Case Report

A 53-year-old woman presented for an initial visit to the dermatology clinic for a growth under the right fifth fingernail of 1 year’s duration. She had no history of trauma to the digit or pain or bleeding. She self-treated with over-the-counter wart remover for several months without improvement. She reported no other skin concerns. She had a medical history of rheumatoid arthritis (RA) and basal cell carcinoma of the nose; she was taking methotrexate and adalimumab for the RA. She had a family history of melanoma in her father.

On physical examination, a firm nontender nodule was noted on the distal nail bed of the right fifth fingernail with onycholysis; the nail plate was otherwise intact (Figure 1). All other nails were normal. A plain radiograph of the involved digit showed no bony abnormality. Excisional biopsy of the nodule was performed and analyzed by histopathology (Figure 2). The biopsy specimen showed a benign epidermis that was acanthotic and surmounted by hyperkeratotic scale. The dermis was fibrotic with collagen bundles assuming a vertical orientation to the long axis of the epidermis, typical of a fibrokeratoma. There were no atypical features in the dermal component or epidermis (Figure 2). These findings were consistent with the diagnosis of acquired digital fibrokeratoma (ADF). The patient tolerated excisional biopsy well and had no evidence of recurrence 4 months following excision.

Comment

History and Clinical Presentation
First described by Bart et al¹ in 1968, ADF is a rare benign fibrous tumor localized to the nail bed or periungual area.¹ Typically, it presents as a solitary flesh-colored papule measuring 3 to 5 mm in diameter. It can be keratotic with a surrounding collarette of elevated skin. Acquired digital fibrokeratoma usually is localized to the digits of the hands or feet; when presenting subungually, it is more commonly found arising from the proximal matrix or nail bed of the great toe. Observed nail changes include longitudinal grooves, trachyonychia, subungual hyperkeratosis, and onycholysis.² The affected nail can be painful, depending on the size and location of the tumor.

Acquired digital fibrokeratoma is more commonly found in middle-aged men; however, it has been reported among patients of various ages and in both sexes.^1,3 In a study of 20 cases, the average duration before presenting for medical advice was 28 months.² Acquired digital fibrokeratoma arises sporadically; some patients report prior local trauma. Lesions typically do not self-resolve.

Diagnosis
The diagnosis of ADF is made using a combination of clinical and histopathological findings. Dermoscopy is helpful and may show homogenous white or milky white structures, likely representing hyperkeratosis, proliferation of capillaries, and an increase in collagen bundles with a surrounding collarette of scale.^4,5 Histopathology shows acanthosis and hyperkeratosis of the epidermis. Collagen bundles assume a characteristic vertical orientation to the long axis of the epidermis.

Two other histomorphologic subtypes, less common than the type I variant, are the type II variant, in which the number of fibroblasts is increased and the number of elastic fibers is decreased, and the type III variant, in which the stroma are edematous and cell poor. There is an even greater reduction in elastic tissue content in the type III variant than in the type I variant. There is evidence that type II ADFs exhibit more hyperkeratosis clinically than the other 2 subtypes, but from a practical perspective, this subclassification is not conducted in routine practice because it does not have clinical significance.⁵

Differential Diagnosis
The clinical differential diagnosis of ADF is broad and includes squamous cell carcinoma, onychomatricoma, onychopapilloma, verruca vulgaris, supernumerary digit, neurofibroma, cellular digital fibroma, and Koenen tumor (periungual fibroma). Almost all of these entities are easily differentiated from ADF on biopsy. A fibrokeratoma does not exhibit the atypia seen in squamous cell carcinoma. The multiple fibroepithelial projections and nail plate perforations characteristic of onychomatricoma are not observed in ADF. Onychopapilloma shows acanthosis and papillomatosis, similar to ADF; however, onychopapilloma lacks the characteristic vertical orientation of collagen in ADF. Verruca vulgaris classically shows koilocytosis, dilated blood vessels in papillae, and hypergranulosis. A supernumerary digit clinically lacks a collarette of scale and often presents in a bilateral fashion on the lateral fifth digits in children; histopathologically, a supernumerary digit is distinct from an ADF in that nerve bundles are abundant in the dermis, defining a form of amputation neuroma. Neurofibroma exhibits a spindle cell proliferation that assumes a patternless disposition in the dermis, accompanied by mucin, mast cells, and delicate collagen. The defining cell populace has a typical serpiginous nuclear outline that is characteristic of a Schwann cell. Cellular digital fibroma can present similar to ADF; it is considered by some to be a mucin-poor variant of superficial acral fibromyxoma. Its morphology is distinct: a proliferation of bland-appearing spindled cells exhibiting a storiform or fascicular growth pattern and CD34 positivity.

The differential diagnosis to consider when ADF is suspected is a Koenen tumor, which resembles a fibrokeratoma clinically and also is localized to the digits. Koenen tumors can be differentiated from fibrokeratoma by its association with tuberous sclerosis; a multiple, rather than solitary, presentation; a distinctive clove-shaped gross appearance; and an appearance on histopathology of stellate-shaped fibroblasts with occasional giant cells. Despite these important differences, Koenen tumor does exhibit a striking morphologic similarity to ADF, given that the vertical orientation of collagen bundles in Koenen tumor is virtually identical to ADF.⁶

Management
There are no known associations between ADF and medication use, including methotrexate and adalimumab, which our patient was taking; additionally, no association with RA or other systemic disorder has been reported.² The preferred treatment of ADF is complete excision to the basal attachment of the tumor; recurrence is uncommon. Alternative therapies include destructive methods, such as cryotherapy, CO₂ laser ablation, and electrodesiccation.²

Case Report

A 53-year-old woman presented for an initial visit to the dermatology clinic for a growth under the right fifth fingernail of 1 year’s duration. She had no history of trauma to the digit or pain or bleeding. She self-treated with over-the-counter wart remover for several months without improvement. She reported no other skin concerns. She had a medical history of rheumatoid arthritis (RA) and basal cell carcinoma of the nose; she was taking methotrexate and adalimumab for the RA. She had a family history of melanoma in her father.

On physical examination, a firm nontender nodule was noted on the distal nail bed of the right fifth fingernail with onycholysis; the nail plate was otherwise intact (Figure 1). All other nails were normal. A plain radiograph of the involved digit showed no bony abnormality. Excisional biopsy of the nodule was performed and analyzed by histopathology (Figure 2). The biopsy specimen showed a benign epidermis that was acanthotic and surmounted by hyperkeratotic scale. The dermis was fibrotic with collagen bundles assuming a vertical orientation to the long axis of the epidermis, typical of a fibrokeratoma. There were no atypical features in the dermal component or epidermis (Figure 2). These findings were consistent with the diagnosis of acquired digital fibrokeratoma (ADF). The patient tolerated excisional biopsy well and had no evidence of recurrence 4 months following excision.

Comment

History and Clinical Presentation
First described by Bart et al¹ in 1968, ADF is a rare benign fibrous tumor localized to the nail bed or periungual area.¹ Typically, it presents as a solitary flesh-colored papule measuring 3 to 5 mm in diameter. It can be keratotic with a surrounding collarette of elevated skin. Acquired digital fibrokeratoma usually is localized to the digits of the hands or feet; when presenting subungually, it is more commonly found arising from the proximal matrix or nail bed of the great toe. Observed nail changes include longitudinal grooves, trachyonychia, subungual hyperkeratosis, and onycholysis.² The affected nail can be painful, depending on the size and location of the tumor.

Acquired digital fibrokeratoma is more commonly found in middle-aged men; however, it has been reported among patients of various ages and in both sexes.^1,3 In a study of 20 cases, the average duration before presenting for medical advice was 28 months.² Acquired digital fibrokeratoma arises sporadically; some patients report prior local trauma. Lesions typically do not self-resolve.

Diagnosis
The diagnosis of ADF is made using a combination of clinical and histopathological findings. Dermoscopy is helpful and may show homogenous white or milky white structures, likely representing hyperkeratosis, proliferation of capillaries, and an increase in collagen bundles with a surrounding collarette of scale.^4,5 Histopathology shows acanthosis and hyperkeratosis of the epidermis. Collagen bundles assume a characteristic vertical orientation to the long axis of the epidermis.

Two other histomorphologic subtypes, less common than the type I variant, are the type II variant, in which the number of fibroblasts is increased and the number of elastic fibers is decreased, and the type III variant, in which the stroma are edematous and cell poor. There is an even greater reduction in elastic tissue content in the type III variant than in the type I variant. There is evidence that type II ADFs exhibit more hyperkeratosis clinically than the other 2 subtypes, but from a practical perspective, this subclassification is not conducted in routine practice because it does not have clinical significance.⁵

Differential Diagnosis
The clinical differential diagnosis of ADF is broad and includes squamous cell carcinoma, onychomatricoma, onychopapilloma, verruca vulgaris, supernumerary digit, neurofibroma, cellular digital fibroma, and Koenen tumor (periungual fibroma). Almost all of these entities are easily differentiated from ADF on biopsy. A fibrokeratoma does not exhibit the atypia seen in squamous cell carcinoma. The multiple fibroepithelial projections and nail plate perforations characteristic of onychomatricoma are not observed in ADF. Onychopapilloma shows acanthosis and papillomatosis, similar to ADF; however, onychopapilloma lacks the characteristic vertical orientation of collagen in ADF. Verruca vulgaris classically shows koilocytosis, dilated blood vessels in papillae, and hypergranulosis. A supernumerary digit clinically lacks a collarette of scale and often presents in a bilateral fashion on the lateral fifth digits in children; histopathologically, a supernumerary digit is distinct from an ADF in that nerve bundles are abundant in the dermis, defining a form of amputation neuroma. Neurofibroma exhibits a spindle cell proliferation that assumes a patternless disposition in the dermis, accompanied by mucin, mast cells, and delicate collagen. The defining cell populace has a typical serpiginous nuclear outline that is characteristic of a Schwann cell. Cellular digital fibroma can present similar to ADF; it is considered by some to be a mucin-poor variant of superficial acral fibromyxoma. Its morphology is distinct: a proliferation of bland-appearing spindled cells exhibiting a storiform or fascicular growth pattern and CD34 positivity.

The differential diagnosis to consider when ADF is suspected is a Koenen tumor, which resembles a fibrokeratoma clinically and also is localized to the digits. Koenen tumors can be differentiated from fibrokeratoma by its association with tuberous sclerosis; a multiple, rather than solitary, presentation; a distinctive clove-shaped gross appearance; and an appearance on histopathology of stellate-shaped fibroblasts with occasional giant cells. Despite these important differences, Koenen tumor does exhibit a striking morphologic similarity to ADF, given that the vertical orientation of collagen bundles in Koenen tumor is virtually identical to ADF.⁶

Management
There are no known associations between ADF and medication use, including methotrexate and adalimumab, which our patient was taking; additionally, no association with RA or other systemic disorder has been reported.² The preferred treatment of ADF is complete excision to the basal attachment of the tumor; recurrence is uncommon. Alternative therapies include destructive methods, such as cryotherapy, CO₂ laser ablation, and electrodesiccation.²

Case Report

A 53-year-old woman presented for an initial visit to the dermatology clinic for a growth under the right fifth fingernail of 1 year’s duration. She had no history of trauma to the digit or pain or bleeding. She self-treated with over-the-counter wart remover for several months without improvement. She reported no other skin concerns. She had a medical history of rheumatoid arthritis (RA) and basal cell carcinoma of the nose; she was taking methotrexate and adalimumab for the RA. She had a family history of melanoma in her father.

On physical examination, a firm nontender nodule was noted on the distal nail bed of the right fifth fingernail with onycholysis; the nail plate was otherwise intact (Figure 1). All other nails were normal. A plain radiograph of the involved digit showed no bony abnormality. Excisional biopsy of the nodule was performed and analyzed by histopathology (Figure 2). The biopsy specimen showed a benign epidermis that was acanthotic and surmounted by hyperkeratotic scale. The dermis was fibrotic with collagen bundles assuming a vertical orientation to the long axis of the epidermis, typical of a fibrokeratoma. There were no atypical features in the dermal component or epidermis (Figure 2). These findings were consistent with the diagnosis of acquired digital fibrokeratoma (ADF). The patient tolerated excisional biopsy well and had no evidence of recurrence 4 months following excision.

Comment

History and Clinical Presentation
First described by Bart et al¹ in 1968, ADF is a rare benign fibrous tumor localized to the nail bed or periungual area.¹ Typically, it presents as a solitary flesh-colored papule measuring 3 to 5 mm in diameter. It can be keratotic with a surrounding collarette of elevated skin. Acquired digital fibrokeratoma usually is localized to the digits of the hands or feet; when presenting subungually, it is more commonly found arising from the proximal matrix or nail bed of the great toe. Observed nail changes include longitudinal grooves, trachyonychia, subungual hyperkeratosis, and onycholysis.² The affected nail can be painful, depending on the size and location of the tumor.

Acquired digital fibrokeratoma is more commonly found in middle-aged men; however, it has been reported among patients of various ages and in both sexes.^1,3 In a study of 20 cases, the average duration before presenting for medical advice was 28 months.² Acquired digital fibrokeratoma arises sporadically; some patients report prior local trauma. Lesions typically do not self-resolve.

Diagnosis
The diagnosis of ADF is made using a combination of clinical and histopathological findings. Dermoscopy is helpful and may show homogenous white or milky white structures, likely representing hyperkeratosis, proliferation of capillaries, and an increase in collagen bundles with a surrounding collarette of scale.^4,5 Histopathology shows acanthosis and hyperkeratosis of the epidermis. Collagen bundles assume a characteristic vertical orientation to the long axis of the epidermis.

Two other histomorphologic subtypes, less common than the type I variant, are the type II variant, in which the number of fibroblasts is increased and the number of elastic fibers is decreased, and the type III variant, in which the stroma are edematous and cell poor. There is an even greater reduction in elastic tissue content in the type III variant than in the type I variant. There is evidence that type II ADFs exhibit more hyperkeratosis clinically than the other 2 subtypes, but from a practical perspective, this subclassification is not conducted in routine practice because it does not have clinical significance.⁵

Differential Diagnosis
The clinical differential diagnosis of ADF is broad and includes squamous cell carcinoma, onychomatricoma, onychopapilloma, verruca vulgaris, supernumerary digit, neurofibroma, cellular digital fibroma, and Koenen tumor (periungual fibroma). Almost all of these entities are easily differentiated from ADF on biopsy. A fibrokeratoma does not exhibit the atypia seen in squamous cell carcinoma. The multiple fibroepithelial projections and nail plate perforations characteristic of onychomatricoma are not observed in ADF. Onychopapilloma shows acanthosis and papillomatosis, similar to ADF; however, onychopapilloma lacks the characteristic vertical orientation of collagen in ADF. Verruca vulgaris classically shows koilocytosis, dilated blood vessels in papillae, and hypergranulosis. A supernumerary digit clinically lacks a collarette of scale and often presents in a bilateral fashion on the lateral fifth digits in children; histopathologically, a supernumerary digit is distinct from an ADF in that nerve bundles are abundant in the dermis, defining a form of amputation neuroma. Neurofibroma exhibits a spindle cell proliferation that assumes a patternless disposition in the dermis, accompanied by mucin, mast cells, and delicate collagen. The defining cell populace has a typical serpiginous nuclear outline that is characteristic of a Schwann cell. Cellular digital fibroma can present similar to ADF; it is considered by some to be a mucin-poor variant of superficial acral fibromyxoma. Its morphology is distinct: a proliferation of bland-appearing spindled cells exhibiting a storiform or fascicular growth pattern and CD34 positivity.

The differential diagnosis to consider when ADF is suspected is a Koenen tumor, which resembles a fibrokeratoma clinically and also is localized to the digits. Koenen tumors can be differentiated from fibrokeratoma by its association with tuberous sclerosis; a multiple, rather than solitary, presentation; a distinctive clove-shaped gross appearance; and an appearance on histopathology of stellate-shaped fibroblasts with occasional giant cells. Despite these important differences, Koenen tumor does exhibit a striking morphologic similarity to ADF, given that the vertical orientation of collagen bundles in Koenen tumor is virtually identical to ADF.⁶

Management
There are no known associations between ADF and medication use, including methotrexate and adalimumab, which our patient was taking; additionally, no association with RA or other systemic disorder has been reported.² The preferred treatment of ADF is complete excision to the basal attachment of the tumor; recurrence is uncommon. Alternative therapies include destructive methods, such as cryotherapy, CO₂ laser ablation, and electrodesiccation.²

The National Defense Authorization Act for Fiscal Year 2017¹ has changed military medicine, including substantial reduction in military medical personnel as positions are converted to combat functions. As a result, there will be fewer military dermatologists, which means many US soldiers, sailors, airmen, and marines will seek medical care outside of military treatment facilities. This article highlights some unique treatment considerations in this patient population for our civilian dermatology colleagues.

Medical Readiness

In 2015, General Joseph F. Dunford Jr, 19th Chairman of the Joint Chiefs of Staff, made readiness his top priority for the US Armed Forces.² Readiness refers to service members’ ability to deploy to locations across the globe and perform their military duties with little advanced notice, which requires personnel to be medically prepared at all times to leave home and perform their duties in locations with limited medical support.

Medical readiness is maintaining a unit that is medically able to perform its military function both at home and in a deployed environment. Military members’ medical readiness status is carefully tracked and determined via annual physical, dental, hearing, and vision examinations, as well as human immunodeficiency virus status and immunizations. The readiness status of the unit (ie, the number of troops ready to deploy at any given time) is available to commanders at all levels at any time. Each military branch has tracking systems that allow commanders to know when a member is past due for an examination or if a member’s medical status has changed, making them nondeployable. When a member is nondeployable, it affects the unit’s ability to perform its mission and degrades its readiness. If readiness is suboptimal, the military cannot deploy and complete its missions, which is why readiness is a top priority. The primary function of military medicine is to support the medical readiness of the force.

Deployment Eligibility

A unique aspect of military medicine that can be foreign to civilian physicians is the unit commanders’ authority to request and receive information on military members’ medical conditions as they relate to readiness. Under most circumstances, an individual’s medical information is his/her private information; however, that is not always the case in the military. If a member’s medical status changes and he/she becomes nondeployable, by regulation the commander can be privy to pertinent aspects of that member’s medical condition as it affects unit readiness, including the diagnosis, treatment plan, and prognosis. Commanders need this information to aid in the member’s recovery, ensure training does not impact his/her care, and identify possible need of replacement.

Published accession guidelines are used to determine medical eligibility for service.³ These instructions are organized by major organ systems and broad disease categories. They provide guidance on medically disqualifying conditions. The Table outlines those conditions that apply to the skin.³ Individual military branches may have additional regulations with guidance on medically disqualifying conditions that are job specific. Additional regulations also are available based on an area of military operation that can be more restrictive and specific to those locations.⁴

Readiness and Patient Care

Importantly, readiness should not be seen as a roadblock to appropriate patient care. Patients should receive treatment that is appropriate for their medical condition. Much of the difficulty within military medicine is understanding and communicating how the natural disease history, prognosis, and treatment of their respective medical conditions will impact members’ service.

In some cases, the condition and/or treatment is incompatible with military service. Consider the following scenario: A 23-year-old active-duty soldier with a history of psoriasis developed widespread disease of 1 year’s duration and was referred to a civilian dermatologist due to nonavailability of a military dermatologist. After topical and light-based therapies failed, he was started on ustekinumab, which cleared the psoriasis. He wanted to continue on ustekinumab due to its good efficacy, but his unit was set to deploy in the coming year, and the drug made him medically nondeployable due to its immunosuppressive nature.

This real-life example was a difficult case to disposition. The service member was unsure if he could perform his military duties and deploy without continuing treatment with ustekinumab. His prior dermatology notes were requested to better assess the severity of his baseline disease, followed by a candid discussion between the military dermatologist and the patient about treatment options and their respective ramifications to his military career. One option included continuing ustekinumab, which would initiate an MEB evaluation and likely result in separation. Another option was UV therapy, which would not prompt an MEB evaluation but would not be available in deployed environments. Apremilast was offered as a third treatment option and could be used in place of UV therapy during deployment along with topical medications. This patient opted to continue treatment with ustekinumab, resulting in MEB review and separation from military service.

Dermatology Treatment Considerations

Civilian dermatologists should be aware of specific considerations when treating active US service members with common cutaneous diagnoses such as acne, atopic dermatitis (AD), psoriasis, dissecting cellulitis of the scalp (DCS), and lupus erythematosus (LE). This discussion is not meant to be all-inclusive but provides information and examples related to common treatment challenges in this patient population.

Acne
Acne is common in the active-duty military population. Typically, acne should be treated per recommended guidelines based on type and severity.⁸ Medical evaluation board review is warranted in cases of severe acne that is unresponsive to treatment and interferes with a service member’s performance.^5,6 Unique situations in the active-duty military population include the following:

• Use of minocycline. Aircrew members have unique restrictions on many medications,⁶ including minocycline, which is restricted in this population due to vestibular side effects. Doxycycline is an acceptable alternative for aircrew members; however, even this medication may require a ground trial to ensure there are no idiosyncratic effects.

• Use of isotretinoin, which is not permitted in aircrew members, submariners, or divers. If they take this medication, they will be temporarily removed from duty for the duration of treatment and for a period of time after completion (1–3 months, depending on service). Isotretinoin also is not used during deployment due to potential side effects, the need for laboratory monitoring, and iPLEDGE system requirements.

Atopic Dermatitis
A history of AD after the 12th birthday is considered a disqualifying condition with regard to military service,³ though mild and well-controlled disease can easily be overlooked during entrance physical examinations. Members frequently present with eczema flares following field training exercises where they are outdoors for many hours and have been exposed to grass or other environmental triggers while wearing military gear that is heavy and occlusive, which is further exacerbated by being unable to bathe or care for their skin as they would at home.

Separation from the military is considered when AD is moderate to severe, is unresponsive to treatment, and/or interferes with performance of duty. Severity often can be evaluated based on the impact of AD on performance of duties in addition to clinical appearance. A pilot who is distracted by itching presents a potentially dangerous situation. A soldier whose AD flares every time he/she goes to the field, requiring him/her to return home early to control symptoms, can be considered moderate to severe due to lack of ability to do his/her job away from home base.

Response to treatment is more often where trouble lies for military members with AD, as patients are only permitted to take emollients, preferred cleansers, and topical medications to field training exercises and deployments. UV therapy is used to control disease in the military population but is not an option in deployed environments. Classic immunosuppressants (eg, methotrexate, mycophenolate mofetil, azathioprine, cyclosporine) may result in a good response to treatment; however, due to their side-effect profiles, need for laboratory monitoring, and immunosuppressive nature, long-term use of those medications will result in a nondeployable status. Dupilumab does not appear to have the immunosuppressive effects of other biologics; however, the medication requires refrigeration,⁹ which currently precludes its use in the deployed environment, as it would be difficult to ensure supply and storage in remote areas.

Service members with a history of AD are exempt from the smallpox vaccine due to concerns about eczema vaccinatum.¹⁰

Psoriasis
Psoriasis is another dermatologic condition that does not meet military admission standards,³ and mild undiagnosed cases may be overlooked during the entrance physical examination. Because psoriasis commonly affects young adults, it may manifest in service members after entering service. If psoriasis is extensive or refractory to treatment, an MEB evaluation may be required.^5,6 Widespread psoriasis can result in considerable discomfort when wearing body armor and other military gear. Severe localized disease can have duty implications; service members with treatment-resistant scalp psoriasis or pustular psoriasis of the feet may have difficulty wearing helmets or military boots, respectively.

Most service members with limited psoriasis vulgaris can be managed with topical steroids and steroid-sparing agents such as calcipotriene. Some service members opt not to aggressively treat their psoriasis if it is limited in nature and not symptomatic.

When discussing systemic treatments beyond light therapy in those with refractory disease, apremilast can be a good first-line treatment option.¹¹ It is an oral medication, has minimal monitoring requirements, and lacks immunosuppressive side effects; therefore, it does not adversely impact deployability. If patients do not improve in 4 months with apremilast, biologics should then be considered; however, biologics have service implications, the most important being inability to deploy while taking the medication. In rare circumstances, military dermatologists may discuss utilizing biologic therapy only in the nondeployed setting. In these cases, service members are counseled that biologic therapy will be discontinued if they deploy in the future and treatment will be sustained with topicals and/or apremilast through the deployment. The treatment plan also should be communicated to the patient’s primary care provider to ensure that he/she is in agreement.

Dissecting Cellulitis of the Scalp
Dissecting cellulitis of the scalp may result in separation if the condition is unresponsive to treatment and/or interferes with satisfactory performance of duty.⁵ In addition to causing considerable pain, this condition can prevent service members from wearing combat helmets, which limits their ability to train and deploy. One of the authors (S.C.) has had more service members undergo an MEB evaluation for DCS than any of the other conditions mentioned.

Topical tretinoin and topical antibiotics can be used in conjunction with either doxycycline or minocycline to treat DCS, with the addition of intralesional corticosteroids for painful nodules. Fluctuant lesions are treated with incision and drainage. If there is inadequate response to treatment after 2 to 3 months, oral clindamycin and rifampin can be tried for 3 months. As an alternative measure or if the condition is refractory to oral clindamycin and rifampin, isotretinoin can then be used. One of the authors (S.C.) typically recommends a temporary no-helmet profile to the patient’s primary care provider until his/her next dermatology appointment. If the patient still has substantial disease despite these treatment options, it is recommended that the patient be issued a permanent profile for no helmet wear, which will prompt an MEB evaluation. Although tumor necrosis factor α inhibitors can work well in patients with DCS, the use of biologics is not conducive to continued service.

Lupus Erythematosus
A history of LE is disqualifying from military service. Patients who develop LE while on active duty will be referred for MEB evaluation if their disease is unresponsive to treatment and/or interferes with the satisfactory performance of duty.^5,6 In general, connective tissue diseases have an array of physical implications that can affect military service, including photosensitivity, joint inflammation, and internal organ involvement. Similar to the other dermatologic conditions described, treatment of connective tissue diseases also can present challenges to continued military service. Considerations in the case of LE that are unique to military service members include the following:

• Sun exposure. Most military service members are required to work outside in all manners of conditions, which include hot, sunny, humid, and/or dry climates. Often physicians might counsel sun-sensitive patients with LE to avoid being outside during daylight hours, limit window exposure at work, and avoid daytime driving when possible; however, these recommendations are not possible for many, if not most, service members.

• Immunosuppressive therapies are incompatible with military deployment; therefore, prescribing methotrexate, cyclosporine, mycophenolate mofetil, rituximab, or belimumab for treatment of LE would prompt an MEB evaluation if the treatment is necessary to control the disease.

Final Thoughts

The recent changes to military medicine are needed to meet our country’s defense requirements and will ultimately result in civilian specialists playing a larger role in the care of our military population. This article highlights unique factors civilian dermatologists must consider when treating active-duty military patients to ensure they remain deployable during treatment.

The National Defense Authorization Act for Fiscal Year 2017¹ has changed military medicine, including substantial reduction in military medical personnel as positions are converted to combat functions. As a result, there will be fewer military dermatologists, which means many US soldiers, sailors, airmen, and marines will seek medical care outside of military treatment facilities. This article highlights some unique treatment considerations in this patient population for our civilian dermatology colleagues.

Medical Readiness

In 2015, General Joseph F. Dunford Jr, 19th Chairman of the Joint Chiefs of Staff, made readiness his top priority for the US Armed Forces.² Readiness refers to service members’ ability to deploy to locations across the globe and perform their military duties with little advanced notice, which requires personnel to be medically prepared at all times to leave home and perform their duties in locations with limited medical support.

Medical readiness is maintaining a unit that is medically able to perform its military function both at home and in a deployed environment. Military members’ medical readiness status is carefully tracked and determined via annual physical, dental, hearing, and vision examinations, as well as human immunodeficiency virus status and immunizations. The readiness status of the unit (ie, the number of troops ready to deploy at any given time) is available to commanders at all levels at any time. Each military branch has tracking systems that allow commanders to know when a member is past due for an examination or if a member’s medical status has changed, making them nondeployable. When a member is nondeployable, it affects the unit’s ability to perform its mission and degrades its readiness. If readiness is suboptimal, the military cannot deploy and complete its missions, which is why readiness is a top priority. The primary function of military medicine is to support the medical readiness of the force.

Deployment Eligibility

A unique aspect of military medicine that can be foreign to civilian physicians is the unit commanders’ authority to request and receive information on military members’ medical conditions as they relate to readiness. Under most circumstances, an individual’s medical information is his/her private information; however, that is not always the case in the military. If a member’s medical status changes and he/she becomes nondeployable, by regulation the commander can be privy to pertinent aspects of that member’s medical condition as it affects unit readiness, including the diagnosis, treatment plan, and prognosis. Commanders need this information to aid in the member’s recovery, ensure training does not impact his/her care, and identify possible need of replacement.

Published accession guidelines are used to determine medical eligibility for service.³ These instructions are organized by major organ systems and broad disease categories. They provide guidance on medically disqualifying conditions. The Table outlines those conditions that apply to the skin.³ Individual military branches may have additional regulations with guidance on medically disqualifying conditions that are job specific. Additional regulations also are available based on an area of military operation that can be more restrictive and specific to those locations.⁴

Readiness and Patient Care

Importantly, readiness should not be seen as a roadblock to appropriate patient care. Patients should receive treatment that is appropriate for their medical condition. Much of the difficulty within military medicine is understanding and communicating how the natural disease history, prognosis, and treatment of their respective medical conditions will impact members’ service.

In some cases, the condition and/or treatment is incompatible with military service. Consider the following scenario: A 23-year-old active-duty soldier with a history of psoriasis developed widespread disease of 1 year’s duration and was referred to a civilian dermatologist due to nonavailability of a military dermatologist. After topical and light-based therapies failed, he was started on ustekinumab, which cleared the psoriasis. He wanted to continue on ustekinumab due to its good efficacy, but his unit was set to deploy in the coming year, and the drug made him medically nondeployable due to its immunosuppressive nature.

This real-life example was a difficult case to disposition. The service member was unsure if he could perform his military duties and deploy without continuing treatment with ustekinumab. His prior dermatology notes were requested to better assess the severity of his baseline disease, followed by a candid discussion between the military dermatologist and the patient about treatment options and their respective ramifications to his military career. One option included continuing ustekinumab, which would initiate an MEB evaluation and likely result in separation. Another option was UV therapy, which would not prompt an MEB evaluation but would not be available in deployed environments. Apremilast was offered as a third treatment option and could be used in place of UV therapy during deployment along with topical medications. This patient opted to continue treatment with ustekinumab, resulting in MEB review and separation from military service.

Dermatology Treatment Considerations

Civilian dermatologists should be aware of specific considerations when treating active US service members with common cutaneous diagnoses such as acne, atopic dermatitis (AD), psoriasis, dissecting cellulitis of the scalp (DCS), and lupus erythematosus (LE). This discussion is not meant to be all-inclusive but provides information and examples related to common treatment challenges in this patient population.

Acne
Acne is common in the active-duty military population. Typically, acne should be treated per recommended guidelines based on type and severity.⁸ Medical evaluation board review is warranted in cases of severe acne that is unresponsive to treatment and interferes with a service member’s performance.^5,6 Unique situations in the active-duty military population include the following:

• Use of minocycline. Aircrew members have unique restrictions on many medications,⁶ including minocycline, which is restricted in this population due to vestibular side effects. Doxycycline is an acceptable alternative for aircrew members; however, even this medication may require a ground trial to ensure there are no idiosyncratic effects.

• Use of isotretinoin, which is not permitted in aircrew members, submariners, or divers. If they take this medication, they will be temporarily removed from duty for the duration of treatment and for a period of time after completion (1–3 months, depending on service). Isotretinoin also is not used during deployment due to potential side effects, the need for laboratory monitoring, and iPLEDGE system requirements.

Atopic Dermatitis
A history of AD after the 12th birthday is considered a disqualifying condition with regard to military service,³ though mild and well-controlled disease can easily be overlooked during entrance physical examinations. Members frequently present with eczema flares following field training exercises where they are outdoors for many hours and have been exposed to grass or other environmental triggers while wearing military gear that is heavy and occlusive, which is further exacerbated by being unable to bathe or care for their skin as they would at home.

Separation from the military is considered when AD is moderate to severe, is unresponsive to treatment, and/or interferes with performance of duty. Severity often can be evaluated based on the impact of AD on performance of duties in addition to clinical appearance. A pilot who is distracted by itching presents a potentially dangerous situation. A soldier whose AD flares every time he/she goes to the field, requiring him/her to return home early to control symptoms, can be considered moderate to severe due to lack of ability to do his/her job away from home base.

Response to treatment is more often where trouble lies for military members with AD, as patients are only permitted to take emollients, preferred cleansers, and topical medications to field training exercises and deployments. UV therapy is used to control disease in the military population but is not an option in deployed environments. Classic immunosuppressants (eg, methotrexate, mycophenolate mofetil, azathioprine, cyclosporine) may result in a good response to treatment; however, due to their side-effect profiles, need for laboratory monitoring, and immunosuppressive nature, long-term use of those medications will result in a nondeployable status. Dupilumab does not appear to have the immunosuppressive effects of other biologics; however, the medication requires refrigeration,⁹ which currently precludes its use in the deployed environment, as it would be difficult to ensure supply and storage in remote areas.

Service members with a history of AD are exempt from the smallpox vaccine due to concerns about eczema vaccinatum.¹⁰

Psoriasis
Psoriasis is another dermatologic condition that does not meet military admission standards,³ and mild undiagnosed cases may be overlooked during the entrance physical examination. Because psoriasis commonly affects young adults, it may manifest in service members after entering service. If psoriasis is extensive or refractory to treatment, an MEB evaluation may be required.^5,6 Widespread psoriasis can result in considerable discomfort when wearing body armor and other military gear. Severe localized disease can have duty implications; service members with treatment-resistant scalp psoriasis or pustular psoriasis of the feet may have difficulty wearing helmets or military boots, respectively.

Most service members with limited psoriasis vulgaris can be managed with topical steroids and steroid-sparing agents such as calcipotriene. Some service members opt not to aggressively treat their psoriasis if it is limited in nature and not symptomatic.

When discussing systemic treatments beyond light therapy in those with refractory disease, apremilast can be a good first-line treatment option.¹¹ It is an oral medication, has minimal monitoring requirements, and lacks immunosuppressive side effects; therefore, it does not adversely impact deployability. If patients do not improve in 4 months with apremilast, biologics should then be considered; however, biologics have service implications, the most important being inability to deploy while taking the medication. In rare circumstances, military dermatologists may discuss utilizing biologic therapy only in the nondeployed setting. In these cases, service members are counseled that biologic therapy will be discontinued if they deploy in the future and treatment will be sustained with topicals and/or apremilast through the deployment. The treatment plan also should be communicated to the patient’s primary care provider to ensure that he/she is in agreement.

Dissecting Cellulitis of the Scalp
Dissecting cellulitis of the scalp may result in separation if the condition is unresponsive to treatment and/or interferes with satisfactory performance of duty.⁵ In addition to causing considerable pain, this condition can prevent service members from wearing combat helmets, which limits their ability to train and deploy. One of the authors (S.C.) has had more service members undergo an MEB evaluation for DCS than any of the other conditions mentioned.

Topical tretinoin and topical antibiotics can be used in conjunction with either doxycycline or minocycline to treat DCS, with the addition of intralesional corticosteroids for painful nodules. Fluctuant lesions are treated with incision and drainage. If there is inadequate response to treatment after 2 to 3 months, oral clindamycin and rifampin can be tried for 3 months. As an alternative measure or if the condition is refractory to oral clindamycin and rifampin, isotretinoin can then be used. One of the authors (S.C.) typically recommends a temporary no-helmet profile to the patient’s primary care provider until his/her next dermatology appointment. If the patient still has substantial disease despite these treatment options, it is recommended that the patient be issued a permanent profile for no helmet wear, which will prompt an MEB evaluation. Although tumor necrosis factor α inhibitors can work well in patients with DCS, the use of biologics is not conducive to continued service.

Lupus Erythematosus
A history of LE is disqualifying from military service. Patients who develop LE while on active duty will be referred for MEB evaluation if their disease is unresponsive to treatment and/or interferes with the satisfactory performance of duty.^5,6 In general, connective tissue diseases have an array of physical implications that can affect military service, including photosensitivity, joint inflammation, and internal organ involvement. Similar to the other dermatologic conditions described, treatment of connective tissue diseases also can present challenges to continued military service. Considerations in the case of LE that are unique to military service members include the following:

• Sun exposure. Most military service members are required to work outside in all manners of conditions, which include hot, sunny, humid, and/or dry climates. Often physicians might counsel sun-sensitive patients with LE to avoid being outside during daylight hours, limit window exposure at work, and avoid daytime driving when possible; however, these recommendations are not possible for many, if not most, service members.

• Immunosuppressive therapies are incompatible with military deployment; therefore, prescribing methotrexate, cyclosporine, mycophenolate mofetil, rituximab, or belimumab for treatment of LE would prompt an MEB evaluation if the treatment is necessary to control the disease.

Final Thoughts

The recent changes to military medicine are needed to meet our country’s defense requirements and will ultimately result in civilian specialists playing a larger role in the care of our military population. This article highlights unique factors civilian dermatologists must consider when treating active-duty military patients to ensure they remain deployable during treatment.

The National Defense Authorization Act for Fiscal Year 2017¹ has changed military medicine, including substantial reduction in military medical personnel as positions are converted to combat functions. As a result, there will be fewer military dermatologists, which means many US soldiers, sailors, airmen, and marines will seek medical care outside of military treatment facilities. This article highlights some unique treatment considerations in this patient population for our civilian dermatology colleagues.

Medical Readiness

In 2015, General Joseph F. Dunford Jr, 19th Chairman of the Joint Chiefs of Staff, made readiness his top priority for the US Armed Forces.² Readiness refers to service members’ ability to deploy to locations across the globe and perform their military duties with little advanced notice, which requires personnel to be medically prepared at all times to leave home and perform their duties in locations with limited medical support.

Medical readiness is maintaining a unit that is medically able to perform its military function both at home and in a deployed environment. Military members’ medical readiness status is carefully tracked and determined via annual physical, dental, hearing, and vision examinations, as well as human immunodeficiency virus status and immunizations. The readiness status of the unit (ie, the number of troops ready to deploy at any given time) is available to commanders at all levels at any time. Each military branch has tracking systems that allow commanders to know when a member is past due for an examination or if a member’s medical status has changed, making them nondeployable. When a member is nondeployable, it affects the unit’s ability to perform its mission and degrades its readiness. If readiness is suboptimal, the military cannot deploy and complete its missions, which is why readiness is a top priority. The primary function of military medicine is to support the medical readiness of the force.

Deployment Eligibility

A unique aspect of military medicine that can be foreign to civilian physicians is the unit commanders’ authority to request and receive information on military members’ medical conditions as they relate to readiness. Under most circumstances, an individual’s medical information is his/her private information; however, that is not always the case in the military. If a member’s medical status changes and he/she becomes nondeployable, by regulation the commander can be privy to pertinent aspects of that member’s medical condition as it affects unit readiness, including the diagnosis, treatment plan, and prognosis. Commanders need this information to aid in the member’s recovery, ensure training does not impact his/her care, and identify possible need of replacement.

Published accession guidelines are used to determine medical eligibility for service.³ These instructions are organized by major organ systems and broad disease categories. They provide guidance on medically disqualifying conditions. The Table outlines those conditions that apply to the skin.³ Individual military branches may have additional regulations with guidance on medically disqualifying conditions that are job specific. Additional regulations also are available based on an area of military operation that can be more restrictive and specific to those locations.⁴

Readiness and Patient Care

Importantly, readiness should not be seen as a roadblock to appropriate patient care. Patients should receive treatment that is appropriate for their medical condition. Much of the difficulty within military medicine is understanding and communicating how the natural disease history, prognosis, and treatment of their respective medical conditions will impact members’ service.

In some cases, the condition and/or treatment is incompatible with military service. Consider the following scenario: A 23-year-old active-duty soldier with a history of psoriasis developed widespread disease of 1 year’s duration and was referred to a civilian dermatologist due to nonavailability of a military dermatologist. After topical and light-based therapies failed, he was started on ustekinumab, which cleared the psoriasis. He wanted to continue on ustekinumab due to its good efficacy, but his unit was set to deploy in the coming year, and the drug made him medically nondeployable due to its immunosuppressive nature.

This real-life example was a difficult case to disposition. The service member was unsure if he could perform his military duties and deploy without continuing treatment with ustekinumab. His prior dermatology notes were requested to better assess the severity of his baseline disease, followed by a candid discussion between the military dermatologist and the patient about treatment options and their respective ramifications to his military career. One option included continuing ustekinumab, which would initiate an MEB evaluation and likely result in separation. Another option was UV therapy, which would not prompt an MEB evaluation but would not be available in deployed environments. Apremilast was offered as a third treatment option and could be used in place of UV therapy during deployment along with topical medications. This patient opted to continue treatment with ustekinumab, resulting in MEB review and separation from military service.

Dermatology Treatment Considerations

Civilian dermatologists should be aware of specific considerations when treating active US service members with common cutaneous diagnoses such as acne, atopic dermatitis (AD), psoriasis, dissecting cellulitis of the scalp (DCS), and lupus erythematosus (LE). This discussion is not meant to be all-inclusive but provides information and examples related to common treatment challenges in this patient population.

Acne
Acne is common in the active-duty military population. Typically, acne should be treated per recommended guidelines based on type and severity.⁸ Medical evaluation board review is warranted in cases of severe acne that is unresponsive to treatment and interferes with a service member’s performance.^5,6 Unique situations in the active-duty military population include the following:

• Use of minocycline. Aircrew members have unique restrictions on many medications,⁶ including minocycline, which is restricted in this population due to vestibular side effects. Doxycycline is an acceptable alternative for aircrew members; however, even this medication may require a ground trial to ensure there are no idiosyncratic effects.

• Use of isotretinoin, which is not permitted in aircrew members, submariners, or divers. If they take this medication, they will be temporarily removed from duty for the duration of treatment and for a period of time after completion (1–3 months, depending on service). Isotretinoin also is not used during deployment due to potential side effects, the need for laboratory monitoring, and iPLEDGE system requirements.

Atopic Dermatitis
A history of AD after the 12th birthday is considered a disqualifying condition with regard to military service,³ though mild and well-controlled disease can easily be overlooked during entrance physical examinations. Members frequently present with eczema flares following field training exercises where they are outdoors for many hours and have been exposed to grass or other environmental triggers while wearing military gear that is heavy and occlusive, which is further exacerbated by being unable to bathe or care for their skin as they would at home.

Separation from the military is considered when AD is moderate to severe, is unresponsive to treatment, and/or interferes with performance of duty. Severity often can be evaluated based on the impact of AD on performance of duties in addition to clinical appearance. A pilot who is distracted by itching presents a potentially dangerous situation. A soldier whose AD flares every time he/she goes to the field, requiring him/her to return home early to control symptoms, can be considered moderate to severe due to lack of ability to do his/her job away from home base.

Response to treatment is more often where trouble lies for military members with AD, as patients are only permitted to take emollients, preferred cleansers, and topical medications to field training exercises and deployments. UV therapy is used to control disease in the military population but is not an option in deployed environments. Classic immunosuppressants (eg, methotrexate, mycophenolate mofetil, azathioprine, cyclosporine) may result in a good response to treatment; however, due to their side-effect profiles, need for laboratory monitoring, and immunosuppressive nature, long-term use of those medications will result in a nondeployable status. Dupilumab does not appear to have the immunosuppressive effects of other biologics; however, the medication requires refrigeration,⁹ which currently precludes its use in the deployed environment, as it would be difficult to ensure supply and storage in remote areas.

Service members with a history of AD are exempt from the smallpox vaccine due to concerns about eczema vaccinatum.¹⁰

Psoriasis
Psoriasis is another dermatologic condition that does not meet military admission standards,³ and mild undiagnosed cases may be overlooked during the entrance physical examination. Because psoriasis commonly affects young adults, it may manifest in service members after entering service. If psoriasis is extensive or refractory to treatment, an MEB evaluation may be required.^5,6 Widespread psoriasis can result in considerable discomfort when wearing body armor and other military gear. Severe localized disease can have duty implications; service members with treatment-resistant scalp psoriasis or pustular psoriasis of the feet may have difficulty wearing helmets or military boots, respectively.

Most service members with limited psoriasis vulgaris can be managed with topical steroids and steroid-sparing agents such as calcipotriene. Some service members opt not to aggressively treat their psoriasis if it is limited in nature and not symptomatic.

When discussing systemic treatments beyond light therapy in those with refractory disease, apremilast can be a good first-line treatment option.¹¹ It is an oral medication, has minimal monitoring requirements, and lacks immunosuppressive side effects; therefore, it does not adversely impact deployability. If patients do not improve in 4 months with apremilast, biologics should then be considered; however, biologics have service implications, the most important being inability to deploy while taking the medication. In rare circumstances, military dermatologists may discuss utilizing biologic therapy only in the nondeployed setting. In these cases, service members are counseled that biologic therapy will be discontinued if they deploy in the future and treatment will be sustained with topicals and/or apremilast through the deployment. The treatment plan also should be communicated to the patient’s primary care provider to ensure that he/she is in agreement.

Dissecting Cellulitis of the Scalp
Dissecting cellulitis of the scalp may result in separation if the condition is unresponsive to treatment and/or interferes with satisfactory performance of duty.⁵ In addition to causing considerable pain, this condition can prevent service members from wearing combat helmets, which limits their ability to train and deploy. One of the authors (S.C.) has had more service members undergo an MEB evaluation for DCS than any of the other conditions mentioned.

Topical tretinoin and topical antibiotics can be used in conjunction with either doxycycline or minocycline to treat DCS, with the addition of intralesional corticosteroids for painful nodules. Fluctuant lesions are treated with incision and drainage. If there is inadequate response to treatment after 2 to 3 months, oral clindamycin and rifampin can be tried for 3 months. As an alternative measure or if the condition is refractory to oral clindamycin and rifampin, isotretinoin can then be used. One of the authors (S.C.) typically recommends a temporary no-helmet profile to the patient’s primary care provider until his/her next dermatology appointment. If the patient still has substantial disease despite these treatment options, it is recommended that the patient be issued a permanent profile for no helmet wear, which will prompt an MEB evaluation. Although tumor necrosis factor α inhibitors can work well in patients with DCS, the use of biologics is not conducive to continued service.

Lupus Erythematosus
A history of LE is disqualifying from military service. Patients who develop LE while on active duty will be referred for MEB evaluation if their disease is unresponsive to treatment and/or interferes with the satisfactory performance of duty.^5,6 In general, connective tissue diseases have an array of physical implications that can affect military service, including photosensitivity, joint inflammation, and internal organ involvement. Similar to the other dermatologic conditions described, treatment of connective tissue diseases also can present challenges to continued military service. Considerations in the case of LE that are unique to military service members include the following:

• Sun exposure. Most military service members are required to work outside in all manners of conditions, which include hot, sunny, humid, and/or dry climates. Often physicians might counsel sun-sensitive patients with LE to avoid being outside during daylight hours, limit window exposure at work, and avoid daytime driving when possible; however, these recommendations are not possible for many, if not most, service members.

• Immunosuppressive therapies are incompatible with military deployment; therefore, prescribing methotrexate, cyclosporine, mycophenolate mofetil, rituximab, or belimumab for treatment of LE would prompt an MEB evaluation if the treatment is necessary to control the disease.

Final Thoughts

The recent changes to military medicine are needed to meet our country’s defense requirements and will ultimately result in civilian specialists playing a larger role in the care of our military population. This article highlights unique factors civilian dermatologists must consider when treating active-duty military patients to ensure they remain deployable during treatment.

In 2017, consumers spent an average of $8.53 billion on nail services.¹ This booming industry is set to grow to more than $15.5 billion by 2024.² Nail polishes and other nail cosmetic trends can present new exposures for consumers, including chemicals that can elicit allergic contact dermatitis. In this article, we discuss new nail trends and their associated allergens, the acrylates.

Tosylamide/Formaldehyde Resin

Traditionally, the most widely recognized nail polish allergen has been tosylamide/formaldehyde resin (TSFR). However, there now are many touted TSFR-free nail polishes on the market, and the rate of positive reactions to this chemical has been declining in recent years. The North American Contact Dermatitis Group reported a positive reaction rate of 1.3% from 2005 through 2006,³ and rates decreased to 0.9% from 2015 through 2016.⁴ An Australian study demonstrated a similar reduction in positive reaction rates to nail polish chemicals, with only 0.7% of patients reacting to TSFR from 2014 to 2016 and 0% in 2017. It is theorized that this reduction occurred from replacing TSFR in traditional nail polishes with other chemicals such as polyester resins and cellulose acetate butyrate.⁵

Acrylate-Based Nail Treatments

Consumers recently have been gravitating toward acrylate-based nail treatments vs traditional nail polishes for a variety of reasons. Often referred to as gels, dips, or shellac, acrylate-based nail treatments represent a hot new trend in nail cosmetics. These manicures are resistant to chipping and scratches, creating a like-new look that lasts for weeks after application. The long-lasting nature of acrylate-based nail polishes has made them wildly popular with consumers.

Traditional acrylic nails consist of a powder polymer mixed with a liquid monomer, which polymerizes when a catalyst is added.⁶ The procedure is time consuming and can take up to 2 hours for application. In contrast, the newer gel manicure can be completed faster and includes application of acrylate-based nail polish, including a base coat, 2 coats of color, and a top coat. Exposure to either a light-emitting diode (30–60 seconds) or UVA (2 minutes) lamp is necessary after each coat is applied for polymerization (Figure 1).⁶ This long-lasting, semipermanent manicure typically is what patients are referring to when they say they have “gel nails.”

Acrylate Allergy

Patients who are allergic to acrylates can present with different patterns of dermatitis. Although the majority of patients present with dermatitis on the hands, fingers, or wrists, up to 10% may only have facial and neck dermatitis.⁸ Less commonly, the abdomen and thighs can be involved.^6,8 Nail technicians most commonly present with pulpitis with cutaneous fissures.⁸ Other symptoms can include subungual hyperkeratosis, onycholysis, and nail dystrophy. Paresthesia, urticaria, and upper respiratory tract symptoms can occur but are less common.^6,8

Acrylate allergy typically is the result of sensitization to the acrylate monomers. In theory, gel nail acrylate materials are polymerized following exposure to a light-emitting diode or UVA lamp; however, there likely is some incomplete polymerization, which can increase the risk for development of allergy. Allergen exposure can occur due to incorrect application of the light source; inadvertent monomer exposure, which occurs when nail technicians wipe extra acrylate off of a client’s finger(s); or inadvertent application of acrylate monomers to objects in the nail technician’s work environment.^6,8

Several acrylate nail allergens have been reported. Many studies have identified 2-hydroxyethyl methacrylate (HEMA) as the most common nail acrylate allergen.^8,9 At least one study identified 2-hydroxypropyl methacrylate as the most common, with HEMA in second place.⁶ Other reported acrylate allergens have included ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, ethyl cyanoacrylate, 1,4-butanediol diacrylate, hydroxypropyl acrylate, and 2-hydroxyethyl acrylate.^8,9

The American Contact Dermatitis Society Core Allergen Series and the North American Contact Dermatitis Group screening series currently include HEMA, methyl methacrylate, ethyl acrylate, ethyl cyanoacrylate, and TSFR.^4,10 Of note, acrylates are not included in the thin-layer rapid use epicutaneous (T.R.U.E.) patch test (SmartPractice), so they will be missed if this series is used.¹¹ In the setting of suspected nail acrylate allergy, some authors recommend initial screening with HEMA and ethyl cyanoacrylate, with extended acrylate testing if both are negative.⁸

Upon patch testing with an acrylate series, patients frequently react to 2 or more acrylates and the reactions can be strong (++) or extreme (+++), which may represent cosensitization or cross-sensitization.⁸ The likelihood of cross-reactivity between acrylates is not clear, though it has been postulated that it is theoretically possible.⁶

An important pearl for patch testers using the chamber method is proper storage of acrylate allergens and assembly of trays prior to patch testing. Similar to all haptens, manufacturers recommend that acrylates should be stored in a refrigerator, but some authors suggest that acrylates should be stored in the freezer.¹² Acrylates are volatile chemicals and rapidly degrade when exposed to air. A methyl methacrylate preparation loaded into an inert quadrate (IQ) chamber and stored at room temperature showed a nearly undetectable amount of any residual methyl methacrylate 24 hours later. Refrigeration of allergens in chambers slowed but did not stop eventual degradation, with nearly all acrylate preparations reaching an undetectable level of allergen by day 8.¹³ Acrylates, along with other volatile allergens, should only be loaded into chambers immediately prior to placement on the patient.

Allergy Prevention

Prevention of nail acrylate allergy among consumers is simple: avoid contact with the offending allergen. Acrylate spillover (ie, applying the acrylate onto the skin) and direct contact with objects and working surfaces contaminated with acrylate-based nail products should be avoided.⁸ Avoidance is more complicated for nail technicians, but it is thought that nitrile gloves allow for the best dexterity and allergen avoidance when acrylate exposure is brief.¹⁴ Allowable exposure times with nitrile gloves may be 15 to 30 minutes. After this times passes, a glove change is required to avoid exposure.¹⁴ Wearing nitrile gloves for longer than 15 to 30 minutes will result in cutaneous exposure and risk for dermatitis in sensitized patients. If longer wear is desired, one option includes cutting the fingertips off of Silver Shield/4H gloves (Honeywell Safety Products USA, Inc), applying them to the distal fingers, and wearing a standard nitrile glove over top, known as the finger stall technique.⁶ In one study, this technique was recommended to nail technicians with acrylate allergy. A telephone survey conducted 4 to 43 months later confirmed that 36% (8/22) of participants were using the technique without symptoms. In this same study, 73% (16/22) had continued working as nail technicians.⁶

Acrylates are used for other medical purposes, including dental procedures, orthopedic procedures, surgical glues, wound dressings, and contact and intraocular lenses. They also have additional cosmetic applications, including eyelash and hair extensions.⁸ Therefore, it is vital that patients disclose any history of acrylate allergy to both their medical and cosmetic providers.

Our Final Interpretation

Acrylate allergy has become increasingly common, and long-lasting nail treatments often are the culprit. Whether through gels, dips, or shellac, repeated exposure to acrylates through nail treatments can increase the risk for allergy. The T.R.U.E. test alone will not make the diagnosis, as acrylates are not present in this patch test system. It is important to remind your allergic patients that acrylates are present in other compounds used for medical and cosmetic purposes. Avoidance is key, and for allergic patients who love to bedazzle their nails, we suggest less-permanent, acrylate-free nail polishes as alternatives.

In 2017, consumers spent an average of $8.53 billion on nail services.¹ This booming industry is set to grow to more than $15.5 billion by 2024.² Nail polishes and other nail cosmetic trends can present new exposures for consumers, including chemicals that can elicit allergic contact dermatitis. In this article, we discuss new nail trends and their associated allergens, the acrylates.

Tosylamide/Formaldehyde Resin

Traditionally, the most widely recognized nail polish allergen has been tosylamide/formaldehyde resin (TSFR). However, there now are many touted TSFR-free nail polishes on the market, and the rate of positive reactions to this chemical has been declining in recent years. The North American Contact Dermatitis Group reported a positive reaction rate of 1.3% from 2005 through 2006,³ and rates decreased to 0.9% from 2015 through 2016.⁴ An Australian study demonstrated a similar reduction in positive reaction rates to nail polish chemicals, with only 0.7% of patients reacting to TSFR from 2014 to 2016 and 0% in 2017. It is theorized that this reduction occurred from replacing TSFR in traditional nail polishes with other chemicals such as polyester resins and cellulose acetate butyrate.⁵

Acrylate-Based Nail Treatments

Consumers recently have been gravitating toward acrylate-based nail treatments vs traditional nail polishes for a variety of reasons. Often referred to as gels, dips, or shellac, acrylate-based nail treatments represent a hot new trend in nail cosmetics. These manicures are resistant to chipping and scratches, creating a like-new look that lasts for weeks after application. The long-lasting nature of acrylate-based nail polishes has made them wildly popular with consumers.

Traditional acrylic nails consist of a powder polymer mixed with a liquid monomer, which polymerizes when a catalyst is added.⁶ The procedure is time consuming and can take up to 2 hours for application. In contrast, the newer gel manicure can be completed faster and includes application of acrylate-based nail polish, including a base coat, 2 coats of color, and a top coat. Exposure to either a light-emitting diode (30–60 seconds) or UVA (2 minutes) lamp is necessary after each coat is applied for polymerization (Figure 1).⁶ This long-lasting, semipermanent manicure typically is what patients are referring to when they say they have “gel nails.”

Acrylate Allergy

Patients who are allergic to acrylates can present with different patterns of dermatitis. Although the majority of patients present with dermatitis on the hands, fingers, or wrists, up to 10% may only have facial and neck dermatitis.⁸ Less commonly, the abdomen and thighs can be involved.^6,8 Nail technicians most commonly present with pulpitis with cutaneous fissures.⁸ Other symptoms can include subungual hyperkeratosis, onycholysis, and nail dystrophy. Paresthesia, urticaria, and upper respiratory tract symptoms can occur but are less common.^6,8

Acrylate allergy typically is the result of sensitization to the acrylate monomers. In theory, gel nail acrylate materials are polymerized following exposure to a light-emitting diode or UVA lamp; however, there likely is some incomplete polymerization, which can increase the risk for development of allergy. Allergen exposure can occur due to incorrect application of the light source; inadvertent monomer exposure, which occurs when nail technicians wipe extra acrylate off of a client’s finger(s); or inadvertent application of acrylate monomers to objects in the nail technician’s work environment.^6,8

Several acrylate nail allergens have been reported. Many studies have identified 2-hydroxyethyl methacrylate (HEMA) as the most common nail acrylate allergen.^8,9 At least one study identified 2-hydroxypropyl methacrylate as the most common, with HEMA in second place.⁶ Other reported acrylate allergens have included ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, ethyl cyanoacrylate, 1,4-butanediol diacrylate, hydroxypropyl acrylate, and 2-hydroxyethyl acrylate.^8,9

The American Contact Dermatitis Society Core Allergen Series and the North American Contact Dermatitis Group screening series currently include HEMA, methyl methacrylate, ethyl acrylate, ethyl cyanoacrylate, and TSFR.^4,10 Of note, acrylates are not included in the thin-layer rapid use epicutaneous (T.R.U.E.) patch test (SmartPractice), so they will be missed if this series is used.¹¹ In the setting of suspected nail acrylate allergy, some authors recommend initial screening with HEMA and ethyl cyanoacrylate, with extended acrylate testing if both are negative.⁸

Upon patch testing with an acrylate series, patients frequently react to 2 or more acrylates and the reactions can be strong (++) or extreme (+++), which may represent cosensitization or cross-sensitization.⁸ The likelihood of cross-reactivity between acrylates is not clear, though it has been postulated that it is theoretically possible.⁶

An important pearl for patch testers using the chamber method is proper storage of acrylate allergens and assembly of trays prior to patch testing. Similar to all haptens, manufacturers recommend that acrylates should be stored in a refrigerator, but some authors suggest that acrylates should be stored in the freezer.¹² Acrylates are volatile chemicals and rapidly degrade when exposed to air. A methyl methacrylate preparation loaded into an inert quadrate (IQ) chamber and stored at room temperature showed a nearly undetectable amount of any residual methyl methacrylate 24 hours later. Refrigeration of allergens in chambers slowed but did not stop eventual degradation, with nearly all acrylate preparations reaching an undetectable level of allergen by day 8.¹³ Acrylates, along with other volatile allergens, should only be loaded into chambers immediately prior to placement on the patient.

Allergy Prevention

Prevention of nail acrylate allergy among consumers is simple: avoid contact with the offending allergen. Acrylate spillover (ie, applying the acrylate onto the skin) and direct contact with objects and working surfaces contaminated with acrylate-based nail products should be avoided.⁸ Avoidance is more complicated for nail technicians, but it is thought that nitrile gloves allow for the best dexterity and allergen avoidance when acrylate exposure is brief.¹⁴ Allowable exposure times with nitrile gloves may be 15 to 30 minutes. After this times passes, a glove change is required to avoid exposure.¹⁴ Wearing nitrile gloves for longer than 15 to 30 minutes will result in cutaneous exposure and risk for dermatitis in sensitized patients. If longer wear is desired, one option includes cutting the fingertips off of Silver Shield/4H gloves (Honeywell Safety Products USA, Inc), applying them to the distal fingers, and wearing a standard nitrile glove over top, known as the finger stall technique.⁶ In one study, this technique was recommended to nail technicians with acrylate allergy. A telephone survey conducted 4 to 43 months later confirmed that 36% (8/22) of participants were using the technique without symptoms. In this same study, 73% (16/22) had continued working as nail technicians.⁶

Acrylates are used for other medical purposes, including dental procedures, orthopedic procedures, surgical glues, wound dressings, and contact and intraocular lenses. They also have additional cosmetic applications, including eyelash and hair extensions.⁸ Therefore, it is vital that patients disclose any history of acrylate allergy to both their medical and cosmetic providers.

Our Final Interpretation

Acrylate allergy has become increasingly common, and long-lasting nail treatments often are the culprit. Whether through gels, dips, or shellac, repeated exposure to acrylates through nail treatments can increase the risk for allergy. The T.R.U.E. test alone will not make the diagnosis, as acrylates are not present in this patch test system. It is important to remind your allergic patients that acrylates are present in other compounds used for medical and cosmetic purposes. Avoidance is key, and for allergic patients who love to bedazzle their nails, we suggest less-permanent, acrylate-free nail polishes as alternatives.

In 2017, consumers spent an average of $8.53 billion on nail services.¹ This booming industry is set to grow to more than $15.5 billion by 2024.² Nail polishes and other nail cosmetic trends can present new exposures for consumers, including chemicals that can elicit allergic contact dermatitis. In this article, we discuss new nail trends and their associated allergens, the acrylates.

Tosylamide/Formaldehyde Resin

Traditionally, the most widely recognized nail polish allergen has been tosylamide/formaldehyde resin (TSFR). However, there now are many touted TSFR-free nail polishes on the market, and the rate of positive reactions to this chemical has been declining in recent years. The North American Contact Dermatitis Group reported a positive reaction rate of 1.3% from 2005 through 2006,³ and rates decreased to 0.9% from 2015 through 2016.⁴ An Australian study demonstrated a similar reduction in positive reaction rates to nail polish chemicals, with only 0.7% of patients reacting to TSFR from 2014 to 2016 and 0% in 2017. It is theorized that this reduction occurred from replacing TSFR in traditional nail polishes with other chemicals such as polyester resins and cellulose acetate butyrate.⁵

Acrylate-Based Nail Treatments

Consumers recently have been gravitating toward acrylate-based nail treatments vs traditional nail polishes for a variety of reasons. Often referred to as gels, dips, or shellac, acrylate-based nail treatments represent a hot new trend in nail cosmetics. These manicures are resistant to chipping and scratches, creating a like-new look that lasts for weeks after application. The long-lasting nature of acrylate-based nail polishes has made them wildly popular with consumers.

Traditional acrylic nails consist of a powder polymer mixed with a liquid monomer, which polymerizes when a catalyst is added.⁶ The procedure is time consuming and can take up to 2 hours for application. In contrast, the newer gel manicure can be completed faster and includes application of acrylate-based nail polish, including a base coat, 2 coats of color, and a top coat. Exposure to either a light-emitting diode (30–60 seconds) or UVA (2 minutes) lamp is necessary after each coat is applied for polymerization (Figure 1).⁶ This long-lasting, semipermanent manicure typically is what patients are referring to when they say they have “gel nails.”

Acrylate Allergy

Patients who are allergic to acrylates can present with different patterns of dermatitis. Although the majority of patients present with dermatitis on the hands, fingers, or wrists, up to 10% may only have facial and neck dermatitis.⁸ Less commonly, the abdomen and thighs can be involved.^6,8 Nail technicians most commonly present with pulpitis with cutaneous fissures.⁸ Other symptoms can include subungual hyperkeratosis, onycholysis, and nail dystrophy. Paresthesia, urticaria, and upper respiratory tract symptoms can occur but are less common.^6,8

Acrylate allergy typically is the result of sensitization to the acrylate monomers. In theory, gel nail acrylate materials are polymerized following exposure to a light-emitting diode or UVA lamp; however, there likely is some incomplete polymerization, which can increase the risk for development of allergy. Allergen exposure can occur due to incorrect application of the light source; inadvertent monomer exposure, which occurs when nail technicians wipe extra acrylate off of a client’s finger(s); or inadvertent application of acrylate monomers to objects in the nail technician’s work environment.^6,8

Several acrylate nail allergens have been reported. Many studies have identified 2-hydroxyethyl methacrylate (HEMA) as the most common nail acrylate allergen.^8,9 At least one study identified 2-hydroxypropyl methacrylate as the most common, with HEMA in second place.⁶ Other reported acrylate allergens have included ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, ethyl cyanoacrylate, 1,4-butanediol diacrylate, hydroxypropyl acrylate, and 2-hydroxyethyl acrylate.^8,9

The American Contact Dermatitis Society Core Allergen Series and the North American Contact Dermatitis Group screening series currently include HEMA, methyl methacrylate, ethyl acrylate, ethyl cyanoacrylate, and TSFR.^4,10 Of note, acrylates are not included in the thin-layer rapid use epicutaneous (T.R.U.E.) patch test (SmartPractice), so they will be missed if this series is used.¹¹ In the setting of suspected nail acrylate allergy, some authors recommend initial screening with HEMA and ethyl cyanoacrylate, with extended acrylate testing if both are negative.⁸

Upon patch testing with an acrylate series, patients frequently react to 2 or more acrylates and the reactions can be strong (++) or extreme (+++), which may represent cosensitization or cross-sensitization.⁸ The likelihood of cross-reactivity between acrylates is not clear, though it has been postulated that it is theoretically possible.⁶

An important pearl for patch testers using the chamber method is proper storage of acrylate allergens and assembly of trays prior to patch testing. Similar to all haptens, manufacturers recommend that acrylates should be stored in a refrigerator, but some authors suggest that acrylates should be stored in the freezer.¹² Acrylates are volatile chemicals and rapidly degrade when exposed to air. A methyl methacrylate preparation loaded into an inert quadrate (IQ) chamber and stored at room temperature showed a nearly undetectable amount of any residual methyl methacrylate 24 hours later. Refrigeration of allergens in chambers slowed but did not stop eventual degradation, with nearly all acrylate preparations reaching an undetectable level of allergen by day 8.¹³ Acrylates, along with other volatile allergens, should only be loaded into chambers immediately prior to placement on the patient.

Allergy Prevention

Prevention of nail acrylate allergy among consumers is simple: avoid contact with the offending allergen. Acrylate spillover (ie, applying the acrylate onto the skin) and direct contact with objects and working surfaces contaminated with acrylate-based nail products should be avoided.⁸ Avoidance is more complicated for nail technicians, but it is thought that nitrile gloves allow for the best dexterity and allergen avoidance when acrylate exposure is brief.¹⁴ Allowable exposure times with nitrile gloves may be 15 to 30 minutes. After this times passes, a glove change is required to avoid exposure.¹⁴ Wearing nitrile gloves for longer than 15 to 30 minutes will result in cutaneous exposure and risk for dermatitis in sensitized patients. If longer wear is desired, one option includes cutting the fingertips off of Silver Shield/4H gloves (Honeywell Safety Products USA, Inc), applying them to the distal fingers, and wearing a standard nitrile glove over top, known as the finger stall technique.⁶ In one study, this technique was recommended to nail technicians with acrylate allergy. A telephone survey conducted 4 to 43 months later confirmed that 36% (8/22) of participants were using the technique without symptoms. In this same study, 73% (16/22) had continued working as nail technicians.⁶

Acrylates are used for other medical purposes, including dental procedures, orthopedic procedures, surgical glues, wound dressings, and contact and intraocular lenses. They also have additional cosmetic applications, including eyelash and hair extensions.⁸ Therefore, it is vital that patients disclose any history of acrylate allergy to both their medical and cosmetic providers.

Our Final Interpretation

Acrylate allergy has become increasingly common, and long-lasting nail treatments often are the culprit. Whether through gels, dips, or shellac, repeated exposure to acrylates through nail treatments can increase the risk for allergy. The T.R.U.E. test alone will not make the diagnosis, as acrylates are not present in this patch test system. It is important to remind your allergic patients that acrylates are present in other compounds used for medical and cosmetic purposes. Avoidance is key, and for allergic patients who love to bedazzle their nails, we suggest less-permanent, acrylate-free nail polishes as alternatives.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

CHICAGO – Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

Many patients with hidradenitis suppurativa (HS) experience depression and anxiety, according to data from a systematic review and meta-analysis of more than 40,000 adults.

Previous studies of psychiatric comorbidities in HS patients have suggested an increased rate of depression, anxiety, and suicide risk, but have varied in methodology. “Therefore, the exact magnitude of the prevalence and odds of depression and anxiety in patients with HS is unclear,” wrote Myrela O. Machado, MD, of the division of dermatology, Women’s College Hospital, Toronto, and colleagues.

In a review of PubMed/MEDLINE, Embase, and PsycINFO electronic databases through July 2018, the researchers identified 10 studies comprising 40,307 adults with HS. The overall prevalence of depression was 16.9%, and in the studies that included a comparison group, the odds ratio for depression was 1.84 for HS patients, compared with controls who did not have HS. The overall prevalence of anxiety was 4.9%, but data were insufficient to determine an odds ratio for anxiety. The study was published in JAMA Dermatology.

All 10 studies assessed depression; 4 assessed anxiety. In subgroup analyses, the prevalence of depression was 11.9% in studies with a diagnosis based on clinical criteria and 26.8% in studies that used a screening instrument. The prevalence was 25.9% for outpatients with HS.


“Although our findings indicate that depression and anxiety may be common among people with HS, whether there is a causal relationship in those associations remains to be proved,” the researchers wrote.

However, they noted, “the consequences of depression and anxiety on HS-related outcomes have recently received more attention.”

The study findings were limited by several factors including the lack of data from structured diagnostic interviews, variation in methodological quality, and variation in comparison groups across studies, as well as a high level of heterogeneity across studies, the researchers noted. However, the results support the need to recognize and treat psychiatric conditions in HS patients, and to develop new management strategies, they said.

Dr. Machado had no financial conflicts to disclose. Several coauthors disclosed relationships with Galderma, LEO Pharma, Janssen, Novartis, AbbVie, Celgene, Naos, Lilly, Sanofi, Valeant, and La Roche-Posay.

SOURCE: Machado M et al. JAMA Dermatol. 2019 June 5. doi: 10.1001/jamadermatol.2019.0759.

Many patients with hidradenitis suppurativa (HS) experience depression and anxiety, according to data from a systematic review and meta-analysis of more than 40,000 adults.

Previous studies of psychiatric comorbidities in HS patients have suggested an increased rate of depression, anxiety, and suicide risk, but have varied in methodology. “Therefore, the exact magnitude of the prevalence and odds of depression and anxiety in patients with HS is unclear,” wrote Myrela O. Machado, MD, of the division of dermatology, Women’s College Hospital, Toronto, and colleagues.

In a review of PubMed/MEDLINE, Embase, and PsycINFO electronic databases through July 2018, the researchers identified 10 studies comprising 40,307 adults with HS. The overall prevalence of depression was 16.9%, and in the studies that included a comparison group, the odds ratio for depression was 1.84 for HS patients, compared with controls who did not have HS. The overall prevalence of anxiety was 4.9%, but data were insufficient to determine an odds ratio for anxiety. The study was published in JAMA Dermatology.

All 10 studies assessed depression; 4 assessed anxiety. In subgroup analyses, the prevalence of depression was 11.9% in studies with a diagnosis based on clinical criteria and 26.8% in studies that used a screening instrument. The prevalence was 25.9% for outpatients with HS.


“Although our findings indicate that depression and anxiety may be common among people with HS, whether there is a causal relationship in those associations remains to be proved,” the researchers wrote.

However, they noted, “the consequences of depression and anxiety on HS-related outcomes have recently received more attention.”

The study findings were limited by several factors including the lack of data from structured diagnostic interviews, variation in methodological quality, and variation in comparison groups across studies, as well as a high level of heterogeneity across studies, the researchers noted. However, the results support the need to recognize and treat psychiatric conditions in HS patients, and to develop new management strategies, they said.

Dr. Machado had no financial conflicts to disclose. Several coauthors disclosed relationships with Galderma, LEO Pharma, Janssen, Novartis, AbbVie, Celgene, Naos, Lilly, Sanofi, Valeant, and La Roche-Posay.

SOURCE: Machado M et al. JAMA Dermatol. 2019 June 5. doi: 10.1001/jamadermatol.2019.0759.

Many patients with hidradenitis suppurativa (HS) experience depression and anxiety, according to data from a systematic review and meta-analysis of more than 40,000 adults.

Previous studies of psychiatric comorbidities in HS patients have suggested an increased rate of depression, anxiety, and suicide risk, but have varied in methodology. “Therefore, the exact magnitude of the prevalence and odds of depression and anxiety in patients with HS is unclear,” wrote Myrela O. Machado, MD, of the division of dermatology, Women’s College Hospital, Toronto, and colleagues.

In a review of PubMed/MEDLINE, Embase, and PsycINFO electronic databases through July 2018, the researchers identified 10 studies comprising 40,307 adults with HS. The overall prevalence of depression was 16.9%, and in the studies that included a comparison group, the odds ratio for depression was 1.84 for HS patients, compared with controls who did not have HS. The overall prevalence of anxiety was 4.9%, but data were insufficient to determine an odds ratio for anxiety. The study was published in JAMA Dermatology.

All 10 studies assessed depression; 4 assessed anxiety. In subgroup analyses, the prevalence of depression was 11.9% in studies with a diagnosis based on clinical criteria and 26.8% in studies that used a screening instrument. The prevalence was 25.9% for outpatients with HS.


“Although our findings indicate that depression and anxiety may be common among people with HS, whether there is a causal relationship in those associations remains to be proved,” the researchers wrote.

However, they noted, “the consequences of depression and anxiety on HS-related outcomes have recently received more attention.”

The study findings were limited by several factors including the lack of data from structured diagnostic interviews, variation in methodological quality, and variation in comparison groups across studies, as well as a high level of heterogeneity across studies, the researchers noted. However, the results support the need to recognize and treat psychiatric conditions in HS patients, and to develop new management strategies, they said.

Dr. Machado had no financial conflicts to disclose. Several coauthors disclosed relationships with Galderma, LEO Pharma, Janssen, Novartis, AbbVie, Celgene, Naos, Lilly, Sanofi, Valeant, and La Roche-Posay.

SOURCE: Machado M et al. JAMA Dermatol. 2019 June 5. doi: 10.1001/jamadermatol.2019.0759.

The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.

However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.

At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, this early exam offers a great opportunity to screen for CHDs – the most common congenital anomaly, with an incidence of about 4-13 per 1,000 live births.
 

The value of early detection

Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.

During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.

An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.

In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.

Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.⁷
 

First-trimester echocardiography benefits

Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.

This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.

Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
 

References

1. J Ultrasound Med. 2019 May;38(5):1269-77.

2. Prenat Diagn. 2005 Mar;25(3):253-60.

3. J Perinat Med. 2018 May 24;46(4):373-8.

4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.

5. National Congenital Heart Disease Audit Report 2013-2016.

6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.

7. Echocardiography. 2018 Feb;35(2):244-57.

8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.

The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.

However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.

At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, this early exam offers a great opportunity to screen for CHDs – the most common congenital anomaly, with an incidence of about 4-13 per 1,000 live births.
 

The value of early detection

Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.

During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.

An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.

In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.

Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.⁷
 

First-trimester echocardiography benefits

Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.

This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.

Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
 

References

1. J Ultrasound Med. 2019 May;38(5):1269-77.

2. Prenat Diagn. 2005 Mar;25(3):253-60.

3. J Perinat Med. 2018 May 24;46(4):373-8.

4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.

5. National Congenital Heart Disease Audit Report 2013-2016.

6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.

7. Echocardiography. 2018 Feb;35(2):244-57.

8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.

The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.

However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.

At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, this early exam offers a great opportunity to screen for CHDs – the most common congenital anomaly, with an incidence of about 4-13 per 1,000 live births.
 

The value of early detection

Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.

During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.

An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.

In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.

Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.⁷
 

First-trimester echocardiography benefits

Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.

This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.

Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
 

References

1. J Ultrasound Med. 2019 May;38(5):1269-77.

2. Prenat Diagn. 2005 Mar;25(3):253-60.

3. J Perinat Med. 2018 May 24;46(4):373-8.

4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.

5. National Congenital Heart Disease Audit Report 2013-2016.

6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.

7. Echocardiography. 2018 Feb;35(2):244-57.

8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.

Regardless of political or ideological views, detecting the embryonic heartbeat in the first trimester is a major milestone for a patient. Measured via ultrasound, normal beating of 90-110 bpm around 6 weeks’ gestation indicates a high probability of a successful pregnancy. Once the embryo becomes a fetus, around gestational weeks 8-9, a strong fetal heartbeat of 140-170 bpm should be detected. Finding a heartbeat is a reassuring sign. However, simply seeing and/or hearing the heart is not enough to ensure that the fetus will develop without problems.

Congenital heart defects (CHDs) are the most common birth defects worldwide and, although many CHDs can be mild forms, approximately 25% are severe forms requiring early detection and intervention.¹ In addition, CHDs in the fetus can cause miscarriage, stillbirth, and infant deaths.

A 2014 analysis of data from the Wisconsin Stillbirth Service Program revealed that approximately 9% of stillbirths after 20 weeks’ gestation and nearly 4% of miscarriages prior to 20 weeks were attributable to congenital heart defects.² An analysis of the Active Malformations Surveillance Program at Brigham and Women’s Hospital also revealed CHDs as a major cause of stillbirths.³ In addition, a retrospective study of the Metropolitan Atlanta Congenital Defects program showed that, although 1-year survival of infants with severe CHDs has improved over the last 4 decades, mortality remains high.¹

Because advances in medicine and surgical procedures have significantly reduced deaths attributable to CHDs, more women with a preexisting heart condition are becoming pregnant. Women who have a CHD, even if corrected, can experience pregnancy complications such as arrhythmias, thrombosis, and cardiac dysfunction. In addition, babies of women with CHDs have a higher risk of developing cardiac defects as well.

Therefore, it is critical that we closely monitor our patients – both the mother and her baby – to ensure that the fetal heart is present, functional, and developing normally. We have invited Dr. Shifa Turan, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland and director of the Fetal Heart Program at the University of Maryland Medical Center, both in Baltimore, to discuss the fetal heart. In this first section of a two-part series, Dr. Turan addresses how we can and should monitor fetal heart development.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
 

References

1. Pediatrics. 2013 May. doi: 10.1542/peds.2012-3435).

2. Am J Med Genet A. 2014 Mar. doi: 10.1002/ajmg.a.36366.

3. Birth Defects Res. 2018 Jan. 29. doi: 10.1002/bdr2.1097.

Regardless of political or ideological views, detecting the embryonic heartbeat in the first trimester is a major milestone for a patient. Measured via ultrasound, normal beating of 90-110 bpm around 6 weeks’ gestation indicates a high probability of a successful pregnancy. Once the embryo becomes a fetus, around gestational weeks 8-9, a strong fetal heartbeat of 140-170 bpm should be detected. Finding a heartbeat is a reassuring sign. However, simply seeing and/or hearing the heart is not enough to ensure that the fetus will develop without problems.

Congenital heart defects (CHDs) are the most common birth defects worldwide and, although many CHDs can be mild forms, approximately 25% are severe forms requiring early detection and intervention.¹ In addition, CHDs in the fetus can cause miscarriage, stillbirth, and infant deaths.

A 2014 analysis of data from the Wisconsin Stillbirth Service Program revealed that approximately 9% of stillbirths after 20 weeks’ gestation and nearly 4% of miscarriages prior to 20 weeks were attributable to congenital heart defects.² An analysis of the Active Malformations Surveillance Program at Brigham and Women’s Hospital also revealed CHDs as a major cause of stillbirths.³ In addition, a retrospective study of the Metropolitan Atlanta Congenital Defects program showed that, although 1-year survival of infants with severe CHDs has improved over the last 4 decades, mortality remains high.¹

Because advances in medicine and surgical procedures have significantly reduced deaths attributable to CHDs, more women with a preexisting heart condition are becoming pregnant. Women who have a CHD, even if corrected, can experience pregnancy complications such as arrhythmias, thrombosis, and cardiac dysfunction. In addition, babies of women with CHDs have a higher risk of developing cardiac defects as well.

Therefore, it is critical that we closely monitor our patients – both the mother and her baby – to ensure that the fetal heart is present, functional, and developing normally. We have invited Dr. Shifa Turan, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland and director of the Fetal Heart Program at the University of Maryland Medical Center, both in Baltimore, to discuss the fetal heart. In this first section of a two-part series, Dr. Turan addresses how we can and should monitor fetal heart development.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
 

References

1. Pediatrics. 2013 May. doi: 10.1542/peds.2012-3435).

2. Am J Med Genet A. 2014 Mar. doi: 10.1002/ajmg.a.36366.

3. Birth Defects Res. 2018 Jan. 29. doi: 10.1002/bdr2.1097.

Regardless of political or ideological views, detecting the embryonic heartbeat in the first trimester is a major milestone for a patient. Measured via ultrasound, normal beating of 90-110 bpm around 6 weeks’ gestation indicates a high probability of a successful pregnancy. Once the embryo becomes a fetus, around gestational weeks 8-9, a strong fetal heartbeat of 140-170 bpm should be detected. Finding a heartbeat is a reassuring sign. However, simply seeing and/or hearing the heart is not enough to ensure that the fetus will develop without problems.

Congenital heart defects (CHDs) are the most common birth defects worldwide and, although many CHDs can be mild forms, approximately 25% are severe forms requiring early detection and intervention.¹ In addition, CHDs in the fetus can cause miscarriage, stillbirth, and infant deaths.

A 2014 analysis of data from the Wisconsin Stillbirth Service Program revealed that approximately 9% of stillbirths after 20 weeks’ gestation and nearly 4% of miscarriages prior to 20 weeks were attributable to congenital heart defects.² An analysis of the Active Malformations Surveillance Program at Brigham and Women’s Hospital also revealed CHDs as a major cause of stillbirths.³ In addition, a retrospective study of the Metropolitan Atlanta Congenital Defects program showed that, although 1-year survival of infants with severe CHDs has improved over the last 4 decades, mortality remains high.¹

Because advances in medicine and surgical procedures have significantly reduced deaths attributable to CHDs, more women with a preexisting heart condition are becoming pregnant. Women who have a CHD, even if corrected, can experience pregnancy complications such as arrhythmias, thrombosis, and cardiac dysfunction. In addition, babies of women with CHDs have a higher risk of developing cardiac defects as well.

Therefore, it is critical that we closely monitor our patients – both the mother and her baby – to ensure that the fetal heart is present, functional, and developing normally. We have invited Dr. Shifa Turan, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland and director of the Fetal Heart Program at the University of Maryland Medical Center, both in Baltimore, to discuss the fetal heart. In this first section of a two-part series, Dr. Turan addresses how we can and should monitor fetal heart development.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
 

References

1. Pediatrics. 2013 May. doi: 10.1542/peds.2012-3435).

2. Am J Med Genet A. 2014 Mar. doi: 10.1002/ajmg.a.36366.

3. Birth Defects Res. 2018 Jan. 29. doi: 10.1002/bdr2.1097.

Implementation of low-dose CT screening for lung cancer in community settings is successfully detecting the disease at an early, more treatable stage, suggests a survey of U.S. lung cancer screening centers.

Such screening led to a 20% reduction in lung cancer mortality in the National Lung Screening Trial (N Engl J Med. 2011;365:395-409), prompting the Centers for Medicare & Medicaid Services to start covering it in 2015. However, fewer than a third of trial practices were community based, and questions lingered regarding applicability of this screening in nonacademic settings.

Investigators working under senior author Jennifer C. King, PhD, senior director of science and research at the GO2 Foundation for Lung Cancer, Washington, administered a 21-question survey to 165 lung cancer screening centers designated as Screening Centers of Excellence asking about their 2016 program data and practices. Overall, 62% of the centers were community based, having no university or other academic affiliation.

Results reported in the Journal of Oncology Practice showed that more than half of 529 lung cancer diagnoses the centers made in 2016 were made at stage I or limited stage, with the same pattern seen for community and academic centers. Findings were similar when analyses instead considered Lung Imaging Reporting and Data System results for 40,000 low-dose CT scans performed that year.

Community and academic centers differed in how they addressed the CMS requirement for a prescreening shared decision making visit led by a health practitioner, with the former more commonly relying on only primary care providers (52% vs. 40%). The centers were similar in how they addressed the CMS requirement for smoking cessation services, with both using referral to a quitline, cessation counseling within the screening facility, and printed educational materials; however, academic centers more commonly followed up with current smokers (52% vs. 36%).

The main barriers to implementing screening were insurance and billing issues, lack of provider referral, lack of patient awareness, and internal work flow challenges, cited by more than half of centers overall. Community centers less often cited staffing and time limitations (35% vs. 53%) and insurance and billing issues (64% vs. 74%), but percentages were similar for other barriers.

“There has been concern about the ability of nonacademic centers to implement lung cancer screening as safely and effectively as academic medical centers,” Dr. King and coauthors wrote. “In this study, we not only demonstrate that lung cancer screening is happening in the community setting, but also that nonacademic screening programs are using similar protocols and are seeing similar findings as academic medical centers.

“These data indicate that responsible implementation is possible in the community and results in a meaningful stage shift for lung cancer diagnoses, and providers should support ongoing implementation of lung cancer screening efforts,” they concluded.

Dr. King reported that she receives honoraria from MedImmune, AstraZeneca, and Genentech; has a consulting or advisory role with GRAIL, Tesaro, AbbVie, and Foundation Medicine; and receives research funding from AstraZeneca. The study was supported by the GO2 Foundation for Lung Cancer.

SOURCE: King JC et al. J Oncol Pract. 2019 May 31. doi: 10.1200/JOP.18.00788.

Implementation of low-dose CT screening for lung cancer in community settings is successfully detecting the disease at an early, more treatable stage, suggests a survey of U.S. lung cancer screening centers.

Such screening led to a 20% reduction in lung cancer mortality in the National Lung Screening Trial (N Engl J Med. 2011;365:395-409), prompting the Centers for Medicare & Medicaid Services to start covering it in 2015. However, fewer than a third of trial practices were community based, and questions lingered regarding applicability of this screening in nonacademic settings.

Investigators working under senior author Jennifer C. King, PhD, senior director of science and research at the GO2 Foundation for Lung Cancer, Washington, administered a 21-question survey to 165 lung cancer screening centers designated as Screening Centers of Excellence asking about their 2016 program data and practices. Overall, 62% of the centers were community based, having no university or other academic affiliation.

Results reported in the Journal of Oncology Practice showed that more than half of 529 lung cancer diagnoses the centers made in 2016 were made at stage I or limited stage, with the same pattern seen for community and academic centers. Findings were similar when analyses instead considered Lung Imaging Reporting and Data System results for 40,000 low-dose CT scans performed that year.

Community and academic centers differed in how they addressed the CMS requirement for a prescreening shared decision making visit led by a health practitioner, with the former more commonly relying on only primary care providers (52% vs. 40%). The centers were similar in how they addressed the CMS requirement for smoking cessation services, with both using referral to a quitline, cessation counseling within the screening facility, and printed educational materials; however, academic centers more commonly followed up with current smokers (52% vs. 36%).

The main barriers to implementing screening were insurance and billing issues, lack of provider referral, lack of patient awareness, and internal work flow challenges, cited by more than half of centers overall. Community centers less often cited staffing and time limitations (35% vs. 53%) and insurance and billing issues (64% vs. 74%), but percentages were similar for other barriers.

“There has been concern about the ability of nonacademic centers to implement lung cancer screening as safely and effectively as academic medical centers,” Dr. King and coauthors wrote. “In this study, we not only demonstrate that lung cancer screening is happening in the community setting, but also that nonacademic screening programs are using similar protocols and are seeing similar findings as academic medical centers.

“These data indicate that responsible implementation is possible in the community and results in a meaningful stage shift for lung cancer diagnoses, and providers should support ongoing implementation of lung cancer screening efforts,” they concluded.

Dr. King reported that she receives honoraria from MedImmune, AstraZeneca, and Genentech; has a consulting or advisory role with GRAIL, Tesaro, AbbVie, and Foundation Medicine; and receives research funding from AstraZeneca. The study was supported by the GO2 Foundation for Lung Cancer.

SOURCE: King JC et al. J Oncol Pract. 2019 May 31. doi: 10.1200/JOP.18.00788.

Implementation of low-dose CT screening for lung cancer in community settings is successfully detecting the disease at an early, more treatable stage, suggests a survey of U.S. lung cancer screening centers.

Such screening led to a 20% reduction in lung cancer mortality in the National Lung Screening Trial (N Engl J Med. 2011;365:395-409), prompting the Centers for Medicare & Medicaid Services to start covering it in 2015. However, fewer than a third of trial practices were community based, and questions lingered regarding applicability of this screening in nonacademic settings.

Investigators working under senior author Jennifer C. King, PhD, senior director of science and research at the GO2 Foundation for Lung Cancer, Washington, administered a 21-question survey to 165 lung cancer screening centers designated as Screening Centers of Excellence asking about their 2016 program data and practices. Overall, 62% of the centers were community based, having no university or other academic affiliation.

Results reported in the Journal of Oncology Practice showed that more than half of 529 lung cancer diagnoses the centers made in 2016 were made at stage I or limited stage, with the same pattern seen for community and academic centers. Findings were similar when analyses instead considered Lung Imaging Reporting and Data System results for 40,000 low-dose CT scans performed that year.

Community and academic centers differed in how they addressed the CMS requirement for a prescreening shared decision making visit led by a health practitioner, with the former more commonly relying on only primary care providers (52% vs. 40%). The centers were similar in how they addressed the CMS requirement for smoking cessation services, with both using referral to a quitline, cessation counseling within the screening facility, and printed educational materials; however, academic centers more commonly followed up with current smokers (52% vs. 36%).

The main barriers to implementing screening were insurance and billing issues, lack of provider referral, lack of patient awareness, and internal work flow challenges, cited by more than half of centers overall. Community centers less often cited staffing and time limitations (35% vs. 53%) and insurance and billing issues (64% vs. 74%), but percentages were similar for other barriers.

“There has been concern about the ability of nonacademic centers to implement lung cancer screening as safely and effectively as academic medical centers,” Dr. King and coauthors wrote. “In this study, we not only demonstrate that lung cancer screening is happening in the community setting, but also that nonacademic screening programs are using similar protocols and are seeing similar findings as academic medical centers.

“These data indicate that responsible implementation is possible in the community and results in a meaningful stage shift for lung cancer diagnoses, and providers should support ongoing implementation of lung cancer screening efforts,” they concluded.

Dr. King reported that she receives honoraria from MedImmune, AstraZeneca, and Genentech; has a consulting or advisory role with GRAIL, Tesaro, AbbVie, and Foundation Medicine; and receives research funding from AstraZeneca. The study was supported by the GO2 Foundation for Lung Cancer.

SOURCE: King JC et al. J Oncol Pract. 2019 May 31. doi: 10.1200/JOP.18.00788.

BIRMINGHAM, ENGLAND – Patients with rheumatoid arthritis (RA) who switch back to an original tumor necrosis factor inhibitor (TNFi) after using a biosimilar product often do so because of ineffectiveness, but this could be largely subjective, research suggests.

Data from the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA), presented at the annual conference of the British Society for Rheumatology, have shown that the majority (81%) of 760 patients who switched from an etanercept originator (ETN-O) product (Enbrel) to an etanercept biosimilar (ETN-B) product (Benepali or Erelzi) remained on the latter at an average of 2 years’ follow-up.

However, of those who switched back to an ETN-O (8%, n = 58), ineffectiveness was the primary reason for doing so in more than half of patients (53%). Of patients who stopped ETN treatment altogether after the biosimilar switch (11%, n = 84), 29% stopped because of inefficacy. Other important reasons for switching back or stopping treatment were adverse events in 28% and 54% of cases, respectively. The switch back to an ETN-O happened within a median time of 4 months (range, 2–6 months).

Patients switching back to an ETN-O tended to be slightly younger than all patients who had switched to an ETN-B (median age 60 vs. 64 years). They were more likely to be female (79% vs. 75%). Median disease activity score in 28 joints (DAS28) at baseline were highest in those who discontinued ETN (3.9 vs. 3.2 for those who switched back and 3.0 for all who had switched to a biosimilar).

It is not known what is driving the purported ineffectiveness, said research assistant Rebecca Davies of the Arthritis Research UK Epidemiology Unit at the University of Manchester (England).

“It could be due to patient factors and a nocebo effect,” she suggested. This is where “negative patient expectations cause treatment to have a more negative effect.” For example, she added, “if a patient is settled on the originator drug and had to mandatorily switch to a biosimilar, it might be that they are more heightened to symptoms.”

Another explanation could be that consultants may be “overcautious” to continuing the biosimilar in patients who had responded well to the originator product, she hypothesized.

“Our next steps are to look at disease activity between 4 and 9 months post switch to determine” the cause of the described ineffectiveness.
 

Educate patients to reduce switchbacks?

Meanwhile data presented by a team of researchers from Imperial College Healthcare NHS Trust in London, headed by Maresa Carulli, MD, suggested that patient education may be an important factor in tackling why patients want to switch back to biosimilar treatment.

Over a 20-month period among 202 patients who were switched to an ETN-B after they had been established on an ETN-O, 27 (13.4%) switched back.

“The majority of patients who switched back to Enbrel reported subjective worsening of disease symptoms with Benepali,” Dr. Carulli and coauthors said in their poster. Indeed, 78% of patients who switched back after an average of just under 6 months reported that their symptoms had become worse on the biosimilar product.

Analysis of the RA patients (n = 16) who switched back demonstrated that DAS28 scores had increased by more than 1.2 points during the period of the switch, but this was “mainly due to increases in visual analog scores [VAS],” they said.

The average change in DAS28 was an increase of 1.32 points during the switch period, the researchers noted. The average changes in DAS28 components were: +5 and +0.44 points for the tender and swollen joint counts, +9.89 points for the erythrocyte sedimentation rate, and +25.56 points for VAS.

Although further data are need, the results “may suggest that a subjective component contributes toward intolerance” of the biosimilar product, the researchers said.

“Consideration of patient education during initiation of biosimilar treatment could be a significant factor in improving compliance with it.”

The BSR receives restricted income from multiple U.K. pharmaceutical companies, which is used to fund the BSRBR-RA. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or any decision to submit manuscripts for publication.

Ms. Davies and Dr. Carulli and team declared having no competing interests.

SOURCES: Davies R et al. Rheumatology. 2019;58(suppl 3), Abstract 022; and Dahanayake C et al. Rheumatology. 2019;58(suppl 3), Abstract 102

BIRMINGHAM, ENGLAND – Patients with rheumatoid arthritis (RA) who switch back to an original tumor necrosis factor inhibitor (TNFi) after using a biosimilar product often do so because of ineffectiveness, but this could be largely subjective, research suggests.

Data from the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA), presented at the annual conference of the British Society for Rheumatology, have shown that the majority (81%) of 760 patients who switched from an etanercept originator (ETN-O) product (Enbrel) to an etanercept biosimilar (ETN-B) product (Benepali or Erelzi) remained on the latter at an average of 2 years’ follow-up.

However, of those who switched back to an ETN-O (8%, n = 58), ineffectiveness was the primary reason for doing so in more than half of patients (53%). Of patients who stopped ETN treatment altogether after the biosimilar switch (11%, n = 84), 29% stopped because of inefficacy. Other important reasons for switching back or stopping treatment were adverse events in 28% and 54% of cases, respectively. The switch back to an ETN-O happened within a median time of 4 months (range, 2–6 months).

Patients switching back to an ETN-O tended to be slightly younger than all patients who had switched to an ETN-B (median age 60 vs. 64 years). They were more likely to be female (79% vs. 75%). Median disease activity score in 28 joints (DAS28) at baseline were highest in those who discontinued ETN (3.9 vs. 3.2 for those who switched back and 3.0 for all who had switched to a biosimilar).

It is not known what is driving the purported ineffectiveness, said research assistant Rebecca Davies of the Arthritis Research UK Epidemiology Unit at the University of Manchester (England).

“It could be due to patient factors and a nocebo effect,” she suggested. This is where “negative patient expectations cause treatment to have a more negative effect.” For example, she added, “if a patient is settled on the originator drug and had to mandatorily switch to a biosimilar, it might be that they are more heightened to symptoms.”

Another explanation could be that consultants may be “overcautious” to continuing the biosimilar in patients who had responded well to the originator product, she hypothesized.

“Our next steps are to look at disease activity between 4 and 9 months post switch to determine” the cause of the described ineffectiveness.
 

Educate patients to reduce switchbacks?

Meanwhile data presented by a team of researchers from Imperial College Healthcare NHS Trust in London, headed by Maresa Carulli, MD, suggested that patient education may be an important factor in tackling why patients want to switch back to biosimilar treatment.

Over a 20-month period among 202 patients who were switched to an ETN-B after they had been established on an ETN-O, 27 (13.4%) switched back.

“The majority of patients who switched back to Enbrel reported subjective worsening of disease symptoms with Benepali,” Dr. Carulli and coauthors said in their poster. Indeed, 78% of patients who switched back after an average of just under 6 months reported that their symptoms had become worse on the biosimilar product.

Analysis of the RA patients (n = 16) who switched back demonstrated that DAS28 scores had increased by more than 1.2 points during the period of the switch, but this was “mainly due to increases in visual analog scores [VAS],” they said.

The average change in DAS28 was an increase of 1.32 points during the switch period, the researchers noted. The average changes in DAS28 components were: +5 and +0.44 points for the tender and swollen joint counts, +9.89 points for the erythrocyte sedimentation rate, and +25.56 points for VAS.

Although further data are need, the results “may suggest that a subjective component contributes toward intolerance” of the biosimilar product, the researchers said.

“Consideration of patient education during initiation of biosimilar treatment could be a significant factor in improving compliance with it.”

The BSR receives restricted income from multiple U.K. pharmaceutical companies, which is used to fund the BSRBR-RA. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or any decision to submit manuscripts for publication.

Ms. Davies and Dr. Carulli and team declared having no competing interests.

SOURCES: Davies R et al. Rheumatology. 2019;58(suppl 3), Abstract 022; and Dahanayake C et al. Rheumatology. 2019;58(suppl 3), Abstract 102

BIRMINGHAM, ENGLAND – Patients with rheumatoid arthritis (RA) who switch back to an original tumor necrosis factor inhibitor (TNFi) after using a biosimilar product often do so because of ineffectiveness, but this could be largely subjective, research suggests.

Data from the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA), presented at the annual conference of the British Society for Rheumatology, have shown that the majority (81%) of 760 patients who switched from an etanercept originator (ETN-O) product (Enbrel) to an etanercept biosimilar (ETN-B) product (Benepali or Erelzi) remained on the latter at an average of 2 years’ follow-up.

However, of those who switched back to an ETN-O (8%, n = 58), ineffectiveness was the primary reason for doing so in more than half of patients (53%). Of patients who stopped ETN treatment altogether after the biosimilar switch (11%, n = 84), 29% stopped because of inefficacy. Other important reasons for switching back or stopping treatment were adverse events in 28% and 54% of cases, respectively. The switch back to an ETN-O happened within a median time of 4 months (range, 2–6 months).

Patients switching back to an ETN-O tended to be slightly younger than all patients who had switched to an ETN-B (median age 60 vs. 64 years). They were more likely to be female (79% vs. 75%). Median disease activity score in 28 joints (DAS28) at baseline were highest in those who discontinued ETN (3.9 vs. 3.2 for those who switched back and 3.0 for all who had switched to a biosimilar).

It is not known what is driving the purported ineffectiveness, said research assistant Rebecca Davies of the Arthritis Research UK Epidemiology Unit at the University of Manchester (England).

“It could be due to patient factors and a nocebo effect,” she suggested. This is where “negative patient expectations cause treatment to have a more negative effect.” For example, she added, “if a patient is settled on the originator drug and had to mandatorily switch to a biosimilar, it might be that they are more heightened to symptoms.”

Another explanation could be that consultants may be “overcautious” to continuing the biosimilar in patients who had responded well to the originator product, she hypothesized.

“Our next steps are to look at disease activity between 4 and 9 months post switch to determine” the cause of the described ineffectiveness.
 

Educate patients to reduce switchbacks?

Meanwhile data presented by a team of researchers from Imperial College Healthcare NHS Trust in London, headed by Maresa Carulli, MD, suggested that patient education may be an important factor in tackling why patients want to switch back to biosimilar treatment.

Over a 20-month period among 202 patients who were switched to an ETN-B after they had been established on an ETN-O, 27 (13.4%) switched back.

“The majority of patients who switched back to Enbrel reported subjective worsening of disease symptoms with Benepali,” Dr. Carulli and coauthors said in their poster. Indeed, 78% of patients who switched back after an average of just under 6 months reported that their symptoms had become worse on the biosimilar product.

Analysis of the RA patients (n = 16) who switched back demonstrated that DAS28 scores had increased by more than 1.2 points during the period of the switch, but this was “mainly due to increases in visual analog scores [VAS],” they said.

The average change in DAS28 was an increase of 1.32 points during the switch period, the researchers noted. The average changes in DAS28 components were: +5 and +0.44 points for the tender and swollen joint counts, +9.89 points for the erythrocyte sedimentation rate, and +25.56 points for VAS.

Although further data are need, the results “may suggest that a subjective component contributes toward intolerance” of the biosimilar product, the researchers said.

“Consideration of patient education during initiation of biosimilar treatment could be a significant factor in improving compliance with it.”

The BSR receives restricted income from multiple U.K. pharmaceutical companies, which is used to fund the BSRBR-RA. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or any decision to submit manuscripts for publication.

Ms. Davies and Dr. Carulli and team declared having no competing interests.

SOURCES: Davies R et al. Rheumatology. 2019;58(suppl 3), Abstract 022; and Dahanayake C et al. Rheumatology. 2019;58(suppl 3), Abstract 102

Subclinical atherosclerosis in the carotid arteries as measured by ultrasound appears to nearly triple the risk of a first cardiovascular event among patients with psoriatic disease, according to findings from a retrospective study.

pixologicstudio/Thinkstock.com

When added to the Framingham risk score, the measurement significantly improved its predictive ability, Curtis Sobchak, MD, and colleagues wrote in Arthritis & Rheumatology.

The findings indicate that carotid ultrasound could be a useful addition to cardiovascular risk stratification among these patients.

“Traditional algorithms do not consider other factors that may contribute to increased cardiovascular risk in rheumatic disease patients and tend to underestimate cardiovascular risk,” wrote Dr. Sobchak of the University of Toronto and coauthors.

“The advantage of ultrasound over other modalities for vascular imaging includes lack of radiation, low cost of the examination, and its widespread use in rheumatology for joint evaluation. Thus, this assessment could potentially be performed ‘at the bedside’ during consultation to provide immediate valuable information to complement clinical data from history, physical examination, and laboratory data,” they added.

The study retrospectively examined a prospective, observational cohort of 559 patients with psoriasis alone or psoriasis and psoriatic arthritis enrolled in the University of Toronto Psoriatic Disease Program. The investigators evaluated five ultrasound measures of atherosclerosis, including total plaque area (TPA), mean carotid intima-media thickness (cIMT), maximal cIMT, plaque category, and TPA category. Then they analyzed the risk relationship with major cardiovascular events (CVEs) classified as myocardial infarction, unstable angina, ischemic stroke, revascularization procedures, or cardiovascular-related death. Minor CVEs included stable angina, exacerbation of congestive heart failure, and transient ischemic attack over a mean follow-up close to 4 years.

The mean baseline TPA was 0.18 cm² and mean cIMT was 639 mcm. Most patients had plaques, including 27.0% with unilateral and 31.5% with bilateral plaques.

The rate of a first CVE during the study period was 1.11 per 100 patient-years, and the rate of a first major CVE was 0.91 per 100 patient-years. The risk of each was significantly related to a higher baseline burden of atherosclerosis.

A multivariate analysis determined that increased TPA at baseline increased the risk of an event by nearly 200% (hazard ratio, 2.85). Mean cIMT was not an independent predictor in the final analysis, “suggesting that TPA is a stronger predictor for CVE than cIMT,” the authors wrote.

Finally, they examined the predictive value of atherosclerosis alone, as well as combined with the Framingham risk score. The 5-year model indicated that the bivariate model was slightly more accurate than the Framingham score alone (area under the curve, 0.84 vs. 0.81), although this was not a significant difference. The predictive value of the Framingham risk score plus maximal cIMT, mean cIMT, or TPA all significantly improved when they were calculated using only high-risk patients (those above the treatment threshold for dyslipidemia).

“To the best of our knowledge this is the first study to assess the utility of various measures of carotid atherosclerosis to predict CVE in patients with psoriasis and PsA [psoriatic arthritis]. ... Combining vascular imaging data with clinical and laboratory measures of traditional cardiovascular risk factors could improve accuracy of cardiovascular risk stratification in patients with psoriatic disease and facilitate earlier initiation of appropriate treatment to reduce CVE in this population,” the investigators wrote.

The study was supported in part by a Young Investigator Operating Grant from the Arthritis Society. Dr. Sobchak had no financial disclosures.

msullivan@mdedge.com

SOURCE: Sobchak C et al. Arthritis Rheumatol. 2019 Jun 5. doi: 10.1002/art.40925.

Subclinical atherosclerosis in the carotid arteries as measured by ultrasound appears to nearly triple the risk of a first cardiovascular event among patients with psoriatic disease, according to findings from a retrospective study.

pixologicstudio/Thinkstock.com

When added to the Framingham risk score, the measurement significantly improved its predictive ability, Curtis Sobchak, MD, and colleagues wrote in Arthritis & Rheumatology.

The findings indicate that carotid ultrasound could be a useful addition to cardiovascular risk stratification among these patients.

“Traditional algorithms do not consider other factors that may contribute to increased cardiovascular risk in rheumatic disease patients and tend to underestimate cardiovascular risk,” wrote Dr. Sobchak of the University of Toronto and coauthors.

“The advantage of ultrasound over other modalities for vascular imaging includes lack of radiation, low cost of the examination, and its widespread use in rheumatology for joint evaluation. Thus, this assessment could potentially be performed ‘at the bedside’ during consultation to provide immediate valuable information to complement clinical data from history, physical examination, and laboratory data,” they added.

The study retrospectively examined a prospective, observational cohort of 559 patients with psoriasis alone or psoriasis and psoriatic arthritis enrolled in the University of Toronto Psoriatic Disease Program. The investigators evaluated five ultrasound measures of atherosclerosis, including total plaque area (TPA), mean carotid intima-media thickness (cIMT), maximal cIMT, plaque category, and TPA category. Then they analyzed the risk relationship with major cardiovascular events (CVEs) classified as myocardial infarction, unstable angina, ischemic stroke, revascularization procedures, or cardiovascular-related death. Minor CVEs included stable angina, exacerbation of congestive heart failure, and transient ischemic attack over a mean follow-up close to 4 years.

The mean baseline TPA was 0.18 cm² and mean cIMT was 639 mcm. Most patients had plaques, including 27.0% with unilateral and 31.5% with bilateral plaques.

The rate of a first CVE during the study period was 1.11 per 100 patient-years, and the rate of a first major CVE was 0.91 per 100 patient-years. The risk of each was significantly related to a higher baseline burden of atherosclerosis.

A multivariate analysis determined that increased TPA at baseline increased the risk of an event by nearly 200% (hazard ratio, 2.85). Mean cIMT was not an independent predictor in the final analysis, “suggesting that TPA is a stronger predictor for CVE than cIMT,” the authors wrote.

Finally, they examined the predictive value of atherosclerosis alone, as well as combined with the Framingham risk score. The 5-year model indicated that the bivariate model was slightly more accurate than the Framingham score alone (area under the curve, 0.84 vs. 0.81), although this was not a significant difference. The predictive value of the Framingham risk score plus maximal cIMT, mean cIMT, or TPA all significantly improved when they were calculated using only high-risk patients (those above the treatment threshold for dyslipidemia).

“To the best of our knowledge this is the first study to assess the utility of various measures of carotid atherosclerosis to predict CVE in patients with psoriasis and PsA [psoriatic arthritis]. ... Combining vascular imaging data with clinical and laboratory measures of traditional cardiovascular risk factors could improve accuracy of cardiovascular risk stratification in patients with psoriatic disease and facilitate earlier initiation of appropriate treatment to reduce CVE in this population,” the investigators wrote.

The study was supported in part by a Young Investigator Operating Grant from the Arthritis Society. Dr. Sobchak had no financial disclosures.

msullivan@mdedge.com

SOURCE: Sobchak C et al. Arthritis Rheumatol. 2019 Jun 5. doi: 10.1002/art.40925.

Subclinical atherosclerosis in the carotid arteries as measured by ultrasound appears to nearly triple the risk of a first cardiovascular event among patients with psoriatic disease, according to findings from a retrospective study.

pixologicstudio/Thinkstock.com

When added to the Framingham risk score, the measurement significantly improved its predictive ability, Curtis Sobchak, MD, and colleagues wrote in Arthritis & Rheumatology.

The findings indicate that carotid ultrasound could be a useful addition to cardiovascular risk stratification among these patients.

“Traditional algorithms do not consider other factors that may contribute to increased cardiovascular risk in rheumatic disease patients and tend to underestimate cardiovascular risk,” wrote Dr. Sobchak of the University of Toronto and coauthors.

“The advantage of ultrasound over other modalities for vascular imaging includes lack of radiation, low cost of the examination, and its widespread use in rheumatology for joint evaluation. Thus, this assessment could potentially be performed ‘at the bedside’ during consultation to provide immediate valuable information to complement clinical data from history, physical examination, and laboratory data,” they added.

The study retrospectively examined a prospective, observational cohort of 559 patients with psoriasis alone or psoriasis and psoriatic arthritis enrolled in the University of Toronto Psoriatic Disease Program. The investigators evaluated five ultrasound measures of atherosclerosis, including total plaque area (TPA), mean carotid intima-media thickness (cIMT), maximal cIMT, plaque category, and TPA category. Then they analyzed the risk relationship with major cardiovascular events (CVEs) classified as myocardial infarction, unstable angina, ischemic stroke, revascularization procedures, or cardiovascular-related death. Minor CVEs included stable angina, exacerbation of congestive heart failure, and transient ischemic attack over a mean follow-up close to 4 years.

The mean baseline TPA was 0.18 cm² and mean cIMT was 639 mcm. Most patients had plaques, including 27.0% with unilateral and 31.5% with bilateral plaques.

The rate of a first CVE during the study period was 1.11 per 100 patient-years, and the rate of a first major CVE was 0.91 per 100 patient-years. The risk of each was significantly related to a higher baseline burden of atherosclerosis.

A multivariate analysis determined that increased TPA at baseline increased the risk of an event by nearly 200% (hazard ratio, 2.85). Mean cIMT was not an independent predictor in the final analysis, “suggesting that TPA is a stronger predictor for CVE than cIMT,” the authors wrote.

Finally, they examined the predictive value of atherosclerosis alone, as well as combined with the Framingham risk score. The 5-year model indicated that the bivariate model was slightly more accurate than the Framingham score alone (area under the curve, 0.84 vs. 0.81), although this was not a significant difference. The predictive value of the Framingham risk score plus maximal cIMT, mean cIMT, or TPA all significantly improved when they were calculated using only high-risk patients (those above the treatment threshold for dyslipidemia).

“To the best of our knowledge this is the first study to assess the utility of various measures of carotid atherosclerosis to predict CVE in patients with psoriasis and PsA [psoriatic arthritis]. ... Combining vascular imaging data with clinical and laboratory measures of traditional cardiovascular risk factors could improve accuracy of cardiovascular risk stratification in patients with psoriatic disease and facilitate earlier initiation of appropriate treatment to reduce CVE in this population,” the investigators wrote.

The study was supported in part by a Young Investigator Operating Grant from the Arthritis Society. Dr. Sobchak had no financial disclosures.

msullivan@mdedge.com

SOURCE: Sobchak C et al. Arthritis Rheumatol. 2019 Jun 5. doi: 10.1002/art.40925.