Clinician Reviews

INDIANAPOLIS – In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.

“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

INDIANAPOLIS – In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.

“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

INDIANAPOLIS – In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.

“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

The Diagnosis: Cutaneous Blastomycosis

A skin biopsy and fungal cultures confirmed the diagnosis of cutaneous blastomycosis. Grocott- Gomori methenamine-silver staining highlighted fungal organisms with refractile walls and broad-based budding consistent with cutaneous blastomycosis (Figure 1). The histopathologic specimen also demonstrated marked pseudoepitheliomatous hyperplasia (Figure 2A) with neutrophilic microabscesses (Figure 2B). Acid-fast bacillus and Fite staining were negative for bacterial organisms. A fungal culture was positive for Blastomyces dermatitidis. Urine and serum blastomycosis antigen were positive. Although Histoplasma serum antigen also was positive, this likely was from cross-reactivity. Chest radiography was negative for lung involvement, and the patient displayed no neurologic symptoms. He was started on oral itraconazole therapy for the treatment of cutaneous blastomycosis.

Blastomyces dermatitidis, the causative organism of blastomycosis, is endemic to the Ohio and Mississippi River valleys, Great Lakes region, and southeastern United States. It is a thermally dimorphic fungus found in soils that grows as a mold at 25 °C and yeast at 37 °C. Primary infection of the lungs—blastomycosis pneumonia—often is the only clinical manifestation¹; however, subsequent hematogenous dissemination to extrapulmonary sites such as the skin, bones, and genitourinary system can occur. Cutaneous blastomycosis, the most common extrapulmonary manifestation, typically follows pulmonary infection. In rare cases, it can occur from direct inoculation.^2,3 Skin lesions can occur anywhere but frequently are found on exposed surfaces of the head, neck, and extremities. Lesions classically present as verrucous crusting plaques with draining microabscesses. Violaceous nodules, ulcers, and pustules also may occur.¹

Diagnosis involves obtaining a thorough history of possible environmental exposures such as the patient’s geographic area of residence, occupation, and outdoor activities involving soil or decaying wood. Because blastomycosis can remain latent, remote exposures are relevant. Definitive diagnosis of cutaneous blastomycosis involves skin biopsy of the lesion with fungal culture, but the yeast’s distinctive thick wall and broad-based budding seen with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining provides a rapid presumptive diagnosis.³ Pseudoepitheliomatous hyperplasia and microabscesses also are characteristic features.² Urine antigen testing for a component of the polysaccharide cell wall has a sensitivity of 93% but a lower specificity of 79% due to cross-reactivity with histoplasmosis.⁴ Treatment consists of itraconazole for mild to moderate blastomycosis or amphotericin B for those with severe disease or central nervous system involvement or those who are immunosuppressed.¹

The differential diagnosis for our patient’s lesion included infectious vs neoplastic etiologies. Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, also is endemic to the Ohio and Mississippi River valleys. It is found in soil and droppings of some bats and birds such as chickens and pigeons. Similar to blastomycosis, the primary infection site most commonly is the lungs. It subsequently may disseminate to the skin or less commonly via direct inoculation of injured skin. It can present as papules, plaques, ulcers, purpura, or abscesses. Unlike blastomycosis, tissue biopsy of a cutaneous lesion reveals granuloma formation and distinctive oval, narrow-based budding yeast.⁵ Atypical mycobacteria are another source of infection to consider. For example, cutaneous Mycobacterium kansasii may present as papules and pustules forming verrucous or granulomatous plaques and ulceration. Histopathologic findings distinguishing mycobacterial infection from blastomycosis include granulomas and acid-fast bacilli in histiocytes.⁶

Noninfectious etiologies in the differential may include cutaneous squamous cell carcinoma or pemphigus vegetans. Squamous cell carcinoma may present with a broad range of clinical features—papules, plaques, or nodules with smooth, scaly, verrucous, or ulcerative secondary features all are possible presentations.⁷ Fairskinned individuals, such as our patient, would be at a higher risk in sun-damaged skin. Histologically, cutaneous squamous cell carcinoma is defined as an invasion of the dermis by neoplastic squamous epithelial cells in the form of cords, sheets, individual cells, nodules, or cystic structures.⁷ Pemphigus vegetans is the rarest variant of a group of autoimmune vesiculobullous diseases known as pemphigus. It can be differentiated from the most common variant—pemphigus vulgaris—by the presence of vegetative plaques in intertriginous areas. However, these verrucous vegetations can be misleading and make clinical diagnosis difficult. Histopathologic findings of hyperkeratosis, pseudoepitheliomatous hyperplasia, papillomatosis, and acantholysis with a suprabasal cleft would confirm the diagnosis.⁸

In summary, cutaneous blastomycosis classically presents as verrucous crusting plaques, as seen in our patient. It is important to conduct a thorough history for environmental exposures, but definitive diagnosis of cutaneous blastomycosis involves skin biopsy with fungal culture. Treatment depends on the severity of disease and organ involvement. Itraconazole would be appropriate for mild to moderate blastomycosis.

The Diagnosis: Cutaneous Blastomycosis

A skin biopsy and fungal cultures confirmed the diagnosis of cutaneous blastomycosis. Grocott- Gomori methenamine-silver staining highlighted fungal organisms with refractile walls and broad-based budding consistent with cutaneous blastomycosis (Figure 1). The histopathologic specimen also demonstrated marked pseudoepitheliomatous hyperplasia (Figure 2A) with neutrophilic microabscesses (Figure 2B). Acid-fast bacillus and Fite staining were negative for bacterial organisms. A fungal culture was positive for Blastomyces dermatitidis. Urine and serum blastomycosis antigen were positive. Although Histoplasma serum antigen also was positive, this likely was from cross-reactivity. Chest radiography was negative for lung involvement, and the patient displayed no neurologic symptoms. He was started on oral itraconazole therapy for the treatment of cutaneous blastomycosis.

Blastomyces dermatitidis, the causative organism of blastomycosis, is endemic to the Ohio and Mississippi River valleys, Great Lakes region, and southeastern United States. It is a thermally dimorphic fungus found in soils that grows as a mold at 25 °C and yeast at 37 °C. Primary infection of the lungs—blastomycosis pneumonia—often is the only clinical manifestation¹; however, subsequent hematogenous dissemination to extrapulmonary sites such as the skin, bones, and genitourinary system can occur. Cutaneous blastomycosis, the most common extrapulmonary manifestation, typically follows pulmonary infection. In rare cases, it can occur from direct inoculation.^2,3 Skin lesions can occur anywhere but frequently are found on exposed surfaces of the head, neck, and extremities. Lesions classically present as verrucous crusting plaques with draining microabscesses. Violaceous nodules, ulcers, and pustules also may occur.¹

Diagnosis involves obtaining a thorough history of possible environmental exposures such as the patient’s geographic area of residence, occupation, and outdoor activities involving soil or decaying wood. Because blastomycosis can remain latent, remote exposures are relevant. Definitive diagnosis of cutaneous blastomycosis involves skin biopsy of the lesion with fungal culture, but the yeast’s distinctive thick wall and broad-based budding seen with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining provides a rapid presumptive diagnosis.³ Pseudoepitheliomatous hyperplasia and microabscesses also are characteristic features.² Urine antigen testing for a component of the polysaccharide cell wall has a sensitivity of 93% but a lower specificity of 79% due to cross-reactivity with histoplasmosis.⁴ Treatment consists of itraconazole for mild to moderate blastomycosis or amphotericin B for those with severe disease or central nervous system involvement or those who are immunosuppressed.¹

The differential diagnosis for our patient’s lesion included infectious vs neoplastic etiologies. Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, also is endemic to the Ohio and Mississippi River valleys. It is found in soil and droppings of some bats and birds such as chickens and pigeons. Similar to blastomycosis, the primary infection site most commonly is the lungs. It subsequently may disseminate to the skin or less commonly via direct inoculation of injured skin. It can present as papules, plaques, ulcers, purpura, or abscesses. Unlike blastomycosis, tissue biopsy of a cutaneous lesion reveals granuloma formation and distinctive oval, narrow-based budding yeast.⁵ Atypical mycobacteria are another source of infection to consider. For example, cutaneous Mycobacterium kansasii may present as papules and pustules forming verrucous or granulomatous plaques and ulceration. Histopathologic findings distinguishing mycobacterial infection from blastomycosis include granulomas and acid-fast bacilli in histiocytes.⁶

Noninfectious etiologies in the differential may include cutaneous squamous cell carcinoma or pemphigus vegetans. Squamous cell carcinoma may present with a broad range of clinical features—papules, plaques, or nodules with smooth, scaly, verrucous, or ulcerative secondary features all are possible presentations.⁷ Fairskinned individuals, such as our patient, would be at a higher risk in sun-damaged skin. Histologically, cutaneous squamous cell carcinoma is defined as an invasion of the dermis by neoplastic squamous epithelial cells in the form of cords, sheets, individual cells, nodules, or cystic structures.⁷ Pemphigus vegetans is the rarest variant of a group of autoimmune vesiculobullous diseases known as pemphigus. It can be differentiated from the most common variant—pemphigus vulgaris—by the presence of vegetative plaques in intertriginous areas. However, these verrucous vegetations can be misleading and make clinical diagnosis difficult. Histopathologic findings of hyperkeratosis, pseudoepitheliomatous hyperplasia, papillomatosis, and acantholysis with a suprabasal cleft would confirm the diagnosis.⁸

In summary, cutaneous blastomycosis classically presents as verrucous crusting plaques, as seen in our patient. It is important to conduct a thorough history for environmental exposures, but definitive diagnosis of cutaneous blastomycosis involves skin biopsy with fungal culture. Treatment depends on the severity of disease and organ involvement. Itraconazole would be appropriate for mild to moderate blastomycosis.

The Diagnosis: Cutaneous Blastomycosis

A skin biopsy and fungal cultures confirmed the diagnosis of cutaneous blastomycosis. Grocott- Gomori methenamine-silver staining highlighted fungal organisms with refractile walls and broad-based budding consistent with cutaneous blastomycosis (Figure 1). The histopathologic specimen also demonstrated marked pseudoepitheliomatous hyperplasia (Figure 2A) with neutrophilic microabscesses (Figure 2B). Acid-fast bacillus and Fite staining were negative for bacterial organisms. A fungal culture was positive for Blastomyces dermatitidis. Urine and serum blastomycosis antigen were positive. Although Histoplasma serum antigen also was positive, this likely was from cross-reactivity. Chest radiography was negative for lung involvement, and the patient displayed no neurologic symptoms. He was started on oral itraconazole therapy for the treatment of cutaneous blastomycosis.

Blastomyces dermatitidis, the causative organism of blastomycosis, is endemic to the Ohio and Mississippi River valleys, Great Lakes region, and southeastern United States. It is a thermally dimorphic fungus found in soils that grows as a mold at 25 °C and yeast at 37 °C. Primary infection of the lungs—blastomycosis pneumonia—often is the only clinical manifestation¹; however, subsequent hematogenous dissemination to extrapulmonary sites such as the skin, bones, and genitourinary system can occur. Cutaneous blastomycosis, the most common extrapulmonary manifestation, typically follows pulmonary infection. In rare cases, it can occur from direct inoculation.^2,3 Skin lesions can occur anywhere but frequently are found on exposed surfaces of the head, neck, and extremities. Lesions classically present as verrucous crusting plaques with draining microabscesses. Violaceous nodules, ulcers, and pustules also may occur.¹

Diagnosis involves obtaining a thorough history of possible environmental exposures such as the patient’s geographic area of residence, occupation, and outdoor activities involving soil or decaying wood. Because blastomycosis can remain latent, remote exposures are relevant. Definitive diagnosis of cutaneous blastomycosis involves skin biopsy of the lesion with fungal culture, but the yeast’s distinctive thick wall and broad-based budding seen with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining provides a rapid presumptive diagnosis.³ Pseudoepitheliomatous hyperplasia and microabscesses also are characteristic features.² Urine antigen testing for a component of the polysaccharide cell wall has a sensitivity of 93% but a lower specificity of 79% due to cross-reactivity with histoplasmosis.⁴ Treatment consists of itraconazole for mild to moderate blastomycosis or amphotericin B for those with severe disease or central nervous system involvement or those who are immunosuppressed.¹

The differential diagnosis for our patient’s lesion included infectious vs neoplastic etiologies. Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, also is endemic to the Ohio and Mississippi River valleys. It is found in soil and droppings of some bats and birds such as chickens and pigeons. Similar to blastomycosis, the primary infection site most commonly is the lungs. It subsequently may disseminate to the skin or less commonly via direct inoculation of injured skin. It can present as papules, plaques, ulcers, purpura, or abscesses. Unlike blastomycosis, tissue biopsy of a cutaneous lesion reveals granuloma formation and distinctive oval, narrow-based budding yeast.⁵ Atypical mycobacteria are another source of infection to consider. For example, cutaneous Mycobacterium kansasii may present as papules and pustules forming verrucous or granulomatous plaques and ulceration. Histopathologic findings distinguishing mycobacterial infection from blastomycosis include granulomas and acid-fast bacilli in histiocytes.⁶

Noninfectious etiologies in the differential may include cutaneous squamous cell carcinoma or pemphigus vegetans. Squamous cell carcinoma may present with a broad range of clinical features—papules, plaques, or nodules with smooth, scaly, verrucous, or ulcerative secondary features all are possible presentations.⁷ Fairskinned individuals, such as our patient, would be at a higher risk in sun-damaged skin. Histologically, cutaneous squamous cell carcinoma is defined as an invasion of the dermis by neoplastic squamous epithelial cells in the form of cords, sheets, individual cells, nodules, or cystic structures.⁷ Pemphigus vegetans is the rarest variant of a group of autoimmune vesiculobullous diseases known as pemphigus. It can be differentiated from the most common variant—pemphigus vulgaris—by the presence of vegetative plaques in intertriginous areas. However, these verrucous vegetations can be misleading and make clinical diagnosis difficult. Histopathologic findings of hyperkeratosis, pseudoepitheliomatous hyperplasia, papillomatosis, and acantholysis with a suprabasal cleft would confirm the diagnosis.⁸

In summary, cutaneous blastomycosis classically presents as verrucous crusting plaques, as seen in our patient. It is important to conduct a thorough history for environmental exposures, but definitive diagnosis of cutaneous blastomycosis involves skin biopsy with fungal culture. Treatment depends on the severity of disease and organ involvement. Itraconazole would be appropriate for mild to moderate blastomycosis.

Anxiety over the U.S. economy intensified in June, with 87% of Americans reporting they are anxious or very anxious about inflation, up eight percentage points from the previous month, results from a new national report from the American Psychiatric Association show.

“The economy seems to have supplanted COVID as a major factor in Americans’ day-to-day anxiety,” APA President Rebecca W. Brendel, MD, JD, said in a news release.

“Knowing that so many Americans are concerned about finances is important because it can prepare clinicians to be ready to approach the subject, which is one that people are often reluctant or ashamed to raise on their own,” Dr. Brendel told this news organization.

What’s the best way to bring up the sensitive topic of money?

“In general, it’s best to start with open-ended questions to allow individuals in therapy to share what is on their minds, explore their concerns, and develop strategies to address these issues. Once a patient raises a concern, that is a good time to ask more about the issues they’ve raised and to explore other potential sources of anxiety or stress,” said Dr. Brendel.

The latest APA poll was conducted by Morning Consult, June 18-20, 2022, among a nationally representative sample of 2,210 adults.

In addition to an uptick in worry about inflation, the poll shows that more than half (51%) of adults are worried about a potential loss of income.

Hispanic adults (66%), mothers (65%), millennials (63%), and genZers (62%) are among the groups most likely to be concerned about income loss.

“Stress is not good for health, mental or physical. So, while it’s a reality that Americans are faced with finding ways of making ends meet, it’s more important than ever to make sure that we are all accessing the care that we need,” said Dr. Brendel.

“People should be aware that there may be low- or no-cost options such as community mental health centers or employer-sponsored resources to address mental health concerns,” she added.
 

Coping with traumatic events

The latest poll also shows that about one-third of adults are worried about gun violence (35% overall, 47% among genZers) or a natural disaster (29%) personally affecting them.

Climate change anxiety is also up slightly in June, compared with May (+4%).

The same goes for mid-term election-related anxiety (+3%) – particularly among Democrats (54% vs. 59%) compared with Republicans (48% vs. 48%).

The latest poll provides insight how Americans would cope after a traumatic event. More adults report they will turn to family and friends for support (60%) than practice self-care (42%), speak openly about their feelings (37%), or seek help from a professional (31%). Nearly one-third (30%) say they will move on from it and not dwell on their feelings.

GenZers are the least likely to say they will speak openly about their feelings (29%) and are less likely than millennials to say they would speak to a health professional (28% vs. 38%).

“While many people show resilience, it’s troubling that most Americans wouldn’t speak openly about their feelings after a traumatic event,” APA CEO and Medical Director Saul Levin, MD, said in the news release.

“In many ways, naming feelings is the most important step toward healing, and this reluctance to air our thoughts may indicate that mental health stigma is still a powerful force in our society,” Dr. Levin said.

After a traumatic current event, 41% of Americans say they consume more news and 30% say they take in more social media, but the majority say this does not impact their mental health, the poll shows.

Two in five adults (43%) say the news of a traumatic event makes them feel more informed, 32% say it makes them feel more anxious, and about one-quarter say it makes them feel overwhelmed (27%) or discouraged (24%).

Dr. Brendel noted that, after a traumatic event, “it’s expected that people may experience anxiety or other symptoms for brief periods of time. However, no two people experience things the same way. If symptoms don’t go away, are overwhelming, or get worse over time, for example, it’s critical to seek help right away.”

The June poll shows that 50% of Americans are anxious about the future of reproductive rights but the poll was conducted before the Dobbs ruling.

Anxiety around COVID-19 continues to ease, with about 47% of Americans saying they are concerned about the pandemic, down 2% among all Americans and 16% among Black Americans since May.

The APA’s Healthy Minds Monthly tracks timely mental health issues throughout the year. The APA also releases its annual Healthy Minds Poll each May in conjunction with Mental Health Awareness Month.

A version of this article first appeared on Medscape.com.

Anxiety over the U.S. economy intensified in June, with 87% of Americans reporting they are anxious or very anxious about inflation, up eight percentage points from the previous month, results from a new national report from the American Psychiatric Association show.

“The economy seems to have supplanted COVID as a major factor in Americans’ day-to-day anxiety,” APA President Rebecca W. Brendel, MD, JD, said in a news release.

“Knowing that so many Americans are concerned about finances is important because it can prepare clinicians to be ready to approach the subject, which is one that people are often reluctant or ashamed to raise on their own,” Dr. Brendel told this news organization.

What’s the best way to bring up the sensitive topic of money?

“In general, it’s best to start with open-ended questions to allow individuals in therapy to share what is on their minds, explore their concerns, and develop strategies to address these issues. Once a patient raises a concern, that is a good time to ask more about the issues they’ve raised and to explore other potential sources of anxiety or stress,” said Dr. Brendel.

The latest APA poll was conducted by Morning Consult, June 18-20, 2022, among a nationally representative sample of 2,210 adults.

In addition to an uptick in worry about inflation, the poll shows that more than half (51%) of adults are worried about a potential loss of income.

Hispanic adults (66%), mothers (65%), millennials (63%), and genZers (62%) are among the groups most likely to be concerned about income loss.

“Stress is not good for health, mental or physical. So, while it’s a reality that Americans are faced with finding ways of making ends meet, it’s more important than ever to make sure that we are all accessing the care that we need,” said Dr. Brendel.

“People should be aware that there may be low- or no-cost options such as community mental health centers or employer-sponsored resources to address mental health concerns,” she added.
 

Coping with traumatic events

The latest poll also shows that about one-third of adults are worried about gun violence (35% overall, 47% among genZers) or a natural disaster (29%) personally affecting them.

Climate change anxiety is also up slightly in June, compared with May (+4%).

The same goes for mid-term election-related anxiety (+3%) – particularly among Democrats (54% vs. 59%) compared with Republicans (48% vs. 48%).

The latest poll provides insight how Americans would cope after a traumatic event. More adults report they will turn to family and friends for support (60%) than practice self-care (42%), speak openly about their feelings (37%), or seek help from a professional (31%). Nearly one-third (30%) say they will move on from it and not dwell on their feelings.

GenZers are the least likely to say they will speak openly about their feelings (29%) and are less likely than millennials to say they would speak to a health professional (28% vs. 38%).

“While many people show resilience, it’s troubling that most Americans wouldn’t speak openly about their feelings after a traumatic event,” APA CEO and Medical Director Saul Levin, MD, said in the news release.

“In many ways, naming feelings is the most important step toward healing, and this reluctance to air our thoughts may indicate that mental health stigma is still a powerful force in our society,” Dr. Levin said.

After a traumatic current event, 41% of Americans say they consume more news and 30% say they take in more social media, but the majority say this does not impact their mental health, the poll shows.

Two in five adults (43%) say the news of a traumatic event makes them feel more informed, 32% say it makes them feel more anxious, and about one-quarter say it makes them feel overwhelmed (27%) or discouraged (24%).

Dr. Brendel noted that, after a traumatic event, “it’s expected that people may experience anxiety or other symptoms for brief periods of time. However, no two people experience things the same way. If symptoms don’t go away, are overwhelming, or get worse over time, for example, it’s critical to seek help right away.”

The June poll shows that 50% of Americans are anxious about the future of reproductive rights but the poll was conducted before the Dobbs ruling.

Anxiety around COVID-19 continues to ease, with about 47% of Americans saying they are concerned about the pandemic, down 2% among all Americans and 16% among Black Americans since May.

The APA’s Healthy Minds Monthly tracks timely mental health issues throughout the year. The APA also releases its annual Healthy Minds Poll each May in conjunction with Mental Health Awareness Month.

A version of this article first appeared on Medscape.com.

Anxiety over the U.S. economy intensified in June, with 87% of Americans reporting they are anxious or very anxious about inflation, up eight percentage points from the previous month, results from a new national report from the American Psychiatric Association show.

“The economy seems to have supplanted COVID as a major factor in Americans’ day-to-day anxiety,” APA President Rebecca W. Brendel, MD, JD, said in a news release.

“Knowing that so many Americans are concerned about finances is important because it can prepare clinicians to be ready to approach the subject, which is one that people are often reluctant or ashamed to raise on their own,” Dr. Brendel told this news organization.

What’s the best way to bring up the sensitive topic of money?

“In general, it’s best to start with open-ended questions to allow individuals in therapy to share what is on their minds, explore their concerns, and develop strategies to address these issues. Once a patient raises a concern, that is a good time to ask more about the issues they’ve raised and to explore other potential sources of anxiety or stress,” said Dr. Brendel.

The latest APA poll was conducted by Morning Consult, June 18-20, 2022, among a nationally representative sample of 2,210 adults.

In addition to an uptick in worry about inflation, the poll shows that more than half (51%) of adults are worried about a potential loss of income.

Hispanic adults (66%), mothers (65%), millennials (63%), and genZers (62%) are among the groups most likely to be concerned about income loss.

“Stress is not good for health, mental or physical. So, while it’s a reality that Americans are faced with finding ways of making ends meet, it’s more important than ever to make sure that we are all accessing the care that we need,” said Dr. Brendel.

“People should be aware that there may be low- or no-cost options such as community mental health centers or employer-sponsored resources to address mental health concerns,” she added.
 

Coping with traumatic events

The latest poll also shows that about one-third of adults are worried about gun violence (35% overall, 47% among genZers) or a natural disaster (29%) personally affecting them.

Climate change anxiety is also up slightly in June, compared with May (+4%).

The same goes for mid-term election-related anxiety (+3%) – particularly among Democrats (54% vs. 59%) compared with Republicans (48% vs. 48%).

The latest poll provides insight how Americans would cope after a traumatic event. More adults report they will turn to family and friends for support (60%) than practice self-care (42%), speak openly about their feelings (37%), or seek help from a professional (31%). Nearly one-third (30%) say they will move on from it and not dwell on their feelings.

GenZers are the least likely to say they will speak openly about their feelings (29%) and are less likely than millennials to say they would speak to a health professional (28% vs. 38%).

“While many people show resilience, it’s troubling that most Americans wouldn’t speak openly about their feelings after a traumatic event,” APA CEO and Medical Director Saul Levin, MD, said in the news release.

“In many ways, naming feelings is the most important step toward healing, and this reluctance to air our thoughts may indicate that mental health stigma is still a powerful force in our society,” Dr. Levin said.

After a traumatic current event, 41% of Americans say they consume more news and 30% say they take in more social media, but the majority say this does not impact their mental health, the poll shows.

Two in five adults (43%) say the news of a traumatic event makes them feel more informed, 32% say it makes them feel more anxious, and about one-quarter say it makes them feel overwhelmed (27%) or discouraged (24%).

Dr. Brendel noted that, after a traumatic event, “it’s expected that people may experience anxiety or other symptoms for brief periods of time. However, no two people experience things the same way. If symptoms don’t go away, are overwhelming, or get worse over time, for example, it’s critical to seek help right away.”

The June poll shows that 50% of Americans are anxious about the future of reproductive rights but the poll was conducted before the Dobbs ruling.

Anxiety around COVID-19 continues to ease, with about 47% of Americans saying they are concerned about the pandemic, down 2% among all Americans and 16% among Black Americans since May.

The APA’s Healthy Minds Monthly tracks timely mental health issues throughout the year. The APA also releases its annual Healthy Minds Poll each May in conjunction with Mental Health Awareness Month.

A version of this article first appeared on Medscape.com.

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

A version of this article first appeared on Medscape.com.

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

A version of this article first appeared on Medscape.com.

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

A version of this article first appeared on Medscape.com.

Two drugs have emerged as the optimal medications for treating insomnia based on the “best-available evidence,” but there are caveats.

In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.

However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.

Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.

For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.

“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.

The findings were published online  in The Lancet.
 

Prevalent, debilitating

Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.

Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.

However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.

In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).

Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).

In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).

“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
 

Best available evidence

What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.

“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.

Another problem was lack of data on other important outcomes, they add.  

“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.

Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”

They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”

In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
 

Shared decisionmaking

In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.  

“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.  

The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two drugs have emerged as the optimal medications for treating insomnia based on the “best-available evidence,” but there are caveats.

In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.

However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.

Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.

For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.

“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.

The findings were published online  in The Lancet.
 

Prevalent, debilitating

Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.

Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.

However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.

In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).

Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).

In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).

“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
 

Best available evidence

What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.

“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.

Another problem was lack of data on other important outcomes, they add.  

“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.

Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”

They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”

In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
 

Shared decisionmaking

In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.  

“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.  

The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two drugs have emerged as the optimal medications for treating insomnia based on the “best-available evidence,” but there are caveats.

In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.

However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.

Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.

For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.

“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.

The findings were published online  in The Lancet.
 

Prevalent, debilitating

Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.

Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.

However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.

In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).

Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).

In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).

“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
 

Best available evidence

What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.

“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.

Another problem was lack of data on other important outcomes, they add.  

“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.

Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”

They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”

In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
 

Shared decisionmaking

In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.  

“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.  

The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.

But a new analysis by ABC News shows that more and more Americans are getting the virus again.

It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.

“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.

The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.

Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.

But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.

Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.

The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.

A version of this article first appeared on WebMD.com.

When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.

But a new analysis by ABC News shows that more and more Americans are getting the virus again.

It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.

“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.

The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.

Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.

But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.

Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.

The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.

A version of this article first appeared on WebMD.com.

When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.

But a new analysis by ABC News shows that more and more Americans are getting the virus again.

It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.

“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.

The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.

Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.

But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.

Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.

The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.

A version of this article first appeared on WebMD.com.

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.