Among patients on low-dose aspirin at risk for recurrent GI bleeding, there were slightly fewer GI bleeds or ulcers when patients were on the proton pump inhibitor rabeprazole (Aciphex) instead of the histamine₂-receptor antagonist famotidine (Pepcid), but the difference was not statistically significant according to a study reported in the January issue of Gastroenterology.

SOURCE: American Gastroenterological Association

In a 270-subject, double-blind, randomized trial in Hong Kong and Japan led by Francis Chan, MD, of the Chinese University of Hong Kong, investigators found, “Among high-risk aspirin users, the incidence of recurrent bleeding is comparable with either use of PPI [proton pump inhibitor] or H₂RA [H₂-receptor antagonist].” However, “since a small difference in efficacy cannot be excluded, PPI probably remains the preferred treatment for long-term protection against upper GI bleeding in high-risk aspirin users” (Gastroenterology. 2016 Sep 15. doi: 10.1053/j.gastro.2016.09.006).

Even so, “our findings suggest that famotidine may be a reasonable alternative option for aspirin users who disfavor long-term PPI therapy,” they said.

Because of concerns about the long-term safety of PPIs, including the association between PPIs and increased risk of serious cardiovascular events in patients on clopidogrel (Plavix), clinicians have been looking for alternatives. The findings reassure that H₂RAs are a reasonable choice; many clinicians have already turned to them.

All 270 subjects had previously had endoscopically confirmed ulcer bleeding while on low-dose aspirin (325 mg or less per day). “Considering clinicians will be most concerned with the adequacy of gastroprotective treatment effect in aspirin users with the highest risk, we exclusively enrolled patients with endoscopy-proven upper GI bleeding,” Dr. Chan and his colleagues said.

After the ulcers healed, the subjects resumed aspirin (80 mg) daily and were randomized to either famotidine 40 mg once daily (n = 132) or rabeprazole 20 mg daily (n = 138) for up to 12 months. Helicobacter pylori was eradicated prior to randomization in patients who tested positive. Subjects were evaluated every 2 months, with repeat endoscopy for symptoms of upper GI bleeding or significant drops in hemoglobin, as well as at the end of the study.

During the 12-month study period, upper GI bleeding recurred in one patient receiving rabeprazole (0.7%) and four receiving famotidine (3.1%; P = .16). The composite endpoint of recurrent bleeding or endoscopic ulcers at month 12 was reached by nine patients in the rabeprazole group (7.9%) and 13 receiving famotidine (12.4%; P = .26).

“Our findings indicate that both treatments are comparable in preventing recurrent upper GI bleeding in high-risk aspirin users, although a small difference in efficacy cannot be excluded,” the investigators said.

Over two-thirds of the subjects were men, and the mean age was 73 years. About a quarter in the PPI group and almost 40% in the H₂RA group had H. pylori cleared before randomization.

The Research Grant Council of Hong Kong funded the work. Dr. Chan has served as a consultant to Pfizer, Eisai, Takeda, and Otsuka, and has received research grants from Pfizer and lecture fees from Pfizer, AstraZeneca, and Takeda. Several other authors reported similar industry disclosures.

[email protected]

Among patients on low-dose aspirin at risk for recurrent GI bleeding, there were slightly fewer GI bleeds or ulcers when patients were on the proton pump inhibitor rabeprazole (Aciphex) instead of the histamine₂-receptor antagonist famotidine (Pepcid), but the difference was not statistically significant according to a study reported in the January issue of Gastroenterology.

SOURCE: American Gastroenterological Association

In a 270-subject, double-blind, randomized trial in Hong Kong and Japan led by Francis Chan, MD, of the Chinese University of Hong Kong, investigators found, “Among high-risk aspirin users, the incidence of recurrent bleeding is comparable with either use of PPI [proton pump inhibitor] or H₂RA [H₂-receptor antagonist].” However, “since a small difference in efficacy cannot be excluded, PPI probably remains the preferred treatment for long-term protection against upper GI bleeding in high-risk aspirin users” (Gastroenterology. 2016 Sep 15. doi: 10.1053/j.gastro.2016.09.006).

Even so, “our findings suggest that famotidine may be a reasonable alternative option for aspirin users who disfavor long-term PPI therapy,” they said.

Because of concerns about the long-term safety of PPIs, including the association between PPIs and increased risk of serious cardiovascular events in patients on clopidogrel (Plavix), clinicians have been looking for alternatives. The findings reassure that H₂RAs are a reasonable choice; many clinicians have already turned to them.

All 270 subjects had previously had endoscopically confirmed ulcer bleeding while on low-dose aspirin (325 mg or less per day). “Considering clinicians will be most concerned with the adequacy of gastroprotective treatment effect in aspirin users with the highest risk, we exclusively enrolled patients with endoscopy-proven upper GI bleeding,” Dr. Chan and his colleagues said.

After the ulcers healed, the subjects resumed aspirin (80 mg) daily and were randomized to either famotidine 40 mg once daily (n = 132) or rabeprazole 20 mg daily (n = 138) for up to 12 months. Helicobacter pylori was eradicated prior to randomization in patients who tested positive. Subjects were evaluated every 2 months, with repeat endoscopy for symptoms of upper GI bleeding or significant drops in hemoglobin, as well as at the end of the study.

During the 12-month study period, upper GI bleeding recurred in one patient receiving rabeprazole (0.7%) and four receiving famotidine (3.1%; P = .16). The composite endpoint of recurrent bleeding or endoscopic ulcers at month 12 was reached by nine patients in the rabeprazole group (7.9%) and 13 receiving famotidine (12.4%; P = .26).

“Our findings indicate that both treatments are comparable in preventing recurrent upper GI bleeding in high-risk aspirin users, although a small difference in efficacy cannot be excluded,” the investigators said.

Over two-thirds of the subjects were men, and the mean age was 73 years. About a quarter in the PPI group and almost 40% in the H₂RA group had H. pylori cleared before randomization.

The Research Grant Council of Hong Kong funded the work. Dr. Chan has served as a consultant to Pfizer, Eisai, Takeda, and Otsuka, and has received research grants from Pfizer and lecture fees from Pfizer, AstraZeneca, and Takeda. Several other authors reported similar industry disclosures.

[email protected]

Among patients on low-dose aspirin at risk for recurrent GI bleeding, there were slightly fewer GI bleeds or ulcers when patients were on the proton pump inhibitor rabeprazole (Aciphex) instead of the histamine₂-receptor antagonist famotidine (Pepcid), but the difference was not statistically significant according to a study reported in the January issue of Gastroenterology.

SOURCE: American Gastroenterological Association

In a 270-subject, double-blind, randomized trial in Hong Kong and Japan led by Francis Chan, MD, of the Chinese University of Hong Kong, investigators found, “Among high-risk aspirin users, the incidence of recurrent bleeding is comparable with either use of PPI [proton pump inhibitor] or H₂RA [H₂-receptor antagonist].” However, “since a small difference in efficacy cannot be excluded, PPI probably remains the preferred treatment for long-term protection against upper GI bleeding in high-risk aspirin users” (Gastroenterology. 2016 Sep 15. doi: 10.1053/j.gastro.2016.09.006).

Even so, “our findings suggest that famotidine may be a reasonable alternative option for aspirin users who disfavor long-term PPI therapy,” they said.

Because of concerns about the long-term safety of PPIs, including the association between PPIs and increased risk of serious cardiovascular events in patients on clopidogrel (Plavix), clinicians have been looking for alternatives. The findings reassure that H₂RAs are a reasonable choice; many clinicians have already turned to them.

All 270 subjects had previously had endoscopically confirmed ulcer bleeding while on low-dose aspirin (325 mg or less per day). “Considering clinicians will be most concerned with the adequacy of gastroprotective treatment effect in aspirin users with the highest risk, we exclusively enrolled patients with endoscopy-proven upper GI bleeding,” Dr. Chan and his colleagues said.

After the ulcers healed, the subjects resumed aspirin (80 mg) daily and were randomized to either famotidine 40 mg once daily (n = 132) or rabeprazole 20 mg daily (n = 138) for up to 12 months. Helicobacter pylori was eradicated prior to randomization in patients who tested positive. Subjects were evaluated every 2 months, with repeat endoscopy for symptoms of upper GI bleeding or significant drops in hemoglobin, as well as at the end of the study.

During the 12-month study period, upper GI bleeding recurred in one patient receiving rabeprazole (0.7%) and four receiving famotidine (3.1%; P = .16). The composite endpoint of recurrent bleeding or endoscopic ulcers at month 12 was reached by nine patients in the rabeprazole group (7.9%) and 13 receiving famotidine (12.4%; P = .26).

“Our findings indicate that both treatments are comparable in preventing recurrent upper GI bleeding in high-risk aspirin users, although a small difference in efficacy cannot be excluded,” the investigators said.

Over two-thirds of the subjects were men, and the mean age was 73 years. About a quarter in the PPI group and almost 40% in the H₂RA group had H. pylori cleared before randomization.

The Research Grant Council of Hong Kong funded the work. Dr. Chan has served as a consultant to Pfizer, Eisai, Takeda, and Otsuka, and has received research grants from Pfizer and lecture fees from Pfizer, AstraZeneca, and Takeda. Several other authors reported similar industry disclosures.

[email protected]

A counseling and shared decision-making visit improved patient knowledge of the eligibility criteria, benefits, and potential risks of lung cancer screening via a low-radiation chest CT scan.

The Center for Medicare & Medicaid Services has added the type of visit addressed in this study to Medicare’s preventive services benefits for individuals meeting certain criteria, but no previous study had looked at how the implementation of such a visit impacted a patient’s knowledge and understanding.

A counseling and shared decision-making visit improved patient knowledge of the eligibility criteria, benefits, and potential risks of lung cancer screening via a low-radiation chest CT scan.

The Center for Medicare & Medicaid Services has added the type of visit addressed in this study to Medicare’s preventive services benefits for individuals meeting certain criteria, but no previous study had looked at how the implementation of such a visit impacted a patient’s knowledge and understanding.

A counseling and shared decision-making visit improved patient knowledge of the eligibility criteria, benefits, and potential risks of lung cancer screening via a low-radiation chest CT scan.

The Center for Medicare & Medicaid Services has added the type of visit addressed in this study to Medicare’s preventive services benefits for individuals meeting certain criteria, but no previous study had looked at how the implementation of such a visit impacted a patient’s knowledge and understanding.

ORLANDO – Ultrasound appears to be an effective tool in diagnosing occult hernia in women with unexplained chronic pelvic pain, according to a retrospective cohort study of 96 women.

“As gynecologists, we are likely to see those patients with chronic pelvic pain in our clinic before other specialists due to the location of their pain,” said Joelle Aoun, MD, an ob.gyn. in the division of minimally invasive gynecologic surgery at Henry Ford Health System in Detroit. “So it’s very important to recognize women with a high clinical suspicion for occult hernia and evaluate them in order to prevent a delayed diagnosis and prolonged suffering.”

Hernias can be more difficult to diagnose in women than in men, Dr. Aoun said at the meeting sponsored by AAGL, and the literature offers conflicting findings since most hernia studies are conducted in men or with mixed gender cohorts.

Dr. Aoun and her coinvestigators conducted a retrospective cohort study from January 2005 to July 2016, identifying 96 women with chronic pelvic pain and focal inguinal tenderness. Protruding fat or visceral tissue on physical exam or observed visually led clinicians to suspect a hernia. A single sonographer performed the musculoskeletal ultrasound.

Investigators diagnosed an occult hernia in more than half of the patients (51 women) based on the physical exam and ultrasound findings. Diagnoses included inguinal, femoral, Spigelian, and umbilical hernias.

All women with an ultrasound-diagnosed hernia were referred to general surgery. A majority – 69% of women – underwent surgical exploration. The remaining 31% of women who declined tended to have lower pain scores, Dr. Aoun said. Surgeons confirmed the hernia diagnosis in 97% of the women, or 34 out of the 35 women who had consented to surgery.

The group with a hernia was older and more likely to have arthritis, but otherwise did not differ significantly from the nonhernia cohort.

“We believe musculoskeletal ultrasound is valuable as an initial imaging modality due to its high predictive value, low cost, and noninvasiveness,” Dr. Aoun said.

Chronic pelvic pain is not uncommon, affecting approximately 15% of women during their reproductive years often with significant impacts on quality of life, workplace productivity, and health care utilization, Dr. Aoun said. This presentation also accounts for about 10% outpatient gynecology consultations and approximately 40% of laparoscopies in the United States, she added.

Dr. Aoun and her colleagues are planning a subsequent study of all the women who opted not to undergo surgery to determine their follow-up pain profiles based on chart review and phone interviews.

Dr. Aoun reported having no relevant financial disclosures.

ORLANDO – Ultrasound appears to be an effective tool in diagnosing occult hernia in women with unexplained chronic pelvic pain, according to a retrospective cohort study of 96 women.

“As gynecologists, we are likely to see those patients with chronic pelvic pain in our clinic before other specialists due to the location of their pain,” said Joelle Aoun, MD, an ob.gyn. in the division of minimally invasive gynecologic surgery at Henry Ford Health System in Detroit. “So it’s very important to recognize women with a high clinical suspicion for occult hernia and evaluate them in order to prevent a delayed diagnosis and prolonged suffering.”

Hernias can be more difficult to diagnose in women than in men, Dr. Aoun said at the meeting sponsored by AAGL, and the literature offers conflicting findings since most hernia studies are conducted in men or with mixed gender cohorts.

Dr. Aoun and her coinvestigators conducted a retrospective cohort study from January 2005 to July 2016, identifying 96 women with chronic pelvic pain and focal inguinal tenderness. Protruding fat or visceral tissue on physical exam or observed visually led clinicians to suspect a hernia. A single sonographer performed the musculoskeletal ultrasound.

Investigators diagnosed an occult hernia in more than half of the patients (51 women) based on the physical exam and ultrasound findings. Diagnoses included inguinal, femoral, Spigelian, and umbilical hernias.

All women with an ultrasound-diagnosed hernia were referred to general surgery. A majority – 69% of women – underwent surgical exploration. The remaining 31% of women who declined tended to have lower pain scores, Dr. Aoun said. Surgeons confirmed the hernia diagnosis in 97% of the women, or 34 out of the 35 women who had consented to surgery.

The group with a hernia was older and more likely to have arthritis, but otherwise did not differ significantly from the nonhernia cohort.

“We believe musculoskeletal ultrasound is valuable as an initial imaging modality due to its high predictive value, low cost, and noninvasiveness,” Dr. Aoun said.

Chronic pelvic pain is not uncommon, affecting approximately 15% of women during their reproductive years often with significant impacts on quality of life, workplace productivity, and health care utilization, Dr. Aoun said. This presentation also accounts for about 10% outpatient gynecology consultations and approximately 40% of laparoscopies in the United States, she added.

Dr. Aoun and her colleagues are planning a subsequent study of all the women who opted not to undergo surgery to determine their follow-up pain profiles based on chart review and phone interviews.

Dr. Aoun reported having no relevant financial disclosures.

ORLANDO – Ultrasound appears to be an effective tool in diagnosing occult hernia in women with unexplained chronic pelvic pain, according to a retrospective cohort study of 96 women.

“As gynecologists, we are likely to see those patients with chronic pelvic pain in our clinic before other specialists due to the location of their pain,” said Joelle Aoun, MD, an ob.gyn. in the division of minimally invasive gynecologic surgery at Henry Ford Health System in Detroit. “So it’s very important to recognize women with a high clinical suspicion for occult hernia and evaluate them in order to prevent a delayed diagnosis and prolonged suffering.”

Hernias can be more difficult to diagnose in women than in men, Dr. Aoun said at the meeting sponsored by AAGL, and the literature offers conflicting findings since most hernia studies are conducted in men or with mixed gender cohorts.

Dr. Aoun and her coinvestigators conducted a retrospective cohort study from January 2005 to July 2016, identifying 96 women with chronic pelvic pain and focal inguinal tenderness. Protruding fat or visceral tissue on physical exam or observed visually led clinicians to suspect a hernia. A single sonographer performed the musculoskeletal ultrasound.

Investigators diagnosed an occult hernia in more than half of the patients (51 women) based on the physical exam and ultrasound findings. Diagnoses included inguinal, femoral, Spigelian, and umbilical hernias.

All women with an ultrasound-diagnosed hernia were referred to general surgery. A majority – 69% of women – underwent surgical exploration. The remaining 31% of women who declined tended to have lower pain scores, Dr. Aoun said. Surgeons confirmed the hernia diagnosis in 97% of the women, or 34 out of the 35 women who had consented to surgery.

The group with a hernia was older and more likely to have arthritis, but otherwise did not differ significantly from the nonhernia cohort.

“We believe musculoskeletal ultrasound is valuable as an initial imaging modality due to its high predictive value, low cost, and noninvasiveness,” Dr. Aoun said.

Chronic pelvic pain is not uncommon, affecting approximately 15% of women during their reproductive years often with significant impacts on quality of life, workplace productivity, and health care utilization, Dr. Aoun said. This presentation also accounts for about 10% outpatient gynecology consultations and approximately 40% of laparoscopies in the United States, she added.

Dr. Aoun and her colleagues are planning a subsequent study of all the women who opted not to undergo surgery to determine their follow-up pain profiles based on chart review and phone interviews.

Dr. Aoun reported having no relevant financial disclosures.

The dapivirine vaginal ring reduced the rate of new HIV-1 infection by 31% in a phase III clinical trial involving 1,959 high-risk women in sub-Saharan Africa, according to a report published in the New England Journal of Medicine.

The dapivirine-containing ring is replaced every month and was used in this study for up to 2 years. It was not associated with any safety concerns, said Annalene Nel, MD, PhD, of the International Partnership for Microbicides, Silver Spring, Md., and her associates.

The International Partnership for Microbicides is a nonprofit group that developed the ring, which can be self-inserted and removed and which provides a sustained release of the antiretroviral drug for at least 4 weeks. QPharma of Malmö, Sweden, manufactures the rings and donated the ones used in this study, but was not otherwise involved in the trial.

The study participants were sexually active women aged 18-45 years (mean age, 26) treated at seven research centers in South Africa and Uganda. Almost all of them (98%) had only one male sexual partner. For the purposes of this trial, the women were asked to attend the participating clinics every 4 weeks to have the rings replaced and to provide a plasma sample. This allowed the researchers to measure the residual amount of dapivirine in the used rings and to measure plasma levels of the drug, both of which were indicators of compliance.

A total of 1,307 women were randomly assigned to receive dapivirine rings and 652 to receive placebo rings. At the data cutoff point, 615 women (31.4%) were still in the trial and 761 (38.8%) had completed it; 583 women (29.8%) had discontinued early. All the participants at one medical center were withdrawn by the sponsor because of high rates of protocol violation at that facility and corresponding high rates of patient nonadherence with the device.

The primary efficacy endpoint – the rate of HIV-1 seroconversion during follow-up – was 4.1 per 100 person-years with the dapivirine ring, compared with 6.1 per 100 person-years with the placebo ring. This represents a 31% lower infection rate with the active treatment (hazard ratio, 0.69). A subgroup analysis that excluded participants at the protocol-violating facility showed a seroconversion rate of 3.6 per 100 person-years with the active treatment vs. 5.4 per 100 person-years with the placebo, a 30% reduction in the infection rate, the investigators said (N Engl J Med. 2016 Dec 1. doi: 10.1056/NEJMoa1602046).

The findings were consistent across other subgroup analyses, including those that categorized the participants according to their adherence levels, as measured by plasma levels and residual ring levels of dapivirine.

The cumulative incidence of adverse events was similar between the two study groups (87.4% and 85.7%, respectively), as was the incidence of grade 3 or 4 adverse events. None of the more serious adverse events were judged to be related to the devices. Mild product-related adverse events occurred in 5 women (0.4%) in the dapivirine group and 3 (0.5%) in the placebo group. There also were no significant differences between the two study groups in the incidence of laboratory abnormalities, rates of sexually transmitted and other genital infections, or pregnancy rates.

The study was funded by the International Partnership for Microbicides, which is supported by the Bill and Melinda Gates Foundation, Irish Aid, the Ministry of Foreign Affairs of Denmark, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the U.K. Department for International Development, the U.S. Agency for International Development, and the President’s Emergency Plan for AIDS Relief.

Dr. Nel reported having no relevant financial disclosures; one of her associates reported ties to Janssen and Johnson & Johnson.

The dapivirine vaginal ring reduced the rate of new HIV-1 infection by 31% in a phase III clinical trial involving 1,959 high-risk women in sub-Saharan Africa, according to a report published in the New England Journal of Medicine.

The dapivirine-containing ring is replaced every month and was used in this study for up to 2 years. It was not associated with any safety concerns, said Annalene Nel, MD, PhD, of the International Partnership for Microbicides, Silver Spring, Md., and her associates.

The International Partnership for Microbicides is a nonprofit group that developed the ring, which can be self-inserted and removed and which provides a sustained release of the antiretroviral drug for at least 4 weeks. QPharma of Malmö, Sweden, manufactures the rings and donated the ones used in this study, but was not otherwise involved in the trial.

The study participants were sexually active women aged 18-45 years (mean age, 26) treated at seven research centers in South Africa and Uganda. Almost all of them (98%) had only one male sexual partner. For the purposes of this trial, the women were asked to attend the participating clinics every 4 weeks to have the rings replaced and to provide a plasma sample. This allowed the researchers to measure the residual amount of dapivirine in the used rings and to measure plasma levels of the drug, both of which were indicators of compliance.

A total of 1,307 women were randomly assigned to receive dapivirine rings and 652 to receive placebo rings. At the data cutoff point, 615 women (31.4%) were still in the trial and 761 (38.8%) had completed it; 583 women (29.8%) had discontinued early. All the participants at one medical center were withdrawn by the sponsor because of high rates of protocol violation at that facility and corresponding high rates of patient nonadherence with the device.

The primary efficacy endpoint – the rate of HIV-1 seroconversion during follow-up – was 4.1 per 100 person-years with the dapivirine ring, compared with 6.1 per 100 person-years with the placebo ring. This represents a 31% lower infection rate with the active treatment (hazard ratio, 0.69). A subgroup analysis that excluded participants at the protocol-violating facility showed a seroconversion rate of 3.6 per 100 person-years with the active treatment vs. 5.4 per 100 person-years with the placebo, a 30% reduction in the infection rate, the investigators said (N Engl J Med. 2016 Dec 1. doi: 10.1056/NEJMoa1602046).

The findings were consistent across other subgroup analyses, including those that categorized the participants according to their adherence levels, as measured by plasma levels and residual ring levels of dapivirine.

The cumulative incidence of adverse events was similar between the two study groups (87.4% and 85.7%, respectively), as was the incidence of grade 3 or 4 adverse events. None of the more serious adverse events were judged to be related to the devices. Mild product-related adverse events occurred in 5 women (0.4%) in the dapivirine group and 3 (0.5%) in the placebo group. There also were no significant differences between the two study groups in the incidence of laboratory abnormalities, rates of sexually transmitted and other genital infections, or pregnancy rates.

The study was funded by the International Partnership for Microbicides, which is supported by the Bill and Melinda Gates Foundation, Irish Aid, the Ministry of Foreign Affairs of Denmark, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the U.K. Department for International Development, the U.S. Agency for International Development, and the President’s Emergency Plan for AIDS Relief.

Dr. Nel reported having no relevant financial disclosures; one of her associates reported ties to Janssen and Johnson & Johnson.

The dapivirine vaginal ring reduced the rate of new HIV-1 infection by 31% in a phase III clinical trial involving 1,959 high-risk women in sub-Saharan Africa, according to a report published in the New England Journal of Medicine.

The dapivirine-containing ring is replaced every month and was used in this study for up to 2 years. It was not associated with any safety concerns, said Annalene Nel, MD, PhD, of the International Partnership for Microbicides, Silver Spring, Md., and her associates.

The International Partnership for Microbicides is a nonprofit group that developed the ring, which can be self-inserted and removed and which provides a sustained release of the antiretroviral drug for at least 4 weeks. QPharma of Malmö, Sweden, manufactures the rings and donated the ones used in this study, but was not otherwise involved in the trial.

The study participants were sexually active women aged 18-45 years (mean age, 26) treated at seven research centers in South Africa and Uganda. Almost all of them (98%) had only one male sexual partner. For the purposes of this trial, the women were asked to attend the participating clinics every 4 weeks to have the rings replaced and to provide a plasma sample. This allowed the researchers to measure the residual amount of dapivirine in the used rings and to measure plasma levels of the drug, both of which were indicators of compliance.

A total of 1,307 women were randomly assigned to receive dapivirine rings and 652 to receive placebo rings. At the data cutoff point, 615 women (31.4%) were still in the trial and 761 (38.8%) had completed it; 583 women (29.8%) had discontinued early. All the participants at one medical center were withdrawn by the sponsor because of high rates of protocol violation at that facility and corresponding high rates of patient nonadherence with the device.

The primary efficacy endpoint – the rate of HIV-1 seroconversion during follow-up – was 4.1 per 100 person-years with the dapivirine ring, compared with 6.1 per 100 person-years with the placebo ring. This represents a 31% lower infection rate with the active treatment (hazard ratio, 0.69). A subgroup analysis that excluded participants at the protocol-violating facility showed a seroconversion rate of 3.6 per 100 person-years with the active treatment vs. 5.4 per 100 person-years with the placebo, a 30% reduction in the infection rate, the investigators said (N Engl J Med. 2016 Dec 1. doi: 10.1056/NEJMoa1602046).

The findings were consistent across other subgroup analyses, including those that categorized the participants according to their adherence levels, as measured by plasma levels and residual ring levels of dapivirine.

The cumulative incidence of adverse events was similar between the two study groups (87.4% and 85.7%, respectively), as was the incidence of grade 3 or 4 adverse events. None of the more serious adverse events were judged to be related to the devices. Mild product-related adverse events occurred in 5 women (0.4%) in the dapivirine group and 3 (0.5%) in the placebo group. There also were no significant differences between the two study groups in the incidence of laboratory abnormalities, rates of sexually transmitted and other genital infections, or pregnancy rates.

The study was funded by the International Partnership for Microbicides, which is supported by the Bill and Melinda Gates Foundation, Irish Aid, the Ministry of Foreign Affairs of Denmark, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the U.K. Department for International Development, the U.S. Agency for International Development, and the President’s Emergency Plan for AIDS Relief.

Dr. Nel reported having no relevant financial disclosures; one of her associates reported ties to Janssen and Johnson & Johnson.

Large and complex airway defects that primary repair cannot fully close require alternative surgical approaches and techniques that are far more difficult to perform, but bioprosthetic materials may be an option to repair large tracheal and bronchial defects that has achieved good results, without postoperative death or defect recurrence, in a small cohort of patients at Massachusetts General Hospital, in Boston.

Brooks Udelsman, MD, and his coauthors reported their results of bioprosthetic repair of central airway defects in eight patients in the Journal of Thoracic and Cardiovascular Surgery (2016 Nov;152:1388-97). “Although our results are derived from a limited number of heterogeneous patients, they suggest that closure of noncircumferential large airway defects with bioprosthetic materials is feasible, safe and reliable,” Dr. Udelsman said. He previously reported the results at the annual meeting of the American Association for Thoracic Surgery, May 14-18, 2016, in Baltimore.

These complex defects typically exceed 5 cm and can involve communication with the esophagus. For repair of smaller defects, surgeons can use a more conventional approach that involves neck flexion, laryngeal release, airway mobilization, and hilar release, but in larger defects, these techniques increase the risk of too much tension on the anastomosis and dehiscence along with airway failure. Large and complex defects occur in patients who have had a previous airway operation or radiation exposure, requiring alternative strategies, the researchers wrote. “Patients in this rare category should be referred to a high-volume center for careful evaluation by a surgeon experienced in complex airway reconstruction before the decision to abandon primary repair is made,” he said. Among the advantages that bioprosthetic materials have over synthetic materials for airway defect repair are easier handling, minimal immunogenic response, and potential for tissue ingrowth, Dr. Udelsman and his coauthors said.

All eight patients in this study, who underwent repair from 2008 to 2015, had significant comorbidities, including previous surgery of the trachea, esophagus, or thyroid. The etiology of the airway defect included HIV-AIDS–associated esophagitis, malignancy, mesh erosion, and complications from extended intubation. Three patients had previous radiation therapy to the neck or chest. Five patients had defects localized to the membranous tracheal wall, two had defects of the mainstem bronchus or bronchus intermedius, and one patient had a defect of the anterior wall of the trachea.

Dr. Udelsman and his coauthors used both aortic homograft and acellular dermal matrix to repair large defects. Their experience confirmed previous reports of the formation of granulation tissue with aortic autografts, underscoring the importance of frequent bronchoscopy and debridement when necessary. And while previous reports have claimed human acellular dermis resists granulation formation, that wasn’t the case in this study. “The exact histologic basis of bioprosthetic incorporation and reepithelialization in these patients is still elusive and will require further study,” the researchers said.

This study also employed the controversial muscle buttress repair in six patients, which helped, at least theoretically, to secure the repairs when leaks occur, to separate suture lines when both the airway and esophagus were repaired and to support the bioprosthetic material to prevent tissue softening, Dr. Udelsman and his coauthors said.

Postoperative examinations confirmed that the operations successfully closed the airway defects in all eight patients. Long term, most resumed oral intake, but three did not for various reasons: one had a pharyngostomy; another had neurocognitive issues preoperatively; and a third with a tracheoesophageal fistula repair and cervical esophagostomy could resume oral intake but depended on tube feeds to meet caloric needs.

All patients developed granulation at the repair site, two of whom required further debridement and one who underwent balloon dilation. Pneumonia was the most common complication within 30 days of surgery, occurring in two patients. Three patients died within 120 days from metastatic disease, and a fourth patient progressed to end-stage AIDS 6 years after the operation and eventually died.

Dr. Udelsman and his coauthors reported having no financial disclosures.
 

Large and complex airway defects that primary repair cannot fully close require alternative surgical approaches and techniques that are far more difficult to perform, but bioprosthetic materials may be an option to repair large tracheal and bronchial defects that has achieved good results, without postoperative death or defect recurrence, in a small cohort of patients at Massachusetts General Hospital, in Boston.

Brooks Udelsman, MD, and his coauthors reported their results of bioprosthetic repair of central airway defects in eight patients in the Journal of Thoracic and Cardiovascular Surgery (2016 Nov;152:1388-97). “Although our results are derived from a limited number of heterogeneous patients, they suggest that closure of noncircumferential large airway defects with bioprosthetic materials is feasible, safe and reliable,” Dr. Udelsman said. He previously reported the results at the annual meeting of the American Association for Thoracic Surgery, May 14-18, 2016, in Baltimore.

These complex defects typically exceed 5 cm and can involve communication with the esophagus. For repair of smaller defects, surgeons can use a more conventional approach that involves neck flexion, laryngeal release, airway mobilization, and hilar release, but in larger defects, these techniques increase the risk of too much tension on the anastomosis and dehiscence along with airway failure. Large and complex defects occur in patients who have had a previous airway operation or radiation exposure, requiring alternative strategies, the researchers wrote. “Patients in this rare category should be referred to a high-volume center for careful evaluation by a surgeon experienced in complex airway reconstruction before the decision to abandon primary repair is made,” he said. Among the advantages that bioprosthetic materials have over synthetic materials for airway defect repair are easier handling, minimal immunogenic response, and potential for tissue ingrowth, Dr. Udelsman and his coauthors said.

All eight patients in this study, who underwent repair from 2008 to 2015, had significant comorbidities, including previous surgery of the trachea, esophagus, or thyroid. The etiology of the airway defect included HIV-AIDS–associated esophagitis, malignancy, mesh erosion, and complications from extended intubation. Three patients had previous radiation therapy to the neck or chest. Five patients had defects localized to the membranous tracheal wall, two had defects of the mainstem bronchus or bronchus intermedius, and one patient had a defect of the anterior wall of the trachea.

Dr. Udelsman and his coauthors used both aortic homograft and acellular dermal matrix to repair large defects. Their experience confirmed previous reports of the formation of granulation tissue with aortic autografts, underscoring the importance of frequent bronchoscopy and debridement when necessary. And while previous reports have claimed human acellular dermis resists granulation formation, that wasn’t the case in this study. “The exact histologic basis of bioprosthetic incorporation and reepithelialization in these patients is still elusive and will require further study,” the researchers said.

This study also employed the controversial muscle buttress repair in six patients, which helped, at least theoretically, to secure the repairs when leaks occur, to separate suture lines when both the airway and esophagus were repaired and to support the bioprosthetic material to prevent tissue softening, Dr. Udelsman and his coauthors said.

Postoperative examinations confirmed that the operations successfully closed the airway defects in all eight patients. Long term, most resumed oral intake, but three did not for various reasons: one had a pharyngostomy; another had neurocognitive issues preoperatively; and a third with a tracheoesophageal fistula repair and cervical esophagostomy could resume oral intake but depended on tube feeds to meet caloric needs.

All patients developed granulation at the repair site, two of whom required further debridement and one who underwent balloon dilation. Pneumonia was the most common complication within 30 days of surgery, occurring in two patients. Three patients died within 120 days from metastatic disease, and a fourth patient progressed to end-stage AIDS 6 years after the operation and eventually died.

Dr. Udelsman and his coauthors reported having no financial disclosures.
 

Large and complex airway defects that primary repair cannot fully close require alternative surgical approaches and techniques that are far more difficult to perform, but bioprosthetic materials may be an option to repair large tracheal and bronchial defects that has achieved good results, without postoperative death or defect recurrence, in a small cohort of patients at Massachusetts General Hospital, in Boston.

Brooks Udelsman, MD, and his coauthors reported their results of bioprosthetic repair of central airway defects in eight patients in the Journal of Thoracic and Cardiovascular Surgery (2016 Nov;152:1388-97). “Although our results are derived from a limited number of heterogeneous patients, they suggest that closure of noncircumferential large airway defects with bioprosthetic materials is feasible, safe and reliable,” Dr. Udelsman said. He previously reported the results at the annual meeting of the American Association for Thoracic Surgery, May 14-18, 2016, in Baltimore.

These complex defects typically exceed 5 cm and can involve communication with the esophagus. For repair of smaller defects, surgeons can use a more conventional approach that involves neck flexion, laryngeal release, airway mobilization, and hilar release, but in larger defects, these techniques increase the risk of too much tension on the anastomosis and dehiscence along with airway failure. Large and complex defects occur in patients who have had a previous airway operation or radiation exposure, requiring alternative strategies, the researchers wrote. “Patients in this rare category should be referred to a high-volume center for careful evaluation by a surgeon experienced in complex airway reconstruction before the decision to abandon primary repair is made,” he said. Among the advantages that bioprosthetic materials have over synthetic materials for airway defect repair are easier handling, minimal immunogenic response, and potential for tissue ingrowth, Dr. Udelsman and his coauthors said.

All eight patients in this study, who underwent repair from 2008 to 2015, had significant comorbidities, including previous surgery of the trachea, esophagus, or thyroid. The etiology of the airway defect included HIV-AIDS–associated esophagitis, malignancy, mesh erosion, and complications from extended intubation. Three patients had previous radiation therapy to the neck or chest. Five patients had defects localized to the membranous tracheal wall, two had defects of the mainstem bronchus or bronchus intermedius, and one patient had a defect of the anterior wall of the trachea.

Dr. Udelsman and his coauthors used both aortic homograft and acellular dermal matrix to repair large defects. Their experience confirmed previous reports of the formation of granulation tissue with aortic autografts, underscoring the importance of frequent bronchoscopy and debridement when necessary. And while previous reports have claimed human acellular dermis resists granulation formation, that wasn’t the case in this study. “The exact histologic basis of bioprosthetic incorporation and reepithelialization in these patients is still elusive and will require further study,” the researchers said.

This study also employed the controversial muscle buttress repair in six patients, which helped, at least theoretically, to secure the repairs when leaks occur, to separate suture lines when both the airway and esophagus were repaired and to support the bioprosthetic material to prevent tissue softening, Dr. Udelsman and his coauthors said.

Postoperative examinations confirmed that the operations successfully closed the airway defects in all eight patients. Long term, most resumed oral intake, but three did not for various reasons: one had a pharyngostomy; another had neurocognitive issues preoperatively; and a third with a tracheoesophageal fistula repair and cervical esophagostomy could resume oral intake but depended on tube feeds to meet caloric needs.

All patients developed granulation at the repair site, two of whom required further debridement and one who underwent balloon dilation. Pneumonia was the most common complication within 30 days of surgery, occurring in two patients. Three patients died within 120 days from metastatic disease, and a fourth patient progressed to end-stage AIDS 6 years after the operation and eventually died.

Dr. Udelsman and his coauthors reported having no financial disclosures.
 

To the Editor:

A 50-year-old man presented with a painful ulcer and a burning sensation on the tongue of 2 days’ duration (Figure, A). The ulcer had a yellowish white appearance with erythematous borders. The patient started taking tinidazole 500 mg twice daily 2 days prior, which was prescribed by his primary care physician for an episode of gastroenteritis. He was not taking any other medications and did not smoke or drink. Routine laboratory test results did not reveal any abnormalities. Based on the physical examination as well as the patient’s medical and medication history, a provisional diagnosis of fixed drug eruption (FDE) due to tinidazole was made. Tinidazole was immediately withdrawn and the patient was prescribed beclomethasone dipropionate ointment twice daily to relieve the burning sensation. A punch biopsy of the lesion was recommended; however, the patient opted to wait a week after discontinuing the drug. At follow-up 1 week later, complete healing of the ulcer was observed with no scarring and the burning sensation had resolved (Figure, B). After obtaining informed consent from the patient, an oral challenge test was conducted in the office with 50 mg of tinidazole. Four hours after taking the drug orally, the patient felt a burning sensation and a small ulcerative lesion was observed on the tongue at the same site the next day. The patient was informed of the fixed drug reaction to tinidazole, a drug belonging to the nitroimidazole group, and this information also was conveyed to the patient’s primary care physician.

Tinidazole is a synthetic antiprotozoal and antibacterial agent used primarily in infections such as amebiasis, giardiasis, and trichomoniasis.¹ Tinidazole may be a therapeutic alternative to metronidazole. Fixed drug eruption is a distinctive variant of drug eruption with characteristic recurrence at the same site of skin or mucous membranes. It is characterized by onset of round/oval, erythematous, well-defined macules on the skin and/or mucosa associated with itching and burning.¹ Fixed drug eruption generally is restricted to the mucous membrane and skin, with the lips, palms, soles, glans penis, and groin area being the most common sites. Intraoral involvement, excluding the lips, of FDE is rare. The tongue is a rare site of an FDE.² Fixed drug eruption on the tongue has been reported with clarithromycin.³ Dental clinicians have to be aware of the possibility of FDE due to commonly used drugs such tinidazole, which would help in prompt diagnosis of these lesions.

To the Editor:

A 50-year-old man presented with a painful ulcer and a burning sensation on the tongue of 2 days’ duration (Figure, A). The ulcer had a yellowish white appearance with erythematous borders. The patient started taking tinidazole 500 mg twice daily 2 days prior, which was prescribed by his primary care physician for an episode of gastroenteritis. He was not taking any other medications and did not smoke or drink. Routine laboratory test results did not reveal any abnormalities. Based on the physical examination as well as the patient’s medical and medication history, a provisional diagnosis of fixed drug eruption (FDE) due to tinidazole was made. Tinidazole was immediately withdrawn and the patient was prescribed beclomethasone dipropionate ointment twice daily to relieve the burning sensation. A punch biopsy of the lesion was recommended; however, the patient opted to wait a week after discontinuing the drug. At follow-up 1 week later, complete healing of the ulcer was observed with no scarring and the burning sensation had resolved (Figure, B). After obtaining informed consent from the patient, an oral challenge test was conducted in the office with 50 mg of tinidazole. Four hours after taking the drug orally, the patient felt a burning sensation and a small ulcerative lesion was observed on the tongue at the same site the next day. The patient was informed of the fixed drug reaction to tinidazole, a drug belonging to the nitroimidazole group, and this information also was conveyed to the patient’s primary care physician.

Tinidazole is a synthetic antiprotozoal and antibacterial agent used primarily in infections such as amebiasis, giardiasis, and trichomoniasis.¹ Tinidazole may be a therapeutic alternative to metronidazole. Fixed drug eruption is a distinctive variant of drug eruption with characteristic recurrence at the same site of skin or mucous membranes. It is characterized by onset of round/oval, erythematous, well-defined macules on the skin and/or mucosa associated with itching and burning.¹ Fixed drug eruption generally is restricted to the mucous membrane and skin, with the lips, palms, soles, glans penis, and groin area being the most common sites. Intraoral involvement, excluding the lips, of FDE is rare. The tongue is a rare site of an FDE.² Fixed drug eruption on the tongue has been reported with clarithromycin.³ Dental clinicians have to be aware of the possibility of FDE due to commonly used drugs such tinidazole, which would help in prompt diagnosis of these lesions.

To the Editor:

A 50-year-old man presented with a painful ulcer and a burning sensation on the tongue of 2 days’ duration (Figure, A). The ulcer had a yellowish white appearance with erythematous borders. The patient started taking tinidazole 500 mg twice daily 2 days prior, which was prescribed by his primary care physician for an episode of gastroenteritis. He was not taking any other medications and did not smoke or drink. Routine laboratory test results did not reveal any abnormalities. Based on the physical examination as well as the patient’s medical and medication history, a provisional diagnosis of fixed drug eruption (FDE) due to tinidazole was made. Tinidazole was immediately withdrawn and the patient was prescribed beclomethasone dipropionate ointment twice daily to relieve the burning sensation. A punch biopsy of the lesion was recommended; however, the patient opted to wait a week after discontinuing the drug. At follow-up 1 week later, complete healing of the ulcer was observed with no scarring and the burning sensation had resolved (Figure, B). After obtaining informed consent from the patient, an oral challenge test was conducted in the office with 50 mg of tinidazole. Four hours after taking the drug orally, the patient felt a burning sensation and a small ulcerative lesion was observed on the tongue at the same site the next day. The patient was informed of the fixed drug reaction to tinidazole, a drug belonging to the nitroimidazole group, and this information also was conveyed to the patient’s primary care physician.

Tinidazole is a synthetic antiprotozoal and antibacterial agent used primarily in infections such as amebiasis, giardiasis, and trichomoniasis.¹ Tinidazole may be a therapeutic alternative to metronidazole. Fixed drug eruption is a distinctive variant of drug eruption with characteristic recurrence at the same site of skin or mucous membranes. It is characterized by onset of round/oval, erythematous, well-defined macules on the skin and/or mucosa associated with itching and burning.¹ Fixed drug eruption generally is restricted to the mucous membrane and skin, with the lips, palms, soles, glans penis, and groin area being the most common sites. Intraoral involvement, excluding the lips, of FDE is rare. The tongue is a rare site of an FDE.² Fixed drug eruption on the tongue has been reported with clarithromycin.³ Dental clinicians have to be aware of the possibility of FDE due to commonly used drugs such tinidazole, which would help in prompt diagnosis of these lesions.

Based on the patient’s clinical presentation, he was given a diagnosis of herpes zoster oticus—also known as Ramsay Hunt syndrome. Patients with Ramsay Hunt syndrome typically develop unilateral facial paralysis and erythematous vesicles that appear ipsilaterally on the ear and/or in the mouth. This syndrome is a rare complication of herpes zoster that occurs when latent varicella zoster virus (VZV) infection reactivates and spreads to affect the geniculate ganglion.

An estimated 5 out of every 100,000 people develop Ramsay Hunt syndrome each year in the United States; men and women are equally affected. Any patient who’s had VZV infection runs the risk of developing Ramsay Hunt syndrome, but it most often develops in individuals older than age 60.

Vesicles in the mouth usually develop on the tongue or hard palate. Other symptoms may include tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. Because the symptoms of Ramsay Hunt syndrome suggest a possible infection, the differential diagnosis should include herpes simplex virus type 1, Epstein-Barr virus, group A Streptococcus, and measles.

A diagnosis of Ramsay Hunt syndrome is typically made clinically, but can be confirmed with direct fluorescent antibody (DFA) analysis, polymerase chain reaction (PCR) testing, or viral culture of vesicular exudates. DFA for VZV has an 87% sensitivity. PCR has a higher sensitivity (92%), is widely available, and is the diagnostic test of choice, according to the Centers for Disease Control and Prevention.

Treatment with an oral steroid, such as prednisone, in addition to an antiviral such as acyclovir or valacyclovir, may reduce the likelihood of postherpetic neuralgia and improve facial motor function. However, these benefits have not been demonstrated in randomized controlled trials.

In this case, the FP prescribed oral valacyclovir 1 g 3 times a day for 7 days and oral prednisone 50 mg/d for 5 days for the patient. After one week of treatment, the patient’s symptoms resolved and the vesicles in his mouth crusted over. He did not experience postherpetic neuralgia or have a recurrence.

Adapted from: Moss DA, Crawford P. Sore throat and left ear pain. J Fam Pract. 2015;64:117-119.

Based on the patient’s clinical presentation, he was given a diagnosis of herpes zoster oticus—also known as Ramsay Hunt syndrome. Patients with Ramsay Hunt syndrome typically develop unilateral facial paralysis and erythematous vesicles that appear ipsilaterally on the ear and/or in the mouth. This syndrome is a rare complication of herpes zoster that occurs when latent varicella zoster virus (VZV) infection reactivates and spreads to affect the geniculate ganglion.

An estimated 5 out of every 100,000 people develop Ramsay Hunt syndrome each year in the United States; men and women are equally affected. Any patient who’s had VZV infection runs the risk of developing Ramsay Hunt syndrome, but it most often develops in individuals older than age 60.

Vesicles in the mouth usually develop on the tongue or hard palate. Other symptoms may include tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. Because the symptoms of Ramsay Hunt syndrome suggest a possible infection, the differential diagnosis should include herpes simplex virus type 1, Epstein-Barr virus, group A Streptococcus, and measles.

A diagnosis of Ramsay Hunt syndrome is typically made clinically, but can be confirmed with direct fluorescent antibody (DFA) analysis, polymerase chain reaction (PCR) testing, or viral culture of vesicular exudates. DFA for VZV has an 87% sensitivity. PCR has a higher sensitivity (92%), is widely available, and is the diagnostic test of choice, according to the Centers for Disease Control and Prevention.

Treatment with an oral steroid, such as prednisone, in addition to an antiviral such as acyclovir or valacyclovir, may reduce the likelihood of postherpetic neuralgia and improve facial motor function. However, these benefits have not been demonstrated in randomized controlled trials.

In this case, the FP prescribed oral valacyclovir 1 g 3 times a day for 7 days and oral prednisone 50 mg/d for 5 days for the patient. After one week of treatment, the patient’s symptoms resolved and the vesicles in his mouth crusted over. He did not experience postherpetic neuralgia or have a recurrence.

Adapted from: Moss DA, Crawford P. Sore throat and left ear pain. J Fam Pract. 2015;64:117-119.

Based on the patient’s clinical presentation, he was given a diagnosis of herpes zoster oticus—also known as Ramsay Hunt syndrome. Patients with Ramsay Hunt syndrome typically develop unilateral facial paralysis and erythematous vesicles that appear ipsilaterally on the ear and/or in the mouth. This syndrome is a rare complication of herpes zoster that occurs when latent varicella zoster virus (VZV) infection reactivates and spreads to affect the geniculate ganglion.

An estimated 5 out of every 100,000 people develop Ramsay Hunt syndrome each year in the United States; men and women are equally affected. Any patient who’s had VZV infection runs the risk of developing Ramsay Hunt syndrome, but it most often develops in individuals older than age 60.

Vesicles in the mouth usually develop on the tongue or hard palate. Other symptoms may include tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. Because the symptoms of Ramsay Hunt syndrome suggest a possible infection, the differential diagnosis should include herpes simplex virus type 1, Epstein-Barr virus, group A Streptococcus, and measles.

A diagnosis of Ramsay Hunt syndrome is typically made clinically, but can be confirmed with direct fluorescent antibody (DFA) analysis, polymerase chain reaction (PCR) testing, or viral culture of vesicular exudates. DFA for VZV has an 87% sensitivity. PCR has a higher sensitivity (92%), is widely available, and is the diagnostic test of choice, according to the Centers for Disease Control and Prevention.

Treatment with an oral steroid, such as prednisone, in addition to an antiviral such as acyclovir or valacyclovir, may reduce the likelihood of postherpetic neuralgia and improve facial motor function. However, these benefits have not been demonstrated in randomized controlled trials.

In this case, the FP prescribed oral valacyclovir 1 g 3 times a day for 7 days and oral prednisone 50 mg/d for 5 days for the patient. After one week of treatment, the patient’s symptoms resolved and the vesicles in his mouth crusted over. He did not experience postherpetic neuralgia or have a recurrence.

Adapted from: Moss DA, Crawford P. Sore throat and left ear pain. J Fam Pract. 2015;64:117-119.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that most commonly affects the lungs, eyes, and skin. Cutaneous involvement is reported in 25% to 35% of patients with sarcoidosis and may occur in a variety of forms including macules, papules, plaques, and lupus pernio.^1,2 Dermatologists commonly are confronted with the diagnosis and management of sarcoidosis because of its high incidence of cutaneous involvement. Due to the protean nature of the disease, skin biopsy plays a key role in confirming the diagnosis. Histological evidence of noncaseating granulomas in combination with an appropriate clinical and radiographic picture is necessary for the diagnosis of sarcoidosis.^1,2 Brincker and Wilbek³ first described the link between pulmonary sarcoidosis and an increased incidence of malignancy in 1974. Since then, a number of studies have suggested that sarcoidosis may be associated with an increased risk for hematologic malignancy as well as an increased risk for cancers of the lungs, stomach, colon, liver, and skin.^4,5 To date, few studies exist that examine the relationship between cutaneous sarcoidosis and malignancy.⁶

We describe 3 patients with sarcoidosis who developed squamous cell carcinoma (SCC) of the skin, including 2 black patients, which highlights the potential for SCC development.

Case Reports

Patient 1

A black woman in her 60s with a history of sarcoidosis affecting the lungs and skin that was well controlled with biweekly adalimumab 40 mg subcutaneous injections presented with a new dark painful lesion on the right third finger. She reported the lesion had been present for 1 to 2 years prior to the current presentation and was increasing in size. She had no history of prior skin cancers.

Physical examination revealed a waxy, brown-pigmented papule with overlying scale on the ulnar aspect of the right third digit near the web space (Figure 1A). A shave biopsy revealed atypical keratinocytes involving all layers of the epidermis along with associated parakeratotic scale consistent with a diagnosis of SCC in situ (Figure 1B). Human papillomavirus staining was negative. Due to the location of the lesion, the patient underwent Mohs micrographic surgery and the lesion was completely excised.

Patient 2

A black woman in her 60s with a history of cutaneous sarcoidosis that was maintained on minocycline 100 mg twice daily, chloroquine 250 mg daily, tacrolimus ointment 0.1%, tretinoin cream 0.025%, and intermittent intralesional triamcinolone acetonide injections to the nose, as well as quiescent pulmonary sarcoidosis, developed a new, growing, asymptomatic, hyperpigmented lesion on the left side of the submandibular neck over a period of a few months. A biopsy was performed and the lesion was found to be an SCC, which subsequently was completely excised.

Patient 3

A white man in his 60s with a history of prior quiescent pulmonary sarcoidosis, remote melanoma, and multiple nonmelanoma skin cancers developed scaly papules on the scalp for months, one that was interpreted by an outside pathologist as an invasive SCC (Figure 2A). He was referred to our institution for Mohs micrographic surgery. On presentation when his scalp was shaved for surgery, he was noted to have several violaceous, annular, thin plaques on the scalp (Figure 2B). A biopsy of an annular plaque demonstrated several areas of granulomatous dermatitis consistent with a diagnosis of cutaneous sarcoidosis (Figure 2C). The patient had clinical lymphadenopathy of the neck and supraclavicular region. Given the patient’s history, the differential diagnosis for these lesions included metastatic SCC, lymphoma, and sarcoidosis. The patient underwent a positron emission tomography scan, which demonstrated fluorodeoxyglucose-positive regions in both lungs and the right side of the neck. After evaluation by the pulmonary and otorhinolaryngology departments, including a lymph node biopsy, the positron emission tomography–enhancing lesions were ultimately determined to be consistent with sarcoidosis.

The patient underwent Mohs micrographic surgery for treatment of the scalp SCC and was started on triamcinolone cream 0.1% for the body, clobetasol propionate foam 0.05% for the scalp, and hydroxychloroquine sulfate 400 mg daily for the cutaneous sarcoidosis. His annular scalp lesions resolved, but over the following 12 months the patient had numerous clinically suspicious skin lesions that were biopsied and were consistent with multiple basal cell carcinomas, actinic keratoses, and SCC in situ. They were treated with surgery, cryosurgical destruction with liquid nitrogen, and 5-fluorouracil cream.

Comment

The potential increased risk for malignancy in patients with sarcoidosis has been well documented.^3-6 Brincker and Wilbek³ first reported this association after studying 2544 patients with pulmonary sarcoidosis from 1962 to 1971. In particular, they noted a difference between the expected and observed number of cases of malignancy, particularly lung cancer and lymphoma, in the sarcoidosis population.³ In a study of 10,037 hospitalized sarcoidosis patients from 1964 to 2004, Ji et al⁵ noted a 40% overall increase in the incidence of cancer and found that the risk for malignancy was highest in the year following hospitalization. Interestingly, they found that the risk for developing cutaneous SCC was elevated in sarcoidosis patients even after the first year following hospitalization.⁵ In a retrospective cohort study examining more than 9000 patients, Askling et al⁴ also confirmed the increased incidence of malignancy in sarcoidosis patients. Specifically, the authors found a higher than expected occurrence of skin cancer, both melanoma (standardized incidence ratio, 1.6; 95% confidence interval, 1.1-2.3) and nonmelanoma skin cancer (standardized incidence ratio, 2.8; 95% confidence interval, 2.0-3.8) in patients with sarcoidosis.⁴ Reich et al⁷ cross-matched 30,000 cases from the Kaiser Permanente Northwest Region Tumor Registry against a sarcoidosis registry of 243 cases to evaluate for evidence of linkage between sarcoidosis and malignancy. They concluded that there may be an etiologic relationship between sarcoidosis and malignancy in at least one-quarter of cases in which both are present and hypothesized that granulomas may be the result of a cell-mediated reaction to tumor antigens.⁷

Few published studies specifically address the incidence of malignancy in patients with primarily cutaneous sarcoidosis. Cutaneous sarcoidosis includes nonspecific lesions, such as erythema nodosum, as well as specific lesions, such as papules, plaques, nodules, and lupus pernio.⁸ Alexandrescu et al⁶ evaluated 110 patients with a diagnosis of both sarcoidosis (cutaneous and noncutaneous) and malignancy. Through their analysis, they found that cutaneous sarcoidosis is seen more commonly in patients presenting with sarcoidosis and malignancy (56.4%) than in the total sarcoidosis population (20%–25%). From these findings, the authors concluded that cutaneous sarcoidosis appears to be a subtype of sarcoidosis associated with cancer.⁶

We report 3 cases that specifically illustrate a link between cutaneous sarcoidosis and an increased risk for cutaneous SCC. Because sarcoidosis commonly affects the skin, patients often present to dermatologists for care. Once the initial diagnosis of cutaneous sarcoidosis is made via biopsy, it is natural to be tempted to attribute any new skin lesions to worsening or active disease; however, as cutaneous sarcoidosis may take on a variety of nonspecific forms, it is important to biopsy any unusual lesions. In our case series, patient 3 presented at several different points with scaly scalp lesions. Upon biopsy, several of these lesions were found to be SCCs, while others demonstrated regions of granulomatous inflammation consistent with a diagnosis of cutaneous sarcoidosis. On further review of pathology during the preparation of this manuscript after the initial diagnoses were made, it was further noted that it is challenging to distinguish granulomatous inflammation with reactive pseudoepitheliomatous hyperplasia from SCC. The fact that these lesions were clinically indistinguishable illustrates the critical importance of appropriate-depth biopsy in this situation, and the histopathologic challenges highlighted herein are important for pathologists to remember.

Patients 1 and 2 were both black women, and the fact that these patients both presented with cutaneous SCCs—one of whom was immunosuppressed due to treatment with adalimumab, the other without systemic immunosuppression—exemplifies the need for comprehensive skin examinations in sarcoidosis patients as well as for biopsies of new or unusual lesions.

The mechanism for the development of malignancy in patients with sarcoidosis is unknown and likely is multifactorial. Multiple theories have been proposed.^1,2,5,6,8 Sarcoidosis is marked by the development of granulomas secondary to the interaction between CD4⁺ T cells and antigen-presenting cells, which is mediated by various cytokines and chemokines, including IL-2 and IFN-γ. Patients with sarcoidosis have been found to have oligoclonal T-cell lineages with a limited receptor repertoire, suggestive of selective immune system activation, as well as a deficiency of certain types of regulatory cells, namely natural killer cells.^1,2 This immune dysregulation has been postulated to play an etiologic role in the development of malignancy in sarcoidosis patients.^1,2,5 Furthermore, the chronic inflammation found in the organs commonly affected by both sarcoidosis and malignancy is another possible mechanism.^6,8 Finally, immunosuppression and mutagenesis secondary to the treatment modalities used in sarcoidosis may be another contributing factor.⁶

Conclusion

An association between sarcoidosis and malignancy has been suggested for several decades. We specifically report 3 cases of patients with cutaneous sarcoidosis who presented with concurrent cutaneous SCCs. Given the varied and often nonspecific nature of cutaneous sarcoidosis, these cases highlight the importance of biopsy when sarcoidosis patients present with new and unusual skin lesions. Additionally, they illustrate the importance of thorough skin examinations in sarcoidosis patients as well as some of the challenges these patients pose for dermatologists.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that most commonly affects the lungs, eyes, and skin. Cutaneous involvement is reported in 25% to 35% of patients with sarcoidosis and may occur in a variety of forms including macules, papules, plaques, and lupus pernio.^1,2 Dermatologists commonly are confronted with the diagnosis and management of sarcoidosis because of its high incidence of cutaneous involvement. Due to the protean nature of the disease, skin biopsy plays a key role in confirming the diagnosis. Histological evidence of noncaseating granulomas in combination with an appropriate clinical and radiographic picture is necessary for the diagnosis of sarcoidosis.^1,2 Brincker and Wilbek³ first described the link between pulmonary sarcoidosis and an increased incidence of malignancy in 1974. Since then, a number of studies have suggested that sarcoidosis may be associated with an increased risk for hematologic malignancy as well as an increased risk for cancers of the lungs, stomach, colon, liver, and skin.^4,5 To date, few studies exist that examine the relationship between cutaneous sarcoidosis and malignancy.⁶

We describe 3 patients with sarcoidosis who developed squamous cell carcinoma (SCC) of the skin, including 2 black patients, which highlights the potential for SCC development.

Case Reports

Patient 1

A black woman in her 60s with a history of sarcoidosis affecting the lungs and skin that was well controlled with biweekly adalimumab 40 mg subcutaneous injections presented with a new dark painful lesion on the right third finger. She reported the lesion had been present for 1 to 2 years prior to the current presentation and was increasing in size. She had no history of prior skin cancers.

Physical examination revealed a waxy, brown-pigmented papule with overlying scale on the ulnar aspect of the right third digit near the web space (Figure 1A). A shave biopsy revealed atypical keratinocytes involving all layers of the epidermis along with associated parakeratotic scale consistent with a diagnosis of SCC in situ (Figure 1B). Human papillomavirus staining was negative. Due to the location of the lesion, the patient underwent Mohs micrographic surgery and the lesion was completely excised.

Patient 2

A black woman in her 60s with a history of cutaneous sarcoidosis that was maintained on minocycline 100 mg twice daily, chloroquine 250 mg daily, tacrolimus ointment 0.1%, tretinoin cream 0.025%, and intermittent intralesional triamcinolone acetonide injections to the nose, as well as quiescent pulmonary sarcoidosis, developed a new, growing, asymptomatic, hyperpigmented lesion on the left side of the submandibular neck over a period of a few months. A biopsy was performed and the lesion was found to be an SCC, which subsequently was completely excised.

Patient 3

A white man in his 60s with a history of prior quiescent pulmonary sarcoidosis, remote melanoma, and multiple nonmelanoma skin cancers developed scaly papules on the scalp for months, one that was interpreted by an outside pathologist as an invasive SCC (Figure 2A). He was referred to our institution for Mohs micrographic surgery. On presentation when his scalp was shaved for surgery, he was noted to have several violaceous, annular, thin plaques on the scalp (Figure 2B). A biopsy of an annular plaque demonstrated several areas of granulomatous dermatitis consistent with a diagnosis of cutaneous sarcoidosis (Figure 2C). The patient had clinical lymphadenopathy of the neck and supraclavicular region. Given the patient’s history, the differential diagnosis for these lesions included metastatic SCC, lymphoma, and sarcoidosis. The patient underwent a positron emission tomography scan, which demonstrated fluorodeoxyglucose-positive regions in both lungs and the right side of the neck. After evaluation by the pulmonary and otorhinolaryngology departments, including a lymph node biopsy, the positron emission tomography–enhancing lesions were ultimately determined to be consistent with sarcoidosis.

The patient underwent Mohs micrographic surgery for treatment of the scalp SCC and was started on triamcinolone cream 0.1% for the body, clobetasol propionate foam 0.05% for the scalp, and hydroxychloroquine sulfate 400 mg daily for the cutaneous sarcoidosis. His annular scalp lesions resolved, but over the following 12 months the patient had numerous clinically suspicious skin lesions that were biopsied and were consistent with multiple basal cell carcinomas, actinic keratoses, and SCC in situ. They were treated with surgery, cryosurgical destruction with liquid nitrogen, and 5-fluorouracil cream.

Comment

The potential increased risk for malignancy in patients with sarcoidosis has been well documented.^3-6 Brincker and Wilbek³ first reported this association after studying 2544 patients with pulmonary sarcoidosis from 1962 to 1971. In particular, they noted a difference between the expected and observed number of cases of malignancy, particularly lung cancer and lymphoma, in the sarcoidosis population.³ In a study of 10,037 hospitalized sarcoidosis patients from 1964 to 2004, Ji et al⁵ noted a 40% overall increase in the incidence of cancer and found that the risk for malignancy was highest in the year following hospitalization. Interestingly, they found that the risk for developing cutaneous SCC was elevated in sarcoidosis patients even after the first year following hospitalization.⁵ In a retrospective cohort study examining more than 9000 patients, Askling et al⁴ also confirmed the increased incidence of malignancy in sarcoidosis patients. Specifically, the authors found a higher than expected occurrence of skin cancer, both melanoma (standardized incidence ratio, 1.6; 95% confidence interval, 1.1-2.3) and nonmelanoma skin cancer (standardized incidence ratio, 2.8; 95% confidence interval, 2.0-3.8) in patients with sarcoidosis.⁴ Reich et al⁷ cross-matched 30,000 cases from the Kaiser Permanente Northwest Region Tumor Registry against a sarcoidosis registry of 243 cases to evaluate for evidence of linkage between sarcoidosis and malignancy. They concluded that there may be an etiologic relationship between sarcoidosis and malignancy in at least one-quarter of cases in which both are present and hypothesized that granulomas may be the result of a cell-mediated reaction to tumor antigens.⁷

Few published studies specifically address the incidence of malignancy in patients with primarily cutaneous sarcoidosis. Cutaneous sarcoidosis includes nonspecific lesions, such as erythema nodosum, as well as specific lesions, such as papules, plaques, nodules, and lupus pernio.⁸ Alexandrescu et al⁶ evaluated 110 patients with a diagnosis of both sarcoidosis (cutaneous and noncutaneous) and malignancy. Through their analysis, they found that cutaneous sarcoidosis is seen more commonly in patients presenting with sarcoidosis and malignancy (56.4%) than in the total sarcoidosis population (20%–25%). From these findings, the authors concluded that cutaneous sarcoidosis appears to be a subtype of sarcoidosis associated with cancer.⁶

We report 3 cases that specifically illustrate a link between cutaneous sarcoidosis and an increased risk for cutaneous SCC. Because sarcoidosis commonly affects the skin, patients often present to dermatologists for care. Once the initial diagnosis of cutaneous sarcoidosis is made via biopsy, it is natural to be tempted to attribute any new skin lesions to worsening or active disease; however, as cutaneous sarcoidosis may take on a variety of nonspecific forms, it is important to biopsy any unusual lesions. In our case series, patient 3 presented at several different points with scaly scalp lesions. Upon biopsy, several of these lesions were found to be SCCs, while others demonstrated regions of granulomatous inflammation consistent with a diagnosis of cutaneous sarcoidosis. On further review of pathology during the preparation of this manuscript after the initial diagnoses were made, it was further noted that it is challenging to distinguish granulomatous inflammation with reactive pseudoepitheliomatous hyperplasia from SCC. The fact that these lesions were clinically indistinguishable illustrates the critical importance of appropriate-depth biopsy in this situation, and the histopathologic challenges highlighted herein are important for pathologists to remember.

Patients 1 and 2 were both black women, and the fact that these patients both presented with cutaneous SCCs—one of whom was immunosuppressed due to treatment with adalimumab, the other without systemic immunosuppression—exemplifies the need for comprehensive skin examinations in sarcoidosis patients as well as for biopsies of new or unusual lesions.

The mechanism for the development of malignancy in patients with sarcoidosis is unknown and likely is multifactorial. Multiple theories have been proposed.^1,2,5,6,8 Sarcoidosis is marked by the development of granulomas secondary to the interaction between CD4⁺ T cells and antigen-presenting cells, which is mediated by various cytokines and chemokines, including IL-2 and IFN-γ. Patients with sarcoidosis have been found to have oligoclonal T-cell lineages with a limited receptor repertoire, suggestive of selective immune system activation, as well as a deficiency of certain types of regulatory cells, namely natural killer cells.^1,2 This immune dysregulation has been postulated to play an etiologic role in the development of malignancy in sarcoidosis patients.^1,2,5 Furthermore, the chronic inflammation found in the organs commonly affected by both sarcoidosis and malignancy is another possible mechanism.^6,8 Finally, immunosuppression and mutagenesis secondary to the treatment modalities used in sarcoidosis may be another contributing factor.⁶

Conclusion

An association between sarcoidosis and malignancy has been suggested for several decades. We specifically report 3 cases of patients with cutaneous sarcoidosis who presented with concurrent cutaneous SCCs. Given the varied and often nonspecific nature of cutaneous sarcoidosis, these cases highlight the importance of biopsy when sarcoidosis patients present with new and unusual skin lesions. Additionally, they illustrate the importance of thorough skin examinations in sarcoidosis patients as well as some of the challenges these patients pose for dermatologists.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that most commonly affects the lungs, eyes, and skin. Cutaneous involvement is reported in 25% to 35% of patients with sarcoidosis and may occur in a variety of forms including macules, papules, plaques, and lupus pernio.^1,2 Dermatologists commonly are confronted with the diagnosis and management of sarcoidosis because of its high incidence of cutaneous involvement. Due to the protean nature of the disease, skin biopsy plays a key role in confirming the diagnosis. Histological evidence of noncaseating granulomas in combination with an appropriate clinical and radiographic picture is necessary for the diagnosis of sarcoidosis.^1,2 Brincker and Wilbek³ first described the link between pulmonary sarcoidosis and an increased incidence of malignancy in 1974. Since then, a number of studies have suggested that sarcoidosis may be associated with an increased risk for hematologic malignancy as well as an increased risk for cancers of the lungs, stomach, colon, liver, and skin.^4,5 To date, few studies exist that examine the relationship between cutaneous sarcoidosis and malignancy.⁶

We describe 3 patients with sarcoidosis who developed squamous cell carcinoma (SCC) of the skin, including 2 black patients, which highlights the potential for SCC development.

Case Reports

Patient 1

A black woman in her 60s with a history of sarcoidosis affecting the lungs and skin that was well controlled with biweekly adalimumab 40 mg subcutaneous injections presented with a new dark painful lesion on the right third finger. She reported the lesion had been present for 1 to 2 years prior to the current presentation and was increasing in size. She had no history of prior skin cancers.

Physical examination revealed a waxy, brown-pigmented papule with overlying scale on the ulnar aspect of the right third digit near the web space (Figure 1A). A shave biopsy revealed atypical keratinocytes involving all layers of the epidermis along with associated parakeratotic scale consistent with a diagnosis of SCC in situ (Figure 1B). Human papillomavirus staining was negative. Due to the location of the lesion, the patient underwent Mohs micrographic surgery and the lesion was completely excised.

Patient 2

A black woman in her 60s with a history of cutaneous sarcoidosis that was maintained on minocycline 100 mg twice daily, chloroquine 250 mg daily, tacrolimus ointment 0.1%, tretinoin cream 0.025%, and intermittent intralesional triamcinolone acetonide injections to the nose, as well as quiescent pulmonary sarcoidosis, developed a new, growing, asymptomatic, hyperpigmented lesion on the left side of the submandibular neck over a period of a few months. A biopsy was performed and the lesion was found to be an SCC, which subsequently was completely excised.

Patient 3

A white man in his 60s with a history of prior quiescent pulmonary sarcoidosis, remote melanoma, and multiple nonmelanoma skin cancers developed scaly papules on the scalp for months, one that was interpreted by an outside pathologist as an invasive SCC (Figure 2A). He was referred to our institution for Mohs micrographic surgery. On presentation when his scalp was shaved for surgery, he was noted to have several violaceous, annular, thin plaques on the scalp (Figure 2B). A biopsy of an annular plaque demonstrated several areas of granulomatous dermatitis consistent with a diagnosis of cutaneous sarcoidosis (Figure 2C). The patient had clinical lymphadenopathy of the neck and supraclavicular region. Given the patient’s history, the differential diagnosis for these lesions included metastatic SCC, lymphoma, and sarcoidosis. The patient underwent a positron emission tomography scan, which demonstrated fluorodeoxyglucose-positive regions in both lungs and the right side of the neck. After evaluation by the pulmonary and otorhinolaryngology departments, including a lymph node biopsy, the positron emission tomography–enhancing lesions were ultimately determined to be consistent with sarcoidosis.

The patient underwent Mohs micrographic surgery for treatment of the scalp SCC and was started on triamcinolone cream 0.1% for the body, clobetasol propionate foam 0.05% for the scalp, and hydroxychloroquine sulfate 400 mg daily for the cutaneous sarcoidosis. His annular scalp lesions resolved, but over the following 12 months the patient had numerous clinically suspicious skin lesions that were biopsied and were consistent with multiple basal cell carcinomas, actinic keratoses, and SCC in situ. They were treated with surgery, cryosurgical destruction with liquid nitrogen, and 5-fluorouracil cream.

Comment

The potential increased risk for malignancy in patients with sarcoidosis has been well documented.^3-6 Brincker and Wilbek³ first reported this association after studying 2544 patients with pulmonary sarcoidosis from 1962 to 1971. In particular, they noted a difference between the expected and observed number of cases of malignancy, particularly lung cancer and lymphoma, in the sarcoidosis population.³ In a study of 10,037 hospitalized sarcoidosis patients from 1964 to 2004, Ji et al⁵ noted a 40% overall increase in the incidence of cancer and found that the risk for malignancy was highest in the year following hospitalization. Interestingly, they found that the risk for developing cutaneous SCC was elevated in sarcoidosis patients even after the first year following hospitalization.⁵ In a retrospective cohort study examining more than 9000 patients, Askling et al⁴ also confirmed the increased incidence of malignancy in sarcoidosis patients. Specifically, the authors found a higher than expected occurrence of skin cancer, both melanoma (standardized incidence ratio, 1.6; 95% confidence interval, 1.1-2.3) and nonmelanoma skin cancer (standardized incidence ratio, 2.8; 95% confidence interval, 2.0-3.8) in patients with sarcoidosis.⁴ Reich et al⁷ cross-matched 30,000 cases from the Kaiser Permanente Northwest Region Tumor Registry against a sarcoidosis registry of 243 cases to evaluate for evidence of linkage between sarcoidosis and malignancy. They concluded that there may be an etiologic relationship between sarcoidosis and malignancy in at least one-quarter of cases in which both are present and hypothesized that granulomas may be the result of a cell-mediated reaction to tumor antigens.⁷

Few published studies specifically address the incidence of malignancy in patients with primarily cutaneous sarcoidosis. Cutaneous sarcoidosis includes nonspecific lesions, such as erythema nodosum, as well as specific lesions, such as papules, plaques, nodules, and lupus pernio.⁸ Alexandrescu et al⁶ evaluated 110 patients with a diagnosis of both sarcoidosis (cutaneous and noncutaneous) and malignancy. Through their analysis, they found that cutaneous sarcoidosis is seen more commonly in patients presenting with sarcoidosis and malignancy (56.4%) than in the total sarcoidosis population (20%–25%). From these findings, the authors concluded that cutaneous sarcoidosis appears to be a subtype of sarcoidosis associated with cancer.⁶

We report 3 cases that specifically illustrate a link between cutaneous sarcoidosis and an increased risk for cutaneous SCC. Because sarcoidosis commonly affects the skin, patients often present to dermatologists for care. Once the initial diagnosis of cutaneous sarcoidosis is made via biopsy, it is natural to be tempted to attribute any new skin lesions to worsening or active disease; however, as cutaneous sarcoidosis may take on a variety of nonspecific forms, it is important to biopsy any unusual lesions. In our case series, patient 3 presented at several different points with scaly scalp lesions. Upon biopsy, several of these lesions were found to be SCCs, while others demonstrated regions of granulomatous inflammation consistent with a diagnosis of cutaneous sarcoidosis. On further review of pathology during the preparation of this manuscript after the initial diagnoses were made, it was further noted that it is challenging to distinguish granulomatous inflammation with reactive pseudoepitheliomatous hyperplasia from SCC. The fact that these lesions were clinically indistinguishable illustrates the critical importance of appropriate-depth biopsy in this situation, and the histopathologic challenges highlighted herein are important for pathologists to remember.

Patients 1 and 2 were both black women, and the fact that these patients both presented with cutaneous SCCs—one of whom was immunosuppressed due to treatment with adalimumab, the other without systemic immunosuppression—exemplifies the need for comprehensive skin examinations in sarcoidosis patients as well as for biopsies of new or unusual lesions.

The mechanism for the development of malignancy in patients with sarcoidosis is unknown and likely is multifactorial. Multiple theories have been proposed.^1,2,5,6,8 Sarcoidosis is marked by the development of granulomas secondary to the interaction between CD4⁺ T cells and antigen-presenting cells, which is mediated by various cytokines and chemokines, including IL-2 and IFN-γ. Patients with sarcoidosis have been found to have oligoclonal T-cell lineages with a limited receptor repertoire, suggestive of selective immune system activation, as well as a deficiency of certain types of regulatory cells, namely natural killer cells.^1,2 This immune dysregulation has been postulated to play an etiologic role in the development of malignancy in sarcoidosis patients.^1,2,5 Furthermore, the chronic inflammation found in the organs commonly affected by both sarcoidosis and malignancy is another possible mechanism.^6,8 Finally, immunosuppression and mutagenesis secondary to the treatment modalities used in sarcoidosis may be another contributing factor.⁶

Conclusion

An association between sarcoidosis and malignancy has been suggested for several decades. We specifically report 3 cases of patients with cutaneous sarcoidosis who presented with concurrent cutaneous SCCs. Given the varied and often nonspecific nature of cutaneous sarcoidosis, these cases highlight the importance of biopsy when sarcoidosis patients present with new and unusual skin lesions. Additionally, they illustrate the importance of thorough skin examinations in sarcoidosis patients as well as some of the challenges these patients pose for dermatologists.

Vitiligo is a disorder typified by loss of pigmentation. Worldwide estimates of disease demonstrate 0.4% to 2% prevalence.¹ Vitiligo generally is felt to be an autoimmune disorder with a complex multifactorial inheritance.² Therapeutic options for vitiligo are largely off label and include topical corticosteroids, topical calcineurin inhibitors, narrowband UVB (NB-UVB) light phototherapy, and excimer (308 nm) laser therapy.^3,4 Therapies for vitiligo are time consuming, as most topical therapies require twice-daily application. Additionally, many patients require 2 or more topical therapies due to involvement of both the head and neck as well as other body sites.^3,4 Generalized disease often is treated with NB-UVB therapy 3 times weekly in-office visits, while excimer laser therapy is used for limited disease resistant to topical agents.^3,4

Many barriers to good outcomes and care exist for patients with vitiligo.⁵ Patients may experience reduced quality of life and/or sexual dysfunction because of vitiligo lesions. The purpose of this pilot study was to identify barriers to access of care in vitiligo patients.

Methods

A survey was designed and then reviewed for unclear wording by members of the local vitiligo support group at Mount Sinai St. Luke’s-Roosevelt Hospital and Beth Israel Medical Centers (New York, New York). Linguistic revision and clarifications were added to the survey to correct identified communication problems. The survey was then posted using an Internet-based survey software. Links to the survey were sent via email to 107 individuals in a LISTSERV comprising Vitiligo Support International members who participated in a New York City support group (led by C.G. and N.B.S.). Only 1 email was used per household and only individuals 18 years or older could participate. These individuals were asked to complete a deidentified, 82-question, institutional review board–reviewed and exempted survey addressing issues affecting delivery and receipt of medical care for vitiligo.

Data were analyzed using the χ² test, analysis of variance, or Student t test depending on the type of variable (categorical vs continuous). Fisher exact or Wilcoxon-Mann-Whitney tests were used when distributional assumptions were not met. A type I error rate (α=.05) was used to determine statistical significance. All analyses were performed using SAS 9.3 software.

Results

Respondents

The survey was completed by 81% (n=87) of individuals. The mean (SD) age of the treated patients about whom the respondents communicated was 33 (16) years and 71% (n=62) were women. The majority of respondents (64 [74%]) reported their race as white, followed by African American/black (12 [14%]), Hispanic (7 [8%]), and Asian (4 [5%]). Twenty-nine percent (22/76) of respondents reported a family income of less than $50,000 per year, 34% (26/76) reported an income of $50,000 to $100,000, and 37% (28/76) reported an income greater than $100,000, while 11 respondents did not report income.

Number of Physicians Seen

Respondents had reportedly seen an average (SD) number of 2 (1) physicians in the past/present before being offered any therapy for vitiligo and only 37% (32/87) of respondents reported being offered therapy by the first physician they saw. The number of physicians seen did not have a statistical relationship with years with vitiligo (ie, disease duration), sex, race, age of onset, income level, or number of sites affected.

Number of Sites Affected

The survey identified the following 23 sites affected by vitiligo: scalp, forehead, eyelids, lips, nose, cheeks, chin, neck, chest, stomach, back, upper arms, forearms, hands, wrists, fingers, genitalia, buttocks, thighs, calves/shins, ankles, feet, and toes. The average (SD) number of sites affected was 12 (6). The number of sites affected was correlated to the recommendation for phototherapy, while the recommendation for excimer laser therapy was inversely associated with the number of sites affected. The median number of sites affected for those who were not prescribed phototherapy was 10 (interquartile range [IQR]=9; P=.05); the median number of sites affected for those who were prescribed phototherapy was 15 (IQR=11). The association between the number of sites affected and whether the patient proceeded with phototherapy was not statistically significant. The need for phototherapy was not related to years with vitiligo (ie, disease duration), sex, or race.

Excimer laser therapy was prescribed more often to patients with fewer sites affected (median of 9 [IQR=3] vs median of 15 [IQR=9]; P=.04). Respondents who had fewer sites affected were on average more likely to proceed with excimer laser therapy (median of 8 [IQR=4] vs median of 11 [IQR=5]). The association between the number of sites affected and whether the patient proceeded with excimer laser therapy was not statistically significant.

Access to Topical Medications

Forty-one percent (36/87) of respondents reported difficulty accessing 1 or more topical therapies. Of 52 respondents who were prescribed a topical corticosteroid, 12 (23%) reported difficulty accessing therapy. Of 67 respondents who were prescribed a topical calcineurin inhibitor, 27 (40%) reported difficulty accessing medication (tacrolimus, n=17; pimecrolimus, n=10). Calcipotriene prescription coverage was not specifically addressed in this survey, as it usually is a second-line or adjunctive medication. Difficulty getting topical tacrolimus but not topical corticosteroids was associated with female sex (P=.03) but was not associated with race, income level, or level of education. Difficulty obtaining medication was not related to race, sex, level of education, or income level.

Consequences of Phototherapy

Twenty-three of 34 respondents (68%) who were told they required phototherapy actually received phototherapy and reported paying $38 weekly (IQR=$75). The majority of patients who proceeded with phototherapy lived (17/23 [74%]) or worked (16/23 [70%]) within 20 minutes of the therapy center. Self-reported response to phototherapy was good to very good in 65% (15/23) of respondents and no response in 30% (7/23); only 1 respondent reported worsening vitiligo. Sixty percent (15/25) of respondents said they were not satisfied with phototherapy. Respondents who were satisfied with the outcome of phototherapy had on average fewer sites affected by vitiligo (mean [SD], 10 [8]; P=.05). The association with other demographic and economic parameters (eg, sex, race, level of education, income level) was not statistically significant. Proceeding with phototherapy was not related to race, sex, level of education, or income level.

When questioned how many aspects of daily life (eg, work, home, school) were affected by phototherapy, 40% (35/87) of respondents reported that more than one life parameter was disturbed. Thirty-five percent (8/23) of respondents who received phototherapy reported that it affected their daily life “quite a bit” or “severely.” More respondents were likely to report that the therapy interfered with their life “somewhat,” “quite a bit,” or “severely” (76% [19/25]; 95% confidence interval, 55%-92%; P=.01) rather than “not at all” or “a little.”

Excimer Laser

Nine of 17 respondents (53%) who were recommended to undergo excimer laser therapy actually received therapy and reported paying $100 weekly (IQR=$60).

There was a trend toward significance of excimer usage being associated with lower age quartile (0–20 years)(P=.0553) and income more than $100,000 (P=.0788), neither of which reached statistical significance.

Insurance Coverage

Respondents were offered 7 answer options regarding the reason for noncoverage of topical calcineurin inhibitors. They were allowed to pick more than one reason where appropriate. For individuals who were prescribed topical tacrolimus but did not receive drug (n=17), the following reasons were cited: “no insurance coverage for the medication” (59% [10/17]), “your deductible was too high” (24% [4/17]), “prior authorization failed to produce coverage of the medication” (24% [4/17]), “your copay was prohibitively expensive” (24% [4/17]), “you were uncomfortable with the medication’s side effects” (18% [3/17]), “the tube was too small to cover your skin affected areas” (12% [2/17]), and “other” (29% [5/17]). Three patients selected 3 or more reasons, 8 patients selected 2 reasons, and 5 patients selected one reason.

Comment

It has been reported that patients with vitiligo may have difficulty related to treatment compliance for a variety of reasons.⁵ We identified notable barriers that arise for some, if not all, patients with vitiligo in the United States at some point in their care, including interference with other aspects of daily life, lack of coverage by current health insurance provider, and high out-of-pocket expenses, in addition to the negative effects of vitiligo on quality of life that have already been reported.^6,7 These barriers are not a function of race/ethnicity, income level, or age of onset, but they may be impacted, as in the case of tacrolimus, by female sex. It is clear that, based on this study’s numbers, many patients will be unable to receive and/or comply with recommended treatment plans.

A limitation of this analysis is the study population, a select group of patients who had not been prescribed all the therapies in question. The sample size may not be large enough to demonstrate differences between level of education, race, or income level; however, even with a sample size of 87 respondents, the barriers to access of care are prominent. Larger population-based surveys would potentially tease out patterns of barriers not apparent with a smaller sample. No data were generated specific to calcipotriene, and this medication was not specified as a write-in agent on open question by any respondents; therefore, access to topical calcipotriene cannot be projected from this study. Phototherapy was queried as a nonspecific term and the breakdown of NB-UVB versus psoralen plus UVA was not available for this survey. Data suggesting a burden of socioeconomic barriers have been reported for atopic dermatitis⁸ and psoriasis,⁹ which corroborate the need for greater research in the field of access to care in dermatology.

Despite some advancement in the care of vitiligo, patients often are unable to access preferred or recommended treatment modalities. Standard recommendations for care are initial usage of calcineurin inhibitors for facial involvement and topical high-potency corticosteroids for involvement of the body.^3,4 Based on this survey, it would seem that many patients are not able to receive the standard of care. Similarly, NB-UVB phototherapy and excimer laser therapy are recommended for widespread vitiligo and lesions unresponsive to topical care. It would seem that almost half of our respondents did not have access to one or more of the recommended therapies. Barriers to care may have substantial clinical and psychological outcomes, which were not evaluated in this study but merit future research.

Vitiligo is a disorder typified by loss of pigmentation. Worldwide estimates of disease demonstrate 0.4% to 2% prevalence.¹ Vitiligo generally is felt to be an autoimmune disorder with a complex multifactorial inheritance.² Therapeutic options for vitiligo are largely off label and include topical corticosteroids, topical calcineurin inhibitors, narrowband UVB (NB-UVB) light phototherapy, and excimer (308 nm) laser therapy.^3,4 Therapies for vitiligo are time consuming, as most topical therapies require twice-daily application. Additionally, many patients require 2 or more topical therapies due to involvement of both the head and neck as well as other body sites.^3,4 Generalized disease often is treated with NB-UVB therapy 3 times weekly in-office visits, while excimer laser therapy is used for limited disease resistant to topical agents.^3,4

Many barriers to good outcomes and care exist for patients with vitiligo.⁵ Patients may experience reduced quality of life and/or sexual dysfunction because of vitiligo lesions. The purpose of this pilot study was to identify barriers to access of care in vitiligo patients.

Methods

A survey was designed and then reviewed for unclear wording by members of the local vitiligo support group at Mount Sinai St. Luke’s-Roosevelt Hospital and Beth Israel Medical Centers (New York, New York). Linguistic revision and clarifications were added to the survey to correct identified communication problems. The survey was then posted using an Internet-based survey software. Links to the survey were sent via email to 107 individuals in a LISTSERV comprising Vitiligo Support International members who participated in a New York City support group (led by C.G. and N.B.S.). Only 1 email was used per household and only individuals 18 years or older could participate. These individuals were asked to complete a deidentified, 82-question, institutional review board–reviewed and exempted survey addressing issues affecting delivery and receipt of medical care for vitiligo.

Data were analyzed using the χ² test, analysis of variance, or Student t test depending on the type of variable (categorical vs continuous). Fisher exact or Wilcoxon-Mann-Whitney tests were used when distributional assumptions were not met. A type I error rate (α=.05) was used to determine statistical significance. All analyses were performed using SAS 9.3 software.

Results

Respondents

The survey was completed by 81% (n=87) of individuals. The mean (SD) age of the treated patients about whom the respondents communicated was 33 (16) years and 71% (n=62) were women. The majority of respondents (64 [74%]) reported their race as white, followed by African American/black (12 [14%]), Hispanic (7 [8%]), and Asian (4 [5%]). Twenty-nine percent (22/76) of respondents reported a family income of less than $50,000 per year, 34% (26/76) reported an income of $50,000 to $100,000, and 37% (28/76) reported an income greater than $100,000, while 11 respondents did not report income.

Number of Physicians Seen

Respondents had reportedly seen an average (SD) number of 2 (1) physicians in the past/present before being offered any therapy for vitiligo and only 37% (32/87) of respondents reported being offered therapy by the first physician they saw. The number of physicians seen did not have a statistical relationship with years with vitiligo (ie, disease duration), sex, race, age of onset, income level, or number of sites affected.

Number of Sites Affected

The survey identified the following 23 sites affected by vitiligo: scalp, forehead, eyelids, lips, nose, cheeks, chin, neck, chest, stomach, back, upper arms, forearms, hands, wrists, fingers, genitalia, buttocks, thighs, calves/shins, ankles, feet, and toes. The average (SD) number of sites affected was 12 (6). The number of sites affected was correlated to the recommendation for phototherapy, while the recommendation for excimer laser therapy was inversely associated with the number of sites affected. The median number of sites affected for those who were not prescribed phototherapy was 10 (interquartile range [IQR]=9; P=.05); the median number of sites affected for those who were prescribed phototherapy was 15 (IQR=11). The association between the number of sites affected and whether the patient proceeded with phototherapy was not statistically significant. The need for phototherapy was not related to years with vitiligo (ie, disease duration), sex, or race.

Excimer laser therapy was prescribed more often to patients with fewer sites affected (median of 9 [IQR=3] vs median of 15 [IQR=9]; P=.04). Respondents who had fewer sites affected were on average more likely to proceed with excimer laser therapy (median of 8 [IQR=4] vs median of 11 [IQR=5]). The association between the number of sites affected and whether the patient proceeded with excimer laser therapy was not statistically significant.

Access to Topical Medications

Forty-one percent (36/87) of respondents reported difficulty accessing 1 or more topical therapies. Of 52 respondents who were prescribed a topical corticosteroid, 12 (23%) reported difficulty accessing therapy. Of 67 respondents who were prescribed a topical calcineurin inhibitor, 27 (40%) reported difficulty accessing medication (tacrolimus, n=17; pimecrolimus, n=10). Calcipotriene prescription coverage was not specifically addressed in this survey, as it usually is a second-line or adjunctive medication. Difficulty getting topical tacrolimus but not topical corticosteroids was associated with female sex (P=.03) but was not associated with race, income level, or level of education. Difficulty obtaining medication was not related to race, sex, level of education, or income level.

Consequences of Phototherapy

Twenty-three of 34 respondents (68%) who were told they required phototherapy actually received phototherapy and reported paying $38 weekly (IQR=$75). The majority of patients who proceeded with phototherapy lived (17/23 [74%]) or worked (16/23 [70%]) within 20 minutes of the therapy center. Self-reported response to phototherapy was good to very good in 65% (15/23) of respondents and no response in 30% (7/23); only 1 respondent reported worsening vitiligo. Sixty percent (15/25) of respondents said they were not satisfied with phototherapy. Respondents who were satisfied with the outcome of phototherapy had on average fewer sites affected by vitiligo (mean [SD], 10 [8]; P=.05). The association with other demographic and economic parameters (eg, sex, race, level of education, income level) was not statistically significant. Proceeding with phototherapy was not related to race, sex, level of education, or income level.

When questioned how many aspects of daily life (eg, work, home, school) were affected by phototherapy, 40% (35/87) of respondents reported that more than one life parameter was disturbed. Thirty-five percent (8/23) of respondents who received phototherapy reported that it affected their daily life “quite a bit” or “severely.” More respondents were likely to report that the therapy interfered with their life “somewhat,” “quite a bit,” or “severely” (76% [19/25]; 95% confidence interval, 55%-92%; P=.01) rather than “not at all” or “a little.”

Excimer Laser

Nine of 17 respondents (53%) who were recommended to undergo excimer laser therapy actually received therapy and reported paying $100 weekly (IQR=$60).

There was a trend toward significance of excimer usage being associated with lower age quartile (0–20 years)(P=.0553) and income more than $100,000 (P=.0788), neither of which reached statistical significance.

Insurance Coverage

Respondents were offered 7 answer options regarding the reason for noncoverage of topical calcineurin inhibitors. They were allowed to pick more than one reason where appropriate. For individuals who were prescribed topical tacrolimus but did not receive drug (n=17), the following reasons were cited: “no insurance coverage for the medication” (59% [10/17]), “your deductible was too high” (24% [4/17]), “prior authorization failed to produce coverage of the medication” (24% [4/17]), “your copay was prohibitively expensive” (24% [4/17]), “you were uncomfortable with the medication’s side effects” (18% [3/17]), “the tube was too small to cover your skin affected areas” (12% [2/17]), and “other” (29% [5/17]). Three patients selected 3 or more reasons, 8 patients selected 2 reasons, and 5 patients selected one reason.

Comment

It has been reported that patients with vitiligo may have difficulty related to treatment compliance for a variety of reasons.⁵ We identified notable barriers that arise for some, if not all, patients with vitiligo in the United States at some point in their care, including interference with other aspects of daily life, lack of coverage by current health insurance provider, and high out-of-pocket expenses, in addition to the negative effects of vitiligo on quality of life that have already been reported.^6,7 These barriers are not a function of race/ethnicity, income level, or age of onset, but they may be impacted, as in the case of tacrolimus, by female sex. It is clear that, based on this study’s numbers, many patients will be unable to receive and/or comply with recommended treatment plans.

A limitation of this analysis is the study population, a select group of patients who had not been prescribed all the therapies in question. The sample size may not be large enough to demonstrate differences between level of education, race, or income level; however, even with a sample size of 87 respondents, the barriers to access of care are prominent. Larger population-based surveys would potentially tease out patterns of barriers not apparent with a smaller sample. No data were generated specific to calcipotriene, and this medication was not specified as a write-in agent on open question by any respondents; therefore, access to topical calcipotriene cannot be projected from this study. Phototherapy was queried as a nonspecific term and the breakdown of NB-UVB versus psoralen plus UVA was not available for this survey. Data suggesting a burden of socioeconomic barriers have been reported for atopic dermatitis⁸ and psoriasis,⁹ which corroborate the need for greater research in the field of access to care in dermatology.

Despite some advancement in the care of vitiligo, patients often are unable to access preferred or recommended treatment modalities. Standard recommendations for care are initial usage of calcineurin inhibitors for facial involvement and topical high-potency corticosteroids for involvement of the body.^3,4 Based on this survey, it would seem that many patients are not able to receive the standard of care. Similarly, NB-UVB phototherapy and excimer laser therapy are recommended for widespread vitiligo and lesions unresponsive to topical care. It would seem that almost half of our respondents did not have access to one or more of the recommended therapies. Barriers to care may have substantial clinical and psychological outcomes, which were not evaluated in this study but merit future research.

Vitiligo is a disorder typified by loss of pigmentation. Worldwide estimates of disease demonstrate 0.4% to 2% prevalence.¹ Vitiligo generally is felt to be an autoimmune disorder with a complex multifactorial inheritance.² Therapeutic options for vitiligo are largely off label and include topical corticosteroids, topical calcineurin inhibitors, narrowband UVB (NB-UVB) light phototherapy, and excimer (308 nm) laser therapy.^3,4 Therapies for vitiligo are time consuming, as most topical therapies require twice-daily application. Additionally, many patients require 2 or more topical therapies due to involvement of both the head and neck as well as other body sites.^3,4 Generalized disease often is treated with NB-UVB therapy 3 times weekly in-office visits, while excimer laser therapy is used for limited disease resistant to topical agents.^3,4

Many barriers to good outcomes and care exist for patients with vitiligo.⁵ Patients may experience reduced quality of life and/or sexual dysfunction because of vitiligo lesions. The purpose of this pilot study was to identify barriers to access of care in vitiligo patients.

Methods

A survey was designed and then reviewed for unclear wording by members of the local vitiligo support group at Mount Sinai St. Luke’s-Roosevelt Hospital and Beth Israel Medical Centers (New York, New York). Linguistic revision and clarifications were added to the survey to correct identified communication problems. The survey was then posted using an Internet-based survey software. Links to the survey were sent via email to 107 individuals in a LISTSERV comprising Vitiligo Support International members who participated in a New York City support group (led by C.G. and N.B.S.). Only 1 email was used per household and only individuals 18 years or older could participate. These individuals were asked to complete a deidentified, 82-question, institutional review board–reviewed and exempted survey addressing issues affecting delivery and receipt of medical care for vitiligo.

Data were analyzed using the χ² test, analysis of variance, or Student t test depending on the type of variable (categorical vs continuous). Fisher exact or Wilcoxon-Mann-Whitney tests were used when distributional assumptions were not met. A type I error rate (α=.05) was used to determine statistical significance. All analyses were performed using SAS 9.3 software.

Results

Respondents

The survey was completed by 81% (n=87) of individuals. The mean (SD) age of the treated patients about whom the respondents communicated was 33 (16) years and 71% (n=62) were women. The majority of respondents (64 [74%]) reported their race as white, followed by African American/black (12 [14%]), Hispanic (7 [8%]), and Asian (4 [5%]). Twenty-nine percent (22/76) of respondents reported a family income of less than $50,000 per year, 34% (26/76) reported an income of $50,000 to $100,000, and 37% (28/76) reported an income greater than $100,000, while 11 respondents did not report income.

Number of Physicians Seen

Respondents had reportedly seen an average (SD) number of 2 (1) physicians in the past/present before being offered any therapy for vitiligo and only 37% (32/87) of respondents reported being offered therapy by the first physician they saw. The number of physicians seen did not have a statistical relationship with years with vitiligo (ie, disease duration), sex, race, age of onset, income level, or number of sites affected.

Number of Sites Affected

The survey identified the following 23 sites affected by vitiligo: scalp, forehead, eyelids, lips, nose, cheeks, chin, neck, chest, stomach, back, upper arms, forearms, hands, wrists, fingers, genitalia, buttocks, thighs, calves/shins, ankles, feet, and toes. The average (SD) number of sites affected was 12 (6). The number of sites affected was correlated to the recommendation for phototherapy, while the recommendation for excimer laser therapy was inversely associated with the number of sites affected. The median number of sites affected for those who were not prescribed phototherapy was 10 (interquartile range [IQR]=9; P=.05); the median number of sites affected for those who were prescribed phototherapy was 15 (IQR=11). The association between the number of sites affected and whether the patient proceeded with phototherapy was not statistically significant. The need for phototherapy was not related to years with vitiligo (ie, disease duration), sex, or race.

Excimer laser therapy was prescribed more often to patients with fewer sites affected (median of 9 [IQR=3] vs median of 15 [IQR=9]; P=.04). Respondents who had fewer sites affected were on average more likely to proceed with excimer laser therapy (median of 8 [IQR=4] vs median of 11 [IQR=5]). The association between the number of sites affected and whether the patient proceeded with excimer laser therapy was not statistically significant.

Access to Topical Medications

Forty-one percent (36/87) of respondents reported difficulty accessing 1 or more topical therapies. Of 52 respondents who were prescribed a topical corticosteroid, 12 (23%) reported difficulty accessing therapy. Of 67 respondents who were prescribed a topical calcineurin inhibitor, 27 (40%) reported difficulty accessing medication (tacrolimus, n=17; pimecrolimus, n=10). Calcipotriene prescription coverage was not specifically addressed in this survey, as it usually is a second-line or adjunctive medication. Difficulty getting topical tacrolimus but not topical corticosteroids was associated with female sex (P=.03) but was not associated with race, income level, or level of education. Difficulty obtaining medication was not related to race, sex, level of education, or income level.

Consequences of Phototherapy

Twenty-three of 34 respondents (68%) who were told they required phototherapy actually received phototherapy and reported paying $38 weekly (IQR=$75). The majority of patients who proceeded with phototherapy lived (17/23 [74%]) or worked (16/23 [70%]) within 20 minutes of the therapy center. Self-reported response to phototherapy was good to very good in 65% (15/23) of respondents and no response in 30% (7/23); only 1 respondent reported worsening vitiligo. Sixty percent (15/25) of respondents said they were not satisfied with phototherapy. Respondents who were satisfied with the outcome of phototherapy had on average fewer sites affected by vitiligo (mean [SD], 10 [8]; P=.05). The association with other demographic and economic parameters (eg, sex, race, level of education, income level) was not statistically significant. Proceeding with phototherapy was not related to race, sex, level of education, or income level.

When questioned how many aspects of daily life (eg, work, home, school) were affected by phototherapy, 40% (35/87) of respondents reported that more than one life parameter was disturbed. Thirty-five percent (8/23) of respondents who received phototherapy reported that it affected their daily life “quite a bit” or “severely.” More respondents were likely to report that the therapy interfered with their life “somewhat,” “quite a bit,” or “severely” (76% [19/25]; 95% confidence interval, 55%-92%; P=.01) rather than “not at all” or “a little.”

Excimer Laser

Nine of 17 respondents (53%) who were recommended to undergo excimer laser therapy actually received therapy and reported paying $100 weekly (IQR=$60).

There was a trend toward significance of excimer usage being associated with lower age quartile (0–20 years)(P=.0553) and income more than $100,000 (P=.0788), neither of which reached statistical significance.

Insurance Coverage

Respondents were offered 7 answer options regarding the reason for noncoverage of topical calcineurin inhibitors. They were allowed to pick more than one reason where appropriate. For individuals who were prescribed topical tacrolimus but did not receive drug (n=17), the following reasons were cited: “no insurance coverage for the medication” (59% [10/17]), “your deductible was too high” (24% [4/17]), “prior authorization failed to produce coverage of the medication” (24% [4/17]), “your copay was prohibitively expensive” (24% [4/17]), “you were uncomfortable with the medication’s side effects” (18% [3/17]), “the tube was too small to cover your skin affected areas” (12% [2/17]), and “other” (29% [5/17]). Three patients selected 3 or more reasons, 8 patients selected 2 reasons, and 5 patients selected one reason.

Comment

It has been reported that patients with vitiligo may have difficulty related to treatment compliance for a variety of reasons.⁵ We identified notable barriers that arise for some, if not all, patients with vitiligo in the United States at some point in their care, including interference with other aspects of daily life, lack of coverage by current health insurance provider, and high out-of-pocket expenses, in addition to the negative effects of vitiligo on quality of life that have already been reported.^6,7 These barriers are not a function of race/ethnicity, income level, or age of onset, but they may be impacted, as in the case of tacrolimus, by female sex. It is clear that, based on this study’s numbers, many patients will be unable to receive and/or comply with recommended treatment plans.

A limitation of this analysis is the study population, a select group of patients who had not been prescribed all the therapies in question. The sample size may not be large enough to demonstrate differences between level of education, race, or income level; however, even with a sample size of 87 respondents, the barriers to access of care are prominent. Larger population-based surveys would potentially tease out patterns of barriers not apparent with a smaller sample. No data were generated specific to calcipotriene, and this medication was not specified as a write-in agent on open question by any respondents; therefore, access to topical calcipotriene cannot be projected from this study. Phototherapy was queried as a nonspecific term and the breakdown of NB-UVB versus psoralen plus UVA was not available for this survey. Data suggesting a burden of socioeconomic barriers have been reported for atopic dermatitis⁸ and psoriasis,⁹ which corroborate the need for greater research in the field of access to care in dermatology.

Despite some advancement in the care of vitiligo, patients often are unable to access preferred or recommended treatment modalities. Standard recommendations for care are initial usage of calcineurin inhibitors for facial involvement and topical high-potency corticosteroids for involvement of the body.^3,4 Based on this survey, it would seem that many patients are not able to receive the standard of care. Similarly, NB-UVB phototherapy and excimer laser therapy are recommended for widespread vitiligo and lesions unresponsive to topical care. It would seem that almost half of our respondents did not have access to one or more of the recommended therapies. Barriers to care may have substantial clinical and psychological outcomes, which were not evaluated in this study but merit future research.

SAN FRANCISCO – Obesity is a multifactorial problem, influenced by factors ranging from genetics to lifestyle to the environment. Yet stress can play an outsize role in obesity as well, Elizabeth Prout Parks, MD, said at the annual meeting of the American Academy of Pediatrics.

Although the calorie-in/calorie-out model of energy balance has driven much of the thought about obesity, it’s not that simple, suggested Dr. Parks, the medical director of the Healthy Weight Adolescent Bariatrics Program at the Children’s Hospital of Philadelphia. Physical activity accounts for an estimated 15%-30% of energy expenditure, and thermogenesis accounts for an estimated 10%. But the energy expenditure required for basal metabolism can range from 60% to 75%, a sufficiently wide range for significant variation across different individuals.

Pressmaster/iStockphoto.com

The psychosocial effects can lead to anxiety, depression, disordered eating behaviors such as emotional eating, a sedentary lifestyle, poor sleep, and low maintenance with self-care activities. Further, poor sleep on its own is additionally associated with childhood obesity. The combination of these physiologic and psychosocial effects can increase the risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease or events. While acute stress and chronic stress follow similar pathways in the brain, it’s chronic stress that carries the greater risk of behavioral and physical conditions.

Measuring and understanding child and parental stress

Several clinical assessments can measure stress in children, including the Daily Hassles Scale, which looks at everyday interactions in the environment and factors such as children’s school, family, neighborhood, peers, and lack of resources. The Multidimensional Life Events Rating Questionnaire and Adolescent Stress Questionnaire both are more appropriate for middle school and older adolescents.

In children, the primary biologic indicators of stress are cortisol levels, heart rate, and blood pressure, but it is perceived stress that has been most clearly linked to emotional eating and other disordered eating behaviors, Dr. Parks said. One 2008 study found perceived stress to be associated with emotional eating among middle school students both with and without obesity. A high level of perceived stress in adolescents was associated with a greater waist circumference and body mass index in a 2009 study.

The findings are somewhat more mixed, however, when it comes to parental stress and child weight. A 2012 study identified a link between parents’ perception of their stress and increased fast food consumption in their children, and a 2008 study identified a link between parenting stress and both overweight and underweight children. Yet a different study in 2008 found no association between child obesity and parenting stress. Research in 2011 found a relationship between children’s consumption of fruits and vegetables and their family’s overall functioning, as well as parental psychological stress and child behavior. Within a family, stress can come from financial strain (such as poverty or changes in employment or insurance), the family’s structure, and changes in physical or mental health of one or more family members.
 

Addressing the effects of stress on diet

Clinicians can help families manage the ways stress can lead to obesity by helping them with ideas for increasing fruit and vegetable intake, and planning ahead for on-the-go eating. For example, to ensure children get in their recommended five servings of fruit and vegetables each day, parents can serve fruit with breakfast every day and offer vegetables and/or fruit as a snack. Including side salads and a frozen vegetable with dinner will add two more servings, and children can munch on chopped veggies while parents prepare dinner. Offering fruit as a dessert provides another opportunity to bump up kids’ fruit and veggie intake, Dr. Parks said.

To manage the risk of unhealthy eating when out and about, Dr. Parks recommends planning ahead by packing a snack such as yogurt, fruit and vegetables, a sandwich or wrap, and water.

She described the “apple test” for determining whether someone is eating because of boredom or stress or because of actual hunger.“The next time you are thinking about a mini meal or second helpings at a meal, ask yourself, ‘Would I eat an apple instead?’ ” Dr. Parks said. “If the answer is no, then you probably are not really hungry and just need to get away from food.”

Other things people can consider when about to eat something are whether they are actually hungry and whether a distraction such as the television is contributing to distracted eating. “People may eat when they’re happy, sad, or bored,” Dr. Parks said, noting that outside messages such as commercials, advertisements, and passing restaurants may make someone feel like eating even if they don’t need sustenance at that moment. “Consider whether you really are hungry before you eat,” she said.
 

Avoiding emotional eating and using mindfulness

Additionally, parents and children can avoid emotional eating by skipping the food when they feel angry, tired, nervous, bored, or sad, instead choosing activities such as journaling, taking a walk, listening to music, reading a book, or taking deep breaths while thinking pleasant thoughts. It’s only time to eat if you physically feel hungry, your stomach is rumbling, you are not craving some specific sweet or salty food, or it’s a meal or snack time (or at least 2.5-4 hours since the last time you ate).

Dr. Parks also reviewed ways that mindfulness may help reduce the risk of obesity by reducing stress, enhancing a person’s ability to regulate their everyday behaviors, and teaching individuals to accept discomfort. Another stress reduction strategy is repeated use of “4-7-8 breathing,” which begins with exhalation while the mouth is closed. Then, inhale through the nose for 4 seconds, hold the breath for 7 seconds and slowly exhale out the mouth for 8 seconds.

Reducing the risk of obesity from stress comes from learning to manage stress. Clinicians can play a role in helping both parents and children learn strategies to manage and cope with stress in the short term while developing resilience over the longer term and reducing the likelihood of poor eating and emotional eating.

Dr. Parks reported no disclosures.

[email protected]

SAN FRANCISCO – Obesity is a multifactorial problem, influenced by factors ranging from genetics to lifestyle to the environment. Yet stress can play an outsize role in obesity as well, Elizabeth Prout Parks, MD, said at the annual meeting of the American Academy of Pediatrics.

Although the calorie-in/calorie-out model of energy balance has driven much of the thought about obesity, it’s not that simple, suggested Dr. Parks, the medical director of the Healthy Weight Adolescent Bariatrics Program at the Children’s Hospital of Philadelphia. Physical activity accounts for an estimated 15%-30% of energy expenditure, and thermogenesis accounts for an estimated 10%. But the energy expenditure required for basal metabolism can range from 60% to 75%, a sufficiently wide range for significant variation across different individuals.

Pressmaster/iStockphoto.com

The psychosocial effects can lead to anxiety, depression, disordered eating behaviors such as emotional eating, a sedentary lifestyle, poor sleep, and low maintenance with self-care activities. Further, poor sleep on its own is additionally associated with childhood obesity. The combination of these physiologic and psychosocial effects can increase the risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease or events. While acute stress and chronic stress follow similar pathways in the brain, it’s chronic stress that carries the greater risk of behavioral and physical conditions.

Measuring and understanding child and parental stress

Several clinical assessments can measure stress in children, including the Daily Hassles Scale, which looks at everyday interactions in the environment and factors such as children’s school, family, neighborhood, peers, and lack of resources. The Multidimensional Life Events Rating Questionnaire and Adolescent Stress Questionnaire both are more appropriate for middle school and older adolescents.

In children, the primary biologic indicators of stress are cortisol levels, heart rate, and blood pressure, but it is perceived stress that has been most clearly linked to emotional eating and other disordered eating behaviors, Dr. Parks said. One 2008 study found perceived stress to be associated with emotional eating among middle school students both with and without obesity. A high level of perceived stress in adolescents was associated with a greater waist circumference and body mass index in a 2009 study.

The findings are somewhat more mixed, however, when it comes to parental stress and child weight. A 2012 study identified a link between parents’ perception of their stress and increased fast food consumption in their children, and a 2008 study identified a link between parenting stress and both overweight and underweight children. Yet a different study in 2008 found no association between child obesity and parenting stress. Research in 2011 found a relationship between children’s consumption of fruits and vegetables and their family’s overall functioning, as well as parental psychological stress and child behavior. Within a family, stress can come from financial strain (such as poverty or changes in employment or insurance), the family’s structure, and changes in physical or mental health of one or more family members.
 

Addressing the effects of stress on diet

Clinicians can help families manage the ways stress can lead to obesity by helping them with ideas for increasing fruit and vegetable intake, and planning ahead for on-the-go eating. For example, to ensure children get in their recommended five servings of fruit and vegetables each day, parents can serve fruit with breakfast every day and offer vegetables and/or fruit as a snack. Including side salads and a frozen vegetable with dinner will add two more servings, and children can munch on chopped veggies while parents prepare dinner. Offering fruit as a dessert provides another opportunity to bump up kids’ fruit and veggie intake, Dr. Parks said.

To manage the risk of unhealthy eating when out and about, Dr. Parks recommends planning ahead by packing a snack such as yogurt, fruit and vegetables, a sandwich or wrap, and water.

She described the “apple test” for determining whether someone is eating because of boredom or stress or because of actual hunger.“The next time you are thinking about a mini meal or second helpings at a meal, ask yourself, ‘Would I eat an apple instead?’ ” Dr. Parks said. “If the answer is no, then you probably are not really hungry and just need to get away from food.”

Other things people can consider when about to eat something are whether they are actually hungry and whether a distraction such as the television is contributing to distracted eating. “People may eat when they’re happy, sad, or bored,” Dr. Parks said, noting that outside messages such as commercials, advertisements, and passing restaurants may make someone feel like eating even if they don’t need sustenance at that moment. “Consider whether you really are hungry before you eat,” she said.
 

Avoiding emotional eating and using mindfulness

Additionally, parents and children can avoid emotional eating by skipping the food when they feel angry, tired, nervous, bored, or sad, instead choosing activities such as journaling, taking a walk, listening to music, reading a book, or taking deep breaths while thinking pleasant thoughts. It’s only time to eat if you physically feel hungry, your stomach is rumbling, you are not craving some specific sweet or salty food, or it’s a meal or snack time (or at least 2.5-4 hours since the last time you ate).

Dr. Parks also reviewed ways that mindfulness may help reduce the risk of obesity by reducing stress, enhancing a person’s ability to regulate their everyday behaviors, and teaching individuals to accept discomfort. Another stress reduction strategy is repeated use of “4-7-8 breathing,” which begins with exhalation while the mouth is closed. Then, inhale through the nose for 4 seconds, hold the breath for 7 seconds and slowly exhale out the mouth for 8 seconds.

Reducing the risk of obesity from stress comes from learning to manage stress. Clinicians can play a role in helping both parents and children learn strategies to manage and cope with stress in the short term while developing resilience over the longer term and reducing the likelihood of poor eating and emotional eating.

Dr. Parks reported no disclosures.

[email protected]

SAN FRANCISCO – Obesity is a multifactorial problem, influenced by factors ranging from genetics to lifestyle to the environment. Yet stress can play an outsize role in obesity as well, Elizabeth Prout Parks, MD, said at the annual meeting of the American Academy of Pediatrics.

Although the calorie-in/calorie-out model of energy balance has driven much of the thought about obesity, it’s not that simple, suggested Dr. Parks, the medical director of the Healthy Weight Adolescent Bariatrics Program at the Children’s Hospital of Philadelphia. Physical activity accounts for an estimated 15%-30% of energy expenditure, and thermogenesis accounts for an estimated 10%. But the energy expenditure required for basal metabolism can range from 60% to 75%, a sufficiently wide range for significant variation across different individuals.

Pressmaster/iStockphoto.com

The psychosocial effects can lead to anxiety, depression, disordered eating behaviors such as emotional eating, a sedentary lifestyle, poor sleep, and low maintenance with self-care activities. Further, poor sleep on its own is additionally associated with childhood obesity. The combination of these physiologic and psychosocial effects can increase the risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease or events. While acute stress and chronic stress follow similar pathways in the brain, it’s chronic stress that carries the greater risk of behavioral and physical conditions.

Measuring and understanding child and parental stress

Several clinical assessments can measure stress in children, including the Daily Hassles Scale, which looks at everyday interactions in the environment and factors such as children’s school, family, neighborhood, peers, and lack of resources. The Multidimensional Life Events Rating Questionnaire and Adolescent Stress Questionnaire both are more appropriate for middle school and older adolescents.

In children, the primary biologic indicators of stress are cortisol levels, heart rate, and blood pressure, but it is perceived stress that has been most clearly linked to emotional eating and other disordered eating behaviors, Dr. Parks said. One 2008 study found perceived stress to be associated with emotional eating among middle school students both with and without obesity. A high level of perceived stress in adolescents was associated with a greater waist circumference and body mass index in a 2009 study.

The findings are somewhat more mixed, however, when it comes to parental stress and child weight. A 2012 study identified a link between parents’ perception of their stress and increased fast food consumption in their children, and a 2008 study identified a link between parenting stress and both overweight and underweight children. Yet a different study in 2008 found no association between child obesity and parenting stress. Research in 2011 found a relationship between children’s consumption of fruits and vegetables and their family’s overall functioning, as well as parental psychological stress and child behavior. Within a family, stress can come from financial strain (such as poverty or changes in employment or insurance), the family’s structure, and changes in physical or mental health of one or more family members.
 

Addressing the effects of stress on diet

Clinicians can help families manage the ways stress can lead to obesity by helping them with ideas for increasing fruit and vegetable intake, and planning ahead for on-the-go eating. For example, to ensure children get in their recommended five servings of fruit and vegetables each day, parents can serve fruit with breakfast every day and offer vegetables and/or fruit as a snack. Including side salads and a frozen vegetable with dinner will add two more servings, and children can munch on chopped veggies while parents prepare dinner. Offering fruit as a dessert provides another opportunity to bump up kids’ fruit and veggie intake, Dr. Parks said.

To manage the risk of unhealthy eating when out and about, Dr. Parks recommends planning ahead by packing a snack such as yogurt, fruit and vegetables, a sandwich or wrap, and water.

She described the “apple test” for determining whether someone is eating because of boredom or stress or because of actual hunger.“The next time you are thinking about a mini meal or second helpings at a meal, ask yourself, ‘Would I eat an apple instead?’ ” Dr. Parks said. “If the answer is no, then you probably are not really hungry and just need to get away from food.”

Other things people can consider when about to eat something are whether they are actually hungry and whether a distraction such as the television is contributing to distracted eating. “People may eat when they’re happy, sad, or bored,” Dr. Parks said, noting that outside messages such as commercials, advertisements, and passing restaurants may make someone feel like eating even if they don’t need sustenance at that moment. “Consider whether you really are hungry before you eat,” she said.
 

Avoiding emotional eating and using mindfulness

Additionally, parents and children can avoid emotional eating by skipping the food when they feel angry, tired, nervous, bored, or sad, instead choosing activities such as journaling, taking a walk, listening to music, reading a book, or taking deep breaths while thinking pleasant thoughts. It’s only time to eat if you physically feel hungry, your stomach is rumbling, you are not craving some specific sweet or salty food, or it’s a meal or snack time (or at least 2.5-4 hours since the last time you ate).

Dr. Parks also reviewed ways that mindfulness may help reduce the risk of obesity by reducing stress, enhancing a person’s ability to regulate their everyday behaviors, and teaching individuals to accept discomfort. Another stress reduction strategy is repeated use of “4-7-8 breathing,” which begins with exhalation while the mouth is closed. Then, inhale through the nose for 4 seconds, hold the breath for 7 seconds and slowly exhale out the mouth for 8 seconds.

Reducing the risk of obesity from stress comes from learning to manage stress. Clinicians can play a role in helping both parents and children learn strategies to manage and cope with stress in the short term while developing resilience over the longer term and reducing the likelihood of poor eating and emotional eating.

Dr. Parks reported no disclosures.

[email protected]