Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Both overall and unsubsidized enrollment in the various state and federal health insurance exchanges dropped in 2018, but new data on payments for those policies show that more people paid their premiums in 2019, according to the Centers for Medicare & Medicaid Services.

The number of policies selected with the individual insurance exchanges in late 2018 for which premiums were paid in February 2019 (termed the effectuated enrollment) was almost 10.6 million, or more than 92% of the 11.4 million plans selected during open enrollment, CMS reported. For February 2018, effectuated enrollment was just over 10.5 million, which represented 89.5% of the nearly 11.8 million policies selected during the previous open enrollment.

Over the longer term, the trend has been a rise and a fall as average monthly effectuated enrollment peaked in 2016 and dropped 16.5% by 2018, CMS data show.

A look at the advance premium tax credit (APTC) provides some insight into that decline. The population subsidized by the APTC has been fairly stable since 2016 – effectuated enrollment rose by just over 1% – but the number of unsubsidized enrollees has dropped 40% as 2.5 million people who did not qualify for the APTC left the market, the CMS said.

From 2017 to 2018, there were 47 states with declines in unsubsidized enrollment, with 9 states losing more than 40% of such enrollees. The largest drop in the unsubsidized population (85%) came in Iowa, while Alaska’s 7% gain was the largest increase, the CMS reported.

“As President Trump predicted, people are fleeing the individual market. Obamacare is failing the American people, and the ongoing exodus of the unsubsidized population from the market proves that Obamacare’s sky-high premiums are unaffordable,” CMS Administrator Seema Verma said in a written statement.

[email protected]

Both overall and unsubsidized enrollment in the various state and federal health insurance exchanges dropped in 2018, but new data on payments for those policies show that more people paid their premiums in 2019, according to the Centers for Medicare & Medicaid Services.

The number of policies selected with the individual insurance exchanges in late 2018 for which premiums were paid in February 2019 (termed the effectuated enrollment) was almost 10.6 million, or more than 92% of the 11.4 million plans selected during open enrollment, CMS reported. For February 2018, effectuated enrollment was just over 10.5 million, which represented 89.5% of the nearly 11.8 million policies selected during the previous open enrollment.

Over the longer term, the trend has been a rise and a fall as average monthly effectuated enrollment peaked in 2016 and dropped 16.5% by 2018, CMS data show.

A look at the advance premium tax credit (APTC) provides some insight into that decline. The population subsidized by the APTC has been fairly stable since 2016 – effectuated enrollment rose by just over 1% – but the number of unsubsidized enrollees has dropped 40% as 2.5 million people who did not qualify for the APTC left the market, the CMS said.

From 2017 to 2018, there were 47 states with declines in unsubsidized enrollment, with 9 states losing more than 40% of such enrollees. The largest drop in the unsubsidized population (85%) came in Iowa, while Alaska’s 7% gain was the largest increase, the CMS reported.

“As President Trump predicted, people are fleeing the individual market. Obamacare is failing the American people, and the ongoing exodus of the unsubsidized population from the market proves that Obamacare’s sky-high premiums are unaffordable,” CMS Administrator Seema Verma said in a written statement.

[email protected]

Both overall and unsubsidized enrollment in the various state and federal health insurance exchanges dropped in 2018, but new data on payments for those policies show that more people paid their premiums in 2019, according to the Centers for Medicare & Medicaid Services.

The number of policies selected with the individual insurance exchanges in late 2018 for which premiums were paid in February 2019 (termed the effectuated enrollment) was almost 10.6 million, or more than 92% of the 11.4 million plans selected during open enrollment, CMS reported. For February 2018, effectuated enrollment was just over 10.5 million, which represented 89.5% of the nearly 11.8 million policies selected during the previous open enrollment.

Over the longer term, the trend has been a rise and a fall as average monthly effectuated enrollment peaked in 2016 and dropped 16.5% by 2018, CMS data show.

A look at the advance premium tax credit (APTC) provides some insight into that decline. The population subsidized by the APTC has been fairly stable since 2016 – effectuated enrollment rose by just over 1% – but the number of unsubsidized enrollees has dropped 40% as 2.5 million people who did not qualify for the APTC left the market, the CMS said.

From 2017 to 2018, there were 47 states with declines in unsubsidized enrollment, with 9 states losing more than 40% of such enrollees. The largest drop in the unsubsidized population (85%) came in Iowa, while Alaska’s 7% gain was the largest increase, the CMS reported.

“As President Trump predicted, people are fleeing the individual market. Obamacare is failing the American people, and the ongoing exodus of the unsubsidized population from the market proves that Obamacare’s sky-high premiums are unaffordable,” CMS Administrator Seema Verma said in a written statement.

[email protected]

To the Editor:

Long, dark, and thick eyelashes have been a focal point of society’s perception of beauty for thousands of years,¹ and the use of makeup products such as mascaras, eyeliners, and eye shadows has further increased the perception of attractiveness of the eyes.² Many eyelash enhancement methods have been developed or in some instances have been serendipitously discovered. Bimatoprost ophthalmic solution 0.03% originally was developed as an eye drop that was approved by the US Food and Drug Association (FDA) in 2001 for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. An unexpected side effect of this product was eyelash hypertrichosis.^3,4 As a result, the FDA approved bimatoprost ophthalmic solution 0.03% as an eyelash solution with an eyelid applicator for treatment of eyelash hypotrichosis in 2008.⁵

Because all follicular development occurs during embryogenesis, the number of eyelash follicles does not increase over time.⁶ Bitmatoprost eyelash solution works by prolonging the anagen (growth) phase of the eyelashes and stimulating the transition from the telogen (dormant) phase to the anagen phase. It also has been shown to increase the hair bulb diameter of follicles undergoing the anagen phase, resulting in thicker eyelashes.⁷ Although many patients have enjoyed this unexpected indication, prostaglandin (PG) analogues such as bimatoprost and latanoprost have a well-documented history of ocular side effects when applied directly to the eye. The most common adverse reactions include eye pruritus, conjunctival hyperemia, and eyelid pigmentation.³ The product safety information indicates that eyelid pigmentation typically is reversible.^3,5 Iris pigmentation is perhaps the least desirable side effect of PG analogues and was first noted in latanoprost studies on primates.⁸ The underlying mechanism appears to be due to an increase in melanogenesis that results in an increase in melanin granules without concomitant proliferation of melanocytes, cellular atypia, or evidence of inflammatory reaction. Unfortunately, this pigmentation typically is permanent.^3,5,9

Studies have shown that iris hyperpigmentation can occur when bimatoprost eye drops are applied to the eyes for the treatment of glaucoma and ocular hypertension, but reports associated with bimatoprost eyelash solution are rare.^3,4,10 We report a case of iris hyperpigmentation following cosmetic use of bimatoprost eyelash solution.

An otherwise healthy 63-year-old woman presented to our clinic for an annual skin examination. She noted that she had worsening dark pigmentation of the bilateral irises. The patient did not have any personal or family history of melanoma or ocular nevi, and there were no associated symptoms of eye tearing, pruritus, burning, or discharge. No prior surgical procedures had been performed on or around the eyes, and the patient never used contact lenses. She had been intermittently using bimatoprost eyelash solution prescribed by an outside physician for approximately 3 years to enhance her eyelashes. Although she never applied the product directly into her eyes, she noted that she often was unmethodical in application of the product and that runoff from the product may have occasionally leaked into the eyes. Physical examination revealed bilateral blue irises with ink spot–like, grayish black patches encircling the bilateral pupils (Figure).

There have been several studies of iris hyperpigmentation with use of PG analogues in the treatment of glaucoma. In a phase 3 clinical trial of the safety and efficacy of latanoprost for treatment of ocular hypertension, it was noted that 24 (12%) of 198 patients experienced iris hyperpigmentation and that patients with heterogeneous pigmentation (ie, hazel irises and mixed coloring) were at an increased risk.¹¹ Other studies also have shown an increased risk of iris hyperpigmentation due to heterogeneous phenotype¹² as well as older age.¹³

Reports of bimatoprost eye drops used for treatment of glaucoma have shown a high incidence of iris hyperpigmentation with long-term use. A prospective study conducted in 2012 investigated the adverse events of bimatoprost eye drops in 52 Japanese patients with glaucoma or ocular hypertension. Clinical photographs of the irises, eyelids, and eyelashes were taken at baseline and after 6 months of treatment. It was noted that 50% (26/52) of participants experienced iris hyperpigmentation upon completion of treatment.¹⁰

In our patient, bimatoprost eyelash solution was applied to the top eyelid margins using an applicator; our patient did not use the eye drop formulation, which is directed for use in ocular hypertension or glaucoma. A PubMed search of articles indexed for MEDLINE using the terms bimatoprost and iris hyperpigmentation yielded no published peer-reviewed studies or case reports of iris hyperpigmentation caused by bimatoprost eyelash solution for treatment of eyelid hypotrichosis, which makes this case report novel. With that said, the package insert states iris hyperpigmentation as a side effect in the prescribing information for both a bimatoprost eye drop formulation used to treat ocular hypertension³ as well as a formulation for topical application on the eyelids/eyelashes.⁵ A 2014 retrospective review of long-term safety with bimatoprost eyelash solution for eyelash hypotrichosis reported 4 instances (0.7%) of documented adverse events after 12 months of use in 585 patients, including dry eye, eyelid erythema, ocular pruritus, and low ocular pressure. Iris hyperpigmentation was not reported.¹⁴

The method of bimatoprost application likely is a determining factor in the number of reported adverse events. Studies with similar treatment periods have demonstrated more adverse events associated with bimatoprost eye drops vs eyelash solution.^15,16 When bimatoprost is used in the eye drop formulation for treatment of glaucoma, iris hyperpigmentation has been estimated to occur in 1.5%⁴ to 50%⁹ of cases. To our knowledge, there are no documented cases when bimatoprost eyelash solution is applied with a dermal applicator for treatment of eyelash hypotrichosis.^15,17 These results may be explained using an ocular splash test. In one study using lissamine green dye, decreased delivery of bimatoprost eyelash solution with the dermal applicator was noted vs eye drop application. Additionally, it has been demonstrated that approximately 5% (based on weight) of a one-drop dose of bimatoprost eyelash solution applied to the dermal applicator is actually delivered to the patient.¹⁸ The rest of the solution remains on the applicator.

It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information (eg, clean the face, remove makeup and contact lenses prior to applying the product). The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye. One drop of bimatoprost eyelash solution should be applied to the applicator supplied by the manufacturer and distributed evenly along the skin of the upper eyelid margin at the base of the eyelashes. It is important to blot any excess solution runoff outside the upper eyelid margin.⁵ Of note, our patient admitted to not always doing this step, which may have contributed to her susceptibility to this rare side effect.

Prostaglandin analogues have been observed to cause iris hyperpigmentation when applied directly to the eye for use in the treatment of glaucoma.¹⁹ Theoretically, the same side-effect profile should apply in their use as a dermal application on the eyelids. For this reason, one manufacturer includes iris hyperpigmentation as an adverse side effect in the prescribing information.⁵ It is important for physicians who prescribe bimatoprost eyelash solution to inform patients of this rare yet possible side effect and to instruct patients on proper application to minimize hyperpigmentation.

Our literature review did not demonstrate previous cases of iris hyperpigmentation associated with bimatoprost eyelash solution. One study suggested that 2 patients experienced hypopigmentation; however, this was not clinically significant and was not consistent with the proposed iris pigmentation thought to be caused by bimatoprost eyelash solution.²⁰

Potential future applications and off-label uses of bimatoprost include treatment of eyelash hypotrichosis on the lower eyelid margin and eyebrow hypertrichosis, as well as androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring.²¹ Currently, investigational studies are looking at bimatoprost ophthalmic solution 0.03% for chemotherapy-induced eyelash hypotrichosis with positive results.²² In the future, bimatoprost may be used for other off-label and possibly FDA-approved uses.

To the Editor:

Long, dark, and thick eyelashes have been a focal point of society’s perception of beauty for thousands of years,¹ and the use of makeup products such as mascaras, eyeliners, and eye shadows has further increased the perception of attractiveness of the eyes.² Many eyelash enhancement methods have been developed or in some instances have been serendipitously discovered. Bimatoprost ophthalmic solution 0.03% originally was developed as an eye drop that was approved by the US Food and Drug Association (FDA) in 2001 for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. An unexpected side effect of this product was eyelash hypertrichosis.^3,4 As a result, the FDA approved bimatoprost ophthalmic solution 0.03% as an eyelash solution with an eyelid applicator for treatment of eyelash hypotrichosis in 2008.⁵

Because all follicular development occurs during embryogenesis, the number of eyelash follicles does not increase over time.⁶ Bitmatoprost eyelash solution works by prolonging the anagen (growth) phase of the eyelashes and stimulating the transition from the telogen (dormant) phase to the anagen phase. It also has been shown to increase the hair bulb diameter of follicles undergoing the anagen phase, resulting in thicker eyelashes.⁷ Although many patients have enjoyed this unexpected indication, prostaglandin (PG) analogues such as bimatoprost and latanoprost have a well-documented history of ocular side effects when applied directly to the eye. The most common adverse reactions include eye pruritus, conjunctival hyperemia, and eyelid pigmentation.³ The product safety information indicates that eyelid pigmentation typically is reversible.^3,5 Iris pigmentation is perhaps the least desirable side effect of PG analogues and was first noted in latanoprost studies on primates.⁸ The underlying mechanism appears to be due to an increase in melanogenesis that results in an increase in melanin granules without concomitant proliferation of melanocytes, cellular atypia, or evidence of inflammatory reaction. Unfortunately, this pigmentation typically is permanent.^3,5,9

Studies have shown that iris hyperpigmentation can occur when bimatoprost eye drops are applied to the eyes for the treatment of glaucoma and ocular hypertension, but reports associated with bimatoprost eyelash solution are rare.^3,4,10 We report a case of iris hyperpigmentation following cosmetic use of bimatoprost eyelash solution.

An otherwise healthy 63-year-old woman presented to our clinic for an annual skin examination. She noted that she had worsening dark pigmentation of the bilateral irises. The patient did not have any personal or family history of melanoma or ocular nevi, and there were no associated symptoms of eye tearing, pruritus, burning, or discharge. No prior surgical procedures had been performed on or around the eyes, and the patient never used contact lenses. She had been intermittently using bimatoprost eyelash solution prescribed by an outside physician for approximately 3 years to enhance her eyelashes. Although she never applied the product directly into her eyes, she noted that she often was unmethodical in application of the product and that runoff from the product may have occasionally leaked into the eyes. Physical examination revealed bilateral blue irises with ink spot–like, grayish black patches encircling the bilateral pupils (Figure).

There have been several studies of iris hyperpigmentation with use of PG analogues in the treatment of glaucoma. In a phase 3 clinical trial of the safety and efficacy of latanoprost for treatment of ocular hypertension, it was noted that 24 (12%) of 198 patients experienced iris hyperpigmentation and that patients with heterogeneous pigmentation (ie, hazel irises and mixed coloring) were at an increased risk.¹¹ Other studies also have shown an increased risk of iris hyperpigmentation due to heterogeneous phenotype¹² as well as older age.¹³

Reports of bimatoprost eye drops used for treatment of glaucoma have shown a high incidence of iris hyperpigmentation with long-term use. A prospective study conducted in 2012 investigated the adverse events of bimatoprost eye drops in 52 Japanese patients with glaucoma or ocular hypertension. Clinical photographs of the irises, eyelids, and eyelashes were taken at baseline and after 6 months of treatment. It was noted that 50% (26/52) of participants experienced iris hyperpigmentation upon completion of treatment.¹⁰

In our patient, bimatoprost eyelash solution was applied to the top eyelid margins using an applicator; our patient did not use the eye drop formulation, which is directed for use in ocular hypertension or glaucoma. A PubMed search of articles indexed for MEDLINE using the terms bimatoprost and iris hyperpigmentation yielded no published peer-reviewed studies or case reports of iris hyperpigmentation caused by bimatoprost eyelash solution for treatment of eyelid hypotrichosis, which makes this case report novel. With that said, the package insert states iris hyperpigmentation as a side effect in the prescribing information for both a bimatoprost eye drop formulation used to treat ocular hypertension³ as well as a formulation for topical application on the eyelids/eyelashes.⁵ A 2014 retrospective review of long-term safety with bimatoprost eyelash solution for eyelash hypotrichosis reported 4 instances (0.7%) of documented adverse events after 12 months of use in 585 patients, including dry eye, eyelid erythema, ocular pruritus, and low ocular pressure. Iris hyperpigmentation was not reported.¹⁴

The method of bimatoprost application likely is a determining factor in the number of reported adverse events. Studies with similar treatment periods have demonstrated more adverse events associated with bimatoprost eye drops vs eyelash solution.^15,16 When bimatoprost is used in the eye drop formulation for treatment of glaucoma, iris hyperpigmentation has been estimated to occur in 1.5%⁴ to 50%⁹ of cases. To our knowledge, there are no documented cases when bimatoprost eyelash solution is applied with a dermal applicator for treatment of eyelash hypotrichosis.^15,17 These results may be explained using an ocular splash test. In one study using lissamine green dye, decreased delivery of bimatoprost eyelash solution with the dermal applicator was noted vs eye drop application. Additionally, it has been demonstrated that approximately 5% (based on weight) of a one-drop dose of bimatoprost eyelash solution applied to the dermal applicator is actually delivered to the patient.¹⁸ The rest of the solution remains on the applicator.

It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information (eg, clean the face, remove makeup and contact lenses prior to applying the product). The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye. One drop of bimatoprost eyelash solution should be applied to the applicator supplied by the manufacturer and distributed evenly along the skin of the upper eyelid margin at the base of the eyelashes. It is important to blot any excess solution runoff outside the upper eyelid margin.⁵ Of note, our patient admitted to not always doing this step, which may have contributed to her susceptibility to this rare side effect.

Prostaglandin analogues have been observed to cause iris hyperpigmentation when applied directly to the eye for use in the treatment of glaucoma.¹⁹ Theoretically, the same side-effect profile should apply in their use as a dermal application on the eyelids. For this reason, one manufacturer includes iris hyperpigmentation as an adverse side effect in the prescribing information.⁵ It is important for physicians who prescribe bimatoprost eyelash solution to inform patients of this rare yet possible side effect and to instruct patients on proper application to minimize hyperpigmentation.

Our literature review did not demonstrate previous cases of iris hyperpigmentation associated with bimatoprost eyelash solution. One study suggested that 2 patients experienced hypopigmentation; however, this was not clinically significant and was not consistent with the proposed iris pigmentation thought to be caused by bimatoprost eyelash solution.²⁰

Potential future applications and off-label uses of bimatoprost include treatment of eyelash hypotrichosis on the lower eyelid margin and eyebrow hypertrichosis, as well as androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring.²¹ Currently, investigational studies are looking at bimatoprost ophthalmic solution 0.03% for chemotherapy-induced eyelash hypotrichosis with positive results.²² In the future, bimatoprost may be used for other off-label and possibly FDA-approved uses.

To the Editor:

Long, dark, and thick eyelashes have been a focal point of society’s perception of beauty for thousands of years,¹ and the use of makeup products such as mascaras, eyeliners, and eye shadows has further increased the perception of attractiveness of the eyes.² Many eyelash enhancement methods have been developed or in some instances have been serendipitously discovered. Bimatoprost ophthalmic solution 0.03% originally was developed as an eye drop that was approved by the US Food and Drug Association (FDA) in 2001 for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. An unexpected side effect of this product was eyelash hypertrichosis.^3,4 As a result, the FDA approved bimatoprost ophthalmic solution 0.03% as an eyelash solution with an eyelid applicator for treatment of eyelash hypotrichosis in 2008.⁵

Because all follicular development occurs during embryogenesis, the number of eyelash follicles does not increase over time.⁶ Bitmatoprost eyelash solution works by prolonging the anagen (growth) phase of the eyelashes and stimulating the transition from the telogen (dormant) phase to the anagen phase. It also has been shown to increase the hair bulb diameter of follicles undergoing the anagen phase, resulting in thicker eyelashes.⁷ Although many patients have enjoyed this unexpected indication, prostaglandin (PG) analogues such as bimatoprost and latanoprost have a well-documented history of ocular side effects when applied directly to the eye. The most common adverse reactions include eye pruritus, conjunctival hyperemia, and eyelid pigmentation.³ The product safety information indicates that eyelid pigmentation typically is reversible.^3,5 Iris pigmentation is perhaps the least desirable side effect of PG analogues and was first noted in latanoprost studies on primates.⁸ The underlying mechanism appears to be due to an increase in melanogenesis that results in an increase in melanin granules without concomitant proliferation of melanocytes, cellular atypia, or evidence of inflammatory reaction. Unfortunately, this pigmentation typically is permanent.^3,5,9

Studies have shown that iris hyperpigmentation can occur when bimatoprost eye drops are applied to the eyes for the treatment of glaucoma and ocular hypertension, but reports associated with bimatoprost eyelash solution are rare.^3,4,10 We report a case of iris hyperpigmentation following cosmetic use of bimatoprost eyelash solution.

An otherwise healthy 63-year-old woman presented to our clinic for an annual skin examination. She noted that she had worsening dark pigmentation of the bilateral irises. The patient did not have any personal or family history of melanoma or ocular nevi, and there were no associated symptoms of eye tearing, pruritus, burning, or discharge. No prior surgical procedures had been performed on or around the eyes, and the patient never used contact lenses. She had been intermittently using bimatoprost eyelash solution prescribed by an outside physician for approximately 3 years to enhance her eyelashes. Although she never applied the product directly into her eyes, she noted that she often was unmethodical in application of the product and that runoff from the product may have occasionally leaked into the eyes. Physical examination revealed bilateral blue irises with ink spot–like, grayish black patches encircling the bilateral pupils (Figure).

There have been several studies of iris hyperpigmentation with use of PG analogues in the treatment of glaucoma. In a phase 3 clinical trial of the safety and efficacy of latanoprost for treatment of ocular hypertension, it was noted that 24 (12%) of 198 patients experienced iris hyperpigmentation and that patients with heterogeneous pigmentation (ie, hazel irises and mixed coloring) were at an increased risk.¹¹ Other studies also have shown an increased risk of iris hyperpigmentation due to heterogeneous phenotype¹² as well as older age.¹³

Reports of bimatoprost eye drops used for treatment of glaucoma have shown a high incidence of iris hyperpigmentation with long-term use. A prospective study conducted in 2012 investigated the adverse events of bimatoprost eye drops in 52 Japanese patients with glaucoma or ocular hypertension. Clinical photographs of the irises, eyelids, and eyelashes were taken at baseline and after 6 months of treatment. It was noted that 50% (26/52) of participants experienced iris hyperpigmentation upon completion of treatment.¹⁰

In our patient, bimatoprost eyelash solution was applied to the top eyelid margins using an applicator; our patient did not use the eye drop formulation, which is directed for use in ocular hypertension or glaucoma. A PubMed search of articles indexed for MEDLINE using the terms bimatoprost and iris hyperpigmentation yielded no published peer-reviewed studies or case reports of iris hyperpigmentation caused by bimatoprost eyelash solution for treatment of eyelid hypotrichosis, which makes this case report novel. With that said, the package insert states iris hyperpigmentation as a side effect in the prescribing information for both a bimatoprost eye drop formulation used to treat ocular hypertension³ as well as a formulation for topical application on the eyelids/eyelashes.⁵ A 2014 retrospective review of long-term safety with bimatoprost eyelash solution for eyelash hypotrichosis reported 4 instances (0.7%) of documented adverse events after 12 months of use in 585 patients, including dry eye, eyelid erythema, ocular pruritus, and low ocular pressure. Iris hyperpigmentation was not reported.¹⁴

The method of bimatoprost application likely is a determining factor in the number of reported adverse events. Studies with similar treatment periods have demonstrated more adverse events associated with bimatoprost eye drops vs eyelash solution.^15,16 When bimatoprost is used in the eye drop formulation for treatment of glaucoma, iris hyperpigmentation has been estimated to occur in 1.5%⁴ to 50%⁹ of cases. To our knowledge, there are no documented cases when bimatoprost eyelash solution is applied with a dermal applicator for treatment of eyelash hypotrichosis.^15,17 These results may be explained using an ocular splash test. In one study using lissamine green dye, decreased delivery of bimatoprost eyelash solution with the dermal applicator was noted vs eye drop application. Additionally, it has been demonstrated that approximately 5% (based on weight) of a one-drop dose of bimatoprost eyelash solution applied to the dermal applicator is actually delivered to the patient.¹⁸ The rest of the solution remains on the applicator.

It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information (eg, clean the face, remove makeup and contact lenses prior to applying the product). The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye. One drop of bimatoprost eyelash solution should be applied to the applicator supplied by the manufacturer and distributed evenly along the skin of the upper eyelid margin at the base of the eyelashes. It is important to blot any excess solution runoff outside the upper eyelid margin.⁵ Of note, our patient admitted to not always doing this step, which may have contributed to her susceptibility to this rare side effect.

Prostaglandin analogues have been observed to cause iris hyperpigmentation when applied directly to the eye for use in the treatment of glaucoma.¹⁹ Theoretically, the same side-effect profile should apply in their use as a dermal application on the eyelids. For this reason, one manufacturer includes iris hyperpigmentation as an adverse side effect in the prescribing information.⁵ It is important for physicians who prescribe bimatoprost eyelash solution to inform patients of this rare yet possible side effect and to instruct patients on proper application to minimize hyperpigmentation.

Our literature review did not demonstrate previous cases of iris hyperpigmentation associated with bimatoprost eyelash solution. One study suggested that 2 patients experienced hypopigmentation; however, this was not clinically significant and was not consistent with the proposed iris pigmentation thought to be caused by bimatoprost eyelash solution.²⁰

Potential future applications and off-label uses of bimatoprost include treatment of eyelash hypotrichosis on the lower eyelid margin and eyebrow hypertrichosis, as well as androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring.²¹ Currently, investigational studies are looking at bimatoprost ophthalmic solution 0.03% for chemotherapy-induced eyelash hypotrichosis with positive results.²² In the future, bimatoprost may be used for other off-label and possibly FDA-approved uses.

I wear a suit every day to work. I count the time between shifts in months, not days. Rather than looking for subtle diagnostic clues hidden in clinical information, I find myself up to my elbows in performance and financial data. Instead of meetings complicated by challenging family dynamics, I spend my time calming the waters between clinical departments that each feel slighted.

And yet, when people ask me what I do, I do not say I am a health system CEO. Rather, I am a hospitalist. I say it, not out of habit, but with pride and clear intention. Almost 20 years ago, I had to explain to my parents what a hospitalist was as I made the transition from primary care doctor to hospitalist. I told them that hospitalists take care of sick people who are in the hospital, but also are charged with making the hospital a better place to take care of people. I hope that in some small way, in every role I have had over the past 20 years as a hospitalist, I have been able to do that.

While the small changes we can all make every day are important, massive changes to health care, hospitals, and providers are coming. The forces driving these changes are manifold, complex, and powerful. Individual hospitalists, hospital groups, and hospitals will be challenged to keep up with responding to these changes. I hope, though, that our field, hospital medicine, will not be sitting there, waiting for the changes to come, but will instead be one of the forces for change.

I also believe that hospital medicine and health care delivery systems should drive the change in a coordinated and collaborative partnership. A partnership not built on self-advocacy but one in which we remember why we exist – to take care of people. A force for change that preserves the essential, evolves what needs improvement, and revolutionizes the archaic.

Partnerships between hospitalist groups and health care administration will always face the day-to-day challenges of balancing the need for resources with the ability to provide them, agreeing on how to measure and assess quality, and aligning rewards with priorities. However, by working together in venues that allow us to think beyond the day-to-day issues, we in hospital medicine will be leaders in the change that is coming. I believe that today, the Society of Hospital Medicine must be one of those venues. Through its committees, meetings, advocacy, publications, and most importantly, members, SHM will continue to shape the future of care delivery in this country and beyond.

SHM has been my professional home for almost 20 years, helping me think about how to make the hospital a better place to take care of people. Recent examples of SHM and its members partnering in this area include advocacy work to improve alternative payment models, such as Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), as well as educational efforts for its members on how to navigate the current rules around MACRA.

For many years, SHM has been the leader in professional organizations for leading the way on quality improvement. Through the Center for Quality Improvement, SHM not only offers robust educational tools to better enable members to lead efforts at their home institutions but also has led multi-institutional efforts to reduce harm that have been recognized nationally for their impact.

As we move further down the path from volume to value toward population health, the SHM Board will be sure that the society continues to be a leader for both its members and the health system at large as we face these changes. We have the opportunity in front of us to collectively embrace and create the changes coming toward us with that shared purpose of making wherever it is that we care for people better places to provide that care. How could one not be proud to say, with intent, “I am a hospitalist,” regardless of what it is that brings each of us to SHM.
 

Dr. Whelan is CEO of Banner–University Medical Center Tucson (Ariz.) and a member of the SHM Board of Directors.

I wear a suit every day to work. I count the time between shifts in months, not days. Rather than looking for subtle diagnostic clues hidden in clinical information, I find myself up to my elbows in performance and financial data. Instead of meetings complicated by challenging family dynamics, I spend my time calming the waters between clinical departments that each feel slighted.

And yet, when people ask me what I do, I do not say I am a health system CEO. Rather, I am a hospitalist. I say it, not out of habit, but with pride and clear intention. Almost 20 years ago, I had to explain to my parents what a hospitalist was as I made the transition from primary care doctor to hospitalist. I told them that hospitalists take care of sick people who are in the hospital, but also are charged with making the hospital a better place to take care of people. I hope that in some small way, in every role I have had over the past 20 years as a hospitalist, I have been able to do that.

While the small changes we can all make every day are important, massive changes to health care, hospitals, and providers are coming. The forces driving these changes are manifold, complex, and powerful. Individual hospitalists, hospital groups, and hospitals will be challenged to keep up with responding to these changes. I hope, though, that our field, hospital medicine, will not be sitting there, waiting for the changes to come, but will instead be one of the forces for change.

I also believe that hospital medicine and health care delivery systems should drive the change in a coordinated and collaborative partnership. A partnership not built on self-advocacy but one in which we remember why we exist – to take care of people. A force for change that preserves the essential, evolves what needs improvement, and revolutionizes the archaic.

Partnerships between hospitalist groups and health care administration will always face the day-to-day challenges of balancing the need for resources with the ability to provide them, agreeing on how to measure and assess quality, and aligning rewards with priorities. However, by working together in venues that allow us to think beyond the day-to-day issues, we in hospital medicine will be leaders in the change that is coming. I believe that today, the Society of Hospital Medicine must be one of those venues. Through its committees, meetings, advocacy, publications, and most importantly, members, SHM will continue to shape the future of care delivery in this country and beyond.

SHM has been my professional home for almost 20 years, helping me think about how to make the hospital a better place to take care of people. Recent examples of SHM and its members partnering in this area include advocacy work to improve alternative payment models, such as Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), as well as educational efforts for its members on how to navigate the current rules around MACRA.

For many years, SHM has been the leader in professional organizations for leading the way on quality improvement. Through the Center for Quality Improvement, SHM not only offers robust educational tools to better enable members to lead efforts at their home institutions but also has led multi-institutional efforts to reduce harm that have been recognized nationally for their impact.

As we move further down the path from volume to value toward population health, the SHM Board will be sure that the society continues to be a leader for both its members and the health system at large as we face these changes. We have the opportunity in front of us to collectively embrace and create the changes coming toward us with that shared purpose of making wherever it is that we care for people better places to provide that care. How could one not be proud to say, with intent, “I am a hospitalist,” regardless of what it is that brings each of us to SHM.
 

Dr. Whelan is CEO of Banner–University Medical Center Tucson (Ariz.) and a member of the SHM Board of Directors.

I wear a suit every day to work. I count the time between shifts in months, not days. Rather than looking for subtle diagnostic clues hidden in clinical information, I find myself up to my elbows in performance and financial data. Instead of meetings complicated by challenging family dynamics, I spend my time calming the waters between clinical departments that each feel slighted.

And yet, when people ask me what I do, I do not say I am a health system CEO. Rather, I am a hospitalist. I say it, not out of habit, but with pride and clear intention. Almost 20 years ago, I had to explain to my parents what a hospitalist was as I made the transition from primary care doctor to hospitalist. I told them that hospitalists take care of sick people who are in the hospital, but also are charged with making the hospital a better place to take care of people. I hope that in some small way, in every role I have had over the past 20 years as a hospitalist, I have been able to do that.

While the small changes we can all make every day are important, massive changes to health care, hospitals, and providers are coming. The forces driving these changes are manifold, complex, and powerful. Individual hospitalists, hospital groups, and hospitals will be challenged to keep up with responding to these changes. I hope, though, that our field, hospital medicine, will not be sitting there, waiting for the changes to come, but will instead be one of the forces for change.

I also believe that hospital medicine and health care delivery systems should drive the change in a coordinated and collaborative partnership. A partnership not built on self-advocacy but one in which we remember why we exist – to take care of people. A force for change that preserves the essential, evolves what needs improvement, and revolutionizes the archaic.

Partnerships between hospitalist groups and health care administration will always face the day-to-day challenges of balancing the need for resources with the ability to provide them, agreeing on how to measure and assess quality, and aligning rewards with priorities. However, by working together in venues that allow us to think beyond the day-to-day issues, we in hospital medicine will be leaders in the change that is coming. I believe that today, the Society of Hospital Medicine must be one of those venues. Through its committees, meetings, advocacy, publications, and most importantly, members, SHM will continue to shape the future of care delivery in this country and beyond.

SHM has been my professional home for almost 20 years, helping me think about how to make the hospital a better place to take care of people. Recent examples of SHM and its members partnering in this area include advocacy work to improve alternative payment models, such as Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), as well as educational efforts for its members on how to navigate the current rules around MACRA.

For many years, SHM has been the leader in professional organizations for leading the way on quality improvement. Through the Center for Quality Improvement, SHM not only offers robust educational tools to better enable members to lead efforts at their home institutions but also has led multi-institutional efforts to reduce harm that have been recognized nationally for their impact.

As we move further down the path from volume to value toward population health, the SHM Board will be sure that the society continues to be a leader for both its members and the health system at large as we face these changes. We have the opportunity in front of us to collectively embrace and create the changes coming toward us with that shared purpose of making wherever it is that we care for people better places to provide that care. How could one not be proud to say, with intent, “I am a hospitalist,” regardless of what it is that brings each of us to SHM.
 

Dr. Whelan is CEO of Banner–University Medical Center Tucson (Ariz.) and a member of the SHM Board of Directors.

The Diagnosis: Granulosis Rubra Nasi 

A history of prominent nasal sweating was later elicited and the patient was subsequently diagnosed with granulosis rubra nasi. She was instructed to continue daily use of topical pimecrolimus with the addition of topical atropine, resulting in complete resolution of the eruption at 6-week follow-up (Figure, A). She was then maintained on topical atropine monotherapy, only noting recurrence with cessation of the atropine (Figure, B).  

Other successful treatment regimens of granulosis rubra nasi include injection of botulinum toxin into the nose,¹ monotherapy with topical tacrolimus,² topical indomethacin, steroids, and cryotherapy, among other modalities.¹ Topical atropine and pimecrolimus were selected as first-line agents for treating our pediatric patient due to tolerability and their anti-inflammatory and anticholinergic properties.  

Granulosis rubra nasi is a form of focal hyperhidrosis that presents as erythematous papules, pustules, and vesicles of the midface, especially the nose.3 It is a fairly rare condition that can mimic many other common clinical entities, including comedonal acne, nevus comedonicus, periorificial dermatitis, and tinea faciei, but is resistant to treatments aimed at these disorders. It was first described as a "peculiar disease of the skin of the nose in children" in a case report by Jadassohn⁴ in 1901. It is most common in children aged 7 to 12 years and typically resolves at puberty; adults rarely are affected. Although the etiology has not yet been elucidated, autosomal-dominant transmission has been described, and the cutaneous changes are hypothesized to be secondary to hyperhidrosis.⁵ This postulation is further corroborated by a case report of a pheochromocytoma-associated granulosis rubra nasi that resolved with surgical excision of the pheochromocytoma.⁶ It is not uncommon for patients to have concomitant palmoplantar hyperhidrosis and acrocyanosis.⁵ Histopathologic examination is not necessary for diagnosis, but when performed, it discloses a mononuclear cellular infiltrate surrounding eccrine sweat ducts, blood vessels, and lymphatics without other abnormalities of the epidermis or pilosebaceous unit.^1-3,7 
 

The Diagnosis: Granulosis Rubra Nasi 

A history of prominent nasal sweating was later elicited and the patient was subsequently diagnosed with granulosis rubra nasi. She was instructed to continue daily use of topical pimecrolimus with the addition of topical atropine, resulting in complete resolution of the eruption at 6-week follow-up (Figure, A). She was then maintained on topical atropine monotherapy, only noting recurrence with cessation of the atropine (Figure, B).  

Other successful treatment regimens of granulosis rubra nasi include injection of botulinum toxin into the nose,¹ monotherapy with topical tacrolimus,² topical indomethacin, steroids, and cryotherapy, among other modalities.¹ Topical atropine and pimecrolimus were selected as first-line agents for treating our pediatric patient due to tolerability and their anti-inflammatory and anticholinergic properties.  

Granulosis rubra nasi is a form of focal hyperhidrosis that presents as erythematous papules, pustules, and vesicles of the midface, especially the nose.3 It is a fairly rare condition that can mimic many other common clinical entities, including comedonal acne, nevus comedonicus, periorificial dermatitis, and tinea faciei, but is resistant to treatments aimed at these disorders. It was first described as a "peculiar disease of the skin of the nose in children" in a case report by Jadassohn⁴ in 1901. It is most common in children aged 7 to 12 years and typically resolves at puberty; adults rarely are affected. Although the etiology has not yet been elucidated, autosomal-dominant transmission has been described, and the cutaneous changes are hypothesized to be secondary to hyperhidrosis.⁵ This postulation is further corroborated by a case report of a pheochromocytoma-associated granulosis rubra nasi that resolved with surgical excision of the pheochromocytoma.⁶ It is not uncommon for patients to have concomitant palmoplantar hyperhidrosis and acrocyanosis.⁵ Histopathologic examination is not necessary for diagnosis, but when performed, it discloses a mononuclear cellular infiltrate surrounding eccrine sweat ducts, blood vessels, and lymphatics without other abnormalities of the epidermis or pilosebaceous unit.^1-3,7 
 

The Diagnosis: Granulosis Rubra Nasi 

A history of prominent nasal sweating was later elicited and the patient was subsequently diagnosed with granulosis rubra nasi. She was instructed to continue daily use of topical pimecrolimus with the addition of topical atropine, resulting in complete resolution of the eruption at 6-week follow-up (Figure, A). She was then maintained on topical atropine monotherapy, only noting recurrence with cessation of the atropine (Figure, B).  

Other successful treatment regimens of granulosis rubra nasi include injection of botulinum toxin into the nose,¹ monotherapy with topical tacrolimus,² topical indomethacin, steroids, and cryotherapy, among other modalities.¹ Topical atropine and pimecrolimus were selected as first-line agents for treating our pediatric patient due to tolerability and their anti-inflammatory and anticholinergic properties.  

Granulosis rubra nasi is a form of focal hyperhidrosis that presents as erythematous papules, pustules, and vesicles of the midface, especially the nose.3 It is a fairly rare condition that can mimic many other common clinical entities, including comedonal acne, nevus comedonicus, periorificial dermatitis, and tinea faciei, but is resistant to treatments aimed at these disorders. It was first described as a "peculiar disease of the skin of the nose in children" in a case report by Jadassohn⁴ in 1901. It is most common in children aged 7 to 12 years and typically resolves at puberty; adults rarely are affected. Although the etiology has not yet been elucidated, autosomal-dominant transmission has been described, and the cutaneous changes are hypothesized to be secondary to hyperhidrosis.⁵ This postulation is further corroborated by a case report of a pheochromocytoma-associated granulosis rubra nasi that resolved with surgical excision of the pheochromocytoma.⁶ It is not uncommon for patients to have concomitant palmoplantar hyperhidrosis and acrocyanosis.⁵ Histopathologic examination is not necessary for diagnosis, but when performed, it discloses a mononuclear cellular infiltrate surrounding eccrine sweat ducts, blood vessels, and lymphatics without other abnormalities of the epidermis or pilosebaceous unit.^1-3,7 
 

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.

To improve patient care and outcomes, leading dermatologists from the Cutis and Dermatology News Editorial Boards answered 5 questions on monitoring acne patients on oral therapy. Here’s what we found.

Do you check potassium levels for patients taking spironolactone for acne?

Half of dermatologists surveyed never check potassium levels for patients taking spironolactone for acne. For those who do check levels, 8% do it at baseline only, 8% at baseline and every 6 months, 23% at baseline and yearly, and 13% at baseline and for dosing changes.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Although some dermatologists are still checking for potassium levels in patients taking spironolactone for acne, there is a clear trend toward foregoing laboratory monitoring. This change was likely spurred by a retrospective study of healthy young women taking spironolactone for acne that found a hyperkalemia rate of 0.72%, which is practically equivalent to the 0.76% baseline rate of hyperkalemia in this age group. Furthermore, since repeat testing in 6 of 13 patients showed normal values, the original potassium measurements may have been erroneous. Based on this study, routine potassium monitoring is likely unnecessary for healthy young women taking spironolactone for acne (Plovanich et al). In another retrospective study of women aged 18 to 65 years taking spironolactone for acne, women aged 46 to 65 years had a significantly higher rate of hyperkalemia with spironolactone compared with women aged 18 to 45 years (2/12 women [16.7%] vs 1/112 women [<1%]; P=.0245). Based on this study, potassium monitoring may be indicated for women older than 45 years taking spironolactone for acne (Thiede et al). 

Next page: Cholesterol levels

Do you monitor cholesterol levels in patients taking isotretinoin?

Almost two-thirds of dermatologists indicated that they monitor all cholesterol levels in patients taking isotretinoin, including low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triglycerides, but almost one-third monitor triglycerides only. Five percent do not monitor cholesterol levels.

Do you routinely monitor cholesterol levels in patients taking isotretinoin?

More than 80% of dermatologists surveyed routinely monitor cholesterol levels in patients taking isotretinoin, with almost half (45%) at baseline and every 2 to 3 months. Eight percent check levels at baseline only, 28% at baseline and monthly, and 3% at baseline and end of therapy. Eighteen percent indicated they do not routinely monitor cholesterol levels. 

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

In this survey, dermatologists most often check cholesterol levels at baseline and then every 2 to 3 months, with most monitoring all cholesterol types. Elevations in cholesterol are by far the most common laboratory abnormality seen with isotretinoin therapy. In a retrospective study of 515 patients undergoing isotretinoin treatment of acne, mild to moderate triglyceride elevations were seen in 23.5% of patients (Hansen et al). At least in part, these elevations are likely due to the fact the levels were not drawn during fasting. Keep in mind that triglyceride-induced pancreatitis due to isotretinoin is remarkably rare, so monthly screening for triglycerides is likely not warranted. It is reasonable to monitor triglyceride levels during isotretinoin dose adjustments and for patients whose values are trending upward. 

Next page: Monitoring CBC

Do you routinely monitor complete blood cell count (CBC) in patients taking isotretinoin?

More than half (55%) of dermatologists surveyed routinely monitor complete blood cell (CBC) counts in patients taking isotretinoin, while 45% do not. Of those who do monitor CBC, 13% do so at baseline only, 26% at baseline and monthly, 13% at baseline only and every 2 to 3 months, and only 3% at baseline and end of therapy.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Slightly more than half of dermatologists in this survey are obtaining CBC for their patients taking isotretinoin for acne and many of those are performing the test at baseline and monthly. Multiple studies as well as American Academy of Dermatology guidelines have substantiated that routine CBC monitoring is unwarranted in healthy patients, as abnormal values usually resolve or remain stable with therapy (American Academy of Dermatology, Isotretinoin: Recommendations). Therefore, it is worthwhile to consider foregoing CBC testing or obtaining just a baseline CBC in healthy patients being treated with isotretinoin.

Next page: Pregnancy testing

Which pregnancy test do you perform on female patients taking isotretinoin?

More than 40% of dermatologists surveyed use the urine β-human chorionic gonadotropin (hCG) pregnancy test for female patients taking isotretinoin, while 30% use the serum B-hCG test; 28% indicated that they use both tests.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

The iPLEDGE program was implemented in 2006 to avoid fetal exposure to isotretinoin and requires pregnancy testing (urine or serum) for females of childbearing potential taking isotretinoin. In a study of pregnancy-related adverse events associated with isotretinoin reported to the US Food and Drug Administration, 6740 total pregnancies were reported from 1997 to 2017. The rate peaked with 768 pregnancies in 2006 and then decreased. Because several hundred pregnancies in women taking isotretinoin have been reported yearly in the last 10 years, there is a clear need to have better systems in place and patient education to prevent fetal exposure to isotretinoin. 

Next page: More tips from derms

More Tips From Dermatologists

The dermatologists we polled had the following advice for their peers:

I see lab monitoring as an opportunity to engage patients and families in co-directing their care (ie, practice patient- and family-centered care). Some families and patients like frequent monitoring and some want as few blood draws as possible. I do my best to make sure the decision includes components of the patients’ preferences, medical evidence and my best clinical judgement.—Craig Burkhart, MD, MS, MPH (Chapel Hill, North Caroline)

Being familiar with and following the standard of care guidelines for the individual oral therapies used in the treatment of acne is very important. However, it is equally as important to assure the individual patient (medical history, physical examination, social history, etc) is taken into consideration to determine if additional monitoring is required.—Fran E. Cook-Bolden, MD (New York, New York)

The trend seems to be towards less routine monitoring other than pregnancy. Baseline tests may pick out the occasional patient with comorbidities that would preclude or delay treatment, but the majority of patients may not need the repetitive and costly testing that we have done in the past.—Richard Glogau, MD (San Francisco, California)
I have loosened my lab monitoring with isotretinoin over the past few years. If a patient has normal lipid values, comprehensive panel and complete blood cell count for the first 3 months of tests, I skip labs until the end of therapy.—Lawrence J. Green, MD (Washington, DC)

Interestingly, we focus quite a bit of attention on the risk of pregnancy with isotretinoin, and often don't focus enough on the risk with spironolactone. In our practice, we are careful to warn the patients on spironolactone about pregnancy prevention.—Stephen Stone, MD (Springfield, Illinois)

About This Survey

The survey was fielded electronically to Cutis and Dermatology News Editorial Board Members within the United States from May 5, 2019, to June 23, 2019. A total of 40 usable responses were received.

To improve patient care and outcomes, leading dermatologists from the Cutis and Dermatology News Editorial Boards answered 5 questions on monitoring acne patients on oral therapy. Here’s what we found.

Do you check potassium levels for patients taking spironolactone for acne?

Half of dermatologists surveyed never check potassium levels for patients taking spironolactone for acne. For those who do check levels, 8% do it at baseline only, 8% at baseline and every 6 months, 23% at baseline and yearly, and 13% at baseline and for dosing changes.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Although some dermatologists are still checking for potassium levels in patients taking spironolactone for acne, there is a clear trend toward foregoing laboratory monitoring. This change was likely spurred by a retrospective study of healthy young women taking spironolactone for acne that found a hyperkalemia rate of 0.72%, which is practically equivalent to the 0.76% baseline rate of hyperkalemia in this age group. Furthermore, since repeat testing in 6 of 13 patients showed normal values, the original potassium measurements may have been erroneous. Based on this study, routine potassium monitoring is likely unnecessary for healthy young women taking spironolactone for acne (Plovanich et al). In another retrospective study of women aged 18 to 65 years taking spironolactone for acne, women aged 46 to 65 years had a significantly higher rate of hyperkalemia with spironolactone compared with women aged 18 to 45 years (2/12 women [16.7%] vs 1/112 women [<1%]; P=.0245). Based on this study, potassium monitoring may be indicated for women older than 45 years taking spironolactone for acne (Thiede et al). 

Next page: Cholesterol levels

Do you monitor cholesterol levels in patients taking isotretinoin?

Almost two-thirds of dermatologists indicated that they monitor all cholesterol levels in patients taking isotretinoin, including low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triglycerides, but almost one-third monitor triglycerides only. Five percent do not monitor cholesterol levels.

Do you routinely monitor cholesterol levels in patients taking isotretinoin?

More than 80% of dermatologists surveyed routinely monitor cholesterol levels in patients taking isotretinoin, with almost half (45%) at baseline and every 2 to 3 months. Eight percent check levels at baseline only, 28% at baseline and monthly, and 3% at baseline and end of therapy. Eighteen percent indicated they do not routinely monitor cholesterol levels. 

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

In this survey, dermatologists most often check cholesterol levels at baseline and then every 2 to 3 months, with most monitoring all cholesterol types. Elevations in cholesterol are by far the most common laboratory abnormality seen with isotretinoin therapy. In a retrospective study of 515 patients undergoing isotretinoin treatment of acne, mild to moderate triglyceride elevations were seen in 23.5% of patients (Hansen et al). At least in part, these elevations are likely due to the fact the levels were not drawn during fasting. Keep in mind that triglyceride-induced pancreatitis due to isotretinoin is remarkably rare, so monthly screening for triglycerides is likely not warranted. It is reasonable to monitor triglyceride levels during isotretinoin dose adjustments and for patients whose values are trending upward. 

Next page: Monitoring CBC

Do you routinely monitor complete blood cell count (CBC) in patients taking isotretinoin?

More than half (55%) of dermatologists surveyed routinely monitor complete blood cell (CBC) counts in patients taking isotretinoin, while 45% do not. Of those who do monitor CBC, 13% do so at baseline only, 26% at baseline and monthly, 13% at baseline only and every 2 to 3 months, and only 3% at baseline and end of therapy.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Slightly more than half of dermatologists in this survey are obtaining CBC for their patients taking isotretinoin for acne and many of those are performing the test at baseline and monthly. Multiple studies as well as American Academy of Dermatology guidelines have substantiated that routine CBC monitoring is unwarranted in healthy patients, as abnormal values usually resolve or remain stable with therapy (American Academy of Dermatology, Isotretinoin: Recommendations). Therefore, it is worthwhile to consider foregoing CBC testing or obtaining just a baseline CBC in healthy patients being treated with isotretinoin.

Next page: Pregnancy testing

Which pregnancy test do you perform on female patients taking isotretinoin?

More than 40% of dermatologists surveyed use the urine β-human chorionic gonadotropin (hCG) pregnancy test for female patients taking isotretinoin, while 30% use the serum B-hCG test; 28% indicated that they use both tests.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

The iPLEDGE program was implemented in 2006 to avoid fetal exposure to isotretinoin and requires pregnancy testing (urine or serum) for females of childbearing potential taking isotretinoin. In a study of pregnancy-related adverse events associated with isotretinoin reported to the US Food and Drug Administration, 6740 total pregnancies were reported from 1997 to 2017. The rate peaked with 768 pregnancies in 2006 and then decreased. Because several hundred pregnancies in women taking isotretinoin have been reported yearly in the last 10 years, there is a clear need to have better systems in place and patient education to prevent fetal exposure to isotretinoin. 

Next page: More tips from derms

More Tips From Dermatologists

The dermatologists we polled had the following advice for their peers:

I see lab monitoring as an opportunity to engage patients and families in co-directing their care (ie, practice patient- and family-centered care). Some families and patients like frequent monitoring and some want as few blood draws as possible. I do my best to make sure the decision includes components of the patients’ preferences, medical evidence and my best clinical judgement.—Craig Burkhart, MD, MS, MPH (Chapel Hill, North Caroline)

Being familiar with and following the standard of care guidelines for the individual oral therapies used in the treatment of acne is very important. However, it is equally as important to assure the individual patient (medical history, physical examination, social history, etc) is taken into consideration to determine if additional monitoring is required.—Fran E. Cook-Bolden, MD (New York, New York)

The trend seems to be towards less routine monitoring other than pregnancy. Baseline tests may pick out the occasional patient with comorbidities that would preclude or delay treatment, but the majority of patients may not need the repetitive and costly testing that we have done in the past.—Richard Glogau, MD (San Francisco, California)
I have loosened my lab monitoring with isotretinoin over the past few years. If a patient has normal lipid values, comprehensive panel and complete blood cell count for the first 3 months of tests, I skip labs until the end of therapy.—Lawrence J. Green, MD (Washington, DC)

Interestingly, we focus quite a bit of attention on the risk of pregnancy with isotretinoin, and often don't focus enough on the risk with spironolactone. In our practice, we are careful to warn the patients on spironolactone about pregnancy prevention.—Stephen Stone, MD (Springfield, Illinois)

About This Survey

The survey was fielded electronically to Cutis and Dermatology News Editorial Board Members within the United States from May 5, 2019, to June 23, 2019. A total of 40 usable responses were received.

To improve patient care and outcomes, leading dermatologists from the Cutis and Dermatology News Editorial Boards answered 5 questions on monitoring acne patients on oral therapy. Here’s what we found.

Do you check potassium levels for patients taking spironolactone for acne?

Half of dermatologists surveyed never check potassium levels for patients taking spironolactone for acne. For those who do check levels, 8% do it at baseline only, 8% at baseline and every 6 months, 23% at baseline and yearly, and 13% at baseline and for dosing changes.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Although some dermatologists are still checking for potassium levels in patients taking spironolactone for acne, there is a clear trend toward foregoing laboratory monitoring. This change was likely spurred by a retrospective study of healthy young women taking spironolactone for acne that found a hyperkalemia rate of 0.72%, which is practically equivalent to the 0.76% baseline rate of hyperkalemia in this age group. Furthermore, since repeat testing in 6 of 13 patients showed normal values, the original potassium measurements may have been erroneous. Based on this study, routine potassium monitoring is likely unnecessary for healthy young women taking spironolactone for acne (Plovanich et al). In another retrospective study of women aged 18 to 65 years taking spironolactone for acne, women aged 46 to 65 years had a significantly higher rate of hyperkalemia with spironolactone compared with women aged 18 to 45 years (2/12 women [16.7%] vs 1/112 women [<1%]; P=.0245). Based on this study, potassium monitoring may be indicated for women older than 45 years taking spironolactone for acne (Thiede et al). 

Next page: Cholesterol levels

Do you monitor cholesterol levels in patients taking isotretinoin?

Almost two-thirds of dermatologists indicated that they monitor all cholesterol levels in patients taking isotretinoin, including low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triglycerides, but almost one-third monitor triglycerides only. Five percent do not monitor cholesterol levels.

Do you routinely monitor cholesterol levels in patients taking isotretinoin?

More than 80% of dermatologists surveyed routinely monitor cholesterol levels in patients taking isotretinoin, with almost half (45%) at baseline and every 2 to 3 months. Eight percent check levels at baseline only, 28% at baseline and monthly, and 3% at baseline and end of therapy. Eighteen percent indicated they do not routinely monitor cholesterol levels. 

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

In this survey, dermatologists most often check cholesterol levels at baseline and then every 2 to 3 months, with most monitoring all cholesterol types. Elevations in cholesterol are by far the most common laboratory abnormality seen with isotretinoin therapy. In a retrospective study of 515 patients undergoing isotretinoin treatment of acne, mild to moderate triglyceride elevations were seen in 23.5% of patients (Hansen et al). At least in part, these elevations are likely due to the fact the levels were not drawn during fasting. Keep in mind that triglyceride-induced pancreatitis due to isotretinoin is remarkably rare, so monthly screening for triglycerides is likely not warranted. It is reasonable to monitor triglyceride levels during isotretinoin dose adjustments and for patients whose values are trending upward. 

Next page: Monitoring CBC

Do you routinely monitor complete blood cell count (CBC) in patients taking isotretinoin?

More than half (55%) of dermatologists surveyed routinely monitor complete blood cell (CBC) counts in patients taking isotretinoin, while 45% do not. Of those who do monitor CBC, 13% do so at baseline only, 26% at baseline and monthly, 13% at baseline only and every 2 to 3 months, and only 3% at baseline and end of therapy.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Slightly more than half of dermatologists in this survey are obtaining CBC for their patients taking isotretinoin for acne and many of those are performing the test at baseline and monthly. Multiple studies as well as American Academy of Dermatology guidelines have substantiated that routine CBC monitoring is unwarranted in healthy patients, as abnormal values usually resolve or remain stable with therapy (American Academy of Dermatology, Isotretinoin: Recommendations). Therefore, it is worthwhile to consider foregoing CBC testing or obtaining just a baseline CBC in healthy patients being treated with isotretinoin.

Next page: Pregnancy testing

Which pregnancy test do you perform on female patients taking isotretinoin?

More than 40% of dermatologists surveyed use the urine β-human chorionic gonadotropin (hCG) pregnancy test for female patients taking isotretinoin, while 30% use the serum B-hCG test; 28% indicated that they use both tests.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

The iPLEDGE program was implemented in 2006 to avoid fetal exposure to isotretinoin and requires pregnancy testing (urine or serum) for females of childbearing potential taking isotretinoin. In a study of pregnancy-related adverse events associated with isotretinoin reported to the US Food and Drug Administration, 6740 total pregnancies were reported from 1997 to 2017. The rate peaked with 768 pregnancies in 2006 and then decreased. Because several hundred pregnancies in women taking isotretinoin have been reported yearly in the last 10 years, there is a clear need to have better systems in place and patient education to prevent fetal exposure to isotretinoin. 

Next page: More tips from derms

More Tips From Dermatologists

The dermatologists we polled had the following advice for their peers:

I see lab monitoring as an opportunity to engage patients and families in co-directing their care (ie, practice patient- and family-centered care). Some families and patients like frequent monitoring and some want as few blood draws as possible. I do my best to make sure the decision includes components of the patients’ preferences, medical evidence and my best clinical judgement.—Craig Burkhart, MD, MS, MPH (Chapel Hill, North Caroline)

Being familiar with and following the standard of care guidelines for the individual oral therapies used in the treatment of acne is very important. However, it is equally as important to assure the individual patient (medical history, physical examination, social history, etc) is taken into consideration to determine if additional monitoring is required.—Fran E. Cook-Bolden, MD (New York, New York)

The trend seems to be towards less routine monitoring other than pregnancy. Baseline tests may pick out the occasional patient with comorbidities that would preclude or delay treatment, but the majority of patients may not need the repetitive and costly testing that we have done in the past.—Richard Glogau, MD (San Francisco, California)
I have loosened my lab monitoring with isotretinoin over the past few years. If a patient has normal lipid values, comprehensive panel and complete blood cell count for the first 3 months of tests, I skip labs until the end of therapy.—Lawrence J. Green, MD (Washington, DC)

Interestingly, we focus quite a bit of attention on the risk of pregnancy with isotretinoin, and often don't focus enough on the risk with spironolactone. In our practice, we are careful to warn the patients on spironolactone about pregnancy prevention.—Stephen Stone, MD (Springfield, Illinois)

About This Survey

The survey was fielded electronically to Cutis and Dermatology News Editorial Board Members within the United States from May 5, 2019, to June 23, 2019. A total of 40 usable responses were received.

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]