Topical hypochlorous acid is an underutilized tool in the management of atopic dermatitis (AD), Joseph F. Fowler, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“I definitely like hypochlorous acid products to reduce microbial load and improve itching,” said Dr. Fowler, a dermatologist at the University of Louisville (Ky.). “It’s certainly a useful adjunct – not your primary treatment – in managing atopic dermatitis, especially when infected.”

Topical stabilized hypochlorous acid for use on the skin is commercially available over the counter in gel and liquid spray forms. It’s not bleach, which is sodium hypochlorite. In fact, for use on the skin, hypochlorous acid is better than bleach, since it doesn’t stain dark clothes, it’s nonirritating, and it doesn’t smell like bleach.

“We’re not entirely sure why it has an anti-itch effect, but that might partly be due to its inhibition of mast cell degranulation. It stops the mast cell from releasing its itch-o-genic properties into the skin. It also inhibits phospholipase A2, resulting in reduction of leukotrienes and prostaglandins, which may also account for the anti-itch effect,” Dr. Fowler said.

Hypochlorous acid has a powerful antimicrobial effect. It is highly effective at rapidly killing a broad range of bacteria, viruses, and fungi, including Staphylococcus aureus, a pathogen of particular relevance in AD. After the Environmental Protection Agency added hypochlorous acid to its list of disinfectants known to be effective against coronavirus, commercial interest in the use of hypochlorous acid in higher concentrations as a disinfectant in office buildings, hospitals, and for other large-scale applications has ballooned. The product, made via a process involving electrolyzation of water, is inexpensive. It’s also nontoxic: It’s not perceived by the immune system as foreign, since hypochlorous acid is produced during the human innate immune response.

Dr. Fowler reported serving as a consultant to and on the speakers bureau for SmartPractice, and receiving research funding from Asana, Edesa Biotech, J&J, and Novartis.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Topical hypochlorous acid is an underutilized tool in the management of atopic dermatitis (AD), Joseph F. Fowler, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“I definitely like hypochlorous acid products to reduce microbial load and improve itching,” said Dr. Fowler, a dermatologist at the University of Louisville (Ky.). “It’s certainly a useful adjunct – not your primary treatment – in managing atopic dermatitis, especially when infected.”

Topical stabilized hypochlorous acid for use on the skin is commercially available over the counter in gel and liquid spray forms. It’s not bleach, which is sodium hypochlorite. In fact, for use on the skin, hypochlorous acid is better than bleach, since it doesn’t stain dark clothes, it’s nonirritating, and it doesn’t smell like bleach.

“We’re not entirely sure why it has an anti-itch effect, but that might partly be due to its inhibition of mast cell degranulation. It stops the mast cell from releasing its itch-o-genic properties into the skin. It also inhibits phospholipase A2, resulting in reduction of leukotrienes and prostaglandins, which may also account for the anti-itch effect,” Dr. Fowler said.

Hypochlorous acid has a powerful antimicrobial effect. It is highly effective at rapidly killing a broad range of bacteria, viruses, and fungi, including Staphylococcus aureus, a pathogen of particular relevance in AD. After the Environmental Protection Agency added hypochlorous acid to its list of disinfectants known to be effective against coronavirus, commercial interest in the use of hypochlorous acid in higher concentrations as a disinfectant in office buildings, hospitals, and for other large-scale applications has ballooned. The product, made via a process involving electrolyzation of water, is inexpensive. It’s also nontoxic: It’s not perceived by the immune system as foreign, since hypochlorous acid is produced during the human innate immune response.

Dr. Fowler reported serving as a consultant to and on the speakers bureau for SmartPractice, and receiving research funding from Asana, Edesa Biotech, J&J, and Novartis.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Topical hypochlorous acid is an underutilized tool in the management of atopic dermatitis (AD), Joseph F. Fowler, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“I definitely like hypochlorous acid products to reduce microbial load and improve itching,” said Dr. Fowler, a dermatologist at the University of Louisville (Ky.). “It’s certainly a useful adjunct – not your primary treatment – in managing atopic dermatitis, especially when infected.”

Topical stabilized hypochlorous acid for use on the skin is commercially available over the counter in gel and liquid spray forms. It’s not bleach, which is sodium hypochlorite. In fact, for use on the skin, hypochlorous acid is better than bleach, since it doesn’t stain dark clothes, it’s nonirritating, and it doesn’t smell like bleach.

“We’re not entirely sure why it has an anti-itch effect, but that might partly be due to its inhibition of mast cell degranulation. It stops the mast cell from releasing its itch-o-genic properties into the skin. It also inhibits phospholipase A2, resulting in reduction of leukotrienes and prostaglandins, which may also account for the anti-itch effect,” Dr. Fowler said.

Hypochlorous acid has a powerful antimicrobial effect. It is highly effective at rapidly killing a broad range of bacteria, viruses, and fungi, including Staphylococcus aureus, a pathogen of particular relevance in AD. After the Environmental Protection Agency added hypochlorous acid to its list of disinfectants known to be effective against coronavirus, commercial interest in the use of hypochlorous acid in higher concentrations as a disinfectant in office buildings, hospitals, and for other large-scale applications has ballooned. The product, made via a process involving electrolyzation of water, is inexpensive. It’s also nontoxic: It’s not perceived by the immune system as foreign, since hypochlorous acid is produced during the human innate immune response.

Dr. Fowler reported serving as a consultant to and on the speakers bureau for SmartPractice, and receiving research funding from Asana, Edesa Biotech, J&J, and Novartis.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

In women, breast cancer is the leading cancer diagnosis and the second leading cause of cancer-related death,¹ as well as the most common malignancy to metastasize to the skin.² Cutaneous breast carcinoma may present as cutaneous metastasis or can occur secondary to direct tumor extension. Five percent to 10% of women with breast cancer will present clinically with metastatic cutaneous disease, most commonly as a recurrence of early-stage breast carcinoma.²

In a published meta-analysis that investigated the incidence of tumors most commonly found to metastasize to the skin, Krathen et al³ found that cutaneous metastases occurred in 24% of patients with breast cancer (N=1903). In 2 large retrospective studies from tumor registry data, breast cancer was found to be the most common tumor involving metastasis to the skin, and 3.5% of the breast cancer cases identified in the registry had cutaneous metastasis as the presenting sign (n=35) at time of diagnosis.⁴

We report an unusual presentation of cutaneous metastatic lobular breast carcinoma that involved diffuse cutaneous lesions and rapid progression from onset of the breast mass to development of clinically apparent metastatic skin lesions.

Case Report

A 59-year-old woman with an unremarkable medical history presented to our dermatology clinic for evaluation of new widespread lesions that developed over a period of months. The eruption was asymptomatic and consisted of numerous bumpy lesions that reportedly started on the patient’s neck and progressively spread to involve the trunk. Physical examination revealed multiple flesh-colored, firm nodules scattered across the upper back, neck, and chest (Figure 1). Bilateral cervical and axillary lymphadenopathy also was noted. Upon questioning regarding family history of malignancy, the patient reported that her brother had been diagnosed with colon cancer. Although she was not up to date on age-appropriate malignancy screenings, she did report having a diagnostic mammogram 1 year prior that revealed a suspicious lesion on the left breast. A repeat mammogram of the left breast 6 months later was read as unremarkable.

Two 3-mm representative punch biopsies were performed. Hematoxylin and eosin staining revealed a basket-weave stratum corneum with underlying epidermal atrophy. A relatively monomorphic epithelioid cell infiltrate extending from the superficial reticular dermis into the deep dermis and displaying an open chromatin pattern and pink cytoplasm was observed, as well as dermal collagen thickening. Linear, single-filing cells along with focal irregular nests and scattered cells were observed (Figure 2). Immunohistochemical staining was positive for cytokeratin 7 (Figure 3A), epithelial membrane antigen, and estrogen receptor (Figure 3B) along with gross cystic disease fluid protein 15; focal progesterone receptor positivity also was present. Cytokeratin 20, cytokeratin 5/6, carcinoembryonic antigen, p63, CDX2, paired box gene 8, thyroid transcription factor 1, and human epidermal growth factor receptor 2/neu stains were negative. Findings identified in both biopsies were consistent with metastatic cutaneous lobular breast carcinoma.

A complete blood cell count and complete metabolic panels were within normal limits, aside from a mildly elevated alkaline phosphatase level. Breast ultrasonography was unremarkable. Stereotactic breast magnetic resonance imaging (MRI) revealed a 9.4-cm mass in the upper outer quadrant of the right breast as well as enlarged lymph nodes 2.2 cm from the left axilla. A subsequent bone scan demonstrated focal activity in the left lateral fourth rib, left costochondral junction, and right anterolateral fifth rib—it was unclear whether these lesions were metastatic or secondary to trauma from a fall the patient reportedly had sustained 2 weeks prior. Lumbar MRI without gadolinium contrast revealed extensive abnormal heterogeneous signal intensity of osseous structures consistent with osseous metastasis.

Subsequent diagnostic bilateral breast ultrasonography and percutaneous left lymph node biopsy revealed pathology consistent with metastatic lobular breast carcinoma with near total effacement of the lymph node and extracapsular extension concordant with previous MRI findings. The mass in the upper outer quadrant of the right breast that previously was observed on MRI was not identifiable on this ultrasound. It was recommended that the patient pursue MRI-guided breast biopsy to have the breast lesion further characterized. She was referred to surgical oncology at a tertiary center for management; however, the patient was lost to follow-up, and there are no records available indicating the patient pursued any treatment. Although we were unable to confirm the patient’s breast lesion that previously was seen on MRI was the cause of the metastatic disease, the overall clinical picture supported metastatic lobular breast carcinoma.

Comment

Tumor metastasis to the skin accounts for approximately 2% of all skin cancers⁵ and typically is observed in advanced stages of cancer. In women, breast carcinoma is the most common type of cancer to exhibit this behavior.² Invasive ductal carcinoma represents the most common histologic subtype of breast cancer overall,^6,7 and breast adenocarcinomas, including lobular and ductal breast carcinomas, are the most common histologic subtypes to exhibit metastatic cutaneous lesions.⁸

Invasive lobular breast carcinoma represents approximately 10% of invasive breast cancer cases. Compared to invasive ductal carcinoma, there tends to be a delay in diagnosis often leading to larger tumor sizes relative to the former upon detection and with lymph node invasion. These findings may be explained by the greater difficulty of detecting invasive lobular carcinomas by mammography and clinical breast examination compared to invasive ductal carcinomas.^9-11 Additionally, invasive lobular carcinomas are more likely to be positive for estrogen and progesterone receptors compared to invasive ductal carcinomas,¹² which also was consistent in our case.

Cutaneous metastases of breast cancer most commonly are found on the anterior chest wall and can present as a wide spectrum of lesions, with nodules as the most common primary dermatologic manifestation.¹³ Cutaneous metastatic lesions commonly have been described as firm, mobile, round or oval, solitary or grouped nodules. The color of the nodules varies and may be flesh-colored, brown, blue, black, pink, and/or red-brown. The lesions often are asymptomatic but may ulcerate.²

In our case, the distribution of lesions was a unique aspect that is not typical of most cases of metastatic cutaneous breast carcinoma. The nodules appeared more scattered and involved multiple body regions, including the back, neck, and chest. Although cutaneous breast cancer metastases have been documented to extend to these body regions, a review of PubMed articles indexed for MEDLINE using the terms cutaneous metastatic lobular breast carcinoma, breast carcinoma, and metastatic breast cancer suggested that it is uncommon for these multiple areas to be simultaneously affected.^4,14 Rather, the more common clinical presentation of cutaneous metastatic breast carcinoma is as a solitary nodule or group of nodules localized to a single anatomic region.¹⁴

Another notable feature of our case was the rapid development of the cutaneous lesions relative to the primary tumor. This patient developed diffuse lesions over a period of several months, and given that her mammogram performed the previous year was negative for any abnormalities, one could suggest that the metastatic lesions developed less than a year from onset of the primary tumor. A previous study involving 41 patients with a known clinical primary visceral malignancy (ie, breast, lung, colon, esophageal, gastric, pancreatic, kidney, thyroid, prostate, or ovarian origin) found that it takes approximately 3 years on average for cutaneous metastases to develop from the onset of cancer diagnosis (range, 1–177 months).¹⁴ In the aforementioned study, 94% of patients had stage III or IV disease at time of skin metastasis, with the majority of those demonstrating stage IV disease. However, it also is possible that these breast tumors evaded detection or were too small to be identified on prior imaging.¹⁴ A review of our patient’s medical records did not indicate documentation of any visual or palpable breast changes prior to the onset of the clinically detected metastatic nodules.

Conclusion

Biopsy with immunohistochemical staining ultimately yielded the diagnosis of metastatic lobular breast carcinoma in our patient. Providers should be aware of the varying clinical presentations that may arise in the setting of cutaneous metastasis. When faced with lesions suspicious for cutaneous metastasis, biopsy is warranted to determine the correct diagnosis and ensure appropriate management. Upon diagnosis of cutaneous metastasis, prompt coordination with the primary care provider and appropriate referral to multidisciplinary teams is necessary. Clinical providers also should maintain a high index of suspicion when evaluating patients with cutaneous metastasis who have a history of normal malignancy screenings.

In women, breast cancer is the leading cancer diagnosis and the second leading cause of cancer-related death,¹ as well as the most common malignancy to metastasize to the skin.² Cutaneous breast carcinoma may present as cutaneous metastasis or can occur secondary to direct tumor extension. Five percent to 10% of women with breast cancer will present clinically with metastatic cutaneous disease, most commonly as a recurrence of early-stage breast carcinoma.²

In a published meta-analysis that investigated the incidence of tumors most commonly found to metastasize to the skin, Krathen et al³ found that cutaneous metastases occurred in 24% of patients with breast cancer (N=1903). In 2 large retrospective studies from tumor registry data, breast cancer was found to be the most common tumor involving metastasis to the skin, and 3.5% of the breast cancer cases identified in the registry had cutaneous metastasis as the presenting sign (n=35) at time of diagnosis.⁴

We report an unusual presentation of cutaneous metastatic lobular breast carcinoma that involved diffuse cutaneous lesions and rapid progression from onset of the breast mass to development of clinically apparent metastatic skin lesions.

Case Report

A 59-year-old woman with an unremarkable medical history presented to our dermatology clinic for evaluation of new widespread lesions that developed over a period of months. The eruption was asymptomatic and consisted of numerous bumpy lesions that reportedly started on the patient’s neck and progressively spread to involve the trunk. Physical examination revealed multiple flesh-colored, firm nodules scattered across the upper back, neck, and chest (Figure 1). Bilateral cervical and axillary lymphadenopathy also was noted. Upon questioning regarding family history of malignancy, the patient reported that her brother had been diagnosed with colon cancer. Although she was not up to date on age-appropriate malignancy screenings, she did report having a diagnostic mammogram 1 year prior that revealed a suspicious lesion on the left breast. A repeat mammogram of the left breast 6 months later was read as unremarkable.

Two 3-mm representative punch biopsies were performed. Hematoxylin and eosin staining revealed a basket-weave stratum corneum with underlying epidermal atrophy. A relatively monomorphic epithelioid cell infiltrate extending from the superficial reticular dermis into the deep dermis and displaying an open chromatin pattern and pink cytoplasm was observed, as well as dermal collagen thickening. Linear, single-filing cells along with focal irregular nests and scattered cells were observed (Figure 2). Immunohistochemical staining was positive for cytokeratin 7 (Figure 3A), epithelial membrane antigen, and estrogen receptor (Figure 3B) along with gross cystic disease fluid protein 15; focal progesterone receptor positivity also was present. Cytokeratin 20, cytokeratin 5/6, carcinoembryonic antigen, p63, CDX2, paired box gene 8, thyroid transcription factor 1, and human epidermal growth factor receptor 2/neu stains were negative. Findings identified in both biopsies were consistent with metastatic cutaneous lobular breast carcinoma.

A complete blood cell count and complete metabolic panels were within normal limits, aside from a mildly elevated alkaline phosphatase level. Breast ultrasonography was unremarkable. Stereotactic breast magnetic resonance imaging (MRI) revealed a 9.4-cm mass in the upper outer quadrant of the right breast as well as enlarged lymph nodes 2.2 cm from the left axilla. A subsequent bone scan demonstrated focal activity in the left lateral fourth rib, left costochondral junction, and right anterolateral fifth rib—it was unclear whether these lesions were metastatic or secondary to trauma from a fall the patient reportedly had sustained 2 weeks prior. Lumbar MRI without gadolinium contrast revealed extensive abnormal heterogeneous signal intensity of osseous structures consistent with osseous metastasis.

Subsequent diagnostic bilateral breast ultrasonography and percutaneous left lymph node biopsy revealed pathology consistent with metastatic lobular breast carcinoma with near total effacement of the lymph node and extracapsular extension concordant with previous MRI findings. The mass in the upper outer quadrant of the right breast that previously was observed on MRI was not identifiable on this ultrasound. It was recommended that the patient pursue MRI-guided breast biopsy to have the breast lesion further characterized. She was referred to surgical oncology at a tertiary center for management; however, the patient was lost to follow-up, and there are no records available indicating the patient pursued any treatment. Although we were unable to confirm the patient’s breast lesion that previously was seen on MRI was the cause of the metastatic disease, the overall clinical picture supported metastatic lobular breast carcinoma.

Comment

Tumor metastasis to the skin accounts for approximately 2% of all skin cancers⁵ and typically is observed in advanced stages of cancer. In women, breast carcinoma is the most common type of cancer to exhibit this behavior.² Invasive ductal carcinoma represents the most common histologic subtype of breast cancer overall,^6,7 and breast adenocarcinomas, including lobular and ductal breast carcinomas, are the most common histologic subtypes to exhibit metastatic cutaneous lesions.⁸

Invasive lobular breast carcinoma represents approximately 10% of invasive breast cancer cases. Compared to invasive ductal carcinoma, there tends to be a delay in diagnosis often leading to larger tumor sizes relative to the former upon detection and with lymph node invasion. These findings may be explained by the greater difficulty of detecting invasive lobular carcinomas by mammography and clinical breast examination compared to invasive ductal carcinomas.^9-11 Additionally, invasive lobular carcinomas are more likely to be positive for estrogen and progesterone receptors compared to invasive ductal carcinomas,¹² which also was consistent in our case.

Cutaneous metastases of breast cancer most commonly are found on the anterior chest wall and can present as a wide spectrum of lesions, with nodules as the most common primary dermatologic manifestation.¹³ Cutaneous metastatic lesions commonly have been described as firm, mobile, round or oval, solitary or grouped nodules. The color of the nodules varies and may be flesh-colored, brown, blue, black, pink, and/or red-brown. The lesions often are asymptomatic but may ulcerate.²

In our case, the distribution of lesions was a unique aspect that is not typical of most cases of metastatic cutaneous breast carcinoma. The nodules appeared more scattered and involved multiple body regions, including the back, neck, and chest. Although cutaneous breast cancer metastases have been documented to extend to these body regions, a review of PubMed articles indexed for MEDLINE using the terms cutaneous metastatic lobular breast carcinoma, breast carcinoma, and metastatic breast cancer suggested that it is uncommon for these multiple areas to be simultaneously affected.^4,14 Rather, the more common clinical presentation of cutaneous metastatic breast carcinoma is as a solitary nodule or group of nodules localized to a single anatomic region.¹⁴

Another notable feature of our case was the rapid development of the cutaneous lesions relative to the primary tumor. This patient developed diffuse lesions over a period of several months, and given that her mammogram performed the previous year was negative for any abnormalities, one could suggest that the metastatic lesions developed less than a year from onset of the primary tumor. A previous study involving 41 patients with a known clinical primary visceral malignancy (ie, breast, lung, colon, esophageal, gastric, pancreatic, kidney, thyroid, prostate, or ovarian origin) found that it takes approximately 3 years on average for cutaneous metastases to develop from the onset of cancer diagnosis (range, 1–177 months).¹⁴ In the aforementioned study, 94% of patients had stage III or IV disease at time of skin metastasis, with the majority of those demonstrating stage IV disease. However, it also is possible that these breast tumors evaded detection or were too small to be identified on prior imaging.¹⁴ A review of our patient’s medical records did not indicate documentation of any visual or palpable breast changes prior to the onset of the clinically detected metastatic nodules.

Conclusion

Biopsy with immunohistochemical staining ultimately yielded the diagnosis of metastatic lobular breast carcinoma in our patient. Providers should be aware of the varying clinical presentations that may arise in the setting of cutaneous metastasis. When faced with lesions suspicious for cutaneous metastasis, biopsy is warranted to determine the correct diagnosis and ensure appropriate management. Upon diagnosis of cutaneous metastasis, prompt coordination with the primary care provider and appropriate referral to multidisciplinary teams is necessary. Clinical providers also should maintain a high index of suspicion when evaluating patients with cutaneous metastasis who have a history of normal malignancy screenings.

In women, breast cancer is the leading cancer diagnosis and the second leading cause of cancer-related death,¹ as well as the most common malignancy to metastasize to the skin.² Cutaneous breast carcinoma may present as cutaneous metastasis or can occur secondary to direct tumor extension. Five percent to 10% of women with breast cancer will present clinically with metastatic cutaneous disease, most commonly as a recurrence of early-stage breast carcinoma.²

In a published meta-analysis that investigated the incidence of tumors most commonly found to metastasize to the skin, Krathen et al³ found that cutaneous metastases occurred in 24% of patients with breast cancer (N=1903). In 2 large retrospective studies from tumor registry data, breast cancer was found to be the most common tumor involving metastasis to the skin, and 3.5% of the breast cancer cases identified in the registry had cutaneous metastasis as the presenting sign (n=35) at time of diagnosis.⁴

We report an unusual presentation of cutaneous metastatic lobular breast carcinoma that involved diffuse cutaneous lesions and rapid progression from onset of the breast mass to development of clinically apparent metastatic skin lesions.

Case Report

A 59-year-old woman with an unremarkable medical history presented to our dermatology clinic for evaluation of new widespread lesions that developed over a period of months. The eruption was asymptomatic and consisted of numerous bumpy lesions that reportedly started on the patient’s neck and progressively spread to involve the trunk. Physical examination revealed multiple flesh-colored, firm nodules scattered across the upper back, neck, and chest (Figure 1). Bilateral cervical and axillary lymphadenopathy also was noted. Upon questioning regarding family history of malignancy, the patient reported that her brother had been diagnosed with colon cancer. Although she was not up to date on age-appropriate malignancy screenings, she did report having a diagnostic mammogram 1 year prior that revealed a suspicious lesion on the left breast. A repeat mammogram of the left breast 6 months later was read as unremarkable.

Two 3-mm representative punch biopsies were performed. Hematoxylin and eosin staining revealed a basket-weave stratum corneum with underlying epidermal atrophy. A relatively monomorphic epithelioid cell infiltrate extending from the superficial reticular dermis into the deep dermis and displaying an open chromatin pattern and pink cytoplasm was observed, as well as dermal collagen thickening. Linear, single-filing cells along with focal irregular nests and scattered cells were observed (Figure 2). Immunohistochemical staining was positive for cytokeratin 7 (Figure 3A), epithelial membrane antigen, and estrogen receptor (Figure 3B) along with gross cystic disease fluid protein 15; focal progesterone receptor positivity also was present. Cytokeratin 20, cytokeratin 5/6, carcinoembryonic antigen, p63, CDX2, paired box gene 8, thyroid transcription factor 1, and human epidermal growth factor receptor 2/neu stains were negative. Findings identified in both biopsies were consistent with metastatic cutaneous lobular breast carcinoma.

A complete blood cell count and complete metabolic panels were within normal limits, aside from a mildly elevated alkaline phosphatase level. Breast ultrasonography was unremarkable. Stereotactic breast magnetic resonance imaging (MRI) revealed a 9.4-cm mass in the upper outer quadrant of the right breast as well as enlarged lymph nodes 2.2 cm from the left axilla. A subsequent bone scan demonstrated focal activity in the left lateral fourth rib, left costochondral junction, and right anterolateral fifth rib—it was unclear whether these lesions were metastatic or secondary to trauma from a fall the patient reportedly had sustained 2 weeks prior. Lumbar MRI without gadolinium contrast revealed extensive abnormal heterogeneous signal intensity of osseous structures consistent with osseous metastasis.

Subsequent diagnostic bilateral breast ultrasonography and percutaneous left lymph node biopsy revealed pathology consistent with metastatic lobular breast carcinoma with near total effacement of the lymph node and extracapsular extension concordant with previous MRI findings. The mass in the upper outer quadrant of the right breast that previously was observed on MRI was not identifiable on this ultrasound. It was recommended that the patient pursue MRI-guided breast biopsy to have the breast lesion further characterized. She was referred to surgical oncology at a tertiary center for management; however, the patient was lost to follow-up, and there are no records available indicating the patient pursued any treatment. Although we were unable to confirm the patient’s breast lesion that previously was seen on MRI was the cause of the metastatic disease, the overall clinical picture supported metastatic lobular breast carcinoma.

Comment

Tumor metastasis to the skin accounts for approximately 2% of all skin cancers⁵ and typically is observed in advanced stages of cancer. In women, breast carcinoma is the most common type of cancer to exhibit this behavior.² Invasive ductal carcinoma represents the most common histologic subtype of breast cancer overall,^6,7 and breast adenocarcinomas, including lobular and ductal breast carcinomas, are the most common histologic subtypes to exhibit metastatic cutaneous lesions.⁸

Invasive lobular breast carcinoma represents approximately 10% of invasive breast cancer cases. Compared to invasive ductal carcinoma, there tends to be a delay in diagnosis often leading to larger tumor sizes relative to the former upon detection and with lymph node invasion. These findings may be explained by the greater difficulty of detecting invasive lobular carcinomas by mammography and clinical breast examination compared to invasive ductal carcinomas.^9-11 Additionally, invasive lobular carcinomas are more likely to be positive for estrogen and progesterone receptors compared to invasive ductal carcinomas,¹² which also was consistent in our case.

Cutaneous metastases of breast cancer most commonly are found on the anterior chest wall and can present as a wide spectrum of lesions, with nodules as the most common primary dermatologic manifestation.¹³ Cutaneous metastatic lesions commonly have been described as firm, mobile, round or oval, solitary or grouped nodules. The color of the nodules varies and may be flesh-colored, brown, blue, black, pink, and/or red-brown. The lesions often are asymptomatic but may ulcerate.²

In our case, the distribution of lesions was a unique aspect that is not typical of most cases of metastatic cutaneous breast carcinoma. The nodules appeared more scattered and involved multiple body regions, including the back, neck, and chest. Although cutaneous breast cancer metastases have been documented to extend to these body regions, a review of PubMed articles indexed for MEDLINE using the terms cutaneous metastatic lobular breast carcinoma, breast carcinoma, and metastatic breast cancer suggested that it is uncommon for these multiple areas to be simultaneously affected.^4,14 Rather, the more common clinical presentation of cutaneous metastatic breast carcinoma is as a solitary nodule or group of nodules localized to a single anatomic region.¹⁴

Another notable feature of our case was the rapid development of the cutaneous lesions relative to the primary tumor. This patient developed diffuse lesions over a period of several months, and given that her mammogram performed the previous year was negative for any abnormalities, one could suggest that the metastatic lesions developed less than a year from onset of the primary tumor. A previous study involving 41 patients with a known clinical primary visceral malignancy (ie, breast, lung, colon, esophageal, gastric, pancreatic, kidney, thyroid, prostate, or ovarian origin) found that it takes approximately 3 years on average for cutaneous metastases to develop from the onset of cancer diagnosis (range, 1–177 months).¹⁴ In the aforementioned study, 94% of patients had stage III or IV disease at time of skin metastasis, with the majority of those demonstrating stage IV disease. However, it also is possible that these breast tumors evaded detection or were too small to be identified on prior imaging.¹⁴ A review of our patient’s medical records did not indicate documentation of any visual or palpable breast changes prior to the onset of the clinically detected metastatic nodules.

Conclusion

Biopsy with immunohistochemical staining ultimately yielded the diagnosis of metastatic lobular breast carcinoma in our patient. Providers should be aware of the varying clinical presentations that may arise in the setting of cutaneous metastasis. When faced with lesions suspicious for cutaneous metastasis, biopsy is warranted to determine the correct diagnosis and ensure appropriate management. Upon diagnosis of cutaneous metastasis, prompt coordination with the primary care provider and appropriate referral to multidisciplinary teams is necessary. Clinical providers also should maintain a high index of suspicion when evaluating patients with cutaneous metastasis who have a history of normal malignancy screenings.

Patients with early, undifferentiated arthritis may benefit from milder or stronger treatments, depending on the number of their risk factors for developing rheumatoid arthritis, researchers say.

Thinkstock/ LarsNeumann

If the finding is borne out by further research, clinicians could consider treating some of these patients with hydroxychloroquine, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) rather than methotrexate, said Pascal de Jong, MD, PhD, a rheumatologist at Erasmus Medical Center in Rotterdam, the Netherlands.

“Maybe those patients with fewer risk factors should get less intensive treatment,” he said in an interview. The study by de Jong and colleagues was published online Jan. 23 in Rheumatology.

The European Alliance of Associations for Rheumatology recommends starting treatment with methotrexate for patients who are at risk for persistent arthritis, which it says is “factually synonymous” with rheumatoid arthritis.

But these recommendations are based on studies involving patients with established rheumatoid arthritis, Dr. de Jong said.

In an earlier study, he and his colleagues found that hydroxychloroquine can be just as effective as methotrexate for patients newly diagnosed with rheumatoid arthritis who don’t have autoantibodies. This led them to wonder whether their findings might apply to some subgroups of patients with early arthritis.

As an initial test of this idea, they identified 130 patients from the Rotterdam Early Arthritis Cohort (tREACH) trial who had at least one swollen joint but who did meet the diagnostic criteria for rheumatoid arthritis.

They sorted the patients into groups on the basis of the number of risk factors for persistent arthritis. The risk factors were autoantibody positivity (rheumatoid factor and/or anticitrullinated protein antibody), polyarthritis (more than four swollen joints), erosive disease, and elevations in levels of acute-phase reactants.

Thirty-one patients had none of these risk factors, 66 patients had one risk factor, and the remaining 33 patients had at least two risk factors.

After 2 years of follow-up, 74% of the patients who had had no risk factors had recovered from their arthritis and had not taken disease-modifying antirheumatic drugs (DMARDs) for at least 6 months (DMARD-free remission). Among the patients who had had one risk factor, 48% achieved DMARD-free remission. Among those who had had two risk factors, 45% achieved DMARD-free remission. The differences between the group that had had no risk factors and the other two groups were statistically significant (P < .05).

The researchers found that those patients who had been experiencing their symptoms for fewer than 6 months were more likely to achieve disease-free remission.

They also sorted patients into different groups on the basis of the treatments they received. One group of 30 comprised all patients who had been initially treated with methotrexate and included patients who had also received other drugs. One group of 40 received hydroxychloroquine initially, and one group of 60 comprised patients who had received no DMARDs initially and included those who had received NSAIDs or glucocorticoids.

There was no statistically significant difference in DMARD-free remission rates among the treatment groups. However, among those patients who were not treated initially with DMARDs, the chance of sustaining DMARD-free remission for more than a year was lower in comparison with the patients who received methotrexate initially (odds ratio, 4.28; 95% confidence interval, 1.34-13.72; P < .05).

Those patients who had fewer baseline risk factors were more likely to have their medication dosages tapered, and they were at lower risk for flares. Patients with more risk factors were more likely to require an intensificiation of treatment, such as with the use of biologicals.

Methotrexate is more likely to cause side effects such as nausea, fatigue, and hair loss than hydroxychloroquine, Dr. de Jong said. “If the medication is better tolerated, it also influences the compliance of the patient,” he said.

The study could help rheumatologists determine which patients need the most aggressive treatment, agreed Kevin Deane, MD, PhD, associate professor of medicine, division of rheumatology, the University of Colorado, Aurora.

“That’s a common clinical problem,” he said. “Somebody comes in with sort of mild arthritis, and you don’t quite know what it is yet.”

But he added that more research is needed to understand what treatment works best for those patients whose arthritis has not yet been differentiated. Primary care physicians who suspect inflammatory arthritis should refer their patients to rheumatologists and should test for rheumatoid factors and anticyclic citrullinated peptide, Dr. Deane said.

The authors and Dr. Deane have disclosed no relevant financial relationships.

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

Patients with early, undifferentiated arthritis may benefit from milder or stronger treatments, depending on the number of their risk factors for developing rheumatoid arthritis, researchers say.

Thinkstock/ LarsNeumann

If the finding is borne out by further research, clinicians could consider treating some of these patients with hydroxychloroquine, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) rather than methotrexate, said Pascal de Jong, MD, PhD, a rheumatologist at Erasmus Medical Center in Rotterdam, the Netherlands.

“Maybe those patients with fewer risk factors should get less intensive treatment,” he said in an interview. The study by de Jong and colleagues was published online Jan. 23 in Rheumatology.

The European Alliance of Associations for Rheumatology recommends starting treatment with methotrexate for patients who are at risk for persistent arthritis, which it says is “factually synonymous” with rheumatoid arthritis.

But these recommendations are based on studies involving patients with established rheumatoid arthritis, Dr. de Jong said.

In an earlier study, he and his colleagues found that hydroxychloroquine can be just as effective as methotrexate for patients newly diagnosed with rheumatoid arthritis who don’t have autoantibodies. This led them to wonder whether their findings might apply to some subgroups of patients with early arthritis.

As an initial test of this idea, they identified 130 patients from the Rotterdam Early Arthritis Cohort (tREACH) trial who had at least one swollen joint but who did meet the diagnostic criteria for rheumatoid arthritis.

They sorted the patients into groups on the basis of the number of risk factors for persistent arthritis. The risk factors were autoantibody positivity (rheumatoid factor and/or anticitrullinated protein antibody), polyarthritis (more than four swollen joints), erosive disease, and elevations in levels of acute-phase reactants.

Thirty-one patients had none of these risk factors, 66 patients had one risk factor, and the remaining 33 patients had at least two risk factors.

After 2 years of follow-up, 74% of the patients who had had no risk factors had recovered from their arthritis and had not taken disease-modifying antirheumatic drugs (DMARDs) for at least 6 months (DMARD-free remission). Among the patients who had had one risk factor, 48% achieved DMARD-free remission. Among those who had had two risk factors, 45% achieved DMARD-free remission. The differences between the group that had had no risk factors and the other two groups were statistically significant (P < .05).

The researchers found that those patients who had been experiencing their symptoms for fewer than 6 months were more likely to achieve disease-free remission.

They also sorted patients into different groups on the basis of the treatments they received. One group of 30 comprised all patients who had been initially treated with methotrexate and included patients who had also received other drugs. One group of 40 received hydroxychloroquine initially, and one group of 60 comprised patients who had received no DMARDs initially and included those who had received NSAIDs or glucocorticoids.

There was no statistically significant difference in DMARD-free remission rates among the treatment groups. However, among those patients who were not treated initially with DMARDs, the chance of sustaining DMARD-free remission for more than a year was lower in comparison with the patients who received methotrexate initially (odds ratio, 4.28; 95% confidence interval, 1.34-13.72; P < .05).

Those patients who had fewer baseline risk factors were more likely to have their medication dosages tapered, and they were at lower risk for flares. Patients with more risk factors were more likely to require an intensificiation of treatment, such as with the use of biologicals.

Methotrexate is more likely to cause side effects such as nausea, fatigue, and hair loss than hydroxychloroquine, Dr. de Jong said. “If the medication is better tolerated, it also influences the compliance of the patient,” he said.

The study could help rheumatologists determine which patients need the most aggressive treatment, agreed Kevin Deane, MD, PhD, associate professor of medicine, division of rheumatology, the University of Colorado, Aurora.

“That’s a common clinical problem,” he said. “Somebody comes in with sort of mild arthritis, and you don’t quite know what it is yet.”

But he added that more research is needed to understand what treatment works best for those patients whose arthritis has not yet been differentiated. Primary care physicians who suspect inflammatory arthritis should refer their patients to rheumatologists and should test for rheumatoid factors and anticyclic citrullinated peptide, Dr. Deane said.

The authors and Dr. Deane have disclosed no relevant financial relationships.

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

Patients with early, undifferentiated arthritis may benefit from milder or stronger treatments, depending on the number of their risk factors for developing rheumatoid arthritis, researchers say.

Thinkstock/ LarsNeumann

If the finding is borne out by further research, clinicians could consider treating some of these patients with hydroxychloroquine, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) rather than methotrexate, said Pascal de Jong, MD, PhD, a rheumatologist at Erasmus Medical Center in Rotterdam, the Netherlands.

“Maybe those patients with fewer risk factors should get less intensive treatment,” he said in an interview. The study by de Jong and colleagues was published online Jan. 23 in Rheumatology.

The European Alliance of Associations for Rheumatology recommends starting treatment with methotrexate for patients who are at risk for persistent arthritis, which it says is “factually synonymous” with rheumatoid arthritis.

But these recommendations are based on studies involving patients with established rheumatoid arthritis, Dr. de Jong said.

In an earlier study, he and his colleagues found that hydroxychloroquine can be just as effective as methotrexate for patients newly diagnosed with rheumatoid arthritis who don’t have autoantibodies. This led them to wonder whether their findings might apply to some subgroups of patients with early arthritis.

As an initial test of this idea, they identified 130 patients from the Rotterdam Early Arthritis Cohort (tREACH) trial who had at least one swollen joint but who did meet the diagnostic criteria for rheumatoid arthritis.

They sorted the patients into groups on the basis of the number of risk factors for persistent arthritis. The risk factors were autoantibody positivity (rheumatoid factor and/or anticitrullinated protein antibody), polyarthritis (more than four swollen joints), erosive disease, and elevations in levels of acute-phase reactants.

Thirty-one patients had none of these risk factors, 66 patients had one risk factor, and the remaining 33 patients had at least two risk factors.

After 2 years of follow-up, 74% of the patients who had had no risk factors had recovered from their arthritis and had not taken disease-modifying antirheumatic drugs (DMARDs) for at least 6 months (DMARD-free remission). Among the patients who had had one risk factor, 48% achieved DMARD-free remission. Among those who had had two risk factors, 45% achieved DMARD-free remission. The differences between the group that had had no risk factors and the other two groups were statistically significant (P < .05).

The researchers found that those patients who had been experiencing their symptoms for fewer than 6 months were more likely to achieve disease-free remission.

They also sorted patients into different groups on the basis of the treatments they received. One group of 30 comprised all patients who had been initially treated with methotrexate and included patients who had also received other drugs. One group of 40 received hydroxychloroquine initially, and one group of 60 comprised patients who had received no DMARDs initially and included those who had received NSAIDs or glucocorticoids.

There was no statistically significant difference in DMARD-free remission rates among the treatment groups. However, among those patients who were not treated initially with DMARDs, the chance of sustaining DMARD-free remission for more than a year was lower in comparison with the patients who received methotrexate initially (odds ratio, 4.28; 95% confidence interval, 1.34-13.72; P < .05).

Those patients who had fewer baseline risk factors were more likely to have their medication dosages tapered, and they were at lower risk for flares. Patients with more risk factors were more likely to require an intensificiation of treatment, such as with the use of biologicals.

Methotrexate is more likely to cause side effects such as nausea, fatigue, and hair loss than hydroxychloroquine, Dr. de Jong said. “If the medication is better tolerated, it also influences the compliance of the patient,” he said.

The study could help rheumatologists determine which patients need the most aggressive treatment, agreed Kevin Deane, MD, PhD, associate professor of medicine, division of rheumatology, the University of Colorado, Aurora.

“That’s a common clinical problem,” he said. “Somebody comes in with sort of mild arthritis, and you don’t quite know what it is yet.”

But he added that more research is needed to understand what treatment works best for those patients whose arthritis has not yet been differentiated. Primary care physicians who suspect inflammatory arthritis should refer their patients to rheumatologists and should test for rheumatoid factors and anticyclic citrullinated peptide, Dr. Deane said.

The authors and Dr. Deane have disclosed no relevant financial relationships.

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

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

Help your patients understand pancreatitis testing and treatment options, symptoms and complications by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/pancreatitis.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

Help your patients understand pancreatitis testing and treatment options, symptoms and complications by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/pancreatitis.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

Help your patients understand pancreatitis testing and treatment options, symptoms and complications by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/pancreatitis.

The use of low-dose aspirin among older people shows no effect in reducing the incidence of certain cancer types. However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.

“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open. 

“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.

In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.

“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.

“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
 

Aspirin/cancer research in older people lacking

With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.

However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.

To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.

The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.

Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.

The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.

However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.

A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.

“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
 

Mechanism speculation focuses on COX-2 pathway

Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.  

In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.

“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.

The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.

Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.

“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”

Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.

“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”

The study authors and Dr. McNeil disclosed no relevant financial relationships.

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

The use of low-dose aspirin among older people shows no effect in reducing the incidence of certain cancer types. However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.

“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open. 

“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.

In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.

“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.

“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
 

Aspirin/cancer research in older people lacking

With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.

However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.

To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.

The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.

Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.

The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.

However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.

A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.

“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
 

Mechanism speculation focuses on COX-2 pathway

Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.  

In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.

“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.

The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.

Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.

“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”

Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.

“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”

The study authors and Dr. McNeil disclosed no relevant financial relationships.

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

The use of low-dose aspirin among older people shows no effect in reducing the incidence of certain cancer types. However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.

“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open. 

“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.

In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.

“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.

“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
 

Aspirin/cancer research in older people lacking

With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.

However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.

To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.

The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.

Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.

The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.

However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.

A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.

“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
 

Mechanism speculation focuses on COX-2 pathway

Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.  

In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.

“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.

The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.

Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.

“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”

Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.

“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”

The study authors and Dr. McNeil disclosed no relevant financial relationships.

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

Background: The PARTHENON clinical development program has conducted several clinical trials to assess the effectiveness of ticagrelor in multiple cardiovascular diseases. A prior study revealed the addition of ticagrelor to aspirin in patients with history of MI showed a small benefit in cardiovascular outcomes but with increased bleeding risk. While this effect was seen in both patients with and without diabetes, the absolute benefit for those with diabetes was considered large because of their higher baseline risk. Given this, investigators wanted to know if addition of ticagrelor to aspirin could also be beneficial in diabetics with known coronary disease but without history of MI or stroke.

Further studies into risk stratification based on prothrombotic versus bleeding risk could be beneficial in identifying specific groups that could benefit from DAPT. Conclusions from this study suggest the benefit of DAPT in diabetics does not outweigh its risk.

Bottom line: Addition of ticagrelor to aspirin in diabetic patients with stable coronary disease and no prior MI or stroke is not recommended.

Citation: Steg PG et al. Ticagrelor in patients with stable coronary disease and diabetes. N Eng J Med. 2019 Oct 3;381(14):1309-20.

Dr. Breitbach is assistant professor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: The PARTHENON clinical development program has conducted several clinical trials to assess the effectiveness of ticagrelor in multiple cardiovascular diseases. A prior study revealed the addition of ticagrelor to aspirin in patients with history of MI showed a small benefit in cardiovascular outcomes but with increased bleeding risk. While this effect was seen in both patients with and without diabetes, the absolute benefit for those with diabetes was considered large because of their higher baseline risk. Given this, investigators wanted to know if addition of ticagrelor to aspirin could also be beneficial in diabetics with known coronary disease but without history of MI or stroke.

Further studies into risk stratification based on prothrombotic versus bleeding risk could be beneficial in identifying specific groups that could benefit from DAPT. Conclusions from this study suggest the benefit of DAPT in diabetics does not outweigh its risk.

Bottom line: Addition of ticagrelor to aspirin in diabetic patients with stable coronary disease and no prior MI or stroke is not recommended.

Citation: Steg PG et al. Ticagrelor in patients with stable coronary disease and diabetes. N Eng J Med. 2019 Oct 3;381(14):1309-20.

Dr. Breitbach is assistant professor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: The PARTHENON clinical development program has conducted several clinical trials to assess the effectiveness of ticagrelor in multiple cardiovascular diseases. A prior study revealed the addition of ticagrelor to aspirin in patients with history of MI showed a small benefit in cardiovascular outcomes but with increased bleeding risk. While this effect was seen in both patients with and without diabetes, the absolute benefit for those with diabetes was considered large because of their higher baseline risk. Given this, investigators wanted to know if addition of ticagrelor to aspirin could also be beneficial in diabetics with known coronary disease but without history of MI or stroke.

Further studies into risk stratification based on prothrombotic versus bleeding risk could be beneficial in identifying specific groups that could benefit from DAPT. Conclusions from this study suggest the benefit of DAPT in diabetics does not outweigh its risk.

Bottom line: Addition of ticagrelor to aspirin in diabetic patients with stable coronary disease and no prior MI or stroke is not recommended.

Citation: Steg PG et al. Ticagrelor in patients with stable coronary disease and diabetes. N Eng J Med. 2019 Oct 3;381(14):1309-20.

Dr. Breitbach is assistant professor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

Researchers from the National Institute of Neurological Disorders and Stroke studying the brains of patients who died from COVID-19, “consistently” found microvascular damage—but no signs of COVID-19 infection. Of the 19 patients in the study, 14 had chronic illnesses, including diabetes mellitus and hypertension, and 11 had ben found dead or had died unexpectedly. Of the 16 with available medical histories, one had delirium and the others had respiratory or unknown symptoms. Two had pulmonary embolism.

                Patients with COVID-19 often have neurological problems, such as headaches, delirium, and dizziness. Some have strokes. Several studies have shown that COVID-19 can cause inflammation and blood vessel damage, but the precise mode of action is still unclear. In this study, the researchers used a magnetic resonance imaging (MRI) scanner 4 to 10 times more sensitive than most MRI scanners to examine samples of the olfactory bulbs and brainstems from the samples.

                In 9 patients, the MRI scan showed punctate hyperintensities (bright spots representing areas of microvascular injury and fibrinogen leakage) that often indicate inflammation. In 10 brains, they found punctate hypointensities (dark spots) that corresponded to congested blood vessels, with surrounding areas of fibrinogen leakage and relatively intact vasculature. Areas of linear hypointensities (dark spots) were interpreted as microhemorrhages.

                Using the scans as a guide, the researchers examined the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaked blood proteins into the brain. This, the researchers say, seemed to trigger an immune reaction. The spots were surrounded by T cells from the blood and the brain’s own immune cells. In contrast, the dark spots contained clotted and leaky blood vessels but no immune response.

                Moreover, although they used several methods for detecting genetic material or proteins from SAS-CoV-2, they found none. It’s possible, the researchers say, that the virus was cleared by the time of death or that viral copy numbers were undetectable by their assays.

                We were completely surprised,” said Avindra Nath, MD, NINDS clinical director. “Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases.”

                In future, Nath says, they plan to study how COVID-19 harms the blood vessels and whether that produces some of the short- and long-term symptoms seen. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”

Researchers from the National Institute of Neurological Disorders and Stroke studying the brains of patients who died from COVID-19, “consistently” found microvascular damage—but no signs of COVID-19 infection. Of the 19 patients in the study, 14 had chronic illnesses, including diabetes mellitus and hypertension, and 11 had ben found dead or had died unexpectedly. Of the 16 with available medical histories, one had delirium and the others had respiratory or unknown symptoms. Two had pulmonary embolism.

                Patients with COVID-19 often have neurological problems, such as headaches, delirium, and dizziness. Some have strokes. Several studies have shown that COVID-19 can cause inflammation and blood vessel damage, but the precise mode of action is still unclear. In this study, the researchers used a magnetic resonance imaging (MRI) scanner 4 to 10 times more sensitive than most MRI scanners to examine samples of the olfactory bulbs and brainstems from the samples.

                In 9 patients, the MRI scan showed punctate hyperintensities (bright spots representing areas of microvascular injury and fibrinogen leakage) that often indicate inflammation. In 10 brains, they found punctate hypointensities (dark spots) that corresponded to congested blood vessels, with surrounding areas of fibrinogen leakage and relatively intact vasculature. Areas of linear hypointensities (dark spots) were interpreted as microhemorrhages.

                Using the scans as a guide, the researchers examined the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaked blood proteins into the brain. This, the researchers say, seemed to trigger an immune reaction. The spots were surrounded by T cells from the blood and the brain’s own immune cells. In contrast, the dark spots contained clotted and leaky blood vessels but no immune response.

                Moreover, although they used several methods for detecting genetic material or proteins from SAS-CoV-2, they found none. It’s possible, the researchers say, that the virus was cleared by the time of death or that viral copy numbers were undetectable by their assays.

                We were completely surprised,” said Avindra Nath, MD, NINDS clinical director. “Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases.”

                In future, Nath says, they plan to study how COVID-19 harms the blood vessels and whether that produces some of the short- and long-term symptoms seen. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”

Researchers from the National Institute of Neurological Disorders and Stroke studying the brains of patients who died from COVID-19, “consistently” found microvascular damage—but no signs of COVID-19 infection. Of the 19 patients in the study, 14 had chronic illnesses, including diabetes mellitus and hypertension, and 11 had ben found dead or had died unexpectedly. Of the 16 with available medical histories, one had delirium and the others had respiratory or unknown symptoms. Two had pulmonary embolism.

                Patients with COVID-19 often have neurological problems, such as headaches, delirium, and dizziness. Some have strokes. Several studies have shown that COVID-19 can cause inflammation and blood vessel damage, but the precise mode of action is still unclear. In this study, the researchers used a magnetic resonance imaging (MRI) scanner 4 to 10 times more sensitive than most MRI scanners to examine samples of the olfactory bulbs and brainstems from the samples.

                In 9 patients, the MRI scan showed punctate hyperintensities (bright spots representing areas of microvascular injury and fibrinogen leakage) that often indicate inflammation. In 10 brains, they found punctate hypointensities (dark spots) that corresponded to congested blood vessels, with surrounding areas of fibrinogen leakage and relatively intact vasculature. Areas of linear hypointensities (dark spots) were interpreted as microhemorrhages.

                Using the scans as a guide, the researchers examined the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaked blood proteins into the brain. This, the researchers say, seemed to trigger an immune reaction. The spots were surrounded by T cells from the blood and the brain’s own immune cells. In contrast, the dark spots contained clotted and leaky blood vessels but no immune response.

                Moreover, although they used several methods for detecting genetic material or proteins from SAS-CoV-2, they found none. It’s possible, the researchers say, that the virus was cleared by the time of death or that viral copy numbers were undetectable by their assays.

                We were completely surprised,” said Avindra Nath, MD, NINDS clinical director. “Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases.”

                In future, Nath says, they plan to study how COVID-19 harms the blood vessels and whether that produces some of the short- and long-term symptoms seen. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”

Coinfection with COVID-19 and influenza was reported early in the pandemic. Although both infections on their own can cause severe complications and death, coinfection can double the odds of death when compared with COVID infection alone. Moreover, those odds can be raised by chronic medical conditions and environmental or occupational factors, such as congregate living settings, say physicians who report on the first 2 confirmed cases of COVID-19 and influenza coinfection among US Department of Defense personnel within the US Central Command area of responsibility.

                In the first case, a 56-year-old contractor presented to a Role I clinic with anorexia, fever, chills, and headache, which had begun 3 days before. His initial vital signs were “unremarkable,” and he did not have symptoms of respiratory distress. An antigen test was positive for influenza type A. A COVID-19 test also was positive. He was placed on isolation and treated with oseltamivir, amlodipine, hydrochlorothiazide, and losartan. His condition did not warrant hospitalization. Of 3 close contacts, 1 tested positive and was isolated. Two remained asymptomatic during the 14-day quarantine. Ten days after onset, the patient returned to duty.

                The second patient, a 34-year-old officer in the Army, was initially identified as a close contact of a confirmed COVID-19 case and placed in quarantine. He was asymptomatic but tested positive and was placed in isolation with precautions. As with the first patient, his vital signs were unremarkable. He continued to be asymptomatic, although he reported myalgias 2 days later. Since those are a classic sign of seasonal influenzas, he was tested and proved positive for type B influenza. He, too, was started on oseltamivir. By the end of the first week, he experienced loss of taste and smell, cough, and shortness of breath, but his vital signs remained normal. His symptoms improved through supportive care. All 6 of his close contacts remained asymptomatic. Ten days after his symptoms began, he also returned to duty.

                Influenza-associated deaths among the US military have been relatively few, the authors say, most likely because of the good preexisting health status of the US military, prompt detection with rapid influenza diagnostic tests, several effective antiviral therapeutics, and a “robust, compulsory vaccination program.” Nonetheless, neither patient had received the 2020-2021 influenza vaccine, which underscores the importance of this intervention, the authors say.

                Because both infections present with a wide variety of clinical manifestations and overlapping symptoms, providers should stay alert to the possibility of coinfection, especially among personnel who are higher risk. For instance, as a linguist who interacted daily with host nation partners, the civilian contractor had a high occupational exposure.

                While the authors only discuss 2 cases, a Medical Surveillance Monthly Report editorial comment says their report “nevertheless supports the importance of implementing force health protection (FHP) measures to prevent, detect, and respond to the spread of both of these health threats.” It’s particularly important, the comment notes, in the current context of a drawdown in forces in many deployed locations, as further losses of personnel to illness may degrade the execution of critical missions.

Coinfection with COVID-19 and influenza was reported early in the pandemic. Although both infections on their own can cause severe complications and death, coinfection can double the odds of death when compared with COVID infection alone. Moreover, those odds can be raised by chronic medical conditions and environmental or occupational factors, such as congregate living settings, say physicians who report on the first 2 confirmed cases of COVID-19 and influenza coinfection among US Department of Defense personnel within the US Central Command area of responsibility.

                In the first case, a 56-year-old contractor presented to a Role I clinic with anorexia, fever, chills, and headache, which had begun 3 days before. His initial vital signs were “unremarkable,” and he did not have symptoms of respiratory distress. An antigen test was positive for influenza type A. A COVID-19 test also was positive. He was placed on isolation and treated with oseltamivir, amlodipine, hydrochlorothiazide, and losartan. His condition did not warrant hospitalization. Of 3 close contacts, 1 tested positive and was isolated. Two remained asymptomatic during the 14-day quarantine. Ten days after onset, the patient returned to duty.

                The second patient, a 34-year-old officer in the Army, was initially identified as a close contact of a confirmed COVID-19 case and placed in quarantine. He was asymptomatic but tested positive and was placed in isolation with precautions. As with the first patient, his vital signs were unremarkable. He continued to be asymptomatic, although he reported myalgias 2 days later. Since those are a classic sign of seasonal influenzas, he was tested and proved positive for type B influenza. He, too, was started on oseltamivir. By the end of the first week, he experienced loss of taste and smell, cough, and shortness of breath, but his vital signs remained normal. His symptoms improved through supportive care. All 6 of his close contacts remained asymptomatic. Ten days after his symptoms began, he also returned to duty.

                Influenza-associated deaths among the US military have been relatively few, the authors say, most likely because of the good preexisting health status of the US military, prompt detection with rapid influenza diagnostic tests, several effective antiviral therapeutics, and a “robust, compulsory vaccination program.” Nonetheless, neither patient had received the 2020-2021 influenza vaccine, which underscores the importance of this intervention, the authors say.

                Because both infections present with a wide variety of clinical manifestations and overlapping symptoms, providers should stay alert to the possibility of coinfection, especially among personnel who are higher risk. For instance, as a linguist who interacted daily with host nation partners, the civilian contractor had a high occupational exposure.

                While the authors only discuss 2 cases, a Medical Surveillance Monthly Report editorial comment says their report “nevertheless supports the importance of implementing force health protection (FHP) measures to prevent, detect, and respond to the spread of both of these health threats.” It’s particularly important, the comment notes, in the current context of a drawdown in forces in many deployed locations, as further losses of personnel to illness may degrade the execution of critical missions.

Coinfection with COVID-19 and influenza was reported early in the pandemic. Although both infections on their own can cause severe complications and death, coinfection can double the odds of death when compared with COVID infection alone. Moreover, those odds can be raised by chronic medical conditions and environmental or occupational factors, such as congregate living settings, say physicians who report on the first 2 confirmed cases of COVID-19 and influenza coinfection among US Department of Defense personnel within the US Central Command area of responsibility.

                In the first case, a 56-year-old contractor presented to a Role I clinic with anorexia, fever, chills, and headache, which had begun 3 days before. His initial vital signs were “unremarkable,” and he did not have symptoms of respiratory distress. An antigen test was positive for influenza type A. A COVID-19 test also was positive. He was placed on isolation and treated with oseltamivir, amlodipine, hydrochlorothiazide, and losartan. His condition did not warrant hospitalization. Of 3 close contacts, 1 tested positive and was isolated. Two remained asymptomatic during the 14-day quarantine. Ten days after onset, the patient returned to duty.

                The second patient, a 34-year-old officer in the Army, was initially identified as a close contact of a confirmed COVID-19 case and placed in quarantine. He was asymptomatic but tested positive and was placed in isolation with precautions. As with the first patient, his vital signs were unremarkable. He continued to be asymptomatic, although he reported myalgias 2 days later. Since those are a classic sign of seasonal influenzas, he was tested and proved positive for type B influenza. He, too, was started on oseltamivir. By the end of the first week, he experienced loss of taste and smell, cough, and shortness of breath, but his vital signs remained normal. His symptoms improved through supportive care. All 6 of his close contacts remained asymptomatic. Ten days after his symptoms began, he also returned to duty.

                Influenza-associated deaths among the US military have been relatively few, the authors say, most likely because of the good preexisting health status of the US military, prompt detection with rapid influenza diagnostic tests, several effective antiviral therapeutics, and a “robust, compulsory vaccination program.” Nonetheless, neither patient had received the 2020-2021 influenza vaccine, which underscores the importance of this intervention, the authors say.

                Because both infections present with a wide variety of clinical manifestations and overlapping symptoms, providers should stay alert to the possibility of coinfection, especially among personnel who are higher risk. For instance, as a linguist who interacted daily with host nation partners, the civilian contractor had a high occupational exposure.

                While the authors only discuss 2 cases, a Medical Surveillance Monthly Report editorial comment says their report “nevertheless supports the importance of implementing force health protection (FHP) measures to prevent, detect, and respond to the spread of both of these health threats.” It’s particularly important, the comment notes, in the current context of a drawdown in forces in many deployed locations, as further losses of personnel to illness may degrade the execution of critical missions.

A bag of Doritos, that’s all Princess wanted.

StHelena/Getty Images

Her mom calls her Princess, but her real name is Lindsey. She’s 17 and lives with her mom, Sandra, a nurse, outside Atlanta. On May 17, 2020, a Sunday, Lindsey decided she didn’t want breakfast; she wanted Doritos. So she left home and walked to Family Dollar, taking her pants off on the way, while her mom followed on foot, talking to the police on her phone as they went.

Lindsey has autism. It can be hard for her to communicate and navigate social situations. She thrives on routine and gets special help at school. Or got help, before the coronavirus pandemic closed schools and forced tens of millions of children to stay home. Sandra said that’s when their living hell started.

“It’s like her brain was wired,” she said. “She’d just put on her jacket, and she’s out the door. And I’m chasing her.”

On May 17, Sandra chased her all the way to Family Dollar. Hours later, Lindsey was in jail, charged with assaulting her mom. (KHN and NPR are not using the family’s last name.)

Lindsey is 1 of almost 3 million children in the United States who have a serious emotional or behavioral health condition. When the pandemic forced schools and doctors’ offices to close last spring, it also cut children off from the trained teachers and therapists who understand their needs.

As a result, many, like Lindsey, spiraled into EDs and even police custody. Federal data shows a nationwide surge of children in mental health crisis during the pandemic – a surge that’s further taxing an already overstretched safety net.
 

‘Take her’

Even after schools closed, Lindsey continued to wake up early, get dressed and wait for the bus. When she realized it had stopped coming, Sandra said, her daughter just started walking out of the house, wandering, a few times a week.

In those situations, Sandra did what many families in crisis report they’ve had to do since the pandemic began: Race through the short list of places she could call for help.

First, her state’s mental health crisis hotline. But they often put Sandra on hold.

“This is ridiculous,” she said of the wait. “It’s supposed to be a crisis team. But I’m on hold for 40, 50 minutes. And by the time you get on the phone, [the crisis] is done!”

Then there’s the local hospital’s ED, but Sandra said she had taken Lindsey there for previous crises and been told there isn’t much they can do.

That’s why, on May 17, when Lindsey walked to Family Dollar in just a red T-shirt and underwear to get that bag of Doritos, Sandra called the last option on her list: the police.

Sandra arrived at the store before the police and paid for the chips. According to Sandra and police records, when an officer approached, Lindsey grew agitated and hit her mom on the back, hard.

Sandra said she explained to the officer: “‘She’s autistic. You know, I’m okay. I’m a nurse. I just need to take her home and give her her medication.’ ”

Lindsey takes a mood stabilizer, but because she left home before breakfast, she hadn’t taken it that morning. The officer asked if Sandra wanted to take her to the nearest hospital.

The hospital wouldn’t be able to help Lindsey, Sandra said. It hadn’t before. “They already told me: ‘Ma’am, there’s nothing we can do.’ They just check her labs, it’s fine, and they ship her back home. There’s nothing [the hospital] can do,” she recalled telling the officer.

Sandra asked if the police could drive her daughter home so the teen could take her medication, but the officer said no, they couldn’t. The only other thing they could do, the officer said, was take Lindsey to jail for hitting her mom.

“I’ve tried everything,” Sandra said, exasperated. She paced the parking lot, feeling hopeless, sad and out of options. Finally, in tears, she told the officers: “Take her.”

Lindsey does not like to be touched and fought back when authorities tried to handcuff her. Several officers wrestled her to the ground. At that point, Sandra protested and said an officer threatened to arrest her, too, if she didn’t back away. Lindsey was taken to jail, where she spent much of the night until Sandra was able to post bail.

Clayton County Solicitor-General Charles Brooks denied that Sandra was threatened with arrest and said that, while Lindsey’s case is still pending, his office “is working to ensure that the resolution in this matter involves a plan for medication compliance and not punitive action.”

Sandra isn’t alone in her experience. Multiple families interviewed for this story reported similar experiences of calling in the police when a child was in crisis because caretakers didn’t feel they had any other option.
 

‘The whole system is really grinding to a halt’

Roughly 6% of U.S. children ages 6-17 years are living with serious emotional or behavioral difficulties, including children with autism, severe anxiety, depression and trauma-related mental health conditions.

Many of these children depend on schools for access to vital therapies. When schools and doctors’ offices stopped providing in-person services last spring, kids were untethered from the people and supports they rely on.

“The lack of in-person services is really detrimental,” said Susan Duffy, MD,a pediatrician and professor of emergency medicine at Brown University, Providence, R.I.

Marjorie, a mother in Florida, said her 15-year-old son has suffered during these disruptions. He has ADHD and oppositional defiant disorder, a condition marked by frequent and persistent hostility. Little things – like being asked to do schoolwork – can send him into a rage, leading to holes punched in walls, broken doors and violent threats. (The family’s last name or her son’s first name are not used to protect her son’s privacy and future prospects.)

The pandemic has shifted both school and her son’s therapy sessions online. But Marjorie said virtual therapy isn’t working because her son doesn’t focus well during sessions and tries to watch television instead. Lately, she has simply been canceling them.

“I was paying for appointments and there was no therapeutic value,” Marjorie said.

The issues cut across socioeconomic lines – affecting families with private insurance, like Marjorie, as well as those who receive coverage through Medicaid, a federal-state program that provides health insurance to low-income people and those with disabilities.

In the first few months of the pandemic, between March and May, children on Medicaid received 44% fewer outpatient mental health services – including therapy and in-home support – compared with the same time period in 2019, according to the Centers for Medicare & Medicaid Services. That’s even after accounting for increased telehealth appointments.

And while the nation’s EDs have seen a decline in overall visits, there was a relative increase in mental health visits for kids in 2020, compared with 2019.

The Centers for Disease Control and Prevention found that, from April to October 2020, hospitals across the United States saw a 24% increase in the proportion of mental health emergency visits for children aged 5-11 years, and a 31% increase for children aged 12-17.

“Proportionally, the number of mental health visits is far more significant than it has been in the past,” said Dr. Duffy. “Not only are we seeing more children, more children are being admitted” to inpatient care.

That’s because there are fewer outpatient services now available to children, she said, and because the conditions of the children showing up at EDs “are more serious.”

This crisis is not only making life harder for these kids and their families, but it’s also stressing the entire health care system.

Child and adolescent psychiatrists working in hospitals around the country said children are increasingly “boarding” in EDs for days, waiting for inpatient admission to a regular hospital or psychiatric hospital.

Before the pandemic, there was already a shortage of inpatient psychiatric beds for children, said Christopher Bellonci, MD, a child psychiatrist at Judge Baker Children’s Center in Boston. That shortage has only gotten worse as hospitals cut capacity to allow for more physical distancing within psychiatric units.

“The whole system is really grinding to a halt at a time when we have unprecedented need,” Dr. Bellonci said.
 

‘A signal that the rest of your system doesn’t work’

Psychiatrists on the front lines share the frustrations of parents struggling to find help for their children.

Part of the problem is there have never been enough psychiatrists and therapists trained to work with children, intervening in the early stages of their illness, said Jennifer Havens, MD, a child psychiatrist at New York University.

“Tons of people showing up in emergency rooms in bad shape is a signal that the rest of your system doesn’t work,” she said.

Too often, Dr. Havens said, services aren’t available until children are older – and in crisis. “Often for people who don’t have access to services, we wait until they’re too big to be managed.”

While the pandemic has made life harder for Marjorie and her son in Florida, she said it has always been difficult to find the support and care he needs. Last fall, he needed a psychiatric evaluation, but the nearest specialist who would accept her commercial insurance was 100 miles away, in Alabama.

“Even when you have the money or you have the insurance, it is still a travesty,” Marjorie said. “You cannot get help for these kids.”

Parents are frustrated, and so are psychiatrists on the front lines. C.J. Glawe, MD, who leads the psychiatric crisis department at Nationwide Children’s Hospital in Columbus, Ohio, said that once a child is stabilized after a crisis it can be hard to explain to parents that they may not be able to find follow-up care anywhere near their home.

“Especially when I can clearly tell you I know exactly what you need, I just can’t give it to you,” Dr. Glawe said. “It’s demoralizing.”

When states and communities fail to provide children the services they need to live at home, kids can deteriorate and even wind up in jail, like Lindsey. At that point, Dr. Glawe said, the cost and level of care required will be even higher, whether that’s hospitalization or long stays in residential treatment facilities.

That’s exactly the scenario Sandra, Lindsey’s mom, is hoping to avoid for her Princess.

“For me, as a nurse and as a provider, that will be the last thing for my daughter,” she said. “It’s like [state and local leaders] leave it to the school and the parent to deal with, and they don’t care. And that’s the problem. It’s sad because, if I’m not here...”

Her voice trailed off as tears welled.

“She didn’t ask to have autism.”

To help families like Sandra’s and Marjorie’s, advocates said, all levels of government need to invest in creating a mental health system that’s accessible to anyone who needs it.

But given that many states have seen their revenues drop because of the pandemic, there’s a concern services will instead be cut – at a time when the need has never been greater.

This story is part of a reporting partnership that includes NPR, Illinois Public Media and Kaiser Health News. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

A bag of Doritos, that’s all Princess wanted.

StHelena/Getty Images

Her mom calls her Princess, but her real name is Lindsey. She’s 17 and lives with her mom, Sandra, a nurse, outside Atlanta. On May 17, 2020, a Sunday, Lindsey decided she didn’t want breakfast; she wanted Doritos. So she left home and walked to Family Dollar, taking her pants off on the way, while her mom followed on foot, talking to the police on her phone as they went.

Lindsey has autism. It can be hard for her to communicate and navigate social situations. She thrives on routine and gets special help at school. Or got help, before the coronavirus pandemic closed schools and forced tens of millions of children to stay home. Sandra said that’s when their living hell started.

“It’s like her brain was wired,” she said. “She’d just put on her jacket, and she’s out the door. And I’m chasing her.”

On May 17, Sandra chased her all the way to Family Dollar. Hours later, Lindsey was in jail, charged with assaulting her mom. (KHN and NPR are not using the family’s last name.)

Lindsey is 1 of almost 3 million children in the United States who have a serious emotional or behavioral health condition. When the pandemic forced schools and doctors’ offices to close last spring, it also cut children off from the trained teachers and therapists who understand their needs.

As a result, many, like Lindsey, spiraled into EDs and even police custody. Federal data shows a nationwide surge of children in mental health crisis during the pandemic – a surge that’s further taxing an already overstretched safety net.
 

‘Take her’

Even after schools closed, Lindsey continued to wake up early, get dressed and wait for the bus. When she realized it had stopped coming, Sandra said, her daughter just started walking out of the house, wandering, a few times a week.

In those situations, Sandra did what many families in crisis report they’ve had to do since the pandemic began: Race through the short list of places she could call for help.

First, her state’s mental health crisis hotline. But they often put Sandra on hold.

“This is ridiculous,” she said of the wait. “It’s supposed to be a crisis team. But I’m on hold for 40, 50 minutes. And by the time you get on the phone, [the crisis] is done!”

Then there’s the local hospital’s ED, but Sandra said she had taken Lindsey there for previous crises and been told there isn’t much they can do.

That’s why, on May 17, when Lindsey walked to Family Dollar in just a red T-shirt and underwear to get that bag of Doritos, Sandra called the last option on her list: the police.

Sandra arrived at the store before the police and paid for the chips. According to Sandra and police records, when an officer approached, Lindsey grew agitated and hit her mom on the back, hard.

Sandra said she explained to the officer: “‘She’s autistic. You know, I’m okay. I’m a nurse. I just need to take her home and give her her medication.’ ”

Lindsey takes a mood stabilizer, but because she left home before breakfast, she hadn’t taken it that morning. The officer asked if Sandra wanted to take her to the nearest hospital.

The hospital wouldn’t be able to help Lindsey, Sandra said. It hadn’t before. “They already told me: ‘Ma’am, there’s nothing we can do.’ They just check her labs, it’s fine, and they ship her back home. There’s nothing [the hospital] can do,” she recalled telling the officer.

Sandra asked if the police could drive her daughter home so the teen could take her medication, but the officer said no, they couldn’t. The only other thing they could do, the officer said, was take Lindsey to jail for hitting her mom.

“I’ve tried everything,” Sandra said, exasperated. She paced the parking lot, feeling hopeless, sad and out of options. Finally, in tears, she told the officers: “Take her.”

Lindsey does not like to be touched and fought back when authorities tried to handcuff her. Several officers wrestled her to the ground. At that point, Sandra protested and said an officer threatened to arrest her, too, if she didn’t back away. Lindsey was taken to jail, where she spent much of the night until Sandra was able to post bail.

Clayton County Solicitor-General Charles Brooks denied that Sandra was threatened with arrest and said that, while Lindsey’s case is still pending, his office “is working to ensure that the resolution in this matter involves a plan for medication compliance and not punitive action.”

Sandra isn’t alone in her experience. Multiple families interviewed for this story reported similar experiences of calling in the police when a child was in crisis because caretakers didn’t feel they had any other option.
 

‘The whole system is really grinding to a halt’

Roughly 6% of U.S. children ages 6-17 years are living with serious emotional or behavioral difficulties, including children with autism, severe anxiety, depression and trauma-related mental health conditions.

Many of these children depend on schools for access to vital therapies. When schools and doctors’ offices stopped providing in-person services last spring, kids were untethered from the people and supports they rely on.

“The lack of in-person services is really detrimental,” said Susan Duffy, MD,a pediatrician and professor of emergency medicine at Brown University, Providence, R.I.

Marjorie, a mother in Florida, said her 15-year-old son has suffered during these disruptions. He has ADHD and oppositional defiant disorder, a condition marked by frequent and persistent hostility. Little things – like being asked to do schoolwork – can send him into a rage, leading to holes punched in walls, broken doors and violent threats. (The family’s last name or her son’s first name are not used to protect her son’s privacy and future prospects.)

The pandemic has shifted both school and her son’s therapy sessions online. But Marjorie said virtual therapy isn’t working because her son doesn’t focus well during sessions and tries to watch television instead. Lately, she has simply been canceling them.

“I was paying for appointments and there was no therapeutic value,” Marjorie said.

The issues cut across socioeconomic lines – affecting families with private insurance, like Marjorie, as well as those who receive coverage through Medicaid, a federal-state program that provides health insurance to low-income people and those with disabilities.

In the first few months of the pandemic, between March and May, children on Medicaid received 44% fewer outpatient mental health services – including therapy and in-home support – compared with the same time period in 2019, according to the Centers for Medicare & Medicaid Services. That’s even after accounting for increased telehealth appointments.

And while the nation’s EDs have seen a decline in overall visits, there was a relative increase in mental health visits for kids in 2020, compared with 2019.

The Centers for Disease Control and Prevention found that, from April to October 2020, hospitals across the United States saw a 24% increase in the proportion of mental health emergency visits for children aged 5-11 years, and a 31% increase for children aged 12-17.

“Proportionally, the number of mental health visits is far more significant than it has been in the past,” said Dr. Duffy. “Not only are we seeing more children, more children are being admitted” to inpatient care.

That’s because there are fewer outpatient services now available to children, she said, and because the conditions of the children showing up at EDs “are more serious.”

This crisis is not only making life harder for these kids and their families, but it’s also stressing the entire health care system.

Child and adolescent psychiatrists working in hospitals around the country said children are increasingly “boarding” in EDs for days, waiting for inpatient admission to a regular hospital or psychiatric hospital.

Before the pandemic, there was already a shortage of inpatient psychiatric beds for children, said Christopher Bellonci, MD, a child psychiatrist at Judge Baker Children’s Center in Boston. That shortage has only gotten worse as hospitals cut capacity to allow for more physical distancing within psychiatric units.

“The whole system is really grinding to a halt at a time when we have unprecedented need,” Dr. Bellonci said.
 

‘A signal that the rest of your system doesn’t work’

Psychiatrists on the front lines share the frustrations of parents struggling to find help for their children.

Part of the problem is there have never been enough psychiatrists and therapists trained to work with children, intervening in the early stages of their illness, said Jennifer Havens, MD, a child psychiatrist at New York University.

“Tons of people showing up in emergency rooms in bad shape is a signal that the rest of your system doesn’t work,” she said.

Too often, Dr. Havens said, services aren’t available until children are older – and in crisis. “Often for people who don’t have access to services, we wait until they’re too big to be managed.”

While the pandemic has made life harder for Marjorie and her son in Florida, she said it has always been difficult to find the support and care he needs. Last fall, he needed a psychiatric evaluation, but the nearest specialist who would accept her commercial insurance was 100 miles away, in Alabama.

“Even when you have the money or you have the insurance, it is still a travesty,” Marjorie said. “You cannot get help for these kids.”

Parents are frustrated, and so are psychiatrists on the front lines. C.J. Glawe, MD, who leads the psychiatric crisis department at Nationwide Children’s Hospital in Columbus, Ohio, said that once a child is stabilized after a crisis it can be hard to explain to parents that they may not be able to find follow-up care anywhere near their home.

“Especially when I can clearly tell you I know exactly what you need, I just can’t give it to you,” Dr. Glawe said. “It’s demoralizing.”

When states and communities fail to provide children the services they need to live at home, kids can deteriorate and even wind up in jail, like Lindsey. At that point, Dr. Glawe said, the cost and level of care required will be even higher, whether that’s hospitalization or long stays in residential treatment facilities.

That’s exactly the scenario Sandra, Lindsey’s mom, is hoping to avoid for her Princess.

“For me, as a nurse and as a provider, that will be the last thing for my daughter,” she said. “It’s like [state and local leaders] leave it to the school and the parent to deal with, and they don’t care. And that’s the problem. It’s sad because, if I’m not here...”

Her voice trailed off as tears welled.

“She didn’t ask to have autism.”

To help families like Sandra’s and Marjorie’s, advocates said, all levels of government need to invest in creating a mental health system that’s accessible to anyone who needs it.

But given that many states have seen their revenues drop because of the pandemic, there’s a concern services will instead be cut – at a time when the need has never been greater.

This story is part of a reporting partnership that includes NPR, Illinois Public Media and Kaiser Health News. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

A bag of Doritos, that’s all Princess wanted.

StHelena/Getty Images

Her mom calls her Princess, but her real name is Lindsey. She’s 17 and lives with her mom, Sandra, a nurse, outside Atlanta. On May 17, 2020, a Sunday, Lindsey decided she didn’t want breakfast; she wanted Doritos. So she left home and walked to Family Dollar, taking her pants off on the way, while her mom followed on foot, talking to the police on her phone as they went.

Lindsey has autism. It can be hard for her to communicate and navigate social situations. She thrives on routine and gets special help at school. Or got help, before the coronavirus pandemic closed schools and forced tens of millions of children to stay home. Sandra said that’s when their living hell started.

“It’s like her brain was wired,” she said. “She’d just put on her jacket, and she’s out the door. And I’m chasing her.”

On May 17, Sandra chased her all the way to Family Dollar. Hours later, Lindsey was in jail, charged with assaulting her mom. (KHN and NPR are not using the family’s last name.)

Lindsey is 1 of almost 3 million children in the United States who have a serious emotional or behavioral health condition. When the pandemic forced schools and doctors’ offices to close last spring, it also cut children off from the trained teachers and therapists who understand their needs.

As a result, many, like Lindsey, spiraled into EDs and even police custody. Federal data shows a nationwide surge of children in mental health crisis during the pandemic – a surge that’s further taxing an already overstretched safety net.
 

‘Take her’

Even after schools closed, Lindsey continued to wake up early, get dressed and wait for the bus. When she realized it had stopped coming, Sandra said, her daughter just started walking out of the house, wandering, a few times a week.

In those situations, Sandra did what many families in crisis report they’ve had to do since the pandemic began: Race through the short list of places she could call for help.

First, her state’s mental health crisis hotline. But they often put Sandra on hold.

“This is ridiculous,” she said of the wait. “It’s supposed to be a crisis team. But I’m on hold for 40, 50 minutes. And by the time you get on the phone, [the crisis] is done!”

Then there’s the local hospital’s ED, but Sandra said she had taken Lindsey there for previous crises and been told there isn’t much they can do.

That’s why, on May 17, when Lindsey walked to Family Dollar in just a red T-shirt and underwear to get that bag of Doritos, Sandra called the last option on her list: the police.

Sandra arrived at the store before the police and paid for the chips. According to Sandra and police records, when an officer approached, Lindsey grew agitated and hit her mom on the back, hard.

Sandra said she explained to the officer: “‘She’s autistic. You know, I’m okay. I’m a nurse. I just need to take her home and give her her medication.’ ”

Lindsey takes a mood stabilizer, but because she left home before breakfast, she hadn’t taken it that morning. The officer asked if Sandra wanted to take her to the nearest hospital.

The hospital wouldn’t be able to help Lindsey, Sandra said. It hadn’t before. “They already told me: ‘Ma’am, there’s nothing we can do.’ They just check her labs, it’s fine, and they ship her back home. There’s nothing [the hospital] can do,” she recalled telling the officer.

Sandra asked if the police could drive her daughter home so the teen could take her medication, but the officer said no, they couldn’t. The only other thing they could do, the officer said, was take Lindsey to jail for hitting her mom.

“I’ve tried everything,” Sandra said, exasperated. She paced the parking lot, feeling hopeless, sad and out of options. Finally, in tears, she told the officers: “Take her.”

Lindsey does not like to be touched and fought back when authorities tried to handcuff her. Several officers wrestled her to the ground. At that point, Sandra protested and said an officer threatened to arrest her, too, if she didn’t back away. Lindsey was taken to jail, where she spent much of the night until Sandra was able to post bail.

Clayton County Solicitor-General Charles Brooks denied that Sandra was threatened with arrest and said that, while Lindsey’s case is still pending, his office “is working to ensure that the resolution in this matter involves a plan for medication compliance and not punitive action.”

Sandra isn’t alone in her experience. Multiple families interviewed for this story reported similar experiences of calling in the police when a child was in crisis because caretakers didn’t feel they had any other option.
 

‘The whole system is really grinding to a halt’

Roughly 6% of U.S. children ages 6-17 years are living with serious emotional or behavioral difficulties, including children with autism, severe anxiety, depression and trauma-related mental health conditions.

Many of these children depend on schools for access to vital therapies. When schools and doctors’ offices stopped providing in-person services last spring, kids were untethered from the people and supports they rely on.

“The lack of in-person services is really detrimental,” said Susan Duffy, MD,a pediatrician and professor of emergency medicine at Brown University, Providence, R.I.

Marjorie, a mother in Florida, said her 15-year-old son has suffered during these disruptions. He has ADHD and oppositional defiant disorder, a condition marked by frequent and persistent hostility. Little things – like being asked to do schoolwork – can send him into a rage, leading to holes punched in walls, broken doors and violent threats. (The family’s last name or her son’s first name are not used to protect her son’s privacy and future prospects.)

The pandemic has shifted both school and her son’s therapy sessions online. But Marjorie said virtual therapy isn’t working because her son doesn’t focus well during sessions and tries to watch television instead. Lately, she has simply been canceling them.

“I was paying for appointments and there was no therapeutic value,” Marjorie said.

The issues cut across socioeconomic lines – affecting families with private insurance, like Marjorie, as well as those who receive coverage through Medicaid, a federal-state program that provides health insurance to low-income people and those with disabilities.

In the first few months of the pandemic, between March and May, children on Medicaid received 44% fewer outpatient mental health services – including therapy and in-home support – compared with the same time period in 2019, according to the Centers for Medicare & Medicaid Services. That’s even after accounting for increased telehealth appointments.

And while the nation’s EDs have seen a decline in overall visits, there was a relative increase in mental health visits for kids in 2020, compared with 2019.

The Centers for Disease Control and Prevention found that, from April to October 2020, hospitals across the United States saw a 24% increase in the proportion of mental health emergency visits for children aged 5-11 years, and a 31% increase for children aged 12-17.

“Proportionally, the number of mental health visits is far more significant than it has been in the past,” said Dr. Duffy. “Not only are we seeing more children, more children are being admitted” to inpatient care.

That’s because there are fewer outpatient services now available to children, she said, and because the conditions of the children showing up at EDs “are more serious.”

This crisis is not only making life harder for these kids and their families, but it’s also stressing the entire health care system.

Child and adolescent psychiatrists working in hospitals around the country said children are increasingly “boarding” in EDs for days, waiting for inpatient admission to a regular hospital or psychiatric hospital.

Before the pandemic, there was already a shortage of inpatient psychiatric beds for children, said Christopher Bellonci, MD, a child psychiatrist at Judge Baker Children’s Center in Boston. That shortage has only gotten worse as hospitals cut capacity to allow for more physical distancing within psychiatric units.

“The whole system is really grinding to a halt at a time when we have unprecedented need,” Dr. Bellonci said.
 

‘A signal that the rest of your system doesn’t work’

Psychiatrists on the front lines share the frustrations of parents struggling to find help for their children.

Part of the problem is there have never been enough psychiatrists and therapists trained to work with children, intervening in the early stages of their illness, said Jennifer Havens, MD, a child psychiatrist at New York University.

“Tons of people showing up in emergency rooms in bad shape is a signal that the rest of your system doesn’t work,” she said.

Too often, Dr. Havens said, services aren’t available until children are older – and in crisis. “Often for people who don’t have access to services, we wait until they’re too big to be managed.”

While the pandemic has made life harder for Marjorie and her son in Florida, she said it has always been difficult to find the support and care he needs. Last fall, he needed a psychiatric evaluation, but the nearest specialist who would accept her commercial insurance was 100 miles away, in Alabama.

“Even when you have the money or you have the insurance, it is still a travesty,” Marjorie said. “You cannot get help for these kids.”

Parents are frustrated, and so are psychiatrists on the front lines. C.J. Glawe, MD, who leads the psychiatric crisis department at Nationwide Children’s Hospital in Columbus, Ohio, said that once a child is stabilized after a crisis it can be hard to explain to parents that they may not be able to find follow-up care anywhere near their home.

“Especially when I can clearly tell you I know exactly what you need, I just can’t give it to you,” Dr. Glawe said. “It’s demoralizing.”

When states and communities fail to provide children the services they need to live at home, kids can deteriorate and even wind up in jail, like Lindsey. At that point, Dr. Glawe said, the cost and level of care required will be even higher, whether that’s hospitalization or long stays in residential treatment facilities.

That’s exactly the scenario Sandra, Lindsey’s mom, is hoping to avoid for her Princess.

“For me, as a nurse and as a provider, that will be the last thing for my daughter,” she said. “It’s like [state and local leaders] leave it to the school and the parent to deal with, and they don’t care. And that’s the problem. It’s sad because, if I’m not here...”

Her voice trailed off as tears welled.

“She didn’t ask to have autism.”

To help families like Sandra’s and Marjorie’s, advocates said, all levels of government need to invest in creating a mental health system that’s accessible to anyone who needs it.

But given that many states have seen their revenues drop because of the pandemic, there’s a concern services will instead be cut – at a time when the need has never been greater.

This story is part of a reporting partnership that includes NPR, Illinois Public Media and Kaiser Health News. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.