Article

Key clinical point: Fetal cerebral blood flow redistribution assessed by antenatal Doppler scanning is a strong and independent indicator of a composite adverse perinatal outcome (CAPO) and stillbirth in low-resource settings.

Main finding: Middle cerebral artery pulsatility index (PI) <5^th percentile (adjusted odds ratio [aOR] 2.08; P = .013), cerebroplacental ratio (CPR) <5^th percentile (aOR 2.22; P = .02), and uterine artery PI >95^th percentile (aOR 2.36; P = .041) showed a significant association with CAPO. CPR <5^th percentile was significantly associated with stillbirth (aOR 4.82; P = .038).

Study details: Findings are from a single-center prospective cohort study including 995 singleton pregnant women who enrolled in antenatal care after <24 weeks of pregnancy and showed no obvious fetal abnormalities on an antenatal ultrasound scan.

Disclosures: The study was sponsored by Grand Challenges Canada and University Medical Center Utrecht, The Netherlands. No conflict of interests was reported.

Source: Ali S et al. BJOG. 2022 (Feb 4). Doi: 10.1111/1471-0528.17115.

Key clinical point: Fetal cerebral blood flow redistribution assessed by antenatal Doppler scanning is a strong and independent indicator of a composite adverse perinatal outcome (CAPO) and stillbirth in low-resource settings.

Main finding: Middle cerebral artery pulsatility index (PI) <5^th percentile (adjusted odds ratio [aOR] 2.08; P = .013), cerebroplacental ratio (CPR) <5^th percentile (aOR 2.22; P = .02), and uterine artery PI >95^th percentile (aOR 2.36; P = .041) showed a significant association with CAPO. CPR <5^th percentile was significantly associated with stillbirth (aOR 4.82; P = .038).

Study details: Findings are from a single-center prospective cohort study including 995 singleton pregnant women who enrolled in antenatal care after <24 weeks of pregnancy and showed no obvious fetal abnormalities on an antenatal ultrasound scan.

Disclosures: The study was sponsored by Grand Challenges Canada and University Medical Center Utrecht, The Netherlands. No conflict of interests was reported.

Source: Ali S et al. BJOG. 2022 (Feb 4). Doi: 10.1111/1471-0528.17115.

Key clinical point: Fetal cerebral blood flow redistribution assessed by antenatal Doppler scanning is a strong and independent indicator of a composite adverse perinatal outcome (CAPO) and stillbirth in low-resource settings.

Main finding: Middle cerebral artery pulsatility index (PI) <5^th percentile (adjusted odds ratio [aOR] 2.08; P = .013), cerebroplacental ratio (CPR) <5^th percentile (aOR 2.22; P = .02), and uterine artery PI >95^th percentile (aOR 2.36; P = .041) showed a significant association with CAPO. CPR <5^th percentile was significantly associated with stillbirth (aOR 4.82; P = .038).

Study details: Findings are from a single-center prospective cohort study including 995 singleton pregnant women who enrolled in antenatal care after <24 weeks of pregnancy and showed no obvious fetal abnormalities on an antenatal ultrasound scan.

Disclosures: The study was sponsored by Grand Challenges Canada and University Medical Center Utrecht, The Netherlands. No conflict of interests was reported.

Source: Ali S et al. BJOG. 2022 (Feb 4). Doi: 10.1111/1471-0528.17115.

Key clinical point: In women at low risk for aneuploidy, single-nucleotide polymorphism-based cell-free DNA (cfDNA) screening for trisomies 21, 18, and 13 (T21, T18, T13, respectively) demonstrates similar high sensitivity, specificity, and positive predictive value (PPV) as those in high-risk women.

Main finding: In low-risk vs. high-risk women, T21 was detected with similar sensitivity (100% vs. 98.8%; P = 1.0), specificity (99.98% vs. 99.96%; P = .61), and a high PPV (85.71% vs. 97.53%; P = .06), with analogous results for T18 and T13.

Study details: Findings are from a multicenter, prospective, observational SMART study including 17,851 pregnant women undergoing cfDNA screening for aneuploidy and 22q11.2DS, along with DNA analysis of the fetus or newborn. Of these, 13,043 pregnancies were at low risk for aneuploidy, with the rest being high risk.

Disclosures: The study was funded by Natera, Inc, CA, USA. Some of the authors, including the lead author, received institutional research support from Natera. M Egbert, Z Demko, M Rabinowitz, and K Martin serve as an employee/consultant of Natera and own stocks/options. J Hyett has participated in expert consultancies for and B Jacobson reports research clinical diagnostic trials with Natera, among others.

Source: Dar P et al. Am J Obstet Gynecol. 2022 (Jan 24). Doi: 10.1016/j.ajog.2022.01.019.

Key clinical point: In women at low risk for aneuploidy, single-nucleotide polymorphism-based cell-free DNA (cfDNA) screening for trisomies 21, 18, and 13 (T21, T18, T13, respectively) demonstrates similar high sensitivity, specificity, and positive predictive value (PPV) as those in high-risk women.

Main finding: In low-risk vs. high-risk women, T21 was detected with similar sensitivity (100% vs. 98.8%; P = 1.0), specificity (99.98% vs. 99.96%; P = .61), and a high PPV (85.71% vs. 97.53%; P = .06), with analogous results for T18 and T13.

Study details: Findings are from a multicenter, prospective, observational SMART study including 17,851 pregnant women undergoing cfDNA screening for aneuploidy and 22q11.2DS, along with DNA analysis of the fetus or newborn. Of these, 13,043 pregnancies were at low risk for aneuploidy, with the rest being high risk.

Disclosures: The study was funded by Natera, Inc, CA, USA. Some of the authors, including the lead author, received institutional research support from Natera. M Egbert, Z Demko, M Rabinowitz, and K Martin serve as an employee/consultant of Natera and own stocks/options. J Hyett has participated in expert consultancies for and B Jacobson reports research clinical diagnostic trials with Natera, among others.

Source: Dar P et al. Am J Obstet Gynecol. 2022 (Jan 24). Doi: 10.1016/j.ajog.2022.01.019.

Key clinical point: In women at low risk for aneuploidy, single-nucleotide polymorphism-based cell-free DNA (cfDNA) screening for trisomies 21, 18, and 13 (T21, T18, T13, respectively) demonstrates similar high sensitivity, specificity, and positive predictive value (PPV) as those in high-risk women.

Main finding: In low-risk vs. high-risk women, T21 was detected with similar sensitivity (100% vs. 98.8%; P = 1.0), specificity (99.98% vs. 99.96%; P = .61), and a high PPV (85.71% vs. 97.53%; P = .06), with analogous results for T18 and T13.

Study details: Findings are from a multicenter, prospective, observational SMART study including 17,851 pregnant women undergoing cfDNA screening for aneuploidy and 22q11.2DS, along with DNA analysis of the fetus or newborn. Of these, 13,043 pregnancies were at low risk for aneuploidy, with the rest being high risk.

Disclosures: The study was funded by Natera, Inc, CA, USA. Some of the authors, including the lead author, received institutional research support from Natera. M Egbert, Z Demko, M Rabinowitz, and K Martin serve as an employee/consultant of Natera and own stocks/options. J Hyett has participated in expert consultancies for and B Jacobson reports research clinical diagnostic trials with Natera, among others.

Source: Dar P et al. Am J Obstet Gynecol. 2022 (Jan 24). Doi: 10.1016/j.ajog.2022.01.019.

Improved treatments for breast cancer (BC) and effective screening programs have resulted in a BC mortality rate reduction of 41% since 1989.¹ Because BC is the leading cause of cancer in women, these mortality improvements have resulted in more than 3 million BC survivors in the United States.^2,3 With longer-term survival, there is increasing interest in late-onset recurrences.^4,5 A recent study has provided an improved understanding of the risk of lateonset recurrence in women with 10 years of disease-free survival, an important finding for women’s health providers because oncologists do not typically follow survivors after 10 years of disease-free survival.⁴

Recent study looks at incidence of late-onset recurrence

Pederson and colleagues evaluated all patients diagnosed with BC in Denmark from 1987 through 2004.⁴ Those patients without evidence of recurrence at 10 years were then followed utilizing population-based linked registries to identify patients who subsequently developed a local, regional, or distant late-onset recurrence. The authors evaluated the frequency of late recurrence and identified associations with demographic and tumor characteristics.

What they found

A total of 36,920 patients were diagnosed with BC in Denmark between 1987-2004, of whom 20,315 (55%) were identified as disease free for at least 10 years. Late-onset recurrence occurred in 2,595 (12.8%) with the strongest associations of recurrence seen in patients who had a tumor size >2 cm and lymph node‒positive (involving 4 or more nodes) disease (24.6%), compared with 12.7% in patients with tumors <2 cm and node-negative disease. Several other factors were associated with a higher risk of late-onset recurrence and are included in the TABLE. Half of the recurrences occurred between 10 and 15 years after the primary diagnosis.

Prior research

These findings are consistent with another recent study showing that BC patients have a 1% to 2%/year risk of recurrence after 10 disease-free years.⁵ Strengths of this study include:

• population-based, including all women with BC
• long-term follow-up for up to 32 years
• universal health care in Denmark, which results in robust and linked databases and very few missing data points.

There were two notable weaknesses to consider:

• Treatment regimens changed considerably during the time frame of the study (1997-2018), particularly the duration of tamoxifen use in patients with HR-positive disease. In this study nearly all patients received 5 years or less of tamoxifen. Since the mid-2010s, 10 years of hormonal adjuvant therapy has become routine in HR-positive BC, which reduces recurrences, including late-onset recurrence.⁶ The effect of 10 years of tamoxifen would very likely have resulted in less late-onset recurrence in the HR-positive population in this study.
• There is a lack of racial diversity in the Danish population, and the study findings may not translate to Black patients who have a higher frequency of triple-negative BC with a different risk of late-onset recurrence.⁷

Practice takeaways

Cancer surveillance. There are 3+ million BC survivors in the United States, and a 55%+ likelihood that they will be disease free for 10 years. This is clearly an important population to the women’s health care provider. This study, and previous research, suggests that among 10-year-disease-free survivors, 1% to 2% will recur annually, with higher rates amongst HR-positive, lymph-node positive women under age 40, and in the first 5 years following the 10-year post–initial diagnosis mark, so ongoing surveillance is imperative. Annual clinical breast examinations along with annual (not biennial) mammography should be performed.⁸ Digital breast tomosynthesis has improved specificity and sensitivity for BC detection and is the preferred modality when it is available.

Management of menopausal symptoms. These findings also have implications for menopausal hormone therapy for patients with symptoms. Because HR-positive patients have an increased risk of late-onset recurrence, nonhormonal therapies should be considered as first-line therapy for patients with menopausal symptoms. If hormone therapy is being considered, providers and patients should use shared decision making to balance the potential benefits (reduction in symptoms, possible cardiovascular benefits, and reduction in bone loss) with the risks (increased risk of recurrence and venous thromboembolism), even if patients are remote from the original diagnosis (ie, 10-year disease-free survival).

Topical estrogen therapies would be preferred for patients with significant urogenital atrophic symptoms who fail nonhormonal therapies due to substantially less systemic absorption and the lack of need to add a progestin.^9,10 If oral therapy is being considered, I carefully counsel these women about the likely increased risk of recurrence and, if possible, include their breast oncologist in the discussion. ●

Improved treatments for breast cancer (BC) and effective screening programs have resulted in a BC mortality rate reduction of 41% since 1989.¹ Because BC is the leading cause of cancer in women, these mortality improvements have resulted in more than 3 million BC survivors in the United States.^2,3 With longer-term survival, there is increasing interest in late-onset recurrences.^4,5 A recent study has provided an improved understanding of the risk of lateonset recurrence in women with 10 years of disease-free survival, an important finding for women’s health providers because oncologists do not typically follow survivors after 10 years of disease-free survival.⁴

Recent study looks at incidence of late-onset recurrence

Pederson and colleagues evaluated all patients diagnosed with BC in Denmark from 1987 through 2004.⁴ Those patients without evidence of recurrence at 10 years were then followed utilizing population-based linked registries to identify patients who subsequently developed a local, regional, or distant late-onset recurrence. The authors evaluated the frequency of late recurrence and identified associations with demographic and tumor characteristics.

What they found

A total of 36,920 patients were diagnosed with BC in Denmark between 1987-2004, of whom 20,315 (55%) were identified as disease free for at least 10 years. Late-onset recurrence occurred in 2,595 (12.8%) with the strongest associations of recurrence seen in patients who had a tumor size >2 cm and lymph node‒positive (involving 4 or more nodes) disease (24.6%), compared with 12.7% in patients with tumors <2 cm and node-negative disease. Several other factors were associated with a higher risk of late-onset recurrence and are included in the TABLE. Half of the recurrences occurred between 10 and 15 years after the primary diagnosis.

Prior research

These findings are consistent with another recent study showing that BC patients have a 1% to 2%/year risk of recurrence after 10 disease-free years.⁵ Strengths of this study include:

• population-based, including all women with BC
• long-term follow-up for up to 32 years
• universal health care in Denmark, which results in robust and linked databases and very few missing data points.

There were two notable weaknesses to consider:

• Treatment regimens changed considerably during the time frame of the study (1997-2018), particularly the duration of tamoxifen use in patients with HR-positive disease. In this study nearly all patients received 5 years or less of tamoxifen. Since the mid-2010s, 10 years of hormonal adjuvant therapy has become routine in HR-positive BC, which reduces recurrences, including late-onset recurrence.⁶ The effect of 10 years of tamoxifen would very likely have resulted in less late-onset recurrence in the HR-positive population in this study.
• There is a lack of racial diversity in the Danish population, and the study findings may not translate to Black patients who have a higher frequency of triple-negative BC with a different risk of late-onset recurrence.⁷

Practice takeaways

Cancer surveillance. There are 3+ million BC survivors in the United States, and a 55%+ likelihood that they will be disease free for 10 years. This is clearly an important population to the women’s health care provider. This study, and previous research, suggests that among 10-year-disease-free survivors, 1% to 2% will recur annually, with higher rates amongst HR-positive, lymph-node positive women under age 40, and in the first 5 years following the 10-year post–initial diagnosis mark, so ongoing surveillance is imperative. Annual clinical breast examinations along with annual (not biennial) mammography should be performed.⁸ Digital breast tomosynthesis has improved specificity and sensitivity for BC detection and is the preferred modality when it is available.

Management of menopausal symptoms. These findings also have implications for menopausal hormone therapy for patients with symptoms. Because HR-positive patients have an increased risk of late-onset recurrence, nonhormonal therapies should be considered as first-line therapy for patients with menopausal symptoms. If hormone therapy is being considered, providers and patients should use shared decision making to balance the potential benefits (reduction in symptoms, possible cardiovascular benefits, and reduction in bone loss) with the risks (increased risk of recurrence and venous thromboembolism), even if patients are remote from the original diagnosis (ie, 10-year disease-free survival).

Topical estrogen therapies would be preferred for patients with significant urogenital atrophic symptoms who fail nonhormonal therapies due to substantially less systemic absorption and the lack of need to add a progestin.^9,10 If oral therapy is being considered, I carefully counsel these women about the likely increased risk of recurrence and, if possible, include their breast oncologist in the discussion. ●

Improved treatments for breast cancer (BC) and effective screening programs have resulted in a BC mortality rate reduction of 41% since 1989.¹ Because BC is the leading cause of cancer in women, these mortality improvements have resulted in more than 3 million BC survivors in the United States.^2,3 With longer-term survival, there is increasing interest in late-onset recurrences.^4,5 A recent study has provided an improved understanding of the risk of lateonset recurrence in women with 10 years of disease-free survival, an important finding for women’s health providers because oncologists do not typically follow survivors after 10 years of disease-free survival.⁴

Recent study looks at incidence of late-onset recurrence

Pederson and colleagues evaluated all patients diagnosed with BC in Denmark from 1987 through 2004.⁴ Those patients without evidence of recurrence at 10 years were then followed utilizing population-based linked registries to identify patients who subsequently developed a local, regional, or distant late-onset recurrence. The authors evaluated the frequency of late recurrence and identified associations with demographic and tumor characteristics.

What they found

A total of 36,920 patients were diagnosed with BC in Denmark between 1987-2004, of whom 20,315 (55%) were identified as disease free for at least 10 years. Late-onset recurrence occurred in 2,595 (12.8%) with the strongest associations of recurrence seen in patients who had a tumor size >2 cm and lymph node‒positive (involving 4 or more nodes) disease (24.6%), compared with 12.7% in patients with tumors <2 cm and node-negative disease. Several other factors were associated with a higher risk of late-onset recurrence and are included in the TABLE. Half of the recurrences occurred between 10 and 15 years after the primary diagnosis.

Prior research

These findings are consistent with another recent study showing that BC patients have a 1% to 2%/year risk of recurrence after 10 disease-free years.⁵ Strengths of this study include:

• population-based, including all women with BC
• long-term follow-up for up to 32 years
• universal health care in Denmark, which results in robust and linked databases and very few missing data points.

There were two notable weaknesses to consider:

• Treatment regimens changed considerably during the time frame of the study (1997-2018), particularly the duration of tamoxifen use in patients with HR-positive disease. In this study nearly all patients received 5 years or less of tamoxifen. Since the mid-2010s, 10 years of hormonal adjuvant therapy has become routine in HR-positive BC, which reduces recurrences, including late-onset recurrence.⁶ The effect of 10 years of tamoxifen would very likely have resulted in less late-onset recurrence in the HR-positive population in this study.
• There is a lack of racial diversity in the Danish population, and the study findings may not translate to Black patients who have a higher frequency of triple-negative BC with a different risk of late-onset recurrence.⁷

Practice takeaways

Cancer surveillance. There are 3+ million BC survivors in the United States, and a 55%+ likelihood that they will be disease free for 10 years. This is clearly an important population to the women’s health care provider. This study, and previous research, suggests that among 10-year-disease-free survivors, 1% to 2% will recur annually, with higher rates amongst HR-positive, lymph-node positive women under age 40, and in the first 5 years following the 10-year post–initial diagnosis mark, so ongoing surveillance is imperative. Annual clinical breast examinations along with annual (not biennial) mammography should be performed.⁸ Digital breast tomosynthesis has improved specificity and sensitivity for BC detection and is the preferred modality when it is available.

Management of menopausal symptoms. These findings also have implications for menopausal hormone therapy for patients with symptoms. Because HR-positive patients have an increased risk of late-onset recurrence, nonhormonal therapies should be considered as first-line therapy for patients with menopausal symptoms. If hormone therapy is being considered, providers and patients should use shared decision making to balance the potential benefits (reduction in symptoms, possible cardiovascular benefits, and reduction in bone loss) with the risks (increased risk of recurrence and venous thromboembolism), even if patients are remote from the original diagnosis (ie, 10-year disease-free survival).

Topical estrogen therapies would be preferred for patients with significant urogenital atrophic symptoms who fail nonhormonal therapies due to substantially less systemic absorption and the lack of need to add a progestin.^9,10 If oral therapy is being considered, I carefully counsel these women about the likely increased risk of recurrence and, if possible, include their breast oncologist in the discussion. ●

Use of positive airway pressure (PAP) devices for treatment of sleep apnea was first described in 1981. Subsequent use of PAP devices expanded to treat patients with respiratory failure. While the treatment in this population has rapidly gained widespread use and undoubtedly has reduced morbidity and mortality in these populations, policies governing these prescriptions have not really kept up with the burgeoning need.

In 2020, Drs. Peter Gay and Robert Owens brought together a technical expert panel (TEP) to systematically review the CMS policies with an eye to remove “regulatory barriers” to improve access for these patients with the mantra: “the right device gets to the right patient at the right time.”

The panel focused on “Optimal NIV Medicare Access Promotion (ONMAP),” and members with specific expertise were recruited for five patient groups: Thoracic Restrictive Disorders (TRD), COPD, Central Sleep Apnea (CSA), Hypoventilation Syndromes (HVS), and Obstructive Sleep Apnea (OSA). Each group reviewed the current coverage, outlined the deficiencies, and suggested revisions. Herein, I will briefly highlight each group’s most important points.
 

TRD: The goal for this group was to bring the US standards of care closer to the rest of the world. This group advocates that the start of noninvasive ventilation (NIV) should be substantially earlier, to provide the largest improvement in disease outcome and stability. Other prominent features submitted included arterial blood gases (ABG) to not be the only form of CO₂ measurement allowed; paying for a second device if patients are using NIV continuously; qualification for a BiPAP to include if vital capacity is ≤ 80%; and, to obtain a home mechanical ventilator, a patient must either fail BiPAP or have extreme loss of function, high pressure requirements, or need mouthpiece ventilation.

CSA: The big challenges with this diagnosis related to qualifying coverage language in the current policies, which are confusing for many providers. Additionally, these policies often deny certain PAP devices and/or oxygen therapy. The group proposed: a single definition of CSA; eliminate discussion of hypoventilation; mirror qualifying symptoms, and, continuing coverage, to the same as that for OSA treatment; and remove need for a prior failure of BiPAP without a backup rate (BUR). The group also had specific recommendations for when oxygen therapy should be covered in patients with CSA.

COPD: This group also focused on the oxygen therapy and promoting use of devices with a BUR. Two problematic areas included the requirement that nocturnal oxygen saturation must drop to ≤ 88% for at least 5 cumulative minutes, and, that patients must begin with an S mode device (no BUR) for at least 2 months and can only then be prescribed a device with a BUR if CO₂ fails to drop. The group advocates for the removal of both, the need for a nocturnal oximetry test, and, to “try” an S mode device. The panel advocated giving the prescribing physician discretion in making this determination. The panel also provided recommendations on when a home mechanical ventilator (HMV) should be considered instead of BiPAP therapy.

HVS: Hypoventilation syndromes are a heterogeneous group of disorders with hypercapnia, defined as a Paco₂ ≥45 mm Hg. This panel noted that the current coverage criteria are outdated and fail to recognize the spectrum of disease severity and advances in technology, which often leads to circumvention by prescribing more costly home mechanical ventilators (HMV). Consistent with the TRD group, this panel recommended acceptance of surrogate noninvasive end tidal and transcutaneous Pco₂ and venous blood gases in lieu of arterial blood gases. Additionally, they suggested no longer requiring CO₂ measures while using prescribed oxygen; eliminating the need for a sleep study to avoid delays in care for patients being discharged from the hospital; removing spirometry as a requirement; and no longer a failure of BiPAP without a BUR.

OSA: The initial purpose of examining OSA in this process was to examine when BiPAP should be utilized for treatment; however, it necessitated examination of the entire policy for PAP. The areas that were identified as needing revision included: expansion of the symptom list for patients with OSA; revising the “4 hour rule,” suggesting that 2 hours has been proven to provide benefit; eliminating the need for another sleep study to re-qualify for PAP or supplemental oxygen; and embracing telehealth as a way to improve accessibility for follow-up visits.

For details, please review the papers published in the November 2021 issue of the journal CHEST^® (2021; 160[5]:1579-1990, e377-e543).

We now await what CMS will do with our recommendations and work for “the right device to the right patient at the right time.”

Acknowledgment: Drs. Gerald Criner, Nicholas Hill, Babak Mohklesi, Timothy Morgenthaler, and Lisa Wolfe assisted with the content.

Use of positive airway pressure (PAP) devices for treatment of sleep apnea was first described in 1981. Subsequent use of PAP devices expanded to treat patients with respiratory failure. While the treatment in this population has rapidly gained widespread use and undoubtedly has reduced morbidity and mortality in these populations, policies governing these prescriptions have not really kept up with the burgeoning need.

In 2020, Drs. Peter Gay and Robert Owens brought together a technical expert panel (TEP) to systematically review the CMS policies with an eye to remove “regulatory barriers” to improve access for these patients with the mantra: “the right device gets to the right patient at the right time.”

The panel focused on “Optimal NIV Medicare Access Promotion (ONMAP),” and members with specific expertise were recruited for five patient groups: Thoracic Restrictive Disorders (TRD), COPD, Central Sleep Apnea (CSA), Hypoventilation Syndromes (HVS), and Obstructive Sleep Apnea (OSA). Each group reviewed the current coverage, outlined the deficiencies, and suggested revisions. Herein, I will briefly highlight each group’s most important points.
 

TRD: The goal for this group was to bring the US standards of care closer to the rest of the world. This group advocates that the start of noninvasive ventilation (NIV) should be substantially earlier, to provide the largest improvement in disease outcome and stability. Other prominent features submitted included arterial blood gases (ABG) to not be the only form of CO₂ measurement allowed; paying for a second device if patients are using NIV continuously; qualification for a BiPAP to include if vital capacity is ≤ 80%; and, to obtain a home mechanical ventilator, a patient must either fail BiPAP or have extreme loss of function, high pressure requirements, or need mouthpiece ventilation.

CSA: The big challenges with this diagnosis related to qualifying coverage language in the current policies, which are confusing for many providers. Additionally, these policies often deny certain PAP devices and/or oxygen therapy. The group proposed: a single definition of CSA; eliminate discussion of hypoventilation; mirror qualifying symptoms, and, continuing coverage, to the same as that for OSA treatment; and remove need for a prior failure of BiPAP without a backup rate (BUR). The group also had specific recommendations for when oxygen therapy should be covered in patients with CSA.

COPD: This group also focused on the oxygen therapy and promoting use of devices with a BUR. Two problematic areas included the requirement that nocturnal oxygen saturation must drop to ≤ 88% for at least 5 cumulative minutes, and, that patients must begin with an S mode device (no BUR) for at least 2 months and can only then be prescribed a device with a BUR if CO₂ fails to drop. The group advocates for the removal of both, the need for a nocturnal oximetry test, and, to “try” an S mode device. The panel advocated giving the prescribing physician discretion in making this determination. The panel also provided recommendations on when a home mechanical ventilator (HMV) should be considered instead of BiPAP therapy.

HVS: Hypoventilation syndromes are a heterogeneous group of disorders with hypercapnia, defined as a Paco₂ ≥45 mm Hg. This panel noted that the current coverage criteria are outdated and fail to recognize the spectrum of disease severity and advances in technology, which often leads to circumvention by prescribing more costly home mechanical ventilators (HMV). Consistent with the TRD group, this panel recommended acceptance of surrogate noninvasive end tidal and transcutaneous Pco₂ and venous blood gases in lieu of arterial blood gases. Additionally, they suggested no longer requiring CO₂ measures while using prescribed oxygen; eliminating the need for a sleep study to avoid delays in care for patients being discharged from the hospital; removing spirometry as a requirement; and no longer a failure of BiPAP without a BUR.

OSA: The initial purpose of examining OSA in this process was to examine when BiPAP should be utilized for treatment; however, it necessitated examination of the entire policy for PAP. The areas that were identified as needing revision included: expansion of the symptom list for patients with OSA; revising the “4 hour rule,” suggesting that 2 hours has been proven to provide benefit; eliminating the need for another sleep study to re-qualify for PAP or supplemental oxygen; and embracing telehealth as a way to improve accessibility for follow-up visits.

For details, please review the papers published in the November 2021 issue of the journal CHEST^® (2021; 160[5]:1579-1990, e377-e543).

We now await what CMS will do with our recommendations and work for “the right device to the right patient at the right time.”

Acknowledgment: Drs. Gerald Criner, Nicholas Hill, Babak Mohklesi, Timothy Morgenthaler, and Lisa Wolfe assisted with the content.

Use of positive airway pressure (PAP) devices for treatment of sleep apnea was first described in 1981. Subsequent use of PAP devices expanded to treat patients with respiratory failure. While the treatment in this population has rapidly gained widespread use and undoubtedly has reduced morbidity and mortality in these populations, policies governing these prescriptions have not really kept up with the burgeoning need.

In 2020, Drs. Peter Gay and Robert Owens brought together a technical expert panel (TEP) to systematically review the CMS policies with an eye to remove “regulatory barriers” to improve access for these patients with the mantra: “the right device gets to the right patient at the right time.”

The panel focused on “Optimal NIV Medicare Access Promotion (ONMAP),” and members with specific expertise were recruited for five patient groups: Thoracic Restrictive Disorders (TRD), COPD, Central Sleep Apnea (CSA), Hypoventilation Syndromes (HVS), and Obstructive Sleep Apnea (OSA). Each group reviewed the current coverage, outlined the deficiencies, and suggested revisions. Herein, I will briefly highlight each group’s most important points.
 

TRD: The goal for this group was to bring the US standards of care closer to the rest of the world. This group advocates that the start of noninvasive ventilation (NIV) should be substantially earlier, to provide the largest improvement in disease outcome and stability. Other prominent features submitted included arterial blood gases (ABG) to not be the only form of CO₂ measurement allowed; paying for a second device if patients are using NIV continuously; qualification for a BiPAP to include if vital capacity is ≤ 80%; and, to obtain a home mechanical ventilator, a patient must either fail BiPAP or have extreme loss of function, high pressure requirements, or need mouthpiece ventilation.

CSA: The big challenges with this diagnosis related to qualifying coverage language in the current policies, which are confusing for many providers. Additionally, these policies often deny certain PAP devices and/or oxygen therapy. The group proposed: a single definition of CSA; eliminate discussion of hypoventilation; mirror qualifying symptoms, and, continuing coverage, to the same as that for OSA treatment; and remove need for a prior failure of BiPAP without a backup rate (BUR). The group also had specific recommendations for when oxygen therapy should be covered in patients with CSA.

COPD: This group also focused on the oxygen therapy and promoting use of devices with a BUR. Two problematic areas included the requirement that nocturnal oxygen saturation must drop to ≤ 88% for at least 5 cumulative minutes, and, that patients must begin with an S mode device (no BUR) for at least 2 months and can only then be prescribed a device with a BUR if CO₂ fails to drop. The group advocates for the removal of both, the need for a nocturnal oximetry test, and, to “try” an S mode device. The panel advocated giving the prescribing physician discretion in making this determination. The panel also provided recommendations on when a home mechanical ventilator (HMV) should be considered instead of BiPAP therapy.

HVS: Hypoventilation syndromes are a heterogeneous group of disorders with hypercapnia, defined as a Paco₂ ≥45 mm Hg. This panel noted that the current coverage criteria are outdated and fail to recognize the spectrum of disease severity and advances in technology, which often leads to circumvention by prescribing more costly home mechanical ventilators (HMV). Consistent with the TRD group, this panel recommended acceptance of surrogate noninvasive end tidal and transcutaneous Pco₂ and venous blood gases in lieu of arterial blood gases. Additionally, they suggested no longer requiring CO₂ measures while using prescribed oxygen; eliminating the need for a sleep study to avoid delays in care for patients being discharged from the hospital; removing spirometry as a requirement; and no longer a failure of BiPAP without a BUR.

OSA: The initial purpose of examining OSA in this process was to examine when BiPAP should be utilized for treatment; however, it necessitated examination of the entire policy for PAP. The areas that were identified as needing revision included: expansion of the symptom list for patients with OSA; revising the “4 hour rule,” suggesting that 2 hours has been proven to provide benefit; eliminating the need for another sleep study to re-qualify for PAP or supplemental oxygen; and embracing telehealth as a way to improve accessibility for follow-up visits.

For details, please review the papers published in the November 2021 issue of the journal CHEST^® (2021; 160[5]:1579-1990, e377-e543).

We now await what CMS will do with our recommendations and work for “the right device to the right patient at the right time.”

Acknowledgment: Drs. Gerald Criner, Nicholas Hill, Babak Mohklesi, Timothy Morgenthaler, and Lisa Wolfe assisted with the content.

As an Advanced Practice Provider, when and why might a patient with uterine fibroids be scheduled to visit with you?

Ms. Haibach: Typically, with the flow of how our practice runs, a patient would schedule with me as an initial visit to explore their abnormal or heavy bleeding. Oftentimes, a patient is unsure with what they have going on medically and will view APPs as a safe place to start. Other times, I will see a patient for a general wellness exam who will mention heavier menses over the years or just a change in their bleeding pattern-- longer flow, things like that.

It may stem from something that seems out of the ordinary for them or a symptom impacting their life. For example, if a patient says, “I have to run home and change my clothes,” or “I'm bleeding through my bed sheets.” Those statements prompt further evaluation. At times, patients who have already been diagnosed with fibroids, will come to see me if they have chosen medical management over surgical management of their fibroids. They continue to follow up with me to reevaluate the success of their treatment plan periodically. So, whether I start them on a plan, or a physician does, they can follow up with me to revisit their medical plan and ensure it remains appropriate.

You touched on this a bit, but can you dive deeper into exactly what you are looking for as part of that visit? 

Ms. Haibach: Definitely. With an initial consult to me, the number one question that I would ask my patients first is, what is your most bothersome symptom? With this question, I'm looking to determine: is it pain that brought you to me? Is it heavy bleeding? Do you feel bulk and bloaty? Are you having issues getting pregnant? Do you have bowel or bladder issues?

The information I get from that one initial question, helps guide the remainder of my visit. If bleeding is the main concern, we would focus on getting that under control. So, we need to suppress the menses with medication options. If bulk and bloating is the main concern, for instance the patient feels like they have a pregnant-looking abdomen, typically surgical options are warranted. If the main complaint is infertility, we do have fertility specialists in our practice who remove fibroids to aid patients in achieving pregnancy.

The most important purpose of this visit is to really listen to the patient to find out how these symptoms are impacting their daily lives. From there, I can use that information to guide my treatment plan.

So, once it is determined that the patient is a good surgical candidate, what would be the next steps?

Ms. Haibach: If at the end of my visit, I determine that a patient is potentially a suitable surgical candidate, the first thing I would do is order appropriate imaging. For example, if the patient is interested in uterine preservation for future fertility, she is likely going to opt for a laparoscopic myomectomy, where fibroids would be removed, and her uterus would be left in place. In that case, she would require an MRI for fibroid mapping. If a woman has completed childbearing, then oftentimes a pelvic ultrasound would suffice, at least to start, since she'd likely elect hysterectomy if she has reached her fertility goals.

I would also perform an endometrial biopsy to rule out malignant process before going into surgery. To optimize a patient for our MIGS surgeons, I gather a thorough medical history to ensure their comorbidities are appropriately managed. For example, diabetes is under control, sleep apnea is being treated, no active infections. If there is anything else going on that needs to be addressed, I'd refer them to the appropriate provider first.

Once I have acceptable imaging, a negative endometrial biopsy and an adequate medical history, I would then assist the patient in scheduling with one of the surgeons on my team for a consult and physical exam to determine surgery planning. Once they see our physician, a surgery date is booked. The patient would come back to see me within 30 days of surgery, and we would do a preoperative education appointment. I see them again 2 weeks after surgery for a post-op visit. We’d perform the post-of visit virtually in our practice. We would see the patient sooner if there are any other concerns that arise post-operatively.

What if the patient is not a surgical candidate? How do you as an APP assist in ongoing medical management?

Ms. Haibach: The presence of fibroids alone, without symptoms, often does not require surgical intervention. There are occasions where a patient is, for example, seen in the emergency room for abdominal pain, whereas they’ll get a CT scan of the abdomen pelvis, and a fibroid is incidentally found. At that point, they are instructed to see gynecology for follow-up. If the patient was unaware of the fibroid, has no symptoms and there's no concerning imaging features, then management with ongoing surveillance (repeat imaging and office follow up) and instructions on when to return is usually appropriate.

Depending on the symptoms, medical management typically includes hormonal suppression of menses in the form of a birth control pill or an IUD. If bleeding is the main concern, it is my goal to at least slow her bleeding, if not try to stop it. Not all women are good candidates for hormone therapy, so there is a medication option that is non-hormonal. In my role, I would start a medication plan for a patient and initiate a new medication such as hormonal suppression in the form of birth control, IUD, non-hormonal medications etc.

Typically, when I do that, I'll have the patient follow up with me in about two to three months to reassess the medication’s effectiveness. The goal of the reassessment is to determine if it is working for her life, to be sure there are no major side-effects, and just to make sure she is amenable to the plan. As part of the medical management, sometimes it is necessary to monitor blood counts for anemia to be certain that medical management is still appropriate for her.

From your experience in practicing, are you more likely to be visited by one age bracket or ethnicity over another? 

Ms. Haibach: Actually, data tells us that most fibroids occur in women of reproductive age. They are also diagnosed in African American women two to three times more frequently than in white women. Fibroids are infrequently seen in premenstrual women. A relief of symptoms of the fibroids often occurs at the time of menopause, when the menstrual cyclicity seizes and steroid hormone levels decrease. My demographic is consistent with the above statistics. I tend to see women within the ages of  20’s-50’s and more often African Americans.

Was there anything else that you'd like to mention?

Ms. Haibach: Abnormal bleeding can be very stressful for women. APPs are a great place to start an abnormal bleeding or fibroid work-up. Patients should rest assure that although we cannot perform surgery, APPs can help get them in the right direction for the best care possible.

As an Advanced Practice Provider, when and why might a patient with uterine fibroids be scheduled to visit with you?

Ms. Haibach: Typically, with the flow of how our practice runs, a patient would schedule with me as an initial visit to explore their abnormal or heavy bleeding. Oftentimes, a patient is unsure with what they have going on medically and will view APPs as a safe place to start. Other times, I will see a patient for a general wellness exam who will mention heavier menses over the years or just a change in their bleeding pattern-- longer flow, things like that.

It may stem from something that seems out of the ordinary for them or a symptom impacting their life. For example, if a patient says, “I have to run home and change my clothes,” or “I'm bleeding through my bed sheets.” Those statements prompt further evaluation. At times, patients who have already been diagnosed with fibroids, will come to see me if they have chosen medical management over surgical management of their fibroids. They continue to follow up with me to reevaluate the success of their treatment plan periodically. So, whether I start them on a plan, or a physician does, they can follow up with me to revisit their medical plan and ensure it remains appropriate.

You touched on this a bit, but can you dive deeper into exactly what you are looking for as part of that visit? 

Ms. Haibach: Definitely. With an initial consult to me, the number one question that I would ask my patients first is, what is your most bothersome symptom? With this question, I'm looking to determine: is it pain that brought you to me? Is it heavy bleeding? Do you feel bulk and bloaty? Are you having issues getting pregnant? Do you have bowel or bladder issues?

The information I get from that one initial question, helps guide the remainder of my visit. If bleeding is the main concern, we would focus on getting that under control. So, we need to suppress the menses with medication options. If bulk and bloating is the main concern, for instance the patient feels like they have a pregnant-looking abdomen, typically surgical options are warranted. If the main complaint is infertility, we do have fertility specialists in our practice who remove fibroids to aid patients in achieving pregnancy.

The most important purpose of this visit is to really listen to the patient to find out how these symptoms are impacting their daily lives. From there, I can use that information to guide my treatment plan.

So, once it is determined that the patient is a good surgical candidate, what would be the next steps?

Ms. Haibach: If at the end of my visit, I determine that a patient is potentially a suitable surgical candidate, the first thing I would do is order appropriate imaging. For example, if the patient is interested in uterine preservation for future fertility, she is likely going to opt for a laparoscopic myomectomy, where fibroids would be removed, and her uterus would be left in place. In that case, she would require an MRI for fibroid mapping. If a woman has completed childbearing, then oftentimes a pelvic ultrasound would suffice, at least to start, since she'd likely elect hysterectomy if she has reached her fertility goals.

I would also perform an endometrial biopsy to rule out malignant process before going into surgery. To optimize a patient for our MIGS surgeons, I gather a thorough medical history to ensure their comorbidities are appropriately managed. For example, diabetes is under control, sleep apnea is being treated, no active infections. If there is anything else going on that needs to be addressed, I'd refer them to the appropriate provider first.

Once I have acceptable imaging, a negative endometrial biopsy and an adequate medical history, I would then assist the patient in scheduling with one of the surgeons on my team for a consult and physical exam to determine surgery planning. Once they see our physician, a surgery date is booked. The patient would come back to see me within 30 days of surgery, and we would do a preoperative education appointment. I see them again 2 weeks after surgery for a post-op visit. We’d perform the post-of visit virtually in our practice. We would see the patient sooner if there are any other concerns that arise post-operatively.

What if the patient is not a surgical candidate? How do you as an APP assist in ongoing medical management?

Ms. Haibach: The presence of fibroids alone, without symptoms, often does not require surgical intervention. There are occasions where a patient is, for example, seen in the emergency room for abdominal pain, whereas they’ll get a CT scan of the abdomen pelvis, and a fibroid is incidentally found. At that point, they are instructed to see gynecology for follow-up. If the patient was unaware of the fibroid, has no symptoms and there's no concerning imaging features, then management with ongoing surveillance (repeat imaging and office follow up) and instructions on when to return is usually appropriate.

Depending on the symptoms, medical management typically includes hormonal suppression of menses in the form of a birth control pill or an IUD. If bleeding is the main concern, it is my goal to at least slow her bleeding, if not try to stop it. Not all women are good candidates for hormone therapy, so there is a medication option that is non-hormonal. In my role, I would start a medication plan for a patient and initiate a new medication such as hormonal suppression in the form of birth control, IUD, non-hormonal medications etc.

Typically, when I do that, I'll have the patient follow up with me in about two to three months to reassess the medication’s effectiveness. The goal of the reassessment is to determine if it is working for her life, to be sure there are no major side-effects, and just to make sure she is amenable to the plan. As part of the medical management, sometimes it is necessary to monitor blood counts for anemia to be certain that medical management is still appropriate for her.

From your experience in practicing, are you more likely to be visited by one age bracket or ethnicity over another? 

Ms. Haibach: Actually, data tells us that most fibroids occur in women of reproductive age. They are also diagnosed in African American women two to three times more frequently than in white women. Fibroids are infrequently seen in premenstrual women. A relief of symptoms of the fibroids often occurs at the time of menopause, when the menstrual cyclicity seizes and steroid hormone levels decrease. My demographic is consistent with the above statistics. I tend to see women within the ages of  20’s-50’s and more often African Americans.

Was there anything else that you'd like to mention?

Ms. Haibach: Abnormal bleeding can be very stressful for women. APPs are a great place to start an abnormal bleeding or fibroid work-up. Patients should rest assure that although we cannot perform surgery, APPs can help get them in the right direction for the best care possible.

As an Advanced Practice Provider, when and why might a patient with uterine fibroids be scheduled to visit with you?

Ms. Haibach: Typically, with the flow of how our practice runs, a patient would schedule with me as an initial visit to explore their abnormal or heavy bleeding. Oftentimes, a patient is unsure with what they have going on medically and will view APPs as a safe place to start. Other times, I will see a patient for a general wellness exam who will mention heavier menses over the years or just a change in their bleeding pattern-- longer flow, things like that.

It may stem from something that seems out of the ordinary for them or a symptom impacting their life. For example, if a patient says, “I have to run home and change my clothes,” or “I'm bleeding through my bed sheets.” Those statements prompt further evaluation. At times, patients who have already been diagnosed with fibroids, will come to see me if they have chosen medical management over surgical management of their fibroids. They continue to follow up with me to reevaluate the success of their treatment plan periodically. So, whether I start them on a plan, or a physician does, they can follow up with me to revisit their medical plan and ensure it remains appropriate.

You touched on this a bit, but can you dive deeper into exactly what you are looking for as part of that visit? 

Ms. Haibach: Definitely. With an initial consult to me, the number one question that I would ask my patients first is, what is your most bothersome symptom? With this question, I'm looking to determine: is it pain that brought you to me? Is it heavy bleeding? Do you feel bulk and bloaty? Are you having issues getting pregnant? Do you have bowel or bladder issues?

The information I get from that one initial question, helps guide the remainder of my visit. If bleeding is the main concern, we would focus on getting that under control. So, we need to suppress the menses with medication options. If bulk and bloating is the main concern, for instance the patient feels like they have a pregnant-looking abdomen, typically surgical options are warranted. If the main complaint is infertility, we do have fertility specialists in our practice who remove fibroids to aid patients in achieving pregnancy.

The most important purpose of this visit is to really listen to the patient to find out how these symptoms are impacting their daily lives. From there, I can use that information to guide my treatment plan.

So, once it is determined that the patient is a good surgical candidate, what would be the next steps?

Ms. Haibach: If at the end of my visit, I determine that a patient is potentially a suitable surgical candidate, the first thing I would do is order appropriate imaging. For example, if the patient is interested in uterine preservation for future fertility, she is likely going to opt for a laparoscopic myomectomy, where fibroids would be removed, and her uterus would be left in place. In that case, she would require an MRI for fibroid mapping. If a woman has completed childbearing, then oftentimes a pelvic ultrasound would suffice, at least to start, since she'd likely elect hysterectomy if she has reached her fertility goals.

I would also perform an endometrial biopsy to rule out malignant process before going into surgery. To optimize a patient for our MIGS surgeons, I gather a thorough medical history to ensure their comorbidities are appropriately managed. For example, diabetes is under control, sleep apnea is being treated, no active infections. If there is anything else going on that needs to be addressed, I'd refer them to the appropriate provider first.

Once I have acceptable imaging, a negative endometrial biopsy and an adequate medical history, I would then assist the patient in scheduling with one of the surgeons on my team for a consult and physical exam to determine surgery planning. Once they see our physician, a surgery date is booked. The patient would come back to see me within 30 days of surgery, and we would do a preoperative education appointment. I see them again 2 weeks after surgery for a post-op visit. We’d perform the post-of visit virtually in our practice. We would see the patient sooner if there are any other concerns that arise post-operatively.

What if the patient is not a surgical candidate? How do you as an APP assist in ongoing medical management?

Ms. Haibach: The presence of fibroids alone, without symptoms, often does not require surgical intervention. There are occasions where a patient is, for example, seen in the emergency room for abdominal pain, whereas they’ll get a CT scan of the abdomen pelvis, and a fibroid is incidentally found. At that point, they are instructed to see gynecology for follow-up. If the patient was unaware of the fibroid, has no symptoms and there's no concerning imaging features, then management with ongoing surveillance (repeat imaging and office follow up) and instructions on when to return is usually appropriate.

Depending on the symptoms, medical management typically includes hormonal suppression of menses in the form of a birth control pill or an IUD. If bleeding is the main concern, it is my goal to at least slow her bleeding, if not try to stop it. Not all women are good candidates for hormone therapy, so there is a medication option that is non-hormonal. In my role, I would start a medication plan for a patient and initiate a new medication such as hormonal suppression in the form of birth control, IUD, non-hormonal medications etc.

Typically, when I do that, I'll have the patient follow up with me in about two to three months to reassess the medication’s effectiveness. The goal of the reassessment is to determine if it is working for her life, to be sure there are no major side-effects, and just to make sure she is amenable to the plan. As part of the medical management, sometimes it is necessary to monitor blood counts for anemia to be certain that medical management is still appropriate for her.

From your experience in practicing, are you more likely to be visited by one age bracket or ethnicity over another? 

Ms. Haibach: Actually, data tells us that most fibroids occur in women of reproductive age. They are also diagnosed in African American women two to three times more frequently than in white women. Fibroids are infrequently seen in premenstrual women. A relief of symptoms of the fibroids often occurs at the time of menopause, when the menstrual cyclicity seizes and steroid hormone levels decrease. My demographic is consistent with the above statistics. I tend to see women within the ages of  20’s-50’s and more often African Americans.

Was there anything else that you'd like to mention?

Ms. Haibach: Abnormal bleeding can be very stressful for women. APPs are a great place to start an abnormal bleeding or fibroid work-up. Patients should rest assure that although we cannot perform surgery, APPs can help get them in the right direction for the best care possible.

In this issue:

• 4 Explanatory Notes and Abbreviation Key
• 9 Veterans Integrated Service Network (VISN) Guide
• 14 Department of Veterans Affairs Health Care Facilities
• 118 Centers of Excellence
• 135 TRICARE Region Guide
• 146 Department of Defense Health Care Facilities

Read now

In this issue:

• 4 Explanatory Notes and Abbreviation Key
• 9 Veterans Integrated Service Network (VISN) Guide
• 14 Department of Veterans Affairs Health Care Facilities
• 118 Centers of Excellence
• 135 TRICARE Region Guide
• 146 Department of Defense Health Care Facilities

Read now

In this issue:

• 4 Explanatory Notes and Abbreviation Key
• 9 Veterans Integrated Service Network (VISN) Guide
• 14 Department of Veterans Affairs Health Care Facilities
• 118 Centers of Excellence
• 135 TRICARE Region Guide
• 146 Department of Defense Health Care Facilities

Read now

The Diagnosis: Basal Cell Carcinoma

Histopathology was consistent with fungating basal cell carcinoma (BCC). The nodules were comprised of syncytial basaloid cells with high nuclear to cytoplasmic ratios, numerous mitotic figures, fibromyxoid stroma, and peripheral nuclear palisading (Figure). Fortunately, no perineural or lymphovascular invasion was identified, and the margins of the specimen were negative. Despite the high-risk nature of giant BCC, the mass was solitary without notable local invasion, leaving it amendable to surgery. On follow-up, the patient has remained recurrence free, and her hemoglobin level has since stabilized.

Skin cancer is the most common malignancy worldwide, and BCC accounts for more than 80% of nonmelanoma skin cancers in the United States. The incidence is on the rise due to the aging population and increasing cumulative skin exposure.¹ Risk factors include both individual physical characteristics and environmental exposures. Individuals with lighter skin tones, red and blonde hair, and blue and green eyes are at an increased risk.² UV radiation exposure is the most important cause of BCC.³ Chronic immunosuppression and exposure to arsenic, ionizing radiation, and psoralen plus UVA radiation also have been linked to the development of BCC.^4-6 Basal cell carcinomas most commonly arise on sun-exposed areas such as the face, though more than 10% of cases appear on the trunk.⁷ Lesions characteristically remain localized, and growth rate is variable; however, when left untreated, BCCs have the potential to become locally destructive and difficult to treat.

Advanced BCCs are tumors that penetrate deeply into the skin. They often are not amenable to traditional therapy and/ or metastasize. Those that grow to a diameter greater than 5 cm, as in our patient, are known as giant BCCs. Only 0.5% to 1% of BCCs are giant BCCs⁸ ; they typically are more aggressive in nature with higher rates of local recurrence and metastasis. Individuals who develop giant BCCs either have had a delay in access to medical care or a history of BCC that was inadequately managed.^9,10 During the COVID-19 pandemic, patient access to health care was substantially impacted during lockdowns. As in our patient, skin neoplasms and other medical conditions may present in later stages due to medical neglect.^11,12 Metastasis is rare, even in advanced BCCs. A review of the literature from 1984 estimated that the incidence of metastasis of BCCs is 1 in 1000 to 35,000. Metastasis portends a poor prognosis with a median overall survival of 8 to 14 months.¹³ An updated review in 2013 found similar outcomes.¹⁴

The choice of management for BCCs depends on the risk for recurrence as well as individual patient factors. Characteristics such as tumor size, location, histology, whether it is a primary or recurrent lesion, and the presence of chronic skin disease determine the recurrence rate.¹⁵ The management of advanced BCCs often requires a multidisciplinary approach, as these neoplasms may not be amenable to local therapy without causing substantial morbidity. Mohs micrographic surgery is the treatment of choice for BCCs at high risk for recurrence.¹⁶ Standard surgical excision with postoperative margin assessment is acceptable when Mohs micrographic surgery is not available.¹⁷ Radiation therapy is an alternative for patients who are not candidates for surgery.¹⁸

Recently, improved understanding of the molecular pathogenesis of BCCs has led to the development of novel systemic therapies. The Hedgehog signaling pathway has been found to play a critical role in the development of most BCCs.¹⁹ Vismodegib and sonidegib are small-molecule inhibitors of the Hedgehog signaling pathway approved for the treatment of locally advanced and metastatic BCCs that are not amenable to surgery or radiation. Approximately 50% of advanced BCCs respond to these therapies; however, long-term treatment may be limited by intolerable side effects and the development of resistance.²⁰ Basal cell carcinomas that spread to lymph nodes or distant sites are treated with traditional systemic therapy. Historically, conventional cytotoxic chemotherapies, such as platinum-containing regimens, were employed with limited benefit and notable morbidity.²¹

The differential diagnosis for our patient included several other cutaneous neoplasms. Squamous cell carcinoma is the second most common type of skin cancer. Similar to BCC, it can reach a substantial size if left untreated. Risk factors include chronic inflammation, exposure to radiation or chemical carcinogens, burns, human papillomavirus, and other chronic infections. Giant squamous cell carcinomas have high malignant potential and require imaging to assess the extent of invasion and for metastasis. Surgery typically is necessary for both staging and treatment. Adjuvant therapy also may be necessary.^22,23

Internal malignant neoplasms rarely present as cutaneous metastases. Breast cancer, melanoma, and cancers of the upper respiratory tract most frequently metastasize to the skin. Although colorectal cancer (CRC) rarely metastasizes to the skin, it is an important cause of cutaneous metastasis due to its high incidence in the general population. When it does spread to the skin, CRC preferentially affects the abdominal wall. Lesions typically resemble the primary tumor but may appear anaplastic. The occurrence of cutaneous metastasis suggests latestage disease and carries a poor prognosis.²⁴

Merkel cell carcinoma and melanoma are aggressive skin cancers with high mortality rates. The former is rarer but more lethal. Merkel cell carcinomas typically occur in elderly white men on sun-exposed areas of the skin. Tumors present as asymptomatic, rapidly expanding, blue-red, firm nodules. Immunosuppression and UV light exposure are notable risk factors.²⁵ Of the 4 major subtypes of cutaneous melanoma, superficial spreading is the most common, followed by nodular, lentigo maligna, and acral lentiginous.²⁶ Superficial spreading melanoma characteristically presents as an expanding asymmetric macule or thin plaque with irregular borders and variation in size and color (black, brown, or red). Nodular melanoma usually presents as symmetric in shape and color (amelanotic, black, or brown). Early recognition by both the patient and clinician is essential in preventing tumor growth and progression.²⁷

Our patient’s presentation was highly concerning for cutaneous metastasis given her history of CRC. Furthermore, the finding of severe anemia was atypical for skin cancer and more characteristic of the prior malignancy. Imaging revealed a locally confined mass with no evidence of extension, lymph node involvement, or additional lesions. The diagnosis was clinched with histopathologic examination.

The Diagnosis: Basal Cell Carcinoma

Histopathology was consistent with fungating basal cell carcinoma (BCC). The nodules were comprised of syncytial basaloid cells with high nuclear to cytoplasmic ratios, numerous mitotic figures, fibromyxoid stroma, and peripheral nuclear palisading (Figure). Fortunately, no perineural or lymphovascular invasion was identified, and the margins of the specimen were negative. Despite the high-risk nature of giant BCC, the mass was solitary without notable local invasion, leaving it amendable to surgery. On follow-up, the patient has remained recurrence free, and her hemoglobin level has since stabilized.

Skin cancer is the most common malignancy worldwide, and BCC accounts for more than 80% of nonmelanoma skin cancers in the United States. The incidence is on the rise due to the aging population and increasing cumulative skin exposure.¹ Risk factors include both individual physical characteristics and environmental exposures. Individuals with lighter skin tones, red and blonde hair, and blue and green eyes are at an increased risk.² UV radiation exposure is the most important cause of BCC.³ Chronic immunosuppression and exposure to arsenic, ionizing radiation, and psoralen plus UVA radiation also have been linked to the development of BCC.^4-6 Basal cell carcinomas most commonly arise on sun-exposed areas such as the face, though more than 10% of cases appear on the trunk.⁷ Lesions characteristically remain localized, and growth rate is variable; however, when left untreated, BCCs have the potential to become locally destructive and difficult to treat.

Advanced BCCs are tumors that penetrate deeply into the skin. They often are not amenable to traditional therapy and/ or metastasize. Those that grow to a diameter greater than 5 cm, as in our patient, are known as giant BCCs. Only 0.5% to 1% of BCCs are giant BCCs⁸ ; they typically are more aggressive in nature with higher rates of local recurrence and metastasis. Individuals who develop giant BCCs either have had a delay in access to medical care or a history of BCC that was inadequately managed.^9,10 During the COVID-19 pandemic, patient access to health care was substantially impacted during lockdowns. As in our patient, skin neoplasms and other medical conditions may present in later stages due to medical neglect.^11,12 Metastasis is rare, even in advanced BCCs. A review of the literature from 1984 estimated that the incidence of metastasis of BCCs is 1 in 1000 to 35,000. Metastasis portends a poor prognosis with a median overall survival of 8 to 14 months.¹³ An updated review in 2013 found similar outcomes.¹⁴

The choice of management for BCCs depends on the risk for recurrence as well as individual patient factors. Characteristics such as tumor size, location, histology, whether it is a primary or recurrent lesion, and the presence of chronic skin disease determine the recurrence rate.¹⁵ The management of advanced BCCs often requires a multidisciplinary approach, as these neoplasms may not be amenable to local therapy without causing substantial morbidity. Mohs micrographic surgery is the treatment of choice for BCCs at high risk for recurrence.¹⁶ Standard surgical excision with postoperative margin assessment is acceptable when Mohs micrographic surgery is not available.¹⁷ Radiation therapy is an alternative for patients who are not candidates for surgery.¹⁸

Recently, improved understanding of the molecular pathogenesis of BCCs has led to the development of novel systemic therapies. The Hedgehog signaling pathway has been found to play a critical role in the development of most BCCs.¹⁹ Vismodegib and sonidegib are small-molecule inhibitors of the Hedgehog signaling pathway approved for the treatment of locally advanced and metastatic BCCs that are not amenable to surgery or radiation. Approximately 50% of advanced BCCs respond to these therapies; however, long-term treatment may be limited by intolerable side effects and the development of resistance.²⁰ Basal cell carcinomas that spread to lymph nodes or distant sites are treated with traditional systemic therapy. Historically, conventional cytotoxic chemotherapies, such as platinum-containing regimens, were employed with limited benefit and notable morbidity.²¹

The differential diagnosis for our patient included several other cutaneous neoplasms. Squamous cell carcinoma is the second most common type of skin cancer. Similar to BCC, it can reach a substantial size if left untreated. Risk factors include chronic inflammation, exposure to radiation or chemical carcinogens, burns, human papillomavirus, and other chronic infections. Giant squamous cell carcinomas have high malignant potential and require imaging to assess the extent of invasion and for metastasis. Surgery typically is necessary for both staging and treatment. Adjuvant therapy also may be necessary.^22,23

Internal malignant neoplasms rarely present as cutaneous metastases. Breast cancer, melanoma, and cancers of the upper respiratory tract most frequently metastasize to the skin. Although colorectal cancer (CRC) rarely metastasizes to the skin, it is an important cause of cutaneous metastasis due to its high incidence in the general population. When it does spread to the skin, CRC preferentially affects the abdominal wall. Lesions typically resemble the primary tumor but may appear anaplastic. The occurrence of cutaneous metastasis suggests latestage disease and carries a poor prognosis.²⁴

Merkel cell carcinoma and melanoma are aggressive skin cancers with high mortality rates. The former is rarer but more lethal. Merkel cell carcinomas typically occur in elderly white men on sun-exposed areas of the skin. Tumors present as asymptomatic, rapidly expanding, blue-red, firm nodules. Immunosuppression and UV light exposure are notable risk factors.²⁵ Of the 4 major subtypes of cutaneous melanoma, superficial spreading is the most common, followed by nodular, lentigo maligna, and acral lentiginous.²⁶ Superficial spreading melanoma characteristically presents as an expanding asymmetric macule or thin plaque with irregular borders and variation in size and color (black, brown, or red). Nodular melanoma usually presents as symmetric in shape and color (amelanotic, black, or brown). Early recognition by both the patient and clinician is essential in preventing tumor growth and progression.²⁷

Our patient’s presentation was highly concerning for cutaneous metastasis given her history of CRC. Furthermore, the finding of severe anemia was atypical for skin cancer and more characteristic of the prior malignancy. Imaging revealed a locally confined mass with no evidence of extension, lymph node involvement, or additional lesions. The diagnosis was clinched with histopathologic examination.

The Diagnosis: Basal Cell Carcinoma

Histopathology was consistent with fungating basal cell carcinoma (BCC). The nodules were comprised of syncytial basaloid cells with high nuclear to cytoplasmic ratios, numerous mitotic figures, fibromyxoid stroma, and peripheral nuclear palisading (Figure). Fortunately, no perineural or lymphovascular invasion was identified, and the margins of the specimen were negative. Despite the high-risk nature of giant BCC, the mass was solitary without notable local invasion, leaving it amendable to surgery. On follow-up, the patient has remained recurrence free, and her hemoglobin level has since stabilized.

Skin cancer is the most common malignancy worldwide, and BCC accounts for more than 80% of nonmelanoma skin cancers in the United States. The incidence is on the rise due to the aging population and increasing cumulative skin exposure.¹ Risk factors include both individual physical characteristics and environmental exposures. Individuals with lighter skin tones, red and blonde hair, and blue and green eyes are at an increased risk.² UV radiation exposure is the most important cause of BCC.³ Chronic immunosuppression and exposure to arsenic, ionizing radiation, and psoralen plus UVA radiation also have been linked to the development of BCC.^4-6 Basal cell carcinomas most commonly arise on sun-exposed areas such as the face, though more than 10% of cases appear on the trunk.⁷ Lesions characteristically remain localized, and growth rate is variable; however, when left untreated, BCCs have the potential to become locally destructive and difficult to treat.

Advanced BCCs are tumors that penetrate deeply into the skin. They often are not amenable to traditional therapy and/ or metastasize. Those that grow to a diameter greater than 5 cm, as in our patient, are known as giant BCCs. Only 0.5% to 1% of BCCs are giant BCCs⁸ ; they typically are more aggressive in nature with higher rates of local recurrence and metastasis. Individuals who develop giant BCCs either have had a delay in access to medical care or a history of BCC that was inadequately managed.^9,10 During the COVID-19 pandemic, patient access to health care was substantially impacted during lockdowns. As in our patient, skin neoplasms and other medical conditions may present in later stages due to medical neglect.^11,12 Metastasis is rare, even in advanced BCCs. A review of the literature from 1984 estimated that the incidence of metastasis of BCCs is 1 in 1000 to 35,000. Metastasis portends a poor prognosis with a median overall survival of 8 to 14 months.¹³ An updated review in 2013 found similar outcomes.¹⁴

The choice of management for BCCs depends on the risk for recurrence as well as individual patient factors. Characteristics such as tumor size, location, histology, whether it is a primary or recurrent lesion, and the presence of chronic skin disease determine the recurrence rate.¹⁵ The management of advanced BCCs often requires a multidisciplinary approach, as these neoplasms may not be amenable to local therapy without causing substantial morbidity. Mohs micrographic surgery is the treatment of choice for BCCs at high risk for recurrence.¹⁶ Standard surgical excision with postoperative margin assessment is acceptable when Mohs micrographic surgery is not available.¹⁷ Radiation therapy is an alternative for patients who are not candidates for surgery.¹⁸

Recently, improved understanding of the molecular pathogenesis of BCCs has led to the development of novel systemic therapies. The Hedgehog signaling pathway has been found to play a critical role in the development of most BCCs.¹⁹ Vismodegib and sonidegib are small-molecule inhibitors of the Hedgehog signaling pathway approved for the treatment of locally advanced and metastatic BCCs that are not amenable to surgery or radiation. Approximately 50% of advanced BCCs respond to these therapies; however, long-term treatment may be limited by intolerable side effects and the development of resistance.²⁰ Basal cell carcinomas that spread to lymph nodes or distant sites are treated with traditional systemic therapy. Historically, conventional cytotoxic chemotherapies, such as platinum-containing regimens, were employed with limited benefit and notable morbidity.²¹

The differential diagnosis for our patient included several other cutaneous neoplasms. Squamous cell carcinoma is the second most common type of skin cancer. Similar to BCC, it can reach a substantial size if left untreated. Risk factors include chronic inflammation, exposure to radiation or chemical carcinogens, burns, human papillomavirus, and other chronic infections. Giant squamous cell carcinomas have high malignant potential and require imaging to assess the extent of invasion and for metastasis. Surgery typically is necessary for both staging and treatment. Adjuvant therapy also may be necessary.^22,23

Internal malignant neoplasms rarely present as cutaneous metastases. Breast cancer, melanoma, and cancers of the upper respiratory tract most frequently metastasize to the skin. Although colorectal cancer (CRC) rarely metastasizes to the skin, it is an important cause of cutaneous metastasis due to its high incidence in the general population. When it does spread to the skin, CRC preferentially affects the abdominal wall. Lesions typically resemble the primary tumor but may appear anaplastic. The occurrence of cutaneous metastasis suggests latestage disease and carries a poor prognosis.²⁴

Merkel cell carcinoma and melanoma are aggressive skin cancers with high mortality rates. The former is rarer but more lethal. Merkel cell carcinomas typically occur in elderly white men on sun-exposed areas of the skin. Tumors present as asymptomatic, rapidly expanding, blue-red, firm nodules. Immunosuppression and UV light exposure are notable risk factors.²⁵ Of the 4 major subtypes of cutaneous melanoma, superficial spreading is the most common, followed by nodular, lentigo maligna, and acral lentiginous.²⁶ Superficial spreading melanoma characteristically presents as an expanding asymmetric macule or thin plaque with irregular borders and variation in size and color (black, brown, or red). Nodular melanoma usually presents as symmetric in shape and color (amelanotic, black, or brown). Early recognition by both the patient and clinician is essential in preventing tumor growth and progression.²⁷

Our patient’s presentation was highly concerning for cutaneous metastasis given her history of CRC. Furthermore, the finding of severe anemia was atypical for skin cancer and more characteristic of the prior malignancy. Imaging revealed a locally confined mass with no evidence of extension, lymph node involvement, or additional lesions. The diagnosis was clinched with histopathologic examination.

To the Editor:

Sarcoidosis is a multisystem, noncaseating, granulomatous disorder thought to occur from a combination of immunologic, genetic, and environmental factors.¹ Often referred to as the “great imitator,” the cutaneous manifestations of sarcoidosis encompass many morphologies, including papules, plaques, nodules, and scars.¹ We report an unusual case of sarcoidosis presenting as telangiectatic macules on the lower extremities.

A woman in her early 30s presented with a burning, pruritic, erythematous, telangiectatic eruption on the lower extremities with concurrent ankle swelling of 4 weeks’ duration. The patient denied any fevers, chills, recent infections, or new medications. Evaluation by her primary care physician during the time of the eruption included unremarkable antinuclear antibodies, thyroid stimulating hormone level, complete blood cell count, comprehensive metabolic panel, urinalysis, chest radiography, and lower-extremity Doppler ultrasonography.

Physical examination at the current presentation revealed numerous scattered, faint, erythematous, blanchable macules on the lower extremities along with mild pitting edema (Figure 1). The patient’s current medications included cetirizine, which she had been taking for years, as well as an intrauterine device. A punch biopsy from the right lower leg revealed small, well-demarcated sarcoidal granulomatous inflammation surrounding vascular structures and skin appendages (Figure 2). No foreign bodies were observed with polarized light microscopy. Microscopic findings suggestive of an infection, including caseation necrosis and suppurative inflammation, also were absent. Angiotensin-converting enzyme levels were normal. Myeloperoxidase and proteinase 3 IgG antibody levels were evaluated due to potential vascular involvement but were negative. An infectious cause of the sarcoidal granulomas was unlikely given histopathologic findings and negative tuberculosis skin testing, which the patient underwent annually for her job, so a tissue culture was not performed. The patient was prescribed triamcinolone acetonide cream 0.1% for the itching and burning at the initial visit and was continued on this treatment after the diagnosis of sarcoidosis was made. At 2-month follow-up, the patient’s eruption had nearly resolved with topical therapy.

Cutaneous manifestation occurs in 20% to 35% of sarcoidosis cases and may develop in the presence or absence of systemic disease. Approximately 60% of individuals with cutaneous sarcoidosis are found to have systemic involvement; therefore, careful monitoring and diagnostic workup are important in the management of these patients.² While most cases of cutaneous sarcoidosis are papular, it is important for clinicians to maintain a level of suspicion for sarcoidosis in any uncertain dermatologic presentation.^1,2 Evidence of telangiectasias has been shown in rarer forms of sarcoidosis (eg, angiolupoid), but the lesions usually are confined to the face, ears, or neck.³ Granulomatous vasculitis has been reported in a small number of individuals with ulcerative sarcoidosis.⁴ In our case, no ulcerations were present, possibly indicating an early lesion or an entirely novel process. Lastly, although reticular dermal granulomas are found in drug-induced interstitial granulomatous dermatitis, these lesions often are dispersed interstitially amongst collagen bundles and are associated with necrobiosis of collagen and eosinophilic/neutrophilic infiltrates.⁵ The lack of these characteristic pathologic findings in our patient along with no known reported cases of cetirizine-induced granulomatous dermatitis led us to rule out reticular dermal granulomas as a diagnosis. We present our case as a reminder of the diversity of cutaneous sarcoidosis manifestations and the importance of early diagnosis of these lesions.

To the Editor:

Sarcoidosis is a multisystem, noncaseating, granulomatous disorder thought to occur from a combination of immunologic, genetic, and environmental factors.¹ Often referred to as the “great imitator,” the cutaneous manifestations of sarcoidosis encompass many morphologies, including papules, plaques, nodules, and scars.¹ We report an unusual case of sarcoidosis presenting as telangiectatic macules on the lower extremities.

A woman in her early 30s presented with a burning, pruritic, erythematous, telangiectatic eruption on the lower extremities with concurrent ankle swelling of 4 weeks’ duration. The patient denied any fevers, chills, recent infections, or new medications. Evaluation by her primary care physician during the time of the eruption included unremarkable antinuclear antibodies, thyroid stimulating hormone level, complete blood cell count, comprehensive metabolic panel, urinalysis, chest radiography, and lower-extremity Doppler ultrasonography.

Physical examination at the current presentation revealed numerous scattered, faint, erythematous, blanchable macules on the lower extremities along with mild pitting edema (Figure 1). The patient’s current medications included cetirizine, which she had been taking for years, as well as an intrauterine device. A punch biopsy from the right lower leg revealed small, well-demarcated sarcoidal granulomatous inflammation surrounding vascular structures and skin appendages (Figure 2). No foreign bodies were observed with polarized light microscopy. Microscopic findings suggestive of an infection, including caseation necrosis and suppurative inflammation, also were absent. Angiotensin-converting enzyme levels were normal. Myeloperoxidase and proteinase 3 IgG antibody levels were evaluated due to potential vascular involvement but were negative. An infectious cause of the sarcoidal granulomas was unlikely given histopathologic findings and negative tuberculosis skin testing, which the patient underwent annually for her job, so a tissue culture was not performed. The patient was prescribed triamcinolone acetonide cream 0.1% for the itching and burning at the initial visit and was continued on this treatment after the diagnosis of sarcoidosis was made. At 2-month follow-up, the patient’s eruption had nearly resolved with topical therapy.

Cutaneous manifestation occurs in 20% to 35% of sarcoidosis cases and may develop in the presence or absence of systemic disease. Approximately 60% of individuals with cutaneous sarcoidosis are found to have systemic involvement; therefore, careful monitoring and diagnostic workup are important in the management of these patients.² While most cases of cutaneous sarcoidosis are papular, it is important for clinicians to maintain a level of suspicion for sarcoidosis in any uncertain dermatologic presentation.^1,2 Evidence of telangiectasias has been shown in rarer forms of sarcoidosis (eg, angiolupoid), but the lesions usually are confined to the face, ears, or neck.³ Granulomatous vasculitis has been reported in a small number of individuals with ulcerative sarcoidosis.⁴ In our case, no ulcerations were present, possibly indicating an early lesion or an entirely novel process. Lastly, although reticular dermal granulomas are found in drug-induced interstitial granulomatous dermatitis, these lesions often are dispersed interstitially amongst collagen bundles and are associated with necrobiosis of collagen and eosinophilic/neutrophilic infiltrates.⁵ The lack of these characteristic pathologic findings in our patient along with no known reported cases of cetirizine-induced granulomatous dermatitis led us to rule out reticular dermal granulomas as a diagnosis. We present our case as a reminder of the diversity of cutaneous sarcoidosis manifestations and the importance of early diagnosis of these lesions.

To the Editor:

Sarcoidosis is a multisystem, noncaseating, granulomatous disorder thought to occur from a combination of immunologic, genetic, and environmental factors.¹ Often referred to as the “great imitator,” the cutaneous manifestations of sarcoidosis encompass many morphologies, including papules, plaques, nodules, and scars.¹ We report an unusual case of sarcoidosis presenting as telangiectatic macules on the lower extremities.

A woman in her early 30s presented with a burning, pruritic, erythematous, telangiectatic eruption on the lower extremities with concurrent ankle swelling of 4 weeks’ duration. The patient denied any fevers, chills, recent infections, or new medications. Evaluation by her primary care physician during the time of the eruption included unremarkable antinuclear antibodies, thyroid stimulating hormone level, complete blood cell count, comprehensive metabolic panel, urinalysis, chest radiography, and lower-extremity Doppler ultrasonography.

Physical examination at the current presentation revealed numerous scattered, faint, erythematous, blanchable macules on the lower extremities along with mild pitting edema (Figure 1). The patient’s current medications included cetirizine, which she had been taking for years, as well as an intrauterine device. A punch biopsy from the right lower leg revealed small, well-demarcated sarcoidal granulomatous inflammation surrounding vascular structures and skin appendages (Figure 2). No foreign bodies were observed with polarized light microscopy. Microscopic findings suggestive of an infection, including caseation necrosis and suppurative inflammation, also were absent. Angiotensin-converting enzyme levels were normal. Myeloperoxidase and proteinase 3 IgG antibody levels were evaluated due to potential vascular involvement but were negative. An infectious cause of the sarcoidal granulomas was unlikely given histopathologic findings and negative tuberculosis skin testing, which the patient underwent annually for her job, so a tissue culture was not performed. The patient was prescribed triamcinolone acetonide cream 0.1% for the itching and burning at the initial visit and was continued on this treatment after the diagnosis of sarcoidosis was made. At 2-month follow-up, the patient’s eruption had nearly resolved with topical therapy.

Cutaneous manifestation occurs in 20% to 35% of sarcoidosis cases and may develop in the presence or absence of systemic disease. Approximately 60% of individuals with cutaneous sarcoidosis are found to have systemic involvement; therefore, careful monitoring and diagnostic workup are important in the management of these patients.² While most cases of cutaneous sarcoidosis are papular, it is important for clinicians to maintain a level of suspicion for sarcoidosis in any uncertain dermatologic presentation.^1,2 Evidence of telangiectasias has been shown in rarer forms of sarcoidosis (eg, angiolupoid), but the lesions usually are confined to the face, ears, or neck.³ Granulomatous vasculitis has been reported in a small number of individuals with ulcerative sarcoidosis.⁴ In our case, no ulcerations were present, possibly indicating an early lesion or an entirely novel process. Lastly, although reticular dermal granulomas are found in drug-induced interstitial granulomatous dermatitis, these lesions often are dispersed interstitially amongst collagen bundles and are associated with necrobiosis of collagen and eosinophilic/neutrophilic infiltrates.⁵ The lack of these characteristic pathologic findings in our patient along with no known reported cases of cetirizine-induced granulomatous dermatitis led us to rule out reticular dermal granulomas as a diagnosis. We present our case as a reminder of the diversity of cutaneous sarcoidosis manifestations and the importance of early diagnosis of these lesions.

To the Editor:

Acute graft-vs-host disease (GVHD) remains a limitation to hematopoietic stem cell transplantation (HSCT) in 20% to 50% of patients after transplant. Furthermore, failed treatment with corticosteroids is frequent and portends a poor prognosis.¹ Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder thought to represent an adverse drug reaction, though its pathogenesis remains unclear. Severe forms of acute GVHD can mimic TEN clinically and histologically. Both can present with widespread cutaneous and mucosal bullae, erosions, and desquamation. Toxic epidermal necrolysis in the context of allogeneic hematopoietic stem cell transplantation is extremely rare, with almost 100% mortality in adult patients. Features that favor acute GVHD over TEN include diarrhea, elevation in bilirubin level, and chimerism.² However, these features might be absent, posing a therapeutic dilemma, as current treatment preferences for each of these entities differ.

Growing evidence supports the use of anti–tumor necrosis factor (TNF) α drugs for the treatment of TEN. Success has been reported with both anti–TNF-α monoclonal antibodies as well as the soluble fusion protein etanercept.^3,4 The use of TNF-α inhibitors in acute GVHD remains anecdotal.

A 58-year-old man (patient 1) with a history of acute myelogenous leukemia presented with a pruritic morbilliform eruption 28 days after HSCT. There was no desquamation or mucosal involvement and the biopsy obtained was histologically suggestive of grade 2 acute GVHD. His immunosuppressive regimen included sirolimus and cyclophosphamide. He was receiving trimethoprim-sulfamethoxazole (TMP-SMX), voriconazole, and acyclovir for infectious prophylaxis. At the time of presentation, he was treated with high-dose systemic steroids (prednisone 2 mg/kg/d) for acute GVHD with partial improvement. Upon tapering of the steroids 3 weeks after initiating TMP-SMX and 1 week after initiating voriconazole, he developed painful desquamation and erosions involving 95% of the body surface area (BSA), necessitating admission to the local burn unit (Figure 1). Biopsies demonstrated full-thickness epidermal necrosis with subepidermal blistering and interface dermatitis (Figure 2). No gastrointestinal tract involvement of acute GVHD was noted. The patient was a 100% donor chimera, supporting the diagnosis of acute GVHD; however, the patient and donor carried the HLA-C*06:02 allele, which previously has been described in association with TMP-SMX–related Stevens-Johnson syndrome/TEN.⁵ In addition, causality assessment using the algorithm of drug causality for epidermal necrolysis indicated TMP-SMX as a probable cause and voriconazole as a possible cause. The diagnosis of TEN with a SCORe of Toxic Epidermal Necrosis (SCORTEN) of 4 in the setting of acute GVHD was favored, though grade 4 acute GVHD could not be excluded. Trimethoprim-sulfamethoxazole was discontinued, and voriconazole was changed to posaconazole. He received supportive care along with 1 dose of 25-mg subcutaneous etanercept and 3 days of intravenous immunoglobulin (IVIG). Skin re-epithelialization was complete by 3 weeks. At 4 weeks, the patient developed a new asymptomatic erythematous eruption. Biopsies demonstrated changes of acute and chronic GVHD (Figure 3) that resolved with up-titration of sirolimus. The patient remained hospitalized for 96 days and continued to follow up with his transplant team as well as ophthalmology and dermatology. He died 2 years after HSCT.

A 67-year-old woman (patient 2) with high-grade myelodysplastic syndrome presented with an erythematous morbilliform eruption on the torso on day 20 after a matched unrelated HSCT that histologically was consistent with grade 2 GVHD (Figure 4). She had been receiving sirolimus and tacrolimus for GVHD prophylaxis. Infectious prophylaxis included acyclovir, pentamidine, micafungin, and TMP-SMX. Despite high-dose systemic steroids, the rash progressed and ultimately involved 80% BSA. A positive Nikolsky sign was noted involving 21% BSA (Figure 5), in addition to oral and genital mucosal ulcers. She denied nausea, vomiting, fever, or diarrhea. Chimerism studies were negative. Trimethoprim-sulfamethoxazole was discontinued, and she was transferred to a burn unit. Biopsies showed full-thickness epidermal necrosis. A diagnosis of TEN with a SCORTEN of 4 in the setting of acute GVHD was favored; grade 4 acute GVHD could not be excluded. Steroids were discontinued. Because laboratory studies indicated IgA deficiency, IVIG was not considered as a systemic option for therapy. The patient received 1 dose of infliximab (5 mg/kg). Cyclophosphamide 1600 mg weekly was added for GVHD therapy. The wounds progressively healed, and 2 weeks into her admission she was noted to have only 3% BSA with denuded skin. The patient was transferred to the cancer treatment center for further management of the malignancy. Unfortunately, after 2 months she died due to ischemic colitis that was confirmed on autopsy.

Graft-vs-host disease and TEN are rare, life-threatening complications seen in patients with allogeneic HSCT.² Graft-vs-host disease and TEN share clinicopathologic characteristics and effector immune mechanisms, largely the substantial role of T-cell activation and tissue destruction, which occur through mediators such as TNF-α.^6-8

Given the sparse lymphocytic infiltrate, keratinocyte death in TEN is thought to result from soluble molecules, including TNF-α and TNF-related apoptosis-inducing ligand.⁹ Tumor necrosis factor α has been identified in blister fluid, biopsy specimens, and serum of patients with TEN. Tumor necrosis factor α increases the expression of keratinocyte-inducible nitric oxide synthase, which upregulates keratinocyte Fas ligand expression and subsequent Fas- and caspase-8–mediated keratinocyte cell death.¹⁰

Acute GVHD results from donor lymphocyte activation after infusion into damaged recipient tissues that previously have been radiated or chemoablated. Mismatches in histocompatibility complexes between donor cells and recipient tissue antigens serve as the initial trigger for immune activation. Activation of antigen-presenting cells followed by activation, proliferation, differentiation, and migration of donor T cells ultimately results in destruction of the target tissue.¹¹ Immune mediators, such as TNF-α and lymphotoxin α (another member of the TNF superfamily), play a nonredundant role in the pathogenesis of GVHD.¹²

Current treatment strategies for severe acute GVHD and TEN differ. In North America, high-dose IVIG frequently is used as first-line systemic therapy, while high-dose systemic corticosteroids rarely are used.¹³ Studies have demonstrated successful use of anti–TNF-α drugs for the treatment of TEN.^3,4 Moreover, etanercept has shown to effectively inhibit lymphotoxin α.¹⁴ Similarly, TNF inhibition in the management of steroid-refractory acute GVHD has been successful.¹ These studies coupled with the underlying immune mechanisms that both diseases share encouraged initiating a trial of anti–TNF-α therapy in our patients.

Patient 1 merits further discussion because he was both a 100% donor chimera as well as a carrier of an human leukocyte antigen susceptibility candidate allele to TMP-SMX. Historical features of his presentation are consistent with either steroid-refractory GVHD or TEN superimposed on acute GVHD. His initial presentation of the more typical macular exanthem of cutaneous acute GVHD was both biopsy proven and supported by clinical improvement with steroid therapy, which was later followed by a robust blistering mucocutaneous presentation approximately 3 weeks after the administration of TMP-SMX and 1 week after initiating voriconazole that improved with IVIG and etanercept.

It is difficult to determine if TEN represents a continuum or result of the underlying drivers of acute GVHD vs a drug reaction. Although there is insufficient evidence to establish a clear-cut diagnosis of TEN, these cases illustrate the need for better diagnostic techniques to allow differentiation between TEN and grade 4 acute GVHD, and in the context of uncertainty, TNF-α inhibition poses a viable therapeutic strategy for these 2 often lethal conditions. Our cases do unequivocally indicate the benefit of this therapeutic modality, add to the current body of literature supporting the use of TNF-α inhibitors in patients such as ours without an official TEN diagnosis, and may guide future investigative efforts.

To the Editor:

Acute graft-vs-host disease (GVHD) remains a limitation to hematopoietic stem cell transplantation (HSCT) in 20% to 50% of patients after transplant. Furthermore, failed treatment with corticosteroids is frequent and portends a poor prognosis.¹ Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder thought to represent an adverse drug reaction, though its pathogenesis remains unclear. Severe forms of acute GVHD can mimic TEN clinically and histologically. Both can present with widespread cutaneous and mucosal bullae, erosions, and desquamation. Toxic epidermal necrolysis in the context of allogeneic hematopoietic stem cell transplantation is extremely rare, with almost 100% mortality in adult patients. Features that favor acute GVHD over TEN include diarrhea, elevation in bilirubin level, and chimerism.² However, these features might be absent, posing a therapeutic dilemma, as current treatment preferences for each of these entities differ.

Growing evidence supports the use of anti–tumor necrosis factor (TNF) α drugs for the treatment of TEN. Success has been reported with both anti–TNF-α monoclonal antibodies as well as the soluble fusion protein etanercept.^3,4 The use of TNF-α inhibitors in acute GVHD remains anecdotal.

A 58-year-old man (patient 1) with a history of acute myelogenous leukemia presented with a pruritic morbilliform eruption 28 days after HSCT. There was no desquamation or mucosal involvement and the biopsy obtained was histologically suggestive of grade 2 acute GVHD. His immunosuppressive regimen included sirolimus and cyclophosphamide. He was receiving trimethoprim-sulfamethoxazole (TMP-SMX), voriconazole, and acyclovir for infectious prophylaxis. At the time of presentation, he was treated with high-dose systemic steroids (prednisone 2 mg/kg/d) for acute GVHD with partial improvement. Upon tapering of the steroids 3 weeks after initiating TMP-SMX and 1 week after initiating voriconazole, he developed painful desquamation and erosions involving 95% of the body surface area (BSA), necessitating admission to the local burn unit (Figure 1). Biopsies demonstrated full-thickness epidermal necrosis with subepidermal blistering and interface dermatitis (Figure 2). No gastrointestinal tract involvement of acute GVHD was noted. The patient was a 100% donor chimera, supporting the diagnosis of acute GVHD; however, the patient and donor carried the HLA-C*06:02 allele, which previously has been described in association with TMP-SMX–related Stevens-Johnson syndrome/TEN.⁵ In addition, causality assessment using the algorithm of drug causality for epidermal necrolysis indicated TMP-SMX as a probable cause and voriconazole as a possible cause. The diagnosis of TEN with a SCORe of Toxic Epidermal Necrosis (SCORTEN) of 4 in the setting of acute GVHD was favored, though grade 4 acute GVHD could not be excluded. Trimethoprim-sulfamethoxazole was discontinued, and voriconazole was changed to posaconazole. He received supportive care along with 1 dose of 25-mg subcutaneous etanercept and 3 days of intravenous immunoglobulin (IVIG). Skin re-epithelialization was complete by 3 weeks. At 4 weeks, the patient developed a new asymptomatic erythematous eruption. Biopsies demonstrated changes of acute and chronic GVHD (Figure 3) that resolved with up-titration of sirolimus. The patient remained hospitalized for 96 days and continued to follow up with his transplant team as well as ophthalmology and dermatology. He died 2 years after HSCT.

A 67-year-old woman (patient 2) with high-grade myelodysplastic syndrome presented with an erythematous morbilliform eruption on the torso on day 20 after a matched unrelated HSCT that histologically was consistent with grade 2 GVHD (Figure 4). She had been receiving sirolimus and tacrolimus for GVHD prophylaxis. Infectious prophylaxis included acyclovir, pentamidine, micafungin, and TMP-SMX. Despite high-dose systemic steroids, the rash progressed and ultimately involved 80% BSA. A positive Nikolsky sign was noted involving 21% BSA (Figure 5), in addition to oral and genital mucosal ulcers. She denied nausea, vomiting, fever, or diarrhea. Chimerism studies were negative. Trimethoprim-sulfamethoxazole was discontinued, and she was transferred to a burn unit. Biopsies showed full-thickness epidermal necrosis. A diagnosis of TEN with a SCORTEN of 4 in the setting of acute GVHD was favored; grade 4 acute GVHD could not be excluded. Steroids were discontinued. Because laboratory studies indicated IgA deficiency, IVIG was not considered as a systemic option for therapy. The patient received 1 dose of infliximab (5 mg/kg). Cyclophosphamide 1600 mg weekly was added for GVHD therapy. The wounds progressively healed, and 2 weeks into her admission she was noted to have only 3% BSA with denuded skin. The patient was transferred to the cancer treatment center for further management of the malignancy. Unfortunately, after 2 months she died due to ischemic colitis that was confirmed on autopsy.

Graft-vs-host disease and TEN are rare, life-threatening complications seen in patients with allogeneic HSCT.² Graft-vs-host disease and TEN share clinicopathologic characteristics and effector immune mechanisms, largely the substantial role of T-cell activation and tissue destruction, which occur through mediators such as TNF-α.^6-8

Given the sparse lymphocytic infiltrate, keratinocyte death in TEN is thought to result from soluble molecules, including TNF-α and TNF-related apoptosis-inducing ligand.⁹ Tumor necrosis factor α has been identified in blister fluid, biopsy specimens, and serum of patients with TEN. Tumor necrosis factor α increases the expression of keratinocyte-inducible nitric oxide synthase, which upregulates keratinocyte Fas ligand expression and subsequent Fas- and caspase-8–mediated keratinocyte cell death.¹⁰

Acute GVHD results from donor lymphocyte activation after infusion into damaged recipient tissues that previously have been radiated or chemoablated. Mismatches in histocompatibility complexes between donor cells and recipient tissue antigens serve as the initial trigger for immune activation. Activation of antigen-presenting cells followed by activation, proliferation, differentiation, and migration of donor T cells ultimately results in destruction of the target tissue.¹¹ Immune mediators, such as TNF-α and lymphotoxin α (another member of the TNF superfamily), play a nonredundant role in the pathogenesis of GVHD.¹²

Current treatment strategies for severe acute GVHD and TEN differ. In North America, high-dose IVIG frequently is used as first-line systemic therapy, while high-dose systemic corticosteroids rarely are used.¹³ Studies have demonstrated successful use of anti–TNF-α drugs for the treatment of TEN.^3,4 Moreover, etanercept has shown to effectively inhibit lymphotoxin α.¹⁴ Similarly, TNF inhibition in the management of steroid-refractory acute GVHD has been successful.¹ These studies coupled with the underlying immune mechanisms that both diseases share encouraged initiating a trial of anti–TNF-α therapy in our patients.

Patient 1 merits further discussion because he was both a 100% donor chimera as well as a carrier of an human leukocyte antigen susceptibility candidate allele to TMP-SMX. Historical features of his presentation are consistent with either steroid-refractory GVHD or TEN superimposed on acute GVHD. His initial presentation of the more typical macular exanthem of cutaneous acute GVHD was both biopsy proven and supported by clinical improvement with steroid therapy, which was later followed by a robust blistering mucocutaneous presentation approximately 3 weeks after the administration of TMP-SMX and 1 week after initiating voriconazole that improved with IVIG and etanercept.

It is difficult to determine if TEN represents a continuum or result of the underlying drivers of acute GVHD vs a drug reaction. Although there is insufficient evidence to establish a clear-cut diagnosis of TEN, these cases illustrate the need for better diagnostic techniques to allow differentiation between TEN and grade 4 acute GVHD, and in the context of uncertainty, TNF-α inhibition poses a viable therapeutic strategy for these 2 often lethal conditions. Our cases do unequivocally indicate the benefit of this therapeutic modality, add to the current body of literature supporting the use of TNF-α inhibitors in patients such as ours without an official TEN diagnosis, and may guide future investigative efforts.

To the Editor:

Acute graft-vs-host disease (GVHD) remains a limitation to hematopoietic stem cell transplantation (HSCT) in 20% to 50% of patients after transplant. Furthermore, failed treatment with corticosteroids is frequent and portends a poor prognosis.¹ Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder thought to represent an adverse drug reaction, though its pathogenesis remains unclear. Severe forms of acute GVHD can mimic TEN clinically and histologically. Both can present with widespread cutaneous and mucosal bullae, erosions, and desquamation. Toxic epidermal necrolysis in the context of allogeneic hematopoietic stem cell transplantation is extremely rare, with almost 100% mortality in adult patients. Features that favor acute GVHD over TEN include diarrhea, elevation in bilirubin level, and chimerism.² However, these features might be absent, posing a therapeutic dilemma, as current treatment preferences for each of these entities differ.

Growing evidence supports the use of anti–tumor necrosis factor (TNF) α drugs for the treatment of TEN. Success has been reported with both anti–TNF-α monoclonal antibodies as well as the soluble fusion protein etanercept.^3,4 The use of TNF-α inhibitors in acute GVHD remains anecdotal.

A 58-year-old man (patient 1) with a history of acute myelogenous leukemia presented with a pruritic morbilliform eruption 28 days after HSCT. There was no desquamation or mucosal involvement and the biopsy obtained was histologically suggestive of grade 2 acute GVHD. His immunosuppressive regimen included sirolimus and cyclophosphamide. He was receiving trimethoprim-sulfamethoxazole (TMP-SMX), voriconazole, and acyclovir for infectious prophylaxis. At the time of presentation, he was treated with high-dose systemic steroids (prednisone 2 mg/kg/d) for acute GVHD with partial improvement. Upon tapering of the steroids 3 weeks after initiating TMP-SMX and 1 week after initiating voriconazole, he developed painful desquamation and erosions involving 95% of the body surface area (BSA), necessitating admission to the local burn unit (Figure 1). Biopsies demonstrated full-thickness epidermal necrosis with subepidermal blistering and interface dermatitis (Figure 2). No gastrointestinal tract involvement of acute GVHD was noted. The patient was a 100% donor chimera, supporting the diagnosis of acute GVHD; however, the patient and donor carried the HLA-C*06:02 allele, which previously has been described in association with TMP-SMX–related Stevens-Johnson syndrome/TEN.⁵ In addition, causality assessment using the algorithm of drug causality for epidermal necrolysis indicated TMP-SMX as a probable cause and voriconazole as a possible cause. The diagnosis of TEN with a SCORe of Toxic Epidermal Necrosis (SCORTEN) of 4 in the setting of acute GVHD was favored, though grade 4 acute GVHD could not be excluded. Trimethoprim-sulfamethoxazole was discontinued, and voriconazole was changed to posaconazole. He received supportive care along with 1 dose of 25-mg subcutaneous etanercept and 3 days of intravenous immunoglobulin (IVIG). Skin re-epithelialization was complete by 3 weeks. At 4 weeks, the patient developed a new asymptomatic erythematous eruption. Biopsies demonstrated changes of acute and chronic GVHD (Figure 3) that resolved with up-titration of sirolimus. The patient remained hospitalized for 96 days and continued to follow up with his transplant team as well as ophthalmology and dermatology. He died 2 years after HSCT.

A 67-year-old woman (patient 2) with high-grade myelodysplastic syndrome presented with an erythematous morbilliform eruption on the torso on day 20 after a matched unrelated HSCT that histologically was consistent with grade 2 GVHD (Figure 4). She had been receiving sirolimus and tacrolimus for GVHD prophylaxis. Infectious prophylaxis included acyclovir, pentamidine, micafungin, and TMP-SMX. Despite high-dose systemic steroids, the rash progressed and ultimately involved 80% BSA. A positive Nikolsky sign was noted involving 21% BSA (Figure 5), in addition to oral and genital mucosal ulcers. She denied nausea, vomiting, fever, or diarrhea. Chimerism studies were negative. Trimethoprim-sulfamethoxazole was discontinued, and she was transferred to a burn unit. Biopsies showed full-thickness epidermal necrosis. A diagnosis of TEN with a SCORTEN of 4 in the setting of acute GVHD was favored; grade 4 acute GVHD could not be excluded. Steroids were discontinued. Because laboratory studies indicated IgA deficiency, IVIG was not considered as a systemic option for therapy. The patient received 1 dose of infliximab (5 mg/kg). Cyclophosphamide 1600 mg weekly was added for GVHD therapy. The wounds progressively healed, and 2 weeks into her admission she was noted to have only 3% BSA with denuded skin. The patient was transferred to the cancer treatment center for further management of the malignancy. Unfortunately, after 2 months she died due to ischemic colitis that was confirmed on autopsy.

Graft-vs-host disease and TEN are rare, life-threatening complications seen in patients with allogeneic HSCT.² Graft-vs-host disease and TEN share clinicopathologic characteristics and effector immune mechanisms, largely the substantial role of T-cell activation and tissue destruction, which occur through mediators such as TNF-α.^6-8

Given the sparse lymphocytic infiltrate, keratinocyte death in TEN is thought to result from soluble molecules, including TNF-α and TNF-related apoptosis-inducing ligand.⁹ Tumor necrosis factor α has been identified in blister fluid, biopsy specimens, and serum of patients with TEN. Tumor necrosis factor α increases the expression of keratinocyte-inducible nitric oxide synthase, which upregulates keratinocyte Fas ligand expression and subsequent Fas- and caspase-8–mediated keratinocyte cell death.¹⁰

Acute GVHD results from donor lymphocyte activation after infusion into damaged recipient tissues that previously have been radiated or chemoablated. Mismatches in histocompatibility complexes between donor cells and recipient tissue antigens serve as the initial trigger for immune activation. Activation of antigen-presenting cells followed by activation, proliferation, differentiation, and migration of donor T cells ultimately results in destruction of the target tissue.¹¹ Immune mediators, such as TNF-α and lymphotoxin α (another member of the TNF superfamily), play a nonredundant role in the pathogenesis of GVHD.¹²

Current treatment strategies for severe acute GVHD and TEN differ. In North America, high-dose IVIG frequently is used as first-line systemic therapy, while high-dose systemic corticosteroids rarely are used.¹³ Studies have demonstrated successful use of anti–TNF-α drugs for the treatment of TEN.^3,4 Moreover, etanercept has shown to effectively inhibit lymphotoxin α.¹⁴ Similarly, TNF inhibition in the management of steroid-refractory acute GVHD has been successful.¹ These studies coupled with the underlying immune mechanisms that both diseases share encouraged initiating a trial of anti–TNF-α therapy in our patients.

Patient 1 merits further discussion because he was both a 100% donor chimera as well as a carrier of an human leukocyte antigen susceptibility candidate allele to TMP-SMX. Historical features of his presentation are consistent with either steroid-refractory GVHD or TEN superimposed on acute GVHD. His initial presentation of the more typical macular exanthem of cutaneous acute GVHD was both biopsy proven and supported by clinical improvement with steroid therapy, which was later followed by a robust blistering mucocutaneous presentation approximately 3 weeks after the administration of TMP-SMX and 1 week after initiating voriconazole that improved with IVIG and etanercept.

It is difficult to determine if TEN represents a continuum or result of the underlying drivers of acute GVHD vs a drug reaction. Although there is insufficient evidence to establish a clear-cut diagnosis of TEN, these cases illustrate the need for better diagnostic techniques to allow differentiation between TEN and grade 4 acute GVHD, and in the context of uncertainty, TNF-α inhibition poses a viable therapeutic strategy for these 2 often lethal conditions. Our cases do unequivocally indicate the benefit of this therapeutic modality, add to the current body of literature supporting the use of TNF-α inhibitors in patients such as ours without an official TEN diagnosis, and may guide future investigative efforts.

To the Editor:

A 71-year-old Hispanic man with a history of vitiligo presented with an acute-onset blistering rash on the face, arms, and hands. Physical examination demonstrated photodistributed erythematous plaques with overlying vesicles and erosions with hemorrhagic crust on the face, neck, dorsal aspects of the hands, and wrists (Figure). Further history revealed that the patient applied a new cream that was recommended to treat vitiligo the night before the rash onset; he obtained the cream from a Central American market without a prescription. He had gone running in the park without any form of sun protection and then developed the rash within several hours. He denied taking any other medications or supplements. The involvement of sun-protected areas (ie, upper eyelids, nasolabial folds, submental area) was explained when the patient further elaborated that he had performed supine exercises during his outdoor recreation. He brought his new cream into the clinic, which was found to contain prescription-strength methoxsalen (8-methoxypsoralen), confirming the diagnosis of acute phototoxic contact dermatitis. The acute reaction had subsided, and the patient already had discontinued the causative agent. He was counseled on further avoidance of the cream and sun-protective measures.

The photosensitizing properties of certain compounds have been harnessed for therapeutic purposes. For example, psoralen plus UVA therapy has been used for psoriasis and vitiligo and photodynamic therapy for actinic keratoses and superficial nonmelanoma skin cancers.¹ However, these agents can induce severe phototoxicity if UV light exposure is not carefully monitored, as seen in our patient. This case is a classic example of phototoxic contact dermatitis and highlights the importance of obtaining a detailed patient history to allow for proper diagnosis and identification of the causative agent. Importantly, because prescription-strength topical medications are readily available over-the-counter, particularly in stores specializing in international goods, patients should be questioned about the use of all topical and systemic medications, both prescription and nonprescription.²

To the Editor:

A 71-year-old Hispanic man with a history of vitiligo presented with an acute-onset blistering rash on the face, arms, and hands. Physical examination demonstrated photodistributed erythematous plaques with overlying vesicles and erosions with hemorrhagic crust on the face, neck, dorsal aspects of the hands, and wrists (Figure). Further history revealed that the patient applied a new cream that was recommended to treat vitiligo the night before the rash onset; he obtained the cream from a Central American market without a prescription. He had gone running in the park without any form of sun protection and then developed the rash within several hours. He denied taking any other medications or supplements. The involvement of sun-protected areas (ie, upper eyelids, nasolabial folds, submental area) was explained when the patient further elaborated that he had performed supine exercises during his outdoor recreation. He brought his new cream into the clinic, which was found to contain prescription-strength methoxsalen (8-methoxypsoralen), confirming the diagnosis of acute phototoxic contact dermatitis. The acute reaction had subsided, and the patient already had discontinued the causative agent. He was counseled on further avoidance of the cream and sun-protective measures.

The photosensitizing properties of certain compounds have been harnessed for therapeutic purposes. For example, psoralen plus UVA therapy has been used for psoriasis and vitiligo and photodynamic therapy for actinic keratoses and superficial nonmelanoma skin cancers.¹ However, these agents can induce severe phototoxicity if UV light exposure is not carefully monitored, as seen in our patient. This case is a classic example of phototoxic contact dermatitis and highlights the importance of obtaining a detailed patient history to allow for proper diagnosis and identification of the causative agent. Importantly, because prescription-strength topical medications are readily available over-the-counter, particularly in stores specializing in international goods, patients should be questioned about the use of all topical and systemic medications, both prescription and nonprescription.²

To the Editor:

A 71-year-old Hispanic man with a history of vitiligo presented with an acute-onset blistering rash on the face, arms, and hands. Physical examination demonstrated photodistributed erythematous plaques with overlying vesicles and erosions with hemorrhagic crust on the face, neck, dorsal aspects of the hands, and wrists (Figure). Further history revealed that the patient applied a new cream that was recommended to treat vitiligo the night before the rash onset; he obtained the cream from a Central American market without a prescription. He had gone running in the park without any form of sun protection and then developed the rash within several hours. He denied taking any other medications or supplements. The involvement of sun-protected areas (ie, upper eyelids, nasolabial folds, submental area) was explained when the patient further elaborated that he had performed supine exercises during his outdoor recreation. He brought his new cream into the clinic, which was found to contain prescription-strength methoxsalen (8-methoxypsoralen), confirming the diagnosis of acute phototoxic contact dermatitis. The acute reaction had subsided, and the patient already had discontinued the causative agent. He was counseled on further avoidance of the cream and sun-protective measures.

The photosensitizing properties of certain compounds have been harnessed for therapeutic purposes. For example, psoralen plus UVA therapy has been used for psoriasis and vitiligo and photodynamic therapy for actinic keratoses and superficial nonmelanoma skin cancers.¹ However, these agents can induce severe phototoxicity if UV light exposure is not carefully monitored, as seen in our patient. This case is a classic example of phototoxic contact dermatitis and highlights the importance of obtaining a detailed patient history to allow for proper diagnosis and identification of the causative agent. Importantly, because prescription-strength topical medications are readily available over-the-counter, particularly in stores specializing in international goods, patients should be questioned about the use of all topical and systemic medications, both prescription and nonprescription.²