HOUSTON—Acute hemostatic treatment with a clotting protein does not improve short- or long-term outcomes in patients with intracerebral hemorrhage (ICH), according to research presented at the International Stroke Conference 2017.

This is not the first time rFVII has been investigated as an acute treatment for ICH, said Dr. Gladstone. In the large phase III FAST trial, rFVII reduced the growth of hematoma, but did not improve survival or functional outcome in an unselected population.

No medical interventions are available for patients with ICH, and investigators hope to identify a narrower patient population with active bleeding that might be more responsive to rFVII. This goal prompted the initiation of the SPOTLIGHT and STOP-IT studies, said Dr. Gladstone. The former study was Canadian, and the latter American.

Spot Sign Imaging Biomarker

For both studies, researchers stratified patients using the spot sign, a relatively new imaging biomarker thought to reflect active bleeding in the ICH hematoma. The hyperintense signal can easily be seen on cerebral angiography.

“It shows up like a flashlight as a bright spot in the margin of the hematoma,” Dr. Gladstone said. “When we see this, we know this patient has a possible active bleed that is likely to expand and get worse. They are at highest risk for ICH expansion and should be the best candidates for hemostatic therapy.”

Spot-positive patients were randomized to placebo or to a single IV bolus of 80 µg/kg of rFVII given in the emergency department within 6.5 hours of stroke onset. Spot-negative patients were enrolled in a prospective observational cohort, which provided data to support the sign’s use as a predictor of outcome.

Exclusion criteria included brainstem ICH; ICH with secondary cause (eg, tumor or trauma); additional treatments such as plasma or prothrombin; acute coronary ischemia; history of other strokes, angioplasty, or stenting; past thrombotic events; a Glasgow Coma Scale score less than 8; or a modified Rankin Scale (mRS) score more than 2.

These criteria, plus the relative infrequency of ICH events, compared with other cerebrovascular events, made recruitment difficult. After six years, the trials together enrolled 69 spot-positive and 72 spot-negative patients. Both studies were stopped because of the low numbers and insufficient funds.

The studies’ primary efficacy end point was 24-hour ICH volume. Secondary outcomes were 24-hour total ICH plus intraventricular hemorrhage volumes, 90-day mRS of 5 to 6, and comparisons between the spot-negative and spot-positive groups. The primary safety outcome was acute myocardial infarction, ischemic stroke, or pulmonary embolism within four days of treatment.

Results by Spot Status

Patients’ mean age was 70, although spot-positive patients were older than spot-negative patients (71 vs 61). Spot-positive patients were also less likely to have a Glasgow Coma Scale score of 15 to 16 (56% vs 66%). The mean NIH Stroke Scale score was 16 in the spot-positive group and 10 in the spot-negative group. Intraventricular hemorrhage was also more common in the spot-positive group (44% vs 18%).

After researchers adjusted for baseline ICH volume and onset-to-needle time, rFVII exerted no significant effect on either 24-hour ICH volume or 24-hour total volume. In the treated group, median ICH volume increased from 16 mL at baseline to 22 mL by 24 hours. In the placebo group, it increased from 20 mL at baseline to 29 mL at 24 hours.

In the treated group, the median total volume (ICH plus intraventricular hemorrhage) increased from 24 mL at baseline to 26 mL at 24 hours. In the placebo group, it increased from 25 mL at baseline to 31 mL at 24 hours. Researchers did not observe a significant difference between groups in the number of patients who had a volume increase of more than 6 mL or more than 33% (41% vs 43%).

A Predictor of Continued Bleeding

Spot-negative patients had lower baseline and 24-hour total hematoma volumes. In the spot-negative group, total volumes increased from a median of 13 mL at baseline to 14 mL at 24 hours. Significantly fewer spot-negative patients than spot-positive patients had hematoma growth of more than 6 mL or 33% (11% vs 43%).

The spot sign was a good predictor of continued bleeding. In all spot-positive patients, median ICH volume expanded by a median of 9 mL over 24 hours (ie, from 20 mL to 29 mL), compared with a median ICH expansion of 1 mL over 24 hours (ie, from 12 mL to 13 mL) for spot-negative patients.

There were no significant differences in 90-day mRS scores between the treated and placebo groups. One-fifth of each group had a score of 1–2, and one-fifth died. The proportion of patients with mRS scores of 3 to 5 also was similar between the groups.

Despite similar scores, the spot-negative patients had significantly better outcomes. Approximately 38% had an mRS of 0–1 at 90 days. Six percent of this group died.

In addition, treatment time intervals were prolonged in these studies, compared with those that have been achieved with antithrombotic therapy in ischemic stroke. Time from stroke onset to the emergency department was similar in both spot-positive groups taking rFVII and spot-positive controls (64 min and 66 min). Onset-to-CT time was significantly longer in the rFVII patients than in controls (89 min vs 83 min). Door-to-needle time was also longer in the rFVII patients than in controls (104 min vs 87 min), as was onset-to-needle time (195 min vs 161 min).

Thirty-seven percent of spot-positive patients receiving rFVII were treated in less than three hours. This proportion was significantly lower than the 65% that were treated that quickly in the spot-positive placebo group. No significant adverse events were related to rFVII.

Future Directions

“The spot sign predicted final ICH volume, but the magnitude of ICH expansion was small: less than we expected,” Dr. Gladstone said. “The median absolute ICH volume increase overall was only 2.5 mm, which is surprisingly small for this group of patients. And I do believe that treatment was administered too late, after most of the ICH expansion had already happened.”

Nonetheless, “there is much to learn here,” he said. “The biggest issue is that treatment was just too little, too late. We need to be catching these patients at a much earlier phase to make a difference, and that is probably the largest reason we did not see a difference.

“The spot sign “was a statistically significant predictor of final ICH volumes,” Dr. Gladstone said. It is easy to recognize on an imaging study that is routinely acquired for stroke patients.

“We are also beginning to understand that there are many different types of spot signs associated with different kinds of bleeding at different times,” he said. “We need to understand this variation further, and this should allow us to characterize the patients who are likely to be big bleeders.”

—Michelle G. Sullivan

HOUSTON—Acute hemostatic treatment with a clotting protein does not improve short- or long-term outcomes in patients with intracerebral hemorrhage (ICH), according to research presented at the International Stroke Conference 2017.

This is not the first time rFVII has been investigated as an acute treatment for ICH, said Dr. Gladstone. In the large phase III FAST trial, rFVII reduced the growth of hematoma, but did not improve survival or functional outcome in an unselected population.

No medical interventions are available for patients with ICH, and investigators hope to identify a narrower patient population with active bleeding that might be more responsive to rFVII. This goal prompted the initiation of the SPOTLIGHT and STOP-IT studies, said Dr. Gladstone. The former study was Canadian, and the latter American.

Spot Sign Imaging Biomarker

For both studies, researchers stratified patients using the spot sign, a relatively new imaging biomarker thought to reflect active bleeding in the ICH hematoma. The hyperintense signal can easily be seen on cerebral angiography.

“It shows up like a flashlight as a bright spot in the margin of the hematoma,” Dr. Gladstone said. “When we see this, we know this patient has a possible active bleed that is likely to expand and get worse. They are at highest risk for ICH expansion and should be the best candidates for hemostatic therapy.”

Spot-positive patients were randomized to placebo or to a single IV bolus of 80 µg/kg of rFVII given in the emergency department within 6.5 hours of stroke onset. Spot-negative patients were enrolled in a prospective observational cohort, which provided data to support the sign’s use as a predictor of outcome.

Exclusion criteria included brainstem ICH; ICH with secondary cause (eg, tumor or trauma); additional treatments such as plasma or prothrombin; acute coronary ischemia; history of other strokes, angioplasty, or stenting; past thrombotic events; a Glasgow Coma Scale score less than 8; or a modified Rankin Scale (mRS) score more than 2.

These criteria, plus the relative infrequency of ICH events, compared with other cerebrovascular events, made recruitment difficult. After six years, the trials together enrolled 69 spot-positive and 72 spot-negative patients. Both studies were stopped because of the low numbers and insufficient funds.

The studies’ primary efficacy end point was 24-hour ICH volume. Secondary outcomes were 24-hour total ICH plus intraventricular hemorrhage volumes, 90-day mRS of 5 to 6, and comparisons between the spot-negative and spot-positive groups. The primary safety outcome was acute myocardial infarction, ischemic stroke, or pulmonary embolism within four days of treatment.

Results by Spot Status

Patients’ mean age was 70, although spot-positive patients were older than spot-negative patients (71 vs 61). Spot-positive patients were also less likely to have a Glasgow Coma Scale score of 15 to 16 (56% vs 66%). The mean NIH Stroke Scale score was 16 in the spot-positive group and 10 in the spot-negative group. Intraventricular hemorrhage was also more common in the spot-positive group (44% vs 18%).

After researchers adjusted for baseline ICH volume and onset-to-needle time, rFVII exerted no significant effect on either 24-hour ICH volume or 24-hour total volume. In the treated group, median ICH volume increased from 16 mL at baseline to 22 mL by 24 hours. In the placebo group, it increased from 20 mL at baseline to 29 mL at 24 hours.

In the treated group, the median total volume (ICH plus intraventricular hemorrhage) increased from 24 mL at baseline to 26 mL at 24 hours. In the placebo group, it increased from 25 mL at baseline to 31 mL at 24 hours. Researchers did not observe a significant difference between groups in the number of patients who had a volume increase of more than 6 mL or more than 33% (41% vs 43%).

A Predictor of Continued Bleeding

Spot-negative patients had lower baseline and 24-hour total hematoma volumes. In the spot-negative group, total volumes increased from a median of 13 mL at baseline to 14 mL at 24 hours. Significantly fewer spot-negative patients than spot-positive patients had hematoma growth of more than 6 mL or 33% (11% vs 43%).

The spot sign was a good predictor of continued bleeding. In all spot-positive patients, median ICH volume expanded by a median of 9 mL over 24 hours (ie, from 20 mL to 29 mL), compared with a median ICH expansion of 1 mL over 24 hours (ie, from 12 mL to 13 mL) for spot-negative patients.

There were no significant differences in 90-day mRS scores between the treated and placebo groups. One-fifth of each group had a score of 1–2, and one-fifth died. The proportion of patients with mRS scores of 3 to 5 also was similar between the groups.

Despite similar scores, the spot-negative patients had significantly better outcomes. Approximately 38% had an mRS of 0–1 at 90 days. Six percent of this group died.

In addition, treatment time intervals were prolonged in these studies, compared with those that have been achieved with antithrombotic therapy in ischemic stroke. Time from stroke onset to the emergency department was similar in both spot-positive groups taking rFVII and spot-positive controls (64 min and 66 min). Onset-to-CT time was significantly longer in the rFVII patients than in controls (89 min vs 83 min). Door-to-needle time was also longer in the rFVII patients than in controls (104 min vs 87 min), as was onset-to-needle time (195 min vs 161 min).

Thirty-seven percent of spot-positive patients receiving rFVII were treated in less than three hours. This proportion was significantly lower than the 65% that were treated that quickly in the spot-positive placebo group. No significant adverse events were related to rFVII.

Future Directions

“The spot sign predicted final ICH volume, but the magnitude of ICH expansion was small: less than we expected,” Dr. Gladstone said. “The median absolute ICH volume increase overall was only 2.5 mm, which is surprisingly small for this group of patients. And I do believe that treatment was administered too late, after most of the ICH expansion had already happened.”

Nonetheless, “there is much to learn here,” he said. “The biggest issue is that treatment was just too little, too late. We need to be catching these patients at a much earlier phase to make a difference, and that is probably the largest reason we did not see a difference.

“The spot sign “was a statistically significant predictor of final ICH volumes,” Dr. Gladstone said. It is easy to recognize on an imaging study that is routinely acquired for stroke patients.

“We are also beginning to understand that there are many different types of spot signs associated with different kinds of bleeding at different times,” he said. “We need to understand this variation further, and this should allow us to characterize the patients who are likely to be big bleeders.”

—Michelle G. Sullivan

HOUSTON—Acute hemostatic treatment with a clotting protein does not improve short- or long-term outcomes in patients with intracerebral hemorrhage (ICH), according to research presented at the International Stroke Conference 2017.

This is not the first time rFVII has been investigated as an acute treatment for ICH, said Dr. Gladstone. In the large phase III FAST trial, rFVII reduced the growth of hematoma, but did not improve survival or functional outcome in an unselected population.

No medical interventions are available for patients with ICH, and investigators hope to identify a narrower patient population with active bleeding that might be more responsive to rFVII. This goal prompted the initiation of the SPOTLIGHT and STOP-IT studies, said Dr. Gladstone. The former study was Canadian, and the latter American.

Spot Sign Imaging Biomarker

For both studies, researchers stratified patients using the spot sign, a relatively new imaging biomarker thought to reflect active bleeding in the ICH hematoma. The hyperintense signal can easily be seen on cerebral angiography.

“It shows up like a flashlight as a bright spot in the margin of the hematoma,” Dr. Gladstone said. “When we see this, we know this patient has a possible active bleed that is likely to expand and get worse. They are at highest risk for ICH expansion and should be the best candidates for hemostatic therapy.”

Spot-positive patients were randomized to placebo or to a single IV bolus of 80 µg/kg of rFVII given in the emergency department within 6.5 hours of stroke onset. Spot-negative patients were enrolled in a prospective observational cohort, which provided data to support the sign’s use as a predictor of outcome.

Exclusion criteria included brainstem ICH; ICH with secondary cause (eg, tumor or trauma); additional treatments such as plasma or prothrombin; acute coronary ischemia; history of other strokes, angioplasty, or stenting; past thrombotic events; a Glasgow Coma Scale score less than 8; or a modified Rankin Scale (mRS) score more than 2.

These criteria, plus the relative infrequency of ICH events, compared with other cerebrovascular events, made recruitment difficult. After six years, the trials together enrolled 69 spot-positive and 72 spot-negative patients. Both studies were stopped because of the low numbers and insufficient funds.

The studies’ primary efficacy end point was 24-hour ICH volume. Secondary outcomes were 24-hour total ICH plus intraventricular hemorrhage volumes, 90-day mRS of 5 to 6, and comparisons between the spot-negative and spot-positive groups. The primary safety outcome was acute myocardial infarction, ischemic stroke, or pulmonary embolism within four days of treatment.

Results by Spot Status

Patients’ mean age was 70, although spot-positive patients were older than spot-negative patients (71 vs 61). Spot-positive patients were also less likely to have a Glasgow Coma Scale score of 15 to 16 (56% vs 66%). The mean NIH Stroke Scale score was 16 in the spot-positive group and 10 in the spot-negative group. Intraventricular hemorrhage was also more common in the spot-positive group (44% vs 18%).

After researchers adjusted for baseline ICH volume and onset-to-needle time, rFVII exerted no significant effect on either 24-hour ICH volume or 24-hour total volume. In the treated group, median ICH volume increased from 16 mL at baseline to 22 mL by 24 hours. In the placebo group, it increased from 20 mL at baseline to 29 mL at 24 hours.

In the treated group, the median total volume (ICH plus intraventricular hemorrhage) increased from 24 mL at baseline to 26 mL at 24 hours. In the placebo group, it increased from 25 mL at baseline to 31 mL at 24 hours. Researchers did not observe a significant difference between groups in the number of patients who had a volume increase of more than 6 mL or more than 33% (41% vs 43%).

A Predictor of Continued Bleeding

Spot-negative patients had lower baseline and 24-hour total hematoma volumes. In the spot-negative group, total volumes increased from a median of 13 mL at baseline to 14 mL at 24 hours. Significantly fewer spot-negative patients than spot-positive patients had hematoma growth of more than 6 mL or 33% (11% vs 43%).

The spot sign was a good predictor of continued bleeding. In all spot-positive patients, median ICH volume expanded by a median of 9 mL over 24 hours (ie, from 20 mL to 29 mL), compared with a median ICH expansion of 1 mL over 24 hours (ie, from 12 mL to 13 mL) for spot-negative patients.

There were no significant differences in 90-day mRS scores between the treated and placebo groups. One-fifth of each group had a score of 1–2, and one-fifth died. The proportion of patients with mRS scores of 3 to 5 also was similar between the groups.

Despite similar scores, the spot-negative patients had significantly better outcomes. Approximately 38% had an mRS of 0–1 at 90 days. Six percent of this group died.

In addition, treatment time intervals were prolonged in these studies, compared with those that have been achieved with antithrombotic therapy in ischemic stroke. Time from stroke onset to the emergency department was similar in both spot-positive groups taking rFVII and spot-positive controls (64 min and 66 min). Onset-to-CT time was significantly longer in the rFVII patients than in controls (89 min vs 83 min). Door-to-needle time was also longer in the rFVII patients than in controls (104 min vs 87 min), as was onset-to-needle time (195 min vs 161 min).

Thirty-seven percent of spot-positive patients receiving rFVII were treated in less than three hours. This proportion was significantly lower than the 65% that were treated that quickly in the spot-positive placebo group. No significant adverse events were related to rFVII.

Future Directions

“The spot sign predicted final ICH volume, but the magnitude of ICH expansion was small: less than we expected,” Dr. Gladstone said. “The median absolute ICH volume increase overall was only 2.5 mm, which is surprisingly small for this group of patients. And I do believe that treatment was administered too late, after most of the ICH expansion had already happened.”

Nonetheless, “there is much to learn here,” he said. “The biggest issue is that treatment was just too little, too late. We need to be catching these patients at a much earlier phase to make a difference, and that is probably the largest reason we did not see a difference.

“The spot sign “was a statistically significant predictor of final ICH volumes,” Dr. Gladstone said. It is easy to recognize on an imaging study that is routinely acquired for stroke patients.

“We are also beginning to understand that there are many different types of spot signs associated with different kinds of bleeding at different times,” he said. “We need to understand this variation further, and this should allow us to characterize the patients who are likely to be big bleeders.”

—Michelle G. Sullivan

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Click here to download the PDF.

Click here to download the PDF.

PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.

“Multivariate analyses have not identified any feature that distinguishes PPI-REE from EoE. Why? Because they are probably the same disorder,” reported Stuart J. Spechler, MD, AGAF, codirector of the center for esophageal diseases at Baylor University Medical Center at Dallas.

PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.

“Multivariate analyses have not identified any feature that distinguishes PPI-REE from EoE. Why? Because they are probably the same disorder,” reported Stuart J. Spechler, MD, AGAF, codirector of the center for esophageal diseases at Baylor University Medical Center at Dallas.

PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.

“Multivariate analyses have not identified any feature that distinguishes PPI-REE from EoE. Why? Because they are probably the same disorder,” reported Stuart J. Spechler, MD, AGAF, codirector of the center for esophageal diseases at Baylor University Medical Center at Dallas.

HOUSTON—Compared with standard platinum coils, second-generation hydrogel coils decrease the likelihood of adverse outcomes in the endovascular treatment of medium-sized intracranial aneurysms, according to research presented at the International Stroke Conference 2017. Hydrogel coils provide greater packing density and are associated with decreased risks of aneurysm recurrence and retreatment, compared with standard coils, according to the researchers.

Approximately 85% of subarachnoid hemorrhages result from ruptured intracranial aneurysms, which can be detected with CT angiography. A randomized controlled trial published in 2002 demonstrated that endovascular coiling was superior to neurosurgical clipping in the treatment of ruptured aneurysms. A drawback of coiling, however, is that it entails a relatively high rate of aneurysm recurrence. A novel approach adds a soft hydrogel filament into platinum coils. The hydrogel, once in contact with liquid, increases in volume, resulting in a greater fill of the underlying aneurysm.

Between October 2009 and February 2014, Prof. Taschner and colleagues randomized 513 participants, and 29 patients were excluded from the analysis. The analysis included 243 patients treated with hydrogel coils and 241 patients treated with platinum coils. Of this population, 208 participants (43%) were treated for ruptured aneurysms.

Mean packing density was significantly higher in patients treated with hydrogel coils (39%), compared with patients treated with platinum coils (31%). At 18 months, the major recurrence rate was 12% in patients receiving hydrogel coils and 18% in patients receiving platinum coils. The retreatment rate at 18 months was 3% in patients receiving hydrogel coils and 6% in patients receiving platinum coils. The researchers found no difference in modified Rankin Scale score or mortality rate between groups.

In total, 45 patients in the hydrogel coil group and 66 controls had an adverse composite primary outcome. The hydrogel coils thus reduced the proportion of adverse composite primary outcomes, compared with platinum coils, by 8.4%, said Prof. Taschner.

—Erik Greb

Suggested Reading

Gaba RC, Ansari SA, Roy SS, et al. Embolization of intracranial aneurysms with hydrogel-coated coils versus inert platinum coils: effects on packing density, coil length and quantity, procedure performance, cost, length of hospital stay, and durability of therapy. Stroke. 2006;37(6):1443-1450.

Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366(9488):809-817.

White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet. 2011;377(9778):1655-1662.

HOUSTON—Compared with standard platinum coils, second-generation hydrogel coils decrease the likelihood of adverse outcomes in the endovascular treatment of medium-sized intracranial aneurysms, according to research presented at the International Stroke Conference 2017. Hydrogel coils provide greater packing density and are associated with decreased risks of aneurysm recurrence and retreatment, compared with standard coils, according to the researchers.

Approximately 85% of subarachnoid hemorrhages result from ruptured intracranial aneurysms, which can be detected with CT angiography. A randomized controlled trial published in 2002 demonstrated that endovascular coiling was superior to neurosurgical clipping in the treatment of ruptured aneurysms. A drawback of coiling, however, is that it entails a relatively high rate of aneurysm recurrence. A novel approach adds a soft hydrogel filament into platinum coils. The hydrogel, once in contact with liquid, increases in volume, resulting in a greater fill of the underlying aneurysm.

Between October 2009 and February 2014, Prof. Taschner and colleagues randomized 513 participants, and 29 patients were excluded from the analysis. The analysis included 243 patients treated with hydrogel coils and 241 patients treated with platinum coils. Of this population, 208 participants (43%) were treated for ruptured aneurysms.

Mean packing density was significantly higher in patients treated with hydrogel coils (39%), compared with patients treated with platinum coils (31%). At 18 months, the major recurrence rate was 12% in patients receiving hydrogel coils and 18% in patients receiving platinum coils. The retreatment rate at 18 months was 3% in patients receiving hydrogel coils and 6% in patients receiving platinum coils. The researchers found no difference in modified Rankin Scale score or mortality rate between groups.

In total, 45 patients in the hydrogel coil group and 66 controls had an adverse composite primary outcome. The hydrogel coils thus reduced the proportion of adverse composite primary outcomes, compared with platinum coils, by 8.4%, said Prof. Taschner.

—Erik Greb

Suggested Reading

Gaba RC, Ansari SA, Roy SS, et al. Embolization of intracranial aneurysms with hydrogel-coated coils versus inert platinum coils: effects on packing density, coil length and quantity, procedure performance, cost, length of hospital stay, and durability of therapy. Stroke. 2006;37(6):1443-1450.

Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366(9488):809-817.

White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet. 2011;377(9778):1655-1662.

HOUSTON—Compared with standard platinum coils, second-generation hydrogel coils decrease the likelihood of adverse outcomes in the endovascular treatment of medium-sized intracranial aneurysms, according to research presented at the International Stroke Conference 2017. Hydrogel coils provide greater packing density and are associated with decreased risks of aneurysm recurrence and retreatment, compared with standard coils, according to the researchers.

Approximately 85% of subarachnoid hemorrhages result from ruptured intracranial aneurysms, which can be detected with CT angiography. A randomized controlled trial published in 2002 demonstrated that endovascular coiling was superior to neurosurgical clipping in the treatment of ruptured aneurysms. A drawback of coiling, however, is that it entails a relatively high rate of aneurysm recurrence. A novel approach adds a soft hydrogel filament into platinum coils. The hydrogel, once in contact with liquid, increases in volume, resulting in a greater fill of the underlying aneurysm.

Between October 2009 and February 2014, Prof. Taschner and colleagues randomized 513 participants, and 29 patients were excluded from the analysis. The analysis included 243 patients treated with hydrogel coils and 241 patients treated with platinum coils. Of this population, 208 participants (43%) were treated for ruptured aneurysms.

Mean packing density was significantly higher in patients treated with hydrogel coils (39%), compared with patients treated with platinum coils (31%). At 18 months, the major recurrence rate was 12% in patients receiving hydrogel coils and 18% in patients receiving platinum coils. The retreatment rate at 18 months was 3% in patients receiving hydrogel coils and 6% in patients receiving platinum coils. The researchers found no difference in modified Rankin Scale score or mortality rate between groups.

In total, 45 patients in the hydrogel coil group and 66 controls had an adverse composite primary outcome. The hydrogel coils thus reduced the proportion of adverse composite primary outcomes, compared with platinum coils, by 8.4%, said Prof. Taschner.

—Erik Greb

Suggested Reading

Gaba RC, Ansari SA, Roy SS, et al. Embolization of intracranial aneurysms with hydrogel-coated coils versus inert platinum coils: effects on packing density, coil length and quantity, procedure performance, cost, length of hospital stay, and durability of therapy. Stroke. 2006;37(6):1443-1450.

Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366(9488):809-817.

White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet. 2011;377(9778):1655-1662.

Trichomycosis axillaris

Trichomycosis axillaris (TA) is a bacterial infection of the genus Corynebacterium that affects hairs in the axilla. Predisposing factors include poor local hygiene, hyperhidrosis, obesity, and warm, humid climates. Gram-positive diphtheroids, classically Corynebacterium tenuis, mix with sweat on hair shafts and subsequently produce a cementing material. In the majority of cases, bacterial infection causes keratin damage to the hair shaft with sparing of the cortex. However, recent cases have reported significant invasion of the hair cortex by bacterial structures.

TA is often a clinical diagnosis. Histopathology reveals a discontinuous thick-layer coating of bacterial structures adhered to the hair shafts. Periodic acid–Schiff, gram, and Grocott silver stains are all positive. Examination of hairs with 20% hydrogen peroxide solution can provide a microscopic diagnosis. Wood lamp examination produces a weak, yellow fluorescence, and potassium hydroxide test demonstrates yellowish material of minimal translucency surrounding the hair cortex.

Complete resolution can be achieved by shaving off all the axillary hairs. It is imperative to maintain good hygiene and keep the area dry and clean. To prevent recurrence, topical benzoyl peroxide or topical antibiotics such as erythromycin and clindamycin can be applied. If axillary hyperhidrosis is concurrently present, aluminum chloride hexahydrate solution can decrease sweating and reduce the risk of bacterial regrowth. Injections of botulinum toxin can be used to treat the hyperhidrosis as well. 

This patient responded well to topical erythromycin lotion.

This case and photo are courtesy of Jessica Cervantes, University of Miami Miller School of Medicine, and Dr. Bilu Martin.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/edermatologynews. To submit a case for possible publication, send an email to [email protected].

Trichomycosis axillaris

Trichomycosis axillaris (TA) is a bacterial infection of the genus Corynebacterium that affects hairs in the axilla. Predisposing factors include poor local hygiene, hyperhidrosis, obesity, and warm, humid climates. Gram-positive diphtheroids, classically Corynebacterium tenuis, mix with sweat on hair shafts and subsequently produce a cementing material. In the majority of cases, bacterial infection causes keratin damage to the hair shaft with sparing of the cortex. However, recent cases have reported significant invasion of the hair cortex by bacterial structures.

TA is often a clinical diagnosis. Histopathology reveals a discontinuous thick-layer coating of bacterial structures adhered to the hair shafts. Periodic acid–Schiff, gram, and Grocott silver stains are all positive. Examination of hairs with 20% hydrogen peroxide solution can provide a microscopic diagnosis. Wood lamp examination produces a weak, yellow fluorescence, and potassium hydroxide test demonstrates yellowish material of minimal translucency surrounding the hair cortex.

Complete resolution can be achieved by shaving off all the axillary hairs. It is imperative to maintain good hygiene and keep the area dry and clean. To prevent recurrence, topical benzoyl peroxide or topical antibiotics such as erythromycin and clindamycin can be applied. If axillary hyperhidrosis is concurrently present, aluminum chloride hexahydrate solution can decrease sweating and reduce the risk of bacterial regrowth. Injections of botulinum toxin can be used to treat the hyperhidrosis as well. 

This patient responded well to topical erythromycin lotion.

This case and photo are courtesy of Jessica Cervantes, University of Miami Miller School of Medicine, and Dr. Bilu Martin.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/edermatologynews. To submit a case for possible publication, send an email to [email protected].

Trichomycosis axillaris

Trichomycosis axillaris (TA) is a bacterial infection of the genus Corynebacterium that affects hairs in the axilla. Predisposing factors include poor local hygiene, hyperhidrosis, obesity, and warm, humid climates. Gram-positive diphtheroids, classically Corynebacterium tenuis, mix with sweat on hair shafts and subsequently produce a cementing material. In the majority of cases, bacterial infection causes keratin damage to the hair shaft with sparing of the cortex. However, recent cases have reported significant invasion of the hair cortex by bacterial structures.

TA is often a clinical diagnosis. Histopathology reveals a discontinuous thick-layer coating of bacterial structures adhered to the hair shafts. Periodic acid–Schiff, gram, and Grocott silver stains are all positive. Examination of hairs with 20% hydrogen peroxide solution can provide a microscopic diagnosis. Wood lamp examination produces a weak, yellow fluorescence, and potassium hydroxide test demonstrates yellowish material of minimal translucency surrounding the hair cortex.

Complete resolution can be achieved by shaving off all the axillary hairs. It is imperative to maintain good hygiene and keep the area dry and clean. To prevent recurrence, topical benzoyl peroxide or topical antibiotics such as erythromycin and clindamycin can be applied. If axillary hyperhidrosis is concurrently present, aluminum chloride hexahydrate solution can decrease sweating and reduce the risk of bacterial regrowth. Injections of botulinum toxin can be used to treat the hyperhidrosis as well. 

This patient responded well to topical erythromycin lotion.

This case and photo are courtesy of Jessica Cervantes, University of Miami Miller School of Medicine, and Dr. Bilu Martin.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/edermatologynews. To submit a case for possible publication, send an email to [email protected].

MIAMI—Among patients with Parkinson’s disease with well-defined morning off episodes, 83% achieved an on-medication state within 45 minutes of treatment with sublingual apomorphine film, according to research presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Investigators presented preliminary results from an open-label dose titration phase of a phase III trial.

The sublingual apomorphine film, known as APL-130277, is being developed by Marlborough, Massachusetts-based Sunovion Pharmaceuticals. Apomorphine injected subcutaneously is approved for the acute, intermittent treatment of off episodes, but it is not widely used, possibly because of its parenteral administration, researchers have said. The dissolvable film consists of an apomorphine drug layer and a second layer that is designed to neutralize acid generation and enhance drug permeability. The film appeared to be effective in a phase II open-label study.

Daily Off Episodes

Participants were older than 18, had idiopathic Parkinson’s disease, and had a modified Hoehn and Yahr stage between 1 and 3 on medication. Participants were responsive to levodopa and had more than two hours of off time per day. Patients were receiving stable doses of levodopa–carbidopa. Investigators excluded patients with psychosis, dementia, or impulse control disorders; mouth cankers or sores; or prior treatment of Parkinson’s disease with a neurosurgical procedure, continuous subcutaneous apomorphine infusion, or levodopa–carbidopa enteral suspension. They also excluded patients who received subcutaneous apomorphine within seven days before screening or were taking 5-HT3 antagonists, dopamine antagonists (other than quetiapine or clozapine), or dopamine-depleting agents.

Three days prior to the dose-titration phase, patients initiated treatment with trimethobenzamide or domperidone, which may reduce nausea and vomiting that can occur during the initiation of apomorphine therapy. Patients arrived at a clinic in an off state, having not taken their regular morning levodopa dose or other adjunctive medication later than midnight, and received 10 mg of APL-130277. Investigators assessed patients using the Unified Parkinson’s Disease Rating Scale Part III prior to dosing and 15, 30, 45, 60, and 90 minutes after dosing. Patients who responded with a fully on response (ie, patients and investigators agreed that medication was benefiting mobility, stiffness, and slowness such that patients had adequate motor function to perform their normal daily activities) were considered to have completed the dose- titration phase and could proceed to randomization for the maintenance treatment phase. Patients who responded to a dose could try the next highest dose at a subsequent titration visit to assess the potential for an improved response at the higher dose. Doses increased by 5-mg increments up to 35 mg.

Of 76 patients who entered the dose-titration phase, 63 (83%) turned fully on with treatment. Among patients who turned fully on, 24 (38%) did so within 15 minutes, and 49 (78%) did so within 30 minutes. The median dose turning patients to fully on was 20 mg. Patients who turned fully on assessed time to onset as between five and 12 minutes.

Safety Data

In a presentation of preliminary safety data from the dose-titration phase, Stuart Isaacson, MD, Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida, and colleagues reported that five of the 76 patients who entered the dose-titration phase discontinued the trial due to adverse events—two due to nausea, one due to somnolence, one due to headache, and one due to presyncope. Another two patients withdrew consent, and nine patients who did not turn on at the 35-mg dose were discontinued from the trial. Other reported adverse events included dizziness, yawning, vomiting, and symptomatic hypotension. Most adverse events were considered mild. “In this preliminary analysis, APL-130277 was well tolerated in patients in the dose-titration phase,” Dr. Isaacson and colleagues concluded.

—Jake Remaly

Suggested Reading

Hauser RA, Olanow CW, Dzyngel B, et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson’s disease. Mov Disord. 2016;31(9):1366-1372.

MIAMI—Among patients with Parkinson’s disease with well-defined morning off episodes, 83% achieved an on-medication state within 45 minutes of treatment with sublingual apomorphine film, according to research presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Investigators presented preliminary results from an open-label dose titration phase of a phase III trial.

The sublingual apomorphine film, known as APL-130277, is being developed by Marlborough, Massachusetts-based Sunovion Pharmaceuticals. Apomorphine injected subcutaneously is approved for the acute, intermittent treatment of off episodes, but it is not widely used, possibly because of its parenteral administration, researchers have said. The dissolvable film consists of an apomorphine drug layer and a second layer that is designed to neutralize acid generation and enhance drug permeability. The film appeared to be effective in a phase II open-label study.

Daily Off Episodes

Participants were older than 18, had idiopathic Parkinson’s disease, and had a modified Hoehn and Yahr stage between 1 and 3 on medication. Participants were responsive to levodopa and had more than two hours of off time per day. Patients were receiving stable doses of levodopa–carbidopa. Investigators excluded patients with psychosis, dementia, or impulse control disorders; mouth cankers or sores; or prior treatment of Parkinson’s disease with a neurosurgical procedure, continuous subcutaneous apomorphine infusion, or levodopa–carbidopa enteral suspension. They also excluded patients who received subcutaneous apomorphine within seven days before screening or were taking 5-HT3 antagonists, dopamine antagonists (other than quetiapine or clozapine), or dopamine-depleting agents.

Three days prior to the dose-titration phase, patients initiated treatment with trimethobenzamide or domperidone, which may reduce nausea and vomiting that can occur during the initiation of apomorphine therapy. Patients arrived at a clinic in an off state, having not taken their regular morning levodopa dose or other adjunctive medication later than midnight, and received 10 mg of APL-130277. Investigators assessed patients using the Unified Parkinson’s Disease Rating Scale Part III prior to dosing and 15, 30, 45, 60, and 90 minutes after dosing. Patients who responded with a fully on response (ie, patients and investigators agreed that medication was benefiting mobility, stiffness, and slowness such that patients had adequate motor function to perform their normal daily activities) were considered to have completed the dose- titration phase and could proceed to randomization for the maintenance treatment phase. Patients who responded to a dose could try the next highest dose at a subsequent titration visit to assess the potential for an improved response at the higher dose. Doses increased by 5-mg increments up to 35 mg.

Of 76 patients who entered the dose-titration phase, 63 (83%) turned fully on with treatment. Among patients who turned fully on, 24 (38%) did so within 15 minutes, and 49 (78%) did so within 30 minutes. The median dose turning patients to fully on was 20 mg. Patients who turned fully on assessed time to onset as between five and 12 minutes.

Safety Data

In a presentation of preliminary safety data from the dose-titration phase, Stuart Isaacson, MD, Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida, and colleagues reported that five of the 76 patients who entered the dose-titration phase discontinued the trial due to adverse events—two due to nausea, one due to somnolence, one due to headache, and one due to presyncope. Another two patients withdrew consent, and nine patients who did not turn on at the 35-mg dose were discontinued from the trial. Other reported adverse events included dizziness, yawning, vomiting, and symptomatic hypotension. Most adverse events were considered mild. “In this preliminary analysis, APL-130277 was well tolerated in patients in the dose-titration phase,” Dr. Isaacson and colleagues concluded.

—Jake Remaly

Suggested Reading

Hauser RA, Olanow CW, Dzyngel B, et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson’s disease. Mov Disord. 2016;31(9):1366-1372.

MIAMI—Among patients with Parkinson’s disease with well-defined morning off episodes, 83% achieved an on-medication state within 45 minutes of treatment with sublingual apomorphine film, according to research presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Investigators presented preliminary results from an open-label dose titration phase of a phase III trial.

The sublingual apomorphine film, known as APL-130277, is being developed by Marlborough, Massachusetts-based Sunovion Pharmaceuticals. Apomorphine injected subcutaneously is approved for the acute, intermittent treatment of off episodes, but it is not widely used, possibly because of its parenteral administration, researchers have said. The dissolvable film consists of an apomorphine drug layer and a second layer that is designed to neutralize acid generation and enhance drug permeability. The film appeared to be effective in a phase II open-label study.

Daily Off Episodes

Participants were older than 18, had idiopathic Parkinson’s disease, and had a modified Hoehn and Yahr stage between 1 and 3 on medication. Participants were responsive to levodopa and had more than two hours of off time per day. Patients were receiving stable doses of levodopa–carbidopa. Investigators excluded patients with psychosis, dementia, or impulse control disorders; mouth cankers or sores; or prior treatment of Parkinson’s disease with a neurosurgical procedure, continuous subcutaneous apomorphine infusion, or levodopa–carbidopa enteral suspension. They also excluded patients who received subcutaneous apomorphine within seven days before screening or were taking 5-HT3 antagonists, dopamine antagonists (other than quetiapine or clozapine), or dopamine-depleting agents.

Three days prior to the dose-titration phase, patients initiated treatment with trimethobenzamide or domperidone, which may reduce nausea and vomiting that can occur during the initiation of apomorphine therapy. Patients arrived at a clinic in an off state, having not taken their regular morning levodopa dose or other adjunctive medication later than midnight, and received 10 mg of APL-130277. Investigators assessed patients using the Unified Parkinson’s Disease Rating Scale Part III prior to dosing and 15, 30, 45, 60, and 90 minutes after dosing. Patients who responded with a fully on response (ie, patients and investigators agreed that medication was benefiting mobility, stiffness, and slowness such that patients had adequate motor function to perform their normal daily activities) were considered to have completed the dose- titration phase and could proceed to randomization for the maintenance treatment phase. Patients who responded to a dose could try the next highest dose at a subsequent titration visit to assess the potential for an improved response at the higher dose. Doses increased by 5-mg increments up to 35 mg.

Of 76 patients who entered the dose-titration phase, 63 (83%) turned fully on with treatment. Among patients who turned fully on, 24 (38%) did so within 15 minutes, and 49 (78%) did so within 30 minutes. The median dose turning patients to fully on was 20 mg. Patients who turned fully on assessed time to onset as between five and 12 minutes.

Safety Data

In a presentation of preliminary safety data from the dose-titration phase, Stuart Isaacson, MD, Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida, and colleagues reported that five of the 76 patients who entered the dose-titration phase discontinued the trial due to adverse events—two due to nausea, one due to somnolence, one due to headache, and one due to presyncope. Another two patients withdrew consent, and nine patients who did not turn on at the 35-mg dose were discontinued from the trial. Other reported adverse events included dizziness, yawning, vomiting, and symptomatic hypotension. Most adverse events were considered mild. “In this preliminary analysis, APL-130277 was well tolerated in patients in the dose-titration phase,” Dr. Isaacson and colleagues concluded.

—Jake Remaly

Suggested Reading

Hauser RA, Olanow CW, Dzyngel B, et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson’s disease. Mov Disord. 2016;31(9):1366-1372.

Teen years, no doubt, come with expected challenges. For teens with Down syndrome (DS), the challenges are exponentially greater. Although DS is associated with mental retardation, the vast majority of people with DS have only mild to moderate intellectual disability. Still, this can lead to a great deal of internal stress for the adolescent and anxiety and stress for the parents.

Many issues must be considered for the adolescent with DS. Annual surveillance changes as the child ages and the need for intervention do as well. For example, 50% of children with DS are born with congenital heart defect. During infancy, it is important to do echocardiograms to identify and follow specific lesions. Approximately 57% of adolescents with DS will develop mitral valve prolapse and 10% will develop aortic regurgitation.¹ Therefore, close evaluation should be done, listening for new onset murmurs, clicks, and unexplained fatigue, and, if these are identified, an echocardiogram should be repeated.
 

George Doyle/Thinkstock

Dr. Pearce is a pediatrician in Frankfort, Ill. She reported no relevant financial disclosures. Email her at [email protected]

References

1. J Pediatr Health Care. 2006 May-Jun;20(3):198-205.

2. Pediatrics. 2011. doi: 10.1542/peds.2011-1605.

3. Clin Obes. 2015;5(2):52-9.

Correction, 7/26/17: An earlier version of this article misstated a recommendation about radiologic evaluation of the cervical spine in asymptomatic children

Teen years, no doubt, come with expected challenges. For teens with Down syndrome (DS), the challenges are exponentially greater. Although DS is associated with mental retardation, the vast majority of people with DS have only mild to moderate intellectual disability. Still, this can lead to a great deal of internal stress for the adolescent and anxiety and stress for the parents.

Many issues must be considered for the adolescent with DS. Annual surveillance changes as the child ages and the need for intervention do as well. For example, 50% of children with DS are born with congenital heart defect. During infancy, it is important to do echocardiograms to identify and follow specific lesions. Approximately 57% of adolescents with DS will develop mitral valve prolapse and 10% will develop aortic regurgitation.¹ Therefore, close evaluation should be done, listening for new onset murmurs, clicks, and unexplained fatigue, and, if these are identified, an echocardiogram should be repeated.
 

George Doyle/Thinkstock

Dr. Pearce is a pediatrician in Frankfort, Ill. She reported no relevant financial disclosures. Email her at [email protected]

References

1. J Pediatr Health Care. 2006 May-Jun;20(3):198-205.

2. Pediatrics. 2011. doi: 10.1542/peds.2011-1605.

3. Clin Obes. 2015;5(2):52-9.

Correction, 7/26/17: An earlier version of this article misstated a recommendation about radiologic evaluation of the cervical spine in asymptomatic children

Teen years, no doubt, come with expected challenges. For teens with Down syndrome (DS), the challenges are exponentially greater. Although DS is associated with mental retardation, the vast majority of people with DS have only mild to moderate intellectual disability. Still, this can lead to a great deal of internal stress for the adolescent and anxiety and stress for the parents.

Many issues must be considered for the adolescent with DS. Annual surveillance changes as the child ages and the need for intervention do as well. For example, 50% of children with DS are born with congenital heart defect. During infancy, it is important to do echocardiograms to identify and follow specific lesions. Approximately 57% of adolescents with DS will develop mitral valve prolapse and 10% will develop aortic regurgitation.¹ Therefore, close evaluation should be done, listening for new onset murmurs, clicks, and unexplained fatigue, and, if these are identified, an echocardiogram should be repeated.
 

George Doyle/Thinkstock

Dr. Pearce is a pediatrician in Frankfort, Ill. She reported no relevant financial disclosures. Email her at [email protected]

References

1. J Pediatr Health Care. 2006 May-Jun;20(3):198-205.

2. Pediatrics. 2011. doi: 10.1542/peds.2011-1605.

3. Clin Obes. 2015;5(2):52-9.

Correction, 7/26/17: An earlier version of this article misstated a recommendation about radiologic evaluation of the cervical spine in asymptomatic children

ATLANTA – Formaldehyde has various clinical presentations and variable thresholds to trigger allergic contact dermatitis, so it requires a high index of suspicion, according to Salma de la Feld, MD.

It may present as irritant contact dermatitis, allergic contact dermatitis (especially to the hands and face), airborne allergic contact dermatitis, or systemic allergic contact dermatitis (to aspartame).

Doug Brunk/Frontline Medical News

Fragrance

Fragrance, which was named Allergen of the Year in 2007, is another common contact allergen. An estimated 4%-11% of the worldwide population is allergic to fragrance mix, while 1.6%-10.8% is allergic to balsam of Peru. T.R.U.E. tests for the allergen often yield false-negative results. Clinicians who fail to test for fragrance mix 2 will miss about one-third of fragrance allergic contact dermatitis diagnoses. “If the distribution is scattered, you want to be suspicious for fragrance allergy,” Dr. de la Feld said. “Sometimes patients get exposed inadvertently by their significant other or by a family member who is spraying a fragrant product.” Treatment is avoidance. “You want to tell patients to look for products labeled as fragrance free,” she said. “ ‘Unscented’ does not count. When patients tell you that they’re not using any perfume, you want to ask them if they’ve put any on their clothes.”

Systemic contact dermatitis

Dr. de la Feld finished her presentation by discussing systemic contact dermatitis, which she defined as a rash from systemic exposure to an allergen in someone who was previously sensitized. Alternative names for the condition include endogenous contact eczema, systemically-induced contact dermatitis, and internal-external contact-type hypersensitivity. She acknowledged that not all dermatologists believe systemic contact dermatitis to be a true clinical condition, but she does.

“It’s most classically and commonly reported with nickel and balsam of Peru and more slowly with some other allergens,” she said. “It can have multiple clinical presentations, and it’s not always widespread.” The three most common presentations are dyshidrotic hand eczema, sites of prior contact dermatitis (from contact or patch test), and anogenital and/or flexural areas (Baboon syndrome). There are other reports of systemic contact dermatitis presenting as disseminated patchy dermatitis, generalized erythroderma, cheilitis, and lichen planus of the lip.

Dr. de la Feld reported having no relevant financial disclosures.

[email protected]

Correction, 3/28/17: In an earlier version of this article Dr. de la Feld's name was misstated in the photo caption.

ATLANTA – Formaldehyde has various clinical presentations and variable thresholds to trigger allergic contact dermatitis, so it requires a high index of suspicion, according to Salma de la Feld, MD.

It may present as irritant contact dermatitis, allergic contact dermatitis (especially to the hands and face), airborne allergic contact dermatitis, or systemic allergic contact dermatitis (to aspartame).

Doug Brunk/Frontline Medical News

Fragrance

Fragrance, which was named Allergen of the Year in 2007, is another common contact allergen. An estimated 4%-11% of the worldwide population is allergic to fragrance mix, while 1.6%-10.8% is allergic to balsam of Peru. T.R.U.E. tests for the allergen often yield false-negative results. Clinicians who fail to test for fragrance mix 2 will miss about one-third of fragrance allergic contact dermatitis diagnoses. “If the distribution is scattered, you want to be suspicious for fragrance allergy,” Dr. de la Feld said. “Sometimes patients get exposed inadvertently by their significant other or by a family member who is spraying a fragrant product.” Treatment is avoidance. “You want to tell patients to look for products labeled as fragrance free,” she said. “ ‘Unscented’ does not count. When patients tell you that they’re not using any perfume, you want to ask them if they’ve put any on their clothes.”

Systemic contact dermatitis

Dr. de la Feld finished her presentation by discussing systemic contact dermatitis, which she defined as a rash from systemic exposure to an allergen in someone who was previously sensitized. Alternative names for the condition include endogenous contact eczema, systemically-induced contact dermatitis, and internal-external contact-type hypersensitivity. She acknowledged that not all dermatologists believe systemic contact dermatitis to be a true clinical condition, but she does.

“It’s most classically and commonly reported with nickel and balsam of Peru and more slowly with some other allergens,” she said. “It can have multiple clinical presentations, and it’s not always widespread.” The three most common presentations are dyshidrotic hand eczema, sites of prior contact dermatitis (from contact or patch test), and anogenital and/or flexural areas (Baboon syndrome). There are other reports of systemic contact dermatitis presenting as disseminated patchy dermatitis, generalized erythroderma, cheilitis, and lichen planus of the lip.

Dr. de la Feld reported having no relevant financial disclosures.

[email protected]

Correction, 3/28/17: In an earlier version of this article Dr. de la Feld's name was misstated in the photo caption.

ATLANTA – Formaldehyde has various clinical presentations and variable thresholds to trigger allergic contact dermatitis, so it requires a high index of suspicion, according to Salma de la Feld, MD.

It may present as irritant contact dermatitis, allergic contact dermatitis (especially to the hands and face), airborne allergic contact dermatitis, or systemic allergic contact dermatitis (to aspartame).

Doug Brunk/Frontline Medical News

Fragrance

Fragrance, which was named Allergen of the Year in 2007, is another common contact allergen. An estimated 4%-11% of the worldwide population is allergic to fragrance mix, while 1.6%-10.8% is allergic to balsam of Peru. T.R.U.E. tests for the allergen often yield false-negative results. Clinicians who fail to test for fragrance mix 2 will miss about one-third of fragrance allergic contact dermatitis diagnoses. “If the distribution is scattered, you want to be suspicious for fragrance allergy,” Dr. de la Feld said. “Sometimes patients get exposed inadvertently by their significant other or by a family member who is spraying a fragrant product.” Treatment is avoidance. “You want to tell patients to look for products labeled as fragrance free,” she said. “ ‘Unscented’ does not count. When patients tell you that they’re not using any perfume, you want to ask them if they’ve put any on their clothes.”

Systemic contact dermatitis

Dr. de la Feld finished her presentation by discussing systemic contact dermatitis, which she defined as a rash from systemic exposure to an allergen in someone who was previously sensitized. Alternative names for the condition include endogenous contact eczema, systemically-induced contact dermatitis, and internal-external contact-type hypersensitivity. She acknowledged that not all dermatologists believe systemic contact dermatitis to be a true clinical condition, but she does.

“It’s most classically and commonly reported with nickel and balsam of Peru and more slowly with some other allergens,” she said. “It can have multiple clinical presentations, and it’s not always widespread.” The three most common presentations are dyshidrotic hand eczema, sites of prior contact dermatitis (from contact or patch test), and anogenital and/or flexural areas (Baboon syndrome). There are other reports of systemic contact dermatitis presenting as disseminated patchy dermatitis, generalized erythroderma, cheilitis, and lichen planus of the lip.

Dr. de la Feld reported having no relevant financial disclosures.

[email protected]

Correction, 3/28/17: In an earlier version of this article Dr. de la Feld's name was misstated in the photo caption.

THE CASE

A 30-year-old woman presented to our emergency department with severe polyarthralgia, a high-grade fever (102.6º F), and a diffuse maculopapular rash on her trunk and extremities. She had returned from her honeymoon in Jamaica 6 days earlier. During her time there, she ate local cuisine, hiked in the jungle, and was bitten by many mosquitoes. The patient was nauseous, and had been experiencing headaches, generalized weakness, and fatigue. Her physical exam revealed a maculopapular rash on her trunk and upper extremities. She had tenderness and pain, as well as decreased range of motion in her ankles, knees, and wrists. The patient had no erythema, swelling, petechiae, or bruising. She had a past medical history of Graves’ disease and had received all of her childhood immunizations.

THE DIAGNOSIS

Our lab work-up included a complete blood count, liver function tests, blood pathogens for malaria, and serologic tests for dengue fever, measles, mumps, rubella, Lyme disease, human immunodeficiency virus (HIV), and parvovirus. We ruled out dengue fever because the patient had no evidence of hemorrhage, thrombocytopenia, rising hematocrit, or neutropenia. HIV antibody screening tests were performed, although, in retrospect, confirmatory HIV quantitative RNA testing should’ve been obtained because of the acute nature of the patient’s symptoms. Regardless, the work-up was negative, with the exception of a positive parvovirus immunoglobulin G (IgG).

Given our patient’s travel history, unremarkable lab results, and physical exam (notably the rash and joint pain), we suspected that she was infected with the chikungunya virus and tested for it. The results of chikungunya serum titers returned 13 days later and were positive for both immunoglobulin M (IgM) and IgG, confirming our suspicion.

DISCUSSION

Chikungunya is a viral infection that is most commonly transmitted to humans via mosquitoes. The infection was first identified in West Africa in the mid-1900s and predominantly occurs in tropical and subtropical regions due to the numbers of mosquitoes in those areas. Since 2000, outbreaks have been most common in Africa and Asia, with the largest outbreaks occurring from 2005 to 2006.^1,2 Chikungunya has since become more widespread in the Indian Ocean islands, and in 2013, it was first identified in the Caribbean islands. As of March 2017, over one million cases have been reported in the Americas, according to the Pan American Health Organization.³ In 2014, 12 locally transmitted cases were reported in Florida.⁴

The most common mosquito vectors for chikungunya are the Aedes albopictus (Asian tiger mosquito) and Aedes aegypti mosquitoes. These mosquitoes also transmit dengue fever, yellow fever, and Zika virus. Both of these mosquitoes are well-adapted to urban areas and can breed in standing water. A aegypti mosquitoes are found only in the southern United States, while A albopictus mosquitoes can be found in more temperate climates—areas like New York, New Jersey, and Pennsylvania.⁴ Both species are daytime biters, so their activity peaks during the dawn and dusk periods. Because local mosquito vectors exist as far north as New York, local transmission and outbreaks are possible in many parts of the United States.

When to suspect chikungunya, and what to look for

Suspect chikungunya in patients returning from endemic areas. After a 3- to 7-day incubation period, the clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever. Headache, nausea, and conjunctivitis may also occur. Polyarthralgia and arthritis usually present in symmetrical distal joints and are accompanied by face and trunk flushing that is followed by a maculopapular rash. The rash predominantly appears on the trunk and limbs, but can also occur on the face, palms, and soles. Tendons and ligaments—especially the Achilles tendon—may become inflamed, as well. Symptoms typically resolve within 2 to 3 weeks, although polyarthralgia may last for months or even years.

The clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever.

There is no known risk of transmission through breast milk or in utero, although vertical transmission through vaginal or cesarean birth is common in viremic women. Blood-borne transmission can occur in the laboratory, nosocomially, or through the transfusion of blood products if exposure occurs during the early viremic phase.^1,2 Dual infections are possible (typically with yellow fever, malaria, Zika virus, or dengue fever) and should be considered based on the patient’s travel history.⁵ Abnormal laboratory findings are less common, but may include lymphopenia (most common), thrombocytopenia, elevations in blood urea nitrogen and creatinine (indicating an acute kidney injury), and elevated liver transaminases.

Chikungunya is generally considered a self-limiting disease, but severe atypical manifestations can lead to meningoencephalitis, respiratory failure, and even death. Severe disease is more commonly seen in infants, patients over age 65 years, and in those with chronic medical conditions.

The differential diagnosis for chikungunya virus includes dengue fever, Zika virus, malaria, measles, rubella, parvovirus, primary HIV infection, Lyme disease, and other inflammatory joint conditions. The differential depends on where a patient lives, their travel history, and exposures.

Dengue and chikungunya have similar features, which often make them difficult to distinguish. However, patients with dengue fever present more often with neutropenia, thrombocytopenia, and signs or symptoms of shock or hemorrhage.⁶ The chikungunya rash is typically a maculopapular rash on the trunk, hands, and feet that appears within the first 2 days of illness, as opposed to dengue, which has a similar rash, but appears later in the disease (Days 2-5). Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) if dengue fever is suspected, as they can worsen hemorrhaging.⁷

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands.

Zika virus typically presents with milder symptoms compared to chikungunya. Patients may have a skin rash and occasionally, conjunctivitis, but limited high fevers or joint pain. Zika rash is maculopapular, but typically starts on the face on the first day of the illness. Zika has been associated with neurological complications such as Guillain-Barré syndrome and microcephaly in fetuses of infected pregnant woman.⁸

Choice of testing modality depends on when symptoms began

Laboratory diagnosis of chikungunya can be accomplished 3 ways: viral culture, reverse transcriptase-polymerase chain reaction (RT-PCR) viral RNA, and serology.¹ The choice of which modality to use depends on the time between the onset of symptoms and the date on which a serum sample is drawn.

• If the patient presents within the first 3 days of illness, viral culture can detect chikungunya. Chikungunya virus testing is available through the Centers for Disease Control and Prevention (CDC), some state laboratories, and one commercial lab.⁸ Viral cultures are considered the gold standard for diagnosis, but a requirement for an elevated biosafety level, as well as a longer incubation time, make them less useful in the clinical setting.^1,9
• If symptoms started less than 5 to 8 days prior, serum should be sent for RT-PCR for viral RNA.
• If symptoms occurred more than 8 days prior, serum should be sent for IgM and IgG serologic testing.

If the acute sample was negative (and chikungunya is still suspected), a second serum sample should be drawn 2 to 3 weeks later during the convalescent phase and sent for IgG serologic testing.

There are no specific treatments or vaccines available for chikungunya, but both live and inactivated vaccines are being tested. To prevent chikungunya virus infection, advise patients traveling to endemic areas to reduce mosquito exposure by avoiding outdoor activities during dusk and dawn, wearing long-sleeved shirts and long pants, and using an insect repellent that contains DEET. Recommend that patients who will be sleeping in a high-risk area use bed netting treated with permethrin. The CDC Web site has excellent additional information, available at http://www.cdc.gov/chikungunya.¹⁰

Our patient was briefly hospitalized due to intractable pain. She was discharged after 2 days and given prescriptions for motrin 800 mg and percocet 5/325 mg for breakthrough pain. Her wrist and ankle pain persisted after discharge, but slowly resolved after 2 to 3 months.

THE TAKEAWAY

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands, and mosquito vectors found in parts of the United States are enhancing the possibility of local outbreaks. Travel to endemic regions—and the classic symptoms of fever, polyarthralgia, and a maculopapular rash—should lead you to put chikungunya high on the differential. Chikungunya is considered a reportable disease and treatment is largely supportive. Co-infections are possible and should be considered based on the patient’s travel history.

THE CASE

A 30-year-old woman presented to our emergency department with severe polyarthralgia, a high-grade fever (102.6º F), and a diffuse maculopapular rash on her trunk and extremities. She had returned from her honeymoon in Jamaica 6 days earlier. During her time there, she ate local cuisine, hiked in the jungle, and was bitten by many mosquitoes. The patient was nauseous, and had been experiencing headaches, generalized weakness, and fatigue. Her physical exam revealed a maculopapular rash on her trunk and upper extremities. She had tenderness and pain, as well as decreased range of motion in her ankles, knees, and wrists. The patient had no erythema, swelling, petechiae, or bruising. She had a past medical history of Graves’ disease and had received all of her childhood immunizations.

THE DIAGNOSIS

Our lab work-up included a complete blood count, liver function tests, blood pathogens for malaria, and serologic tests for dengue fever, measles, mumps, rubella, Lyme disease, human immunodeficiency virus (HIV), and parvovirus. We ruled out dengue fever because the patient had no evidence of hemorrhage, thrombocytopenia, rising hematocrit, or neutropenia. HIV antibody screening tests were performed, although, in retrospect, confirmatory HIV quantitative RNA testing should’ve been obtained because of the acute nature of the patient’s symptoms. Regardless, the work-up was negative, with the exception of a positive parvovirus immunoglobulin G (IgG).

Given our patient’s travel history, unremarkable lab results, and physical exam (notably the rash and joint pain), we suspected that she was infected with the chikungunya virus and tested for it. The results of chikungunya serum titers returned 13 days later and were positive for both immunoglobulin M (IgM) and IgG, confirming our suspicion.

DISCUSSION

Chikungunya is a viral infection that is most commonly transmitted to humans via mosquitoes. The infection was first identified in West Africa in the mid-1900s and predominantly occurs in tropical and subtropical regions due to the numbers of mosquitoes in those areas. Since 2000, outbreaks have been most common in Africa and Asia, with the largest outbreaks occurring from 2005 to 2006.^1,2 Chikungunya has since become more widespread in the Indian Ocean islands, and in 2013, it was first identified in the Caribbean islands. As of March 2017, over one million cases have been reported in the Americas, according to the Pan American Health Organization.³ In 2014, 12 locally transmitted cases were reported in Florida.⁴

The most common mosquito vectors for chikungunya are the Aedes albopictus (Asian tiger mosquito) and Aedes aegypti mosquitoes. These mosquitoes also transmit dengue fever, yellow fever, and Zika virus. Both of these mosquitoes are well-adapted to urban areas and can breed in standing water. A aegypti mosquitoes are found only in the southern United States, while A albopictus mosquitoes can be found in more temperate climates—areas like New York, New Jersey, and Pennsylvania.⁴ Both species are daytime biters, so their activity peaks during the dawn and dusk periods. Because local mosquito vectors exist as far north as New York, local transmission and outbreaks are possible in many parts of the United States.

When to suspect chikungunya, and what to look for

Suspect chikungunya in patients returning from endemic areas. After a 3- to 7-day incubation period, the clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever. Headache, nausea, and conjunctivitis may also occur. Polyarthralgia and arthritis usually present in symmetrical distal joints and are accompanied by face and trunk flushing that is followed by a maculopapular rash. The rash predominantly appears on the trunk and limbs, but can also occur on the face, palms, and soles. Tendons and ligaments—especially the Achilles tendon—may become inflamed, as well. Symptoms typically resolve within 2 to 3 weeks, although polyarthralgia may last for months or even years.

The clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever.

There is no known risk of transmission through breast milk or in utero, although vertical transmission through vaginal or cesarean birth is common in viremic women. Blood-borne transmission can occur in the laboratory, nosocomially, or through the transfusion of blood products if exposure occurs during the early viremic phase.^1,2 Dual infections are possible (typically with yellow fever, malaria, Zika virus, or dengue fever) and should be considered based on the patient’s travel history.⁵ Abnormal laboratory findings are less common, but may include lymphopenia (most common), thrombocytopenia, elevations in blood urea nitrogen and creatinine (indicating an acute kidney injury), and elevated liver transaminases.

Chikungunya is generally considered a self-limiting disease, but severe atypical manifestations can lead to meningoencephalitis, respiratory failure, and even death. Severe disease is more commonly seen in infants, patients over age 65 years, and in those with chronic medical conditions.

The differential diagnosis for chikungunya virus includes dengue fever, Zika virus, malaria, measles, rubella, parvovirus, primary HIV infection, Lyme disease, and other inflammatory joint conditions. The differential depends on where a patient lives, their travel history, and exposures.

Dengue and chikungunya have similar features, which often make them difficult to distinguish. However, patients with dengue fever present more often with neutropenia, thrombocytopenia, and signs or symptoms of shock or hemorrhage.⁶ The chikungunya rash is typically a maculopapular rash on the trunk, hands, and feet that appears within the first 2 days of illness, as opposed to dengue, which has a similar rash, but appears later in the disease (Days 2-5). Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) if dengue fever is suspected, as they can worsen hemorrhaging.⁷

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands.

Zika virus typically presents with milder symptoms compared to chikungunya. Patients may have a skin rash and occasionally, conjunctivitis, but limited high fevers or joint pain. Zika rash is maculopapular, but typically starts on the face on the first day of the illness. Zika has been associated with neurological complications such as Guillain-Barré syndrome and microcephaly in fetuses of infected pregnant woman.⁸

Choice of testing modality depends on when symptoms began

Laboratory diagnosis of chikungunya can be accomplished 3 ways: viral culture, reverse transcriptase-polymerase chain reaction (RT-PCR) viral RNA, and serology.¹ The choice of which modality to use depends on the time between the onset of symptoms and the date on which a serum sample is drawn.

• If the patient presents within the first 3 days of illness, viral culture can detect chikungunya. Chikungunya virus testing is available through the Centers for Disease Control and Prevention (CDC), some state laboratories, and one commercial lab.⁸ Viral cultures are considered the gold standard for diagnosis, but a requirement for an elevated biosafety level, as well as a longer incubation time, make them less useful in the clinical setting.^1,9
• If symptoms started less than 5 to 8 days prior, serum should be sent for RT-PCR for viral RNA.
• If symptoms occurred more than 8 days prior, serum should be sent for IgM and IgG serologic testing.

If the acute sample was negative (and chikungunya is still suspected), a second serum sample should be drawn 2 to 3 weeks later during the convalescent phase and sent for IgG serologic testing.

There are no specific treatments or vaccines available for chikungunya, but both live and inactivated vaccines are being tested. To prevent chikungunya virus infection, advise patients traveling to endemic areas to reduce mosquito exposure by avoiding outdoor activities during dusk and dawn, wearing long-sleeved shirts and long pants, and using an insect repellent that contains DEET. Recommend that patients who will be sleeping in a high-risk area use bed netting treated with permethrin. The CDC Web site has excellent additional information, available at http://www.cdc.gov/chikungunya.¹⁰

Our patient was briefly hospitalized due to intractable pain. She was discharged after 2 days and given prescriptions for motrin 800 mg and percocet 5/325 mg for breakthrough pain. Her wrist and ankle pain persisted after discharge, but slowly resolved after 2 to 3 months.

THE TAKEAWAY

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands, and mosquito vectors found in parts of the United States are enhancing the possibility of local outbreaks. Travel to endemic regions—and the classic symptoms of fever, polyarthralgia, and a maculopapular rash—should lead you to put chikungunya high on the differential. Chikungunya is considered a reportable disease and treatment is largely supportive. Co-infections are possible and should be considered based on the patient’s travel history.

THE CASE

A 30-year-old woman presented to our emergency department with severe polyarthralgia, a high-grade fever (102.6º F), and a diffuse maculopapular rash on her trunk and extremities. She had returned from her honeymoon in Jamaica 6 days earlier. During her time there, she ate local cuisine, hiked in the jungle, and was bitten by many mosquitoes. The patient was nauseous, and had been experiencing headaches, generalized weakness, and fatigue. Her physical exam revealed a maculopapular rash on her trunk and upper extremities. She had tenderness and pain, as well as decreased range of motion in her ankles, knees, and wrists. The patient had no erythema, swelling, petechiae, or bruising. She had a past medical history of Graves’ disease and had received all of her childhood immunizations.

THE DIAGNOSIS

Our lab work-up included a complete blood count, liver function tests, blood pathogens for malaria, and serologic tests for dengue fever, measles, mumps, rubella, Lyme disease, human immunodeficiency virus (HIV), and parvovirus. We ruled out dengue fever because the patient had no evidence of hemorrhage, thrombocytopenia, rising hematocrit, or neutropenia. HIV antibody screening tests were performed, although, in retrospect, confirmatory HIV quantitative RNA testing should’ve been obtained because of the acute nature of the patient’s symptoms. Regardless, the work-up was negative, with the exception of a positive parvovirus immunoglobulin G (IgG).

Given our patient’s travel history, unremarkable lab results, and physical exam (notably the rash and joint pain), we suspected that she was infected with the chikungunya virus and tested for it. The results of chikungunya serum titers returned 13 days later and were positive for both immunoglobulin M (IgM) and IgG, confirming our suspicion.

DISCUSSION

Chikungunya is a viral infection that is most commonly transmitted to humans via mosquitoes. The infection was first identified in West Africa in the mid-1900s and predominantly occurs in tropical and subtropical regions due to the numbers of mosquitoes in those areas. Since 2000, outbreaks have been most common in Africa and Asia, with the largest outbreaks occurring from 2005 to 2006.^1,2 Chikungunya has since become more widespread in the Indian Ocean islands, and in 2013, it was first identified in the Caribbean islands. As of March 2017, over one million cases have been reported in the Americas, according to the Pan American Health Organization.³ In 2014, 12 locally transmitted cases were reported in Florida.⁴

The most common mosquito vectors for chikungunya are the Aedes albopictus (Asian tiger mosquito) and Aedes aegypti mosquitoes. These mosquitoes also transmit dengue fever, yellow fever, and Zika virus. Both of these mosquitoes are well-adapted to urban areas and can breed in standing water. A aegypti mosquitoes are found only in the southern United States, while A albopictus mosquitoes can be found in more temperate climates—areas like New York, New Jersey, and Pennsylvania.⁴ Both species are daytime biters, so their activity peaks during the dawn and dusk periods. Because local mosquito vectors exist as far north as New York, local transmission and outbreaks are possible in many parts of the United States.

When to suspect chikungunya, and what to look for

Suspect chikungunya in patients returning from endemic areas. After a 3- to 7-day incubation period, the clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever. Headache, nausea, and conjunctivitis may also occur. Polyarthralgia and arthritis usually present in symmetrical distal joints and are accompanied by face and trunk flushing that is followed by a maculopapular rash. The rash predominantly appears on the trunk and limbs, but can also occur on the face, palms, and soles. Tendons and ligaments—especially the Achilles tendon—may become inflamed, as well. Symptoms typically resolve within 2 to 3 weeks, although polyarthralgia may last for months or even years.

The clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever.

There is no known risk of transmission through breast milk or in utero, although vertical transmission through vaginal or cesarean birth is common in viremic women. Blood-borne transmission can occur in the laboratory, nosocomially, or through the transfusion of blood products if exposure occurs during the early viremic phase.^1,2 Dual infections are possible (typically with yellow fever, malaria, Zika virus, or dengue fever) and should be considered based on the patient’s travel history.⁵ Abnormal laboratory findings are less common, but may include lymphopenia (most common), thrombocytopenia, elevations in blood urea nitrogen and creatinine (indicating an acute kidney injury), and elevated liver transaminases.

Chikungunya is generally considered a self-limiting disease, but severe atypical manifestations can lead to meningoencephalitis, respiratory failure, and even death. Severe disease is more commonly seen in infants, patients over age 65 years, and in those with chronic medical conditions.

The differential diagnosis for chikungunya virus includes dengue fever, Zika virus, malaria, measles, rubella, parvovirus, primary HIV infection, Lyme disease, and other inflammatory joint conditions. The differential depends on where a patient lives, their travel history, and exposures.

Dengue and chikungunya have similar features, which often make them difficult to distinguish. However, patients with dengue fever present more often with neutropenia, thrombocytopenia, and signs or symptoms of shock or hemorrhage.⁶ The chikungunya rash is typically a maculopapular rash on the trunk, hands, and feet that appears within the first 2 days of illness, as opposed to dengue, which has a similar rash, but appears later in the disease (Days 2-5). Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) if dengue fever is suspected, as they can worsen hemorrhaging.⁷

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands.

Zika virus typically presents with milder symptoms compared to chikungunya. Patients may have a skin rash and occasionally, conjunctivitis, but limited high fevers or joint pain. Zika rash is maculopapular, but typically starts on the face on the first day of the illness. Zika has been associated with neurological complications such as Guillain-Barré syndrome and microcephaly in fetuses of infected pregnant woman.⁸

Choice of testing modality depends on when symptoms began

Laboratory diagnosis of chikungunya can be accomplished 3 ways: viral culture, reverse transcriptase-polymerase chain reaction (RT-PCR) viral RNA, and serology.¹ The choice of which modality to use depends on the time between the onset of symptoms and the date on which a serum sample is drawn.

• If the patient presents within the first 3 days of illness, viral culture can detect chikungunya. Chikungunya virus testing is available through the Centers for Disease Control and Prevention (CDC), some state laboratories, and one commercial lab.⁸ Viral cultures are considered the gold standard for diagnosis, but a requirement for an elevated biosafety level, as well as a longer incubation time, make them less useful in the clinical setting.^1,9
• If symptoms started less than 5 to 8 days prior, serum should be sent for RT-PCR for viral RNA.
• If symptoms occurred more than 8 days prior, serum should be sent for IgM and IgG serologic testing.

If the acute sample was negative (and chikungunya is still suspected), a second serum sample should be drawn 2 to 3 weeks later during the convalescent phase and sent for IgG serologic testing.

There are no specific treatments or vaccines available for chikungunya, but both live and inactivated vaccines are being tested. To prevent chikungunya virus infection, advise patients traveling to endemic areas to reduce mosquito exposure by avoiding outdoor activities during dusk and dawn, wearing long-sleeved shirts and long pants, and using an insect repellent that contains DEET. Recommend that patients who will be sleeping in a high-risk area use bed netting treated with permethrin. The CDC Web site has excellent additional information, available at http://www.cdc.gov/chikungunya.¹⁰

Our patient was briefly hospitalized due to intractable pain. She was discharged after 2 days and given prescriptions for motrin 800 mg and percocet 5/325 mg for breakthrough pain. Her wrist and ankle pain persisted after discharge, but slowly resolved after 2 to 3 months.

THE TAKEAWAY

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands, and mosquito vectors found in parts of the United States are enhancing the possibility of local outbreaks. Travel to endemic regions—and the classic symptoms of fever, polyarthralgia, and a maculopapular rash—should lead you to put chikungunya high on the differential. Chikungunya is considered a reportable disease and treatment is largely supportive. Co-infections are possible and should be considered based on the patient’s travel history.

Air leaks have been reported to be frequent and difficult-to-manage sequelae in some lung resection procedures.  Click here to learn about a new device being used in the thoracic space

Author:

Mark Ellis Ginsburg,

MD, FACS

Associate Clinical Professor of Surgery

Division of Cardiothoracic Surgery

Columbia University Medical Center

New York, NY

Faculty Disclosure: Dr. Ginsburg has received compensation from Medtronic Inc. for his participation in this article. He has no other conflicts of interest to disclose.

Air leaks have been reported to be frequent and difficult-to-manage sequelae in some lung resection procedures.  Click here to learn about a new device being used in the thoracic space

Author:

Mark Ellis Ginsburg,

MD, FACS

Associate Clinical Professor of Surgery

Division of Cardiothoracic Surgery

Columbia University Medical Center

New York, NY

Faculty Disclosure: Dr. Ginsburg has received compensation from Medtronic Inc. for his participation in this article. He has no other conflicts of interest to disclose.

Air leaks have been reported to be frequent and difficult-to-manage sequelae in some lung resection procedures.  Click here to learn about a new device being used in the thoracic space

Author:

Mark Ellis Ginsburg,

MD, FACS

Associate Clinical Professor of Surgery

Division of Cardiothoracic Surgery

Columbia University Medical Center

New York, NY

Faculty Disclosure: Dr. Ginsburg has received compensation from Medtronic Inc. for his participation in this article. He has no other conflicts of interest to disclose.