Click here to access the May 2016 Digital Edition. 

Table of Contents

• Why VA Health Care Is Different
• Anterior Cervical Interbody Fusion Using Polyetheretherketone (PEEK) Cage Device and Local Autograft Bone
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 2
• A Real Welcome Home: Permanent Housing for Homeless Veterans
• Veterans’ Satisfaction With Erectile Dysfunction Treatment
• VA PBM Academic Detailing Service: Implementation and Lessons Learned
• Adherence to Disease-Modifying Therapies in Patients With MS: A Retrospective Cohort Study
• The Role of Fidaxomicin in Clostridium difficile Infection

Click here to access the May 2016 Digital Edition. 

Table of Contents

• Why VA Health Care Is Different
• Anterior Cervical Interbody Fusion Using Polyetheretherketone (PEEK) Cage Device and Local Autograft Bone
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 2
• A Real Welcome Home: Permanent Housing for Homeless Veterans
• Veterans’ Satisfaction With Erectile Dysfunction Treatment
• VA PBM Academic Detailing Service: Implementation and Lessons Learned
• Adherence to Disease-Modifying Therapies in Patients With MS: A Retrospective Cohort Study
• The Role of Fidaxomicin in Clostridium difficile Infection

Click here to access the May 2016 Digital Edition. 

Table of Contents

• Why VA Health Care Is Different
• Anterior Cervical Interbody Fusion Using Polyetheretherketone (PEEK) Cage Device and Local Autograft Bone
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 2
• A Real Welcome Home: Permanent Housing for Homeless Veterans
• Veterans’ Satisfaction With Erectile Dysfunction Treatment
• VA PBM Academic Detailing Service: Implementation and Lessons Learned
• Adherence to Disease-Modifying Therapies in Patients With MS: A Retrospective Cohort Study
• The Role of Fidaxomicin in Clostridium difficile Infection

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

May has arrived, and for the majority of your patients it signals the end of the school year and the beginning of summer vacation. Zika virus is on the minds of most people since its arrival to the Western Hemisphere in March 2015. With the fluidity of this outbreak and almost daily news updates and recommendations, many parents have voiced or will be voicing concerns regarding summer travel destinations.

Many concerns about Zika virus have been previously addressed in this column (“Zika virus: More questions than answers?” by Dr. Kristina Bryant). However, if the decision is to avoid international travel because of the ongoing Zika outbreak, it doesn’t mean your patients get a free pass and will not have to be concerned about acquiring any infectious diseases. They still need to be vigilant about avoiding those pesky vectors that transmit arboviruses and other vector-borne diseases that occur in the United States.

Arboviruses are transmitted by mosquitoes, ticks, or fleas. Most infections are subclinical. If symptoms develop, they are manifested by a generalized febrile illness including fever, headache, myalgia, arthralgia, and rash. Hemorrhagic fever (dengue) or neuroinvasive disease can include aseptic meningitis, encephalitis, or acute flaccid paralysis. Neuroinvasive disease rarely occurs with dengue, Colorado tick fever, and chikungunya infections.

While more than 100 arboviruses can cause infection, some of the more common arboviruses associated with human disease include West Nile, first detected in the United States in 1999 and chikungunya, first reported in the Americas in 2013 with local transmission documented in Florida, Puerto Rico, and the U.S. Virgin Islands in 2014. It is estimated that dengue causes over 100 million cases worldwide annually. Almost 40% of the world’s inhabitants live in endemic areas. The majority of cases on the U.S. mainland are imported. However, it is endemic in all U.S. territories including Guam, American Samoa, the U.S. Virgin Islands, and Puerto Rico. Between September 2015 and March 2016, Hawaii experienced a dengue outbreak involving 264 individuals including 46 children. As of April 16, 2016, there were no infectious individuals on the island.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Other domestic arboviruses causing disease include St. Louis, Eastern, and Western Equine encephalitis, La Crosse encephalitis, Colorado tick fever, and Powassan virus. All are transmitted by mosquitoes with the exception of Powassan and Colorado tick fever, which are transmitted by ticks. The numbers of cases nationally are much lower for these diseases, compared with West Nile, dengue, and chikungunya. National and state-specific information is available for domestic arboviruses at diseasemaps.usgs.gov/mapviewer. Data is compiled by ArboNET, a national arboviral surveillance system that is managed by the Centers for Disease Control and Prevention (CDC) in conjunction with state health departments. Not only is human disease monitored, but it also maintains data on viremic blood donors, dead birds, mosquitoes, veterinary disease cases, and sentinel animals.

Spring and summer are the most active seasons for ticks. Bacterial and spirochetal diseases transmitted by them include rickettsial diseases such as Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis. Tularemia in addition to Lyme and tick-borne relapsing fever are also transmitted by ticks. Babesiosis, which is due to a parasite, and southern tick-associated rash illness (STARI), whose causative agent is yet to be determined, are two additional tick-related diagnoses.

Of note, dengue, chikungunya, and Zika are all transmitted by infected Aedes mosquitoes. There is no enzootic cycle. Just human-mosquito-human transmission. In contrast, West Nile virus is transmitted by Culex mosquitoes in an enzootic cycle between an avian reservoir and humans.

Treatment

There is no specific treatment for arboviral infections. The primary goal is relief of symptoms with fluids, bed rest, and analgesics. For bacterial vector-borne diseases, antibiotic therapy is indicated and is based on the specific pathogen. Doxycycline is the drug of choice for treatment of suspected and confirmed Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis even in children less than 8 years of age. Delay in initiation of antimicrobial therapy pending definitive diagnosis may lead to an adverse outcome. It is also the drug of choice for tick-borne relapsing fever.

Lyme disease is also responsive to antibiotic treatment. Therapy is based on the disease category. (Lyme disease in “Red Book: 2015 Report of the Committee on Infectious Diseases,” [Elk Grove Village, Ill.: American Academy of Pediatrics, 2015, pp. 516-25]).

STARI clinically presents with a lesion that resembles erythema migrans in southern and southeastern states. However, it has not been associated with any of the complications reported with disseminated Lyme disease. Treatment is not recommended.

Tularemia and babesiosis are both responsive to antimicrobial therapy and would best be managed in consultation with an infectious disease physician.

A handy, concise, up to date reference guide about all of the tick-borne diseases including photographs is available at the App Store. The Tickborne Diseases App was developed by the CDC and it is free!

Prevention

The cornerstone of disease prevention is avoidance of mosquito and tick bites, in addition to eliminating mosquito breeding sites. Ticks are generally found near the ground, in brushy or wooded areas. They usually wait for a potential host to brush against them. When this happens, they climb onto the host and find a site to attach.

Is there a role for antimicrobial prophylaxis once a tick has been discovered? There is no data to support antimicrobial prophylaxis to prevent Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis. Prophylaxis with doxycycline or ciprofloxacin is recommended for children and adults after exposure to an intentional release of tularemia and for laboratory workers after inadvertent exposure. For prevention of Lyme disease, a single dose of doxycycline (4 mg/kg, max dose 200 mg) may be offered under limited conditions: The patient is at least 8 years of age, resides in an area where Lyme is highly endemic, the tick removed was engorged, therapy can be initiated within 72 hours after tick removal, and the estimated time of attachment was at least 36 hours. There is inadequate data on the use of amoxicillin.

Remember, not all mosquitoes are alike. Those that transmit chikungunya, dengue, and Zika (Aedes mosquitoes) are primarily daytime mosquitoes, but also can bite at night. West Nile is transmitted by Culex mosquitoes, which feed from dusk to dawn.

Here are some tips to share with your patients that should decrease their chances of acquiring a mosquito or tick-borne disease:

• Apply mosquito repellent only to intact exposed skin when outdoors. Most repellents can be safely used on children at least 2 months of age and older. Avoid applying repellent directly on the child’s hand. Use at least a 20% DEET (N,N-diethyl-meta-toluamide) containing product. Other Environmental Protection Agency–registered repellents are an alternative (Additional information is available at http://www2.epa.gov/insect-repellents). Products containing oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) should not be used on children under 3 years of age.

• Apply permethrin to clothing, hats, boots, and so on. It is designed to repel mosquitoes and ticks. It can last for several washings. It is ideal to spray over nets covering carriers in children younger than 2 months of age.

• Wear long-sleeved shirts and long pants tucked inside of socks when hiking.

• Check for ticks daily, especially under the arms, behind the ears, around the waist, behind the knees, and inside belly buttons after outdoor activities.

• Have your patients learn how to effectively remove a tick. With a fine tipped tweezer, grasp the tick as close to the skin as possible and pull straight up with even pressure. Do not twist or jerk the tick. Do not squash the tick. Place it in a bag and dispose of it. Clean the site after removal with alcohol, iodine, or soap and water.

• Encourage families to mosquito proof their home by using screens on windows and doors, and using air conditioning when available.

• Empty and scrub all items that contain water such as birdbaths, planters, or wading pools around the outside of the home at least weekly because mosquitoes lay eggs in or near free standing water.

• Dogs and cats should be treated for ticks as recommended by the veterinarian.

The impact of the ongoing Zika virus outbreak is uncertain. While it may have an impact on those planning international travel now and in the near future, several arboviral and vector-borne diseases currently exist in the United States. Encouraging our patients to practice interventions to prevent mosquito and tick bites now will also serve to protect them if Zika virus becomes established in the Aedes mosquitoes here in the future and/or if they have plans for international travel. For up to date information on Zika virus for yourself and your patients, visit www.cdc.gov/zika.

Bonnie M. Word, M.D., is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email Dr. Word at [email protected].

May has arrived, and for the majority of your patients it signals the end of the school year and the beginning of summer vacation. Zika virus is on the minds of most people since its arrival to the Western Hemisphere in March 2015. With the fluidity of this outbreak and almost daily news updates and recommendations, many parents have voiced or will be voicing concerns regarding summer travel destinations.

Many concerns about Zika virus have been previously addressed in this column (“Zika virus: More questions than answers?” by Dr. Kristina Bryant). However, if the decision is to avoid international travel because of the ongoing Zika outbreak, it doesn’t mean your patients get a free pass and will not have to be concerned about acquiring any infectious diseases. They still need to be vigilant about avoiding those pesky vectors that transmit arboviruses and other vector-borne diseases that occur in the United States.

Arboviruses are transmitted by mosquitoes, ticks, or fleas. Most infections are subclinical. If symptoms develop, they are manifested by a generalized febrile illness including fever, headache, myalgia, arthralgia, and rash. Hemorrhagic fever (dengue) or neuroinvasive disease can include aseptic meningitis, encephalitis, or acute flaccid paralysis. Neuroinvasive disease rarely occurs with dengue, Colorado tick fever, and chikungunya infections.

While more than 100 arboviruses can cause infection, some of the more common arboviruses associated with human disease include West Nile, first detected in the United States in 1999 and chikungunya, first reported in the Americas in 2013 with local transmission documented in Florida, Puerto Rico, and the U.S. Virgin Islands in 2014. It is estimated that dengue causes over 100 million cases worldwide annually. Almost 40% of the world’s inhabitants live in endemic areas. The majority of cases on the U.S. mainland are imported. However, it is endemic in all U.S. territories including Guam, American Samoa, the U.S. Virgin Islands, and Puerto Rico. Between September 2015 and March 2016, Hawaii experienced a dengue outbreak involving 264 individuals including 46 children. As of April 16, 2016, there were no infectious individuals on the island.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Other domestic arboviruses causing disease include St. Louis, Eastern, and Western Equine encephalitis, La Crosse encephalitis, Colorado tick fever, and Powassan virus. All are transmitted by mosquitoes with the exception of Powassan and Colorado tick fever, which are transmitted by ticks. The numbers of cases nationally are much lower for these diseases, compared with West Nile, dengue, and chikungunya. National and state-specific information is available for domestic arboviruses at diseasemaps.usgs.gov/mapviewer. Data is compiled by ArboNET, a national arboviral surveillance system that is managed by the Centers for Disease Control and Prevention (CDC) in conjunction with state health departments. Not only is human disease monitored, but it also maintains data on viremic blood donors, dead birds, mosquitoes, veterinary disease cases, and sentinel animals.

Spring and summer are the most active seasons for ticks. Bacterial and spirochetal diseases transmitted by them include rickettsial diseases such as Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis. Tularemia in addition to Lyme and tick-borne relapsing fever are also transmitted by ticks. Babesiosis, which is due to a parasite, and southern tick-associated rash illness (STARI), whose causative agent is yet to be determined, are two additional tick-related diagnoses.

Of note, dengue, chikungunya, and Zika are all transmitted by infected Aedes mosquitoes. There is no enzootic cycle. Just human-mosquito-human transmission. In contrast, West Nile virus is transmitted by Culex mosquitoes in an enzootic cycle between an avian reservoir and humans.

Treatment

There is no specific treatment for arboviral infections. The primary goal is relief of symptoms with fluids, bed rest, and analgesics. For bacterial vector-borne diseases, antibiotic therapy is indicated and is based on the specific pathogen. Doxycycline is the drug of choice for treatment of suspected and confirmed Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis even in children less than 8 years of age. Delay in initiation of antimicrobial therapy pending definitive diagnosis may lead to an adverse outcome. It is also the drug of choice for tick-borne relapsing fever.

Lyme disease is also responsive to antibiotic treatment. Therapy is based on the disease category. (Lyme disease in “Red Book: 2015 Report of the Committee on Infectious Diseases,” [Elk Grove Village, Ill.: American Academy of Pediatrics, 2015, pp. 516-25]).

STARI clinically presents with a lesion that resembles erythema migrans in southern and southeastern states. However, it has not been associated with any of the complications reported with disseminated Lyme disease. Treatment is not recommended.

Tularemia and babesiosis are both responsive to antimicrobial therapy and would best be managed in consultation with an infectious disease physician.

A handy, concise, up to date reference guide about all of the tick-borne diseases including photographs is available at the App Store. The Tickborne Diseases App was developed by the CDC and it is free!

Prevention

The cornerstone of disease prevention is avoidance of mosquito and tick bites, in addition to eliminating mosquito breeding sites. Ticks are generally found near the ground, in brushy or wooded areas. They usually wait for a potential host to brush against them. When this happens, they climb onto the host and find a site to attach.

Is there a role for antimicrobial prophylaxis once a tick has been discovered? There is no data to support antimicrobial prophylaxis to prevent Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis. Prophylaxis with doxycycline or ciprofloxacin is recommended for children and adults after exposure to an intentional release of tularemia and for laboratory workers after inadvertent exposure. For prevention of Lyme disease, a single dose of doxycycline (4 mg/kg, max dose 200 mg) may be offered under limited conditions: The patient is at least 8 years of age, resides in an area where Lyme is highly endemic, the tick removed was engorged, therapy can be initiated within 72 hours after tick removal, and the estimated time of attachment was at least 36 hours. There is inadequate data on the use of amoxicillin.

Remember, not all mosquitoes are alike. Those that transmit chikungunya, dengue, and Zika (Aedes mosquitoes) are primarily daytime mosquitoes, but also can bite at night. West Nile is transmitted by Culex mosquitoes, which feed from dusk to dawn.

Here are some tips to share with your patients that should decrease their chances of acquiring a mosquito or tick-borne disease:

• Apply mosquito repellent only to intact exposed skin when outdoors. Most repellents can be safely used on children at least 2 months of age and older. Avoid applying repellent directly on the child’s hand. Use at least a 20% DEET (N,N-diethyl-meta-toluamide) containing product. Other Environmental Protection Agency–registered repellents are an alternative (Additional information is available at http://www2.epa.gov/insect-repellents). Products containing oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) should not be used on children under 3 years of age.

• Apply permethrin to clothing, hats, boots, and so on. It is designed to repel mosquitoes and ticks. It can last for several washings. It is ideal to spray over nets covering carriers in children younger than 2 months of age.

• Wear long-sleeved shirts and long pants tucked inside of socks when hiking.

• Check for ticks daily, especially under the arms, behind the ears, around the waist, behind the knees, and inside belly buttons after outdoor activities.

• Have your patients learn how to effectively remove a tick. With a fine tipped tweezer, grasp the tick as close to the skin as possible and pull straight up with even pressure. Do not twist or jerk the tick. Do not squash the tick. Place it in a bag and dispose of it. Clean the site after removal with alcohol, iodine, or soap and water.

• Encourage families to mosquito proof their home by using screens on windows and doors, and using air conditioning when available.

• Empty and scrub all items that contain water such as birdbaths, planters, or wading pools around the outside of the home at least weekly because mosquitoes lay eggs in or near free standing water.

• Dogs and cats should be treated for ticks as recommended by the veterinarian.

The impact of the ongoing Zika virus outbreak is uncertain. While it may have an impact on those planning international travel now and in the near future, several arboviral and vector-borne diseases currently exist in the United States. Encouraging our patients to practice interventions to prevent mosquito and tick bites now will also serve to protect them if Zika virus becomes established in the Aedes mosquitoes here in the future and/or if they have plans for international travel. For up to date information on Zika virus for yourself and your patients, visit www.cdc.gov/zika.

Bonnie M. Word, M.D., is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email Dr. Word at [email protected].

May has arrived, and for the majority of your patients it signals the end of the school year and the beginning of summer vacation. Zika virus is on the minds of most people since its arrival to the Western Hemisphere in March 2015. With the fluidity of this outbreak and almost daily news updates and recommendations, many parents have voiced or will be voicing concerns regarding summer travel destinations.

Many concerns about Zika virus have been previously addressed in this column (“Zika virus: More questions than answers?” by Dr. Kristina Bryant). However, if the decision is to avoid international travel because of the ongoing Zika outbreak, it doesn’t mean your patients get a free pass and will not have to be concerned about acquiring any infectious diseases. They still need to be vigilant about avoiding those pesky vectors that transmit arboviruses and other vector-borne diseases that occur in the United States.

Arboviruses are transmitted by mosquitoes, ticks, or fleas. Most infections are subclinical. If symptoms develop, they are manifested by a generalized febrile illness including fever, headache, myalgia, arthralgia, and rash. Hemorrhagic fever (dengue) or neuroinvasive disease can include aseptic meningitis, encephalitis, or acute flaccid paralysis. Neuroinvasive disease rarely occurs with dengue, Colorado tick fever, and chikungunya infections.

While more than 100 arboviruses can cause infection, some of the more common arboviruses associated with human disease include West Nile, first detected in the United States in 1999 and chikungunya, first reported in the Americas in 2013 with local transmission documented in Florida, Puerto Rico, and the U.S. Virgin Islands in 2014. It is estimated that dengue causes over 100 million cases worldwide annually. Almost 40% of the world’s inhabitants live in endemic areas. The majority of cases on the U.S. mainland are imported. However, it is endemic in all U.S. territories including Guam, American Samoa, the U.S. Virgin Islands, and Puerto Rico. Between September 2015 and March 2016, Hawaii experienced a dengue outbreak involving 264 individuals including 46 children. As of April 16, 2016, there were no infectious individuals on the island.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Other domestic arboviruses causing disease include St. Louis, Eastern, and Western Equine encephalitis, La Crosse encephalitis, Colorado tick fever, and Powassan virus. All are transmitted by mosquitoes with the exception of Powassan and Colorado tick fever, which are transmitted by ticks. The numbers of cases nationally are much lower for these diseases, compared with West Nile, dengue, and chikungunya. National and state-specific information is available for domestic arboviruses at diseasemaps.usgs.gov/mapviewer. Data is compiled by ArboNET, a national arboviral surveillance system that is managed by the Centers for Disease Control and Prevention (CDC) in conjunction with state health departments. Not only is human disease monitored, but it also maintains data on viremic blood donors, dead birds, mosquitoes, veterinary disease cases, and sentinel animals.

Spring and summer are the most active seasons for ticks. Bacterial and spirochetal diseases transmitted by them include rickettsial diseases such as Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis. Tularemia in addition to Lyme and tick-borne relapsing fever are also transmitted by ticks. Babesiosis, which is due to a parasite, and southern tick-associated rash illness (STARI), whose causative agent is yet to be determined, are two additional tick-related diagnoses.

Of note, dengue, chikungunya, and Zika are all transmitted by infected Aedes mosquitoes. There is no enzootic cycle. Just human-mosquito-human transmission. In contrast, West Nile virus is transmitted by Culex mosquitoes in an enzootic cycle between an avian reservoir and humans.

Treatment

There is no specific treatment for arboviral infections. The primary goal is relief of symptoms with fluids, bed rest, and analgesics. For bacterial vector-borne diseases, antibiotic therapy is indicated and is based on the specific pathogen. Doxycycline is the drug of choice for treatment of suspected and confirmed Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis even in children less than 8 years of age. Delay in initiation of antimicrobial therapy pending definitive diagnosis may lead to an adverse outcome. It is also the drug of choice for tick-borne relapsing fever.

Lyme disease is also responsive to antibiotic treatment. Therapy is based on the disease category. (Lyme disease in “Red Book: 2015 Report of the Committee on Infectious Diseases,” [Elk Grove Village, Ill.: American Academy of Pediatrics, 2015, pp. 516-25]).

STARI clinically presents with a lesion that resembles erythema migrans in southern and southeastern states. However, it has not been associated with any of the complications reported with disseminated Lyme disease. Treatment is not recommended.

Tularemia and babesiosis are both responsive to antimicrobial therapy and would best be managed in consultation with an infectious disease physician.

A handy, concise, up to date reference guide about all of the tick-borne diseases including photographs is available at the App Store. The Tickborne Diseases App was developed by the CDC and it is free!

Prevention

The cornerstone of disease prevention is avoidance of mosquito and tick bites, in addition to eliminating mosquito breeding sites. Ticks are generally found near the ground, in brushy or wooded areas. They usually wait for a potential host to brush against them. When this happens, they climb onto the host and find a site to attach.

Is there a role for antimicrobial prophylaxis once a tick has been discovered? There is no data to support antimicrobial prophylaxis to prevent Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis. Prophylaxis with doxycycline or ciprofloxacin is recommended for children and adults after exposure to an intentional release of tularemia and for laboratory workers after inadvertent exposure. For prevention of Lyme disease, a single dose of doxycycline (4 mg/kg, max dose 200 mg) may be offered under limited conditions: The patient is at least 8 years of age, resides in an area where Lyme is highly endemic, the tick removed was engorged, therapy can be initiated within 72 hours after tick removal, and the estimated time of attachment was at least 36 hours. There is inadequate data on the use of amoxicillin.

Remember, not all mosquitoes are alike. Those that transmit chikungunya, dengue, and Zika (Aedes mosquitoes) are primarily daytime mosquitoes, but also can bite at night. West Nile is transmitted by Culex mosquitoes, which feed from dusk to dawn.

Here are some tips to share with your patients that should decrease their chances of acquiring a mosquito or tick-borne disease:

• Apply mosquito repellent only to intact exposed skin when outdoors. Most repellents can be safely used on children at least 2 months of age and older. Avoid applying repellent directly on the child’s hand. Use at least a 20% DEET (N,N-diethyl-meta-toluamide) containing product. Other Environmental Protection Agency–registered repellents are an alternative (Additional information is available at http://www2.epa.gov/insect-repellents). Products containing oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) should not be used on children under 3 years of age.

• Apply permethrin to clothing, hats, boots, and so on. It is designed to repel mosquitoes and ticks. It can last for several washings. It is ideal to spray over nets covering carriers in children younger than 2 months of age.

• Wear long-sleeved shirts and long pants tucked inside of socks when hiking.

• Check for ticks daily, especially under the arms, behind the ears, around the waist, behind the knees, and inside belly buttons after outdoor activities.

• Have your patients learn how to effectively remove a tick. With a fine tipped tweezer, grasp the tick as close to the skin as possible and pull straight up with even pressure. Do not twist or jerk the tick. Do not squash the tick. Place it in a bag and dispose of it. Clean the site after removal with alcohol, iodine, or soap and water.

• Encourage families to mosquito proof their home by using screens on windows and doors, and using air conditioning when available.

• Empty and scrub all items that contain water such as birdbaths, planters, or wading pools around the outside of the home at least weekly because mosquitoes lay eggs in or near free standing water.

• Dogs and cats should be treated for ticks as recommended by the veterinarian.

The impact of the ongoing Zika virus outbreak is uncertain. While it may have an impact on those planning international travel now and in the near future, several arboviral and vector-borne diseases currently exist in the United States. Encouraging our patients to practice interventions to prevent mosquito and tick bites now will also serve to protect them if Zika virus becomes established in the Aedes mosquitoes here in the future and/or if they have plans for international travel. For up to date information on Zika virus for yourself and your patients, visit www.cdc.gov/zika.

Bonnie M. Word, M.D., is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email Dr. Word at [email protected].

To the Editor: I read with great interest the commentary by Lau and Naugler¹ regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)² and updated in 2016 (3rd edition) in the I/LA-20 guidance document.³

The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.⁴ Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease. 

Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion⁵ of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.

While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.^6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.

Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.^2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.

The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.⁸  These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.

Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.^9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.

Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.

To the Editor: I read with great interest the commentary by Lau and Naugler¹ regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)² and updated in 2016 (3rd edition) in the I/LA-20 guidance document.³

The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.⁴ Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease. 

Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion⁵ of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.

While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.^6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.

Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.^2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.

The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.⁸  These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.

Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.^9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.

Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.

To the Editor: I read with great interest the commentary by Lau and Naugler¹ regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)² and updated in 2016 (3rd edition) in the I/LA-20 guidance document.³

The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.⁴ Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease. 

Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion⁵ of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.

While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.^6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.

Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.^2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.

The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.⁸  These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.

Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.^9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.

Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.

In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.

There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.

It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.

In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references. 

In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.

There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.

It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.

In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references. 

In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.

There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.

It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.

In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references. 

Inspection of the fingernails and toenails should be part of a complete physical examination. A basic understanding of nail anatomy and recognition of several basic types of nail lines and bands allow the clinician to properly diagnose and treat the nail disease, to recognize possible underlying systemic diseases, and to know when to refer the patient to a dermatologist for specialized evaluation and biopsy.

In this review, we delineate the three basic types of nail lines­—white lines (leukonychia striata), brown-black lines (longitudinal melanonychia), and red lines (longitudinal erythronychia)—and the differential diagnosis for each type. We also discuss grooves in the nail plate, or Beau lines.

BASIC NAIL ANATOMY

A fundamental understanding of the anatomy of the nail unit is necessary to understand the origin of nail diseases and underlying pathologic conditions.

The nail unit includes the nail matrix, the lunula, the nail fold, the nail plate, and the nail bed. The nail matrix extends from under the proximal nail fold to the half-moon-shaped area (ie, the lunula) and is responsible for nail plate production. The nail bed lies under the nail plate and on top of the distal phalanx and extends from the lunula to just proximal to the free edge of the nail; its rich blood supply gives it its reddish color.

Nails grow slowly, and this should be kept in mind during the examination. Regrowth of a fingernail takes at least 6 months, and regrowth of a toenail may take 12 to 18 months. Therefore, a defect in the nail plate may reveal an injury that occurred—or a condition that began—several months before.¹

NAIL EXAMINATION ESSENTIALS

A complete examination includes all 20 nail units and the periungual skin. Patients should be instructed to remove nail polish from all nails, as it may camouflage dystrophy or disease of the nail. Photography and careful measurement help document changes over time.

LEUKONYCHIA STRIATA: WHITE NAIL LINES

White nail lines or leukonychia is classified as true or apparent, depending on whether the origin is in the nail matrix or the nail bed.

In true leukonychia, there is abnormal keratinization of the underlying nail matrix, resulting in parakeratosis within the nail plate and an opaque appearance on examination.² The white discoloration is unaffected by pressure, and the opacity moves distally as the nail grows out, which can be documented by serial photography on subsequent visits.

Apparent leukonychia involves abnormal nail bed vasculature, which changes the translucency of the nail plate. The whiteness disappears with pressure, is unaffected by nail growth, and will likely show no change on later visits with serial photography.³

True leukonychia

Leukonychia striata, a subtype of true leuko­nychia, is characterized by transverse or longitudinal bands. It is most often associated with microtrauma, such as from a manicure.⁴ Lines due to trauma are typically more apparent in the central part of the nail plate; they spare the lateral portion and lie parallel to the edge of the proximal nail fold.⁵

Onychomycosis. White longitudinal bands may also be seen in onychomycosis, a fungal infection of the nail accounting for up to 50% of all cases of nail disease. The infection may present as irregular dense longitudinal white or yellowish bands or “spikes” on the nail plate with associated hyperkeratosis, known as a dermatophytoma (Figure 1).

If a fungal infection is suspected, a potassium hydroxide stain can be performed on the subungual debris, which is then examined with direct microscopy.⁶ Alternatively, the physician can send a nail plate clipping in a 10% buffered formalin container with a request for a fungal stain such as periodic acid-Schiff.⁷ Microscopic examination of a dermatophytoma shows a dense mass of dermatophyte hyphae, otherwise known as a fungal abscess.⁸

The physician can play an important role in diagnosis because clinical findings suggestive of a dermatophytoma are associated with a poor response to antifungal therapy.⁹

Inherited diseases. White longitudinal bands are also an important clue to the rare autosomal dominant genodermatoses Hailey-Hailey disease (from mutations of the ATP2A2 gene) and Darier disease (from mutations of the ATP2C1 gene). Patients with Hailey-Hailey disease may have nails with multiple parallel longitudinal white stripes of variable width originating in the lunula and most prominent on the thumbs.^10–12 These patients also have recurrent vesicular eruptions in flexural skin areas, such as the groin, axilla, neck, and periumbilical area causing significant morbidity.

Patients with Darier disease may have nails with alternating red and white longitudinal streaks, described as “candy-cane,”¹³ as well as wedge-shaped distal subungual keratosis accompanied by flat keratotic papules on the proximal nail fold.¹⁴ These nail changes are reported in 92% to 95% of patients with Darier disease.^15,16 Patients typically have skin findings characterized by keratotic papules and plaques predominantly in seborrheic areas and palmoplantar pits, as well as secondary infections and malodor causing significant morbidity.¹⁵ Therefore, knowing the characteristic nail findings in these diseases may lead to more rapid diagnosis and treatment.

Mees lines. Leukonychia striata can present as transverse white lines, commonly known as Mees lines. They are 1- to 2-mm wide horizontal parallel white bands that span the width of the nail plate, usually affecting all fingernails.¹⁷ They are not a common finding and are most often associated with arsenic poisoning. They can also be used to identify the time of poisoning, since they tend to appear 2 months after the initial insult.

Mees lines are also associated with acute systemic stresses, such as acute renal failure, heart failure, ulcerative colitis, breast cancer, infections such as measles and tuberculosis, and systemic lupus erythematosus, and with exposure to toxic metals such as thallium.³

Apparent leukonychia

Apparent leukonychia can alert the physician to systemic diseases, infections, drug side effects, and nutrient deficiencies. Specific nail findings include Muehrcke lines, “half-and-half” nails, and Terry nails.

Muehrcke lines are paired white transverse bands that span the width of the nail bed and run parallel to the distal lunula. They were first described in the fingernails of patients with severe hypoalbuminemia, some of whom also had nephrotic syndrome, which resolved with normalization of the serum albumin level. Muehrcke lines have since been reported in patients with liver disease, malnutrition, chemotherapy, organ transplant, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome.^3,18 They are associated with periods of metabolic stress, ie, when the body’s capacity to synthesize proteins is diminished.¹⁹

Half-and-half nails, or Lindsay nails, are characterized by a white band proximally, a pink or red-brown band distally, and a sharp demarcation between the two (Figure 2). They were originally described in association with chronic renal disease,²⁰ and surprisingly, they resolve with kidney transplant but not with hemodialysis treatment or improvement in hemoglobin or albumin levels.^21–23 Half-and-half nails have been reported with Kawasaki disease, hepatic cirrhosis, Crohn disease, zinc deficiency, chemotherapy, Behçet disease, and pellagra.^3,24,25 They should be distinguished from Terry nails, which are characterized by leukonychia involving more than 80% of the total nail length.²⁶

Terry nails were originally reported in association with hepatic cirrhosis, usually secondary to alcoholism²⁷ but have since been found with heart failure, type 2 diabetes mellitus, pulmonary tuberculosis, reactive arthritis, older age, Hansen disease, and peripheral vascular disease.^3,26,28,29

LONGITUDINAL MELANONYCHIA: VERTICAL BROWN-BLACK NAIL LINES

Longitudinal melanonychia is the presence of black-brown vertical lines in the nail plate. They have a variety of causes, including blood from trauma; bacterial, fungal, or HIV infection; drug therapy (eg, from minocycline); endocrine disorders (Addison disease); exogenous pigmentation; or excess melanin production within the nail matrix.^30–32 They may also be a sign of a benign condition such as benign melanocytic activation, lentigines, or nevi, or a malignant condition such as melanoma (Figure 3).^33,34

When to suspect melanoma and refer

Although melanoma is less commonly associated with brown-black vertical nail lines, awareness of melanoma-associated longitudinal melanonychia reduces the likelihood of delayed diagnosis and improves patient outcomes.³⁵ Also, it is important to remember that although nail melanoma is more common in the 5th and 6th decades of life, it can occur at any age, even in children.³⁶

Findings that raise suspicion of nail melanoma (Table 1)^33,37 and that should prompt referral to a dermatologist who specializes in nails include the following:

• A personal or family history of melanoma
• Involvement of a “high-risk” digit (thumb, index finger, great toe),^30,31,38 although nail melanoma can occur in any digit
• Any new vertical brown-black nail pigmentation in a fair-skinned patient
• Only one nail affected: involvement of more than one nail is common in people with darker skin, and nearly all patients with darker skin exhibit longitudinal melanonychia by age 50³¹
• Changes in the band such as darkening, widening, and bleeding
• A bandwidth greater than 6 mm³³
• A band that is wider proximally than distally³⁴
• Nonuniform color of the line
• Indistinct lateral borders
• Associated with pigmentation of the nail fold (the Hutchinson sign, representing subungual melanoma),^31,39 nail plate dystrophy, bleeding, or ulceration.³³

While these features may help distinguish benign from malignant causes of longitudinal melanonychia, the clinical examination alone may not provide a definitive diagnosis. Delayed diagnosis of nail melanoma carries a high mortality rate; the internist can promote early diagnosis by recognizing the risk factors and clinical signs and referring the patient to a dermatologist for further evaluation with nail biopsy.

LONGITUDINAL ERYTHRONYCHIA: VERTICAL RED NAIL LINES

Longitudinal erythronychia—the presence of one or more linear red bands in the nail unit—can be localized (involving only one nail) or polydactylous (involving more than one nail). The localized form is usually due to a neoplastic process, whereas involvement of more than one nail may indicate an underlying regional or systemic disease.¹³Table 2 lists indications for referral to a nail specialist.

General features on examination

Clinical examination reveals one or more linear, pink-red streaks extending from the proximal nail fold to the distal free edge of the nail plate (Figure 4). The width of the band typically ranges from less than 1 mm to 3 mm.⁴⁰ Other features may include splinter hemorrhages within a red band, a semitransparent distal matrix, distal V-shaped chipping, splitting, onycholysis of the nail plate, and reactive distal nail bed and hyponychial hyperkeratosis. These features can be visible to the naked eye but may be better viewed with a magnifying glass, a 7× loupe, or a dermatoscope.¹³

Localized longitudinal erythronychia is usually seen in middle-aged individuals and is most commonly found on the thumbnail, followed by the index finger.^41,42 The condition may be asymptomatic, but the patient may present with pain or with concern that the split end of the nail catches on fabrics or small objects.⁴²

Glomus tumor

Intense, pulsatile pain with sensitivity to cold and tenderness to palpation is highly suggestive of glomus tumor,⁴³ a benign neoplasm that originates from a neuromyoarterial glomus body. Glomus bodies are located throughout the body but are more highly concentrated in the fingertips, especially beneath the nails, and they regulate skin circulation. Therefore, the nail unit is the most common site for glomus tumor.^44,45 A characteristic feature of subungual glomus tumor is demonstration of tenderness after pin-point palpation of the suspected tumor (positive Love sign).⁴⁵ While it is typical for glomus tumor to affect only one nail, multiple tumors are associated with neurofibromatosis type 1.⁴⁶ Confirmation of this diagnosis requires referral to a dermatologist.

Other causes of localized red nail lines

Onychopapilloma, a benign idiopathic tumor, is the most common cause of localized longitudinal erythronychia. Unlike glomus tumor, it is usually asymptomatic.^42,47 Less common benign conditions are warts, warty dyskeratoma, benign vascular proliferation, a solitary lesion of lichen planus, hemiplegia, and postsurgical scarring of the nail matrix. In some cases, the lines are idiopathic.^42,43

Malignant diseases that can present as localized longitudinal erythronychia include invasive squamous cell carcinoma, squamous cell carcinoma in situ (Bowen disease), and, less frequently, amelanotic melanoma in situ, malignant melanoma, and basal cell carcinoma.⁴² Squamous cell carcinoma in situ most commonly presents in the 5th decade of life and is the malignancy most commonly associated with localized longitudinal erythronychia. Clinically, there is also often nail dystrophy, such as distal subungual keratosis or onycholysis.⁴³

Patients with asymptomatic, stable localized longitudinal erythronychia may be followed closely with photography and measurements. However, any new lesion or a change in an existing lesion should prompt referral to a dermatologist for biopsy.¹³

Red streaks on more than one nail

Polydactylous longitudinal erythronychia usually presents in adults as red streaks on multiple nails and, depending on the presence or absence of symptoms (eg, pain, splitting), may be the patient’s chief complaint or an incidental finding noted by the astute clinician. Often, it is associated with systemic disease, most commonly lichen planus or Darier disease.

Lichen planus is a papulosquamous skin disease with nail involvement in 10% of patients and permanent nail dystrophy in 4%. Common nail findings include thinning, longitudinal ridging, and fissuring, as well as scarring of the nail matrix resulting in pterygium. Linear red streaks may accompany these more typical nail findings.¹³ Patients with Darier disease present with alternating red and white linear bands on multiple nails as in leukonychia striata.

Less frequently, polydactylous longitudinal erythronychia is associated with primary and systemic amyloidosis, hemiplegia, graft-vs-host disease, acantholytic epidermolysis bullosa, acantholytic dyskeratotic epidermal nevus, acrokeratosis verruciformis of Hopf, or pseudobulbar syndrome, or is idiopathic.^13,42,48 Therefore, the physician evaluating a patient with these nail findings should focus on a workup for regional or systemic disease or refer the patient to a dermatologist who specializes in nails.

BEAU LINES

Beau lines are a common finding in clinical practice. They are not true lines, but transverse grooves in the nail plate that arise from the temporary suppression of nail growth within the nail matrix that can occur during periods of acute or chronic stress or systemic illness (Figure 5).⁴⁹

The precipitating event may be local trauma or paronychia, chemotherapeutic agents cytotoxic to the nail matrix, or the abrupt onset of systemic disease.^18,50 The grooves have also been associated with rheumatic fever, malaria, pemphigus, Raynaud disease, and myocardial infarction, as well as following deep-sea dives.^51–53 The distance of a Beau line from the proximal nail fold can provide an estimate of the time of the acute stress, based on an average growth rate of 3 mm per month for fingernails and 1 mm per month for toenails.⁴⁹

Inspection of the fingernails and toenails should be part of a complete physical examination. A basic understanding of nail anatomy and recognition of several basic types of nail lines and bands allow the clinician to properly diagnose and treat the nail disease, to recognize possible underlying systemic diseases, and to know when to refer the patient to a dermatologist for specialized evaluation and biopsy.

In this review, we delineate the three basic types of nail lines­—white lines (leukonychia striata), brown-black lines (longitudinal melanonychia), and red lines (longitudinal erythronychia)—and the differential diagnosis for each type. We also discuss grooves in the nail plate, or Beau lines.

BASIC NAIL ANATOMY

A fundamental understanding of the anatomy of the nail unit is necessary to understand the origin of nail diseases and underlying pathologic conditions.

The nail unit includes the nail matrix, the lunula, the nail fold, the nail plate, and the nail bed. The nail matrix extends from under the proximal nail fold to the half-moon-shaped area (ie, the lunula) and is responsible for nail plate production. The nail bed lies under the nail plate and on top of the distal phalanx and extends from the lunula to just proximal to the free edge of the nail; its rich blood supply gives it its reddish color.

Nails grow slowly, and this should be kept in mind during the examination. Regrowth of a fingernail takes at least 6 months, and regrowth of a toenail may take 12 to 18 months. Therefore, a defect in the nail plate may reveal an injury that occurred—or a condition that began—several months before.¹

NAIL EXAMINATION ESSENTIALS

A complete examination includes all 20 nail units and the periungual skin. Patients should be instructed to remove nail polish from all nails, as it may camouflage dystrophy or disease of the nail. Photography and careful measurement help document changes over time.

LEUKONYCHIA STRIATA: WHITE NAIL LINES

White nail lines or leukonychia is classified as true or apparent, depending on whether the origin is in the nail matrix or the nail bed.

In true leukonychia, there is abnormal keratinization of the underlying nail matrix, resulting in parakeratosis within the nail plate and an opaque appearance on examination.² The white discoloration is unaffected by pressure, and the opacity moves distally as the nail grows out, which can be documented by serial photography on subsequent visits.

Apparent leukonychia involves abnormal nail bed vasculature, which changes the translucency of the nail plate. The whiteness disappears with pressure, is unaffected by nail growth, and will likely show no change on later visits with serial photography.³

True leukonychia

Leukonychia striata, a subtype of true leuko­nychia, is characterized by transverse or longitudinal bands. It is most often associated with microtrauma, such as from a manicure.⁴ Lines due to trauma are typically more apparent in the central part of the nail plate; they spare the lateral portion and lie parallel to the edge of the proximal nail fold.⁵

Onychomycosis. White longitudinal bands may also be seen in onychomycosis, a fungal infection of the nail accounting for up to 50% of all cases of nail disease. The infection may present as irregular dense longitudinal white or yellowish bands or “spikes” on the nail plate with associated hyperkeratosis, known as a dermatophytoma (Figure 1).

If a fungal infection is suspected, a potassium hydroxide stain can be performed on the subungual debris, which is then examined with direct microscopy.⁶ Alternatively, the physician can send a nail plate clipping in a 10% buffered formalin container with a request for a fungal stain such as periodic acid-Schiff.⁷ Microscopic examination of a dermatophytoma shows a dense mass of dermatophyte hyphae, otherwise known as a fungal abscess.⁸

The physician can play an important role in diagnosis because clinical findings suggestive of a dermatophytoma are associated with a poor response to antifungal therapy.⁹

Inherited diseases. White longitudinal bands are also an important clue to the rare autosomal dominant genodermatoses Hailey-Hailey disease (from mutations of the ATP2A2 gene) and Darier disease (from mutations of the ATP2C1 gene). Patients with Hailey-Hailey disease may have nails with multiple parallel longitudinal white stripes of variable width originating in the lunula and most prominent on the thumbs.^10–12 These patients also have recurrent vesicular eruptions in flexural skin areas, such as the groin, axilla, neck, and periumbilical area causing significant morbidity.

Patients with Darier disease may have nails with alternating red and white longitudinal streaks, described as “candy-cane,”¹³ as well as wedge-shaped distal subungual keratosis accompanied by flat keratotic papules on the proximal nail fold.¹⁴ These nail changes are reported in 92% to 95% of patients with Darier disease.^15,16 Patients typically have skin findings characterized by keratotic papules and plaques predominantly in seborrheic areas and palmoplantar pits, as well as secondary infections and malodor causing significant morbidity.¹⁵ Therefore, knowing the characteristic nail findings in these diseases may lead to more rapid diagnosis and treatment.

Mees lines. Leukonychia striata can present as transverse white lines, commonly known as Mees lines. They are 1- to 2-mm wide horizontal parallel white bands that span the width of the nail plate, usually affecting all fingernails.¹⁷ They are not a common finding and are most often associated with arsenic poisoning. They can also be used to identify the time of poisoning, since they tend to appear 2 months after the initial insult.

Mees lines are also associated with acute systemic stresses, such as acute renal failure, heart failure, ulcerative colitis, breast cancer, infections such as measles and tuberculosis, and systemic lupus erythematosus, and with exposure to toxic metals such as thallium.³

Apparent leukonychia

Apparent leukonychia can alert the physician to systemic diseases, infections, drug side effects, and nutrient deficiencies. Specific nail findings include Muehrcke lines, “half-and-half” nails, and Terry nails.

Muehrcke lines are paired white transverse bands that span the width of the nail bed and run parallel to the distal lunula. They were first described in the fingernails of patients with severe hypoalbuminemia, some of whom also had nephrotic syndrome, which resolved with normalization of the serum albumin level. Muehrcke lines have since been reported in patients with liver disease, malnutrition, chemotherapy, organ transplant, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome.^3,18 They are associated with periods of metabolic stress, ie, when the body’s capacity to synthesize proteins is diminished.¹⁹

Half-and-half nails, or Lindsay nails, are characterized by a white band proximally, a pink or red-brown band distally, and a sharp demarcation between the two (Figure 2). They were originally described in association with chronic renal disease,²⁰ and surprisingly, they resolve with kidney transplant but not with hemodialysis treatment or improvement in hemoglobin or albumin levels.^21–23 Half-and-half nails have been reported with Kawasaki disease, hepatic cirrhosis, Crohn disease, zinc deficiency, chemotherapy, Behçet disease, and pellagra.^3,24,25 They should be distinguished from Terry nails, which are characterized by leukonychia involving more than 80% of the total nail length.²⁶

Terry nails were originally reported in association with hepatic cirrhosis, usually secondary to alcoholism²⁷ but have since been found with heart failure, type 2 diabetes mellitus, pulmonary tuberculosis, reactive arthritis, older age, Hansen disease, and peripheral vascular disease.^3,26,28,29

LONGITUDINAL MELANONYCHIA: VERTICAL BROWN-BLACK NAIL LINES

Longitudinal melanonychia is the presence of black-brown vertical lines in the nail plate. They have a variety of causes, including blood from trauma; bacterial, fungal, or HIV infection; drug therapy (eg, from minocycline); endocrine disorders (Addison disease); exogenous pigmentation; or excess melanin production within the nail matrix.^30–32 They may also be a sign of a benign condition such as benign melanocytic activation, lentigines, or nevi, or a malignant condition such as melanoma (Figure 3).^33,34

When to suspect melanoma and refer

Although melanoma is less commonly associated with brown-black vertical nail lines, awareness of melanoma-associated longitudinal melanonychia reduces the likelihood of delayed diagnosis and improves patient outcomes.³⁵ Also, it is important to remember that although nail melanoma is more common in the 5th and 6th decades of life, it can occur at any age, even in children.³⁶

Findings that raise suspicion of nail melanoma (Table 1)^33,37 and that should prompt referral to a dermatologist who specializes in nails include the following:

• A personal or family history of melanoma
• Involvement of a “high-risk” digit (thumb, index finger, great toe),^30,31,38 although nail melanoma can occur in any digit
• Any new vertical brown-black nail pigmentation in a fair-skinned patient
• Only one nail affected: involvement of more than one nail is common in people with darker skin, and nearly all patients with darker skin exhibit longitudinal melanonychia by age 50³¹
• Changes in the band such as darkening, widening, and bleeding
• A bandwidth greater than 6 mm³³
• A band that is wider proximally than distally³⁴
• Nonuniform color of the line
• Indistinct lateral borders
• Associated with pigmentation of the nail fold (the Hutchinson sign, representing subungual melanoma),^31,39 nail plate dystrophy, bleeding, or ulceration.³³

While these features may help distinguish benign from malignant causes of longitudinal melanonychia, the clinical examination alone may not provide a definitive diagnosis. Delayed diagnosis of nail melanoma carries a high mortality rate; the internist can promote early diagnosis by recognizing the risk factors and clinical signs and referring the patient to a dermatologist for further evaluation with nail biopsy.

LONGITUDINAL ERYTHRONYCHIA: VERTICAL RED NAIL LINES

Longitudinal erythronychia—the presence of one or more linear red bands in the nail unit—can be localized (involving only one nail) or polydactylous (involving more than one nail). The localized form is usually due to a neoplastic process, whereas involvement of more than one nail may indicate an underlying regional or systemic disease.¹³Table 2 lists indications for referral to a nail specialist.

General features on examination

Clinical examination reveals one or more linear, pink-red streaks extending from the proximal nail fold to the distal free edge of the nail plate (Figure 4). The width of the band typically ranges from less than 1 mm to 3 mm.⁴⁰ Other features may include splinter hemorrhages within a red band, a semitransparent distal matrix, distal V-shaped chipping, splitting, onycholysis of the nail plate, and reactive distal nail bed and hyponychial hyperkeratosis. These features can be visible to the naked eye but may be better viewed with a magnifying glass, a 7× loupe, or a dermatoscope.¹³

Localized longitudinal erythronychia is usually seen in middle-aged individuals and is most commonly found on the thumbnail, followed by the index finger.^41,42 The condition may be asymptomatic, but the patient may present with pain or with concern that the split end of the nail catches on fabrics or small objects.⁴²

Glomus tumor

Intense, pulsatile pain with sensitivity to cold and tenderness to palpation is highly suggestive of glomus tumor,⁴³ a benign neoplasm that originates from a neuromyoarterial glomus body. Glomus bodies are located throughout the body but are more highly concentrated in the fingertips, especially beneath the nails, and they regulate skin circulation. Therefore, the nail unit is the most common site for glomus tumor.^44,45 A characteristic feature of subungual glomus tumor is demonstration of tenderness after pin-point palpation of the suspected tumor (positive Love sign).⁴⁵ While it is typical for glomus tumor to affect only one nail, multiple tumors are associated with neurofibromatosis type 1.⁴⁶ Confirmation of this diagnosis requires referral to a dermatologist.

Other causes of localized red nail lines

Onychopapilloma, a benign idiopathic tumor, is the most common cause of localized longitudinal erythronychia. Unlike glomus tumor, it is usually asymptomatic.^42,47 Less common benign conditions are warts, warty dyskeratoma, benign vascular proliferation, a solitary lesion of lichen planus, hemiplegia, and postsurgical scarring of the nail matrix. In some cases, the lines are idiopathic.^42,43

Malignant diseases that can present as localized longitudinal erythronychia include invasive squamous cell carcinoma, squamous cell carcinoma in situ (Bowen disease), and, less frequently, amelanotic melanoma in situ, malignant melanoma, and basal cell carcinoma.⁴² Squamous cell carcinoma in situ most commonly presents in the 5th decade of life and is the malignancy most commonly associated with localized longitudinal erythronychia. Clinically, there is also often nail dystrophy, such as distal subungual keratosis or onycholysis.⁴³

Patients with asymptomatic, stable localized longitudinal erythronychia may be followed closely with photography and measurements. However, any new lesion or a change in an existing lesion should prompt referral to a dermatologist for biopsy.¹³

Red streaks on more than one nail

Polydactylous longitudinal erythronychia usually presents in adults as red streaks on multiple nails and, depending on the presence or absence of symptoms (eg, pain, splitting), may be the patient’s chief complaint or an incidental finding noted by the astute clinician. Often, it is associated with systemic disease, most commonly lichen planus or Darier disease.

Lichen planus is a papulosquamous skin disease with nail involvement in 10% of patients and permanent nail dystrophy in 4%. Common nail findings include thinning, longitudinal ridging, and fissuring, as well as scarring of the nail matrix resulting in pterygium. Linear red streaks may accompany these more typical nail findings.¹³ Patients with Darier disease present with alternating red and white linear bands on multiple nails as in leukonychia striata.

Less frequently, polydactylous longitudinal erythronychia is associated with primary and systemic amyloidosis, hemiplegia, graft-vs-host disease, acantholytic epidermolysis bullosa, acantholytic dyskeratotic epidermal nevus, acrokeratosis verruciformis of Hopf, or pseudobulbar syndrome, or is idiopathic.^13,42,48 Therefore, the physician evaluating a patient with these nail findings should focus on a workup for regional or systemic disease or refer the patient to a dermatologist who specializes in nails.

BEAU LINES

Beau lines are a common finding in clinical practice. They are not true lines, but transverse grooves in the nail plate that arise from the temporary suppression of nail growth within the nail matrix that can occur during periods of acute or chronic stress or systemic illness (Figure 5).⁴⁹

The precipitating event may be local trauma or paronychia, chemotherapeutic agents cytotoxic to the nail matrix, or the abrupt onset of systemic disease.^18,50 The grooves have also been associated with rheumatic fever, malaria, pemphigus, Raynaud disease, and myocardial infarction, as well as following deep-sea dives.^51–53 The distance of a Beau line from the proximal nail fold can provide an estimate of the time of the acute stress, based on an average growth rate of 3 mm per month for fingernails and 1 mm per month for toenails.⁴⁹

Inspection of the fingernails and toenails should be part of a complete physical examination. A basic understanding of nail anatomy and recognition of several basic types of nail lines and bands allow the clinician to properly diagnose and treat the nail disease, to recognize possible underlying systemic diseases, and to know when to refer the patient to a dermatologist for specialized evaluation and biopsy.

In this review, we delineate the three basic types of nail lines­—white lines (leukonychia striata), brown-black lines (longitudinal melanonychia), and red lines (longitudinal erythronychia)—and the differential diagnosis for each type. We also discuss grooves in the nail plate, or Beau lines.

BASIC NAIL ANATOMY

A fundamental understanding of the anatomy of the nail unit is necessary to understand the origin of nail diseases and underlying pathologic conditions.

The nail unit includes the nail matrix, the lunula, the nail fold, the nail plate, and the nail bed. The nail matrix extends from under the proximal nail fold to the half-moon-shaped area (ie, the lunula) and is responsible for nail plate production. The nail bed lies under the nail plate and on top of the distal phalanx and extends from the lunula to just proximal to the free edge of the nail; its rich blood supply gives it its reddish color.

Nails grow slowly, and this should be kept in mind during the examination. Regrowth of a fingernail takes at least 6 months, and regrowth of a toenail may take 12 to 18 months. Therefore, a defect in the nail plate may reveal an injury that occurred—or a condition that began—several months before.¹

NAIL EXAMINATION ESSENTIALS

A complete examination includes all 20 nail units and the periungual skin. Patients should be instructed to remove nail polish from all nails, as it may camouflage dystrophy or disease of the nail. Photography and careful measurement help document changes over time.

LEUKONYCHIA STRIATA: WHITE NAIL LINES

White nail lines or leukonychia is classified as true or apparent, depending on whether the origin is in the nail matrix or the nail bed.

In true leukonychia, there is abnormal keratinization of the underlying nail matrix, resulting in parakeratosis within the nail plate and an opaque appearance on examination.² The white discoloration is unaffected by pressure, and the opacity moves distally as the nail grows out, which can be documented by serial photography on subsequent visits.

Apparent leukonychia involves abnormal nail bed vasculature, which changes the translucency of the nail plate. The whiteness disappears with pressure, is unaffected by nail growth, and will likely show no change on later visits with serial photography.³

True leukonychia

Leukonychia striata, a subtype of true leuko­nychia, is characterized by transverse or longitudinal bands. It is most often associated with microtrauma, such as from a manicure.⁴ Lines due to trauma are typically more apparent in the central part of the nail plate; they spare the lateral portion and lie parallel to the edge of the proximal nail fold.⁵

Onychomycosis. White longitudinal bands may also be seen in onychomycosis, a fungal infection of the nail accounting for up to 50% of all cases of nail disease. The infection may present as irregular dense longitudinal white or yellowish bands or “spikes” on the nail plate with associated hyperkeratosis, known as a dermatophytoma (Figure 1).

If a fungal infection is suspected, a potassium hydroxide stain can be performed on the subungual debris, which is then examined with direct microscopy.⁶ Alternatively, the physician can send a nail plate clipping in a 10% buffered formalin container with a request for a fungal stain such as periodic acid-Schiff.⁷ Microscopic examination of a dermatophytoma shows a dense mass of dermatophyte hyphae, otherwise known as a fungal abscess.⁸

The physician can play an important role in diagnosis because clinical findings suggestive of a dermatophytoma are associated with a poor response to antifungal therapy.⁹

Inherited diseases. White longitudinal bands are also an important clue to the rare autosomal dominant genodermatoses Hailey-Hailey disease (from mutations of the ATP2A2 gene) and Darier disease (from mutations of the ATP2C1 gene). Patients with Hailey-Hailey disease may have nails with multiple parallel longitudinal white stripes of variable width originating in the lunula and most prominent on the thumbs.^10–12 These patients also have recurrent vesicular eruptions in flexural skin areas, such as the groin, axilla, neck, and periumbilical area causing significant morbidity.

Patients with Darier disease may have nails with alternating red and white longitudinal streaks, described as “candy-cane,”¹³ as well as wedge-shaped distal subungual keratosis accompanied by flat keratotic papules on the proximal nail fold.¹⁴ These nail changes are reported in 92% to 95% of patients with Darier disease.^15,16 Patients typically have skin findings characterized by keratotic papules and plaques predominantly in seborrheic areas and palmoplantar pits, as well as secondary infections and malodor causing significant morbidity.¹⁵ Therefore, knowing the characteristic nail findings in these diseases may lead to more rapid diagnosis and treatment.

Mees lines. Leukonychia striata can present as transverse white lines, commonly known as Mees lines. They are 1- to 2-mm wide horizontal parallel white bands that span the width of the nail plate, usually affecting all fingernails.¹⁷ They are not a common finding and are most often associated with arsenic poisoning. They can also be used to identify the time of poisoning, since they tend to appear 2 months after the initial insult.

Mees lines are also associated with acute systemic stresses, such as acute renal failure, heart failure, ulcerative colitis, breast cancer, infections such as measles and tuberculosis, and systemic lupus erythematosus, and with exposure to toxic metals such as thallium.³

Apparent leukonychia

Apparent leukonychia can alert the physician to systemic diseases, infections, drug side effects, and nutrient deficiencies. Specific nail findings include Muehrcke lines, “half-and-half” nails, and Terry nails.

Muehrcke lines are paired white transverse bands that span the width of the nail bed and run parallel to the distal lunula. They were first described in the fingernails of patients with severe hypoalbuminemia, some of whom also had nephrotic syndrome, which resolved with normalization of the serum albumin level. Muehrcke lines have since been reported in patients with liver disease, malnutrition, chemotherapy, organ transplant, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome.^3,18 They are associated with periods of metabolic stress, ie, when the body’s capacity to synthesize proteins is diminished.¹⁹

Half-and-half nails, or Lindsay nails, are characterized by a white band proximally, a pink or red-brown band distally, and a sharp demarcation between the two (Figure 2). They were originally described in association with chronic renal disease,²⁰ and surprisingly, they resolve with kidney transplant but not with hemodialysis treatment or improvement in hemoglobin or albumin levels.^21–23 Half-and-half nails have been reported with Kawasaki disease, hepatic cirrhosis, Crohn disease, zinc deficiency, chemotherapy, Behçet disease, and pellagra.^3,24,25 They should be distinguished from Terry nails, which are characterized by leukonychia involving more than 80% of the total nail length.²⁶

Terry nails were originally reported in association with hepatic cirrhosis, usually secondary to alcoholism²⁷ but have since been found with heart failure, type 2 diabetes mellitus, pulmonary tuberculosis, reactive arthritis, older age, Hansen disease, and peripheral vascular disease.^3,26,28,29

LONGITUDINAL MELANONYCHIA: VERTICAL BROWN-BLACK NAIL LINES

Longitudinal melanonychia is the presence of black-brown vertical lines in the nail plate. They have a variety of causes, including blood from trauma; bacterial, fungal, or HIV infection; drug therapy (eg, from minocycline); endocrine disorders (Addison disease); exogenous pigmentation; or excess melanin production within the nail matrix.^30–32 They may also be a sign of a benign condition such as benign melanocytic activation, lentigines, or nevi, or a malignant condition such as melanoma (Figure 3).^33,34

When to suspect melanoma and refer

Although melanoma is less commonly associated with brown-black vertical nail lines, awareness of melanoma-associated longitudinal melanonychia reduces the likelihood of delayed diagnosis and improves patient outcomes.³⁵ Also, it is important to remember that although nail melanoma is more common in the 5th and 6th decades of life, it can occur at any age, even in children.³⁶

Findings that raise suspicion of nail melanoma (Table 1)^33,37 and that should prompt referral to a dermatologist who specializes in nails include the following:

• A personal or family history of melanoma
• Involvement of a “high-risk” digit (thumb, index finger, great toe),^30,31,38 although nail melanoma can occur in any digit
• Any new vertical brown-black nail pigmentation in a fair-skinned patient
• Only one nail affected: involvement of more than one nail is common in people with darker skin, and nearly all patients with darker skin exhibit longitudinal melanonychia by age 50³¹
• Changes in the band such as darkening, widening, and bleeding
• A bandwidth greater than 6 mm³³
• A band that is wider proximally than distally³⁴
• Nonuniform color of the line
• Indistinct lateral borders
• Associated with pigmentation of the nail fold (the Hutchinson sign, representing subungual melanoma),^31,39 nail plate dystrophy, bleeding, or ulceration.³³

While these features may help distinguish benign from malignant causes of longitudinal melanonychia, the clinical examination alone may not provide a definitive diagnosis. Delayed diagnosis of nail melanoma carries a high mortality rate; the internist can promote early diagnosis by recognizing the risk factors and clinical signs and referring the patient to a dermatologist for further evaluation with nail biopsy.

LONGITUDINAL ERYTHRONYCHIA: VERTICAL RED NAIL LINES

Longitudinal erythronychia—the presence of one or more linear red bands in the nail unit—can be localized (involving only one nail) or polydactylous (involving more than one nail). The localized form is usually due to a neoplastic process, whereas involvement of more than one nail may indicate an underlying regional or systemic disease.¹³Table 2 lists indications for referral to a nail specialist.

General features on examination

Clinical examination reveals one or more linear, pink-red streaks extending from the proximal nail fold to the distal free edge of the nail plate (Figure 4). The width of the band typically ranges from less than 1 mm to 3 mm.⁴⁰ Other features may include splinter hemorrhages within a red band, a semitransparent distal matrix, distal V-shaped chipping, splitting, onycholysis of the nail plate, and reactive distal nail bed and hyponychial hyperkeratosis. These features can be visible to the naked eye but may be better viewed with a magnifying glass, a 7× loupe, or a dermatoscope.¹³

Localized longitudinal erythronychia is usually seen in middle-aged individuals and is most commonly found on the thumbnail, followed by the index finger.^41,42 The condition may be asymptomatic, but the patient may present with pain or with concern that the split end of the nail catches on fabrics or small objects.⁴²

Glomus tumor

Intense, pulsatile pain with sensitivity to cold and tenderness to palpation is highly suggestive of glomus tumor,⁴³ a benign neoplasm that originates from a neuromyoarterial glomus body. Glomus bodies are located throughout the body but are more highly concentrated in the fingertips, especially beneath the nails, and they regulate skin circulation. Therefore, the nail unit is the most common site for glomus tumor.^44,45 A characteristic feature of subungual glomus tumor is demonstration of tenderness after pin-point palpation of the suspected tumor (positive Love sign).⁴⁵ While it is typical for glomus tumor to affect only one nail, multiple tumors are associated with neurofibromatosis type 1.⁴⁶ Confirmation of this diagnosis requires referral to a dermatologist.

Other causes of localized red nail lines

Onychopapilloma, a benign idiopathic tumor, is the most common cause of localized longitudinal erythronychia. Unlike glomus tumor, it is usually asymptomatic.^42,47 Less common benign conditions are warts, warty dyskeratoma, benign vascular proliferation, a solitary lesion of lichen planus, hemiplegia, and postsurgical scarring of the nail matrix. In some cases, the lines are idiopathic.^42,43

Malignant diseases that can present as localized longitudinal erythronychia include invasive squamous cell carcinoma, squamous cell carcinoma in situ (Bowen disease), and, less frequently, amelanotic melanoma in situ, malignant melanoma, and basal cell carcinoma.⁴² Squamous cell carcinoma in situ most commonly presents in the 5th decade of life and is the malignancy most commonly associated with localized longitudinal erythronychia. Clinically, there is also often nail dystrophy, such as distal subungual keratosis or onycholysis.⁴³

Patients with asymptomatic, stable localized longitudinal erythronychia may be followed closely with photography and measurements. However, any new lesion or a change in an existing lesion should prompt referral to a dermatologist for biopsy.¹³

Red streaks on more than one nail

Polydactylous longitudinal erythronychia usually presents in adults as red streaks on multiple nails and, depending on the presence or absence of symptoms (eg, pain, splitting), may be the patient’s chief complaint or an incidental finding noted by the astute clinician. Often, it is associated with systemic disease, most commonly lichen planus or Darier disease.

Lichen planus is a papulosquamous skin disease with nail involvement in 10% of patients and permanent nail dystrophy in 4%. Common nail findings include thinning, longitudinal ridging, and fissuring, as well as scarring of the nail matrix resulting in pterygium. Linear red streaks may accompany these more typical nail findings.¹³ Patients with Darier disease present with alternating red and white linear bands on multiple nails as in leukonychia striata.

Less frequently, polydactylous longitudinal erythronychia is associated with primary and systemic amyloidosis, hemiplegia, graft-vs-host disease, acantholytic epidermolysis bullosa, acantholytic dyskeratotic epidermal nevus, acrokeratosis verruciformis of Hopf, or pseudobulbar syndrome, or is idiopathic.^13,42,48 Therefore, the physician evaluating a patient with these nail findings should focus on a workup for regional or systemic disease or refer the patient to a dermatologist who specializes in nails.

BEAU LINES

Beau lines are a common finding in clinical practice. They are not true lines, but transverse grooves in the nail plate that arise from the temporary suppression of nail growth within the nail matrix that can occur during periods of acute or chronic stress or systemic illness (Figure 5).⁴⁹

The precipitating event may be local trauma or paronychia, chemotherapeutic agents cytotoxic to the nail matrix, or the abrupt onset of systemic disease.^18,50 The grooves have also been associated with rheumatic fever, malaria, pemphigus, Raynaud disease, and myocardial infarction, as well as following deep-sea dives.^51–53 The distance of a Beau line from the proximal nail fold can provide an estimate of the time of the acute stress, based on an average growth rate of 3 mm per month for fingernails and 1 mm per month for toenails.⁴⁹