Mixed Topics

To the Editor:

Cutaneous metastases occur more often in the setting of breast carcinoma than other malignancies in women.¹ Although interventions are aimed at halting disease progression, cutaneous metastases indicate widespread disease and are associated with poor prognosis. We present the case of a patient with metastatic breast adenocarcinoma who developed cutaneous metastasis on the trunk after a double mastectomy. The widespread distribution and wide range of clinical manifestations are unique.

An 81-year-old woman presented to the dermatology office for evaluation of a skin eruption that started along a mastectomy scar on the left breast a few months postoperatively. She had a history of stage IV breast adenocarcinoma metastatic to the chest wall that was treated with a double mastectomy 2 years prior. The patient denied associated pain or pruritus and mainly was concerned with the cosmetic appearance. At the time of the initial diagnosis of breast adenocarcinoma, the patient was offered chemotherapy, which she did not tolerate. The patient opted against radiation therapy, as she preferred a more natural approach, such as anticancer shakes, which she was taking from a homeopathic source. She was unaware of the ingredients used in the shakes.

Physical examination revealed multiple grouped, firm, purpuric papules, nodules, and pseudovesicles on a background of violaceous erythema on the chest, abdomen, and flank (Figure 1). The background erythema had a mosaic pattern that extended toward the central back (Figure 2). A scoop shave biopsy of one of the purpuric nodules revealed highly atypical cells with abundant cytoplasm, large nuclei, and prominent nucleoli (Figure 3). Focally, the cells appeared to form glandular structures. Numerous atypical mitotic figures were present. Lymphatic invasion and microcalcifications were identified (Figure 3 [inset]). Immunohistochemical staining for cytokeratin 7 and gross cystic disease fluid protein 15 were strongly positive (Figure 4). Based on the histopathologic and immunohistochemical findings, a diagnosis of cutaneous metastatic breast adenocarcinoma was made. The patient opted to continue the homeopathic anticancer shakes and was subsequently lost to follow-up.

Cutaneous metastases of internal malignancies make up only 2% of all skin tumors,¹ making them relatively uncommon in the dermatologic setting. However, cutaneous metastasis occurs in 23.9% of patients with breast carcinoma, making it the most common tumor after malignant melanoma to metastasize to the skin.² The most common sites for breast carcinoma cutaneous metastasis (BCCM) are the chest wall and abdomen; other sites include the head/neck region and the extremities. The clinical presentation of BCCM varies depending on the mode of dissemination—lymphatic, hematogenous, contiguous growth, or iatrogenic implantation. The most common presentation is nodular carcinoma (47%–80%).^2,3 Other presentations include carcinoma telangiectoides (8%–11%),^2,3 alopecia neoplastica (2%–12%),^2,3 and carcinoma erysipeloides (3%–6%).^2,3 Carcinoma en cuirasse is rare.³

Nodular BCCM may present as firm solitary or grouped papules and nodules that are painless and range in color from flesh colored or pink to red-brown. Histologically, they are composed of atypical neoplastic cells arranged in small nests and cords, usually in a single-file line within the collagen bundles of the dermis.⁴ Carcinoma telangiectoides is characterized by its violaceous hue due to the dilated vascular channels. The lesions are purpuric papules and pseudovesicles appearing on an erythematous base, most commonly contiguous with the surgical scar. Histologically, collections of atypical tumor cells and erythrocytes are present along with dilated blood vessels in the papillary dermis.² Alopecia neoplastica presents as singular or grouped cicatricial patches of hair loss. Lesions of carcinoma erysipeloides present as warm, erythematous, tender, well-defined patches or plaques. Carcinoma en cuirasse is characterized by an erythematous sclerodermoid plaque on the chest wall.²

Our patient’s presentation was unique due to the widespread distribution, unusual pattern, and variable clinical morphologies of the cutaneous metastases. Our patient had findings of both carcinoma telangiectoides and nodular carcinoma. The mosaic violaceous erythema extending toward the mid-back rarely is reported in the literature and indicates extensive intravascular spread of tumor cells in the dermis.

Metastatic breast cancer is associated with a poor prognosis because it typically occurs in advanced stages and often does not respond to treatment.⁵ Although chemotherapy, hormonal therapy, and/or radiation therapy may improve survival, the choice in regimen is guided by cancer histology as well as prior treatments. In our case, the patient chose to continue her homeopathic therapy.

To the Editor:

Cutaneous metastases occur more often in the setting of breast carcinoma than other malignancies in women.¹ Although interventions are aimed at halting disease progression, cutaneous metastases indicate widespread disease and are associated with poor prognosis. We present the case of a patient with metastatic breast adenocarcinoma who developed cutaneous metastasis on the trunk after a double mastectomy. The widespread distribution and wide range of clinical manifestations are unique.

An 81-year-old woman presented to the dermatology office for evaluation of a skin eruption that started along a mastectomy scar on the left breast a few months postoperatively. She had a history of stage IV breast adenocarcinoma metastatic to the chest wall that was treated with a double mastectomy 2 years prior. The patient denied associated pain or pruritus and mainly was concerned with the cosmetic appearance. At the time of the initial diagnosis of breast adenocarcinoma, the patient was offered chemotherapy, which she did not tolerate. The patient opted against radiation therapy, as she preferred a more natural approach, such as anticancer shakes, which she was taking from a homeopathic source. She was unaware of the ingredients used in the shakes.

Physical examination revealed multiple grouped, firm, purpuric papules, nodules, and pseudovesicles on a background of violaceous erythema on the chest, abdomen, and flank (Figure 1). The background erythema had a mosaic pattern that extended toward the central back (Figure 2). A scoop shave biopsy of one of the purpuric nodules revealed highly atypical cells with abundant cytoplasm, large nuclei, and prominent nucleoli (Figure 3). Focally, the cells appeared to form glandular structures. Numerous atypical mitotic figures were present. Lymphatic invasion and microcalcifications were identified (Figure 3 [inset]). Immunohistochemical staining for cytokeratin 7 and gross cystic disease fluid protein 15 were strongly positive (Figure 4). Based on the histopathologic and immunohistochemical findings, a diagnosis of cutaneous metastatic breast adenocarcinoma was made. The patient opted to continue the homeopathic anticancer shakes and was subsequently lost to follow-up.

Cutaneous metastases of internal malignancies make up only 2% of all skin tumors,¹ making them relatively uncommon in the dermatologic setting. However, cutaneous metastasis occurs in 23.9% of patients with breast carcinoma, making it the most common tumor after malignant melanoma to metastasize to the skin.² The most common sites for breast carcinoma cutaneous metastasis (BCCM) are the chest wall and abdomen; other sites include the head/neck region and the extremities. The clinical presentation of BCCM varies depending on the mode of dissemination—lymphatic, hematogenous, contiguous growth, or iatrogenic implantation. The most common presentation is nodular carcinoma (47%–80%).^2,3 Other presentations include carcinoma telangiectoides (8%–11%),^2,3 alopecia neoplastica (2%–12%),^2,3 and carcinoma erysipeloides (3%–6%).^2,3 Carcinoma en cuirasse is rare.³

Nodular BCCM may present as firm solitary or grouped papules and nodules that are painless and range in color from flesh colored or pink to red-brown. Histologically, they are composed of atypical neoplastic cells arranged in small nests and cords, usually in a single-file line within the collagen bundles of the dermis.⁴ Carcinoma telangiectoides is characterized by its violaceous hue due to the dilated vascular channels. The lesions are purpuric papules and pseudovesicles appearing on an erythematous base, most commonly contiguous with the surgical scar. Histologically, collections of atypical tumor cells and erythrocytes are present along with dilated blood vessels in the papillary dermis.² Alopecia neoplastica presents as singular or grouped cicatricial patches of hair loss. Lesions of carcinoma erysipeloides present as warm, erythematous, tender, well-defined patches or plaques. Carcinoma en cuirasse is characterized by an erythematous sclerodermoid plaque on the chest wall.²

Our patient’s presentation was unique due to the widespread distribution, unusual pattern, and variable clinical morphologies of the cutaneous metastases. Our patient had findings of both carcinoma telangiectoides and nodular carcinoma. The mosaic violaceous erythema extending toward the mid-back rarely is reported in the literature and indicates extensive intravascular spread of tumor cells in the dermis.

Metastatic breast cancer is associated with a poor prognosis because it typically occurs in advanced stages and often does not respond to treatment.⁵ Although chemotherapy, hormonal therapy, and/or radiation therapy may improve survival, the choice in regimen is guided by cancer histology as well as prior treatments. In our case, the patient chose to continue her homeopathic therapy.

To the Editor:

Cutaneous metastases occur more often in the setting of breast carcinoma than other malignancies in women.¹ Although interventions are aimed at halting disease progression, cutaneous metastases indicate widespread disease and are associated with poor prognosis. We present the case of a patient with metastatic breast adenocarcinoma who developed cutaneous metastasis on the trunk after a double mastectomy. The widespread distribution and wide range of clinical manifestations are unique.

An 81-year-old woman presented to the dermatology office for evaluation of a skin eruption that started along a mastectomy scar on the left breast a few months postoperatively. She had a history of stage IV breast adenocarcinoma metastatic to the chest wall that was treated with a double mastectomy 2 years prior. The patient denied associated pain or pruritus and mainly was concerned with the cosmetic appearance. At the time of the initial diagnosis of breast adenocarcinoma, the patient was offered chemotherapy, which she did not tolerate. The patient opted against radiation therapy, as she preferred a more natural approach, such as anticancer shakes, which she was taking from a homeopathic source. She was unaware of the ingredients used in the shakes.

Physical examination revealed multiple grouped, firm, purpuric papules, nodules, and pseudovesicles on a background of violaceous erythema on the chest, abdomen, and flank (Figure 1). The background erythema had a mosaic pattern that extended toward the central back (Figure 2). A scoop shave biopsy of one of the purpuric nodules revealed highly atypical cells with abundant cytoplasm, large nuclei, and prominent nucleoli (Figure 3). Focally, the cells appeared to form glandular structures. Numerous atypical mitotic figures were present. Lymphatic invasion and microcalcifications were identified (Figure 3 [inset]). Immunohistochemical staining for cytokeratin 7 and gross cystic disease fluid protein 15 were strongly positive (Figure 4). Based on the histopathologic and immunohistochemical findings, a diagnosis of cutaneous metastatic breast adenocarcinoma was made. The patient opted to continue the homeopathic anticancer shakes and was subsequently lost to follow-up.

Cutaneous metastases of internal malignancies make up only 2% of all skin tumors,¹ making them relatively uncommon in the dermatologic setting. However, cutaneous metastasis occurs in 23.9% of patients with breast carcinoma, making it the most common tumor after malignant melanoma to metastasize to the skin.² The most common sites for breast carcinoma cutaneous metastasis (BCCM) are the chest wall and abdomen; other sites include the head/neck region and the extremities. The clinical presentation of BCCM varies depending on the mode of dissemination—lymphatic, hematogenous, contiguous growth, or iatrogenic implantation. The most common presentation is nodular carcinoma (47%–80%).^2,3 Other presentations include carcinoma telangiectoides (8%–11%),^2,3 alopecia neoplastica (2%–12%),^2,3 and carcinoma erysipeloides (3%–6%).^2,3 Carcinoma en cuirasse is rare.³

Nodular BCCM may present as firm solitary or grouped papules and nodules that are painless and range in color from flesh colored or pink to red-brown. Histologically, they are composed of atypical neoplastic cells arranged in small nests and cords, usually in a single-file line within the collagen bundles of the dermis.⁴ Carcinoma telangiectoides is characterized by its violaceous hue due to the dilated vascular channels. The lesions are purpuric papules and pseudovesicles appearing on an erythematous base, most commonly contiguous with the surgical scar. Histologically, collections of atypical tumor cells and erythrocytes are present along with dilated blood vessels in the papillary dermis.² Alopecia neoplastica presents as singular or grouped cicatricial patches of hair loss. Lesions of carcinoma erysipeloides present as warm, erythematous, tender, well-defined patches or plaques. Carcinoma en cuirasse is characterized by an erythematous sclerodermoid plaque on the chest wall.²

Our patient’s presentation was unique due to the widespread distribution, unusual pattern, and variable clinical morphologies of the cutaneous metastases. Our patient had findings of both carcinoma telangiectoides and nodular carcinoma. The mosaic violaceous erythema extending toward the mid-back rarely is reported in the literature and indicates extensive intravascular spread of tumor cells in the dermis.

Metastatic breast cancer is associated with a poor prognosis because it typically occurs in advanced stages and often does not respond to treatment.⁵ Although chemotherapy, hormonal therapy, and/or radiation therapy may improve survival, the choice in regimen is guided by cancer histology as well as prior treatments. In our case, the patient chose to continue her homeopathic therapy.

To the Editor:

A 62-year-old man presented with an atrophied painful left arm of 17 years’ duration that began when he was hit by a car as a pedestrian. He sustained severe multisystem injuries from the accident, including left brachial plexus and C6 nerve root avulsion injury. When he regained consciousness after 6 weeks in the intensive care unit, he immediately noted diffuse pain throughout the body, especially in the left arm. Since the accident, the patient continued to have diminished sensation to touch and temperature in the left arm. He also had burning, throbbing, and electrical pain in the left arm with light touch as well as spontaneously. He was thoroughly evaluated by a neurologist and was diagnosed with complex regional pain syndrome (CRPS) type II. For the treatment of pain, dorsal column stimulation and hemilaminectomy with exploration of the avulsed nerve root were attempted, both of which had minimal effect. He was maintained on hydromorphone, methadone, and oxazepam. He reported that for many years he was unable move out of bed due to the unbearable pain. With pain medications, he was able to regain most of his independence in his daily life, though the pain and other clinical aspects of CRPS still completely limited his use of the left arm.

Physical examination revealed glossy, cold, hairless skin with hypohidrosis of the left arm, forearm, and hand (Figures 1 and 2A). The left arm was conspicuously atrophied, with the forearm and hand erythematous. The fingers were taut, contracted, and edematous (Figure 2B), and the skin was unable to be pinched. The fingernails on the left hand had dystrophic changes including yellow color and brittleness with longitudinal ridges (Figure 3). The patient could activate the left bicep and tricep muscles against gravity but had minimal function of the deltoid muscle. He also had minimal movement of the left index finger and was unable to move any other digits of the left hand. The patient was continued on pain management treatments and physical therapy for his condition.

Complex regional pain syndrome is a neuropathic disorder of the extremities characterized by pain and a variety of autonomic and motor disturbances such as local edema, limited active range of motion, and vasomotor and trophic skin changes. There are 2 types of CRPS: type II is marked by explicit nerve injury and type I is not. The pathophysiology of CRPS is unknown.^1-3

There is no definite set of diagnostic criteria for CRPS. The lack of any gold-standard diagnostic test for CRPS has made arriving at one valid, widely accepted set of diagnostic criteria impossible.¹ There are 4 widely used sets of diagnostic criteria. One is the International Association for the Study of Pain diagnostic criteria defined in 1994.⁴ However, the criteria rely entirely on subjective symptoms and have been under great scrutiny due to their questionable validity.² Veldman et al⁵ presented other widely used CRPS diagnostic criteria in their prospective study of 829 reflex sympathetic dystrophy patients, which paid particular attention to the early clinical manifestations of CRPS. In 1999, Bruehl et al² proposed their own modified diagnostic criteria, which required physician-assessed signs in 2 of 4 categories to avoid the practice of exclusively relying on subjective symptoms. In addition, during a consensus meeting in Budapest, Hungary, a modified version of the Bruehl criteria was proposed.⁶ All 4 criteria rely solely on detailed history and physical examination, and the choice of diagnostic criteria remains subjective.

The pathophysiology of CRPS also remains unclear. There are several proposed mechanisms such as sympathetic nervous system dysfunction, abnormal inflammatory response, and central nervous system involvement.¹ Psychologic factors, sequelae of nerve injury, and genetic predisposition also have been implicated in the pathophysiology of CRPS.¹ It is likely that several mechanisms variably contribute to each presentation of CRPS.

Many dermatologic findings, in addition to neuromuscular symptoms, accompany CRPS and serve as important clues to making the clinical diagnosis. Complex regional pain syndrome has been thought to have 3 distinct sequential stages of CRPS.^1,3,7 Stage 1—the acute stage—is marked by hyperalgesia, allodynia, sudomotor disturbances, and prominent edema. Stage 2—the dystrophic stage—is characterized by more marked pain and sensory dysfunction, vasomotor dysfunction, development of motor dysfunction, soft tissue edema, skin and articular soft tissue thickening, and development of dystrophic nail changes. Stage 3—the atrophic stage—is marked by decreased pain and sensory disturbances, markedly increased motor dysfunction, waxy atrophic skin changes, progression of dystrophic nail changes, and skeletal cystic and subchondral erosions with diffuse osteoporosis.^1,3,7

The staging model, however, has been called into question.³ In a cluster analysis, Bruehl et al³ arrived at 3 relatively consistent CRPS patient subgroups that did not have notably different pain duration, suggesting the existence of 3 CRPS subtypes, not stages. Their study found that one of the subgroups best represented the clinical presentation of CRPS type II. This subgroup had the greatest pain and sensory abnormalities and the least vasomotor dysfunction of all 3 subgroups. Nonetheless, this study has not settled the discussion, as it only included 113 patients.³ Thus, with future studies, our understanding of CRPS in stages may change, which likely will impact how the clinical diagnosis is made.

There is a lack of high-quality evidence for most treatment interventions for CRPS⁸; however, the current practice is to use an interdisciplinary approach.^1,9,10 The main therapeutic arm of this approach is rehabilitation; physical and occupational therapy can help improve range of motion, contracture, and atrophy. The other 2 arms of the approach are psychologic therapy to improve quality of life and pain management with pharmacologic therapy and/or invasive interventions. The choice of therapy remains empirical; trial and error should be expected in developing an adequate treatment plan for each individual patient.

Many aspects of CRPS remain unclear, and even our current understanding of the disease will inevitably change over time. The syndrome can cause life-changing morbidities in patients, and late diagnosis and treatment are associated with poor prognosis. Because there are many dermatologic findings associated with the disorder, it is crucial for dermatologists to clinically recognize the disorder and to refer patients to appropriate channels so that treatment can be started as soon as possible.

To the Editor:

A 62-year-old man presented with an atrophied painful left arm of 17 years’ duration that began when he was hit by a car as a pedestrian. He sustained severe multisystem injuries from the accident, including left brachial plexus and C6 nerve root avulsion injury. When he regained consciousness after 6 weeks in the intensive care unit, he immediately noted diffuse pain throughout the body, especially in the left arm. Since the accident, the patient continued to have diminished sensation to touch and temperature in the left arm. He also had burning, throbbing, and electrical pain in the left arm with light touch as well as spontaneously. He was thoroughly evaluated by a neurologist and was diagnosed with complex regional pain syndrome (CRPS) type II. For the treatment of pain, dorsal column stimulation and hemilaminectomy with exploration of the avulsed nerve root were attempted, both of which had minimal effect. He was maintained on hydromorphone, methadone, and oxazepam. He reported that for many years he was unable move out of bed due to the unbearable pain. With pain medications, he was able to regain most of his independence in his daily life, though the pain and other clinical aspects of CRPS still completely limited his use of the left arm.

Physical examination revealed glossy, cold, hairless skin with hypohidrosis of the left arm, forearm, and hand (Figures 1 and 2A). The left arm was conspicuously atrophied, with the forearm and hand erythematous. The fingers were taut, contracted, and edematous (Figure 2B), and the skin was unable to be pinched. The fingernails on the left hand had dystrophic changes including yellow color and brittleness with longitudinal ridges (Figure 3). The patient could activate the left bicep and tricep muscles against gravity but had minimal function of the deltoid muscle. He also had minimal movement of the left index finger and was unable to move any other digits of the left hand. The patient was continued on pain management treatments and physical therapy for his condition.

Complex regional pain syndrome is a neuropathic disorder of the extremities characterized by pain and a variety of autonomic and motor disturbances such as local edema, limited active range of motion, and vasomotor and trophic skin changes. There are 2 types of CRPS: type II is marked by explicit nerve injury and type I is not. The pathophysiology of CRPS is unknown.^1-3

There is no definite set of diagnostic criteria for CRPS. The lack of any gold-standard diagnostic test for CRPS has made arriving at one valid, widely accepted set of diagnostic criteria impossible.¹ There are 4 widely used sets of diagnostic criteria. One is the International Association for the Study of Pain diagnostic criteria defined in 1994.⁴ However, the criteria rely entirely on subjective symptoms and have been under great scrutiny due to their questionable validity.² Veldman et al⁵ presented other widely used CRPS diagnostic criteria in their prospective study of 829 reflex sympathetic dystrophy patients, which paid particular attention to the early clinical manifestations of CRPS. In 1999, Bruehl et al² proposed their own modified diagnostic criteria, which required physician-assessed signs in 2 of 4 categories to avoid the practice of exclusively relying on subjective symptoms. In addition, during a consensus meeting in Budapest, Hungary, a modified version of the Bruehl criteria was proposed.⁶ All 4 criteria rely solely on detailed history and physical examination, and the choice of diagnostic criteria remains subjective.

The pathophysiology of CRPS also remains unclear. There are several proposed mechanisms such as sympathetic nervous system dysfunction, abnormal inflammatory response, and central nervous system involvement.¹ Psychologic factors, sequelae of nerve injury, and genetic predisposition also have been implicated in the pathophysiology of CRPS.¹ It is likely that several mechanisms variably contribute to each presentation of CRPS.

Many dermatologic findings, in addition to neuromuscular symptoms, accompany CRPS and serve as important clues to making the clinical diagnosis. Complex regional pain syndrome has been thought to have 3 distinct sequential stages of CRPS.^1,3,7 Stage 1—the acute stage—is marked by hyperalgesia, allodynia, sudomotor disturbances, and prominent edema. Stage 2—the dystrophic stage—is characterized by more marked pain and sensory dysfunction, vasomotor dysfunction, development of motor dysfunction, soft tissue edema, skin and articular soft tissue thickening, and development of dystrophic nail changes. Stage 3—the atrophic stage—is marked by decreased pain and sensory disturbances, markedly increased motor dysfunction, waxy atrophic skin changes, progression of dystrophic nail changes, and skeletal cystic and subchondral erosions with diffuse osteoporosis.^1,3,7

The staging model, however, has been called into question.³ In a cluster analysis, Bruehl et al³ arrived at 3 relatively consistent CRPS patient subgroups that did not have notably different pain duration, suggesting the existence of 3 CRPS subtypes, not stages. Their study found that one of the subgroups best represented the clinical presentation of CRPS type II. This subgroup had the greatest pain and sensory abnormalities and the least vasomotor dysfunction of all 3 subgroups. Nonetheless, this study has not settled the discussion, as it only included 113 patients.³ Thus, with future studies, our understanding of CRPS in stages may change, which likely will impact how the clinical diagnosis is made.

There is a lack of high-quality evidence for most treatment interventions for CRPS⁸; however, the current practice is to use an interdisciplinary approach.^1,9,10 The main therapeutic arm of this approach is rehabilitation; physical and occupational therapy can help improve range of motion, contracture, and atrophy. The other 2 arms of the approach are psychologic therapy to improve quality of life and pain management with pharmacologic therapy and/or invasive interventions. The choice of therapy remains empirical; trial and error should be expected in developing an adequate treatment plan for each individual patient.

Many aspects of CRPS remain unclear, and even our current understanding of the disease will inevitably change over time. The syndrome can cause life-changing morbidities in patients, and late diagnosis and treatment are associated with poor prognosis. Because there are many dermatologic findings associated with the disorder, it is crucial for dermatologists to clinically recognize the disorder and to refer patients to appropriate channels so that treatment can be started as soon as possible.

To the Editor:

A 62-year-old man presented with an atrophied painful left arm of 17 years’ duration that began when he was hit by a car as a pedestrian. He sustained severe multisystem injuries from the accident, including left brachial plexus and C6 nerve root avulsion injury. When he regained consciousness after 6 weeks in the intensive care unit, he immediately noted diffuse pain throughout the body, especially in the left arm. Since the accident, the patient continued to have diminished sensation to touch and temperature in the left arm. He also had burning, throbbing, and electrical pain in the left arm with light touch as well as spontaneously. He was thoroughly evaluated by a neurologist and was diagnosed with complex regional pain syndrome (CRPS) type II. For the treatment of pain, dorsal column stimulation and hemilaminectomy with exploration of the avulsed nerve root were attempted, both of which had minimal effect. He was maintained on hydromorphone, methadone, and oxazepam. He reported that for many years he was unable move out of bed due to the unbearable pain. With pain medications, he was able to regain most of his independence in his daily life, though the pain and other clinical aspects of CRPS still completely limited his use of the left arm.

Physical examination revealed glossy, cold, hairless skin with hypohidrosis of the left arm, forearm, and hand (Figures 1 and 2A). The left arm was conspicuously atrophied, with the forearm and hand erythematous. The fingers were taut, contracted, and edematous (Figure 2B), and the skin was unable to be pinched. The fingernails on the left hand had dystrophic changes including yellow color and brittleness with longitudinal ridges (Figure 3). The patient could activate the left bicep and tricep muscles against gravity but had minimal function of the deltoid muscle. He also had minimal movement of the left index finger and was unable to move any other digits of the left hand. The patient was continued on pain management treatments and physical therapy for his condition.

Complex regional pain syndrome is a neuropathic disorder of the extremities characterized by pain and a variety of autonomic and motor disturbances such as local edema, limited active range of motion, and vasomotor and trophic skin changes. There are 2 types of CRPS: type II is marked by explicit nerve injury and type I is not. The pathophysiology of CRPS is unknown.^1-3

There is no definite set of diagnostic criteria for CRPS. The lack of any gold-standard diagnostic test for CRPS has made arriving at one valid, widely accepted set of diagnostic criteria impossible.¹ There are 4 widely used sets of diagnostic criteria. One is the International Association for the Study of Pain diagnostic criteria defined in 1994.⁴ However, the criteria rely entirely on subjective symptoms and have been under great scrutiny due to their questionable validity.² Veldman et al⁵ presented other widely used CRPS diagnostic criteria in their prospective study of 829 reflex sympathetic dystrophy patients, which paid particular attention to the early clinical manifestations of CRPS. In 1999, Bruehl et al² proposed their own modified diagnostic criteria, which required physician-assessed signs in 2 of 4 categories to avoid the practice of exclusively relying on subjective symptoms. In addition, during a consensus meeting in Budapest, Hungary, a modified version of the Bruehl criteria was proposed.⁶ All 4 criteria rely solely on detailed history and physical examination, and the choice of diagnostic criteria remains subjective.

The pathophysiology of CRPS also remains unclear. There are several proposed mechanisms such as sympathetic nervous system dysfunction, abnormal inflammatory response, and central nervous system involvement.¹ Psychologic factors, sequelae of nerve injury, and genetic predisposition also have been implicated in the pathophysiology of CRPS.¹ It is likely that several mechanisms variably contribute to each presentation of CRPS.

Many dermatologic findings, in addition to neuromuscular symptoms, accompany CRPS and serve as important clues to making the clinical diagnosis. Complex regional pain syndrome has been thought to have 3 distinct sequential stages of CRPS.^1,3,7 Stage 1—the acute stage—is marked by hyperalgesia, allodynia, sudomotor disturbances, and prominent edema. Stage 2—the dystrophic stage—is characterized by more marked pain and sensory dysfunction, vasomotor dysfunction, development of motor dysfunction, soft tissue edema, skin and articular soft tissue thickening, and development of dystrophic nail changes. Stage 3—the atrophic stage—is marked by decreased pain and sensory disturbances, markedly increased motor dysfunction, waxy atrophic skin changes, progression of dystrophic nail changes, and skeletal cystic and subchondral erosions with diffuse osteoporosis.^1,3,7

The staging model, however, has been called into question.³ In a cluster analysis, Bruehl et al³ arrived at 3 relatively consistent CRPS patient subgroups that did not have notably different pain duration, suggesting the existence of 3 CRPS subtypes, not stages. Their study found that one of the subgroups best represented the clinical presentation of CRPS type II. This subgroup had the greatest pain and sensory abnormalities and the least vasomotor dysfunction of all 3 subgroups. Nonetheless, this study has not settled the discussion, as it only included 113 patients.³ Thus, with future studies, our understanding of CRPS in stages may change, which likely will impact how the clinical diagnosis is made.

There is a lack of high-quality evidence for most treatment interventions for CRPS⁸; however, the current practice is to use an interdisciplinary approach.^1,9,10 The main therapeutic arm of this approach is rehabilitation; physical and occupational therapy can help improve range of motion, contracture, and atrophy. The other 2 arms of the approach are psychologic therapy to improve quality of life and pain management with pharmacologic therapy and/or invasive interventions. The choice of therapy remains empirical; trial and error should be expected in developing an adequate treatment plan for each individual patient.

Many aspects of CRPS remain unclear, and even our current understanding of the disease will inevitably change over time. The syndrome can cause life-changing morbidities in patients, and late diagnosis and treatment are associated with poor prognosis. Because there are many dermatologic findings associated with the disorder, it is crucial for dermatologists to clinically recognize the disorder and to refer patients to appropriate channels so that treatment can be started as soon as possible.

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

[email protected]

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

[email protected]

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

[email protected]

The Diagnosis: Cutaneous Metastasis 

Histopathology demonstrated ulceration of the epidermis with necrosis of the papillary dermis. There was a diffuse infiltration of pleomorphic and atypical epithelioid cells in the reticular dermis (Figure). Focally there was ductal and glandular differentiation. The stroma was sclerotic. At the deep aspect of the biopsy specimen, tumor cells intercalated between collagen bundles in linear strands. Atypical mitoses were common, and necrosis en masse was seen. An immunohistochemical panel also was performed. Tissue from the biopsy was strongly positive for CDX-2 and cytokeratin 20 and diffusely negative for cytokeratin 7, gross cystic disease fluid protein 15, and prostate-specific antigen. The other biopsy was sent for cultures and grew no organisms, which confirmed the diagnosis of cutaneous metastasis from the patient's primary colonic adenocarcinoma. Due to the poor prognosis and his overall poor health, our patient opted for palliative care. 

Based on large retrospective studies, the frequency of cutaneous metastasis for patients diagnosed with any malignancy is 0.7% to 9.0%.^1-4 The third most common malignancy in both sexes is colorectal cancer, affecting approximately 5% of the US population.³ The frequency of cutaneous metastases from colorectal cancer is 0.81% to 3.9%.^1,2,4,5 Generally, cutaneous metastases present within 2 to 3 years from diagnosis of primary malignancy.^6,7 The most common sites for cutaneous metastases in a patient with colorectal cancer are the abdomen and pelvic region, often at surgical sites.^1-4,6-9  

The clinical presentation of cutaneous metastases varies greatly, and as a result, they commonly are misdiagnosed.^6,7 Although treatment with many antibiotics and antifungals had failed in our patient, the examination still was concerning for a possible granulomatous infection vs malignancy. With the history of colon cancer, radiation treatment, and chemotherapy, the possible malignancy diagnoses included primary skin cancers, viral tumors, and cutaneous metastasis. The initial evaluations had focused on infectious causes and resulted in 6 weeks of misdiagnosis and inappropriate therapy. Despite cutaneous metastases being uncommon, there should be a high index of suspicion for lesions in patients who have a history of cancer, especially if the lesion does not respond to treatment.^2,6,7  

Physical examination in our patient showed a high tumor burden as well as evidence of carcinoma erysipeloides on the lower abdomen and thighs, in addition to carcinoma en cuirasse throughout the pubic region. Carcinoma erysipeloides was first described in 1893 in a patient with breast cancer: "The erythematous infiltration of the skin was very superficial, and was attended simply by redness with a slight degree of induration. Until touched by the finger the condition might easily have been taken for a slightly-marked form of erysipelas."¹⁰ The clinical findings are a result of lymphatic and vascular obstruction.^3,9 The breast is the most common location to find carcinoma erysipeloides.³ It is an unusual occurrence to find it on the abdomen from colonic adenocarcinoma. The term cancer en cuirasse was coined in 1838 to describe the cutaneous manifestation of breast cancer that caused the skin to resemble the metal breastplate of a cuirasser.⁴ Similar to carcinoma erysipeloides, carcinoma en cuirasse most commonly is found as cutaneous metastasis from breast cancer, not from colonic adenocarcinoma.³  

The histologic characteristics of cutaneous metastases in general are similar to the primary malignancy but can be more poorly differentiated.⁷ Generally, neoplastic cells are seen in the lymphatic and blood vessels, and a large portion of the tumor is confined to the deep dermis and in the subcutaneous fat.^3,6 Histologic features of colonic adenocarcinoma metastases can demonstrate a well-differentiated, glandular architecture with mucin-secreting cells.^3,8,9 There also is a histologic pattern of neoplastic cells arranging themselves between collagen bundles in linear strands; this finding more commonly is seen in adenocarcinoma of the breast but also was seen in our patient.^3,9 With immunohistochemical staining, a truncated panel of cytokeratin 7, cytokeratin 20, and S-100 had a diagnostic accuracy of 100% for cutaneous metastases from colonic adenocarcinoma in one study. The pattern of all colonic adenocarcinomas was cytokeratin 20 positive and cytokeratin 7 and S-100 negative.⁶ 

Cutaneous metastases typically demonstrate widespread and rapidly progressive disease.^3,9 Survival studies of cutaneous metastases showed that 48% to 66% of patients died within the first 6 months.^3,6 Specifically, cutaneous metastases from colorectal cancers showed a median survival of 3 to 5 months.^6,7 Currently there are no treatment guidelines for cutaneous metastases.   

The Diagnosis: Cutaneous Metastasis 

Histopathology demonstrated ulceration of the epidermis with necrosis of the papillary dermis. There was a diffuse infiltration of pleomorphic and atypical epithelioid cells in the reticular dermis (Figure). Focally there was ductal and glandular differentiation. The stroma was sclerotic. At the deep aspect of the biopsy specimen, tumor cells intercalated between collagen bundles in linear strands. Atypical mitoses were common, and necrosis en masse was seen. An immunohistochemical panel also was performed. Tissue from the biopsy was strongly positive for CDX-2 and cytokeratin 20 and diffusely negative for cytokeratin 7, gross cystic disease fluid protein 15, and prostate-specific antigen. The other biopsy was sent for cultures and grew no organisms, which confirmed the diagnosis of cutaneous metastasis from the patient's primary colonic adenocarcinoma. Due to the poor prognosis and his overall poor health, our patient opted for palliative care. 

Based on large retrospective studies, the frequency of cutaneous metastasis for patients diagnosed with any malignancy is 0.7% to 9.0%.^1-4 The third most common malignancy in both sexes is colorectal cancer, affecting approximately 5% of the US population.³ The frequency of cutaneous metastases from colorectal cancer is 0.81% to 3.9%.^1,2,4,5 Generally, cutaneous metastases present within 2 to 3 years from diagnosis of primary malignancy.^6,7 The most common sites for cutaneous metastases in a patient with colorectal cancer are the abdomen and pelvic region, often at surgical sites.^1-4,6-9  

The clinical presentation of cutaneous metastases varies greatly, and as a result, they commonly are misdiagnosed.^6,7 Although treatment with many antibiotics and antifungals had failed in our patient, the examination still was concerning for a possible granulomatous infection vs malignancy. With the history of colon cancer, radiation treatment, and chemotherapy, the possible malignancy diagnoses included primary skin cancers, viral tumors, and cutaneous metastasis. The initial evaluations had focused on infectious causes and resulted in 6 weeks of misdiagnosis and inappropriate therapy. Despite cutaneous metastases being uncommon, there should be a high index of suspicion for lesions in patients who have a history of cancer, especially if the lesion does not respond to treatment.^2,6,7  

Physical examination in our patient showed a high tumor burden as well as evidence of carcinoma erysipeloides on the lower abdomen and thighs, in addition to carcinoma en cuirasse throughout the pubic region. Carcinoma erysipeloides was first described in 1893 in a patient with breast cancer: "The erythematous infiltration of the skin was very superficial, and was attended simply by redness with a slight degree of induration. Until touched by the finger the condition might easily have been taken for a slightly-marked form of erysipelas."¹⁰ The clinical findings are a result of lymphatic and vascular obstruction.^3,9 The breast is the most common location to find carcinoma erysipeloides.³ It is an unusual occurrence to find it on the abdomen from colonic adenocarcinoma. The term cancer en cuirasse was coined in 1838 to describe the cutaneous manifestation of breast cancer that caused the skin to resemble the metal breastplate of a cuirasser.⁴ Similar to carcinoma erysipeloides, carcinoma en cuirasse most commonly is found as cutaneous metastasis from breast cancer, not from colonic adenocarcinoma.³  

The histologic characteristics of cutaneous metastases in general are similar to the primary malignancy but can be more poorly differentiated.⁷ Generally, neoplastic cells are seen in the lymphatic and blood vessels, and a large portion of the tumor is confined to the deep dermis and in the subcutaneous fat.^3,6 Histologic features of colonic adenocarcinoma metastases can demonstrate a well-differentiated, glandular architecture with mucin-secreting cells.^3,8,9 There also is a histologic pattern of neoplastic cells arranging themselves between collagen bundles in linear strands; this finding more commonly is seen in adenocarcinoma of the breast but also was seen in our patient.^3,9 With immunohistochemical staining, a truncated panel of cytokeratin 7, cytokeratin 20, and S-100 had a diagnostic accuracy of 100% for cutaneous metastases from colonic adenocarcinoma in one study. The pattern of all colonic adenocarcinomas was cytokeratin 20 positive and cytokeratin 7 and S-100 negative.⁶ 

Cutaneous metastases typically demonstrate widespread and rapidly progressive disease.^3,9 Survival studies of cutaneous metastases showed that 48% to 66% of patients died within the first 6 months.^3,6 Specifically, cutaneous metastases from colorectal cancers showed a median survival of 3 to 5 months.^6,7 Currently there are no treatment guidelines for cutaneous metastases.   

The Diagnosis: Cutaneous Metastasis 

Histopathology demonstrated ulceration of the epidermis with necrosis of the papillary dermis. There was a diffuse infiltration of pleomorphic and atypical epithelioid cells in the reticular dermis (Figure). Focally there was ductal and glandular differentiation. The stroma was sclerotic. At the deep aspect of the biopsy specimen, tumor cells intercalated between collagen bundles in linear strands. Atypical mitoses were common, and necrosis en masse was seen. An immunohistochemical panel also was performed. Tissue from the biopsy was strongly positive for CDX-2 and cytokeratin 20 and diffusely negative for cytokeratin 7, gross cystic disease fluid protein 15, and prostate-specific antigen. The other biopsy was sent for cultures and grew no organisms, which confirmed the diagnosis of cutaneous metastasis from the patient's primary colonic adenocarcinoma. Due to the poor prognosis and his overall poor health, our patient opted for palliative care. 

Based on large retrospective studies, the frequency of cutaneous metastasis for patients diagnosed with any malignancy is 0.7% to 9.0%.^1-4 The third most common malignancy in both sexes is colorectal cancer, affecting approximately 5% of the US population.³ The frequency of cutaneous metastases from colorectal cancer is 0.81% to 3.9%.^1,2,4,5 Generally, cutaneous metastases present within 2 to 3 years from diagnosis of primary malignancy.^6,7 The most common sites for cutaneous metastases in a patient with colorectal cancer are the abdomen and pelvic region, often at surgical sites.^1-4,6-9  

The clinical presentation of cutaneous metastases varies greatly, and as a result, they commonly are misdiagnosed.^6,7 Although treatment with many antibiotics and antifungals had failed in our patient, the examination still was concerning for a possible granulomatous infection vs malignancy. With the history of colon cancer, radiation treatment, and chemotherapy, the possible malignancy diagnoses included primary skin cancers, viral tumors, and cutaneous metastasis. The initial evaluations had focused on infectious causes and resulted in 6 weeks of misdiagnosis and inappropriate therapy. Despite cutaneous metastases being uncommon, there should be a high index of suspicion for lesions in patients who have a history of cancer, especially if the lesion does not respond to treatment.^2,6,7  

Physical examination in our patient showed a high tumor burden as well as evidence of carcinoma erysipeloides on the lower abdomen and thighs, in addition to carcinoma en cuirasse throughout the pubic region. Carcinoma erysipeloides was first described in 1893 in a patient with breast cancer: "The erythematous infiltration of the skin was very superficial, and was attended simply by redness with a slight degree of induration. Until touched by the finger the condition might easily have been taken for a slightly-marked form of erysipelas."¹⁰ The clinical findings are a result of lymphatic and vascular obstruction.^3,9 The breast is the most common location to find carcinoma erysipeloides.³ It is an unusual occurrence to find it on the abdomen from colonic adenocarcinoma. The term cancer en cuirasse was coined in 1838 to describe the cutaneous manifestation of breast cancer that caused the skin to resemble the metal breastplate of a cuirasser.⁴ Similar to carcinoma erysipeloides, carcinoma en cuirasse most commonly is found as cutaneous metastasis from breast cancer, not from colonic adenocarcinoma.³  

The histologic characteristics of cutaneous metastases in general are similar to the primary malignancy but can be more poorly differentiated.⁷ Generally, neoplastic cells are seen in the lymphatic and blood vessels, and a large portion of the tumor is confined to the deep dermis and in the subcutaneous fat.^3,6 Histologic features of colonic adenocarcinoma metastases can demonstrate a well-differentiated, glandular architecture with mucin-secreting cells.^3,8,9 There also is a histologic pattern of neoplastic cells arranging themselves between collagen bundles in linear strands; this finding more commonly is seen in adenocarcinoma of the breast but also was seen in our patient.^3,9 With immunohistochemical staining, a truncated panel of cytokeratin 7, cytokeratin 20, and S-100 had a diagnostic accuracy of 100% for cutaneous metastases from colonic adenocarcinoma in one study. The pattern of all colonic adenocarcinomas was cytokeratin 20 positive and cytokeratin 7 and S-100 negative.⁶ 

Cutaneous metastases typically demonstrate widespread and rapidly progressive disease.^3,9 Survival studies of cutaneous metastases showed that 48% to 66% of patients died within the first 6 months.^3,6 Specifically, cutaneous metastases from colorectal cancers showed a median survival of 3 to 5 months.^6,7 Currently there are no treatment guidelines for cutaneous metastases.   

Here are the stories our MDedge editors across specialties think you need to know about today:

Are ACE inhibitors protective in COVID-19?

Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.

READ MORE.

AMI: Admissions drop, deaths rise

In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.

READ MORE.

Prenatal, postpartum screening for depression falls short

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

READ MORE.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Are ACE inhibitors protective in COVID-19?

Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.

READ MORE.

AMI: Admissions drop, deaths rise

In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.

READ MORE.

Prenatal, postpartum screening for depression falls short

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

READ MORE.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Are ACE inhibitors protective in COVID-19?

Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.

READ MORE.

AMI: Admissions drop, deaths rise

In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.

READ MORE.

Prenatal, postpartum screening for depression falls short

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

READ MORE.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.