THE COMPARISON

A An 11-year-old Hispanic boy with allergic contact dermatitis (ACD) on the abdomen. The geometric nature of the eruption and proximity to the belt buckle were highly suggestive of ACD to nickel; patch testing was not needed.

B A Black woman with ACD on the neck. A punch biopsy demonstrated spongiotic dermatitis that was typical of ACD. The diagnosis was supported by the patient’s history of dermatitis that developed after new products were applied to the hair. The patient declined patch testing.

C A Hispanic man with ACD on hair-bearing areas on the face where hair dye was used. The patient’s history of dermatitis following the application of hair dye was highly suggestive of ACD; patch testing confirmed the allergen was paraphenylenediamine (PPD).

Photographs courtesy of Richard P. Usatine, MD.

Allergic contact dermatitis (ACD) is an inflammatory condition of the skin caused by an immunologic response to one or more identifiable allergens. A delayed-type immune response (type IV hypersensitivity reaction) occurs after the skin is reexposed to an offending allergen.¹ Severe pruritus is the main symptom of ACD in the early stages, accompanied by erythema, vesicles, and scaling in a distinct pattern corresponding to the allergen’s contact with the skin.² Delayed widespread dermatitis after exposure to an allergen—a phenomenon known as autoeczematization (id reaction)—also may occur.³

The gold-standard diagnostic tool for ACD is patch testing, in which the patient is re-exposed to the suspected contact allergen(s) and observed for the development of dermatitis.⁴ However, ACD can be diagnosed with a detailed patient history including occupation, hobbies, personal care practices, and possible triggers with subsequent rashes. Thorough clinical examination of the skin is paramount. Indicators of possible ACD include dermatitis that persists despite use of appropriate treatment, an unexplained flare of previously quiescent dermatitis, and a diagnosis of dermatitis without a clear cause.¹

Hairdressers, health care workers, and metal workers are at higher risk for ACD.⁵ Occupational ACD has notable socioeconomic implications, as it can result in frequent sick days, inability to perform tasks at work, and in some cases job loss.⁶

Patients with atopic dermatitis have impaired barrier function of the skin, permitting the entrance of allergens and subsequent sensitization.⁷ Allergic contact dermatitis is a challenge to manage, as complete avoidance of the allergen may not be possible.⁸

The underrepresentation of patients with skin of color (SOC) in educational materials as well as socioeconomic health disparities may contribute to the lower rates of diagnosis, patch testing, and treatment of ACD in this patient population.

Epidemiology

An ACD prevalence of 15.2% was reported in a study of 793 Danish patients who underwent skin prick and patch testing.⁹ Alinaghi et al¹⁰ conducted a meta-analysis of 20,107 patients across 28 studies who were patch tested to determine the prevalence of ACD in the general population. The researchers concluded that 20.1% (95% CI, 16.8%- 23.7%) of the general population experienced ACD. They analyzed 22 studies to determine the prevalence of ACD based on specific geographic area including 18,709 individuals from Europe with a prevalence of 19.5% (95% CI, 15.8%-23.4%), 1639 individuals from North America with a prevalence of 20.6% (95% CI, 9.2%-35.2%), and 2 studies from China (no other studies from Asia found) with a prevalence of 20.6% (95% CI, 17.4%-23.9%). Researchers did not find data from studies conducted in Africa or South America.¹⁰

The current available epidemiologic data on ACD are not representative of SOC populations. DeLeo et al¹¹ looked at patch test reaction patterns in association with race and ethnicity in a large sample size (N=19,457); 17,803 (92.9%) of these patients were White and only 1360 (7.1%) were Black. Large-scale, inclusive studies are needed, which can only be achieved with increased suspicion for ACD and increased access to patch testing.

Allergic contact dermatitis is more common in women, with nickel being the most frequently identified allergen (Figure, A).¹⁰ Personal care products often are linked to ACD (Figure, B). An analysis of data from the North American Contact Dermatitis Group revealed that the top 5 personal care product allergens were methylisothiazolinone (a preservative), fragrance mix I, balsam of Peru, quaternium-15 (a preservative), and paraphenylenediamine (PPD)(a common component of hair dye) (Figure, C).¹²

There is a paucity of epidemiologic data among various ethnic groups; however, a few studies have suggested that there is no difference in the frequency rates of positive patch test results in Black vs White populations.^11,13,14 One study of patch test results from 114 Black patients and 877 White patients at the Cleveland Clinic Foundation in Ohio demonstrated a similar allergy frequency of 43.0% and 43.6%, respectively.¹³ However, there were differences in the types of allergen sensitization. Black patients had higher positive patch test rates for PPD than White patients (10.6% vs 4.5%). Black men had a higher frequency of sensitivity to PPD (21.2% vs 4.2%) and imidazolidinyl urea (a formaldehyde-releasing preservative) (9.1% vs 2.6%) compared to White men.¹³

Ethnicity and cultural practices influence epidemiologic patterns of ACD. Darker hair dyes used in Black patients¹⁴ and deeply pigmented PPD dye found in henna tattoos used in Indian and Black patients¹⁵ may lead to increased sensitization to PPD. Allergic contact dermatitis due to formaldehyde is more common in White patients, possibly due to more frequent use of formaldehyde-containing moisturizers, shampoos, and creams.¹⁵

Key clinical features in people with darker skin tones

In patients with SOC, the clinical features of ACD vary, posing a diagnostic challenge. Hyperpigmentation, lichenification, and induration are more likely to be seen than the papules, vesicles, and erythematous dermatitis often described in lighter skin tones or acute ACD. Erythema can be difficult to assess on darker skin and may appear violaceous or very faint pink.¹⁶

Worth noting

A high index of suspicion is necessary when interpreting patch tests in patients with SOC, as patch test kits use a reading plate with graduated intensities of erythema, papulation, and vesicular reactions to determine the likelihood of ACD. The potential contact allergens are placed on the skin on day 1 and covered. Then, on day 3 the allergens are removed. The skin is clinically evaluated using visual assessment and skin palpation. The reactions are graded as negative, irritant reaction, equivocal, weak positive, strong positive, or extreme reaction at around days 3 and 5 to capture both early and delayed reactions.¹⁷ A patch test may be positive even if obvious signs of erythema are not appreciated as expected.

Adjusting the lighting in the examination room, including side lighting, or using a blue background can be helpful in identifying erythema in darker skin tones.^15,16,18 Palpation of the skin also is useful, as even slight texture changes and induration are indicators of a possible skin reaction to the test allergen.¹⁵

Health disparity highlight

Clinical photographs of ACD and patch test results in patients with SOC are not commonplace in the literature. Positive patch test results in patients with darker skin tones vary from those of patients with lighter skin tones, and if the clinician reading the patch test result is not familiar with the findings in darker skin tones, the diagnosis may be delayed or missed.¹⁵

Furthermore, Scott et al¹⁵ highlighted that many dermatology residency training programs have a paucity of SOC education in their curriculum. This lack of representation may contribute to the diagnostic challenges encountered by health care providers.

Timely access to health care and education as well as economic stability are essential for the successful management of patients with ACD. Some individuals with SOC have been disproportionately affected by social determinants of health. Rodriguez-Homs et al¹⁹ demonstrated that the distance needed to travel to a clinic and the poverty rate of the county the patient lives in play a role in referral to a clinician specializing in contact dermatitis.

A retrospective registry review of 2310 patients undergoing patch testing at the Massachusetts General Hospital in Boston revealed that 2.5% were Black, 5.5% were Latinx, 8.3% were Asian, and the remaining 83.7% were White.²⁰ Qian et al²¹ also looked at patch testing patterns among various sociodemographic groups (N=1,107,530) and found that 69% of patients were White and 59% were female. Rates of patch testing among patients who were Black, lesser educated, male, lower income, and younger (children aged 0–12 years) were significantly lower than for other groups when ACD was suspected (P<.0001).²¹ The lower rates of patch testing in patients with SOC may be due to low suspicion of diagnosis, low referral rates due to limited medical insurance, and financial instability, as well as other socioeconomic factors.²⁰

Tamazian et al¹⁶ reviewed pediatric populations at 13 US centers and found that Black children received patch testing less frequently than White and Hispanic children. Another review of pediatric patch testing in patients with SOC found that a less comprehensive panel of allergens was used in this population.²²

The key to resolution of ACD is removal of the offending antigen, and if patients are not being tested, then they risk having a prolonged and complicated course of ACD with a poor prognosis. Patients with SOC also experience greater negative psychosocial impact due to ACD disease burden.^21,23

The lower rates of patch testing in Black patients cannot solely be attributed to difficulty diagnosing ACD in darker skin tones; it is likely due to the impact of social determinants of health. Alleviating health disparities will improve patient outcomes and quality of life.

THE COMPARISON

A An 11-year-old Hispanic boy with allergic contact dermatitis (ACD) on the abdomen. The geometric nature of the eruption and proximity to the belt buckle were highly suggestive of ACD to nickel; patch testing was not needed.

B A Black woman with ACD on the neck. A punch biopsy demonstrated spongiotic dermatitis that was typical of ACD. The diagnosis was supported by the patient’s history of dermatitis that developed after new products were applied to the hair. The patient declined patch testing.

C A Hispanic man with ACD on hair-bearing areas on the face where hair dye was used. The patient’s history of dermatitis following the application of hair dye was highly suggestive of ACD; patch testing confirmed the allergen was paraphenylenediamine (PPD).

Photographs courtesy of Richard P. Usatine, MD.

Allergic contact dermatitis (ACD) is an inflammatory condition of the skin caused by an immunologic response to one or more identifiable allergens. A delayed-type immune response (type IV hypersensitivity reaction) occurs after the skin is reexposed to an offending allergen.¹ Severe pruritus is the main symptom of ACD in the early stages, accompanied by erythema, vesicles, and scaling in a distinct pattern corresponding to the allergen’s contact with the skin.² Delayed widespread dermatitis after exposure to an allergen—a phenomenon known as autoeczematization (id reaction)—also may occur.³

The gold-standard diagnostic tool for ACD is patch testing, in which the patient is re-exposed to the suspected contact allergen(s) and observed for the development of dermatitis.⁴ However, ACD can be diagnosed with a detailed patient history including occupation, hobbies, personal care practices, and possible triggers with subsequent rashes. Thorough clinical examination of the skin is paramount. Indicators of possible ACD include dermatitis that persists despite use of appropriate treatment, an unexplained flare of previously quiescent dermatitis, and a diagnosis of dermatitis without a clear cause.¹

Hairdressers, health care workers, and metal workers are at higher risk for ACD.⁵ Occupational ACD has notable socioeconomic implications, as it can result in frequent sick days, inability to perform tasks at work, and in some cases job loss.⁶

Patients with atopic dermatitis have impaired barrier function of the skin, permitting the entrance of allergens and subsequent sensitization.⁷ Allergic contact dermatitis is a challenge to manage, as complete avoidance of the allergen may not be possible.⁸

The underrepresentation of patients with skin of color (SOC) in educational materials as well as socioeconomic health disparities may contribute to the lower rates of diagnosis, patch testing, and treatment of ACD in this patient population.

Epidemiology

An ACD prevalence of 15.2% was reported in a study of 793 Danish patients who underwent skin prick and patch testing.⁹ Alinaghi et al¹⁰ conducted a meta-analysis of 20,107 patients across 28 studies who were patch tested to determine the prevalence of ACD in the general population. The researchers concluded that 20.1% (95% CI, 16.8%- 23.7%) of the general population experienced ACD. They analyzed 22 studies to determine the prevalence of ACD based on specific geographic area including 18,709 individuals from Europe with a prevalence of 19.5% (95% CI, 15.8%-23.4%), 1639 individuals from North America with a prevalence of 20.6% (95% CI, 9.2%-35.2%), and 2 studies from China (no other studies from Asia found) with a prevalence of 20.6% (95% CI, 17.4%-23.9%). Researchers did not find data from studies conducted in Africa or South America.¹⁰

The current available epidemiologic data on ACD are not representative of SOC populations. DeLeo et al¹¹ looked at patch test reaction patterns in association with race and ethnicity in a large sample size (N=19,457); 17,803 (92.9%) of these patients were White and only 1360 (7.1%) were Black. Large-scale, inclusive studies are needed, which can only be achieved with increased suspicion for ACD and increased access to patch testing.

Allergic contact dermatitis is more common in women, with nickel being the most frequently identified allergen (Figure, A).¹⁰ Personal care products often are linked to ACD (Figure, B). An analysis of data from the North American Contact Dermatitis Group revealed that the top 5 personal care product allergens were methylisothiazolinone (a preservative), fragrance mix I, balsam of Peru, quaternium-15 (a preservative), and paraphenylenediamine (PPD)(a common component of hair dye) (Figure, C).¹²

There is a paucity of epidemiologic data among various ethnic groups; however, a few studies have suggested that there is no difference in the frequency rates of positive patch test results in Black vs White populations.^11,13,14 One study of patch test results from 114 Black patients and 877 White patients at the Cleveland Clinic Foundation in Ohio demonstrated a similar allergy frequency of 43.0% and 43.6%, respectively.¹³ However, there were differences in the types of allergen sensitization. Black patients had higher positive patch test rates for PPD than White patients (10.6% vs 4.5%). Black men had a higher frequency of sensitivity to PPD (21.2% vs 4.2%) and imidazolidinyl urea (a formaldehyde-releasing preservative) (9.1% vs 2.6%) compared to White men.¹³

Ethnicity and cultural practices influence epidemiologic patterns of ACD. Darker hair dyes used in Black patients¹⁴ and deeply pigmented PPD dye found in henna tattoos used in Indian and Black patients¹⁵ may lead to increased sensitization to PPD. Allergic contact dermatitis due to formaldehyde is more common in White patients, possibly due to more frequent use of formaldehyde-containing moisturizers, shampoos, and creams.¹⁵

Key clinical features in people with darker skin tones

In patients with SOC, the clinical features of ACD vary, posing a diagnostic challenge. Hyperpigmentation, lichenification, and induration are more likely to be seen than the papules, vesicles, and erythematous dermatitis often described in lighter skin tones or acute ACD. Erythema can be difficult to assess on darker skin and may appear violaceous or very faint pink.¹⁶

Worth noting

A high index of suspicion is necessary when interpreting patch tests in patients with SOC, as patch test kits use a reading plate with graduated intensities of erythema, papulation, and vesicular reactions to determine the likelihood of ACD. The potential contact allergens are placed on the skin on day 1 and covered. Then, on day 3 the allergens are removed. The skin is clinically evaluated using visual assessment and skin palpation. The reactions are graded as negative, irritant reaction, equivocal, weak positive, strong positive, or extreme reaction at around days 3 and 5 to capture both early and delayed reactions.¹⁷ A patch test may be positive even if obvious signs of erythema are not appreciated as expected.

Adjusting the lighting in the examination room, including side lighting, or using a blue background can be helpful in identifying erythema in darker skin tones.^15,16,18 Palpation of the skin also is useful, as even slight texture changes and induration are indicators of a possible skin reaction to the test allergen.¹⁵

Health disparity highlight

Clinical photographs of ACD and patch test results in patients with SOC are not commonplace in the literature. Positive patch test results in patients with darker skin tones vary from those of patients with lighter skin tones, and if the clinician reading the patch test result is not familiar with the findings in darker skin tones, the diagnosis may be delayed or missed.¹⁵

Furthermore, Scott et al¹⁵ highlighted that many dermatology residency training programs have a paucity of SOC education in their curriculum. This lack of representation may contribute to the diagnostic challenges encountered by health care providers.

Timely access to health care and education as well as economic stability are essential for the successful management of patients with ACD. Some individuals with SOC have been disproportionately affected by social determinants of health. Rodriguez-Homs et al¹⁹ demonstrated that the distance needed to travel to a clinic and the poverty rate of the county the patient lives in play a role in referral to a clinician specializing in contact dermatitis.

A retrospective registry review of 2310 patients undergoing patch testing at the Massachusetts General Hospital in Boston revealed that 2.5% were Black, 5.5% were Latinx, 8.3% were Asian, and the remaining 83.7% were White.²⁰ Qian et al²¹ also looked at patch testing patterns among various sociodemographic groups (N=1,107,530) and found that 69% of patients were White and 59% were female. Rates of patch testing among patients who were Black, lesser educated, male, lower income, and younger (children aged 0–12 years) were significantly lower than for other groups when ACD was suspected (P<.0001).²¹ The lower rates of patch testing in patients with SOC may be due to low suspicion of diagnosis, low referral rates due to limited medical insurance, and financial instability, as well as other socioeconomic factors.²⁰

Tamazian et al¹⁶ reviewed pediatric populations at 13 US centers and found that Black children received patch testing less frequently than White and Hispanic children. Another review of pediatric patch testing in patients with SOC found that a less comprehensive panel of allergens was used in this population.²²

The key to resolution of ACD is removal of the offending antigen, and if patients are not being tested, then they risk having a prolonged and complicated course of ACD with a poor prognosis. Patients with SOC also experience greater negative psychosocial impact due to ACD disease burden.^21,23

The lower rates of patch testing in Black patients cannot solely be attributed to difficulty diagnosing ACD in darker skin tones; it is likely due to the impact of social determinants of health. Alleviating health disparities will improve patient outcomes and quality of life.

THE COMPARISON

A An 11-year-old Hispanic boy with allergic contact dermatitis (ACD) on the abdomen. The geometric nature of the eruption and proximity to the belt buckle were highly suggestive of ACD to nickel; patch testing was not needed.

B A Black woman with ACD on the neck. A punch biopsy demonstrated spongiotic dermatitis that was typical of ACD. The diagnosis was supported by the patient’s history of dermatitis that developed after new products were applied to the hair. The patient declined patch testing.

C A Hispanic man with ACD on hair-bearing areas on the face where hair dye was used. The patient’s history of dermatitis following the application of hair dye was highly suggestive of ACD; patch testing confirmed the allergen was paraphenylenediamine (PPD).

Photographs courtesy of Richard P. Usatine, MD.

Allergic contact dermatitis (ACD) is an inflammatory condition of the skin caused by an immunologic response to one or more identifiable allergens. A delayed-type immune response (type IV hypersensitivity reaction) occurs after the skin is reexposed to an offending allergen.¹ Severe pruritus is the main symptom of ACD in the early stages, accompanied by erythema, vesicles, and scaling in a distinct pattern corresponding to the allergen’s contact with the skin.² Delayed widespread dermatitis after exposure to an allergen—a phenomenon known as autoeczematization (id reaction)—also may occur.³

The gold-standard diagnostic tool for ACD is patch testing, in which the patient is re-exposed to the suspected contact allergen(s) and observed for the development of dermatitis.⁴ However, ACD can be diagnosed with a detailed patient history including occupation, hobbies, personal care practices, and possible triggers with subsequent rashes. Thorough clinical examination of the skin is paramount. Indicators of possible ACD include dermatitis that persists despite use of appropriate treatment, an unexplained flare of previously quiescent dermatitis, and a diagnosis of dermatitis without a clear cause.¹

Hairdressers, health care workers, and metal workers are at higher risk for ACD.⁵ Occupational ACD has notable socioeconomic implications, as it can result in frequent sick days, inability to perform tasks at work, and in some cases job loss.⁶

Patients with atopic dermatitis have impaired barrier function of the skin, permitting the entrance of allergens and subsequent sensitization.⁷ Allergic contact dermatitis is a challenge to manage, as complete avoidance of the allergen may not be possible.⁸

The underrepresentation of patients with skin of color (SOC) in educational materials as well as socioeconomic health disparities may contribute to the lower rates of diagnosis, patch testing, and treatment of ACD in this patient population.

Epidemiology

An ACD prevalence of 15.2% was reported in a study of 793 Danish patients who underwent skin prick and patch testing.⁹ Alinaghi et al¹⁰ conducted a meta-analysis of 20,107 patients across 28 studies who were patch tested to determine the prevalence of ACD in the general population. The researchers concluded that 20.1% (95% CI, 16.8%- 23.7%) of the general population experienced ACD. They analyzed 22 studies to determine the prevalence of ACD based on specific geographic area including 18,709 individuals from Europe with a prevalence of 19.5% (95% CI, 15.8%-23.4%), 1639 individuals from North America with a prevalence of 20.6% (95% CI, 9.2%-35.2%), and 2 studies from China (no other studies from Asia found) with a prevalence of 20.6% (95% CI, 17.4%-23.9%). Researchers did not find data from studies conducted in Africa or South America.¹⁰

The current available epidemiologic data on ACD are not representative of SOC populations. DeLeo et al¹¹ looked at patch test reaction patterns in association with race and ethnicity in a large sample size (N=19,457); 17,803 (92.9%) of these patients were White and only 1360 (7.1%) were Black. Large-scale, inclusive studies are needed, which can only be achieved with increased suspicion for ACD and increased access to patch testing.

Allergic contact dermatitis is more common in women, with nickel being the most frequently identified allergen (Figure, A).¹⁰ Personal care products often are linked to ACD (Figure, B). An analysis of data from the North American Contact Dermatitis Group revealed that the top 5 personal care product allergens were methylisothiazolinone (a preservative), fragrance mix I, balsam of Peru, quaternium-15 (a preservative), and paraphenylenediamine (PPD)(a common component of hair dye) (Figure, C).¹²

There is a paucity of epidemiologic data among various ethnic groups; however, a few studies have suggested that there is no difference in the frequency rates of positive patch test results in Black vs White populations.^11,13,14 One study of patch test results from 114 Black patients and 877 White patients at the Cleveland Clinic Foundation in Ohio demonstrated a similar allergy frequency of 43.0% and 43.6%, respectively.¹³ However, there were differences in the types of allergen sensitization. Black patients had higher positive patch test rates for PPD than White patients (10.6% vs 4.5%). Black men had a higher frequency of sensitivity to PPD (21.2% vs 4.2%) and imidazolidinyl urea (a formaldehyde-releasing preservative) (9.1% vs 2.6%) compared to White men.¹³

Ethnicity and cultural practices influence epidemiologic patterns of ACD. Darker hair dyes used in Black patients¹⁴ and deeply pigmented PPD dye found in henna tattoos used in Indian and Black patients¹⁵ may lead to increased sensitization to PPD. Allergic contact dermatitis due to formaldehyde is more common in White patients, possibly due to more frequent use of formaldehyde-containing moisturizers, shampoos, and creams.¹⁵

Key clinical features in people with darker skin tones

In patients with SOC, the clinical features of ACD vary, posing a diagnostic challenge. Hyperpigmentation, lichenification, and induration are more likely to be seen than the papules, vesicles, and erythematous dermatitis often described in lighter skin tones or acute ACD. Erythema can be difficult to assess on darker skin and may appear violaceous or very faint pink.¹⁶

Worth noting

A high index of suspicion is necessary when interpreting patch tests in patients with SOC, as patch test kits use a reading plate with graduated intensities of erythema, papulation, and vesicular reactions to determine the likelihood of ACD. The potential contact allergens are placed on the skin on day 1 and covered. Then, on day 3 the allergens are removed. The skin is clinically evaluated using visual assessment and skin palpation. The reactions are graded as negative, irritant reaction, equivocal, weak positive, strong positive, or extreme reaction at around days 3 and 5 to capture both early and delayed reactions.¹⁷ A patch test may be positive even if obvious signs of erythema are not appreciated as expected.

Adjusting the lighting in the examination room, including side lighting, or using a blue background can be helpful in identifying erythema in darker skin tones.^15,16,18 Palpation of the skin also is useful, as even slight texture changes and induration are indicators of a possible skin reaction to the test allergen.¹⁵

Health disparity highlight

Clinical photographs of ACD and patch test results in patients with SOC are not commonplace in the literature. Positive patch test results in patients with darker skin tones vary from those of patients with lighter skin tones, and if the clinician reading the patch test result is not familiar with the findings in darker skin tones, the diagnosis may be delayed or missed.¹⁵

Furthermore, Scott et al¹⁵ highlighted that many dermatology residency training programs have a paucity of SOC education in their curriculum. This lack of representation may contribute to the diagnostic challenges encountered by health care providers.

Timely access to health care and education as well as economic stability are essential for the successful management of patients with ACD. Some individuals with SOC have been disproportionately affected by social determinants of health. Rodriguez-Homs et al¹⁹ demonstrated that the distance needed to travel to a clinic and the poverty rate of the county the patient lives in play a role in referral to a clinician specializing in contact dermatitis.

A retrospective registry review of 2310 patients undergoing patch testing at the Massachusetts General Hospital in Boston revealed that 2.5% were Black, 5.5% were Latinx, 8.3% were Asian, and the remaining 83.7% were White.²⁰ Qian et al²¹ also looked at patch testing patterns among various sociodemographic groups (N=1,107,530) and found that 69% of patients were White and 59% were female. Rates of patch testing among patients who were Black, lesser educated, male, lower income, and younger (children aged 0–12 years) were significantly lower than for other groups when ACD was suspected (P<.0001).²¹ The lower rates of patch testing in patients with SOC may be due to low suspicion of diagnosis, low referral rates due to limited medical insurance, and financial instability, as well as other socioeconomic factors.²⁰

Tamazian et al¹⁶ reviewed pediatric populations at 13 US centers and found that Black children received patch testing less frequently than White and Hispanic children. Another review of pediatric patch testing in patients with SOC found that a less comprehensive panel of allergens was used in this population.²²

The key to resolution of ACD is removal of the offending antigen, and if patients are not being tested, then they risk having a prolonged and complicated course of ACD with a poor prognosis. Patients with SOC also experience greater negative psychosocial impact due to ACD disease burden.^21,23

The lower rates of patch testing in Black patients cannot solely be attributed to difficulty diagnosing ACD in darker skin tones; it is likely due to the impact of social determinants of health. Alleviating health disparities will improve patient outcomes and quality of life.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

The Diagnosis: Galli-Galli Disease

Several cutaneous conditions can present as reticulated hyperpigmentation or keratotic papules. Although genetic testing can help identify some of these dermatoses, biopsy typically is sufficient for diagnosis, and genetic testing can be considered for more clinically challenging cases. In our case, the clinical evidence and histopathologic findings were diagnostic of Galli-Galli disease (GGD), an autosomal-dominant genodermatosis with incomplete penetrance. Our patient was unaware of any family members with a diagnosis of GGD; however, she reported a great uncle with similar clinical findings.

Galli-Galli disease is a rare allelic variant of Dowling- Degos disease (DDD), both caused by a loss-of-function mutation in the keratin 5 gene, KRT5. Both conditions present as reticulated papules distributed symmetrically in the flexural regions, most commonly the axillae and groin, but also as comedolike papules, typically in patients aged 30 to 50 years.¹ Cutaneous lesions primarily are of cosmetic concern but can be extremely pruritic, especially for patients with GGD. Gene mutations in protein O-fucosyltransferase 1, POFUT1; protein O-glucosyltransferase 1, POGLUT1; and presenilin enhancer 2, PSENEN, also have been discovered in cases of DDD and GGD.^2,3

Galli-Galli disease and DDD are distinguishable by their histologic appearance. Both diseases show elongated fingerlike rete ridges and a thin suprapapillary epidermis. The basal projections often are described as bulbous or resembling antler horns.⁴ Galli-Galli disease can be differentiated from DDD by focal suprabasal acantholysis with minimal dyskeratosis (quiz images).⁵ Due to the genetic and clinical similarities, many consider GGD an acantholytic variant of DDD rather than its own entity. Indeed, some patients have shown acantholysis in one area of biopsy but not others.⁶

Hailey-Hailey disease (HHD)(also known as benign familial or benign chronic pemphigus) is an autosomaldominant disorder caused by mutation of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1. Clinically, patients tend to present at a wide age range with fragile flaccid vesicles that commonly develop on the neck, axillae, and groin. Histologically, the epidermis is acanthotic with a dilapidated brick wall– like appearance from a few persistent intercellular connections amid widespread acantholysis (Figure 1).⁷ Unlike in autoimmune pemphigus, direct immunofluorescence is negative, and acantholysis spares the adnexal structures. Hailey-Hailey disease does not involve reticulated hyperpigmentation or the elongated bulbous rete seen in GGD. Confluent and reticulated papillomatosis is a rare, typically asymptomatic, hyperpigmented dermatosis. It presents as a conglomeration of scaly hyperpigmented macules or papillomatous papules that coalesce centrally and are reticulated toward the periphery.

Confluent and reticulated papillomatosis most commonly is seen on the trunk, initially presenting in adolescents and young adults. Confluent and reticulated papillomatosis is histologically similar to acanthosis nigricans. Histopathology will show hyperkeratosis, papillomatosis, and minimal to no inflammatory infiltrate, with no elongated rete ridges or acantholysis (Figure 2).⁸

Pemphigus vulgaris is a blistering disease resulting from the development of autoantibodies against desmogleins 1 and 3. Similar to GGD, there is suprabasal acantholysis, which often results in a tombstonelike appearance consisting of separation between the basal layer cells of the epidermis but with maintained attachment to the underlying basement membrane zone. Unlike HHD, the acantholysis tends to involve the follicular epithelium in pemphigus vulgaris (Figure 3). Clinically, the blisters are positive for Nikolsky sign and can be both cutaneous or mucosal, commonly arising initially in the mouth during the fourth or fifth decades of life. Ruptured blisters can result in painful and hemorrhagic erosions.⁹ Direct immunofluorescence exhibits a classic chicken wire–like deposition of IgG and C3 between keratinocytes of the epidermis. Although sometimes difficult to appreciate, the deposition can be more prominent in the lower epidermis, in contrast to pemphigus foliaceus, which can have more prominent deposition in the upper epidermis.

Darier disease (or dyskeratosis follicularis) is an autosomal-dominant genodermatosis caused by mutation of the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2. Clinically, this disorder arises in adolescents as red-brown, greasy, crusted papules in seborrheic areas that may coalesce into papillomatous clusters. Palmar punctate keratoses and pits also are common. Histologically, Darier disease can appear similar to GGD, as both can show acantholysis and dyskeratosis. Darier disease will tend to show more prominent dyskeratosis with corps ronds and grains, as well as thicker villilike projections of keratinocytes into the papillary dermis, in contrast to the thinner, fingerlike or bulbous projections that hang down from the epidermis in GGD (Figure 4).¹⁰

The Diagnosis: Galli-Galli Disease

Several cutaneous conditions can present as reticulated hyperpigmentation or keratotic papules. Although genetic testing can help identify some of these dermatoses, biopsy typically is sufficient for diagnosis, and genetic testing can be considered for more clinically challenging cases. In our case, the clinical evidence and histopathologic findings were diagnostic of Galli-Galli disease (GGD), an autosomal-dominant genodermatosis with incomplete penetrance. Our patient was unaware of any family members with a diagnosis of GGD; however, she reported a great uncle with similar clinical findings.

Galli-Galli disease is a rare allelic variant of Dowling- Degos disease (DDD), both caused by a loss-of-function mutation in the keratin 5 gene, KRT5. Both conditions present as reticulated papules distributed symmetrically in the flexural regions, most commonly the axillae and groin, but also as comedolike papules, typically in patients aged 30 to 50 years.¹ Cutaneous lesions primarily are of cosmetic concern but can be extremely pruritic, especially for patients with GGD. Gene mutations in protein O-fucosyltransferase 1, POFUT1; protein O-glucosyltransferase 1, POGLUT1; and presenilin enhancer 2, PSENEN, also have been discovered in cases of DDD and GGD.^2,3

Galli-Galli disease and DDD are distinguishable by their histologic appearance. Both diseases show elongated fingerlike rete ridges and a thin suprapapillary epidermis. The basal projections often are described as bulbous or resembling antler horns.⁴ Galli-Galli disease can be differentiated from DDD by focal suprabasal acantholysis with minimal dyskeratosis (quiz images).⁵ Due to the genetic and clinical similarities, many consider GGD an acantholytic variant of DDD rather than its own entity. Indeed, some patients have shown acantholysis in one area of biopsy but not others.⁶

Hailey-Hailey disease (HHD)(also known as benign familial or benign chronic pemphigus) is an autosomaldominant disorder caused by mutation of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1. Clinically, patients tend to present at a wide age range with fragile flaccid vesicles that commonly develop on the neck, axillae, and groin. Histologically, the epidermis is acanthotic with a dilapidated brick wall– like appearance from a few persistent intercellular connections amid widespread acantholysis (Figure 1).⁷ Unlike in autoimmune pemphigus, direct immunofluorescence is negative, and acantholysis spares the adnexal structures. Hailey-Hailey disease does not involve reticulated hyperpigmentation or the elongated bulbous rete seen in GGD. Confluent and reticulated papillomatosis is a rare, typically asymptomatic, hyperpigmented dermatosis. It presents as a conglomeration of scaly hyperpigmented macules or papillomatous papules that coalesce centrally and are reticulated toward the periphery.

Confluent and reticulated papillomatosis most commonly is seen on the trunk, initially presenting in adolescents and young adults. Confluent and reticulated papillomatosis is histologically similar to acanthosis nigricans. Histopathology will show hyperkeratosis, papillomatosis, and minimal to no inflammatory infiltrate, with no elongated rete ridges or acantholysis (Figure 2).⁸

Pemphigus vulgaris is a blistering disease resulting from the development of autoantibodies against desmogleins 1 and 3. Similar to GGD, there is suprabasal acantholysis, which often results in a tombstonelike appearance consisting of separation between the basal layer cells of the epidermis but with maintained attachment to the underlying basement membrane zone. Unlike HHD, the acantholysis tends to involve the follicular epithelium in pemphigus vulgaris (Figure 3). Clinically, the blisters are positive for Nikolsky sign and can be both cutaneous or mucosal, commonly arising initially in the mouth during the fourth or fifth decades of life. Ruptured blisters can result in painful and hemorrhagic erosions.⁹ Direct immunofluorescence exhibits a classic chicken wire–like deposition of IgG and C3 between keratinocytes of the epidermis. Although sometimes difficult to appreciate, the deposition can be more prominent in the lower epidermis, in contrast to pemphigus foliaceus, which can have more prominent deposition in the upper epidermis.

Darier disease (or dyskeratosis follicularis) is an autosomal-dominant genodermatosis caused by mutation of the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2. Clinically, this disorder arises in adolescents as red-brown, greasy, crusted papules in seborrheic areas that may coalesce into papillomatous clusters. Palmar punctate keratoses and pits also are common. Histologically, Darier disease can appear similar to GGD, as both can show acantholysis and dyskeratosis. Darier disease will tend to show more prominent dyskeratosis with corps ronds and grains, as well as thicker villilike projections of keratinocytes into the papillary dermis, in contrast to the thinner, fingerlike or bulbous projections that hang down from the epidermis in GGD (Figure 4).¹⁰

The Diagnosis: Galli-Galli Disease

Several cutaneous conditions can present as reticulated hyperpigmentation or keratotic papules. Although genetic testing can help identify some of these dermatoses, biopsy typically is sufficient for diagnosis, and genetic testing can be considered for more clinically challenging cases. In our case, the clinical evidence and histopathologic findings were diagnostic of Galli-Galli disease (GGD), an autosomal-dominant genodermatosis with incomplete penetrance. Our patient was unaware of any family members with a diagnosis of GGD; however, she reported a great uncle with similar clinical findings.

Galli-Galli disease is a rare allelic variant of Dowling- Degos disease (DDD), both caused by a loss-of-function mutation in the keratin 5 gene, KRT5. Both conditions present as reticulated papules distributed symmetrically in the flexural regions, most commonly the axillae and groin, but also as comedolike papules, typically in patients aged 30 to 50 years.¹ Cutaneous lesions primarily are of cosmetic concern but can be extremely pruritic, especially for patients with GGD. Gene mutations in protein O-fucosyltransferase 1, POFUT1; protein O-glucosyltransferase 1, POGLUT1; and presenilin enhancer 2, PSENEN, also have been discovered in cases of DDD and GGD.^2,3

Galli-Galli disease and DDD are distinguishable by their histologic appearance. Both diseases show elongated fingerlike rete ridges and a thin suprapapillary epidermis. The basal projections often are described as bulbous or resembling antler horns.⁴ Galli-Galli disease can be differentiated from DDD by focal suprabasal acantholysis with minimal dyskeratosis (quiz images).⁵ Due to the genetic and clinical similarities, many consider GGD an acantholytic variant of DDD rather than its own entity. Indeed, some patients have shown acantholysis in one area of biopsy but not others.⁶

Hailey-Hailey disease (HHD)(also known as benign familial or benign chronic pemphigus) is an autosomaldominant disorder caused by mutation of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1. Clinically, patients tend to present at a wide age range with fragile flaccid vesicles that commonly develop on the neck, axillae, and groin. Histologically, the epidermis is acanthotic with a dilapidated brick wall– like appearance from a few persistent intercellular connections amid widespread acantholysis (Figure 1).⁷ Unlike in autoimmune pemphigus, direct immunofluorescence is negative, and acantholysis spares the adnexal structures. Hailey-Hailey disease does not involve reticulated hyperpigmentation or the elongated bulbous rete seen in GGD. Confluent and reticulated papillomatosis is a rare, typically asymptomatic, hyperpigmented dermatosis. It presents as a conglomeration of scaly hyperpigmented macules or papillomatous papules that coalesce centrally and are reticulated toward the periphery.

Confluent and reticulated papillomatosis most commonly is seen on the trunk, initially presenting in adolescents and young adults. Confluent and reticulated papillomatosis is histologically similar to acanthosis nigricans. Histopathology will show hyperkeratosis, papillomatosis, and minimal to no inflammatory infiltrate, with no elongated rete ridges or acantholysis (Figure 2).⁸

Pemphigus vulgaris is a blistering disease resulting from the development of autoantibodies against desmogleins 1 and 3. Similar to GGD, there is suprabasal acantholysis, which often results in a tombstonelike appearance consisting of separation between the basal layer cells of the epidermis but with maintained attachment to the underlying basement membrane zone. Unlike HHD, the acantholysis tends to involve the follicular epithelium in pemphigus vulgaris (Figure 3). Clinically, the blisters are positive for Nikolsky sign and can be both cutaneous or mucosal, commonly arising initially in the mouth during the fourth or fifth decades of life. Ruptured blisters can result in painful and hemorrhagic erosions.⁹ Direct immunofluorescence exhibits a classic chicken wire–like deposition of IgG and C3 between keratinocytes of the epidermis. Although sometimes difficult to appreciate, the deposition can be more prominent in the lower epidermis, in contrast to pemphigus foliaceus, which can have more prominent deposition in the upper epidermis.

Darier disease (or dyskeratosis follicularis) is an autosomal-dominant genodermatosis caused by mutation of the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2. Clinically, this disorder arises in adolescents as red-brown, greasy, crusted papules in seborrheic areas that may coalesce into papillomatous clusters. Palmar punctate keratoses and pits also are common. Histologically, Darier disease can appear similar to GGD, as both can show acantholysis and dyskeratosis. Darier disease will tend to show more prominent dyskeratosis with corps ronds and grains, as well as thicker villilike projections of keratinocytes into the papillary dermis, in contrast to the thinner, fingerlike or bulbous projections that hang down from the epidermis in GGD (Figure 4).¹⁰

Click to read more from Federal Health Care Data Trends 2023.

Click to read more from Federal Health Care Data Trends 2023.

Click to read more from Federal Health Care Data Trends 2023.

Click to read more from Federal Health Care Data Trends 2023.

Click to read more from Federal Health Care Data Trends 2023.

Click to read more from Federal Health Care Data Trends 2023.

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner, highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.

In this issue: 

• Limb Loss and Prostheses
• Neurology
  • Traumatic Brain Injury
  • Alzheimer's and Dementia
  • Amyotrophic Lateral Sclerosis (ALS)
  • Parkinson's Disease
  • Migraine and Headache
• Cardiology
• Mental Health
  • Depression
  • Opioid Use Disorder
  • PTSD and Psychedelic Treatments
  • Homelessness
  • Eating Disorders
• Diabetes
• Rheumatoid Arthritis
• Respiratory illnesses
• Women's Health
  • Access to Care
  • Infertility
  • Pregnancy
• HPV and Related Cancers

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner, highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.

In this issue: 

• Limb Loss and Prostheses
• Neurology
  • Traumatic Brain Injury
  • Alzheimer's and Dementia
  • Amyotrophic Lateral Sclerosis (ALS)
  • Parkinson's Disease
  • Migraine and Headache
• Cardiology
• Mental Health
  • Depression
  • Opioid Use Disorder
  • PTSD and Psychedelic Treatments
  • Homelessness
  • Eating Disorders
• Diabetes
• Rheumatoid Arthritis
• Respiratory illnesses
• Women's Health
  • Access to Care
  • Infertility
  • Pregnancy
• HPV and Related Cancers

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner, highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.

In this issue: 

• Limb Loss and Prostheses
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• Cardiology
• Mental Health
  • Depression
  • Opioid Use Disorder
  • PTSD and Psychedelic Treatments
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  • Eating Disorders
• Diabetes
• Rheumatoid Arthritis
• Respiratory illnesses
• Women's Health
  • Access to Care
  • Infertility
  • Pregnancy
• HPV and Related Cancers

Click to view more from Federal Health Care Data Trends 2023.

Click to view more from Federal Health Care Data Trends 2023.

Click to view more from Federal Health Care Data Trends 2023.

HAMBURG – Initiating metformin treatment at gestational diabetes diagnosis was associated with improved glycemic control and reduced gestational weight gain, according to the results of a randomized, placebo-controlled trial.

Overall, the trial’s primary outcome, a composite of insulin initiation or a fasting glucose level ≥ 5.1 mmol/L (92 mg/dL) at gestation weeks 32 or 38, did not differ between women with gestational diabetes randomly assigned to either placebo or metformin. However, women taking metformin were significantly less likely to require insulin and had significantly lower fasting blood glucose levels at weeks 32 and 38.

“With a composite outcome it’s more difficult to find a positive result ... So, although the primary composite outcome was not positive, the components of the primary outcome that are clinically meaningful were positive,” lead study author Fidelma Dunne, PhD, professor and endocrine consultant at the University of Galway, Ireland, said in an interview.

There were no differences in maternal or neonatal morbidities, but there was a nonsignificant increase in small for gestational age (SGA), a finding that has been seen in some but not all previous studies of metformin use in gestational diabetes.

Dr. Dunne presented the findings on Oct. 3 at the annual meeting of the European Association for the Study of Diabetes. The results were simultaneously published in JAMA.

Current recommendations from the United Kingdom’s National Institute for Health and Care Excellence say metformin is a suitable first-line therapy for gestational diabetes. However, both the American Diabetes Association and the Society of Maternal-Fetal Medicine do not, particularly for pregnancies with hypertension or preeclampsia or in those who are at risk for intrauterine growth restriction.

“Gestational diabetes is now reaching epidemic proportions. And of course, the vast majority of these women are in low- and middle-income countries where insulin might not be available, or the storage may not allow it to be used effectively. If you have a medication that in the majority of women is safe and effective it may actually help a lot of women in [those regions],” Dr. Dunne said.

Moreover, she noted, “women with gestational diabetes are testing their sugar with finger pricks four to seven times per day and we ask them to take insulin one to four times a day. So if you can relieve any of that pain related to treatment of their condition than that is a benefit for the women as well.”

Asked to comment, Katrien Benhalima, MD, PhD, of University Hospital Gasthuisberg, KU Leuven, Belgium, said, “I think it’s an interesting study because they investigated something novel, to initiate immediately metformin or placebo. Normally what we do with gestational diabetes is once we get the diagnosis, we treat them with lifestyle, and if that’s insufficient then we start with medical therapy. So this is a novel approach.”

She also agreed with Dr. Dunne that the lack of significance for the primary outcome “isn’t an issue of power but it is a composite outcome. If you look at the individual outcomes, as can be expected, the women taking metformin had less need for insulin treatment.”

But, Dr. Benhalima said, the study still leaves open the SGA issue. “It wasn’t significant, but it’s still something we are worried about in the sense that we feel we need more data, especially in the long-term for the offspring health ... You really need to follow them for 10 years or longer to see an effect.”

So for now, Dr. Benhalima said that she wouldn’t use metformin as a first-line treatment for gestational diabetes. “Normally if lifestyle isn’t enough we will still start insulin ... Another issue is why would you offer everybody medical treatment when pregnancy outcomes can be met with lifestyle alone?”

Then again, she added, “of course metformin is easier than an injection. Treatment satisfaction is improved, and the cost is less.”
 

Primary outcome didn’t differ, but study findings point toward metformin benefit

The double-blind, placebo-controlled trial was conducted at two sites in Ireland, with 510 individuals (535 gestational diabetes pregnancies) enrolled between June 2017 and September 2022. In addition to usual care, they were randomly assigned 1:1 to either placebo or metformin (maximum 2,500 mg) at the time of gestational diabetes diagnosis and continued until delivery.

The primary outcome, a composite of insulin initiation or a fasting glucose ≥ 5.1 mmol/L at gestation weeks 32 or 38, did not differ significantly between the two groups, with risk ratio 0.89 (P = 0.13).

Insulin initiation occurred in 38.4% of the metformin and 51.1% of the placebo groups (relative risk, 0.75, P = .004). The amount of insulin required at the last assessment prior to delivery did not differ between the two groups (P = .17).

Mean fasting glucose was significantly lower with metformin vs. placebo at gestational week 32 (4.9 vs. 5.0 mmol/L; P = .03) and at gestational week 38 (4.5 vs 4.7 mmol/L; P < .001).

On average, those in the metformin group gained less weight between randomization and delivery (0.8 kg vs. 2.0 kg; P = .003).

Gestational week at delivery didn’t differ between the groups, both 39.1 weeks, nor did preterm births prior to 37 weeks’ gestation (9.2% metformin vs. 6.5% placebo; P = .33) or any other pregnancy-related complications.

More participants in the metformin group said that they would choose the drug compared with placebo (76.2% vs. 67.1%, P = .04).

Mean birth weight was lower in the metformin group compared with placebo, 3,393 g vs. 3,506 g (P = .005), with fewer weighing > 4,000 g (7.6% vs. 14.8%; P = .02) or being large for gestational age, i.e., above the 90th percentile (6.5% vs. 14.9%; P = .003).

Proportions of offspring that were SGA (less than 10th percentile) were 5.7% in the metformin group vs. 2.7% with placebo (P = .13).

There were no other significant differences in neonatal variables.

Dr. Dunne told this news organization that her group has recently received funding for long-term follow-up of the SGA offspring. “As other papers have pointed out, if there’s any hint of SGA that’s really important to follow up. So we’re now beginning our longitudinal follow up of the mother and infants to see if the small number that were SGA will in fact turn out to have an increase in body mass index and weight in their childhood and adolescent years.”

The trial was funded by the Health Review Board (HRB) of Ireland, coordinated by the HRB-Clinical Research Facility Galway, and sponsored by the University of Galway, Ireland. Metformin and matched placebo were provided by Merck Healthcare KGaA, Darmstadt, Germany (operating as EMD Serono in the United States), and blood glucose monitoring strips were provided by Ascensia.

Dr. Dunne reported nonfinancial support from Merck and matched placebo and nonfinancial support from Ascensia during the conduct of the study. Dr. Benhalima receives research funds from Flemish Research Fund, study medication from Novo Nordisk, and devices and unrestricted grants from Medtronic and Dexcom.

A version of this article appeared on Medscape.com.

HAMBURG – Initiating metformin treatment at gestational diabetes diagnosis was associated with improved glycemic control and reduced gestational weight gain, according to the results of a randomized, placebo-controlled trial.

Overall, the trial’s primary outcome, a composite of insulin initiation or a fasting glucose level ≥ 5.1 mmol/L (92 mg/dL) at gestation weeks 32 or 38, did not differ between women with gestational diabetes randomly assigned to either placebo or metformin. However, women taking metformin were significantly less likely to require insulin and had significantly lower fasting blood glucose levels at weeks 32 and 38.

“With a composite outcome it’s more difficult to find a positive result ... So, although the primary composite outcome was not positive, the components of the primary outcome that are clinically meaningful were positive,” lead study author Fidelma Dunne, PhD, professor and endocrine consultant at the University of Galway, Ireland, said in an interview.

There were no differences in maternal or neonatal morbidities, but there was a nonsignificant increase in small for gestational age (SGA), a finding that has been seen in some but not all previous studies of metformin use in gestational diabetes.

Dr. Dunne presented the findings on Oct. 3 at the annual meeting of the European Association for the Study of Diabetes. The results were simultaneously published in JAMA.

Current recommendations from the United Kingdom’s National Institute for Health and Care Excellence say metformin is a suitable first-line therapy for gestational diabetes. However, both the American Diabetes Association and the Society of Maternal-Fetal Medicine do not, particularly for pregnancies with hypertension or preeclampsia or in those who are at risk for intrauterine growth restriction.

“Gestational diabetes is now reaching epidemic proportions. And of course, the vast majority of these women are in low- and middle-income countries where insulin might not be available, or the storage may not allow it to be used effectively. If you have a medication that in the majority of women is safe and effective it may actually help a lot of women in [those regions],” Dr. Dunne said.

Moreover, she noted, “women with gestational diabetes are testing their sugar with finger pricks four to seven times per day and we ask them to take insulin one to four times a day. So if you can relieve any of that pain related to treatment of their condition than that is a benefit for the women as well.”

Asked to comment, Katrien Benhalima, MD, PhD, of University Hospital Gasthuisberg, KU Leuven, Belgium, said, “I think it’s an interesting study because they investigated something novel, to initiate immediately metformin or placebo. Normally what we do with gestational diabetes is once we get the diagnosis, we treat them with lifestyle, and if that’s insufficient then we start with medical therapy. So this is a novel approach.”

She also agreed with Dr. Dunne that the lack of significance for the primary outcome “isn’t an issue of power but it is a composite outcome. If you look at the individual outcomes, as can be expected, the women taking metformin had less need for insulin treatment.”

But, Dr. Benhalima said, the study still leaves open the SGA issue. “It wasn’t significant, but it’s still something we are worried about in the sense that we feel we need more data, especially in the long-term for the offspring health ... You really need to follow them for 10 years or longer to see an effect.”

So for now, Dr. Benhalima said that she wouldn’t use metformin as a first-line treatment for gestational diabetes. “Normally if lifestyle isn’t enough we will still start insulin ... Another issue is why would you offer everybody medical treatment when pregnancy outcomes can be met with lifestyle alone?”

Then again, she added, “of course metformin is easier than an injection. Treatment satisfaction is improved, and the cost is less.”
 

Primary outcome didn’t differ, but study findings point toward metformin benefit

The double-blind, placebo-controlled trial was conducted at two sites in Ireland, with 510 individuals (535 gestational diabetes pregnancies) enrolled between June 2017 and September 2022. In addition to usual care, they were randomly assigned 1:1 to either placebo or metformin (maximum 2,500 mg) at the time of gestational diabetes diagnosis and continued until delivery.

The primary outcome, a composite of insulin initiation or a fasting glucose ≥ 5.1 mmol/L at gestation weeks 32 or 38, did not differ significantly between the two groups, with risk ratio 0.89 (P = 0.13).

Insulin initiation occurred in 38.4% of the metformin and 51.1% of the placebo groups (relative risk, 0.75, P = .004). The amount of insulin required at the last assessment prior to delivery did not differ between the two groups (P = .17).

Mean fasting glucose was significantly lower with metformin vs. placebo at gestational week 32 (4.9 vs. 5.0 mmol/L; P = .03) and at gestational week 38 (4.5 vs 4.7 mmol/L; P < .001).

On average, those in the metformin group gained less weight between randomization and delivery (0.8 kg vs. 2.0 kg; P = .003).

Gestational week at delivery didn’t differ between the groups, both 39.1 weeks, nor did preterm births prior to 37 weeks’ gestation (9.2% metformin vs. 6.5% placebo; P = .33) or any other pregnancy-related complications.

More participants in the metformin group said that they would choose the drug compared with placebo (76.2% vs. 67.1%, P = .04).

Mean birth weight was lower in the metformin group compared with placebo, 3,393 g vs. 3,506 g (P = .005), with fewer weighing > 4,000 g (7.6% vs. 14.8%; P = .02) or being large for gestational age, i.e., above the 90th percentile (6.5% vs. 14.9%; P = .003).

Proportions of offspring that were SGA (less than 10th percentile) were 5.7% in the metformin group vs. 2.7% with placebo (P = .13).

There were no other significant differences in neonatal variables.

Dr. Dunne told this news organization that her group has recently received funding for long-term follow-up of the SGA offspring. “As other papers have pointed out, if there’s any hint of SGA that’s really important to follow up. So we’re now beginning our longitudinal follow up of the mother and infants to see if the small number that were SGA will in fact turn out to have an increase in body mass index and weight in their childhood and adolescent years.”

The trial was funded by the Health Review Board (HRB) of Ireland, coordinated by the HRB-Clinical Research Facility Galway, and sponsored by the University of Galway, Ireland. Metformin and matched placebo were provided by Merck Healthcare KGaA, Darmstadt, Germany (operating as EMD Serono in the United States), and blood glucose monitoring strips were provided by Ascensia.

Dr. Dunne reported nonfinancial support from Merck and matched placebo and nonfinancial support from Ascensia during the conduct of the study. Dr. Benhalima receives research funds from Flemish Research Fund, study medication from Novo Nordisk, and devices and unrestricted grants from Medtronic and Dexcom.

A version of this article appeared on Medscape.com.

HAMBURG – Initiating metformin treatment at gestational diabetes diagnosis was associated with improved glycemic control and reduced gestational weight gain, according to the results of a randomized, placebo-controlled trial.

Overall, the trial’s primary outcome, a composite of insulin initiation or a fasting glucose level ≥ 5.1 mmol/L (92 mg/dL) at gestation weeks 32 or 38, did not differ between women with gestational diabetes randomly assigned to either placebo or metformin. However, women taking metformin were significantly less likely to require insulin and had significantly lower fasting blood glucose levels at weeks 32 and 38.

“With a composite outcome it’s more difficult to find a positive result ... So, although the primary composite outcome was not positive, the components of the primary outcome that are clinically meaningful were positive,” lead study author Fidelma Dunne, PhD, professor and endocrine consultant at the University of Galway, Ireland, said in an interview.

There were no differences in maternal or neonatal morbidities, but there was a nonsignificant increase in small for gestational age (SGA), a finding that has been seen in some but not all previous studies of metformin use in gestational diabetes.

Dr. Dunne presented the findings on Oct. 3 at the annual meeting of the European Association for the Study of Diabetes. The results were simultaneously published in JAMA.

Current recommendations from the United Kingdom’s National Institute for Health and Care Excellence say metformin is a suitable first-line therapy for gestational diabetes. However, both the American Diabetes Association and the Society of Maternal-Fetal Medicine do not, particularly for pregnancies with hypertension or preeclampsia or in those who are at risk for intrauterine growth restriction.

“Gestational diabetes is now reaching epidemic proportions. And of course, the vast majority of these women are in low- and middle-income countries where insulin might not be available, or the storage may not allow it to be used effectively. If you have a medication that in the majority of women is safe and effective it may actually help a lot of women in [those regions],” Dr. Dunne said.

Moreover, she noted, “women with gestational diabetes are testing their sugar with finger pricks four to seven times per day and we ask them to take insulin one to four times a day. So if you can relieve any of that pain related to treatment of their condition than that is a benefit for the women as well.”

Asked to comment, Katrien Benhalima, MD, PhD, of University Hospital Gasthuisberg, KU Leuven, Belgium, said, “I think it’s an interesting study because they investigated something novel, to initiate immediately metformin or placebo. Normally what we do with gestational diabetes is once we get the diagnosis, we treat them with lifestyle, and if that’s insufficient then we start with medical therapy. So this is a novel approach.”

She also agreed with Dr. Dunne that the lack of significance for the primary outcome “isn’t an issue of power but it is a composite outcome. If you look at the individual outcomes, as can be expected, the women taking metformin had less need for insulin treatment.”

But, Dr. Benhalima said, the study still leaves open the SGA issue. “It wasn’t significant, but it’s still something we are worried about in the sense that we feel we need more data, especially in the long-term for the offspring health ... You really need to follow them for 10 years or longer to see an effect.”

So for now, Dr. Benhalima said that she wouldn’t use metformin as a first-line treatment for gestational diabetes. “Normally if lifestyle isn’t enough we will still start insulin ... Another issue is why would you offer everybody medical treatment when pregnancy outcomes can be met with lifestyle alone?”

Then again, she added, “of course metformin is easier than an injection. Treatment satisfaction is improved, and the cost is less.”
 

Primary outcome didn’t differ, but study findings point toward metformin benefit

The double-blind, placebo-controlled trial was conducted at two sites in Ireland, with 510 individuals (535 gestational diabetes pregnancies) enrolled between June 2017 and September 2022. In addition to usual care, they were randomly assigned 1:1 to either placebo or metformin (maximum 2,500 mg) at the time of gestational diabetes diagnosis and continued until delivery.

The primary outcome, a composite of insulin initiation or a fasting glucose ≥ 5.1 mmol/L at gestation weeks 32 or 38, did not differ significantly between the two groups, with risk ratio 0.89 (P = 0.13).

Insulin initiation occurred in 38.4% of the metformin and 51.1% of the placebo groups (relative risk, 0.75, P = .004). The amount of insulin required at the last assessment prior to delivery did not differ between the two groups (P = .17).

Mean fasting glucose was significantly lower with metformin vs. placebo at gestational week 32 (4.9 vs. 5.0 mmol/L; P = .03) and at gestational week 38 (4.5 vs 4.7 mmol/L; P < .001).

On average, those in the metformin group gained less weight between randomization and delivery (0.8 kg vs. 2.0 kg; P = .003).

Gestational week at delivery didn’t differ between the groups, both 39.1 weeks, nor did preterm births prior to 37 weeks’ gestation (9.2% metformin vs. 6.5% placebo; P = .33) or any other pregnancy-related complications.

More participants in the metformin group said that they would choose the drug compared with placebo (76.2% vs. 67.1%, P = .04).

Mean birth weight was lower in the metformin group compared with placebo, 3,393 g vs. 3,506 g (P = .005), with fewer weighing > 4,000 g (7.6% vs. 14.8%; P = .02) or being large for gestational age, i.e., above the 90th percentile (6.5% vs. 14.9%; P = .003).

Proportions of offspring that were SGA (less than 10th percentile) were 5.7% in the metformin group vs. 2.7% with placebo (P = .13).

There were no other significant differences in neonatal variables.

Dr. Dunne told this news organization that her group has recently received funding for long-term follow-up of the SGA offspring. “As other papers have pointed out, if there’s any hint of SGA that’s really important to follow up. So we’re now beginning our longitudinal follow up of the mother and infants to see if the small number that were SGA will in fact turn out to have an increase in body mass index and weight in their childhood and adolescent years.”

The trial was funded by the Health Review Board (HRB) of Ireland, coordinated by the HRB-Clinical Research Facility Galway, and sponsored by the University of Galway, Ireland. Metformin and matched placebo were provided by Merck Healthcare KGaA, Darmstadt, Germany (operating as EMD Serono in the United States), and blood glucose monitoring strips were provided by Ascensia.

Dr. Dunne reported nonfinancial support from Merck and matched placebo and nonfinancial support from Ascensia during the conduct of the study. Dr. Benhalima receives research funds from Flemish Research Fund, study medication from Novo Nordisk, and devices and unrestricted grants from Medtronic and Dexcom.

A version of this article appeared on Medscape.com.

Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.

However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.

Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.

“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.  

The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.

However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.

The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.  

The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”  
 

Caution needed when translating findings into clinical practice

The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.

“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”

The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.

Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.

“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.

She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”

The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.

However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”

There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.

Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.

“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
 

Study design and findings

From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.

Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.

The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).

The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).  

The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.

After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.

About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.

In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).

In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.

The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.

The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).

The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.

The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.

A version of this article appeared on Medscape.com.

Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.

However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.

Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.

“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.  

The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.

However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.

The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.  

The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”  
 

Caution needed when translating findings into clinical practice

The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.

“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”

The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.

Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.

“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.

She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”

The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.

However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”

There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.

Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.

“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
 

Study design and findings

From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.

Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.

The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).

The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).  

The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.

After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.

About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.

In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).

In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.

The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.

The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).

The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.

The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.

A version of this article appeared on Medscape.com.

Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.

However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.

Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.

“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.  

The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.

However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.

The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.  

The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”  
 

Caution needed when translating findings into clinical practice

The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.

“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”

The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.

Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.

“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.

She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”

The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.

However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”

There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.

Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.

“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
 

Study design and findings

From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.

Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.

The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).

The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).  

The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.

After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.

About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.

In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).

In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.

The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.

The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).

The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.

The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.

A version of this article appeared on Medscape.com.

Click to read more from Federal Health Care Data Trends 2023.

Click to read more from Federal Health Care Data Trends 2023.

Click to read more from Federal Health Care Data Trends 2023.