In patients hospitalized with cirrhosis, biliary cirrhosis, recent health care exposure, nonwhite race, and cultures taken more than 48 hours after admission all independently predicted that bacteremia would be caused by multidrug-resistant organisms (MDROs), according to a medical record review at CHI St. Luke’s Medical Center, an 850-bed tertiary care center in Houston.

“These variables along with severity of infection and liver disease may help clinicians identify patients who will benefit most from broader-spectrum empiric antimicrobial therapy,” wrote the investigators, led by Jennifer Addo Smith, PharmD, of St. Luke’s, in the Journal of Clinical Gastroenterology.

But local epidemiology remains important. “Although a gram-positive agent (e.g., vancomycin) and a carbapenem-sparing gram-negative agent (e.g., ceftriaxone, cefepime) are reasonable empiric agents at our center, other centers with different resistance patterns may warrant different empiric therapy. Given the low prevalence of VRE [vancomycin-resistant Enterococcus] in this study ... and E. faecium in other studies (4%-7%), an empiric agent active against VRE does not seem to be routinely required,” they said.

The team looked into the issue because there hasn’t been much investigation in the United States of the role of multidrug resistant organisms in bacteremia among patients hospitalized with cirrhosis.

Thirty patients in the study had bacteremia caused by MDROs while 60 had bacteremia from non-MDROs, giving a 33% prevalence of MDRO bacteremia, which was consistent with previous, mostly European studies.

Enterobacteriaceae (43%), Staphylococcus aureus (18%), Streptococcus spp. (11%), Enterococcus spp. (10%), and nonfermenting gram-negative bacilli (6%) were the main causes of bacteremia overall.

Among the 30 MDRO cases, methicillin-resistant S. aureus was isolated in seven (23%); methicillin-resistant coagulase-negative Staphylococci in four (13%); fluoroquinolone-resistant Enterobacteriaceae in nine (30%); extended spectrum beta-lactamase–producing Enterobacteriaceae in three (10%), and VRE in two (7%). No carbapenemase-producing gram-negative bacteria were identified.

The predictors of MDRO bacteremia emerged on multivariate analysis and included biliary cirrhosis (adjusted odds ratio, 11.75; 95% confidence interval, 2.08-66.32); recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88); blood cultures obtained 48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40) and nonwhite race (aOR , 3.35; 95% CI, 1.19-9.38).

Blood cultures past 48 hours and recent health care exposure – generally hospitalization within the past 90 days – were likely surrogates for nosocomial infection.

The link with biliary cirrhosis is unclear. “Compared with other cirrhotic patients, perhaps patients with PBC [primary biliary cholangitis] have had more cumulative antimicrobial exposure because of [their] higher risk for UTIs [urinary tract infections] and therefore are at increased risk for MDROs,” they wrote.

The median age in the study was 59 years. Half of the patients were white; 46% were women. Hepatitis C was the most common cause of cirrhosis, followed by alcohol.

MDRO was defined in the study as bacteria not susceptible to at least one antibiotic in at least three antimicrobial categories; 90 cirrhosis patients without bacteremia served as controls.

The funding source was not reported. Dr. Addo Smith had no disclosures.

[email protected]

SOURCE: Smith JA et al. J Clin Gastroenterol. 2017 Nov 23. doi: 10.1097/MCG.0000000000000964.

*This story was updated on 1/10/2018.

In patients hospitalized with cirrhosis, biliary cirrhosis, recent health care exposure, nonwhite race, and cultures taken more than 48 hours after admission all independently predicted that bacteremia would be caused by multidrug-resistant organisms (MDROs), according to a medical record review at CHI St. Luke’s Medical Center, an 850-bed tertiary care center in Houston.

“These variables along with severity of infection and liver disease may help clinicians identify patients who will benefit most from broader-spectrum empiric antimicrobial therapy,” wrote the investigators, led by Jennifer Addo Smith, PharmD, of St. Luke’s, in the Journal of Clinical Gastroenterology.

But local epidemiology remains important. “Although a gram-positive agent (e.g., vancomycin) and a carbapenem-sparing gram-negative agent (e.g., ceftriaxone, cefepime) are reasonable empiric agents at our center, other centers with different resistance patterns may warrant different empiric therapy. Given the low prevalence of VRE [vancomycin-resistant Enterococcus] in this study ... and E. faecium in other studies (4%-7%), an empiric agent active against VRE does not seem to be routinely required,” they said.

The team looked into the issue because there hasn’t been much investigation in the United States of the role of multidrug resistant organisms in bacteremia among patients hospitalized with cirrhosis.

Thirty patients in the study had bacteremia caused by MDROs while 60 had bacteremia from non-MDROs, giving a 33% prevalence of MDRO bacteremia, which was consistent with previous, mostly European studies.

Enterobacteriaceae (43%), Staphylococcus aureus (18%), Streptococcus spp. (11%), Enterococcus spp. (10%), and nonfermenting gram-negative bacilli (6%) were the main causes of bacteremia overall.

Among the 30 MDRO cases, methicillin-resistant S. aureus was isolated in seven (23%); methicillin-resistant coagulase-negative Staphylococci in four (13%); fluoroquinolone-resistant Enterobacteriaceae in nine (30%); extended spectrum beta-lactamase–producing Enterobacteriaceae in three (10%), and VRE in two (7%). No carbapenemase-producing gram-negative bacteria were identified.

The predictors of MDRO bacteremia emerged on multivariate analysis and included biliary cirrhosis (adjusted odds ratio, 11.75; 95% confidence interval, 2.08-66.32); recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88); blood cultures obtained 48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40) and nonwhite race (aOR , 3.35; 95% CI, 1.19-9.38).

Blood cultures past 48 hours and recent health care exposure – generally hospitalization within the past 90 days – were likely surrogates for nosocomial infection.

The link with biliary cirrhosis is unclear. “Compared with other cirrhotic patients, perhaps patients with PBC [primary biliary cholangitis] have had more cumulative antimicrobial exposure because of [their] higher risk for UTIs [urinary tract infections] and therefore are at increased risk for MDROs,” they wrote.

The median age in the study was 59 years. Half of the patients were white; 46% were women. Hepatitis C was the most common cause of cirrhosis, followed by alcohol.

MDRO was defined in the study as bacteria not susceptible to at least one antibiotic in at least three antimicrobial categories; 90 cirrhosis patients without bacteremia served as controls.

The funding source was not reported. Dr. Addo Smith had no disclosures.

[email protected]

SOURCE: Smith JA et al. J Clin Gastroenterol. 2017 Nov 23. doi: 10.1097/MCG.0000000000000964.

*This story was updated on 1/10/2018.

In patients hospitalized with cirrhosis, biliary cirrhosis, recent health care exposure, nonwhite race, and cultures taken more than 48 hours after admission all independently predicted that bacteremia would be caused by multidrug-resistant organisms (MDROs), according to a medical record review at CHI St. Luke’s Medical Center, an 850-bed tertiary care center in Houston.

“These variables along with severity of infection and liver disease may help clinicians identify patients who will benefit most from broader-spectrum empiric antimicrobial therapy,” wrote the investigators, led by Jennifer Addo Smith, PharmD, of St. Luke’s, in the Journal of Clinical Gastroenterology.

But local epidemiology remains important. “Although a gram-positive agent (e.g., vancomycin) and a carbapenem-sparing gram-negative agent (e.g., ceftriaxone, cefepime) are reasonable empiric agents at our center, other centers with different resistance patterns may warrant different empiric therapy. Given the low prevalence of VRE [vancomycin-resistant Enterococcus] in this study ... and E. faecium in other studies (4%-7%), an empiric agent active against VRE does not seem to be routinely required,” they said.

The team looked into the issue because there hasn’t been much investigation in the United States of the role of multidrug resistant organisms in bacteremia among patients hospitalized with cirrhosis.

Thirty patients in the study had bacteremia caused by MDROs while 60 had bacteremia from non-MDROs, giving a 33% prevalence of MDRO bacteremia, which was consistent with previous, mostly European studies.

Enterobacteriaceae (43%), Staphylococcus aureus (18%), Streptococcus spp. (11%), Enterococcus spp. (10%), and nonfermenting gram-negative bacilli (6%) were the main causes of bacteremia overall.

Among the 30 MDRO cases, methicillin-resistant S. aureus was isolated in seven (23%); methicillin-resistant coagulase-negative Staphylococci in four (13%); fluoroquinolone-resistant Enterobacteriaceae in nine (30%); extended spectrum beta-lactamase–producing Enterobacteriaceae in three (10%), and VRE in two (7%). No carbapenemase-producing gram-negative bacteria were identified.

The predictors of MDRO bacteremia emerged on multivariate analysis and included biliary cirrhosis (adjusted odds ratio, 11.75; 95% confidence interval, 2.08-66.32); recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88); blood cultures obtained 48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40) and nonwhite race (aOR , 3.35; 95% CI, 1.19-9.38).

Blood cultures past 48 hours and recent health care exposure – generally hospitalization within the past 90 days – were likely surrogates for nosocomial infection.

The link with biliary cirrhosis is unclear. “Compared with other cirrhotic patients, perhaps patients with PBC [primary biliary cholangitis] have had more cumulative antimicrobial exposure because of [their] higher risk for UTIs [urinary tract infections] and therefore are at increased risk for MDROs,” they wrote.

The median age in the study was 59 years. Half of the patients were white; 46% were women. Hepatitis C was the most common cause of cirrhosis, followed by alcohol.

MDRO was defined in the study as bacteria not susceptible to at least one antibiotic in at least three antimicrobial categories; 90 cirrhosis patients without bacteremia served as controls.

The funding source was not reported. Dr. Addo Smith had no disclosures.

[email protected]

SOURCE: Smith JA et al. J Clin Gastroenterol. 2017 Nov 23. doi: 10.1097/MCG.0000000000000964.

*This story was updated on 1/10/2018.

To the Editor:

Richner-Hanhart syndrome, also known as tyrosinemia type II or oculocutaneous tyrosinemia, is a rare autosomal-recessive, childhood-onset, metabolic hereditary disease.¹ A deficiency of tyrosine aminotransferase leads to an accumulation of tyrosine amino acid. It is characterized by the association of palmoplantar hyperkeratosis, bilateral keratitis, and neurological disorders.

An 18-month-old girl with recurrent warts of 6 months' duration was admitted to the dermatology department. She had been treated repeatedly with acyclovir for recurrent bilateral herpetic keratitis with major photophobia since 9 months of age with no response. Clinical presentation included punctate hyperkeratosis of the fingers and toes (Figure, A), severe photophobia with decreased visual acuity, and speech delay.

Her medical record showed a break of the growth curve with a weight of 9.25 kg (3rd percentile), a height of 80 cm (50th percentile), and a head circumference of 45 cm (50th percentile). Her parents were nonconsanguineous. The association of bilateral dendritic keratitis with punctate palmoplantar keratosis suggested a diagnosis of Richner-Hanhart syndrome. Diagnosis was confirmed by an elevated plasma level of tyrosine (1580 µmol/L; reference range, 40-80 µmol/L).

A low tyrosine and low phenylalanine diet (no animal proteins) was immediately introduced, with supplementation of amino acids, vitamins, and trace elements. After 8 days, the plasma level of tyrosinemia decreased by a factor of 4 (392 µmol/L). After 1 month, the cutaneous and ocular lesions completely resolved (Figure, B). Discrete psychomotor slowing still persisted for 1 year and then reached complete normalization. Genetic analysis showed a composite heterozygous mutation of the tyrosine aminotransferase gene, TAT, on chromosome 16. The mutation detected in the patient's mother was an A to V substitution at codon 147 (A147V). The second mutation was detected in the father; it was an 8 nucleotides duplication and then a substitution leading to a premature stop codon at codon 37 (R37X).

Richner-Hanhart syndrome is a rare autosomal-recessive disorder that is more common in Italy and in areas where inbreeding is prevalent^1,2; however, no data are available on disease prevalence. It is caused by a homozygous mutation in the TAT gene located on chromosome 16q22.³ Tyrosine aminotransferase is an important enzyme involved in the tyrosine and phenylalanine metabolic degradation pathway located in the hepatic cytosol. Symptoms are due to the accumulation of tyrosine and its metabolite. Diagnosis is confirmed by an elevated plasma level of tyrosine (>500 µmol/L). This oculocutaneous syndrome is characterized by bilateral pseudodendritic keratitis, palmoplantar hyperkeratosis, and a variable degree of mental retardation.1 In contrast to tyrosinemia type II, types I and III do not affect the skin.

Intrafamilial and interfamilial phenotypic variability is reported. A large spectrum of mutations within the TAT gene have been reported.^4-7 These mutations lead to a reduction or an absence in the activity of hepatic tyrosine aminotransferase. The degradation pathway of tyrosine involving TAT occurs mainly in the liver. This process also is present in the mitochondria where the enzyme is called aspartate aminotransferase.^1,2 The mechanism by which Richner-Hanhart syndrome causes painful palmoplantar keratosis and keratitis remains unknown. It has been suggested that intracellular L-tyrosine crystals initiate an inflammation process resulting in the typical skin lesions and keratitis.⁸ There is some evidence that patients with higher values of tyrosine in early life are more likely to develop neurological problems.¹ In addition, phenotype variability has been observed, even among individuals sharing the same pathogenic mutation.⁴

Tyrosinemia type II typically demonstrates ocular symptoms (75% of cases) that usually occur in the first year of life.⁸ They are characterized by photophobia, redness, and increase of lacrimation. Examination reveals a superficial and bilateral punctate keratosis with corneal dystrophy, often misdiagnosed as herpetic keratosis, as in our case, which may delay the diagnosis.^9,10 Bilateral ocular lesions are suggestive, even if they are asymmetric.^8,11 Furthermore, negative fluorescein staining, negative culture, and resistance to antiviral treatment exclude the diagnosis of herpetic keratosis.^9,10

Skin lesions (85% of cases) typically appear in the first year of life. They are characterized by painful, irregular, limited, punctate hyperkeratosis on the palms and soles.¹ They are more frequent in weight-bearing areas and tend to improve during summer, possibly due to a seasonal change in dietary behavior.^4,12 Hyperkeratotic papules in a linear pattern also have been described on the flexor aspects of the fingers or toes.¹³ In our case, the lesions were misdiagnosed as warts for 6 months.

Retarded development affects 60% of patients with tyrosinemia type II. Expression of neurological symptoms is variable and could include mental retardation, nystagmus, tremors, ataxia, and convulsion.⁴ Lifetime follow-up of these patients is recommended.

Early initiation of a tyrosine-phenylalanine-restricted diet in infancy is the most effective therapy for Richner-Hanhart syndrome.¹³ The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into amino acid tyrosine. Thus, dietary treatment of Richner-Hanhart syndrome requires restricting or eliminating foods high in phenylalanine and tyrosine with protein "medical food" substitute. The dietary treatment allows resolution of both eye and skin symptoms after a few days or weeks and also may prevent mental retardation. It is effective in lowering the plasma level to less than 400 µmol/L. The diet must be introduced as soon as Richner-Hanhart syndrome is suspected. Supplementation with essential amino acids, vitamins, and trace elements is needed. Early screening of siblings in families with Richner-Hanhart syndrome history is recommended, even in the absence of clinical findings. Careful dietary control of maternal plasma tyrosine level must be considered during future pregnancy for women.^4,14,15

Richner-Hanhart syndrome should be suspected in patients demonstrating cutaneous lesions, especially palmoplantar keratosis associated with bilateral pseudodendritic corneal lesions unresponsive to antiviral therapy.

To the Editor:

Richner-Hanhart syndrome, also known as tyrosinemia type II or oculocutaneous tyrosinemia, is a rare autosomal-recessive, childhood-onset, metabolic hereditary disease.¹ A deficiency of tyrosine aminotransferase leads to an accumulation of tyrosine amino acid. It is characterized by the association of palmoplantar hyperkeratosis, bilateral keratitis, and neurological disorders.

An 18-month-old girl with recurrent warts of 6 months' duration was admitted to the dermatology department. She had been treated repeatedly with acyclovir for recurrent bilateral herpetic keratitis with major photophobia since 9 months of age with no response. Clinical presentation included punctate hyperkeratosis of the fingers and toes (Figure, A), severe photophobia with decreased visual acuity, and speech delay.

Her medical record showed a break of the growth curve with a weight of 9.25 kg (3rd percentile), a height of 80 cm (50th percentile), and a head circumference of 45 cm (50th percentile). Her parents were nonconsanguineous. The association of bilateral dendritic keratitis with punctate palmoplantar keratosis suggested a diagnosis of Richner-Hanhart syndrome. Diagnosis was confirmed by an elevated plasma level of tyrosine (1580 µmol/L; reference range, 40-80 µmol/L).

A low tyrosine and low phenylalanine diet (no animal proteins) was immediately introduced, with supplementation of amino acids, vitamins, and trace elements. After 8 days, the plasma level of tyrosinemia decreased by a factor of 4 (392 µmol/L). After 1 month, the cutaneous and ocular lesions completely resolved (Figure, B). Discrete psychomotor slowing still persisted for 1 year and then reached complete normalization. Genetic analysis showed a composite heterozygous mutation of the tyrosine aminotransferase gene, TAT, on chromosome 16. The mutation detected in the patient's mother was an A to V substitution at codon 147 (A147V). The second mutation was detected in the father; it was an 8 nucleotides duplication and then a substitution leading to a premature stop codon at codon 37 (R37X).

Richner-Hanhart syndrome is a rare autosomal-recessive disorder that is more common in Italy and in areas where inbreeding is prevalent^1,2; however, no data are available on disease prevalence. It is caused by a homozygous mutation in the TAT gene located on chromosome 16q22.³ Tyrosine aminotransferase is an important enzyme involved in the tyrosine and phenylalanine metabolic degradation pathway located in the hepatic cytosol. Symptoms are due to the accumulation of tyrosine and its metabolite. Diagnosis is confirmed by an elevated plasma level of tyrosine (>500 µmol/L). This oculocutaneous syndrome is characterized by bilateral pseudodendritic keratitis, palmoplantar hyperkeratosis, and a variable degree of mental retardation.1 In contrast to tyrosinemia type II, types I and III do not affect the skin.

Intrafamilial and interfamilial phenotypic variability is reported. A large spectrum of mutations within the TAT gene have been reported.^4-7 These mutations lead to a reduction or an absence in the activity of hepatic tyrosine aminotransferase. The degradation pathway of tyrosine involving TAT occurs mainly in the liver. This process also is present in the mitochondria where the enzyme is called aspartate aminotransferase.^1,2 The mechanism by which Richner-Hanhart syndrome causes painful palmoplantar keratosis and keratitis remains unknown. It has been suggested that intracellular L-tyrosine crystals initiate an inflammation process resulting in the typical skin lesions and keratitis.⁸ There is some evidence that patients with higher values of tyrosine in early life are more likely to develop neurological problems.¹ In addition, phenotype variability has been observed, even among individuals sharing the same pathogenic mutation.⁴

Tyrosinemia type II typically demonstrates ocular symptoms (75% of cases) that usually occur in the first year of life.⁸ They are characterized by photophobia, redness, and increase of lacrimation. Examination reveals a superficial and bilateral punctate keratosis with corneal dystrophy, often misdiagnosed as herpetic keratosis, as in our case, which may delay the diagnosis.^9,10 Bilateral ocular lesions are suggestive, even if they are asymmetric.^8,11 Furthermore, negative fluorescein staining, negative culture, and resistance to antiviral treatment exclude the diagnosis of herpetic keratosis.^9,10

Skin lesions (85% of cases) typically appear in the first year of life. They are characterized by painful, irregular, limited, punctate hyperkeratosis on the palms and soles.¹ They are more frequent in weight-bearing areas and tend to improve during summer, possibly due to a seasonal change in dietary behavior.^4,12 Hyperkeratotic papules in a linear pattern also have been described on the flexor aspects of the fingers or toes.¹³ In our case, the lesions were misdiagnosed as warts for 6 months.

Retarded development affects 60% of patients with tyrosinemia type II. Expression of neurological symptoms is variable and could include mental retardation, nystagmus, tremors, ataxia, and convulsion.⁴ Lifetime follow-up of these patients is recommended.

Early initiation of a tyrosine-phenylalanine-restricted diet in infancy is the most effective therapy for Richner-Hanhart syndrome.¹³ The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into amino acid tyrosine. Thus, dietary treatment of Richner-Hanhart syndrome requires restricting or eliminating foods high in phenylalanine and tyrosine with protein "medical food" substitute. The dietary treatment allows resolution of both eye and skin symptoms after a few days or weeks and also may prevent mental retardation. It is effective in lowering the plasma level to less than 400 µmol/L. The diet must be introduced as soon as Richner-Hanhart syndrome is suspected. Supplementation with essential amino acids, vitamins, and trace elements is needed. Early screening of siblings in families with Richner-Hanhart syndrome history is recommended, even in the absence of clinical findings. Careful dietary control of maternal plasma tyrosine level must be considered during future pregnancy for women.^4,14,15

Richner-Hanhart syndrome should be suspected in patients demonstrating cutaneous lesions, especially palmoplantar keratosis associated with bilateral pseudodendritic corneal lesions unresponsive to antiviral therapy.

To the Editor:

Richner-Hanhart syndrome, also known as tyrosinemia type II or oculocutaneous tyrosinemia, is a rare autosomal-recessive, childhood-onset, metabolic hereditary disease.¹ A deficiency of tyrosine aminotransferase leads to an accumulation of tyrosine amino acid. It is characterized by the association of palmoplantar hyperkeratosis, bilateral keratitis, and neurological disorders.

An 18-month-old girl with recurrent warts of 6 months' duration was admitted to the dermatology department. She had been treated repeatedly with acyclovir for recurrent bilateral herpetic keratitis with major photophobia since 9 months of age with no response. Clinical presentation included punctate hyperkeratosis of the fingers and toes (Figure, A), severe photophobia with decreased visual acuity, and speech delay.

Her medical record showed a break of the growth curve with a weight of 9.25 kg (3rd percentile), a height of 80 cm (50th percentile), and a head circumference of 45 cm (50th percentile). Her parents were nonconsanguineous. The association of bilateral dendritic keratitis with punctate palmoplantar keratosis suggested a diagnosis of Richner-Hanhart syndrome. Diagnosis was confirmed by an elevated plasma level of tyrosine (1580 µmol/L; reference range, 40-80 µmol/L).

A low tyrosine and low phenylalanine diet (no animal proteins) was immediately introduced, with supplementation of amino acids, vitamins, and trace elements. After 8 days, the plasma level of tyrosinemia decreased by a factor of 4 (392 µmol/L). After 1 month, the cutaneous and ocular lesions completely resolved (Figure, B). Discrete psychomotor slowing still persisted for 1 year and then reached complete normalization. Genetic analysis showed a composite heterozygous mutation of the tyrosine aminotransferase gene, TAT, on chromosome 16. The mutation detected in the patient's mother was an A to V substitution at codon 147 (A147V). The second mutation was detected in the father; it was an 8 nucleotides duplication and then a substitution leading to a premature stop codon at codon 37 (R37X).

Richner-Hanhart syndrome is a rare autosomal-recessive disorder that is more common in Italy and in areas where inbreeding is prevalent^1,2; however, no data are available on disease prevalence. It is caused by a homozygous mutation in the TAT gene located on chromosome 16q22.³ Tyrosine aminotransferase is an important enzyme involved in the tyrosine and phenylalanine metabolic degradation pathway located in the hepatic cytosol. Symptoms are due to the accumulation of tyrosine and its metabolite. Diagnosis is confirmed by an elevated plasma level of tyrosine (>500 µmol/L). This oculocutaneous syndrome is characterized by bilateral pseudodendritic keratitis, palmoplantar hyperkeratosis, and a variable degree of mental retardation.1 In contrast to tyrosinemia type II, types I and III do not affect the skin.

Intrafamilial and interfamilial phenotypic variability is reported. A large spectrum of mutations within the TAT gene have been reported.^4-7 These mutations lead to a reduction or an absence in the activity of hepatic tyrosine aminotransferase. The degradation pathway of tyrosine involving TAT occurs mainly in the liver. This process also is present in the mitochondria where the enzyme is called aspartate aminotransferase.^1,2 The mechanism by which Richner-Hanhart syndrome causes painful palmoplantar keratosis and keratitis remains unknown. It has been suggested that intracellular L-tyrosine crystals initiate an inflammation process resulting in the typical skin lesions and keratitis.⁸ There is some evidence that patients with higher values of tyrosine in early life are more likely to develop neurological problems.¹ In addition, phenotype variability has been observed, even among individuals sharing the same pathogenic mutation.⁴

Tyrosinemia type II typically demonstrates ocular symptoms (75% of cases) that usually occur in the first year of life.⁸ They are characterized by photophobia, redness, and increase of lacrimation. Examination reveals a superficial and bilateral punctate keratosis with corneal dystrophy, often misdiagnosed as herpetic keratosis, as in our case, which may delay the diagnosis.^9,10 Bilateral ocular lesions are suggestive, even if they are asymmetric.^8,11 Furthermore, negative fluorescein staining, negative culture, and resistance to antiviral treatment exclude the diagnosis of herpetic keratosis.^9,10

Skin lesions (85% of cases) typically appear in the first year of life. They are characterized by painful, irregular, limited, punctate hyperkeratosis on the palms and soles.¹ They are more frequent in weight-bearing areas and tend to improve during summer, possibly due to a seasonal change in dietary behavior.^4,12 Hyperkeratotic papules in a linear pattern also have been described on the flexor aspects of the fingers or toes.¹³ In our case, the lesions were misdiagnosed as warts for 6 months.

Retarded development affects 60% of patients with tyrosinemia type II. Expression of neurological symptoms is variable and could include mental retardation, nystagmus, tremors, ataxia, and convulsion.⁴ Lifetime follow-up of these patients is recommended.

Early initiation of a tyrosine-phenylalanine-restricted diet in infancy is the most effective therapy for Richner-Hanhart syndrome.¹³ The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into amino acid tyrosine. Thus, dietary treatment of Richner-Hanhart syndrome requires restricting or eliminating foods high in phenylalanine and tyrosine with protein "medical food" substitute. The dietary treatment allows resolution of both eye and skin symptoms after a few days or weeks and also may prevent mental retardation. It is effective in lowering the plasma level to less than 400 µmol/L. The diet must be introduced as soon as Richner-Hanhart syndrome is suspected. Supplementation with essential amino acids, vitamins, and trace elements is needed. Early screening of siblings in families with Richner-Hanhart syndrome history is recommended, even in the absence of clinical findings. Careful dietary control of maternal plasma tyrosine level must be considered during future pregnancy for women.^4,14,15

Richner-Hanhart syndrome should be suspected in patients demonstrating cutaneous lesions, especially palmoplantar keratosis associated with bilateral pseudodendritic corneal lesions unresponsive to antiviral therapy.

In late October 2017, pediatricians from over 25 countries gathered at the annual meeting of the International Society of Social Pediatrics and Child Health in Budapest to develop strategies to address the health and well-being of children on the move. With the staggering global increase in the displacement of children – due to conflict, climate change, natural disasters, and economic deprivation – there is a critical need for action.

An international slate of experts, including pediatricians who are responding to the needs of these children, provided an evidence base for intervention and action. These discussions informed the development of a consensus statement, the Budapest Declaration, that establishes a framework for a global response to the exigencies confronting these children and families.

Courtesy Francis E. Rushton Jr, MD

Dr. Rushton is medical director of the South Carolina Quality Through Innovation in Pediatrics (SCQTIP) network. Dr. Goldhagen is president-elect, International Society for Social Pediatrics and Child Health, and professor of pediatrics, University of Florida, Jacksonville. Email them at [email protected].

In late October 2017, pediatricians from over 25 countries gathered at the annual meeting of the International Society of Social Pediatrics and Child Health in Budapest to develop strategies to address the health and well-being of children on the move. With the staggering global increase in the displacement of children – due to conflict, climate change, natural disasters, and economic deprivation – there is a critical need for action.

An international slate of experts, including pediatricians who are responding to the needs of these children, provided an evidence base for intervention and action. These discussions informed the development of a consensus statement, the Budapest Declaration, that establishes a framework for a global response to the exigencies confronting these children and families.

Courtesy Francis E. Rushton Jr, MD

Dr. Rushton is medical director of the South Carolina Quality Through Innovation in Pediatrics (SCQTIP) network. Dr. Goldhagen is president-elect, International Society for Social Pediatrics and Child Health, and professor of pediatrics, University of Florida, Jacksonville. Email them at [email protected].

In late October 2017, pediatricians from over 25 countries gathered at the annual meeting of the International Society of Social Pediatrics and Child Health in Budapest to develop strategies to address the health and well-being of children on the move. With the staggering global increase in the displacement of children – due to conflict, climate change, natural disasters, and economic deprivation – there is a critical need for action.

An international slate of experts, including pediatricians who are responding to the needs of these children, provided an evidence base for intervention and action. These discussions informed the development of a consensus statement, the Budapest Declaration, that establishes a framework for a global response to the exigencies confronting these children and families.

Courtesy Francis E. Rushton Jr, MD

Dr. Rushton is medical director of the South Carolina Quality Through Innovation in Pediatrics (SCQTIP) network. Dr. Goldhagen is president-elect, International Society for Social Pediatrics and Child Health, and professor of pediatrics, University of Florida, Jacksonville. Email them at [email protected].

To improve patient care and outcomes, leading dermatologists offered their recommendations on pigment correctors. Consideration must be given to:

• dEp Patch Full Face Mask
  Activaderm, Inc
  “This product uses microcurrent to push vitamin C into the skin. Vitamin C, a known antioxidant that usually has a difficult time passing through the stratum corneum, corrects pigmentary abnormalities. The product also comes with a botanical pigment corrector.”—Gary Goldenberg, MD, New York, New York
   
• De-Spot Skin Brightening Corrector
  Peter Thomas Roth Labs LLC
  “This product is a useful over-the-counter adjunct to prescription-strength hydroquinone, with niacinamide as one of the active ingredients.”—Shari Lipner, MD, PhD, New York, New York
   
• Glytone Dark Spot Corrector
  Pierre Fabre Laboratories
  “With 2% hydroquinone, glycolic acid, and kojic acid, you have a highly effective combination of ingredients that work synergistically to lighten areas of skin discoloration.”—Jeannette Graf, MD, Great Neck, New York

Cutis invites readers to send us their recommendations. Bar soap, lip plumper, and night cream will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on pigment correctors. Consideration must be given to:

• dEp Patch Full Face Mask
  Activaderm, Inc
  “This product uses microcurrent to push vitamin C into the skin. Vitamin C, a known antioxidant that usually has a difficult time passing through the stratum corneum, corrects pigmentary abnormalities. The product also comes with a botanical pigment corrector.”—Gary Goldenberg, MD, New York, New York
   
• De-Spot Skin Brightening Corrector
  Peter Thomas Roth Labs LLC
  “This product is a useful over-the-counter adjunct to prescription-strength hydroquinone, with niacinamide as one of the active ingredients.”—Shari Lipner, MD, PhD, New York, New York
   
• Glytone Dark Spot Corrector
  Pierre Fabre Laboratories
  “With 2% hydroquinone, glycolic acid, and kojic acid, you have a highly effective combination of ingredients that work synergistically to lighten areas of skin discoloration.”—Jeannette Graf, MD, Great Neck, New York

Cutis invites readers to send us their recommendations. Bar soap, lip plumper, and night cream will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on pigment correctors. Consideration must be given to:

• dEp Patch Full Face Mask
  Activaderm, Inc
  “This product uses microcurrent to push vitamin C into the skin. Vitamin C, a known antioxidant that usually has a difficult time passing through the stratum corneum, corrects pigmentary abnormalities. The product also comes with a botanical pigment corrector.”—Gary Goldenberg, MD, New York, New York
   
• De-Spot Skin Brightening Corrector
  Peter Thomas Roth Labs LLC
  “This product is a useful over-the-counter adjunct to prescription-strength hydroquinone, with niacinamide as one of the active ingredients.”—Shari Lipner, MD, PhD, New York, New York
   
• Glytone Dark Spot Corrector
  Pierre Fabre Laboratories
  “With 2% hydroquinone, glycolic acid, and kojic acid, you have a highly effective combination of ingredients that work synergistically to lighten areas of skin discoloration.”—Jeannette Graf, MD, Great Neck, New York

Cutis invites readers to send us their recommendations. Bar soap, lip plumper, and night cream will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

Infants experiencing spasms will likely respond to standard first-line treatment, whether or not they also have hypsarrhythmia, according to a multicenter study of the National Infantile Spasms Consortium.

• The investigation included infants between 2 months and 2 years who had been enrolled in the Consortium cohort with new onset spasms.
• 82% of the infants had hypsarrthythmia but the condition was not linked to the child’s average age, gender, any preexisting developmental delay or epilepsy, or their response to first line treatment.

First-line treatment, which consisted of vigabatrin, prednisolone, and adrenocorticotropic hormone (ACTH), was by far the most important variable that predicted the infants’ response to therapy, whether or not they had hypsarrhythmia.

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium. Epilepsia. 2017;58:2098-2103.

Infants experiencing spasms will likely respond to standard first-line treatment, whether or not they also have hypsarrhythmia, according to a multicenter study of the National Infantile Spasms Consortium.

• The investigation included infants between 2 months and 2 years who had been enrolled in the Consortium cohort with new onset spasms.
• 82% of the infants had hypsarrthythmia but the condition was not linked to the child’s average age, gender, any preexisting developmental delay or epilepsy, or their response to first line treatment.

First-line treatment, which consisted of vigabatrin, prednisolone, and adrenocorticotropic hormone (ACTH), was by far the most important variable that predicted the infants’ response to therapy, whether or not they had hypsarrhythmia.

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium. Epilepsia. 2017;58:2098-2103.

Infants experiencing spasms will likely respond to standard first-line treatment, whether or not they also have hypsarrhythmia, according to a multicenter study of the National Infantile Spasms Consortium.

• The investigation included infants between 2 months and 2 years who had been enrolled in the Consortium cohort with new onset spasms.
• 82% of the infants had hypsarrthythmia but the condition was not linked to the child’s average age, gender, any preexisting developmental delay or epilepsy, or their response to first line treatment.

First-line treatment, which consisted of vigabatrin, prednisolone, and adrenocorticotropic hormone (ACTH), was by far the most important variable that predicted the infants’ response to therapy, whether or not they had hypsarrhythmia.

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium. Epilepsia. 2017;58:2098-2103.

Black patients are almost twice as likely to be diagnosed with temporal lobe epilepsy than white patients, despite the fact that black patients make up only 20% of the patient population in the Southeastern United States, according to a recent study.

• The University of Alabama at Birmingham reviewed all the video EEG diagnoses in its seizure monitoring unit from 2000 to 2011.
• Researchers performed a statistical analysis that included multivariate logistic regression to detect factors associated with the temporal lobe epilepsy (TLE) diagnosis.
• The diagnoses in the entire patient population included 630 cases of TLE, 1150 cases of psychogenic nonepileptic seizures, 424 additional focal epilepsies, and 224 generalized epilepsies.
• The population included 77.3% white patients, 20% black patients, and 2.3% patients of other races.
• TLE was diagnosed far more often in black patients than white patients (odds ratio: 1.87).

There were more women in the study population, and black women were responsible for most of the statistical difference in TLE diagnoses.

Racial disparities in temporal lobe epilepsy. Epilepsy Res. 2017;16;140:56-60.

Black patients are almost twice as likely to be diagnosed with temporal lobe epilepsy than white patients, despite the fact that black patients make up only 20% of the patient population in the Southeastern United States, according to a recent study.

• The University of Alabama at Birmingham reviewed all the video EEG diagnoses in its seizure monitoring unit from 2000 to 2011.
• Researchers performed a statistical analysis that included multivariate logistic regression to detect factors associated with the temporal lobe epilepsy (TLE) diagnosis.
• The diagnoses in the entire patient population included 630 cases of TLE, 1150 cases of psychogenic nonepileptic seizures, 424 additional focal epilepsies, and 224 generalized epilepsies.
• The population included 77.3% white patients, 20% black patients, and 2.3% patients of other races.
• TLE was diagnosed far more often in black patients than white patients (odds ratio: 1.87).

There were more women in the study population, and black women were responsible for most of the statistical difference in TLE diagnoses.

Racial disparities in temporal lobe epilepsy. Epilepsy Res. 2017;16;140:56-60.

Black patients are almost twice as likely to be diagnosed with temporal lobe epilepsy than white patients, despite the fact that black patients make up only 20% of the patient population in the Southeastern United States, according to a recent study.

• The University of Alabama at Birmingham reviewed all the video EEG diagnoses in its seizure monitoring unit from 2000 to 2011.
• Researchers performed a statistical analysis that included multivariate logistic regression to detect factors associated with the temporal lobe epilepsy (TLE) diagnosis.
• The diagnoses in the entire patient population included 630 cases of TLE, 1150 cases of psychogenic nonepileptic seizures, 424 additional focal epilepsies, and 224 generalized epilepsies.
• The population included 77.3% white patients, 20% black patients, and 2.3% patients of other races.
• TLE was diagnosed far more often in black patients than white patients (odds ratio: 1.87).

There were more women in the study population, and black women were responsible for most of the statistical difference in TLE diagnoses.

Racial disparities in temporal lobe epilepsy. Epilepsy Res. 2017;16;140:56-60.

A treatment that would reduce the risk of developing amyloid plaques in the brain by 50% could save more than four million Americans from mild cognitive impairment (MCI) and 2.5 million Americans from Alzheimer’s disease by 2060, according to a study published online ahead of print November 29 in Alzheimer’s & Dementia.

The conclusion that modestly effective preventive therapy could greatly improve the Alzheimer’s disease outlook is especially important, given another finding in a new mathematical modeling study by Ron Brookmeyer, PhD, a biostatistician at the University of California, Los Angeles, and colleagues. They assert that 47 million cognitively normal people in the United States may have brain amyloidosis, the physical finding used to define preclinical Alzheimer’s disease.

Model Predicted Increase in Preclinical Alzheimer’s Disease

“This is the first major attempt to forecast these proposed preclinical Alzheimer’s disease and [MCI] due to Alzheimer’s disease numbers. If confirmed, these data [will] provide essential information for public health planning and for informing and guiding the public and private investment in Alzheimer’s and dementia research,” said Dr. Brookmeyer. “We need more research to confirm the findings from this model, and more Alzheimer’s disease and dementia research that includes diverse populations.”

“I want to emphasize that of the 47 million [people] with these Alzheimer’s brain changes, but without clinical symptoms, most will not progress to clinical disease during their lifetimes. In fact, perhaps only one in seven will progress to full-blown dementia.” Nevertheless, the numbers represent a reality that must be confronted and managed proactively, said Dr. Brookmeyer.

The results may sound alarming, he said, “but I have every confidence in them. And they are important because they allow us to understand how many people could potentially benefit from treatment, at what point on the disease continuum it would be useful to implement treatment, and how those treatments could impact public health.”

Studies Provided Rates of Transition Between Disease States

To create predictive models, Dr. Brookmeyer used data from two prospective longitudinal cohort studies: the Mayo Clinic Study of Aging and a study conducted by Stephanie J. Vos, PhD, a postdoctoral researcher at Maastricht University in the Netherlands.

The Mayo Clinic study followed 1,541 cognitively normal older adults and provided data on the rate of transition from normal cognition to MCI. The study by Dr. Vos and her associates followed 353 patients with MCI and brain amyloid and 222 patients with late MCI as they progressed. It is the largest prospective study of progression from MCI to Alzheimer’s disease that also contains data on baseline neurodegeneration and amyloid burden.

“These studies gave us the rates of transition from one state to another,” said Dr. Brookmeyer. “For example, the Mayo Clinic study gave us rates of transition from normal [health] to amyloidosis: 3% of normal 60-year-olds will convert to this state every year.”

Dr. Vos’s study determined rates of progression from MCI to Alzheimer’s dementia, given two preclinical states: asymptomatic amyloid brain plaques alone, or plaques with evidence of neurodegeneration and cognitive signs, said Dr. Brookmeyer. Both of these transitional states were first defined in 2011 in a joint paper by the Alzheimer’s Association and the National Institute on Aging. While acknowledging that the root causes of Alzheimer’s disease are unknown, the paper hypothesized a pathophysiologic time line beginning with a three-stage preclinical phase.

Asymptomatic cerebral amyloidosis is the first stage. It entails amyloid-positive PET brain imaging with an amyloid-binding ligand, a CSF assay with a low level of amyloid-beta 42 in the presence of normal cognition, or both. Stage 2 is one of amyloid positivity and evidence of synaptic dysfunction or early neurodegeneration in the presence of normal cognition. Finally, stage 3 entails amyloid positivity with evidence of neurodegeneration in the presence of subtle cognitive decline.

“Using those definitions, and piecing together the numbers from these studies, we constructed a computer model based on US census population projections to [estimate] how many people might be in these different states of disease,” said Dr. Brookmeyer.

In 2017, six million Americans were in one of the clinical disease states (ie, MCI due to Alzheimer’s disease, early clinical Alzheimer’s disease, or late clinical Alzheimer’s disease). Dr. Brookmeyer and his colleagues predicted that that number would grow to 15 million by 2060. Similarly, in 2017, about 47 million Americans were in one of the preclinical Alzheimer’s disease states, including 22 million with amyloidosis, 8.3 million with neurodegeneration alone, and 16.2 million with both. He projects that this number will increase to 75.7 million by 2060.

Prevention Strategies

The team remodeled those numbers in three hypothetical intervention scenarios. Researchers say that a treatment that slows decline by at least 30% would have a meaningful clinical, financial, and societal impact. However, Dr. Brookmeyer modeled treatment scenarios with a greater effect.

A primary prevention method that reduced the annual risk of new amyloidosis by 50% could decrease the prevalence of MCI by about 700,000 in 2060. A secondary prevention strategy that reduced the annual risk progression to MCI by 50% would decrease the prevalence of MCI by more than two million and the prevalence of Alzheimer’s disease by about 3.8 million.

The results were more complicated with a secondary prevention strategy that would reduce annual risk of conversion from MCI to Alzheimer’s disease by 50%. In this scenario, the prevalence of MCI in 2060 would increase by 2.8 million, but the prevalence of Alzheimer’s disease would decrease by 2.5 million. These scenarios developed over different time courses, said the researchers.

“We find that the highly effective primary prevention strategy resulted in the lowest Alzheimer’s disease prevalence by the year 2060. However, [it] was associated with the largest Alzheimer’s disease prevalence in the 15 years immediately after its introduction ... The explanation for this finding is that the full benefits of delaying amyloidosis, in terms of reduced Alzheimer’s disease prevalence, are not realized for many years because of the long lag time between amyloidosis and clinical Alzheimer’s disease. A take-home message is that the full impact on disease burden of primary prevention that targets the early stages of the pathogenesis of Alzheimer’s disease may not be realized for decades.”

Decreasing preclinical conversion to MCI with a secondary prevention strategy would result in the highest Alzheimer’s disease prevalence reduction for most of the period. But the reduction resulting from the primary prevention strategy would surpass it by 2054.

The intervention targeting conversion from MCI to Alzheimer’s disease would reduce Alzheimer’s disease prevalence the quickest, with a slight decrease in the first three years after introduction. “The explanation for this finding is that MCI is proximate to clinical Alzheimer’s disease diagnosis, and thus the impact of delaying progression of MCI will be seen relatively quickly on Alzheimer’s disease prevalence, compared to interventions that delay onset of amyloidosis or MCI.

“By focusing attention on a concerning reality—that tens of millions of American adults may face the possibility of dementia due to Alzheimer’s disease—the results reported in this new article, if confirmed, illustrate and greatly amplify the need for more research to develop effective treatments and proven prevention strategies for Alzheimer’s disease,” said Dr. Brookmeyer. “This is especially true as we get better at early detection and are able to more accurately identify people who have the early brain changes associated with Alzheimer’s disease and other dementias.”

Dr. Brookmeyer reported receiving fees from Takeda for serving as a member of a data safety monitoring board.

—Michele G. Sullivan

Suggested Reading

Brookmeyer R, Abdalla N, Kawas CH, Corrada MM. Forecasting the prevalence of preclinical and clinical Alzheimer’s disease in the United States. Alzheimers Dement. 2017 Nov 29 [Epub ahead of print].

Derby CA, Katz MJ, Lipton RB, Hall CB. Trends in dementia incidence in a birth cohort analysis of the Einstein Aging Study. JAMA Neurol. 2017;74(11):1345-1351.

Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280-292.

Vos SJ, Verhey F, Frölich L, et al. Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage. Brain. 2015;138(Pt 5):1327-1338.

A treatment that would reduce the risk of developing amyloid plaques in the brain by 50% could save more than four million Americans from mild cognitive impairment (MCI) and 2.5 million Americans from Alzheimer’s disease by 2060, according to a study published online ahead of print November 29 in Alzheimer’s & Dementia.

The conclusion that modestly effective preventive therapy could greatly improve the Alzheimer’s disease outlook is especially important, given another finding in a new mathematical modeling study by Ron Brookmeyer, PhD, a biostatistician at the University of California, Los Angeles, and colleagues. They assert that 47 million cognitively normal people in the United States may have brain amyloidosis, the physical finding used to define preclinical Alzheimer’s disease.

Model Predicted Increase in Preclinical Alzheimer’s Disease

“This is the first major attempt to forecast these proposed preclinical Alzheimer’s disease and [MCI] due to Alzheimer’s disease numbers. If confirmed, these data [will] provide essential information for public health planning and for informing and guiding the public and private investment in Alzheimer’s and dementia research,” said Dr. Brookmeyer. “We need more research to confirm the findings from this model, and more Alzheimer’s disease and dementia research that includes diverse populations.”

“I want to emphasize that of the 47 million [people] with these Alzheimer’s brain changes, but without clinical symptoms, most will not progress to clinical disease during their lifetimes. In fact, perhaps only one in seven will progress to full-blown dementia.” Nevertheless, the numbers represent a reality that must be confronted and managed proactively, said Dr. Brookmeyer.

The results may sound alarming, he said, “but I have every confidence in them. And they are important because they allow us to understand how many people could potentially benefit from treatment, at what point on the disease continuum it would be useful to implement treatment, and how those treatments could impact public health.”

Studies Provided Rates of Transition Between Disease States

To create predictive models, Dr. Brookmeyer used data from two prospective longitudinal cohort studies: the Mayo Clinic Study of Aging and a study conducted by Stephanie J. Vos, PhD, a postdoctoral researcher at Maastricht University in the Netherlands.

The Mayo Clinic study followed 1,541 cognitively normal older adults and provided data on the rate of transition from normal cognition to MCI. The study by Dr. Vos and her associates followed 353 patients with MCI and brain amyloid and 222 patients with late MCI as they progressed. It is the largest prospective study of progression from MCI to Alzheimer’s disease that also contains data on baseline neurodegeneration and amyloid burden.

“These studies gave us the rates of transition from one state to another,” said Dr. Brookmeyer. “For example, the Mayo Clinic study gave us rates of transition from normal [health] to amyloidosis: 3% of normal 60-year-olds will convert to this state every year.”

Dr. Vos’s study determined rates of progression from MCI to Alzheimer’s dementia, given two preclinical states: asymptomatic amyloid brain plaques alone, or plaques with evidence of neurodegeneration and cognitive signs, said Dr. Brookmeyer. Both of these transitional states were first defined in 2011 in a joint paper by the Alzheimer’s Association and the National Institute on Aging. While acknowledging that the root causes of Alzheimer’s disease are unknown, the paper hypothesized a pathophysiologic time line beginning with a three-stage preclinical phase.

Asymptomatic cerebral amyloidosis is the first stage. It entails amyloid-positive PET brain imaging with an amyloid-binding ligand, a CSF assay with a low level of amyloid-beta 42 in the presence of normal cognition, or both. Stage 2 is one of amyloid positivity and evidence of synaptic dysfunction or early neurodegeneration in the presence of normal cognition. Finally, stage 3 entails amyloid positivity with evidence of neurodegeneration in the presence of subtle cognitive decline.

“Using those definitions, and piecing together the numbers from these studies, we constructed a computer model based on US census population projections to [estimate] how many people might be in these different states of disease,” said Dr. Brookmeyer.

In 2017, six million Americans were in one of the clinical disease states (ie, MCI due to Alzheimer’s disease, early clinical Alzheimer’s disease, or late clinical Alzheimer’s disease). Dr. Brookmeyer and his colleagues predicted that that number would grow to 15 million by 2060. Similarly, in 2017, about 47 million Americans were in one of the preclinical Alzheimer’s disease states, including 22 million with amyloidosis, 8.3 million with neurodegeneration alone, and 16.2 million with both. He projects that this number will increase to 75.7 million by 2060.

Prevention Strategies

The team remodeled those numbers in three hypothetical intervention scenarios. Researchers say that a treatment that slows decline by at least 30% would have a meaningful clinical, financial, and societal impact. However, Dr. Brookmeyer modeled treatment scenarios with a greater effect.

A primary prevention method that reduced the annual risk of new amyloidosis by 50% could decrease the prevalence of MCI by about 700,000 in 2060. A secondary prevention strategy that reduced the annual risk progression to MCI by 50% would decrease the prevalence of MCI by more than two million and the prevalence of Alzheimer’s disease by about 3.8 million.

The results were more complicated with a secondary prevention strategy that would reduce annual risk of conversion from MCI to Alzheimer’s disease by 50%. In this scenario, the prevalence of MCI in 2060 would increase by 2.8 million, but the prevalence of Alzheimer’s disease would decrease by 2.5 million. These scenarios developed over different time courses, said the researchers.

“We find that the highly effective primary prevention strategy resulted in the lowest Alzheimer’s disease prevalence by the year 2060. However, [it] was associated with the largest Alzheimer’s disease prevalence in the 15 years immediately after its introduction ... The explanation for this finding is that the full benefits of delaying amyloidosis, in terms of reduced Alzheimer’s disease prevalence, are not realized for many years because of the long lag time between amyloidosis and clinical Alzheimer’s disease. A take-home message is that the full impact on disease burden of primary prevention that targets the early stages of the pathogenesis of Alzheimer’s disease may not be realized for decades.”

Decreasing preclinical conversion to MCI with a secondary prevention strategy would result in the highest Alzheimer’s disease prevalence reduction for most of the period. But the reduction resulting from the primary prevention strategy would surpass it by 2054.

The intervention targeting conversion from MCI to Alzheimer’s disease would reduce Alzheimer’s disease prevalence the quickest, with a slight decrease in the first three years after introduction. “The explanation for this finding is that MCI is proximate to clinical Alzheimer’s disease diagnosis, and thus the impact of delaying progression of MCI will be seen relatively quickly on Alzheimer’s disease prevalence, compared to interventions that delay onset of amyloidosis or MCI.

“By focusing attention on a concerning reality—that tens of millions of American adults may face the possibility of dementia due to Alzheimer’s disease—the results reported in this new article, if confirmed, illustrate and greatly amplify the need for more research to develop effective treatments and proven prevention strategies for Alzheimer’s disease,” said Dr. Brookmeyer. “This is especially true as we get better at early detection and are able to more accurately identify people who have the early brain changes associated with Alzheimer’s disease and other dementias.”

Dr. Brookmeyer reported receiving fees from Takeda for serving as a member of a data safety monitoring board.

—Michele G. Sullivan

Suggested Reading

Brookmeyer R, Abdalla N, Kawas CH, Corrada MM. Forecasting the prevalence of preclinical and clinical Alzheimer’s disease in the United States. Alzheimers Dement. 2017 Nov 29 [Epub ahead of print].

Derby CA, Katz MJ, Lipton RB, Hall CB. Trends in dementia incidence in a birth cohort analysis of the Einstein Aging Study. JAMA Neurol. 2017;74(11):1345-1351.

Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280-292.

Vos SJ, Verhey F, Frölich L, et al. Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage. Brain. 2015;138(Pt 5):1327-1338.

A treatment that would reduce the risk of developing amyloid plaques in the brain by 50% could save more than four million Americans from mild cognitive impairment (MCI) and 2.5 million Americans from Alzheimer’s disease by 2060, according to a study published online ahead of print November 29 in Alzheimer’s & Dementia.

The conclusion that modestly effective preventive therapy could greatly improve the Alzheimer’s disease outlook is especially important, given another finding in a new mathematical modeling study by Ron Brookmeyer, PhD, a biostatistician at the University of California, Los Angeles, and colleagues. They assert that 47 million cognitively normal people in the United States may have brain amyloidosis, the physical finding used to define preclinical Alzheimer’s disease.

Model Predicted Increase in Preclinical Alzheimer’s Disease

“This is the first major attempt to forecast these proposed preclinical Alzheimer’s disease and [MCI] due to Alzheimer’s disease numbers. If confirmed, these data [will] provide essential information for public health planning and for informing and guiding the public and private investment in Alzheimer’s and dementia research,” said Dr. Brookmeyer. “We need more research to confirm the findings from this model, and more Alzheimer’s disease and dementia research that includes diverse populations.”

“I want to emphasize that of the 47 million [people] with these Alzheimer’s brain changes, but without clinical symptoms, most will not progress to clinical disease during their lifetimes. In fact, perhaps only one in seven will progress to full-blown dementia.” Nevertheless, the numbers represent a reality that must be confronted and managed proactively, said Dr. Brookmeyer.

The results may sound alarming, he said, “but I have every confidence in them. And they are important because they allow us to understand how many people could potentially benefit from treatment, at what point on the disease continuum it would be useful to implement treatment, and how those treatments could impact public health.”

Studies Provided Rates of Transition Between Disease States

To create predictive models, Dr. Brookmeyer used data from two prospective longitudinal cohort studies: the Mayo Clinic Study of Aging and a study conducted by Stephanie J. Vos, PhD, a postdoctoral researcher at Maastricht University in the Netherlands.

The Mayo Clinic study followed 1,541 cognitively normal older adults and provided data on the rate of transition from normal cognition to MCI. The study by Dr. Vos and her associates followed 353 patients with MCI and brain amyloid and 222 patients with late MCI as they progressed. It is the largest prospective study of progression from MCI to Alzheimer’s disease that also contains data on baseline neurodegeneration and amyloid burden.

“These studies gave us the rates of transition from one state to another,” said Dr. Brookmeyer. “For example, the Mayo Clinic study gave us rates of transition from normal [health] to amyloidosis: 3% of normal 60-year-olds will convert to this state every year.”

Dr. Vos’s study determined rates of progression from MCI to Alzheimer’s dementia, given two preclinical states: asymptomatic amyloid brain plaques alone, or plaques with evidence of neurodegeneration and cognitive signs, said Dr. Brookmeyer. Both of these transitional states were first defined in 2011 in a joint paper by the Alzheimer’s Association and the National Institute on Aging. While acknowledging that the root causes of Alzheimer’s disease are unknown, the paper hypothesized a pathophysiologic time line beginning with a three-stage preclinical phase.

Asymptomatic cerebral amyloidosis is the first stage. It entails amyloid-positive PET brain imaging with an amyloid-binding ligand, a CSF assay with a low level of amyloid-beta 42 in the presence of normal cognition, or both. Stage 2 is one of amyloid positivity and evidence of synaptic dysfunction or early neurodegeneration in the presence of normal cognition. Finally, stage 3 entails amyloid positivity with evidence of neurodegeneration in the presence of subtle cognitive decline.

“Using those definitions, and piecing together the numbers from these studies, we constructed a computer model based on US census population projections to [estimate] how many people might be in these different states of disease,” said Dr. Brookmeyer.

In 2017, six million Americans were in one of the clinical disease states (ie, MCI due to Alzheimer’s disease, early clinical Alzheimer’s disease, or late clinical Alzheimer’s disease). Dr. Brookmeyer and his colleagues predicted that that number would grow to 15 million by 2060. Similarly, in 2017, about 47 million Americans were in one of the preclinical Alzheimer’s disease states, including 22 million with amyloidosis, 8.3 million with neurodegeneration alone, and 16.2 million with both. He projects that this number will increase to 75.7 million by 2060.

Prevention Strategies

The team remodeled those numbers in three hypothetical intervention scenarios. Researchers say that a treatment that slows decline by at least 30% would have a meaningful clinical, financial, and societal impact. However, Dr. Brookmeyer modeled treatment scenarios with a greater effect.

A primary prevention method that reduced the annual risk of new amyloidosis by 50% could decrease the prevalence of MCI by about 700,000 in 2060. A secondary prevention strategy that reduced the annual risk progression to MCI by 50% would decrease the prevalence of MCI by more than two million and the prevalence of Alzheimer’s disease by about 3.8 million.

The results were more complicated with a secondary prevention strategy that would reduce annual risk of conversion from MCI to Alzheimer’s disease by 50%. In this scenario, the prevalence of MCI in 2060 would increase by 2.8 million, but the prevalence of Alzheimer’s disease would decrease by 2.5 million. These scenarios developed over different time courses, said the researchers.

“We find that the highly effective primary prevention strategy resulted in the lowest Alzheimer’s disease prevalence by the year 2060. However, [it] was associated with the largest Alzheimer’s disease prevalence in the 15 years immediately after its introduction ... The explanation for this finding is that the full benefits of delaying amyloidosis, in terms of reduced Alzheimer’s disease prevalence, are not realized for many years because of the long lag time between amyloidosis and clinical Alzheimer’s disease. A take-home message is that the full impact on disease burden of primary prevention that targets the early stages of the pathogenesis of Alzheimer’s disease may not be realized for decades.”

Decreasing preclinical conversion to MCI with a secondary prevention strategy would result in the highest Alzheimer’s disease prevalence reduction for most of the period. But the reduction resulting from the primary prevention strategy would surpass it by 2054.

The intervention targeting conversion from MCI to Alzheimer’s disease would reduce Alzheimer’s disease prevalence the quickest, with a slight decrease in the first three years after introduction. “The explanation for this finding is that MCI is proximate to clinical Alzheimer’s disease diagnosis, and thus the impact of delaying progression of MCI will be seen relatively quickly on Alzheimer’s disease prevalence, compared to interventions that delay onset of amyloidosis or MCI.

“By focusing attention on a concerning reality—that tens of millions of American adults may face the possibility of dementia due to Alzheimer’s disease—the results reported in this new article, if confirmed, illustrate and greatly amplify the need for more research to develop effective treatments and proven prevention strategies for Alzheimer’s disease,” said Dr. Brookmeyer. “This is especially true as we get better at early detection and are able to more accurately identify people who have the early brain changes associated with Alzheimer’s disease and other dementias.”

Dr. Brookmeyer reported receiving fees from Takeda for serving as a member of a data safety monitoring board.

—Michele G. Sullivan

Suggested Reading

Brookmeyer R, Abdalla N, Kawas CH, Corrada MM. Forecasting the prevalence of preclinical and clinical Alzheimer’s disease in the United States. Alzheimers Dement. 2017 Nov 29 [Epub ahead of print].

Derby CA, Katz MJ, Lipton RB, Hall CB. Trends in dementia incidence in a birth cohort analysis of the Einstein Aging Study. JAMA Neurol. 2017;74(11):1345-1351.

Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280-292.

Vos SJ, Verhey F, Frölich L, et al. Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage. Brain. 2015;138(Pt 5):1327-1338.

Aortoenteric fistulas (AEFs) are an uncommon but lethal form of aortic graft infection with morbidity and mortality rates reported in the literature to range from 14% to 75%. Over a 20-year period, researchers found that nearly half of their patients undergoing repair of their aortoenteric fistulas died within 60 days. The presence of gastrointestinal complications increased the risk of mortality more than threefold, according to the results of a single-center retrospective review of consecutive AEF repairs.

The researchers assessed 50 patients who presented with AEF and had repair during 1995-2014. Sixty percent of the patients were men, and the overall median age was 70 years. The median follow-up for the entire cohort was 14 months. The duodenum was the most common location of the enteric defect, found in 80% of the infections. Overall, 23 patients (46%) died by day 60, according to the report published in the July Journal of the American College of Surgeons.

Univariate analysis showed that advanced age, chronic renal insufficiency, any complications, and GI complications in particular (occurring in 26% of patients) were all associated with an increase in overall mortality (P less than .05). But upon multivariate analysis, gastrointestinal complications (hazard ratio, 3.23; P = .015) and advanced age (HR, 1.07; P = .01) were the only independent predictors of mortality, Atish Chopra, MD, of the division of vascular surgery, Oregon Health & Science University, Portland, and his colleagues wrote.

The institution changed operative procedures in 2007, based upon an earlier assessment of the importance of GI complications performed by the researchers, with greater emphasis placed on ensuring a viable GI reconstruction, and early intervention for mesenteric ischemia. In addition, they surmised that, after 2007, there was improved adherence to achieving wide debridement of nonviable and infected tissue, and to creating a tension-free anastomosis to healthy tissue edges while optimizing nutritional, medical, and antibiotic therapy, according to the researchers.

The authors reported that they had nothing to disclose.

[email protected]

SOURCE: Chopra A et al. J Am Coll Surg 2017 Jul;225(1):9-18.

Aortoenteric fistulas (AEFs) are an uncommon but lethal form of aortic graft infection with morbidity and mortality rates reported in the literature to range from 14% to 75%. Over a 20-year period, researchers found that nearly half of their patients undergoing repair of their aortoenteric fistulas died within 60 days. The presence of gastrointestinal complications increased the risk of mortality more than threefold, according to the results of a single-center retrospective review of consecutive AEF repairs.

The researchers assessed 50 patients who presented with AEF and had repair during 1995-2014. Sixty percent of the patients were men, and the overall median age was 70 years. The median follow-up for the entire cohort was 14 months. The duodenum was the most common location of the enteric defect, found in 80% of the infections. Overall, 23 patients (46%) died by day 60, according to the report published in the July Journal of the American College of Surgeons.

Univariate analysis showed that advanced age, chronic renal insufficiency, any complications, and GI complications in particular (occurring in 26% of patients) were all associated with an increase in overall mortality (P less than .05). But upon multivariate analysis, gastrointestinal complications (hazard ratio, 3.23; P = .015) and advanced age (HR, 1.07; P = .01) were the only independent predictors of mortality, Atish Chopra, MD, of the division of vascular surgery, Oregon Health & Science University, Portland, and his colleagues wrote.

The institution changed operative procedures in 2007, based upon an earlier assessment of the importance of GI complications performed by the researchers, with greater emphasis placed on ensuring a viable GI reconstruction, and early intervention for mesenteric ischemia. In addition, they surmised that, after 2007, there was improved adherence to achieving wide debridement of nonviable and infected tissue, and to creating a tension-free anastomosis to healthy tissue edges while optimizing nutritional, medical, and antibiotic therapy, according to the researchers.

The authors reported that they had nothing to disclose.

[email protected]

SOURCE: Chopra A et al. J Am Coll Surg 2017 Jul;225(1):9-18.

Aortoenteric fistulas (AEFs) are an uncommon but lethal form of aortic graft infection with morbidity and mortality rates reported in the literature to range from 14% to 75%. Over a 20-year period, researchers found that nearly half of their patients undergoing repair of their aortoenteric fistulas died within 60 days. The presence of gastrointestinal complications increased the risk of mortality more than threefold, according to the results of a single-center retrospective review of consecutive AEF repairs.

The researchers assessed 50 patients who presented with AEF and had repair during 1995-2014. Sixty percent of the patients were men, and the overall median age was 70 years. The median follow-up for the entire cohort was 14 months. The duodenum was the most common location of the enteric defect, found in 80% of the infections. Overall, 23 patients (46%) died by day 60, according to the report published in the July Journal of the American College of Surgeons.

Univariate analysis showed that advanced age, chronic renal insufficiency, any complications, and GI complications in particular (occurring in 26% of patients) were all associated with an increase in overall mortality (P less than .05). But upon multivariate analysis, gastrointestinal complications (hazard ratio, 3.23; P = .015) and advanced age (HR, 1.07; P = .01) were the only independent predictors of mortality, Atish Chopra, MD, of the division of vascular surgery, Oregon Health & Science University, Portland, and his colleagues wrote.

The institution changed operative procedures in 2007, based upon an earlier assessment of the importance of GI complications performed by the researchers, with greater emphasis placed on ensuring a viable GI reconstruction, and early intervention for mesenteric ischemia. In addition, they surmised that, after 2007, there was improved adherence to achieving wide debridement of nonviable and infected tissue, and to creating a tension-free anastomosis to healthy tissue edges while optimizing nutritional, medical, and antibiotic therapy, according to the researchers.

The authors reported that they had nothing to disclose.

[email protected]

SOURCE: Chopra A et al. J Am Coll Surg 2017 Jul;225(1):9-18.

Three-dimensional printing has revolutionized the drug and device market and already has changed the lives of millions of patients. The FDA has reviewed more than 100 devices now on the market that were manufactured on 3-D printers, including knee replacements and implants “designed to fit like a missing puzzle piece into a patient’s skull for facial reconstruction,” says FDA Commissioner Scott Gottlieb, MD. The FDA also has approved the first drug produced on a 3-D printer. It has a more porous matrix than that of the drug manufactured in the traditional way, which allows it to dissolve more rapidly. But the technology advances have been moving so fast that they have threatened to outpace safeguards.

Now the FDA is preparing for a “significant wave” of new technologies, Gottlieb says, such as 3-D-printer skin cells for burn victims and is working to provide a regulatory pathway that keeps pace with those advances, helping to keep them safe and effective. To that end, the FDA has issued new guidance to help advise manufacturers on technical aspects of 3-D printing. And as more hospitals and academic centers use their 3-D printers for innovations to use in clinical studies, the FDA also is establishing a regulatory framework for applying existing laws to nontraditional manufacturers.

The Center for Drug Evaluation and Research state-of-the-art 3-D printing facility allows FDA scientists to conduct research to determine how 3-D printing of drugs, for instance, affects drug components. The Center for Devices and Radiological Health also has a 3-D printing facility to investigate the effect of design changes on safety and performance.

Gottlieb calls the technical guidance leapfrog guidance because it helps bridge current policy with innovation. It is only intended, he says, to provide “initial thoughts on an emerging technology with the understanding that our recommendations are likely to evolve as the technology develops in unexpected ways.”

Three-dimensional printing has revolutionized the drug and device market and already has changed the lives of millions of patients. The FDA has reviewed more than 100 devices now on the market that were manufactured on 3-D printers, including knee replacements and implants “designed to fit like a missing puzzle piece into a patient’s skull for facial reconstruction,” says FDA Commissioner Scott Gottlieb, MD. The FDA also has approved the first drug produced on a 3-D printer. It has a more porous matrix than that of the drug manufactured in the traditional way, which allows it to dissolve more rapidly. But the technology advances have been moving so fast that they have threatened to outpace safeguards.

Now the FDA is preparing for a “significant wave” of new technologies, Gottlieb says, such as 3-D-printer skin cells for burn victims and is working to provide a regulatory pathway that keeps pace with those advances, helping to keep them safe and effective. To that end, the FDA has issued new guidance to help advise manufacturers on technical aspects of 3-D printing. And as more hospitals and academic centers use their 3-D printers for innovations to use in clinical studies, the FDA also is establishing a regulatory framework for applying existing laws to nontraditional manufacturers.

The Center for Drug Evaluation and Research state-of-the-art 3-D printing facility allows FDA scientists to conduct research to determine how 3-D printing of drugs, for instance, affects drug components. The Center for Devices and Radiological Health also has a 3-D printing facility to investigate the effect of design changes on safety and performance.

Gottlieb calls the technical guidance leapfrog guidance because it helps bridge current policy with innovation. It is only intended, he says, to provide “initial thoughts on an emerging technology with the understanding that our recommendations are likely to evolve as the technology develops in unexpected ways.”

Three-dimensional printing has revolutionized the drug and device market and already has changed the lives of millions of patients. The FDA has reviewed more than 100 devices now on the market that were manufactured on 3-D printers, including knee replacements and implants “designed to fit like a missing puzzle piece into a patient’s skull for facial reconstruction,” says FDA Commissioner Scott Gottlieb, MD. The FDA also has approved the first drug produced on a 3-D printer. It has a more porous matrix than that of the drug manufactured in the traditional way, which allows it to dissolve more rapidly. But the technology advances have been moving so fast that they have threatened to outpace safeguards.

Now the FDA is preparing for a “significant wave” of new technologies, Gottlieb says, such as 3-D-printer skin cells for burn victims and is working to provide a regulatory pathway that keeps pace with those advances, helping to keep them safe and effective. To that end, the FDA has issued new guidance to help advise manufacturers on technical aspects of 3-D printing. And as more hospitals and academic centers use their 3-D printers for innovations to use in clinical studies, the FDA also is establishing a regulatory framework for applying existing laws to nontraditional manufacturers.

The Center for Drug Evaluation and Research state-of-the-art 3-D printing facility allows FDA scientists to conduct research to determine how 3-D printing of drugs, for instance, affects drug components. The Center for Devices and Radiological Health also has a 3-D printing facility to investigate the effect of design changes on safety and performance.

Gottlieb calls the technical guidance leapfrog guidance because it helps bridge current policy with innovation. It is only intended, he says, to provide “initial thoughts on an emerging technology with the understanding that our recommendations are likely to evolve as the technology develops in unexpected ways.”

For more than two years, this 40-year-old African-American woman has had a lesion on her left maxilla. While it does not cause pain or discomfort, its presence is alarming to the patient. The lesion has grown steadily without responding to various topical OTC medications (tolnaftate, clotrimazole, miconazole, 1% hydrocortisone cream), oral anti-yeast medication, and antibiotics (fluconazole, erythromycin).

The patient claims to be in excellent health otherwise. She reports a strong family history of autoimmune disease, including rheumatoid arthritis and lupus.

EXAMINATION
There is an oval, scaly, atrophic patch on the upper left maxilla, just below the left nostril. The lesion measures 1.2 cm, has well-defined margins, and appears darker than the patient’s type V skin.

No redness or edema are seen, and no nodes are palpable in the area. Examination of the adjacent oral mucosal surface shows nothing amiss.

Under sterile conditions, and after local anesthesia (1% lidocaine with epinephrine) is administered, a 3-mm punch biopsy is obtained from the center of the lesion. The defect is closed with two interrupted nylon sutures.

What is the diagnosis?

This manifestation of an autoimmune process is especially common in younger women of color. DLE primarily affects sun-exposed areas (eg, face, ears, neck) and involves scaly, round-to-oval patches and plaques with atrophic centers and follicular accentuation.

These lesions are frequently misdiagnosed as “fungal.” The differential also includes lichen planus and Jessner lymphocytic infiltrate.

Of the three types of cutaneous lupus erythematosus (discoid, acute, subacute), DLE is the most common. The acute form is defined by a “butterfly rash” across the face, while the subacute form involves multiple round-to-oval scaly lesions in wide photodistribution.

The chronic cutaneous lupus category includes DLE, tumid (characterized by deep, painful, indurated nodules), and panniculitis, which affects large areas of adipose tissue. DLE is, once again, the most common.

DLE can be an entity unto itself or part of a larger diagnosis of systemic lupus erythematosus (SLE). The good news: Only about 15% of patients with DLE progress to SLE. It is debatable whether patients with DLE need a full workup for SLE, since corroborative findings are rarely found.

Emphasis is placed on effective treatment of DLE, which includes the use of class 3 or 4 topical steroids and oral antimalarials (eg, hydroxychloroquine). Even with treatment, DLE can take weeks or months to resolve and often leaves permanent scarring. Ongoing sun protection is necessary to prevent recurrence.

TAKE-HOME LEARNING POINTS

• Discoid lupus erythematosus (DLE) is a common form of chronic cutaneous lupus, which has an autoimmune origin but is triggered by sun exposure.
• DLE typically presents with scaly round-to-oval patches and plaques with atrophic centers and follicular accentuation, often on sun-exposed areas.
• Women of color are at increased risk for lupus, and biopsy is often needed to confirm the diagnosis.
• Only about 15% of DLE patients ever progress to systemic lupus erythematosus (SLE), but DLE can be part of a larger SLE diagnosis.
• Treatment includes topical steroids and oral antimalarials (eg, hydroxychloroquine)—and sun protection is crucial.

For more than two years, this 40-year-old African-American woman has had a lesion on her left maxilla. While it does not cause pain or discomfort, its presence is alarming to the patient. The lesion has grown steadily without responding to various topical OTC medications (tolnaftate, clotrimazole, miconazole, 1% hydrocortisone cream), oral anti-yeast medication, and antibiotics (fluconazole, erythromycin).

The patient claims to be in excellent health otherwise. She reports a strong family history of autoimmune disease, including rheumatoid arthritis and lupus.

EXAMINATION
There is an oval, scaly, atrophic patch on the upper left maxilla, just below the left nostril. The lesion measures 1.2 cm, has well-defined margins, and appears darker than the patient’s type V skin.

No redness or edema are seen, and no nodes are palpable in the area. Examination of the adjacent oral mucosal surface shows nothing amiss.

Under sterile conditions, and after local anesthesia (1% lidocaine with epinephrine) is administered, a 3-mm punch biopsy is obtained from the center of the lesion. The defect is closed with two interrupted nylon sutures.

What is the diagnosis?

This manifestation of an autoimmune process is especially common in younger women of color. DLE primarily affects sun-exposed areas (eg, face, ears, neck) and involves scaly, round-to-oval patches and plaques with atrophic centers and follicular accentuation.

These lesions are frequently misdiagnosed as “fungal.” The differential also includes lichen planus and Jessner lymphocytic infiltrate.

Of the three types of cutaneous lupus erythematosus (discoid, acute, subacute), DLE is the most common. The acute form is defined by a “butterfly rash” across the face, while the subacute form involves multiple round-to-oval scaly lesions in wide photodistribution.

The chronic cutaneous lupus category includes DLE, tumid (characterized by deep, painful, indurated nodules), and panniculitis, which affects large areas of adipose tissue. DLE is, once again, the most common.

DLE can be an entity unto itself or part of a larger diagnosis of systemic lupus erythematosus (SLE). The good news: Only about 15% of patients with DLE progress to SLE. It is debatable whether patients with DLE need a full workup for SLE, since corroborative findings are rarely found.

Emphasis is placed on effective treatment of DLE, which includes the use of class 3 or 4 topical steroids and oral antimalarials (eg, hydroxychloroquine). Even with treatment, DLE can take weeks or months to resolve and often leaves permanent scarring. Ongoing sun protection is necessary to prevent recurrence.

TAKE-HOME LEARNING POINTS

• Discoid lupus erythematosus (DLE) is a common form of chronic cutaneous lupus, which has an autoimmune origin but is triggered by sun exposure.
• DLE typically presents with scaly round-to-oval patches and plaques with atrophic centers and follicular accentuation, often on sun-exposed areas.
• Women of color are at increased risk for lupus, and biopsy is often needed to confirm the diagnosis.
• Only about 15% of DLE patients ever progress to systemic lupus erythematosus (SLE), but DLE can be part of a larger SLE diagnosis.
• Treatment includes topical steroids and oral antimalarials (eg, hydroxychloroquine)—and sun protection is crucial.

For more than two years, this 40-year-old African-American woman has had a lesion on her left maxilla. While it does not cause pain or discomfort, its presence is alarming to the patient. The lesion has grown steadily without responding to various topical OTC medications (tolnaftate, clotrimazole, miconazole, 1% hydrocortisone cream), oral anti-yeast medication, and antibiotics (fluconazole, erythromycin).

The patient claims to be in excellent health otherwise. She reports a strong family history of autoimmune disease, including rheumatoid arthritis and lupus.

EXAMINATION
There is an oval, scaly, atrophic patch on the upper left maxilla, just below the left nostril. The lesion measures 1.2 cm, has well-defined margins, and appears darker than the patient’s type V skin.

No redness or edema are seen, and no nodes are palpable in the area. Examination of the adjacent oral mucosal surface shows nothing amiss.

Under sterile conditions, and after local anesthesia (1% lidocaine with epinephrine) is administered, a 3-mm punch biopsy is obtained from the center of the lesion. The defect is closed with two interrupted nylon sutures.

What is the diagnosis?

This manifestation of an autoimmune process is especially common in younger women of color. DLE primarily affects sun-exposed areas (eg, face, ears, neck) and involves scaly, round-to-oval patches and plaques with atrophic centers and follicular accentuation.

These lesions are frequently misdiagnosed as “fungal.” The differential also includes lichen planus and Jessner lymphocytic infiltrate.

Of the three types of cutaneous lupus erythematosus (discoid, acute, subacute), DLE is the most common. The acute form is defined by a “butterfly rash” across the face, while the subacute form involves multiple round-to-oval scaly lesions in wide photodistribution.

The chronic cutaneous lupus category includes DLE, tumid (characterized by deep, painful, indurated nodules), and panniculitis, which affects large areas of adipose tissue. DLE is, once again, the most common.

DLE can be an entity unto itself or part of a larger diagnosis of systemic lupus erythematosus (SLE). The good news: Only about 15% of patients with DLE progress to SLE. It is debatable whether patients with DLE need a full workup for SLE, since corroborative findings are rarely found.

Emphasis is placed on effective treatment of DLE, which includes the use of class 3 or 4 topical steroids and oral antimalarials (eg, hydroxychloroquine). Even with treatment, DLE can take weeks or months to resolve and often leaves permanent scarring. Ongoing sun protection is necessary to prevent recurrence.

TAKE-HOME LEARNING POINTS

• Discoid lupus erythematosus (DLE) is a common form of chronic cutaneous lupus, which has an autoimmune origin but is triggered by sun exposure.
• DLE typically presents with scaly round-to-oval patches and plaques with atrophic centers and follicular accentuation, often on sun-exposed areas.
• Women of color are at increased risk for lupus, and biopsy is often needed to confirm the diagnosis.
• Only about 15% of DLE patients ever progress to systemic lupus erythematosus (SLE), but DLE can be part of a larger SLE diagnosis.
• Treatment includes topical steroids and oral antimalarials (eg, hydroxychloroquine)—and sun protection is crucial.