Article

The latest research on disease-modifying therapies presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2023 annual meeting is reported by Dr Jennifer Graves from the University of California, San Diego. 

Dr Graves first discusses a small study exploring the effects of an intermittent calorie restriction (ICR) diet on adipokine levels, metabolic and immune/inflammatory biomarkers, and MRI measurements. Researchers found that short-term ICR can improve metabolic and immunologic profiles in patients with MS.  

Next, Dr Graves discusses a trial that successively measured changes in proteins in the cerebrospinal fluid of patients treated with tolebrutinib and ocrelizumab as evidence of therapeutic efficacy. This study provides early evidence of the impact of these medications directly in the central nervous system. 

She then details a study evaluating autologous hematopoietic stem cell transplant (aHSCT) as an MS treatment. The study found that aHSCT has a durable effect for up to 5-10 years compared to our current available regimens.  

Finally, Dr Graves highlights the National MS Society Barancik Prize winner Dr Ruth Ann Marrie. Dr Marrie is a pioneer for her research in comorbidities and their effect on MS treatment decisions, especially in choosing disease-modifying therapies.  

--

Jennifer S.O. Graves, MD, PhD, Associate Professor, Director Neuroimmunology Research, Department of Neurosciences, University of California, San Diego  

Jennifer S.O. Graves, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) on an advisory board for: TG Therapeutics; Bayer 

Received research grant from: Sanofi; EMD Serono; Biogen; ATARA; Octave 

The latest research on disease-modifying therapies presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2023 annual meeting is reported by Dr Jennifer Graves from the University of California, San Diego. 

Dr Graves first discusses a small study exploring the effects of an intermittent calorie restriction (ICR) diet on adipokine levels, metabolic and immune/inflammatory biomarkers, and MRI measurements. Researchers found that short-term ICR can improve metabolic and immunologic profiles in patients with MS.  

Next, Dr Graves discusses a trial that successively measured changes in proteins in the cerebrospinal fluid of patients treated with tolebrutinib and ocrelizumab as evidence of therapeutic efficacy. This study provides early evidence of the impact of these medications directly in the central nervous system. 

She then details a study evaluating autologous hematopoietic stem cell transplant (aHSCT) as an MS treatment. The study found that aHSCT has a durable effect for up to 5-10 years compared to our current available regimens.  

Finally, Dr Graves highlights the National MS Society Barancik Prize winner Dr Ruth Ann Marrie. Dr Marrie is a pioneer for her research in comorbidities and their effect on MS treatment decisions, especially in choosing disease-modifying therapies.  

--

Jennifer S.O. Graves, MD, PhD, Associate Professor, Director Neuroimmunology Research, Department of Neurosciences, University of California, San Diego  

Jennifer S.O. Graves, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) on an advisory board for: TG Therapeutics; Bayer 

Received research grant from: Sanofi; EMD Serono; Biogen; ATARA; Octave 

The latest research on disease-modifying therapies presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2023 annual meeting is reported by Dr Jennifer Graves from the University of California, San Diego. 

Dr Graves first discusses a small study exploring the effects of an intermittent calorie restriction (ICR) diet on adipokine levels, metabolic and immune/inflammatory biomarkers, and MRI measurements. Researchers found that short-term ICR can improve metabolic and immunologic profiles in patients with MS.  

Next, Dr Graves discusses a trial that successively measured changes in proteins in the cerebrospinal fluid of patients treated with tolebrutinib and ocrelizumab as evidence of therapeutic efficacy. This study provides early evidence of the impact of these medications directly in the central nervous system. 

She then details a study evaluating autologous hematopoietic stem cell transplant (aHSCT) as an MS treatment. The study found that aHSCT has a durable effect for up to 5-10 years compared to our current available regimens.  

Finally, Dr Graves highlights the National MS Society Barancik Prize winner Dr Ruth Ann Marrie. Dr Marrie is a pioneer for her research in comorbidities and their effect on MS treatment decisions, especially in choosing disease-modifying therapies.  

--

Jennifer S.O. Graves, MD, PhD, Associate Professor, Director Neuroimmunology Research, Department of Neurosciences, University of California, San Diego  

Jennifer S.O. Graves, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) on an advisory board for: TG Therapeutics; Bayer 

Received research grant from: Sanofi; EMD Serono; Biogen; ATARA; Octave 

The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP). 

SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.

SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.

SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered. 

The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.

Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP. 
 

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP). 

SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.

SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.

SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered. 

The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.

Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP. 
 

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP). 

SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.

SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.

SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered. 

The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.

Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP. 
 

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Dermoscopy revealed an 8-mm scaly brown-black papule that lacked melanocytic features (pigment network, globules, streaks, or homogeneous blue or brown color) but had milia-like cysts and so-called “fat fingers” (short, straight to curved radial projections¹). These findings were consistent with a diagnosis of seborrheic keratosis (SK).

SKs go by many names and are often confused with nevi. Some patients might know them by such names as “age spots” or “liver spots.” Patients often have many SKs on their body; the back and skin folds are common locations. Patients may be unhappy about the way they look and may describe occasional discomfort when the SKs rub against clothes and inflammation that occurs spontaneously or with trauma.

Classic SKs have a well-demarcated border and waxy, stuck-on appearance. There are times when it is difficult to distinguish between an SK and a melanocytic lesion. Thus, a biopsy may be necessary. In addition, SKs are so common that collision lesions may occur. (Collision lesions result when 2 histologically distinct neoplasms occur adjacent to each other and cause an unusual clinical appearance with features of each lesion.) The atypical clinical features in a collision lesion may prompt a biopsy to exclude malignancy.

Dermoscopic features of SKs include well-demarcated borders, milia-like cysts (white circular inclusions), comedo-like openings (brown/black circular inclusions), fissures and ridges, hairpin vessels, and fat fingers.

Cryotherapy is a quick and efficient treatment when a patient would like the lesions removed. Curettage or light electrodessication may be less likely to cause post-inflammatory hypopigmentation in patients with darker skin types. These various destructive therapies are often considered cosmetic and are unlikely to be covered by insurance unless there is documentation of significant inflammation or discomfort. In this case, the lesion was not treated.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermoscopy revealed an 8-mm scaly brown-black papule that lacked melanocytic features (pigment network, globules, streaks, or homogeneous blue or brown color) but had milia-like cysts and so-called “fat fingers” (short, straight to curved radial projections¹). These findings were consistent with a diagnosis of seborrheic keratosis (SK).

SKs go by many names and are often confused with nevi. Some patients might know them by such names as “age spots” or “liver spots.” Patients often have many SKs on their body; the back and skin folds are common locations. Patients may be unhappy about the way they look and may describe occasional discomfort when the SKs rub against clothes and inflammation that occurs spontaneously or with trauma.

Classic SKs have a well-demarcated border and waxy, stuck-on appearance. There are times when it is difficult to distinguish between an SK and a melanocytic lesion. Thus, a biopsy may be necessary. In addition, SKs are so common that collision lesions may occur. (Collision lesions result when 2 histologically distinct neoplasms occur adjacent to each other and cause an unusual clinical appearance with features of each lesion.) The atypical clinical features in a collision lesion may prompt a biopsy to exclude malignancy.

Dermoscopic features of SKs include well-demarcated borders, milia-like cysts (white circular inclusions), comedo-like openings (brown/black circular inclusions), fissures and ridges, hairpin vessels, and fat fingers.

Cryotherapy is a quick and efficient treatment when a patient would like the lesions removed. Curettage or light electrodessication may be less likely to cause post-inflammatory hypopigmentation in patients with darker skin types. These various destructive therapies are often considered cosmetic and are unlikely to be covered by insurance unless there is documentation of significant inflammation or discomfort. In this case, the lesion was not treated.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermoscopy revealed an 8-mm scaly brown-black papule that lacked melanocytic features (pigment network, globules, streaks, or homogeneous blue or brown color) but had milia-like cysts and so-called “fat fingers” (short, straight to curved radial projections¹). These findings were consistent with a diagnosis of seborrheic keratosis (SK).

SKs go by many names and are often confused with nevi. Some patients might know them by such names as “age spots” or “liver spots.” Patients often have many SKs on their body; the back and skin folds are common locations. Patients may be unhappy about the way they look and may describe occasional discomfort when the SKs rub against clothes and inflammation that occurs spontaneously or with trauma.

Classic SKs have a well-demarcated border and waxy, stuck-on appearance. There are times when it is difficult to distinguish between an SK and a melanocytic lesion. Thus, a biopsy may be necessary. In addition, SKs are so common that collision lesions may occur. (Collision lesions result when 2 histologically distinct neoplasms occur adjacent to each other and cause an unusual clinical appearance with features of each lesion.) The atypical clinical features in a collision lesion may prompt a biopsy to exclude malignancy.

Dermoscopic features of SKs include well-demarcated borders, milia-like cysts (white circular inclusions), comedo-like openings (brown/black circular inclusions), fissures and ridges, hairpin vessels, and fat fingers.

Cryotherapy is a quick and efficient treatment when a patient would like the lesions removed. Curettage or light electrodessication may be less likely to cause post-inflammatory hypopigmentation in patients with darker skin types. These various destructive therapies are often considered cosmetic and are unlikely to be covered by insurance unless there is documentation of significant inflammation or discomfort. In this case, the lesion was not treated.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The Diagnosis: Darier Disease

A clinical diagnosis of Darier disease was made from the skin findings of pruritic, malodorous, keratotic papules in a seborrheic distribution and pathognomonic nail dystrophy, along with a family history that demonstrated autosomal-dominant inheritance. The ulcerations were suspected to be caused by a superimposed herpes simplex virus (HSV) infection in the form of eczema herpeticum. The clinical diagnosis was later confirmed via punch biopsy. Pathology results demonstrated focal acantholytic dyskeratosis, which was consistent with Darier disease given the focal nature and lack of acanthosis. The patient’s father and sister also were confirmed to have Darier disease by an outside dermatologist.

Darier disease is a rare keratinizing autosomaldominant genodermatosis that occurs due to a mutation in the ATP2A2 gene, which encodes a sarco/endoplasmic reticulum calcium ATPase pump that decreases cell adhesion between keratinocytes, leading to epidermal acantholysis and dyskeratosis and ultimately a disrupted skin barrier.^1,2 Darier disease often presents in childhood and adolescence with papules in a seborrheic distribution on the central chest and back (Figure, A); the intertriginous folds also may be involved. Darier disease can manifest with palmoplantar pits (Figure, B), a cobblestonelike texture of the oral mucosa, acrokeratosis verruciformis of Hopf, and nail findings with alternating red and white longitudinal streaks in the nail bed resembling a candy cane along with characteristic V nicking deformities of the nails themselves (Figure, C). Chronic flares may occur throughout one’s lifetime, with patients experiencing more symptoms in the summer months due to heat, sweat, and UV light exposure, as well as infections that irritate the skin and worsen dyskeratosis. Studies have revealed an association between Darier disease and neuropsychiatric conditions, including major depressive disorder, schizophrenia, and bipolar disorder.^3,4

The skin barrier is compromised in patients with Darier disease, thereby making secondary infection more likely to occur. Polymerase chain reaction swabs of our patient’s purulent ulcerations were positive for HSV type 1, further strengthening a diagnosis of secondary eczema herpeticum, which occurs when patients have widespread HSV superinfecting pre-existing skin conditions such as atopic dermatitis, Darier disease, and Hailey-Hailey disease.^5-7 The lesions are characterized by a monomorphic eruption of umbilicated vesicles on an erythematous base. Lesions can progress to punched-out ulcers and erosions with hemorrhagic crusts that coalesce, forming scalloped borders, similar to our patient’s presentation.⁸

Hailey-Hailey disease, a genodermatosis that alters calcium signaling with an autosomal-dominant inheritance pattern, was unlikely in our patient due to the presence of nail abnormalities and palmar pits that are characteristic of Darier disease. From a purely histopathologic standpoint, Grover disease was considered with skin biopsy demonstrating acantholytic dyskeratosis but was not compatible with the clinical context. Furthermore, trials of antibiotics with group A Streptococcus and Staphylococcus aureus coverage failed in our patient, and she lacked systemic symptoms that would be supportive of a cellulitis diagnosis. The punched-out lesions suggested that an isolated exacerbation of atopic dermatitis was not sufficient to explain all of the clinical findings.

Eczema herpeticum must be considered in the differential diagnosis for patients with underlying Darier disease and widespread ulcerations. Our patient had more recent punched-out ulcerations in the intertriginous regions, with other areas showing later stages of confluent ulcers with scalloped borders. Delayed diagnosis and treatment of eczema herpeticum combined with severe Darier disease can lead to increased risk for hospitalization and rarely fatality.^8,9

Our patient was started on intravenous acyclovir until the lesions crusted and then was transitioned to a suppressive dose of oral valacyclovir given the widespread distribution. The Darier disease itself was managed with topical steroids and a zinc oxide barrier, serving as protectants to pathogens through microscopic breaks in the skin. Our patient also had a mild case of candidal intertrigo that was exacerbated by obesity and managed with topical ketoconazole. Gabapentin, hydromorphone, and acetaminophen were used for pain. She was discharged 10 days after admission with substantial improvement of both the HSV lesions and the irritation from her Darier disease. At follow-up visits 20 days later and again 6 months after discharge, she had been feeling well without any HSV flares.

The eczema herpeticum likely arose from our patient’s chronic skin barrier impairment attributed to Darier disease, leading to the cutaneous inoculation of HSV. Our patient and her family members had never been evaluated by a dermatologist until late in life during this hospitalization. Medication compliance with a suppressive dose of oral valacyclovir and topical steroids is vital to prevent flares of both eczema herpeticum and Darier disease, respectively. This case highlights the importance of dermatology consultation for complex cutaneous findings, as delayed diagnosis and treatment can lead to increased morbidity and mortality.

The Diagnosis: Darier Disease

A clinical diagnosis of Darier disease was made from the skin findings of pruritic, malodorous, keratotic papules in a seborrheic distribution and pathognomonic nail dystrophy, along with a family history that demonstrated autosomal-dominant inheritance. The ulcerations were suspected to be caused by a superimposed herpes simplex virus (HSV) infection in the form of eczema herpeticum. The clinical diagnosis was later confirmed via punch biopsy. Pathology results demonstrated focal acantholytic dyskeratosis, which was consistent with Darier disease given the focal nature and lack of acanthosis. The patient’s father and sister also were confirmed to have Darier disease by an outside dermatologist.

Darier disease is a rare keratinizing autosomaldominant genodermatosis that occurs due to a mutation in the ATP2A2 gene, which encodes a sarco/endoplasmic reticulum calcium ATPase pump that decreases cell adhesion between keratinocytes, leading to epidermal acantholysis and dyskeratosis and ultimately a disrupted skin barrier.^1,2 Darier disease often presents in childhood and adolescence with papules in a seborrheic distribution on the central chest and back (Figure, A); the intertriginous folds also may be involved. Darier disease can manifest with palmoplantar pits (Figure, B), a cobblestonelike texture of the oral mucosa, acrokeratosis verruciformis of Hopf, and nail findings with alternating red and white longitudinal streaks in the nail bed resembling a candy cane along with characteristic V nicking deformities of the nails themselves (Figure, C). Chronic flares may occur throughout one’s lifetime, with patients experiencing more symptoms in the summer months due to heat, sweat, and UV light exposure, as well as infections that irritate the skin and worsen dyskeratosis. Studies have revealed an association between Darier disease and neuropsychiatric conditions, including major depressive disorder, schizophrenia, and bipolar disorder.^3,4

The skin barrier is compromised in patients with Darier disease, thereby making secondary infection more likely to occur. Polymerase chain reaction swabs of our patient’s purulent ulcerations were positive for HSV type 1, further strengthening a diagnosis of secondary eczema herpeticum, which occurs when patients have widespread HSV superinfecting pre-existing skin conditions such as atopic dermatitis, Darier disease, and Hailey-Hailey disease.^5-7 The lesions are characterized by a monomorphic eruption of umbilicated vesicles on an erythematous base. Lesions can progress to punched-out ulcers and erosions with hemorrhagic crusts that coalesce, forming scalloped borders, similar to our patient’s presentation.⁸

Hailey-Hailey disease, a genodermatosis that alters calcium signaling with an autosomal-dominant inheritance pattern, was unlikely in our patient due to the presence of nail abnormalities and palmar pits that are characteristic of Darier disease. From a purely histopathologic standpoint, Grover disease was considered with skin biopsy demonstrating acantholytic dyskeratosis but was not compatible with the clinical context. Furthermore, trials of antibiotics with group A Streptococcus and Staphylococcus aureus coverage failed in our patient, and she lacked systemic symptoms that would be supportive of a cellulitis diagnosis. The punched-out lesions suggested that an isolated exacerbation of atopic dermatitis was not sufficient to explain all of the clinical findings.

Eczema herpeticum must be considered in the differential diagnosis for patients with underlying Darier disease and widespread ulcerations. Our patient had more recent punched-out ulcerations in the intertriginous regions, with other areas showing later stages of confluent ulcers with scalloped borders. Delayed diagnosis and treatment of eczema herpeticum combined with severe Darier disease can lead to increased risk for hospitalization and rarely fatality.^8,9

Our patient was started on intravenous acyclovir until the lesions crusted and then was transitioned to a suppressive dose of oral valacyclovir given the widespread distribution. The Darier disease itself was managed with topical steroids and a zinc oxide barrier, serving as protectants to pathogens through microscopic breaks in the skin. Our patient also had a mild case of candidal intertrigo that was exacerbated by obesity and managed with topical ketoconazole. Gabapentin, hydromorphone, and acetaminophen were used for pain. She was discharged 10 days after admission with substantial improvement of both the HSV lesions and the irritation from her Darier disease. At follow-up visits 20 days later and again 6 months after discharge, she had been feeling well without any HSV flares.

The eczema herpeticum likely arose from our patient’s chronic skin barrier impairment attributed to Darier disease, leading to the cutaneous inoculation of HSV. Our patient and her family members had never been evaluated by a dermatologist until late in life during this hospitalization. Medication compliance with a suppressive dose of oral valacyclovir and topical steroids is vital to prevent flares of both eczema herpeticum and Darier disease, respectively. This case highlights the importance of dermatology consultation for complex cutaneous findings, as delayed diagnosis and treatment can lead to increased morbidity and mortality.

The Diagnosis: Darier Disease

A clinical diagnosis of Darier disease was made from the skin findings of pruritic, malodorous, keratotic papules in a seborrheic distribution and pathognomonic nail dystrophy, along with a family history that demonstrated autosomal-dominant inheritance. The ulcerations were suspected to be caused by a superimposed herpes simplex virus (HSV) infection in the form of eczema herpeticum. The clinical diagnosis was later confirmed via punch biopsy. Pathology results demonstrated focal acantholytic dyskeratosis, which was consistent with Darier disease given the focal nature and lack of acanthosis. The patient’s father and sister also were confirmed to have Darier disease by an outside dermatologist.

Darier disease is a rare keratinizing autosomaldominant genodermatosis that occurs due to a mutation in the ATP2A2 gene, which encodes a sarco/endoplasmic reticulum calcium ATPase pump that decreases cell adhesion between keratinocytes, leading to epidermal acantholysis and dyskeratosis and ultimately a disrupted skin barrier.^1,2 Darier disease often presents in childhood and adolescence with papules in a seborrheic distribution on the central chest and back (Figure, A); the intertriginous folds also may be involved. Darier disease can manifest with palmoplantar pits (Figure, B), a cobblestonelike texture of the oral mucosa, acrokeratosis verruciformis of Hopf, and nail findings with alternating red and white longitudinal streaks in the nail bed resembling a candy cane along with characteristic V nicking deformities of the nails themselves (Figure, C). Chronic flares may occur throughout one’s lifetime, with patients experiencing more symptoms in the summer months due to heat, sweat, and UV light exposure, as well as infections that irritate the skin and worsen dyskeratosis. Studies have revealed an association between Darier disease and neuropsychiatric conditions, including major depressive disorder, schizophrenia, and bipolar disorder.^3,4

The skin barrier is compromised in patients with Darier disease, thereby making secondary infection more likely to occur. Polymerase chain reaction swabs of our patient’s purulent ulcerations were positive for HSV type 1, further strengthening a diagnosis of secondary eczema herpeticum, which occurs when patients have widespread HSV superinfecting pre-existing skin conditions such as atopic dermatitis, Darier disease, and Hailey-Hailey disease.^5-7 The lesions are characterized by a monomorphic eruption of umbilicated vesicles on an erythematous base. Lesions can progress to punched-out ulcers and erosions with hemorrhagic crusts that coalesce, forming scalloped borders, similar to our patient’s presentation.⁸

Hailey-Hailey disease, a genodermatosis that alters calcium signaling with an autosomal-dominant inheritance pattern, was unlikely in our patient due to the presence of nail abnormalities and palmar pits that are characteristic of Darier disease. From a purely histopathologic standpoint, Grover disease was considered with skin biopsy demonstrating acantholytic dyskeratosis but was not compatible with the clinical context. Furthermore, trials of antibiotics with group A Streptococcus and Staphylococcus aureus coverage failed in our patient, and she lacked systemic symptoms that would be supportive of a cellulitis diagnosis. The punched-out lesions suggested that an isolated exacerbation of atopic dermatitis was not sufficient to explain all of the clinical findings.

Eczema herpeticum must be considered in the differential diagnosis for patients with underlying Darier disease and widespread ulcerations. Our patient had more recent punched-out ulcerations in the intertriginous regions, with other areas showing later stages of confluent ulcers with scalloped borders. Delayed diagnosis and treatment of eczema herpeticum combined with severe Darier disease can lead to increased risk for hospitalization and rarely fatality.^8,9

Our patient was started on intravenous acyclovir until the lesions crusted and then was transitioned to a suppressive dose of oral valacyclovir given the widespread distribution. The Darier disease itself was managed with topical steroids and a zinc oxide barrier, serving as protectants to pathogens through microscopic breaks in the skin. Our patient also had a mild case of candidal intertrigo that was exacerbated by obesity and managed with topical ketoconazole. Gabapentin, hydromorphone, and acetaminophen were used for pain. She was discharged 10 days after admission with substantial improvement of both the HSV lesions and the irritation from her Darier disease. At follow-up visits 20 days later and again 6 months after discharge, she had been feeling well without any HSV flares.

The eczema herpeticum likely arose from our patient’s chronic skin barrier impairment attributed to Darier disease, leading to the cutaneous inoculation of HSV. Our patient and her family members had never been evaluated by a dermatologist until late in life during this hospitalization. Medication compliance with a suppressive dose of oral valacyclovir and topical steroids is vital to prevent flares of both eczema herpeticum and Darier disease, respectively. This case highlights the importance of dermatology consultation for complex cutaneous findings, as delayed diagnosis and treatment can lead to increased morbidity and mortality.

The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).

AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.

CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD. 

Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials. 

Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).

AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.

CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD. 

Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials. 

Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).

AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.

CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD. 

Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials. 

Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of advanced/metastatic breast cancer. 

Breast cancer is the most frequently diagnosed life-threatening cancer and the second-leading cause of cancer-related deaths in women worldwide. In the United States, an estimated 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 women died of the disease. Globally, approximately 2.3 million new diagnoses and 685,000 breast cancer–related deaths were reported in 2020.

Tumor size, nodal spread, and distant metastases (TNM) at the time of diagnosis are key prognostic factors. Immunohistochemistry tumor markers (ie, estrogen receptor [ER], progesterone receptor [PR], and HER2), as well as grade and Ki-67 expression, have also been shown to be independent predictors of breast cancer death and are used together with TNM to guide treatment decisions. 

Despite advances in breast cancer diagnosis and treatment, metastatic recurrence remains a significant problem. Although the incidence of distance relapse is declining and survival times for patients with recurrent disease are improving, 20%-30% of patients with early breast cancer still die of metastatic disease. Metastatic breast cancer recurrence can arise months to decades after initial diagnosis and treatment. 

According to the National Comprehensive Cancer Network (NCCN) guidelines, biopsy is a critical component of the workup for patients with recurrent or stage IV disease. This is because biopsy ensures accurate determination of metastatic/recurrent disease and tumor histology and enables biomarker determination and selection of appropriate treatment. Soft-tissue tumor biopsy is preferred over bone sites unless a portion of the biopsy can be protected from harsh decalcification solution to preserve more accurate evaluation of biomarkers. Determination of HR status (ER and PR) and HER2 status should be repeated in all cases when diagnostic tissue is obtained because ER and PR assays may be falsely negative or falsely positive, and there may be discordance between the primary and metastatic tumors. According to the NCCN panel, re-testing the receptor status of recurrent disease should be performed, particularly when it was previously unknown, originally negative, or not overexpressed. 

Additionally, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include history and physical exam; a complete blood cell count, liver function tests, chest diagnostic CT, bone scan, and radiography of any long or weight-bearing bones that are painful or appear abnormal on bone scan; diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen; and biopsy documentation of first recurrence whenever possible. The use of sodium fluoride PET or PET/CT for evaluating patients with recurrent disease is generally discouraged. 

Presently, metastatic breast cancer remains incurable. However, in recent years, the treatment landscape for metastatic breast cancer has significantly advanced in all breast cancer subtypes, leading to improvements in progression-free survival and even overall survival in some cases. For example, newer, targeted approaches directly address mutation drivers and allow precise delivery of chemotherapeutic agents. Detailed guidance on the treatment of breast cancer can be found here and in the full NCCN guidelines. 

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of advanced/metastatic breast cancer. 

Breast cancer is the most frequently diagnosed life-threatening cancer and the second-leading cause of cancer-related deaths in women worldwide. In the United States, an estimated 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 women died of the disease. Globally, approximately 2.3 million new diagnoses and 685,000 breast cancer–related deaths were reported in 2020.

Tumor size, nodal spread, and distant metastases (TNM) at the time of diagnosis are key prognostic factors. Immunohistochemistry tumor markers (ie, estrogen receptor [ER], progesterone receptor [PR], and HER2), as well as grade and Ki-67 expression, have also been shown to be independent predictors of breast cancer death and are used together with TNM to guide treatment decisions. 

Despite advances in breast cancer diagnosis and treatment, metastatic recurrence remains a significant problem. Although the incidence of distance relapse is declining and survival times for patients with recurrent disease are improving, 20%-30% of patients with early breast cancer still die of metastatic disease. Metastatic breast cancer recurrence can arise months to decades after initial diagnosis and treatment. 

According to the National Comprehensive Cancer Network (NCCN) guidelines, biopsy is a critical component of the workup for patients with recurrent or stage IV disease. This is because biopsy ensures accurate determination of metastatic/recurrent disease and tumor histology and enables biomarker determination and selection of appropriate treatment. Soft-tissue tumor biopsy is preferred over bone sites unless a portion of the biopsy can be protected from harsh decalcification solution to preserve more accurate evaluation of biomarkers. Determination of HR status (ER and PR) and HER2 status should be repeated in all cases when diagnostic tissue is obtained because ER and PR assays may be falsely negative or falsely positive, and there may be discordance between the primary and metastatic tumors. According to the NCCN panel, re-testing the receptor status of recurrent disease should be performed, particularly when it was previously unknown, originally negative, or not overexpressed. 

Additionally, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include history and physical exam; a complete blood cell count, liver function tests, chest diagnostic CT, bone scan, and radiography of any long or weight-bearing bones that are painful or appear abnormal on bone scan; diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen; and biopsy documentation of first recurrence whenever possible. The use of sodium fluoride PET or PET/CT for evaluating patients with recurrent disease is generally discouraged. 

Presently, metastatic breast cancer remains incurable. However, in recent years, the treatment landscape for metastatic breast cancer has significantly advanced in all breast cancer subtypes, leading to improvements in progression-free survival and even overall survival in some cases. For example, newer, targeted approaches directly address mutation drivers and allow precise delivery of chemotherapeutic agents. Detailed guidance on the treatment of breast cancer can be found here and in the full NCCN guidelines. 

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of advanced/metastatic breast cancer. 

Breast cancer is the most frequently diagnosed life-threatening cancer and the second-leading cause of cancer-related deaths in women worldwide. In the United States, an estimated 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 women died of the disease. Globally, approximately 2.3 million new diagnoses and 685,000 breast cancer–related deaths were reported in 2020.

Tumor size, nodal spread, and distant metastases (TNM) at the time of diagnosis are key prognostic factors. Immunohistochemistry tumor markers (ie, estrogen receptor [ER], progesterone receptor [PR], and HER2), as well as grade and Ki-67 expression, have also been shown to be independent predictors of breast cancer death and are used together with TNM to guide treatment decisions. 

Despite advances in breast cancer diagnosis and treatment, metastatic recurrence remains a significant problem. Although the incidence of distance relapse is declining and survival times for patients with recurrent disease are improving, 20%-30% of patients with early breast cancer still die of metastatic disease. Metastatic breast cancer recurrence can arise months to decades after initial diagnosis and treatment. 

According to the National Comprehensive Cancer Network (NCCN) guidelines, biopsy is a critical component of the workup for patients with recurrent or stage IV disease. This is because biopsy ensures accurate determination of metastatic/recurrent disease and tumor histology and enables biomarker determination and selection of appropriate treatment. Soft-tissue tumor biopsy is preferred over bone sites unless a portion of the biopsy can be protected from harsh decalcification solution to preserve more accurate evaluation of biomarkers. Determination of HR status (ER and PR) and HER2 status should be repeated in all cases when diagnostic tissue is obtained because ER and PR assays may be falsely negative or falsely positive, and there may be discordance between the primary and metastatic tumors. According to the NCCN panel, re-testing the receptor status of recurrent disease should be performed, particularly when it was previously unknown, originally negative, or not overexpressed. 

Additionally, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include history and physical exam; a complete blood cell count, liver function tests, chest diagnostic CT, bone scan, and radiography of any long or weight-bearing bones that are painful or appear abnormal on bone scan; diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen; and biopsy documentation of first recurrence whenever possible. The use of sodium fluoride PET or PET/CT for evaluating patients with recurrent disease is generally discouraged. 

Presently, metastatic breast cancer remains incurable. However, in recent years, the treatment landscape for metastatic breast cancer has significantly advanced in all breast cancer subtypes, leading to improvements in progression-free survival and even overall survival in some cases. For example, newer, targeted approaches directly address mutation drivers and allow precise delivery of chemotherapeutic agents. Detailed guidance on the treatment of breast cancer can be found here and in the full NCCN guidelines. 

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

To the Editor:

Cyclosporine is an immunomodulatory medication that impacts T-lymphocyte function through calcineurin inhibition and suppression of IL-2 expression. Oral cyclosporine at low doses (1–3 mg/kg/d) is one of the more common systemic treatment options for moderate to severe atopic dermatitis. At these doses it has been shown to have therapeutic benefit in several skin conditions, including chronic spontaneous urticaria,¹ psoriasis,² and atopic dermatitis.³ When used at higher doses for conditions such as glomerulonephritis or transplantation, adverse effects may be notable, and close monitoring of drug metabolism as well as end-organ function is required. In contrast, severe adverse effects are uncommon with the lower doses of cyclosporine used for cutaneous conditions, and monitoring serum drug levels is not routinely practiced.⁴

A 58-year-old man was referred to clinic with severe atopic dermatitis refractory to maximal topical therapy prescribed by an outside physician. He was started on cyclosporine as an anticipated bridge to dupilumab biologic therapy. He had no history of hypertension, renal disease, or hepatic insufficiency prior to starting therapy. He demonstrated notable clinical improvement at a cyclosporine dosage of 300 mg/d (equating to 3.7 mg/kg/d). Three months after initiation of therapy, the patient presented to a local emergency department with new-onset seizurelike activity, confusion, and agitation. He was normotensive with clinical concern for status epilepticus. An initial laboratory assessment included a complete blood cell count, serum electrolyte panel, and urine toxicology screen, which were unremarkable. Computed tomography of the head showed confluent white-matter hypodensities in the left parietal-temporal-occipital lobes. Magnetic resonance imaging (MRI) of the brain showed innumerable peripherally distributed foci of microhemorrhage and vasogenic edema within the left parietal-temporal-occipital lobes (Figure).

He was intubated and sedated with admission to the medical intensive care unit, where a random cyclosporine level drawn approximately 9 hours after the prior dose was noted to be 263 ng/mL. Although target therapeutic levels for cyclosporine vary based on indication, toxic supratherapeutic levels generally are considered to be greater than 400 ng/mL.⁵ He had no evidence of acute kidney injury, uremia, or hypertension throughout hospitalization. An electroencephalogram showed left parieto-occipital periodic epileptiform discharges with generalized slowing. Cyclosporine was discontinued, and he was started on levetiracetam. His clinical and neuroimaging findings improved over the course of the 1-week hospitalization without any further intervention. Four weeks after hospitalization, he had full neurologic, electroencephalogram, and imaging recovery. Based on the presenting symptoms, transient neuroimaging findings, and full recovery with discontinuation of cyclosporine, the patient was diagnosed with cyclosporine-induced posterior reversible encephalopathy syndrome (PRES).

The diagnosis of PRES requires evidence of acute neurologic symptoms and radiographic findings of cortical/subcortical white-matter changes on computed tomography or MRI consistent with edema. The pathophysiology is not fully understood but appears to be related to vasogenic edema, primarily impacting the posterior aspect of the brain. There have been many reported offending agents, and symptoms typically resolve following cessation of these medications. Cases of cyclosporine-induced PRES have been reported, but most occurred at higher doses within weeks of medication initiation. Two cases of cyclosporine-induced PRES treated with cutaneous dosing have been reported; neither patient was taking it for atopic dermatitis.⁶

Cyclosporine-induced PRES remains a pathophysiologic conundrum. However, there is evidence to support direct endothelial damage causing cellular apoptosis in the brain of mouse models that is medication specific and not necessarily related to the dosages used.⁷ Our case highlights a rare but important adverse event associated with even low-dose cyclosporine use that should be considered in patients currently taking cyclosporine who present with acute neurologic changes.

To the Editor:

Cyclosporine is an immunomodulatory medication that impacts T-lymphocyte function through calcineurin inhibition and suppression of IL-2 expression. Oral cyclosporine at low doses (1–3 mg/kg/d) is one of the more common systemic treatment options for moderate to severe atopic dermatitis. At these doses it has been shown to have therapeutic benefit in several skin conditions, including chronic spontaneous urticaria,¹ psoriasis,² and atopic dermatitis.³ When used at higher doses for conditions such as glomerulonephritis or transplantation, adverse effects may be notable, and close monitoring of drug metabolism as well as end-organ function is required. In contrast, severe adverse effects are uncommon with the lower doses of cyclosporine used for cutaneous conditions, and monitoring serum drug levels is not routinely practiced.⁴

A 58-year-old man was referred to clinic with severe atopic dermatitis refractory to maximal topical therapy prescribed by an outside physician. He was started on cyclosporine as an anticipated bridge to dupilumab biologic therapy. He had no history of hypertension, renal disease, or hepatic insufficiency prior to starting therapy. He demonstrated notable clinical improvement at a cyclosporine dosage of 300 mg/d (equating to 3.7 mg/kg/d). Three months after initiation of therapy, the patient presented to a local emergency department with new-onset seizurelike activity, confusion, and agitation. He was normotensive with clinical concern for status epilepticus. An initial laboratory assessment included a complete blood cell count, serum electrolyte panel, and urine toxicology screen, which were unremarkable. Computed tomography of the head showed confluent white-matter hypodensities in the left parietal-temporal-occipital lobes. Magnetic resonance imaging (MRI) of the brain showed innumerable peripherally distributed foci of microhemorrhage and vasogenic edema within the left parietal-temporal-occipital lobes (Figure).

He was intubated and sedated with admission to the medical intensive care unit, where a random cyclosporine level drawn approximately 9 hours after the prior dose was noted to be 263 ng/mL. Although target therapeutic levels for cyclosporine vary based on indication, toxic supratherapeutic levels generally are considered to be greater than 400 ng/mL.⁵ He had no evidence of acute kidney injury, uremia, or hypertension throughout hospitalization. An electroencephalogram showed left parieto-occipital periodic epileptiform discharges with generalized slowing. Cyclosporine was discontinued, and he was started on levetiracetam. His clinical and neuroimaging findings improved over the course of the 1-week hospitalization without any further intervention. Four weeks after hospitalization, he had full neurologic, electroencephalogram, and imaging recovery. Based on the presenting symptoms, transient neuroimaging findings, and full recovery with discontinuation of cyclosporine, the patient was diagnosed with cyclosporine-induced posterior reversible encephalopathy syndrome (PRES).

The diagnosis of PRES requires evidence of acute neurologic symptoms and radiographic findings of cortical/subcortical white-matter changes on computed tomography or MRI consistent with edema. The pathophysiology is not fully understood but appears to be related to vasogenic edema, primarily impacting the posterior aspect of the brain. There have been many reported offending agents, and symptoms typically resolve following cessation of these medications. Cases of cyclosporine-induced PRES have been reported, but most occurred at higher doses within weeks of medication initiation. Two cases of cyclosporine-induced PRES treated with cutaneous dosing have been reported; neither patient was taking it for atopic dermatitis.⁶

Cyclosporine-induced PRES remains a pathophysiologic conundrum. However, there is evidence to support direct endothelial damage causing cellular apoptosis in the brain of mouse models that is medication specific and not necessarily related to the dosages used.⁷ Our case highlights a rare but important adverse event associated with even low-dose cyclosporine use that should be considered in patients currently taking cyclosporine who present with acute neurologic changes.

To the Editor:

Cyclosporine is an immunomodulatory medication that impacts T-lymphocyte function through calcineurin inhibition and suppression of IL-2 expression. Oral cyclosporine at low doses (1–3 mg/kg/d) is one of the more common systemic treatment options for moderate to severe atopic dermatitis. At these doses it has been shown to have therapeutic benefit in several skin conditions, including chronic spontaneous urticaria,¹ psoriasis,² and atopic dermatitis.³ When used at higher doses for conditions such as glomerulonephritis or transplantation, adverse effects may be notable, and close monitoring of drug metabolism as well as end-organ function is required. In contrast, severe adverse effects are uncommon with the lower doses of cyclosporine used for cutaneous conditions, and monitoring serum drug levels is not routinely practiced.⁴

A 58-year-old man was referred to clinic with severe atopic dermatitis refractory to maximal topical therapy prescribed by an outside physician. He was started on cyclosporine as an anticipated bridge to dupilumab biologic therapy. He had no history of hypertension, renal disease, or hepatic insufficiency prior to starting therapy. He demonstrated notable clinical improvement at a cyclosporine dosage of 300 mg/d (equating to 3.7 mg/kg/d). Three months after initiation of therapy, the patient presented to a local emergency department with new-onset seizurelike activity, confusion, and agitation. He was normotensive with clinical concern for status epilepticus. An initial laboratory assessment included a complete blood cell count, serum electrolyte panel, and urine toxicology screen, which were unremarkable. Computed tomography of the head showed confluent white-matter hypodensities in the left parietal-temporal-occipital lobes. Magnetic resonance imaging (MRI) of the brain showed innumerable peripherally distributed foci of microhemorrhage and vasogenic edema within the left parietal-temporal-occipital lobes (Figure).

He was intubated and sedated with admission to the medical intensive care unit, where a random cyclosporine level drawn approximately 9 hours after the prior dose was noted to be 263 ng/mL. Although target therapeutic levels for cyclosporine vary based on indication, toxic supratherapeutic levels generally are considered to be greater than 400 ng/mL.⁵ He had no evidence of acute kidney injury, uremia, or hypertension throughout hospitalization. An electroencephalogram showed left parieto-occipital periodic epileptiform discharges with generalized slowing. Cyclosporine was discontinued, and he was started on levetiracetam. His clinical and neuroimaging findings improved over the course of the 1-week hospitalization without any further intervention. Four weeks after hospitalization, he had full neurologic, electroencephalogram, and imaging recovery. Based on the presenting symptoms, transient neuroimaging findings, and full recovery with discontinuation of cyclosporine, the patient was diagnosed with cyclosporine-induced posterior reversible encephalopathy syndrome (PRES).

The diagnosis of PRES requires evidence of acute neurologic symptoms and radiographic findings of cortical/subcortical white-matter changes on computed tomography or MRI consistent with edema. The pathophysiology is not fully understood but appears to be related to vasogenic edema, primarily impacting the posterior aspect of the brain. There have been many reported offending agents, and symptoms typically resolve following cessation of these medications. Cases of cyclosporine-induced PRES have been reported, but most occurred at higher doses within weeks of medication initiation. Two cases of cyclosporine-induced PRES treated with cutaneous dosing have been reported; neither patient was taking it for atopic dermatitis.⁶

Cyclosporine-induced PRES remains a pathophysiologic conundrum. However, there is evidence to support direct endothelial damage causing cellular apoptosis in the brain of mouse models that is medication specific and not necessarily related to the dosages used.⁷ Our case highlights a rare but important adverse event associated with even low-dose cyclosporine use that should be considered in patients currently taking cyclosporine who present with acute neurologic changes.

To the Editor:

The recent global mpox (monkeypox) outbreak that started in May 2022 has distinctive risk factors, clinical features, and patient attributes that can portend dissemination of infection. We report a case of Kaposi varicelliform eruption (KVE) over a peeling sunburn after mpox infection. Dermatologists should recognize cutaneous risk factors for dissemination of mpox.

A 35-year-old man who was otherwise healthy presented with a papulopustular eruption that began on the shoulders in an area that had been sunburned 24 to 48 hours earlier. He experienced fever (temperature, 38.6 °C)[101.5 °F]), chills, malaise, and the appearance of a painful penile ulcer. He reported a recent male sexual partner a week prior to the eruption during travel to eastern Asia and a subsequent male partner in the United States 5 days prior to eruption. Physical examination revealed a peeling sunburn with sharp clothing demarcation. Locations with the most notable desquamation—the superior shoulders, dorsal arms, upper chest, and ventral thighs—positively correlated with the highest density of scattered, discrete, erythematous-based pustules and pink papules, some with crusted umbilication (Figures 1 and 2). Lesions spared sun-protected locations except a punctate painful ulcer on the buccal mucosa and a tender well-demarcated ulcer with elevated borders on the ventral penile shaft. HIV antigen/antibody testing was negative; syphilis antibody testing was positive due to a prior infection 1 year earlier with titers down to 1:1. A penile ulcer swab did not detect herpes simplex virus types 1/2 DNA. Pharyngeal, penile, and rectal swabs were negative for chlamydia or gonorrhea DNA. A polymerase chain reaction assay of a pustule was positive for orthopoxvirus, and the Centers for Disease Control and Prevention confirmed Monkeypox virus. On day 12, a penile ulcer biopsy was nonspecific with dense mixed inflammation; immunohistochemical stains for Treponema pallidum and herpes simplex virus types 1/2 were negative. Consideration was given to starting antiviral treatment with tecovirimat, which is approved by the US Food and Drug Administration for smallpox caused by variola virus, through the Centers for Disease Control and Prevention expanded access protocol, but the patient’s symptoms and lesions cleared quickly without intervention. The patient’s recent sexual contact in the United States later tested positive for mpox. Given that the density of our patient’s mpox lesions positively correlated with areas of peeling sunburn with rapid spread during the period of desquamation, he was diagnosed with KVE due to mpox in the setting of a peeling sunburn.

To the Editor:

The recent global mpox (monkeypox) outbreak that started in May 2022 has distinctive risk factors, clinical features, and patient attributes that can portend dissemination of infection. We report a case of Kaposi varicelliform eruption (KVE) over a peeling sunburn after mpox infection. Dermatologists should recognize cutaneous risk factors for dissemination of mpox.

A 35-year-old man who was otherwise healthy presented with a papulopustular eruption that began on the shoulders in an area that had been sunburned 24 to 48 hours earlier. He experienced fever (temperature, 38.6 °C)[101.5 °F]), chills, malaise, and the appearance of a painful penile ulcer. He reported a recent male sexual partner a week prior to the eruption during travel to eastern Asia and a subsequent male partner in the United States 5 days prior to eruption. Physical examination revealed a peeling sunburn with sharp clothing demarcation. Locations with the most notable desquamation—the superior shoulders, dorsal arms, upper chest, and ventral thighs—positively correlated with the highest density of scattered, discrete, erythematous-based pustules and pink papules, some with crusted umbilication (Figures 1 and 2). Lesions spared sun-protected locations except a punctate painful ulcer on the buccal mucosa and a tender well-demarcated ulcer with elevated borders on the ventral penile shaft. HIV antigen/antibody testing was negative; syphilis antibody testing was positive due to a prior infection 1 year earlier with titers down to 1:1. A penile ulcer swab did not detect herpes simplex virus types 1/2 DNA. Pharyngeal, penile, and rectal swabs were negative for chlamydia or gonorrhea DNA. A polymerase chain reaction assay of a pustule was positive for orthopoxvirus, and the Centers for Disease Control and Prevention confirmed Monkeypox virus. On day 12, a penile ulcer biopsy was nonspecific with dense mixed inflammation; immunohistochemical stains for Treponema pallidum and herpes simplex virus types 1/2 were negative. Consideration was given to starting antiviral treatment with tecovirimat, which is approved by the US Food and Drug Administration for smallpox caused by variola virus, through the Centers for Disease Control and Prevention expanded access protocol, but the patient’s symptoms and lesions cleared quickly without intervention. The patient’s recent sexual contact in the United States later tested positive for mpox. Given that the density of our patient’s mpox lesions positively correlated with areas of peeling sunburn with rapid spread during the period of desquamation, he was diagnosed with KVE due to mpox in the setting of a peeling sunburn.

To the Editor:

The recent global mpox (monkeypox) outbreak that started in May 2022 has distinctive risk factors, clinical features, and patient attributes that can portend dissemination of infection. We report a case of Kaposi varicelliform eruption (KVE) over a peeling sunburn after mpox infection. Dermatologists should recognize cutaneous risk factors for dissemination of mpox.

A 35-year-old man who was otherwise healthy presented with a papulopustular eruption that began on the shoulders in an area that had been sunburned 24 to 48 hours earlier. He experienced fever (temperature, 38.6 °C)[101.5 °F]), chills, malaise, and the appearance of a painful penile ulcer. He reported a recent male sexual partner a week prior to the eruption during travel to eastern Asia and a subsequent male partner in the United States 5 days prior to eruption. Physical examination revealed a peeling sunburn with sharp clothing demarcation. Locations with the most notable desquamation—the superior shoulders, dorsal arms, upper chest, and ventral thighs—positively correlated with the highest density of scattered, discrete, erythematous-based pustules and pink papules, some with crusted umbilication (Figures 1 and 2). Lesions spared sun-protected locations except a punctate painful ulcer on the buccal mucosa and a tender well-demarcated ulcer with elevated borders on the ventral penile shaft. HIV antigen/antibody testing was negative; syphilis antibody testing was positive due to a prior infection 1 year earlier with titers down to 1:1. A penile ulcer swab did not detect herpes simplex virus types 1/2 DNA. Pharyngeal, penile, and rectal swabs were negative for chlamydia or gonorrhea DNA. A polymerase chain reaction assay of a pustule was positive for orthopoxvirus, and the Centers for Disease Control and Prevention confirmed Monkeypox virus. On day 12, a penile ulcer biopsy was nonspecific with dense mixed inflammation; immunohistochemical stains for Treponema pallidum and herpes simplex virus types 1/2 were negative. Consideration was given to starting antiviral treatment with tecovirimat, which is approved by the US Food and Drug Administration for smallpox caused by variola virus, through the Centers for Disease Control and Prevention expanded access protocol, but the patient’s symptoms and lesions cleared quickly without intervention. The patient’s recent sexual contact in the United States later tested positive for mpox. Given that the density of our patient’s mpox lesions positively correlated with areas of peeling sunburn with rapid spread during the period of desquamation, he was diagnosed with KVE due to mpox in the setting of a peeling sunburn.

One morning I stepped into the elevator in the lobby of the US Department of Veterans Affairs (VA) medical center where I work, holding a cup of coffee, joining another staffer, a middle-aged man, wearing a veteran’s pin on his employee badge. An older veteran slowly approached the elevator doors, shuffling with each step, and since he was at the front of the elevator, he cheerfully bellowed “Which floor?” as he offered to push the button for us.

“What’s on 12?” he asked in a jovial voice. I smiled. “Aging research,” referring to the Geriatrics Research Education and Clinical Center where I work.¹

“I definitely need that—I forgot where I’m going!” he joked, his fingers hovering over the elevator buttons.

As we reached his floor, the doors opened, he waved with a smile and unsteadily made his way out of the elevator and down the hall to his appointment. As the elevator doors closed behind him, the other staffer turned to me and said with a shrug, “That’ll be me one day,” as he got off at the next floor.

When I got off the elevator and walked toward my office, I reflected on the care that I as a geriatrician and we at the VA hope to provide to aging veterans, now and in the future: Age-Friendly care. Age-Friendly means the compassionate care that we want for those who have served our country, for our loved ones, and for ourselves as we age. Age-Friendly means person-centered, evidence-based care that as we grow older will help us to address challenges that may come with older age, such as falls, cognitive impairment, and polypharmacy. Too often the health care system remains focused on the chief concern or on a clinician’s specialty and may not focus on those important areas where we can potentially intervene to support aging veterans.

The VA has set a goal to become the largest Age-Friendly Health System (AFHS) in the country.² Led by the Institute for Healthcare Improvement and funded by the John A. Hartford Foundation, the Age-Friendly Health Systems Initiative aims to help clinicians and care settings “follow an essential set of evidence-based practices; cause no harm; and align with what matters to the older adult and their family caregivers.”³ An AFHS cares for older adults with attention to the 4Ms—What Matters, Mobility, Mentation, and Medications.⁴ Specifically, in an AFHS, older adults are asked what matters to them so we can align their health care with their goals; clinicians evaluate veterans for safe mobility and fall risk reduction, cognitive impairment and mood disorders, and identify and avoid high-risk medications.⁵ In an AFHS, the 4Ms are practiced as a set, reliably, across settings, so that there should be no wrong door or wrong floor for an older veteran to receive Age-Friendly care within the VA health care system.⁶

Too often our health care system and health professions education have left clinicians unprepared to care for older adults using an Age-Friendly framework; rather, we have been trained in problem-based or disease-based care that can miss the forest for the trees in an older adult living with multiple chronic conditions and/or frailty. We may focus on providing evidence-based care for individual medical conditions while neglecting the often practical interventions that can help an older person age in place by focusing on what matters, supporting safe mobility, addressing cognition and mood, and optimizing medications.¹⁸

The vision of the VA as the largest AFHS in America is urgently needed; nearly half of the veteran population is aged 65 ≥ years, compared with 16% of the general population.¹⁹ Building on the VA’s legacy of creativity and innovation in geriatrics, and the VA’s goal of being a high reliability organization, becoming an AFHS will ensure that for that older veteran stepping off that elevator there is no wrong floor, and no wrong door to receive the Age-Friendly care he deserves and that we all hope for as we age.^1,5,19,20

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System and the New England Geriatric Research Education and Clinical Center. 

One morning I stepped into the elevator in the lobby of the US Department of Veterans Affairs (VA) medical center where I work, holding a cup of coffee, joining another staffer, a middle-aged man, wearing a veteran’s pin on his employee badge. An older veteran slowly approached the elevator doors, shuffling with each step, and since he was at the front of the elevator, he cheerfully bellowed “Which floor?” as he offered to push the button for us.

“What’s on 12?” he asked in a jovial voice. I smiled. “Aging research,” referring to the Geriatrics Research Education and Clinical Center where I work.¹

“I definitely need that—I forgot where I’m going!” he joked, his fingers hovering over the elevator buttons.

As we reached his floor, the doors opened, he waved with a smile and unsteadily made his way out of the elevator and down the hall to his appointment. As the elevator doors closed behind him, the other staffer turned to me and said with a shrug, “That’ll be me one day,” as he got off at the next floor.

When I got off the elevator and walked toward my office, I reflected on the care that I as a geriatrician and we at the VA hope to provide to aging veterans, now and in the future: Age-Friendly care. Age-Friendly means the compassionate care that we want for those who have served our country, for our loved ones, and for ourselves as we age. Age-Friendly means person-centered, evidence-based care that as we grow older will help us to address challenges that may come with older age, such as falls, cognitive impairment, and polypharmacy. Too often the health care system remains focused on the chief concern or on a clinician’s specialty and may not focus on those important areas where we can potentially intervene to support aging veterans.

The VA has set a goal to become the largest Age-Friendly Health System (AFHS) in the country.² Led by the Institute for Healthcare Improvement and funded by the John A. Hartford Foundation, the Age-Friendly Health Systems Initiative aims to help clinicians and care settings “follow an essential set of evidence-based practices; cause no harm; and align with what matters to the older adult and their family caregivers.”³ An AFHS cares for older adults with attention to the 4Ms—What Matters, Mobility, Mentation, and Medications.⁴ Specifically, in an AFHS, older adults are asked what matters to them so we can align their health care with their goals; clinicians evaluate veterans for safe mobility and fall risk reduction, cognitive impairment and mood disorders, and identify and avoid high-risk medications.⁵ In an AFHS, the 4Ms are practiced as a set, reliably, across settings, so that there should be no wrong door or wrong floor for an older veteran to receive Age-Friendly care within the VA health care system.⁶

Too often our health care system and health professions education have left clinicians unprepared to care for older adults using an Age-Friendly framework; rather, we have been trained in problem-based or disease-based care that can miss the forest for the trees in an older adult living with multiple chronic conditions and/or frailty. We may focus on providing evidence-based care for individual medical conditions while neglecting the often practical interventions that can help an older person age in place by focusing on what matters, supporting safe mobility, addressing cognition and mood, and optimizing medications.¹⁸

The vision of the VA as the largest AFHS in America is urgently needed; nearly half of the veteran population is aged 65 ≥ years, compared with 16% of the general population.¹⁹ Building on the VA’s legacy of creativity and innovation in geriatrics, and the VA’s goal of being a high reliability organization, becoming an AFHS will ensure that for that older veteran stepping off that elevator there is no wrong floor, and no wrong door to receive the Age-Friendly care he deserves and that we all hope for as we age.^1,5,19,20

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System and the New England Geriatric Research Education and Clinical Center. 

One morning I stepped into the elevator in the lobby of the US Department of Veterans Affairs (VA) medical center where I work, holding a cup of coffee, joining another staffer, a middle-aged man, wearing a veteran’s pin on his employee badge. An older veteran slowly approached the elevator doors, shuffling with each step, and since he was at the front of the elevator, he cheerfully bellowed “Which floor?” as he offered to push the button for us.

“What’s on 12?” he asked in a jovial voice. I smiled. “Aging research,” referring to the Geriatrics Research Education and Clinical Center where I work.¹

“I definitely need that—I forgot where I’m going!” he joked, his fingers hovering over the elevator buttons.

As we reached his floor, the doors opened, he waved with a smile and unsteadily made his way out of the elevator and down the hall to his appointment. As the elevator doors closed behind him, the other staffer turned to me and said with a shrug, “That’ll be me one day,” as he got off at the next floor.

When I got off the elevator and walked toward my office, I reflected on the care that I as a geriatrician and we at the VA hope to provide to aging veterans, now and in the future: Age-Friendly care. Age-Friendly means the compassionate care that we want for those who have served our country, for our loved ones, and for ourselves as we age. Age-Friendly means person-centered, evidence-based care that as we grow older will help us to address challenges that may come with older age, such as falls, cognitive impairment, and polypharmacy. Too often the health care system remains focused on the chief concern or on a clinician’s specialty and may not focus on those important areas where we can potentially intervene to support aging veterans.

The VA has set a goal to become the largest Age-Friendly Health System (AFHS) in the country.² Led by the Institute for Healthcare Improvement and funded by the John A. Hartford Foundation, the Age-Friendly Health Systems Initiative aims to help clinicians and care settings “follow an essential set of evidence-based practices; cause no harm; and align with what matters to the older adult and their family caregivers.”³ An AFHS cares for older adults with attention to the 4Ms—What Matters, Mobility, Mentation, and Medications.⁴ Specifically, in an AFHS, older adults are asked what matters to them so we can align their health care with their goals; clinicians evaluate veterans for safe mobility and fall risk reduction, cognitive impairment and mood disorders, and identify and avoid high-risk medications.⁵ In an AFHS, the 4Ms are practiced as a set, reliably, across settings, so that there should be no wrong door or wrong floor for an older veteran to receive Age-Friendly care within the VA health care system.⁶

Too often our health care system and health professions education have left clinicians unprepared to care for older adults using an Age-Friendly framework; rather, we have been trained in problem-based or disease-based care that can miss the forest for the trees in an older adult living with multiple chronic conditions and/or frailty. We may focus on providing evidence-based care for individual medical conditions while neglecting the often practical interventions that can help an older person age in place by focusing on what matters, supporting safe mobility, addressing cognition and mood, and optimizing medications.¹⁸

The vision of the VA as the largest AFHS in America is urgently needed; nearly half of the veteran population is aged 65 ≥ years, compared with 16% of the general population.¹⁹ Building on the VA’s legacy of creativity and innovation in geriatrics, and the VA’s goal of being a high reliability organization, becoming an AFHS will ensure that for that older veteran stepping off that elevator there is no wrong floor, and no wrong door to receive the Age-Friendly care he deserves and that we all hope for as we age.^1,5,19,20

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System and the New England Geriatric Research Education and Clinical Center.