular somatic mutation or upregulation or downregulation of genes that differentiates it from other squamous cell carcinomas, which might be disappointing on the front of it, but actually it does mean that precision therapies that have been developed for other squamous cell carcinomas have application in RDEB.”

RDEB SCC shows the greatest similarity with head and neck SCC, Dr. South said. He also stressed that fibrosis is a major driver of cancer development, SCC tumors in RDEB are homogenous, and that frontline therapy is still unclear.

What is clear, however, is that interdisciplinary management of patients is crucial, said Leena Bruckner-Tuderman, MD, professor and chair of the department of dermatology at the University Medical Center, Albert Ludwig University of Freiburg, Germany.

“In severe RDEB, metastatic SCC is the leading cause of death at a young age. We need monitoring, careful diagnostics, and multidisciplinary treatment,” Dr. Bruckner-Tuderman said. The latter should be delivered by a coordinated team that consists of dermatologists, surgeons, radiologists, oncologists, pathologists, geneticists, and (molecular) tumor boards, she advised.

The study had no commercial funding. Dr. Mellerio disclosed financial relationships with Castle Creek Pharmaceuticals and ProQR Therapeutics, and acted as an unpaid advisor to Helpberby Therapeutics. Dr. South disclosed financial relationships with Krystal Biotech Inc. and Amryt Genetics and has been an advisory board member for Abeona Therapeutics and Sanofi Genzyme. Dr. Bruckner-Tuderman disclosed receiving grants or research support from Constant Pharmaceuticals/Tarix Orphan.

LONDON – Preventive oral health should be high on the agenda when managing babies and children with dystrophic epidermolysis bullosa (DEB), pediatric dentist Susanne Krämer told attendees at the first EB World Congress.

Sara Freeman/MDedge News

While it may not be the first thing on the minds of families coming to terms with their children having a chronic and potentially debilitating skin disease, it is important to consider oral health early to ensure healthy dentition and mouth function, both of which will affect the ability to eat and thus nutrition.

When there are a lot of other health issues, “dentistry is not a priority,” Dr. Krämer acknowledged in an interview at the meeting, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). 

Something as simple as brushing teeth can be very distressing for parents of a child with EB, she observed, especially if there is dysphagia and toothpaste may be getting into the airways accidentally.

Oral health was one of the topics that patients with EB and their families said would be good to have some guidance on when they were surveyed by DEBRA International. This led the charity to develop its first clinical practice guideline in 2012. Dr. Krämer was the lead author of the guidelines, which are about to be updated and republished.

The “Oral Health for Patients with Epidermolysis Bullosa – Best Clinical Practice Guidelines” (Int J Paediatr Dent. 2012;22 Suppl 1:1-35) are in the final stages of being revised, said Dr. Krämer, who is head of the department of pediatric dentistry at the University of Chile in Santiago. Although there is not much new evidence since the guidelines were first published, “we do have a lot of new technologies within dentistry that can aid the care of EB,” she said.

LONDON – Preventive oral health should be high on the agenda when managing babies and children with dystrophic epidermolysis bullosa (DEB), pediatric dentist Susanne Krämer told attendees at the first EB World Congress.

Sara Freeman/MDedge News

While it may not be the first thing on the minds of families coming to terms with their children having a chronic and potentially debilitating skin disease, it is important to consider oral health early to ensure healthy dentition and mouth function, both of which will affect the ability to eat and thus nutrition.

When there are a lot of other health issues, “dentistry is not a priority,” Dr. Krämer acknowledged in an interview at the meeting, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). 

Something as simple as brushing teeth can be very distressing for parents of a child with EB, she observed, especially if there is dysphagia and toothpaste may be getting into the airways accidentally.

Oral health was one of the topics that patients with EB and their families said would be good to have some guidance on when they were surveyed by DEBRA International. This led the charity to develop its first clinical practice guideline in 2012. Dr. Krämer was the lead author of the guidelines, which are about to be updated and republished.

The “Oral Health for Patients with Epidermolysis Bullosa – Best Clinical Practice Guidelines” (Int J Paediatr Dent. 2012;22 Suppl 1:1-35) are in the final stages of being revised, said Dr. Krämer, who is head of the department of pediatric dentistry at the University of Chile in Santiago. Although there is not much new evidence since the guidelines were first published, “we do have a lot of new technologies within dentistry that can aid the care of EB,” she said.

LONDON – Preventive oral health should be high on the agenda when managing babies and children with dystrophic epidermolysis bullosa (DEB), pediatric dentist Susanne Krämer told attendees at the first EB World Congress.

Sara Freeman/MDedge News

While it may not be the first thing on the minds of families coming to terms with their children having a chronic and potentially debilitating skin disease, it is important to consider oral health early to ensure healthy dentition and mouth function, both of which will affect the ability to eat and thus nutrition.

When there are a lot of other health issues, “dentistry is not a priority,” Dr. Krämer acknowledged in an interview at the meeting, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). 

Something as simple as brushing teeth can be very distressing for parents of a child with EB, she observed, especially if there is dysphagia and toothpaste may be getting into the airways accidentally.

Oral health was one of the topics that patients with EB and their families said would be good to have some guidance on when they were surveyed by DEBRA International. This led the charity to develop its first clinical practice guideline in 2012. Dr. Krämer was the lead author of the guidelines, which are about to be updated and republished.

The “Oral Health for Patients with Epidermolysis Bullosa – Best Clinical Practice Guidelines” (Int J Paediatr Dent. 2012;22 Suppl 1:1-35) are in the final stages of being revised, said Dr. Krämer, who is head of the department of pediatric dentistry at the University of Chile in Santiago. Although there is not much new evidence since the guidelines were first published, “we do have a lot of new technologies within dentistry that can aid the care of EB,” she said.